{"studies":[{"id":1,"slug":"a-comparison-of-the-efficacy-and-toxic-effects-of-sustained-vs-immediate-release-niacin-in-hypercholesterolemic-patients","title":"A comparison of the efficacy and toxic effects of sustained vs immediate-release niacin in hypercholesterolemic patients","seo_title":"Sustained-Release vs Immediate-Release Niacin: Which Is Safer for Cholesterol?","publication_title":"A comparison of the efficacy and toxic effects of sustained vs immediate-release niacin in hypercholesterolemic patients","publication_url":"https://pubmed.ncbi.nlm.nih.gov/8309029/","pmid":"8309029","date":"2022-12-21","publication_year":1994,"description":"The effects on cholesterol of modified \"sustained release\" niacin was compared to immediate release niacin (aka nicotinic acid) and showed that sustained release tends to lower LDL more, while immediate release raises HDL more at all dosage levels. The key takeway though is that 52% of the patients taking sustained release developed signs of liver toxixity, while 0% of the ones taking immediate release did.","body_markdown":null,"study_type":"rct","model":"human","sample_size":46,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":"500mg to 3000mg/day immediate-release vs sustained-release","dose_mg_kg":null,"dose_absolute_mg":3000,"dose_human_equiv_g":3,"outcome":"mixed","effect_size":null,"mechanisms":[{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"dyslipidemia","name":"dyslipidemia"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"},{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"}]},{"id":2,"slug":"a-detoxification-intervention-for-gulf-war-illness-a-pilot-randomized-controlled-trial","title":"A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial","seo_title":"Niacin Detox Protocol Reduces Gulf War Illness Symptoms in Pilot Trial","publication_title":"A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862571/","pmid":null,"date":"2022-11-27","publication_year":2019,"description":"~30% of Gulf War veterans got Gulf War Illness, which is likely caused by toxic exposure to pesticides and chemical warfare agents. There is no known medical treatment. A regimen of niacin, sauna and exercise cured 11 of 22 participants.","body_markdown":null,"study_type":"rct","model":"human","sample_size":32,"duration":"4 weeks","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"gulf-war-illness","name":"gulf-war-illness"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"},{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"}]},{"id":3,"slug":"a-novel-treatment-target-for-parkinsons-disease","title":"A novel treatment target for Parkinson's disease","seo_title":"Niacin May Help Parkinson's Disease via GPR109A Anti-Inflammatory Effects","publication_title":"A novel treatment target for Parkinson's disease","publication_url":"https://www.sciencedirect.com/science/article/abs/pii/S0022510X14006777","pmid":null,"date":"2021-09-12","publication_year":2015,"description":"The GPR109A receptor and its agonists (niacin and butyrate) have anti-inflammatory actions in the skin, gut and retina. For Parkinson's disease, niacin supplementation may have 3 benefits: lower inflammation via GPR109A-related mechanisms, increase dopamine production in brain by supplying NADPH and boosting mitochondrial functions by increasing the NAD/NADH ratio.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nadph","name":"NADPH"},{"slug":"nad","name":"NAD+"},{"slug":"nadh","name":"NADH"}],"conditions":[{"slug":"parkinsons","name":"parkinsons"},{"slug":"neuroinflammation","name":"neuroinflammation"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":4,"slug":"a-prospective-and-comparative-investigation-of-blood-sflt-1-p1gf-and-niacin-concentrations-in-women-with-premature-ovarian-insufficiency","title":"A prospective and comparative investigation of blood sFlt-1, P1GF, and niacin concentrations in women with premature ovarian insufficiency","seo_title":"Low Niacin May Contribute to Premature Ovarian Insufficiency in Women","publication_title":"A prospective and comparative investigation of blood sFlt-1, P1GF, and niacin concentrations in women with premature ovarian insufficiency","publication_url":"https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.15554","pmid":null,"date":"2023-05-14","publication_year":2023,"description":"Niacin supplementation may prevent premature menopause. Women with premature menopause have significantly lower levels of niacin. Niacin levels lowest in women most severe symptoms.","body_markdown":null,"study_type":"cohort","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"fertility","name":"fertility"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":5,"slug":"acne-vulgaris-is-a-special-clinical-type-of-pellagra","title":"Acne Vulgaris Is a Special Clinical Type of Pellagra","seo_title":"Acne and Niacin Deficiency: Acne Vulgaris Linked to Pellagra-Like Condition","publication_title":"Acne Vulgaris Is a Special Clinical Type of Pellagra","publication_url":"https://www.sciencepublishinggroup.com/journal/paperinfo?journalid=254&doi=10.11648/j.ajcem.20210906.13","pmid":null,"date":"2023-03-26","publication_year":2021,"description":"People with acne often have abnormal lipid profiles and elevated oily secretion on their skin. Foam cells are an important pathological change in acne lesions. Acne is not a skin disease induced by infection, because no bacteria, fungi or parasites can be seen in early phase of acne lesion. The foam cells in acne lesions are white blood cells that have ingested large amounts of lipids. Niacin is the only vitamin that promotes the ability of HDL to scoop up cholesterol particles from plaques in the heart's blood vessels and move those particles to the liver for disposal, which prevents foam cell formation. Foam cells in acne lesions suggest that patients with acne are deficient in niacin and that acne can be considered a type of pellagra (niacin deficiency).","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"dermatitis","name":"dermatitis"},{"slug":"pellagra","name":"pellagra"},{"slug":"dyslipidemia","name":"dyslipidemia"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":6,"slug":"action-of-nicotinic-acid-on-the-reversion-of-hypoxic-inflammatory-link-on-3t3-l1-adipocytes","title":"Action of nicotinic acid on the reversion of hypoxic-inflammatory link on 3T3-L1 adipocytes","seo_title":"Niacin Breaks the Hypoxia-Inflammation Cycle in Fat Cells","publication_title":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862071/","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862071/","pmid":null,"date":"2022-11-27","publication_year":2016,"description":"Niacin reduces inflammation caused by low levels of oxygen in tissue that is associated with obesity.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nf-kb","name":"NF-kB"},{"slug":"adiponectin","name":"adiponectin"},{"slug":"gpr109a","name":"GPR109A"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"obesity","name":"obesity"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":7,"slug":"activated-niacin-receptor-hca2-inhibits-chemoattractant-mediated-macrophage-migration-via-gβγ-pkc-erk1-2-pathway-and-heterologous-receptor-desensitization","title":"Activated niacin receptor HCA2 inhibits chemoattractant-mediated macrophage migration via Gβγ/PKC/ERK1/2 pathway and heterologous receptor desensitization","seo_title":null,"publication_title":"Activated niacin receptor HCA2 inhibits chemoattractant-mediated macrophage migration via Gβγ/PKC/ERK1/2 pathway and heterologous receptor desensitization","publication_url":"https://www.nature.com/articles/srep42279","pmid":null,"date":"2021-09-12","publication_year":2017,"description":"GPR109A (aka HCA2) is highly expressed in immune cells and together with niacin seems to inhibit proinflammatory aspects of immune cell activity.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"macrophage","name":"macrophage"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"atherosclerosis","name":"atherosclerosis"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":8,"slug":"activation-of-gpr109a-receptor-for-niacin-and-the-commensal-metabolite-butyrate-suppresses-colonic-inflammation-and-carcinogenesis-1","title":"Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis","seo_title":"Niacin and Butyrate Activate GPR109A to Suppress Colon Cancer Risk","publication_title":"Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305274/","pmid":null,"date":"2022-06-18","publication_year":2014,"description":"Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner in mice. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"il-18","name":"IL-18"},{"slug":"il-10","name":"IL-10"},{"slug":"treg","name":"Treg"},{"slug":"butyrate","name":"butyrate"}],"conditions":[{"slug":"colitis","name":"colitis"},{"slug":"colorectal-cancer","name":"colorectal-cancer"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":9,"slug":"activation-of-gpr109a-receptor-for-niacin-and-the-commensal-metabolite-butyrate-suppresses-colonic-inflammation-and-carcinogenesis","title":"Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis","seo_title":"GPR109A: Niacin and Butyrate Receptor Protects Against Colitis and Colon Cancer","publication_title":"Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis","publication_url":"https://www.cell.com/immunity/fulltext/S1074-7613(13)00564-5","pmid":null,"date":"2021-11-23","publication_year":2014,"description":"GPR109A expressed in immune cells as well as in colonic tissue is necessary for protection against colitis and colon carcinogenesis. Niacin suppresses colitis and colon cancer in a GPR109A-dependent manner. GPR109A is key in mediating the beneficial effects of gut microbiota and dietary fiber in colon. Niacin suppresses atherosclerosis by activating GPR109A in immune cells. GPR109A mediates butyrate effects in colon and is a critical molecular link between colonic bacteria and dietary fiber and the host.","body_markdown":"## Overview\n\nThis 2014 Cell Immunity paper (Thangaraju et al.) is one of the most cited in the GPR109A literature. It demonstrates that GPR109A — the receptor activated by both niacin and the gut metabolite butyrate — plays a protective role against colonic inflammation and colon cancer. The study establishes GPR109A as a critical molecular link between the gut microbiome, dietary fiber, and host immune defense.\n\n## Key Findings\n\n**GPR109A is required for colonic immune protection.** Mice lacking GPR109A showed increased susceptibility to colitis and colon carcinogenesis when challenged with inflammation-inducing agents. This indicates GPR109A's function is not redundant — it is necessary, not just helpful.\n\n**Niacin suppresses colitis and colon cancer via GPR109A.** When GPR109A was activated by niacin in wild-type mice, colitis was suppressed. In GPR109A-knockout mice, niacin had no protective effect — confirming the mechanism is GPR109A-dependent, not a general effect of niacin on inflammation.\n\n**Butyrate activates GPR109A in the colon.** The short-chain fatty acid butyrate — produced by gut bacteria fermenting dietary fiber — also activates GPR109A. This discovery positioned GPR109A as the receptor mediating the well-known anti-inflammatory and anti-cancer effects of dietary fiber and a healthy gut microbiome.\n\n**GPR109A induces IL-18 in colonocytes and Treg differentiation.** The mechanism involves GPR109A activation inducing production of interleukin-18 (IL-18) in colon epithelial cells, which then promotes regulatory T cell (Treg) differentiation — suppressing excessive immune response while maintaining tolerance.\n\n## The Broader Picture\n\nThis paper describes a coherent circuit:\n\n1. Dietary fiber → gut bacteria ferment it → **butyrate** produced\n2. Butyrate activates **GPR109A** on colonic epithelial cells and immune cells\n3. GPR109A activation → **IL-18** secretion from colonocytes\n4. IL-18 → Treg differentiation → suppression of colonic inflammation\n5. Disruption of this circuit (dysbiosis, low fiber, GPR109A loss) → colitis, increased cancer risk\n\nNiacin, as a pharmacological agonist of GPR109A, can activate this circuit even when dietary butyrate is insufficient — for example, in patients with dysbiosis or low-fiber diets.\n\n## Niacin and Atherosclerosis: Same Receptor\n\nThe paper also notes that GPR109A activation by niacin suppresses atherosclerosis via immune cells, specifically by reducing macrophage activation. This connects niacin's lipid-modifying effects and its anti-inflammatory effects through the same receptor.\n\n## Why This Matters\n\nThis study explains why:\n\n- Niacin (nicotinic acid) has anti-inflammatory effects in the colon at therapeutic doses\n- The gut microbiome matters for colon cancer prevention\n- Dietary fiber has protective effects that are mechanistically explainable\n- Niacinamide would not produce these same GPR109A-mediated effects in the colon\n\nFor researchers and clinicians investigating niacin in inflammatory bowel disease, colon cancer prevention, or the gut-immune axis, this Cell Immunity paper is the foundational reference for GPR109A's role in colonic biology.","study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"il-18","name":"IL-18"},{"slug":"il-10","name":"IL-10"},{"slug":"treg","name":"Treg"},{"slug":"butyrate","name":"butyrate"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"colitis","name":"colitis"},{"slug":"colorectal-cancer","name":"colorectal-cancer"},{"slug":"inflammation","name":"inflammation"},{"slug":"atherosclerosis","name":"atherosclerosis"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":10,"slug":"activation-of-the-receptor-gpr109a-for-niacin-and-the-commensal-metabolite-butyrate-suppresses-colonic-inflammation-and-carcinogenesis","title":"Activation of the receptor (Gpr109a) for niacin and the commensal metabolite butyrate suppresses colonic inflammation and carcinogenesis","seo_title":"GPR109A Activation by Niacin and Butyrate Suppresses Colon Cancer","publication_title":"Activation of the receptor (Gpr109a) for niacin and the commensal metabolite butyrate suppresses colonic inflammation and carcinogenesis","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4305274/","pmid":null,"date":"2021-09-12","publication_year":2014,"description":"GPR109A plays an essential role in gut health. GPR109A deficiency worsens colitis and colonic inflammation in mice. GPR109A expression is necessary for immune health. Antibiotics mess up butyrate producing gut bacteria, thus reducing GPR109A.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"il-18","name":"IL-18"},{"slug":"treg","name":"Treg"},{"slug":"butyrate","name":"butyrate"}],"conditions":[{"slug":"colitis","name":"colitis"},{"slug":"colorectal-cancer","name":"colorectal-cancer"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":11,"slug":"anti-inflammatory-effects-of-nicotinic-acid","title":"Anti-inflammatory effects of nicotinic acid","seo_title":"Anti-Inflammatory Effects of Nicotinic Acid: How Niacin Reduces Inflammation","publication_title":"Anti-inflammatory effects of nicotinic acid","publication_url":"https://pubmed.ncbi.nlm.nih.gov/19781706/","pmid":"19781706","date":"2021-10-04","publication_year":2010,"description":"Niacin has multi-faceted anti inflammatory properties that act in both localized and systemic ways. A major area of its activity is in tissue related to fat storage via the GPR109A receptor. Dosing cells with TNF-alpha ( an inflammatory substance ) showed that niacin treated cells increased the atheroprotective hormone adiponectin and reduced macrophage chemotaxis","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"adiponectin","name":"adiponectin"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"atherosclerosis","name":"atherosclerosis"},{"slug":"obesity","name":"obesity"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":12,"slug":"anti-inflammatory-effects-of-nicotinic-acid-in-adipocytes-demonstrated-by-suppression-of-fractalkine-rantes-and-mcp-1-and-upregulation-of-adiponectin","title":"Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin","seo_title":"Niacin Reduces Inflammatory Cytokines in Fat Cells and Boosts Adiponectin","publication_title":"https://pubmed.ncbi.nlm.nih.gov/19781706/","publication_url":"https://pubmed.ncbi.nlm.nih.gov/19781706/","pmid":"19781706","date":"2021-09-16","publication_year":2010,"description":"Adipose tissue (body tissue used for the storage of fat) is major site of action for niacin. When adding a white blood cell attractant to adipose tissue, niacin suppresses the pro-atherogenic (plaque inducing) chemokines and upregulates the atheroprotective (protective against plaque and improves metabolism of sugar) adiponectin.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"adiponectin","name":"adiponectin"},{"slug":"macrophage","name":"macrophage"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"atherosclerosis","name":"atherosclerosis"},{"slug":"obesity","name":"obesity"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":13,"slug":"antiatherothrombotic-effects-of-nicotinic-acid","title":"Antiatherothrombotic effects of nicotinic acid","seo_title":"Niacin Reduces Blood Clot Risk and Supports Heart Health","publication_title":"Antiatherothrombotic effects of nicotinic acid","publication_url":"https://www.atherosclerosis-journal.com/article/S0021-9150(03)00328-9/fulltext","pmid":null,"date":"2022-06-18","publication_year":2003,"description":"Niacin reduces blood viscosity through a variety of mechanisms, thus improving blood flow and perfusion through choke points of the vasculature. Finally, niacin has cardioprotective effects that may limit ischemia–reperfusion injury. By preserving glycolysis during periods of inadequate blood supply and improving blood flow to the heart after a stroke, niacin can improve the functional recovery of the muscular tissue of the heart.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"prostaglandin","name":"prostaglandin"},{"slug":"pgd2","name":"PGD2"}],"conditions":[{"slug":"atherosclerosis","name":"atherosclerosis"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"}]},{"id":14,"slug":"antidepressants-may-lead-to-a-decrease-in-niacin-and-nad-in-patients-with-poor-dietary-intake","title":"Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake","seo_title":"Niacin and NAD+: How Antidepressants May Deplete Both","publication_title":"Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake","publication_url":"https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(14)00461-7","pmid":null,"date":"2022-12-21","publication_year":2015,"description":"Authors hypothesis that antidepressants tilt tryptophan metabolism towards making serotonin instead of niacin, which in turn can lead to niacin/NAD+ deficiency that exacerbates common psychiatric problems.","body_markdown":null,"study_type":"mechanistic","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"negative","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"tryptophan","name":"tryptophan"}],"conditions":[{"slug":"depression","name":"depression"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":15,"slug":"bacteria-boost-mammalian-host-nad-metabolism-by-engaging-the-deamidated-biosynthesis-pathway","title":"Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway","seo_title":"Gut Bacteria Boost Host NAD+ Metabolism via Deamidated Biosynthesis","publication_title":"https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30059-0","publication_url":"https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30059-0","pmid":null,"date":"2023-03-11","publication_year":2020,"description":"This research used stable isotope tracing and microbiota-depleted mice to reveal that salvage NAD+ precursor supplements like nicotinamide (NAM) and nicotinamide ribose (NMR) don't actually boost NAD+, but depend on bacteria to first convert them into nicotinic acid. And that the resulting nicotinic acid is the converts to NAD+ via the Preiss Handler pathway.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":16,"slug":"bacterial-pnca-improves-diet-induced-nafld-in-mice-by-enabling-the-transition-from-nicotinamide-to-nicotinic-acid","title":"Bacterial PncA improves diet-induced NAFLD in mice by enabling the transition from nicotinamide to nicotinic acid","seo_title":"Gut Bacteria Convert Niacin Precursors to Protect Against Fatty Liver","publication_title":"https://www.nature.com/articles/s42003-023-04613-8","publication_url":"https://www.nature.com/articles/s42003-023-04613-8","pmid":null,"date":"2023-03-11","publication_year":2023,"description":"Gut bacteria play an important role in NAD production. NAD boosting effect of oral NAM (nicotinamide) NR (nicotinamide riboside) is largely dependent on gut bacteria breaking them down to nicotinic acid, and that nicotinic acid being processed via Preiss Handler pathway. Nicotinic acid highly efficient at boosting NAD in mammals.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"liver","name":"liver"},{"slug":"obesity","name":"obesity"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":17,"slug":"blood-levels-of-nicotinic-acid-negatively-correlate-with-hearing-ability-in-healthy-older-men","title":"Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men","seo_title":"Study Finds Niacin Blood Levels Linked to Hearing Ability in Older Men","publication_title":"Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men","publication_url":"https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-023-03796-3","pmid":null,"date":"2023-03-03","publication_year":2023,"description":"Higher levels of nicotinic acid in blood are strongly correlated with better hearing ability in  42 Japanese senior men.","body_markdown":null,"study_type":"cohort","model":"human","sample_size":42,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"hearing-loss","name":"hearing-loss"},{"slug":"aging","name":"aging"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":18,"slug":"control-of-brain-tumor-growth-by-reactivating-myeloid-cells-with-niacin","title":"Control of brain tumor growth by reactivating myeloid cells with niacin","seo_title":"Niacin Activates Immune Cells to Suppress Brain Tumor Growth","publication_title":"Control of brain tumor growth by reactivating myeloid cells with niacin","publication_url":"https://www.science.org/doi/10.1126/scitranslmed.aay9924?rss=1&","pmid":null,"date":"2021-09-16","publication_year":2020,"description":"Niacin treatment of mice bearing intracranial brain tumor initiative cells increased macrophage representation within the tumor, reduced tumor size, and prolonged survival.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"brain-tumor","name":"brain-tumor"},{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":19,"slug":"coronavirus-infection-and-parp-expression-dysregulate-the-nad-metabolome-an-actionable-component-of-innate-immunity","title":"Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity","seo_title":"COVID-19 Disrupts NAD+ Metabolism — Niacin as a Potential Countermeasure","publication_title":"Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834058/","pmid":null,"date":"2022-06-18","publication_year":2020,"description":"The antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.","body_markdown":null,"study_type":"mechanistic","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"parp","name":"PARP"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":20,"slug":"curcumin-nicotinate-selectively-induces-cancer-cell-apoptosis-and-cycle-arrest-through-a-p53-mediated-mechanism","title":"Curcumin Nicotinate Selectively Induces Cancer Cell Apoptosis and Cycle Arrest through a P53-Mediated Mechanism","seo_title":"Curcumin-Niacin Compound Selectively Kills Cancer Cells via p53 Pathway","publication_title":"Curcumin Nicotinate Selectively Induces Cancer Cell Apoptosis and Cycle Arrest through a P53-Mediated Mechanism","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891632/","pmid":null,"date":"2022-01-12","publication_year":2019,"description":"Curcumin is an anticancer agent, it has demonstrates potent anti-proliferative activity in a wide range of cancer cells, including liver, breast, lung, stomach, colon, prostate, head and neck cancers. This study modified curcumin by adding 2 niacins molecules to it to make Curcumin Nicotinate. They tested it out on some cancer cell cultures and it showed that the Curcumin Nicotinate improved the anti cancer effect of curcumin by improving its cell selectivity.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"combination","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"p53","name":"p53"},{"slug":"apoptosis","name":"apoptosis"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":21,"slug":"decreased-expression-of-g-protein-coupled-receptors-gpr43-and-gpr109a-in-psoriatic-skin-can-be-restored-by-topical-application-of-sodium-butyrate","title":"Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate","seo_title":"GPR109A Deficient in Psoriasis Skin — Topical Butyrate Restores Expression","publication_title":"Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate","publication_url":"https://pubmed.ncbi.nlm.nih.gov/30209581/","pmid":"30209581","date":"2021-09-16","publication_year":2018,"description":"Psoriatic skin has reduced GPR109A expression, topical sodium butyrate increases GPR109A expression in skin and is potentially useful in psoriasis therapy.","body_markdown":"## Overview\n\nThis 2018 study (PubMed 30209581) investigated GPR43 and GPR109A receptor expression in psoriatic skin compared to healthy skin. Key findings: psoriatic plaques show significantly reduced GPR109A (and GPR43) expression, and topical application of sodium butyrate can restore GPR109A expression in psoriatic skin. This adds molecular detail to the connection between the niacin receptor, gut metabolites, and inflammatory skin disease.\n\n## GPR109A in the Skin\n\nGPR109A is a G-protein-coupled receptor expressed in fat cells (where niacin activates it to cause the characteristic flush), immune cells, colonic epithelium, and skin cells including keratinocytes. When activated, GPR109A generally produces anti-inflammatory effects: reduced cytokine production, promotion of regulatory immune responses, and reduced oxidative stress. In skin cells, GPR109A activation may help regulate the immune hyperactivation that characterizes psoriasis.\n\n## What the Study Found\n\n**Psoriatic skin has lower GPR109A expression.** Skin biopsies from psoriasis patients showed significantly reduced expression of both GPR109A and GPR43 compared to healthy skin. The molecular brake on inflammation — the receptor that niacin or butyrate would normally activate — is less available in psoriatic tissue.\n\n**Topical sodium butyrate restores GPR109A.** When sodium butyrate was applied topically to psoriatic skin, GPR109A expression increased. This suggests the reduced receptor expression is not permanent and can be upregulated by its natural ligand.\n\n## Why Butyrate?\n\nButyrate is a short-chain fatty acid produced by gut bacteria fermenting dietary fiber. It activates both GPR43 and GPR109A — the same receptor that niacin activates, though through different binding kinetics.\n\n## Connection to Niacin\n\nThis paper is part of a growing literature suggesting that reduced GPR109A activity in skin may be a feature — not just a consequence — of psoriasis, and that restoring GPR109A function through its known agonists (niacin, butyrate) could be therapeutically relevant.\n\nNicotinic acid activates GPR109A in keratinocytes and skin-resident immune cells. A related keratinocyte study also showed that nicotinic acid (not niacinamide) preferentially raises NAD+ in skin cells. Together, these findings suggest a mechanistic basis for investigating nicotinic acid specifically — not the niacinamide used in skincare — for psoriasis research.\n\n## Implications\n\n- Psoriatic skin has a deficit in the anti-inflammatory receptor that niacin and butyrate activate\n- This deficit may contribute to the inability of psoriatic tissue to resolve inflammation normally\n- Restoring GPR109A expression via topical or systemic agonists is a potential therapeutic avenue\n- The interplay between gut microbiome health, dietary fiber, and skin inflammation has a plausible molecular mechanism through GPR109A","study_type":"cohort","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"butyrate","route":"topical","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"butyrate","name":"butyrate"},{"slug":"t-cell","name":"T-cell"}],"conditions":[{"slug":"psoriasis","name":"psoriasis"},{"slug":"inflammation","name":"inflammation"},{"slug":"dermatitis","name":"dermatitis"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":22,"slug":"deficiency-of-metabolite-sensing-receptor-hca2-impairs-the-salutary-effect-of-niacin-in-hemorrhagic-shock","title":"Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock","seo_title":"Niacin Protects Against Hemorrhagic Shock Through the HCA2 Receptor","publication_title":"Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock","publication_url":"https://www.sciencedirect.com/science/article/pii/S0925443919300092","pmid":null,"date":"2023-03-12","publication_year":2019,"description":"Niacin improves organ function and survival following hemorrhagic shock. Rats and mice where bled 60% of their blood volume, and replaced with Ringers lactate solution to induce hemorrhagic shock ( deprive tissue of oxygen and blood ). After 10 minutes of shock the animals where split into 3 groups and injected with nicotinic acid, NMN or DMSO, at 3 levels of dosing. Niacin at 10mg/kg, which was the highest dose given, had by far the best level of survivability. Rats, given NMN even at a 5x higher dose than niacin at 50mg/kg did not achieve a survival rate to the level observed in the 10mg/kg or the even 5mg/kg treated mice. Use of GPR109A knockout mice confirmed that the niacin GPR109A receptor plays a major role in the survivability enhancing effect of niacin.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"intravenous","dose_reported":"10mg/kg highest dose","dose_mg_kg":10,"dose_absolute_mg":null,"dose_human_equiv_g":0.121,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"sepsis","name":"sepsis"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":23,"slug":"deficient-butyrate-producing-capacity-in-the-gut-microbiome-of-myalgic-encephalomyelitis-chronic-fatigue-syndrome-patients-is-associated-with-fatigue-symptoms","title":"Deficient butyrate-producing capacity in the gut microbiome of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients is associated with fatigue symptoms","seo_title":"Chronic Fatigue Syndrome Linked to Low Butyrate-Producing Gut Bacteria","publication_title":"Deficient butyrate-producing capacity in the gut microbiome of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients is associated with fatigue symptoms","publication_url":"https://www.medrxiv.org/content/10.1101/2021.10.27.21265575v1","pmid":null,"date":"2021-11-23","publication_year":2021,"description":"People with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome have a deficit in the butyrate-producing capacity of the gut microbiome. The relationships observed among symptom severity and gut microbiome disturbances suggests a causal linkage and support research into interventions that boost butyrate production.","body_markdown":null,"study_type":"cohort","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"butyrate","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"butyrate","name":"butyrate"}],"conditions":[{"slug":"me-cfs","name":"ME-CFS"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":24,"slug":"dietary-niacin-intake-predicts-the-decrease-of-liver-fat-content-during-a-lifestyle-intervention","title":"Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention","seo_title":"Higher Dietary Niacin Intake Predicts Greater Liver Fat Loss During Lifestyle Intervention","publication_title":"Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention","publication_url":"https://www.nature.com/articles/s41598-018-38002-7","pmid":null,"date":"2023-11-30","publication_year":2019,"description":"In 58 patients with fatty liver disease, the ones with the most niacin in their diet had the most favorable outcome, with a 37% reduction in liver fat after 9 months of lifestyle interventions, vs only 10% reduction in the patients eating the least niacin.","body_markdown":null,"study_type":"cohort","model":"human","sample_size":58,"duration":"9 months","blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"liver","name":"liver"},{"slug":"obesity","name":"obesity"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":25,"slug":"dietary-nicotinic-acid-supplementation-improves-hepatic-zinc-uptake-and-offers-hepatoprotection-against-oxidative-damage","title":"Dietary nicotinic acid supplementation improves hepatic zinc uptake and offers hepatoprotection against oxidative damage","seo_title":"Nicotinic Acid Improves Liver Zinc Uptake and Protects Against Oxidative Damage","publication_title":"Dietary nicotinic acid supplementation improves hepatic zinc uptake and offers hepatoprotection against oxidative damage","publication_url":"https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/dietary-nicotinic-acid-supplementation-improves-hepatic-zinc-uptake-and-offers-hepatoprotection-against-oxidative-damage/9D74C9569F29C909991AF47C7AFCE810","pmid":null,"date":"2023-09-08","publication_year":2013,"description":"In rats, supplementing with high levels of nicotinic acid in diet before experiencing cell damage (induced by tert-butyl hydroperoxide injections) helped protect the liver, preserving its normal structure and improving its ability to absorb zinc, a beneficial element. This effect was less pronounced if the NA was increased after the cell damage had occurred. Rats with a deficiency of nicotinic acid in their diet exhibited the highest level of liver damage.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadph","name":"NADPH"}],"conditions":[{"slug":"liver","name":"liver"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":26,"slug":"dyssebacia-an-early-cutaneous-marker-of-niacin-deficiency","title":"Dyssebacia: An Early Cutaneous Marker of Niacin Deficiency","seo_title":"Dyssebacia: Oily Skin Patches as an Early Warning Sign of Niacin Deficiency","publication_title":"Dyssebacia: An Early Cutaneous Marker of Niacin Deficiency","publication_url":"https://ijmds.org/index.php/ijmds/article/view/410","pmid":null,"date":"2023-03-26","publication_year":2014,"description":"Dyssebacia ( reddening, greasy, flaky scales often around nose and mouth ) is a sign of niacin deficiency.","body_markdown":null,"study_type":"case-report","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"neutral","effect_size":null,"mechanisms":[],"conditions":[{"slug":"dermatitis","name":"dermatitis"},{"slug":"pellagra","name":"pellagra"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":27,"slug":"effect-of-different-levels-of-niacin-on-serum-biochemical-parameters-antioxidant-status-cytokine-levels-inflammatory-gene-expression-and-colonic-microbial-composition-in-weaned-piglets","title":"Effect of Different Levels of Niacin on Serum Biochemical Parameters, Antioxidant Status, Cytokine Levels, Inflammatory Gene Expression and Colonic Microbial Composition in Weaned Piglets","seo_title":"How Niacin Dose Shapes Gut Microbiome and Inflammation Markers","publication_title":"https://www.mdpi.com/2076-2615/12/21/3018","publication_url":"https://www.mdpi.com/2076-2615/12/21/3018","pmid":null,"date":"2022-11-27","publication_year":2022,"description":"Piglets separated from their mother in agriculture tend to struggle health wise. Supplementing their diet with niacin significantly improves their survivability via factors like improved colonic microbial diversity, intestinal health, reduced intestinal inflammation and improved overall immunity.","body_markdown":null,"study_type":"animal","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nf-kb","name":"NF-kB"},{"slug":"il-10","name":"IL-10"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"},{"slug":"butyrate","name":"butyrate"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"colitis","name":"colitis"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"},{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":28,"slug":"effect-of-huntingtons-and-alzheimers-diseases-on-the-transport-of-nicotinic-acid-or-nicotinamide-across-the-human-blood-brain-barrier","title":"Effect of Huntington's and Alzheimer's diseases on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier","seo_title":"Alzheimer's and Huntington's Reduce Niacin Transport Across the Blood-Brain Barrier","publication_title":"Effect of Huntington's and Alzheimer's diseases on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier","publication_url":"https://pubmed.ncbi.nlm.nih.gov/1837697/","pmid":"1837697","date":"2021-10-23","publication_year":1991,"description":"Looked into how niacin and nicotinamide cross blood brain barrier in control, Huntington & Alzheimer patients. Nicotinamide had higher uptake in brain tissue than niacin. No statistical difference in concentrations across the groups. It was observed that niacin and nicotinamide concentrated in red blood cells vs plasma over time.","body_markdown":null,"study_type":"mechanistic","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"neutral","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"alzheimers","name":"alzheimers"},{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":29,"slug":"effect-of-nicotinic-acid-on-zinc-and-iron-metabolism","title":"Effect of nicotinic acid on zinc and iron metabolism","seo_title":"Niacin's Effect on Zinc and Iron Absorption and Metabolism","publication_title":"Effect of nicotinic acid on zinc and iron metabolism","publication_url":"https://pubmed.ncbi.nlm.nih.gov/9353874/","pmid":"9353874","date":"2021-09-10","publication_year":1997,"description":"Mice fed 3x the Niacin of a standard mouse diet increased zinc absorption by 70.9%, they also seemed to have more protein mass and denser skeletons.","body_markdown":"tbd","study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":30,"slug":"effect-of-pharmacological-doses-of-niacin-on-testicular-structure-and-function-in-normal-and-diabetic-rats","title":"Effect of pharmacological doses of niacin on testicular structure and function in normal and diabetic rats","seo_title":"Niacin Protects Testicular Function in Diabetic Rats at Pharmacological Doses","publication_title":"Effect of pharmacological doses of niacin on testicular structure and function in normal and diabetic rats","publication_url":"https://pubmed.ncbi.nlm.nih.gov/30191583/","pmid":"30191583","date":"2022-12-21","publication_year":2018,"description":"Feeding normal and diabetic rats 800mg of niacin per kg of diet increased testicular weight in all rats and decreased testicular MDA (a biomarker for cancer). Normal rats, but not diabetic ones, also had an increase in sperm count and serum testosterone.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":800,"dose_absolute_mg":null,"dose_human_equiv_g":9.68,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadph","name":"NADPH"}],"conditions":[{"slug":"fertility","name":"fertility"},{"slug":"diabetes","name":"diabetes"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":31,"slug":"effectiveness-of-niacin-supplementation-for-patients-with-type-2-diabetes-a-meta-analysis-of-randomized-controlled-trials","title":"Effectiveness of niacin supplementation for patients with type 2 diabetes:  A meta-analysis of randomized controlled trials","seo_title":"Niacin and Type 2 Diabetes: What Clinical Trial Meta-Analyses Show","publication_title":"Effectiveness of niacin supplementation for patients with type 2 diabetes: A meta-analysis of randomized controlled trials","publication_url":"https://journals.lww.com/md-journal/fulltext/2020/07170/effectiveness_of_niacin_supplementation_for.94.aspx","pmid":null,"date":"2023-05-14","publication_year":2020,"description":"Review of many clinical trials concludes niacin supplementation can improve lipid profiles without affecting the glycemic levels for patients with Type 2 diabetes.","body_markdown":null,"study_type":"meta-analysis","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"gpr109a","name":"GPR109A"}],"conditions":[{"slug":"diabetes","name":"diabetes"},{"slug":"dyslipidemia","name":"dyslipidemia"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":32,"slug":"effects-of-an-oral-mixture-containing-glycine-glutamine-and-niacin-on-memory-gh-and-igf-i-secretion-in-middle-aged-and-elderly-subjects","title":"Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects","seo_title":"Glycine + Niacin Combination: Growth Hormone Up 70%, Memory Unchanged","publication_title":"Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects","publication_url":"https://pubmed.ncbi.nlm.nih.gov/14609312/","pmid":"14609312","date":"2022-01-12","publication_year":2003,"description":"A clinical trial found that 10g/day of glycine, glutamine, and niacin raised growth hormone by 70% in middle-aged and elderly adults over 3 weeks. GH increased because niacin suppresses the free fatty acids that inhibit GH release. Despite the GH rise, IGF-I and memory scores did not change — the GH signal did not translate downstream.","body_markdown":"## Overview\n\nThis 2003 clinical trial (Arwert et al., *Journal of Nutritional Biochemistry*) tested whether an oral mixture of glycine, glutamine, and niacin could raise growth hormone (GH) levels and improve cognitive function in middle-aged and elderly adults. The three-component combination was chosen because each ingredient has independently been reported to stimulate GH secretion through distinct mechanisms.\n\n42 healthy participants aged 40–75 received 10 grams of the mixture daily for three weeks. The primary outcomes were serum GH, IGF-I, and performance on standardized memory and mood assessments.\n\n## Key Findings\n\n**Growth hormone increased by roughly 70%.** This is a meaningful effect. GH secretion declines sharply with age; interventions that restore even partial GH output are of significant interest in aging research. The effect appeared to hold across the age range studied.\n\n**IGF-I did not change.** IGF-1 is the downstream mediator of most of GH's anabolic and neurological effects — it is the signal that GH triggers the liver to produce. The absence of IGF-I change is the study's central finding to explain. Possible reasons include: the three-week window was insufficient for hepatic adaptation; baseline IGF-I levels were already at a ceiling; or the GH pulses generated were too brief to sustain hepatic IGF-I synthesis.\n\n**No improvement in memory or mood.** Cognitive and psychological outcomes showed no statistically significant changes. The authors attribute this to the absent IGF-I response: since IGF-I appears to mediate GH's neurological benefits, a GH increase without downstream IGF-I elevation may not translate to functional brain effects.\n\n## Why Glycine, Glutamine, and Niacin?\n\nEach component targets a different node in the GH-regulatory axis:\n\n**Glycine** is an inhibitory neurotransmitter that may modulate hypothalamic GH-releasing hormone (GHRH) signaling. It is also studied for improving slow-wave sleep quality — significant because the body's largest GH pulse occurs during deep sleep.\n\n**Glutamine** is the most abundant amino acid in circulation and a precursor for several neurotransmitters. Some studies report it stimulates GH secretion, possibly by influencing hypothalamic pH or GHRH release.\n\n**Niacin** (nicotinic acid) suppresses circulating free fatty acids (FFAs). FFAs are established inhibitors of GH secretion — they exert negative feedback on GH pulses. By activating GPR109A in adipocytes and acutely reducing lipolysis, niacin lowers the FFA brake on GH release. This is the clearest and most mechanistically supported component of the combination.\n\nTogether, the three ingredients address multiple points in GH regulation simultaneously rather than relying on a single pathway.\n\n## Limitations\n\nThe trial was small (42 subjects), open-label (no placebo arm), and short (three weeks). Without a control group, the GH increase cannot be definitively attributed to the mixture rather than regression to the mean or expectation effects. The lack of IGF-I and cognitive response substantially limits the practical interpretation of the GH finding.\n\n## Relevance to Niacin Research\n\nFor researchers focused on niacin specifically, this study documents niacin's ability to modulate GH secretion through FFA suppression — an indirect but mechanistically coherent pathway. Niacin's inhibition of adipose lipolysis (the mechanism behind both the flushing response and the lipid-modifying effects) is sufficient to meaningfully reduce the FFA signal that inhibits GH release.\n\nThe GH-without-IGF-I finding also adds nuance to discussions of GH optimization: raising GH alone may not be sufficient to produce the downstream benefits (lean mass, cognitive function, recovery) that researchers associate with GH. The GH–IGF-I axis functions as a unit. Interventions that raise GH without moving IGF-I may be acting too far upstream, or too briefly, to generate the physiological effects of interest.","study_type":"rct","model":"human","sample_size":42,"duration":"3 weeks","blinded":null,"intervention":"combination","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"mixed","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"}],"conditions":[{"slug":"aging","name":"aging"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":33,"slug":"effects-of-dietary-nicotinic-acid-supplementation-on-meat-quality-carcass-characteristics-lipid-metabolism-and-tibia-parameters-of-wulong-geese","title":"Effects of dietary nicotinic acid supplementation on meat quality, carcass characteristics, lipid metabolism, and tibia parameters of Wulong geese","seo_title":"Niacin Supplementation Improves Lipid Metabolism and Meat Quality","publication_title":"Effects of dietary nicotinic acid supplementation on meat quality, carcass characteristics, lipid metabolism, and tibia parameters of Wulong geese","publication_url":"https://www.sciencedirect.com/science/article/pii/S0032579121004533","pmid":null,"date":"2023-12-12","publication_year":2021,"description":"Feeding geese nicotnic acid improves muscle & fat tone, bone density, lipid metabolism. 80mg/kg per day was found to be optimal dose for improving quality of geese tibia ( longest bone in leg ).","body_markdown":null,"study_type":"animal","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":80,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"dyslipidemia","name":"dyslipidemia"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":34,"slug":"effects-of-melatonin-supplementation-on-insulin-levels-and-insulin-resistance-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials","title":"Effects of Melatonin Supplementation on Insulin Levels and Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","seo_title":"Melatonin and Insulin Resistance: Meta-Analysis Shows Reduced Fasting Insulin","publication_title":"Effects of Melatonin Supplementation on Insulin Levels and Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","publication_url":"https://pubmed.ncbi.nlm.nih.gov/34496412/","pmid":"34496412","date":"2021-09-15","publication_year":2021,"description":"Studies show that melatonin ameliorates hyperinsulinemia, insulin resistance, and insulin sensitivity.","body_markdown":null,"study_type":"meta-analysis","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[],"conditions":[{"slug":"insulin-resistance","name":"insulin-resistance"},{"slug":"diabetes","name":"diabetes"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":35,"slug":"effects-of-niacin-and-vitamin-c-on-blood-sugar","title":"Effects of Niacin and Vitamin C on Blood Sugar","seo_title":"Niacin and Vitamin C Effects on Blood Sugar: What the Research Shows","publication_title":"Effects of Niacin and Vitamin C on Blood Sugar","publication_url":"https://doi.org/10.1152/ajplegacy.1958.192.3.511","pmid":null,"date":"2023-05-14","publication_year":1958,"description":"Rats in group 1 received no treatment. Rats in group 2 received daily 100 mg/kg body weight niacin injections. Rats in group 3 received daily 50 mg/kg body weight vitamin C injections. Rats in group 4 received both niacin and vitamin C injections.\n\nBlood sugar levels were measured before and after treatment. The results showed that niacin and vitamin C both lowered blood sugar levels in normal rats. Niacin was more effective than vitamin C in lowering blood sugar levels in diabetic rats. The combination of niacin and vitamin C was the most effective in lowering blood sugar levels in diabetic rats.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"intraperitoneal","dose_reported":null,"dose_mg_kg":100,"dose_absolute_mg":null,"dose_human_equiv_g":1.21,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"diabetes","name":"diabetes"},{"slug":"insulin-resistance","name":"insulin-resistance"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":36,"slug":"emerging-roles-of-gpr109a-in-regulation-of-neuroinflammation-in-neurological-diseases-and-pain","title":"Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain","seo_title":"GPR109A in Neurological Disease: Anti-Inflammatory Roles in the Brain and Pain","publication_title":"Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain","publication_url":"https://journals.lww.com/nrronline/Fulltext/2023/04000/Emerging_roles_of_GPR109A_in_regulation_of.10.aspx","pmid":null,"date":"2023-03-17","publication_year":2023,"description":"Summary of GPR109A (niacin receptor) role in inflammation of the nervous system, especially the brain, and how activation of GPR109A plays a role in healing may conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and pathological pain.","body_markdown":null,"study_type":"review","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"},{"slug":"macrophage","name":"macrophage"},{"slug":"prostaglandin","name":"prostaglandin"},{"slug":"pgd2","name":"PGD2"}],"conditions":[{"slug":"neuroinflammation","name":"neuroinflammation"},{"slug":"alzheimers","name":"alzheimers"},{"slug":"parkinsons","name":"parkinsons"},{"slug":"multiple-sclerosis","name":"multiple-sclerosis"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":37,"slug":"fifteen-year-mortality-in-coronary-drug-project-patients-long-term-benefit-with-niacin","title":"Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin","seo_title":"15-Year Follow-Up: Niacin Reduces Long-Term Heart Disease Mortality","publication_title":"Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin","publication_url":"https://pubmed.ncbi.nlm.nih.gov/3782631/","pmid":"3782631","date":"2021-09-14","publication_year":1986,"description":"9 years after the conclusion of a long term study on various drugs to reduce risk of death of people who had a heart attack, only the niacin group showed a statistically significant, 11% reduction in mortality than in the placebo group. This was after they stopped taking the niacin 9 years earlier, indicating a long term benefit.","body_markdown":null,"study_type":"rct","model":"human","sample_size":8341,"duration":"15 years","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":3000,"dose_human_equiv_g":3,"outcome":"positive","effect_size":"11% mortality reduction","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"gpr109a","name":"GPR109A"}],"conditions":[{"slug":"atherosclerosis","name":"atherosclerosis"},{"slug":"dyslipidemia","name":"dyslipidemia"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"},{"slug":"why-not-mainstream","title":"Why Your Doctor Doesn't Know About This"}]},{"id":38,"slug":"gut-dysbiosis-dysregulates-central-and-systemic-homeostasis-via-decreased-melatonin-andsuboptimal-mitochondria-functioning-pathoetiological-and-pathophysiological-implications","title":"Gut dysbiosis dysregulates central and systemic homeostasis via decreased melatonin and suboptimal mitochondria functioning: pathoetiological and pathophysiological implications.","seo_title":"Gut Dysbiosis Lowers Melatonin and Impairs Mitochondria Throughout the Body","publication_title":"http://www.melatonin-research.net/index.php/MR/article/view/30/266","publication_url":"http://www.melatonin-research.net/index.php/MR/article/view/30/266","pmid":null,"date":"2021-10-26","publication_year":2019,"description":"In depth review of how deficiency of butyrate and melatonin compromise gut and overall mitochondrial function and lead to lower levels of other key molecules in cellular metabolism like sirtuins, PGC-1α and NAD+.","body_markdown":null,"study_type":"review","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"neutral","effect_size":null,"mechanisms":[{"slug":"butyrate","name":"butyrate"},{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"},{"slug":"atp","name":"ATP"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":39,"slug":"notes-gut-melatonin-a-potent-candidate-in-the-diversified-journey-of-melatonin-research","title":"Gut melatonin: A potent candidate in the diversified journey of melatonin research","seo_title":"Gut Melatonin: How the Gut Produces Melatonin Independent of Light","publication_title":"Gut melatonin: A potent candidate in the diversified journey of melatonin research","publication_url":"https://www.sciencedirect.com/science/article/pii/S0016648020304469","pmid":null,"date":"2021-09-02","publication_year":2020,"description":"This paper investigates the production melatonin in the gut, notably it being unrelated to the day/light cycle and how eating patterns affect its production, and what the produced melatonin may be used for.","body_markdown":"**Key takeaways**\n\n - The Gut is one of the leading sources of melatonin production in the body\n - Light has now impact on amount of melatonin produced in the gut\n - Increasing Tryptophan intake increases production\n - L-Tryptophan => Serotonin => Melatonin\n - Once produced, it stays in gut or enters circulation\n - In gut melatonin has paracrine, autocrine or luminal actions\n\n   **Paracrine**: a cell targets a nearby cell \\\n   **Autocrine**: a cell targets itself, releasing a signal that can bind to receptors on its own surface.\\\n   **Luminal**: acting on interior of cell\n - In circulation melatonin has endocrine action\n\n   **Endocrine**: the hormone is distributed in blood and binds to distant target cells","study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"tryptophan","name":"tryptophan"},{"slug":"melatonin","name":"melatonin"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":40,"slug":"high-dietary-niacin-intake-is-associated-with-decreased-chromosome-translocation-frequency-in-airline-pilots","title":"High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots","seo_title":"High Niacin Intake Reduces Radiation-Induced DNA Damage in Airline Pilots","publication_title":"High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots","publication_url":"https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/high-dietary-niacin-intake-is-associated-with-decreased-chromosome-translocation-frequency-in-airline-pilots/D69D0AB9C39BFFC04B5BB55A67BFFDFC","pmid":null,"date":"2021-09-18","publication_year":2008,"description":"Statistical analysis of 82 airline pilots showed a 42 % decrease in the frequency of chromosome translocations (ie DNA damage from higher rates of ionizing radiation while flying) for those with high compared with low dietary niacin.","body_markdown":null,"study_type":"cohort","model":"human","sample_size":82,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"42% decrease in chromosome translocations","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":41,"slug":"impact-of-nuclear-de-novo-nad-synthesis-via-histone-dynamics-on-dna-repair-during-cellular-senescence-to-prevent-tumorigenesis","title":"Impact of Nuclear De Novo NAD+ Synthesis via Histone Dynamics on DNA Repair during Cellular Senescence To Prevent Tumorigenesis","seo_title":"Nuclear NAD+ Synthesis Powers DNA Repair and Prevents Tumor Formation","publication_title":"Impact of Nuclear De Novo NAD+ Synthesis via Histone Dynamics on DNA Repair during Cellular Senescence To Prevent Tumorigenesis","publication_url":"https://pubmed.ncbi.nlm.nih.gov/36278823/","pmid":"36278823","date":"2022-11-27","publication_year":2022,"description":"The de novo production of NAD+ in the cell nucleus is central to the DNA repair capacity of aging cells and thus against preventing tumors.","body_markdown":null,"study_type":"mechanistic","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"sirt1","name":"SIRT1"},{"slug":"dna-repair","name":"DNA-repair"},{"slug":"hdac","name":"HDAC"},{"slug":"p53","name":"p53"}],"conditions":[{"slug":"cancer","name":"cancer"},{"slug":"aging","name":"aging"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":42,"slug":"inflammation-stimulates-niacin-receptor-gpr109a-hca2-expression-in-adipose-tissue-and-macrophages","title":"Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages","seo_title":"Inflammation Upregulates GPR109A/HCA2 Niacin Receptor in Fat Tissue and Immune Cells","publication_title":"Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242443/","pmid":null,"date":"2022-06-18","publication_year":2014,"description":"Many of the beneficial and adverse effects of niacin are mediated via GPR109, which is highly expressed in adipose tissue and macrophages. Multiple infectious and inflammatory stimuli stimulate GPR109A expression in adipose tissue and in macrophages.","body_markdown":null,"study_type":"mechanistic","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"macrophage","name":"macrophage"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":43,"slug":"intestinal-flora-as-a-potential-strategy-to-fight-sars-cov-2-infection","title":"Intestinal Flora as a Potential Strategy to Fight SARS-CoV-2 Infection","seo_title":"Could Gut Microbiome Health Help Fight COVID-19 Infection?","publication_title":"Intestinal Flora as a Potential Strategy to Fight SARS-CoV-2 Infection","publication_url":"https://www.frontiersin.org/articles/10.3389/fmicb.2020.01388/full","pmid":null,"date":"2021-11-23","publication_year":2020,"description":"Many microbial metabolites, especially butyrate, found in the intestinal flora, are extremely important in regulating systemic and pulmonary immune and inflammatory responses and have a wide range of anti-inflammatory and immunity enhancing functions. Improving intestinal micro-ecology via like butyrate supplementation may partially mediate the effects of SARS-CoV-2 on the both local gastrointestinal response and systemic immune response of the host, and thus be a target for COVID-19 prevention and treatment.","body_markdown":null,"study_type":"review","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"butyrate","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"butyrate","name":"butyrate"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"il-10","name":"IL-10"},{"slug":"t-cell","name":"T-cell"},{"slug":"treg","name":"Treg"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":44,"slug":"intravenous-niacin-acutely-improves-the-efficiency-of-dietary-fat-storage-in-lean-and-obese-humans","title":"Intravenous Niacin Acutely Improves the Efficiency of Dietary Fat Storage in Lean and Obese Humans","seo_title":"IV Niacin Changes How the Body Stores Dietary Fat in Lean and Obese People","publication_title":"Intravenous Niacin Acutely Improves the Efficiency of Dietary Fat Storage in Lean and Obese Humans","publication_url":"https://diabetesjournals.org/diabetes/article/61/12/3172/33779/Intravenous-Niacin-Acutely-Improves-the-Efficiency","pmid":null,"date":"2023-05-14","publication_year":2012,"description":"24 healthy men and women with a mean age of 35 years, where injected Intravenously w/ 1g of niacin or placebo for 2 weeks. The niacin group ended up with acutely lower levels of FFAs (free fatty acids, fats floating around in the bloodstream) and significantly higher levels of triglyceride stored in visceral adipose tissue. This may help to reduce the amount of fat that is stored in the liver and other organs, which can help to improve insulin sensitivity and reduce the risk of metabolic complications. IE niacin may help people with diabetes and obesity to lose weight and improve their health.","body_markdown":null,"study_type":"rct","model":"human","sample_size":24,"duration":"2 weeks","blinded":null,"intervention":"nicotinic-acid","route":"intravenous","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":1000,"dose_human_equiv_g":1,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"adiponectin","name":"adiponectin"}],"conditions":[{"slug":"obesity","name":"obesity"},{"slug":"insulin-resistance","name":"insulin-resistance"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":45,"slug":"iron-deficiency-reduces-the-efficacy-of-tryptophan-as-a-niacin-precursor","title":"Iron deficiency reduces the efficacy of tryptophan as a niacin precursor","seo_title":"Iron Deficiency Blocks Tryptophan-to-Niacin Conversion in the Body","publication_title":"Iron deficiency reduces the efficacy of tryptophan as a niacin precursor","publication_url":"https://pubmed.ncbi.nlm.nih.gov/8120664/","pmid":"8120664","date":"2023-09-08","publication_year":1994,"description":"Iron deficiency impairs body converting tryptophan to niacin. Chicks fed the iron-deficient diets had markedly lower hemoglobin concentrations than those fed the iron-adequate diets. Regardless of iron level, chicks had linear growth responses to either nicotinic acid or tryptophan supplementation. Low bio-available iron contributes to niacin deficiency in populations.","body_markdown":null,"study_type":"animal","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"tryptophan","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"pellagra","name":"pellagra"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":46,"slug":"leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice","title":"Leucine-nicotinic acid synergy stimulates AMPK/Sirt1 signaling and regulates lipid metabolism and lifespan in Caenorhabditis elegans, and hyperlipidemia and atherosclerosis in mice","seo_title":"Leucine and Niacin Synergy Activates AMPK and SIRT1 to Regulate Fat Metabolism","publication_title":"Leucine-nicotinic acid synergy stimulates AMPK/Sirt1 signaling and regulates lipid metabolism and lifespan in Caenorhabditis elegans, and hyperlipidemia and atherosclerosis in mice","publication_url":"https://europepmc.org/article/PMC/PMC5435603","pmid":null,"date":"2022-06-18","publication_year":2017,"description":"Low dose niacin (50 mg/kg diet and 250 mg/kg diet) when supplemented in combination with leucine (24 g/kg diet) has a similar effect on lowering cholesterol in mice than standard therapeutic dose (1000 mg/kg diet) of niacin without leucine supplementation. Leucine amplifies niacin effect on lipid metabolism, hyperlipidemia and atherosclerosis in mice, at least in part by activation of the AMPK/Sirt1 axis.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":"50 mg/kg diet (low), 250 mg/kg diet (mid), 1000 mg/kg diet (high)","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Low-dose niacin + leucine comparable to standard therapeutic dose niacin alone","mechanisms":[{"slug":"ampk","name":"AMPK"},{"slug":"sirt1","name":"SIRT1"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"dyslipidemia","name":"dyslipidemia"},{"slug":"atherosclerosis","name":"atherosclerosis"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":47,"slug":"low-nad-levels-are-associated-with-a-decline-of-spermatogenesis-in-transgenic-andy-and-aging-mice","title":"Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice","seo_title":"Low NAD+ Linked to Reduced Sperm Production in Aging Mice","publication_title":"Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice","publication_url":"https://www.frontiersin.org/articles/10.3389/fendo.2022.896356/full","pmid":null,"date":"2023-05-14","publication_year":2022,"description":"A study in mice found that niacin supplementation increased NAD+ levels in the testes, which led to an improvement in sperm count and sperm motility.  NAD+ deficient mice have ~30% smaller testes (balls) than the control mice (~1.5g vs ~2.17g). NAD+ is essential for spermatogenesis and that NAD+ deficiency leads to male infertility.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"NAD+ deficient mice have ~30% smaller testes than controls (~1.5g vs ~2.17g)","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"}],"conditions":[{"slug":"fertility","name":"fertility"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":48,"slug":"melatonin-alleviates-titanium-nanoparticles-induced-osteolysis-via-activation-of-butyrate-gpr109a-signaling-pathway","title":"Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway","seo_title":"Melatonin Protects Bone From Implant Particle Damage via GPR109A","publication_title":"Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway","publication_url":"https://pubmed.ncbi.nlm.nih.gov/34092246/","pmid":"34092246","date":"2021-09-13","publication_year":2021,"description":"Supplementing mice with melatonin increases butyrate production in their gut via bacteria, conversely antibiotics severely impair this butyrate production. When mice are poisoned with titanium nanoparticles to induce bone deterioration, butyrate has a protective effect against bone loss. This protective effect is specifically dependent on the GPR109A receptor that seems to be activated by the butyrate enriched gut microbiota.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"butyrate","name":"butyrate"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":49,"slug":"melatonin-as-a-master-regulator-of-cell-death-and-inflammation-molecular-mechanisms-and-clinical-implications-for-newborn-care","title":"Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care","seo_title":"Melatonin as a Master Regulator of Inflammation and Cell Death in Newborns","publication_title":"Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care","publication_url":"https://www.nature.com/articles/s41419-019-1556-7","pmid":null,"date":"2021-09-15","publication_year":2019,"description":"Supplementing melatonin is safe. Melatonin is a potent anti-oxidant and anti-inflammatory agent, it's found in all cells and can easily cross all physiological barriers in body. Melatonin levels decreases with age. Melatonin therapy looks promising for a wide range of health issues in newborn babies.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nf-kb","name":"NF-kB"},{"slug":"apoptosis","name":"apoptosis"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":50,"slug":"melatonin-in-mitochondria-mitigating-clear-and-present-dangers","title":"Melatonin in Mitochondria: Mitigating Clear and Present Dangers","seo_title":"Melatonin in Mitochondria: How It Protects Cells from Oxidative Damage","publication_title":"Melatonin in Mitochondria: Mitigating Clear and Present Dangers","publication_url":"https://journals.physiology.org/doi/full/10.1152/physiol.00034.2019","pmid":null,"date":"2021-09-15","publication_year":2020,"description":"It's inferred that the majority of melatonin is created inside the mitochondria, independent of the pineal daylight associated melatonin. Melatonin has a 3 billion year history of use inside cells as a highly efficient anti-oxidant. It functions as an anti-oxidant for both plants and animals. It stimulates synthesis of other antioxidants like glutathione. It's the \"swiss army knife\" of anti-oxidants and uniquely positioned as the \"fox in the hen house\" inside the mitochondria where many free radicals originate. Melatonin reverses the Warburg effect and aids in arresting cancer cell growth.","body_markdown":null,"study_type":"review","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadh","name":"NADH"},{"slug":"atp","name":"ATP"}],"conditions":[{"slug":"cancer","name":"cancer"},{"slug":"inflammation","name":"inflammation"},{"slug":"aging","name":"aging"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":51,"slug":"melatonin-protects-human-red-blood-cells-from-oxidative-hemolysis-new-insights-into-the-radical-scavenging-activity","title":"Melatonin protects human red blood cells from oxidative hemolysis: new insights into the radical-scavenging activity","seo_title":"Melatonin Shields Red Blood Cells From Oxidative Destruction","publication_title":"Melatonin protects human red blood cells from oxidative hemolysis: new insights into the radical-scavenging activity","publication_url":"https://pubmed.ncbi.nlm.nih.gov/10496145/","pmid":"10496145","date":"2021-09-18","publication_year":1999,"description":"Red blood cells exposed to oxidative stress will consume melatonin and use it for protect against deterioration.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nadph","name":"NADPH"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":52,"slug":"melatonin-supplementation-ameliorates-myocardial-connexin-43-disorders-and-arrhythmia-risk-of-hypertensive-and-obese-rats","title":"Melatonin supplementation ameliorates myocardial connexin-43 disorders and arrhythmia risk of hypertensive and obese rats","seo_title":"Melatonin Reduces Arrhythmia Risk in Hypertensive and Obese Animal Models","publication_title":"Melatonin supplementation ameliorates myocardial connexin-43 disorders and arrhythmia risk of hypertensive and obese rats","publication_url":"https://academic.oup.com/eurheartj/article/39/suppl_1/ehy566.P5704/5082649","pmid":"5082649","date":"2021-10-24","publication_year":2018,"description":"Melatonin supplementation benefits male hypertensive and female obese rats due to suppression of metabolic disorders and lethal arrhythmia risk. Arrhythmia is a problem with the rate or rhythm of your heartbeat. Protection against arrhythmia may attributed, at least in part, to up-regulation of myocardial Cx43, which is a protein that is essential for the formation of heart structures.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"obesity","name":"obesity"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":53,"slug":"melatonin-treats-h-pylori-and-gastric-ulcers","title":"Melatonin Treats H Pylori and Gastric Ulcers","seo_title":"Melatonin Treats H. pylori Infection and Gastric Ulcers in Multiple Studies","publication_title":"Melatonin Treats H Pylori and Gastric Ulcers","publication_url":"https://www.naturalmedicinejournal.com/journal/2014-09/melatonin-treats-h-pylori-and-gastric-ulcers","pmid":null,"date":"2021-09-19","publication_year":2014,"description":"In various studies where patients are treated for gastric ulcers, those on melatonin did better.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"cox-2","name":"COX-2"},{"slug":"prostaglandin","name":"prostaglandin"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":54,"slug":"melatonin-regulation-of-biomolecular-condensates-in-neurodegenerative-disorders","title":"Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders","seo_title":"Melatonin and Neurodegenerative Disorders: Protein Condensate Regulation","publication_title":"Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders","publication_url":"https://www.mdpi.com/2076-3921/10/9/1483/htm","pmid":null,"date":"2021-09-18","publication_year":2021,"description":"Melatonin plays a key role in intracellular membrane integrity, especially when a cell is in under stress. Melatonin plays role in maintaining a high ATP:ADP ratio, which suppresses glycolysis. Supplemental melatonin shown to accumulate in all cells, accumulates 10x in membrane compared to mitochondria. Plays unique role in fat/water interfaces, as it can combine with both. Biomolecular condensates play a big role in brain disorders and are shaped by complex relationships between membraneless organelles, membranes/lipid rafts, ATP, RNA, and most of all, stress. Melatonin's intimate association with each of these decisive influencers may position it as an important mediator of sorting out of these condensates in health and disease via ATP-dependent mechanisms.","body_markdown":null,"study_type":"review","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Supplemental melatonin accumulates 10x in membrane compared to mitochondria","mechanisms":[{"slug":"atp","name":"ATP"}],"conditions":[{"slug":"alzheimers","name":"alzheimers"},{"slug":"parkinsons","name":"parkinsons"},{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":55,"slug":"nad-deficiency-congenital-malformations-and-niacin-supplementation","title":"NAD Deficiency, Congenital Malformations, and Niacin Supplementation","seo_title":"NAD+ Deficiency Causes Birth Defects — Niacin May Prevent Them","publication_title":"NAD Deficiency, Congenital Malformations, and Niacin Supplementation","publication_url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1616361","pmid":null,"date":"2021-09-14","publication_year":2017,"description":"Disruption of NAD synthesis caused a deficiency of NAD and birth defects in humans and mice. Niacin supplementation during pregnancy prevented the birth defects in mice.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Niacin supplementation prevented birth defects in NAD-deficient mice","mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"fertility","name":"fertility"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":56,"slug":"nad-homeostasis-in-human-health-and-disease","title":"NAD+ homeostasis in human health and disease","seo_title":"NAD+ Deficiency and Disease: How Niacin Restores NAD+ Levels","publication_title":"NAD+ homeostasis in human health and disease","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261484/","pmid":null,"date":"2022-11-27","publication_year":2021,"description":"In depth review of NAD+, how its made in the human body, how it becomes deficient, and how its deficiency is a causal factor of a wide range of diseases. And how boosting NAD+ via enhancing agents like niacin ( especially niacin since it is the primary, so called Preiss-Handler pathway of manufacture ) can help cure a wide range of diseases.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadh","name":"NADH"},{"slug":"sirt1","name":"SIRT1"},{"slug":"parp","name":"PARP"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"ampk","name":"AMPK"}],"conditions":[{"slug":"aging","name":"aging"},{"slug":"cancer","name":"cancer"},{"slug":"neuroinflammation","name":"neuroinflammation"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":57,"slug":"nad-repletion-rescues-female-fertility-during-reproductive-aging","title":"NAD+ repletion rescues female fertility during reproductive aging","seo_title":"NAD+ Repletion Restored Fertility in Aging Mice (NMN and Niacin Study)","publication_title":"NAD+ repletion rescues female fertility during reproductive aging","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063679/","pmid":null,"date":"2022-12-21","publication_year":2020,"description":"Loss of fertility is associated with lower NAD+ levels. Restoring NAD+ in aged mice by putting nicotinamide mononucleotide (NMN) in their drinking water at 2g/L restored their fertility as well as the adverse effect of old age on the development of the embryo.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"NMN","route":"oral","dose_reported":"2g/L in drinking water","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Restored fertility in aged mice","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"}],"conditions":[{"slug":"fertility","name":"fertility"},{"slug":"aging","name":"aging"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":58,"slug":"network-pharmacology-and-bioinformatics-analyses-identify-intersection-genes-of-niacin-and-covid-19-as-potential-therapeutic-targets","title":"Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets","seo_title":"Niacin and COVID-19: Shared Gene Targets Identified as Therapeutic Candidates","publication_title":"Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets","publication_url":"https://academic.oup.com/bib/article/22/2/1279/5964187","pmid":"5964187","date":"2021-09-16","publication_year":2021,"description":"Computer modeling shows niacin a key to therapy for covid via enhancing the immune system, inhibiting inflammation and regulating cellular microenvironment.","body_markdown":"## Overview\n\nThis 2021 network pharmacology study (*Briefings in Bioinformatics*) used computational approaches to identify molecular targets shared between niacin's known pharmacological actions and COVID-19 pathophysiology. Network pharmacology combines protein-protein interaction networks, drug-target databases, and gene ontology enrichment to systematically identify mechanistic overlaps — rather than testing niacin in patients directly.\n\nThe study identified a set of intersection genes that niacin modulates and that are also implicated in COVID-19's disease mechanisms, suggesting potential therapeutic relevance.\n\n## Approach and Key Findings\n\n**Network pharmacology is a bioinformatics method**, not a clinical trial. The researchers built interaction networks for niacin's known molecular targets (from drug databases) and for COVID-19 disease genes (from literature and pathway databases), then identified the overlap. This overlap represents the molecular space where niacin could theoretically influence COVID-19 pathophysiology.\n\n**Three primary mechanisms emerged from the intersection:**\n\n1. **Immune enhancement.** Key immune-regulating genes appeared in the overlap, including genes involved in T cell activation and innate immune signaling. Niacin has documented immunomodulatory effects — both anti-inflammatory (via GPR109A on macrophages and neutrophils) and immune-supporting (via NAD+ repletion for immune cell function).\n\n2. **Inflammation inhibition.** Genes related to cytokine signaling — particularly pathways relevant to the cytokine storm mechanism in severe COVID-19 — appeared in the intersection. Niacin's activation of GPR109A suppresses NF-κB-driven pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β) in macrophages, which are central mediators of COVID-19 hyperinflammation.\n\n3. **Cellular microenvironment regulation.** The analysis identified genes involved in oxidative stress response, cellular senescence, and metabolic adaptation — all disrupted by SARS-CoV-2 infection and all influenced by NAD+ availability and niacin's effects on cellular metabolism.\n\n## Why NAD+ Connects Niacin and COVID-19\n\nCOVID-19 infection disrupts NAD+ metabolism. SARS-CoV-2 infection activates PARP enzymes (poly-ADP-ribose polymerases), which consume NAD+ as part of the cellular stress and DNA damage response. PARP hyperactivation during severe infection can deplete cellular NAD+ reserves, impairing mitochondrial function, immune cell activity, and the sirtuin-dependent epigenetic responses needed to control viral replication.\n\nA companion study in this directory (*Coronavirus infection and PARP expression dysregulate the NAD metabolome: an actionable component of innate immunity*) documents this PARP-NAD+ depletion mechanism directly in COVID-19 patients. Niacin, as the primary driver of NAD+ synthesis via the Preiss-Handler pathway, can replenish NAD+ faster than NR or NMN in some contexts, potentially restoring immune cell function during active infection.\n\n## Limitations\n\nNetwork pharmacology identifies plausible mechanisms — it does not establish clinical efficacy. Computational target identification has high false positive rates, and intersection genes may not represent actionable drug targets even when mechanistically coherent. This study should be interpreted as hypothesis-generating, identifying a molecular rationale for further clinical investigation of niacin in COVID-19, not as evidence that niacin treats COVID-19.\n\nNo randomized controlled trials specifically testing niacin for COVID-19 treatment have published definitive results as of this writing.\n\n## Relevance to the Niacin Literature\n\nFor researchers, this study matters because it situates niacin within the COVID-19 mechanism landscape using a systematic approach. The three mechanisms it identifies — immune enhancement, anti-inflammatory activity, and NAD+ repletion — are supported by mechanistic evidence from other niacin studies. The computational overlap is not surprising given niacin's documented anti-inflammatory effects via GPR109A and its role as a NAD+ precursor, but having those connections mapped against the COVID-19 disease network is useful for researchers exploring nutritional or pharmacological NAD+ support in infectious disease contexts.","study_type":"mechanistic","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"},{"slug":"nad","name":"NAD+"},{"slug":"t-cell","name":"T-cell"},{"slug":"macrophage","name":"macrophage"},{"slug":"parp","name":"PARP"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":59,"slug":"new-perspectives-on-the-use-of-niacin-in-the-treatment-of-lipid-disorders","title":"New Perspectives on the Use of Niacin in the Treatment of Lipid Disorders","seo_title":"Niacin for Lipid Disorders: Updated Clinical Perspectives","publication_title":"New Perspectives on the Use of Niacin in the Treatment of Lipid Disorders","publication_url":"https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/216937","pmid":"216937","date":"2021-09-10","publication_year":2002,"description":"An overview of research showing supplementing niacin lowers the risk of heart attack frequency and severity.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"adiponectin","name":"adiponectin"}],"conditions":[{"slug":"dyslipidemia","name":"dyslipidemia"},{"slug":"atherosclerosis","name":"atherosclerosis"}],"pathways":[{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":60,"slug":"niacin-ameliorates-ulcerative-colitis-via-prostaglandin-d2‐mediated-d-prostanoid-receptor-1-activation","title":"Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation","seo_title":null,"publication_title":"Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412792/","pmid":null,"date":"2023-09-08","publication_year":2017,"description":"Out of 26 patients with moderate ulcerative colitis (inflammation of the colon) who were unresponsive to conventional treatments, 92.3% responded positively and 88.5% went into remission after receiving a daily niacin enema treatment for 6 weeks. The had no serious side effects, showed notable improvements in intestinal healing,  reduced symptoms like rectal bleeding and stool frequency. Niacin is a promising, well-tolerated alternative for inducing clinical remission of ulcerative colitis.","body_markdown":null,"study_type":"rct","model":"human","sample_size":26,"duration":"6 weeks","blinded":null,"intervention":"nicotinic-acid","route":"enema","dose_reported":"daily niacin enema","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"92.3% responded positively, 88.5% achieved remission","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"pgd2","name":"PGD2"},{"slug":"prostaglandin","name":"prostaglandin"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"colitis","name":"colitis"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":61,"slug":"notes-on-niacin-and-its-metabolites-as-master-regulators-of-macrophage-activation","title":"Niacin and its metabolites as master regulators of macrophage activation","seo_title":"Niacin Metabolites as Key Regulators of Macrophage Immune Activation","publication_title":"Niacin and its metabolites as master regulators of macrophage activation","publication_url":"https://pubmed.ncbi.nlm.nih.gov/27771381/","pmid":"27771381","date":"2021-09-09","publication_year":2016,"description":"The focus is on how niacin and its metabolites enable white blood cells to react to a changing microenvironment (macrophage plasticity). It also discusses the anti-oxidant and anti-inflammatory aspects of niacin.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"macrophage","name":"macrophage"},{"slug":"nad","name":"NAD+"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"il-10","name":"IL-10"},{"slug":"tnf-alpha","name":"TNF-alpha"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":62,"slug":"niacin-attenuates-lung-inflammation-and-improves-survival-during-sepsis-by-downregulating-the-nuclear-factor-κb-pathway","title":"Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-κB pathway","seo_title":null,"publication_title":"Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-κB pathway","publication_url":"https://pubmed.ncbi.nlm.nih.gov/20975550/","pmid":"20975550","date":"2021-09-27","publication_year":2011,"description":"Rats injected with e coli bacteria to induce lung inflammation survived better with high dose (~1% of diet) niacin supplementation. The reduced lung inflammation and damage was associated with downregulation of the NF-κB (Nuclear Factor Kappa B) pathway.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":"~1% of diet","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Improved survival and reduced lung inflammation","mechanisms":[{"slug":"nf-kb","name":"NF-kB"},{"slug":"gpr109a","name":"GPR109A"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"sepsis","name":"sepsis"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":63,"slug":"niacin-attenuates-pulmonary-hypertension-through-h-pgds-in-macrophages","title":"Niacin Attenuates Pulmonary Hypertension Through H-PGDS in Macrophages","seo_title":"Niacin Lowers Pulmonary Hypertension by Reprogramming Lung Macrophages","publication_title":"Niacin Attenuates Pulmonary Hypertension Through H-PGDS in Macrophages","publication_url":"https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.316784","pmid":null,"date":"2021-09-16","publication_year":2021,"description":"When mice are induced with pulmonary hypertension via drugs and low oxygen, those on niacin have less severe outcomes, due to enhanced macrophage activity and release of  PGD2.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Less severe pulmonary hypertension outcomes","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"pgd2","name":"PGD2"},{"slug":"prostaglandin","name":"prostaglandin"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":64,"slug":"niacin-attenuates-the-production-of-pro-inflammatory-cytokines-in-lps-induced-mouse-alveolar-macrophages-by-hca2-dependent-mechanisms","title":"Niacin attenuates the production of pro-inflammatory cytokines in LPS-induced mouse alveolar macrophages by HCA2 dependent mechanisms","seo_title":"Niacin Reduces Lung Inflammation via HCA2 Receptor in Macrophages","publication_title":"Niacin attenuates the production of pro-inflammatory cytokines in LPS-induced mouse alveolar macrophages by HCA2 dependent mechanisms","publication_url":"https://pubmed.ncbi.nlm.nih.gov/25038318/","pmid":"25038318","date":"2021-10-04","publication_year":2014,"description":"Explores protective effect of niacin on lung tissue by dosing mouse lung white blood cells with niacin and exposing them to inflammatory toxins (Lipopolysaccharides). This demonstrated strong anti-inflammatory effects of niacin ( reduced levels of TNF-α, IL-6 and IL-1β) and that the protective effect depends on expression of GPR109A.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Reduced levels of TNF-alpha, IL-6 and IL-1beta","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"tnf-alpha","name":"TNF-alpha"},{"slug":"il-6","name":"IL-6"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":65,"slug":"niacin-cures-systemic-nad-deficiency-and-improves-muscle-performance-in-adult-onset-mitochondrial-myopathy","title":"Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy","seo_title":"Niacin Raises NAD+ 8-Fold and Restores Muscle Strength in Mitochondrial Disease","publication_title":"Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy","publication_url":"https://pubmed.ncbi.nlm.nih.gov/32386566/","pmid":"32386566","date":"2021-09-14","publication_year":2020,"description":"Patients with mitochondrial myopathy (which is associated with NAD+ deficiency) received ~1g niacin daily for 4 months. This resulting in increasing blood NAD+ levels in all patients, up to 8x, improved muscle strength, improved respiratory chain activity and reduced fatty liver.","body_markdown":"## Overview\n\nThis 2020 study (Pirinen et al., *Cell Metabolism*) is among the most important clinical demonstrations of niacin's role as a NAD+ precursor. It enrolled patients with adult-onset mitochondrial myopathy — a condition characterized by systemic NAD+ deficiency caused by mitochondrial DNA mutations — and treated them with niacin (nicotinic acid) at approximately 1 gram per day for four months.\n\nThe results are some of the most striking in the niacin literature: NAD+ levels in blood and muscle rose dramatically in all patients, with some showing up to an 8-fold increase in muscle NAD+ concentration. Alongside the biochemical changes, patients showed measurable improvements in muscle strength and respiratory chain activity, and reduced liver fat accumulation.\n\n## Key Findings\n\n**NAD+ increased up to 8-fold in blood and muscle.** This magnitude of NAD+ restoration from oral niacin is exceptional. NAD+ is central to mitochondrial energy production (as a cofactor in the electron transport chain) and to sirtuin and PARP enzyme activity (which govern DNA repair, gene expression, and cellular stress responses). In mitochondrial myopathy patients, where NAD+ is chronically depleted, this restoration is functionally significant.\n\n**Muscle strength improved.** Patients showed measurable gains in muscle performance metrics over the four-month period. Given that mitochondrial myopathy is a progressive condition, any functional improvement — rather than just biochemical marker change — represents a clinically meaningful outcome.\n\n**Respiratory chain activity recovered.** The complexes of the mitochondrial electron transport chain (particularly Complex I) showed improved activity. This is the direct downstream consequence of restored NAD+ availability: more NAD+ means more electron transfer through Complex I, more ATP synthesis, and better mitochondrial function.\n\n**Fatty liver was reduced.** Liver fat accumulation is a secondary consequence of mitochondrial dysfunction and NAD+ depletion. Its reduction with niacin treatment is consistent with the well-documented role of NAD+ in hepatic lipid metabolism and niacin's direct effects on the liver.\n\n## Why Niacin Works Here: The NAD+ Precursor Pathway\n\nNiacin (nicotinic acid) is one of three main NAD+ precursors, alongside nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). What distinguishes nicotinic acid from the others is the pathway it uses:\n\n- **Nicotinic acid** enters the Preiss-Handler pathway: nicotinic acid → NaMN → NaAD → NAD+. This pathway is distinct from the NR/NMN salvage pathway.\n- In disease states where specific salvage enzymes are depleted or dysfunctional, the Preiss-Handler route may be more effective at restoring NAD+.\n- Nicotinic acid also engages the de novo synthesis pathway more directly in some tissues than NR or NMN.\n\nIn this study, the dramatic NAD+ restoration from nicotinic acid suggests that in mitochondrial myopathy, the Preiss-Handler pathway is intact and capable of processing high niacin doses into NAD+ even when mitochondrial function is compromised.\n\n## Niacin vs. Other NAD+ Precursors\n\nThis study is frequently cited in debates about which NAD+ precursor is most effective clinically. While NR and NMN have been studied primarily for aging-related NAD+ decline, niacin's Preiss-Handler pathway provides a distinct and potentially complementary route.\n\nThe 8-fold NAD+ increase from nicotinic acid in this disease population substantially exceeds most reported results from NR or NMN in typical aging populations (which tend to show 40–60% increases in blood NAD+). Whether this gap is disease-specific, dose-specific, or a genuine pathway advantage remains an open research question. This study does not directly compare nicotinic acid to NR or NMN in the same patients.\n\n## Clinical Context\n\nMitochondrial myopathy is a rare disease and the trial was small. The dramatic results should not be extrapolated directly to healthy aging populations. However, the study provides clear proof of concept that:\n\n1. Oral niacin (nicotinic acid) meaningfully and dramatically raises systemic NAD+ levels\n2. NAD+ deficiency reversal can translate to measurable functional improvement, not just biochemical marker change\n3. Nicotinic acid specifically — not niacinamide, NR, or NMN — was the intervention studied and found effective here\n\nFor researchers working on niacin, NAD+ metabolism, aging, mitochondrial disease, or muscle function, this *Cell Metabolism* paper is foundational. It is the most direct human evidence that niacin supplementation is a potent NAD+ repletion strategy, not merely a lipid-modifying drug.","study_type":"rct","model":"human","sample_size":null,"duration":"4 months","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":"~1g niacin daily","dose_mg_kg":null,"dose_absolute_mg":1000,"dose_human_equiv_g":1,"outcome":"positive","effect_size":"NAD+ levels increased up to 8x; improved muscle strength","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"},{"slug":"parp","name":"PARP"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"liver","name":"liver"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":66,"slug":"niacin-fine-tunes-energy-homeostasis-through-canonical-gpr109a-signaling","title":"Niacin fine-tunes energy homeostasis through canonical GPR109A signaling","seo_title":"Niacin Regulates Weight and Energy via GPR109A Signaling in Mice","publication_title":"Niacin fine-tunes energy homeostasis through canonical GPR109A signaling","publication_url":"https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201801951R","pmid":null,"date":"2021-09-11","publication_year":2019,"description":"When fed a high fat diet + niacin, mice deficient in niacin receptor GPR109A got fat and had fatty livers. While mice with normal GPR109A receptors didn't get fat and didn't end up with fatty livers.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"GPR109A-deficient mice developed obesity and fatty liver on high-fat diet + niacin; wild-type mice did not","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"ampk","name":"AMPK"}],"conditions":[{"slug":"obesity","name":"obesity"},{"slug":"liver","name":"liver"},{"slug":"insulin-resistance","name":"insulin-resistance"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":67,"slug":"niacin-for-treatment-of-nonalcoholic-fatty-liver-disease-nafld-novel-use-for-an-old-drug","title":"Niacin for treatment of nonalcoholic fatty liver disease (NAFLD): novel use for an old drug?","seo_title":"Niacin Reduced Liver Fat 40% in NAFLD Patients in 6-Month Trial","publication_title":"Niacin for treatment of nonalcoholic fatty liver disease (NAFLD): novel use for an old drug?","publication_url":"https://www.lipidjournal.com/article/S1933-2874(19)30290-9/fulltext","pmid":null,"date":"2021-09-10","publication_year":2019,"description":"39 patients taking 2g/day extended release niacin for ~6 months had a ~40% reduction in liver fat.  Other markers of inflammation such as CRP (C-reactive protein) where also reduced.","body_markdown":null,"study_type":"rct","model":"human","sample_size":39,"duration":"~6 months","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":"2g/day extended release niacin","dose_mg_kg":null,"dose_absolute_mg":2000,"dose_human_equiv_g":2,"outcome":"positive","effect_size":"~40% reduction in liver fat","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"liver","name":"liver"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":68,"slug":"niacin-in-the-central-nervous-system-an-update-of-biological-aspects-and-clinical-applications","title":"Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications","seo_title":"Niacin in the Brain: Neuroprotective Effects and Clinical Applications","publication_title":"Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/","pmid":null,"date":"2021-09-14","publication_year":2019,"description":"In depth review of how niacin and its metabolites play a key role in brain and nerve health. Alzheimers and Niacin intake are inversely correlated. Niacin helps cells stay alive when blood supply is cutoff.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"Alzheimer's and niacin intake are inversely correlated","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"},{"slug":"parp","name":"PARP"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"alzheimers","name":"alzheimers"},{"slug":"parkinsons","name":"parkinsons"},{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":69,"slug":"niacin-protects-against-uvb-radiation-induced-apoptosis-in-cultured-human-skin-keratinocytes","title":"Niacin protects against UVB radiation-induced apoptosis in cultured human skin keratinocytes","seo_title":"Niacin Protects Skin Cells Against UV-B Radiation Damage and Cell Death","publication_title":"Niacin protects against UVB radiation-induced apoptosis in cultured human skin keratinocytes","publication_url":"https://www.spandidos-publications.com/10.3892/ijmm.2012.886","pmid":null,"date":"2021-11-23","publication_year":2012,"description":"Niacin pretreatment of skin cells protects against UV-induced cell death and apoptosis by enhancing the pro-survival pathways including AKT, mTOR and S6 in skin keratinocytes. Oral and external niacin is safe and appears to be a promising chemo-preventive supplement for reducing the mutagenic, immunosuppressive and cell damage effects of sunlight. This is also the first study providing a molecular mechanism to support that niacin can be utilized as a skin photo-damage protective agent.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"mtor","name":"mTOR"},{"slug":"apoptosis","name":"apoptosis"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"cancer","name":"cancer"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":70,"slug":"niacin-reduces-abdominal-fat-pilot-study","title":"Niacin reduces abdominal fat: pilot study","seo_title":"Niacin Reduces Abdominal Fat: Pilot Study Results","publication_title":"https://www.aidsmap.com/news/feb-2002/niacin-reduces-abdominal-fat-pilot-study","publication_url":"https://www.aidsmap.com/news/feb-2002/niacin-reduces-abdominal-fat-pilot-study","pmid":null,"date":"2022-11-27","publication_year":2002,"description":"Participants in an open label study at Kaiser Permanente in San Francisco supplemented ~3g niacin a day. After about 1 year, 81% of patients had an by an average reduction of 27% in intra-abdominal fat. The degree of fat loss was associated with the degree of increase in HDL cholesterol and a reduced Total Cholesterol/HDL cholesterol ratio.","body_markdown":"## Overview\n\nThis pilot study, reported by researchers at Kaiser Permanente San Francisco, examined the effect of extended-release niacin supplementation on body composition in patients with HIV-associated lipodystrophy — a condition characterized by abnormal fat redistribution, including visceral fat accumulation, associated with antiretroviral therapy. The study was one of the first to specifically measure niacin's effect on intra-abdominal fat using imaging (likely CT scan-based measurement of visceral adiposity).\n\nParticipants received approximately 3 grams of niacin per day. After roughly one year, fat distribution was reassessed.\n\n## Key Findings\n\n**81% of participants experienced measurable reductions in intra-abdominal fat,** with an average reduction of 27% in visceral adiposity across the group. This is a notable effect for a single nutritional intervention, particularly in a population where visceral fat accumulation is driven by drug-associated metabolic disruption.\n\n**Fat loss correlated with lipid improvements.** The degree of abdominal fat reduction tracked with the degree of increase in HDL cholesterol and improvement in the Total Cholesterol to HDL ratio. This correlation suggests a shared mechanism — likely GPR109A-mediated effects on adipose metabolism — rather than independent effects on fat and lipids.\n\n**This was an open-label pilot.** There was no placebo or control arm. The population was specific (HIV+ patients on antiretrovirals), which limits direct extrapolation to general metabolic obesity.\n\n## Mechanism: Why Would Niacin Reduce Visceral Fat?\n\nSeveral pathways are plausible:\n\n**GPR109A activation in adipocytes.** Niacin activates the GPR109A receptor on fat cells, acutely suppressing lipolysis (the release of free fatty acids from fat stores). While this sounds counterproductive for fat loss, chronically reduced free fatty acid flux appears to improve insulin sensitivity and adipose tissue remodeling. Visceral fat is metabolically distinct from subcutaneous fat and particularly sensitive to insulin-mediated signaling.\n\n**Improved insulin sensitivity.** Niacin's acute anti-lipolytic effect reduces circulating free fatty acids, which are a primary driver of peripheral insulin resistance. Lower FFAs → improved insulin signaling → reduced de novo lipogenesis and visceral fat accumulation over time.\n\n**HDL-mediated reverse cholesterol transport.** Niacin raises HDL more than nearly any other intervention. HDL particles help remove excess lipid from peripheral tissues, potentially including visceral depots. The observed correlation between HDL improvement and fat reduction in this study is consistent with this mechanism.\n\n**Growth hormone axis.** As documented in other niacin research, FFA suppression by niacin removes a brake on GH secretion. GH promotes lipolysis preferentially in visceral fat. This GH-mediated mechanism may partially explain the preferential reduction in intra-abdominal rather than subcutaneous fat.\n\n## Context: Niacin and Body Composition\n\nThis pilot study sits within a broader pattern in the niacin literature connecting niacin status and intake with metabolic health markers:\n\n- Separate NHANES analyses link higher dietary niacin to lower obesity prevalence\n- Animal studies using GPR109A-knockout models show progressive weight gain and liver fat accumulation when the niacin receptor is absent\n- The melatonin + niacin rat study documented additive anti-obesity effects when both were combined\n- HIV lipodystrophy research is a useful model for studying visceral fat interventions because the fat accumulation is more severe and faster-moving than in typical metabolic obesity\n\n## Limitations\n\nThis was a small, uncontrolled pilot in a specialized population on multiple medications. The 3g/day dose of niacin is pharmacological (not achievable from diet alone) and carries known side effects, particularly flushing and, at high doses, hepatotoxicity risk. Extended-release formulations reduce flushing but carry higher hepatotoxicity risk than immediate-release niacin. This study's applicability to non-HIV populations pursuing niacin for visceral fat reduction should be interpreted cautiously.\n\nThe result is hypothesis-generating, not confirmatory. It merits follow-up in controlled trials with general population obesity populations.","study_type":"cohort","model":"human","sample_size":null,"duration":"~1 year","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":3000,"dose_human_equiv_g":3,"outcome":"positive","effect_size":"27% reduction in intra-abdominal fat in 81% of participants","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"adiponectin","name":"adiponectin"}],"conditions":[{"slug":"obesity","name":"obesity"},{"slug":"dyslipidemia","name":"dyslipidemia"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":71,"slug":"niacin-regresses-collagen-content-in-human-hepatic-stellate-cells-from-liver-transplant-donors-with-fibrotic-non-alcoholic-steatohepatitis-nash","title":"Niacin regresses collagen content in human hepatic stellate cells from liver transplant donors with fibrotic non-alcoholic steatohepatitis (NASH)","seo_title":"Niacin Reduces Liver Fibrosis Collagen in NASH Patients' Stellate Cells","publication_title":"Niacin regresses collagen content in human hepatic stellate cells from liver transplant donors with fibrotic non-alcoholic steatohepatitis (NASH)","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274597/","pmid":null,"date":"2022-12-13","publication_year":2022,"description":"Taking niacin ~1-3g daily clears up liver collagen and fat deposits which are associated with liver disease. It also prevents them from forming.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"liver","name":"liver"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":72,"slug":"niacin-requirements-for-genomic-stability","title":"Niacin requirements for genomic stability","seo_title":"Niacin and Cancer Risk: NAD+ Deficiency Linked to Genomic Instability","publication_title":"Niacin requirements for genomic stability","publication_url":"https://pubmed.ncbi.nlm.nih.gov/22138132/","pmid":"22138132","date":"2021-09-14","publication_year":2011,"description":"Niacin involved with over 400 NAD+ dependent reactions. Essentially all cancer patients are deficient in niacin. Exposing mice to high levels of UVB radiation to induce skin cancer showed that mice on the highest doses of niacin had the lowest rate of skin cancer at 28% compared to 68% in the control group.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"p53","name":"p53"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":73,"slug":"niacin-reverses-migratory-macrophage-foam-cell-arrest-mediated-by-oxldl-in-vitro","title":"Niacin Reverses Migratory Macrophage Foam Cell Arrest Mediated by oxLDL In Vitro","seo_title":"Niacin Frees Trapped Foam Cells — A Key Step in Reversing Plaque","publication_title":"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114643","publication_url":"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114643","pmid":null,"date":"2021-10-23","publication_year":2014,"description":"Oxidized Low Density Cholesterol, oxLDL induced inhibition of macrophage migration may be reversed by Niacin, which explains part of Niacin's atheroprotective effects on cardiovascular disease independent of its effects on plasma lipids. Macrophage foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls. Niacin also inhibited the formation of peroxynitrite (which is a powerful oxidant exhibiting a wide array of tissue damaging effects)","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"macrophage","name":"macrophage"},{"slug":"gpr109a","name":"GPR109A"}],"conditions":[{"slug":"atherosclerosis","name":"atherosclerosis"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":74,"slug":"niacin-mediated-rejuvenation-of-macrophage-microglia-enhances-remyelination-of-the-aging-central-nervous-system","title":"Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system","seo_title":"Niacin Rejuvenates Brain Immune Cells to Restore Myelin in the Aging CNS","publication_title":"https://link.springer.com/article/10.1007/s00401-020-02129-7","publication_url":"https://link.springer.com/article/10.1007/s00401-020-02129-7","pmid":null,"date":"2021-09-16","publication_year":2020,"description":"Niacin via its ability to enhance macrophage and microglia is great for repairing (myelin) sheaths that protect nerve fibers, which deteriorate in diseases like multiple sclerosis.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"macrophage","name":"macrophage"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"multiple-sclerosis","name":"multiple-sclerosis"},{"slug":"neuroinflammation","name":"neuroinflammation"},{"slug":"aging","name":"aging"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":75,"slug":"nicotinic-acid-inhibits-glioma-invasion-by-facilitating-snail1-degradation","title":"Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation","seo_title":"Niacin Blocks Brain Tumor Invasion by Degrading the Snail1 Protein","publication_title":"Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation","publication_url":"https://www.nature.com/articles/srep43173","pmid":null,"date":"2022-09-24","publication_year":2017,"description":"This study grafted malignant gliomas cells (which are one of the most common types of primary brain tumors) into rat brains to see if nicotinic acid administration would help regulate the implanted tumor. ~70% of the allografted rats that were continuously administered with nicotinic acid  were still alive on day 58. 100% of control group died by day 24. Biopsy showed much less tumor spread in nicotinic acid rats. Their results suggest that niacin the helps prevent the invasion of other kinds of malignant cells such as melanoma ( skin cancer ) cells and that this points to a general role of nicotinic acid in regulating tumor invasion.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"~70% survival at day 58 in treated vs 0% survival by day 24 in controls","mechanisms":[{"slug":"apoptosis","name":"apoptosis"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"brain-tumor","name":"brain-tumor"},{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":76,"slug":"nicotinic-acid-inhibits-vascular-inflammation-via-the-sirt1-dependent-signaling-pathway☆","title":"Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway","seo_title":null,"publication_title":"Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway","publication_url":"https://www.sciencedirect.com/science/article/abs/pii/S095528631500162X","pmid":null,"date":"2021-09-15","publication_year":2015,"description":"Feeding rabbits Niacin up-regulated SIRT1 expression, which is involved with DNA repair. Rabbits where then subjected to stress via a collar on an artery in their neck and it was shown that niacin protects against blood vessel inflammation via the SIRT1/CD40-dependent signaling pathway.","body_markdown":null,"study_type":"animal","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"sirt1","name":"SIRT1"},{"slug":"nf-kb","name":"NF-kB"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"atherosclerosis","name":"atherosclerosis"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":77,"slug":"nicotinic-acid-is-a-common-regulator-of-heat-sensing-trpv1-4-ion-channels","title":"Nicotinic Acid is a Common Regulator of Heat-Sensing TRPV1-4 Ion Channels","seo_title":"Niacin Regulates Heat-Sensing and Pain Channels TRPV1 to TRPV4","publication_title":"Nicotinic Acid is a Common Regulator of Heat-Sensing TRPV1-4 Ion Channels","publication_url":"https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4894441/","pmid":null,"date":"2021-10-23","publication_year":2016,"description":"NA activates the capsaicin receptor TRPV1 by lowering the activation threshold for heat, causing channel activation at physiological body temperature. Conversely it inhibits TRPV4 by raising activation temp to above body temp, ~41 celsius. Overall, the effects on TRPV1 and TRPV3 are potentiating while those on TRPV2 and TRPV4 are inhibitory. Little is known about the detailed structures of TRPV2-4. The TRPV receptors play a role in the flushing response.","body_markdown":null,"study_type":"mechanistic","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"neutral","effect_size":null,"mechanisms":[{"slug":"ca2","name":"Ca2+"},{"slug":"prostaglandin","name":"prostaglandin"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"},{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":78,"slug":"nicotinic-acid-long-term-effectiveness-in-a-patient-with-bipolar-type-ii-disorder-a-case-of-vitamin-dependency","title":"Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency","seo_title":"Niacin Long-Term Effectiveness for Bipolar Type II: A Case of Vitamin Dependency","publication_title":"Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852710/","pmid":null,"date":"2022-09-24","publication_year":2018,"description":"Case report of a patient with bipolar disorder who had been on lithium and other bipolar meds who was able to get off all meds after starting taking 1g niacin 3 times a day. He has been stable for 11 years on this niacin supplementation regimen. Stopping niacin leads a return of his symptoms within 2-3 days and clears up in one day after resuming the niacin regimen.","body_markdown":null,"study_type":"case-report","model":"human","sample_size":1,"duration":"11 years","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":3000,"dose_human_equiv_g":3,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"}],"conditions":[{"slug":"depression","name":"depression"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":79,"slug":"nicotinic-acid-treatment-shifts-the-fibrinolytic-balance-favourably-and-decreases-plasma-fibrinogen-in-hypertriglyceridaemic-men","title":"Nicotinic Acid Treatment Shifts the Fibrinolytic Balance Favourably and Decreases Plasma Fibrinogen in Hypertriglyceridaemic Men","seo_title":"Niacin Improves Blood Clot Dissolution and Lowers Fibrinogen Levels","publication_title":"Nicotinic Acid Treatment Shifts the Fibrinolytic Balance Favourably and Decreases Plasma Fibrinogen in Hypertriglyceridaemic Men","publication_url":"https://academic.oup.com/eurjpc/article/4/3/165/5927431","pmid":"5927431","date":"2023-03-26","publication_year":1997,"description":"23 hypertriglyceridaemic men took 4g/day of niacin for 6 weeks and saw very significant improvements in lipoprotein concentrations (reducing very low density cholesterol and triglycerides by ~50%) as well as reduced blood clotting and thrombosis factors.","body_markdown":null,"study_type":"rct","model":"human","sample_size":23,"duration":"6 weeks","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":4000,"dose_human_equiv_g":4,"outcome":"positive","effect_size":"~50% reduction in VLDL and triglycerides","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"adiponectin","name":"adiponectin"}],"conditions":[{"slug":"dyslipidemia","name":"dyslipidemia"},{"slug":"atherosclerosis","name":"atherosclerosis"}],"pathways":[{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":80,"slug":"open-accessreview-minireview-exploring-the-biological-cycle-of-vitamin-b3-and-its-influence-on-oxidative-stress-further-molecular-and-clinical-aspects","title":"Open AccessReview Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects","seo_title":"Vitamin B3 Biology: How Niacin Combats Oxidative Stress","publication_title":"Open AccessReview Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects","publication_url":"https://www.mdpi.com/1420-3049/25/15/3323","pmid":null,"date":"2021-09-14","publication_year":2020,"description":"Overview of how niacin and its metabolites like NAD, NADP, NADPH play a key role in cellular signaling, apoptosis, balancing intestinal flora and gene expression. Without external supply of supply of niacin, the genome becomes unstable via the antioxidant system no longer functioning efficiently, which ultimately leads to cell death.","body_markdown":null,"study_type":"review","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadh","name":"NADH"},{"slug":"nadph","name":"NADPH"},{"slug":"parp","name":"PARP"},{"slug":"sirt1","name":"SIRT1"},{"slug":"apoptosis","name":"apoptosis"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":81,"slug":"oral-niacin-prevents-photocarcinogenesis-and-photoimmunosuppression-in-mice","title":"Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice","seo_title":"Oral Niacin Prevents UV-Induced Skin Cancer and Immune Suppression in Mice","publication_title":"Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice","publication_url":"https://pubmed.ncbi.nlm.nih.gov/10453439/","pmid":"10453439","date":"2021-09-18","publication_year":1999,"description":"Mice subjected to high dose ultraviolet light for about 6 months while fed a diet supplemented with 0%, 0.1%, 0.5%, or 1.0% (by dry weight of feed) of niacin showed 68%, 60%, 48%, and 28% rates of skin cancer respectively, indicating a protective effect. Elevated levels of NAD found in niacin supplemented mice. NAD modulates the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":"~6 months","blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":"0.1%, 0.5%, 1.0% by dry weight of feed","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"skin cancer rates: 68% (control) vs 28% (1% niacin)","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"p53","name":"p53"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":82,"slug":"periodontitis-and-intake-of-thiamine-riboflavin-and-niacin-among-korean-adults","title":"Periodontitis and intake of thiamine, riboflavin and niacin among Korean adults","seo_title":"Low Niacin Intake Linked to Higher Gum Disease Risk in Korean Adults","publication_title":"Periodontitis and intake of thiamine, riboflavin and niacin among Korean adults","publication_url":"https://onlinelibrary.wiley.com/doi/full/10.1111/cdoe.12496","pmid":null,"date":"2021-09-12","publication_year":2019,"description":"Low niacin in diet leads to higher (~125%) rates of severe gum infection.","body_markdown":null,"study_type":"ecological","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"~125% higher rates of severe periodontitis with low niacin intake","mechanisms":[{"slug":"nf-kb","name":"NF-kB"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":83,"slug":"pharmacological-bypass-of-nad-salvage-pathway-protects-neurons-from-chemotherapy-induced-degeneration","title":"Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration","seo_title":"Boosting NAD+ Protects Neurons From Chemotherapy-Induced Nerve Damage","publication_title":"Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration","publication_url":"https://pubmed.ncbi.nlm.nih.gov/30257945/","pmid":"30257945","date":"2023-03-12","publication_year":2018,"description":"Axon degeneration from NMN accumulation can be prevented by bypassing the NAD+ salvage pathway (which is associated with the production of NMN) by providing nicotinic acid riboside (a precursor to nicotinic acid mononucleotide) as substrate for the body to make NAD+ via the primary Preiss Handler pathway instead.","body_markdown":null,"study_type":"mechanistic","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"atp","name":"ATP"}],"conditions":[{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":84,"slug":"pharmacological-intakes-of-niacin-increase-bone-marrow-poly-adp-ribose-and-the-latency-of-ethylnitrosourea-induced-carcinogenesis-in-rats","title":"Pharmacological Intakes of Niacin Increase Bone Marrow Poly(ADP-Ribose) and the Latency of Ethylnitrosourea-Induced Carcinogenesis in Rats","seo_title":"High-Dose Niacin Boosts PARP Activity and Slows Cancer Development","publication_title":"Pharmacological Intakes of Niacin Increase Bone Marrow Poly(ADP-Ribose) and the Latency of Ethylnitrosourea-Induced Carcinogenesis in Rats","publication_url":"https://pubmed.ncbi.nlm.nih.gov/11773517/","pmid":"11773517","date":"2021-09-10","publication_year":2001,"description":"Rats fed high niacin diet and then poisoned with ethylnitrosourea (a potent mutagen) survived for longer and had increase amounts of NAD+ (1-1.5x) and ADP-ribose in their bone marrow.","body_markdown":"tbd","study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"1-1.5x increase in NAD+ and ADP-ribose in bone marrow","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":85,"slug":"physiological-and-anti-obesity-effects-of-melatonin-and-niacin-supplements-in-rat-models","title":"Physiological and Anti-obesity Effects of Melatonin and Niacin Supplements in Rat Models","seo_title":"Melatonin and Niacin Supplements Reduced Body Fat in Rat Models","publication_title":"Physiological and Anti-obesity Effects of Melatonin and Niacin Supplements in Rat Models","publication_url":"https://dergipark.org.tr/tr/download/article-file/1756386","pmid":"1756386","date":"2021-09-16","publication_year":2021,"description":"Rats where given unlimited access to food and a controlled amount of exercise. Those taking niacin + melatonin lost statistically significantly more weight, compared to control, niacin only and melatonin only groups. Suggests a synergy between niacin & melatonin supplementation for anti-obesity. It's noted that mice lacking the niacin receptor GPR109A had progressive weight gain and liver fat accumulation.","body_markdown":"## Overview\n\nThis animal study examined the effects of melatonin supplementation, niacin supplementation, and their combination on body weight and metabolic parameters in rats given ad libitum food access with a controlled exercise protocol. The study's interest lies in testing whether niacin and melatonin have additive or synergistic effects on body weight regulation — since both have individually been reported to influence adipose metabolism through partially overlapping mechanisms.\n\n## Key Findings\n\n**The niacin + melatonin group lost significantly more weight** than controls, niacin-only, or melatonin-only groups. The combination outperformed either supplement alone, suggesting an additive or synergistic interaction rather than the same mechanism acting twice.\n\n**Niacin alone showed metabolic effects** consistent with the broader literature: improvements in lipid profiles and some reduction in adiposity measures. Melatonin alone also produced weight-related effects, consistent with its documented role in circadian regulation of metabolism.\n\n**GPR109A-knockout findings provide mechanism.** The study notes that mice lacking the niacin receptor GPR109A show progressive weight gain and liver fat accumulation — establishing GPR109A activation as a causal node in the niacin–metabolism relationship, not merely a correlate.\n\n## Why Might Niacin and Melatonin Interact?\n\nThe two molecules converge on metabolic regulation through different but complementary mechanisms:\n\n**Niacin's route: GPR109A → adipose metabolism.** Niacin activates GPR109A on adipocytes, acutely suppressing lipolysis and free fatty acid release. This improves insulin sensitivity by reducing the FFA-driven suppression of glucose uptake. Over time, GPR109A activation appears to remodel adipose tissue, particularly visceral fat. Separately, niacin's FFA suppression reduces the brake on GH secretion, which promotes lipolysis in visceral depots when GH pulses occur.\n\n**Melatonin's route: circadian regulation of adipose and energy expenditure.** Melatonin is the primary circadian timing signal. It regulates thermogenesis in brown adipose tissue, modulates leptin and adiponectin secretion, and influences insulin sensitivity through circadian mechanisms. Disrupted melatonin signaling (as in shift workers or sleep-deprived populations) is strongly associated with obesity and metabolic syndrome.\n\n**The intersection: GPR109A appears in both pathways.** Melatonin signaling affects adipose tissue function, and GPR109A is expressed in adipose tissue where it responds to niacin. A separate paper in this directory (*Melatonin alleviates titanium nanoparticles-induced osteolysis via activation of butyrate-GPR109A signaling pathway*) demonstrates GPR109A is a downstream effector in melatonin-related signaling in some tissues. The convergence on GPR109A-expressing adipose cells is a plausible basis for the observed synergy.\n\n## The GPR109A-Knockout Evidence\n\nThe observation that GPR109A-knockout mice gain weight progressively and accumulate liver fat provides mechanistic grounding for this study's findings. It positions GPR109A not as a pharmacological curiosity (niacin's flush receptor) but as a physiologically necessary component of adipose tissue homeostasis — one that responds to niacin in its absence would otherwise be activated by the gut metabolite butyrate (produced from dietary fiber fermentation).\n\nThis connects to the broader butyrate/GPR109A/fiber literature: a high-fiber diet producing butyrate may partially substitute for niacin's GPR109A activation in adipose tissue. Niacin supplementation becomes more impactful in low-fiber dietary contexts where butyrate-mediated GPR109A activation is reduced.\n\n## Limitations and Translation\n\nThis is a rat study. The doses and combination ratios do not directly translate to human supplementation protocols. Rat adipose metabolism differs from human adipose in important ways, particularly the ratio of brown to white fat. Results should be treated as mechanistic evidence generating hypotheses for human investigation, not as dosing guidance.\n\nThe positive finding from combining niacin and melatonin is consistent with their complementary mechanisms, but controlled human trials with dual supplementation have not been published as of this writing.\n\n## For Researchers\n\nThis study is relevant for those investigating: niacin and weight management, GPR109A as a metabolic target, melatonin and metabolic syndrome, or circadian-metabolic interactions. The GPR109A-knockout data is particularly useful as a positive control establishing causal necessity of the receptor in maintaining healthy adiposity.","study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"combination","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"melatonin","name":"melatonin"},{"slug":"adiponectin","name":"adiponectin"}],"conditions":[{"slug":"obesity","name":"obesity"},{"slug":"insulin-resistance","name":"insulin-resistance"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":86,"slug":"plasma-acetylcholine-and-nicotinic-acid-are-correlated-with-focused-preference-for-photographed-females-in-depressed-males-an-economic-game-study","title":"Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study","seo_title":"Niacin and Acetylcholine Levels Influence Social Preferences in Depressed Men","publication_title":"Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study","publication_url":"https://www.nature.com/articles/s41598-020-75115-4","pmid":null,"date":"2022-12-02","publication_year":2020,"description":"This study showed depressed males have a narrower preference for female photographs (only preferring good looking ones) which is a marker for lower cognitive flexibility. The less nicotinic acid in their body, the narrower their preference. This indicates nicotinic acid may regulate human social decision-making (especially preference-related behaviors) by acting on the HCAR2 in microglia (the resident immune cells of the brain and spinal cord which constantly patrol the cerebral microenvironment to respond to pathogens and damage).","body_markdown":null,"study_type":"cohort","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"depression","name":"depression"},{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":87,"slug":"plasma-melatonin-levels-in-psoriasis","title":"Plasma melatonin levels in psoriasis","seo_title":"Psoriasis and Melatonin: Altered Plasma Levels Found in Psoriasis Patients","publication_title":"Plasma melatonin levels in psoriasis","publication_url":"https://pubmed.ncbi.nlm.nih.gov/2459876/","pmid":"2459876","date":"2021-10-24","publication_year":1988,"description":"People with psoriasis tend to have lower levels of melatonin than average at 2 a.m and higher than average at 6am, 8 am & noon.","body_markdown":null,"study_type":"cohort","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"melatonin","name":"melatonin"}],"conditions":[{"slug":"psoriasis","name":"psoriasis"},{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":88,"slug":"politics-and-pellagra-the-epidemic-of-pellagra-in-the-u-s-in-the-early-twentieth-century","title":"Politics and Pellagra: The Epidemic of Pellagra in the U.S. in the Early Twentieth Century","seo_title":"How Politics Delayed America's Discovery of Niacin Deficiency and Pellagra","publication_title":"Politics and Pellagra: The Epidemic of Pellagra in the U.S. in the Early Twentieth Century","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2589605/pdf/yjbm00051-0058.pdf","pmid":null,"date":"2022-12-02","publication_year":2000,"description":"The 1906 to 1940 epidemic of pellagra was around 3 million cases, with 1 in 30 resulting in death.  A Dr Goldberger was appointed to study the cause. Even though correctly identified the root cause as a nutritional deficiency (later to be confirmed as niacin specifically) his prognosis was rejected by politicians in affected regions since they basically didn't want to admit that a diet consisting of largely degerminated cornmeal (which was a key economic export) was not appropriate for human wellbeing. The invention of degerminating corn, which removes nutrients but prolongs shelf-life, coincided with the appearance of the disease. Goldberger would cure orphans suffering from pellagra by feeding them a more varied diet including fresh milk and meat.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"pellagra","name":"pellagra"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"},{"slug":"why-not-mainstream","title":"Why Your Doctor Doesn't Know About This"}]},{"id":89,"slug":"nicotinic-acid-a-case-for-a-vitamin-that-moonlights-for-cancer","title":"Prevention of Cancer by Vitamin B3 (Nicotinamide and Nicotinic Acid)","seo_title":"Nicotinic Acid as a Cancer Treatment: The Case for Niacin's Anti-Tumor Role","publication_title":"Prevention of Cancer by Vitamin B3 (Nicotinamide and Nicotinic Acid)","publication_url":"https://link.springer.com/chapter/10.1007/978-1-4615-2882-1_10","pmid":null,"date":"2021-09-19","publication_year":1994,"description":"Nicotinamide, Nicotinic acid (niacin) and the related aromatic amides have been shown to have striking indications of possessing anticarcinogenic properties.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"combination","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"dna-repair","name":"DNA-repair"},{"slug":"p53","name":"p53"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":90,"slug":"protective-effects-of-niacin-against-methylmercury-induced-genotoxicity-and-alterations-in-antioxidant-status-in-rats","title":"Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats","seo_title":"Niacin Protects DNA From Mercury Toxicity and Restores Antioxidant Defenses","publication_title":"Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats","publication_url":"https://pubmed.ncbi.nlm.nih.gov/26914397/","pmid":"26914397","date":"2022-11-27","publication_year":2016,"description":"Rats being poisoned with methylmercury have less adverse effects when their diet is supplemented with niacin (50md/day).","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":"50 mg/day","dose_mg_kg":null,"dose_absolute_mg":50,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadph","name":"NADPH"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"}]},{"id":91,"slug":"relationship-between-dietary-niacin-intake-and-erectile-dysfunction-a-population-based-study","title":"Relationship between dietary niacin intake and erectile dysfunction: a population-based study","seo_title":"Niacin and Erectile Dysfunction: Men with High Intake Had 56% Lower Risk","publication_title":"Relationship between dietary niacin intake and erectile dysfunction: a population-based study","publication_url":"https://pubmed.ncbi.nlm.nih.gov/38305697/","pmid":"38305697","date":"2024-11-02","publication_year":2024,"description":"A large U.S. study found men with higher dietary niacin (vitamin B3) intake had a lower risk of erectile dysfunction (ED). Men in the highest third of niacin intake were 56% less likely to have ED compared to those in the lowest third. This link held true even after accounting for other factors like age, weight, and health conditions.","body_markdown":"## Overview\n\nThis 2024 epidemiological study (published in *Translational Andrology and Urology*) examined the relationship between dietary niacin (vitamin B3) intake and erectile dysfunction (ED) using data from the National Health and Nutrition Examination Survey (NHANES) — a large, nationally representative U.S. population sample. The dataset included thousands of adult men, with dietary intake assessed via 24-hour dietary recall and ED status determined by a validated questionnaire.\n\nThis is an observational study, so it does not establish that niacin prevents or treats ED — but the magnitude and consistency of the association make it a significant addition to the niacin research literature.\n\n## Key Findings\n\n**Men in the highest third of niacin intake were 56% less likely to have ED** compared to men in the lowest third, after adjusting for age, body mass index, physical activity, smoking, alcohol use, diabetes, hypertension, and cardiovascular disease. This is a large effect for a dietary factor in an adjusted model.\n\n**The relationship was dose-dependent.** Across tertiles of niacin intake, ED risk decreased progressively. Men in the middle tertile also had lower ED rates than the lowest group, consistent with a gradient rather than a threshold effect.\n\n**The association held across subgroups.** Subgroup analyses showed the niacin–ED relationship was present in men with and without cardiovascular disease, with and without diabetes, and across age groups — suggesting the mechanism is not mediated solely through cardiovascular risk factor modification.\n\n## Proposed Mechanisms\n\nThe researchers propose several pathways through which niacin may reduce ED risk:\n\n**Endothelial function.** Erection depends on nitric oxide (NO)-mediated vasodilation in penile vasculature. Niacin has been shown to raise HDL cholesterol and reduce LDL and triglycerides — lipid profiles associated with better endothelial health. A healthier vascular endothelium generates NO more effectively, supporting the erectile response.\n\n**Anti-inflammatory effects via GPR109A.** Niacin activates GPR109A receptors in immune cells and vascular tissue, reducing production of pro-inflammatory cytokines. Chronic low-grade inflammation is a recognized contributor to endothelial dysfunction and ED.\n\n**NAD+ metabolism.** As a precursor to NAD+, niacin supports mitochondrial function and cellular energy production in smooth muscle cells. The smooth muscle of penile corpora cavernosa must relax for erection to occur, and this process is energy-dependent.\n\n**Testosterone and gonadotropin axis.** Some evidence (from animal and small human studies) suggests niacin's effects on GH secretion and lipid metabolism may indirectly support testosterone production, though this is less established than the vascular mechanisms.\n\n## Clinical Context\n\nA separate randomized controlled trial (Ng et al., 2011) found that niacin supplementation (1500 mg/day for 12 weeks) significantly improved erectile function in men with both ED and dyslipidemia, specifically for orgasmic function and intercourse satisfaction scores. The NHANES population data presented here, while observational, is consistent with that intervention finding.\n\nCurrent dietary niacin intake in the U.S. population varies considerably — men in the lowest intake tertile may be consuming below optimal amounts from dietary sources alone (meat, fish, fortified grains). The study does not distinguish between niacin forms (nicotinic acid vs. niacinamide in food sources) or account for supplement use separately.\n\n## What This Means\n\nThis study adds to a growing body of evidence connecting niacin status to vascular and sexual health. The mechanisms are coherent: niacin improves lipid profiles, reduces vascular inflammation, supports endothelial function, and contributes to NAD+ synthesis — all of which feed into erectile physiology.\n\nFor researchers investigating niacin's role in men's health, this NHANES analysis provides the largest population-level evidence to date for the niacin–ED association. The 56% reduction in ED odds at higher dietary niacin intake, in a well-adjusted model, is a finding that warrants further investigation in prospective and interventional designs.","study_type":"cohort","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"dietary","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"56% lower ED risk in highest vs lowest tertile","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":92,"slug":"reversing-chronic-kidney-disease-with-niacin-and-sodium-bicarbonate","title":"Reversing Chronic Kidney Disease with Niacin and Sodium Bicarbonate","seo_title":"Niacin and Chronic Kidney Disease: 25 CKD Patients Improved in 3 Months","publication_title":"Reversing Chronic Kidney Disease with Niacin and Sodium Bicarbonate","publication_url":"http://orthomolecular.org/resources/omns/v17n22.shtml","pmid":null,"date":"2023-02-15","publication_year":2021,"description":"25 individuals with CKD (chronic kidney disease) stages 2-4 treated with a combination of supplements, including 500mg niacin 3x/day for three months, improved the disease by at least one stage.","body_markdown":"## Overview\n\nThis case series, published in the Orthomolecular Medicine News Service, reports on 25 patients with chronic kidney disease (CKD) at stages 2 through 4 who were treated with a combination protocol including **500 mg nicotinic acid (niacin) three times per day** — 1,500 mg/day total — along with sodium bicarbonate and other supportive supplements. After three months, all 25 individuals improved by at least one CKD stage, and some improved by two stages.\n\n**Important:** The study specifies **nicotinic acid** — the form of vitamin B3 that activates the GPR109A receptor and produces the characteristic niacin flush. Niacinamide (nicotinamide), the more common supplement sold as \"niacin,\" does not produce these effects and was not the compound studied.\n\n## What Is CKD?\n\nChronic kidney disease is defined by progressive loss of kidney function measured by estimated glomerular filtration rate (eGFR). The staging system:\n\n- **Stage 1**: eGFR ≥ 90 (normal or high, with kidney damage markers)\n- **Stage 2**: eGFR 60–89 (mildly reduced)\n- **Stage 3**: eGFR 30–59 (moderately reduced)\n- **Stage 4**: eGFR 15–29 (severely reduced)\n- **Stage 5**: eGFR < 15 (kidney failure)\n\nCKD is typically considered irreversible and progressive. Conventional treatment focuses on slowing the decline, not reversing it.\n\n## The Protocol\n\nThe combination treatment used in this case series:\n\n- **Nicotinic acid**: 500 mg, three times daily (1,500 mg/day total)\n- **Sodium bicarbonate**: to address metabolic acidosis, a common CKD complication\n- Additional supportive supplements (detailed in the source publication)\n\n## Results\n\nAll 25 participants improved by at least one CKD stage over three months — a finding that stands out because conventional medicine treats CKD progression as a one-way decline.\n\n## Why Niacin May Help Kidneys\n\nSeveral mechanisms may explain the benefit:\n\n**Phosphate reduction.** Niacin reduces phosphate absorption in the gut. Elevated phosphate is a known driver of CKD progression and cardiovascular complications. Niacin functions similarly to pharmaceutical phosphate binders — standard CKD therapy — via a different pathway.\n\n**GPR109A activation.** Nicotinic acid activates the GPR109A receptor, which has anti-inflammatory effects in multiple tissues. Chronic inflammation drives CKD progression, and GPR109A agonism may reduce some of this inflammatory burden. The same receptor activated by niacin in fat cells (causing the flush) is also expressed in kidney tissue and immune cells.\n\n**NAD+ precursor.** Niacin is a precursor to NAD+, essential for cellular energy. NAD+ depletion is associated with acute kidney injury and chronic disease progression. Restoring NAD+ levels through nicotinic acid supplementation may support renal cell repair.\n\n## Limitations\n\nThis is a case series — observational, not a randomized controlled trial. With 25 patients and no control group, confounding factors cannot be excluded. Sodium bicarbonate alone can improve eGFR in acidotic patients, making it difficult to attribute improvement specifically to niacin. Larger controlled trials are needed.\n\n## Context in GPR109A Research\n\nThis case series fits within a broader literature on niacin's systemic effects mediated through GPR109A. The same receptor that mediates the niacin flush is expressed in kidney tissue, intestinal epithelium, and immune cells — and its activation appears to have anti-inflammatory and cytoprotective effects across organ systems.","study_type":"case-report","model":"human","sample_size":25,"duration":"3 months","blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":"500 mg 3x/day","dose_mg_kg":null,"dose_absolute_mg":1500,"dose_human_equiv_g":1.5,"outcome":"positive","effect_size":"all 25 patients improved by at least one CKD stage","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"ckd","name":"CKD"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":93,"slug":"small-molecule-antagonists-of-naadp-induced-ca2-release-in-t-lymphocytes-suggest-potential-therapeutic-agents-for-autoimmune-disease","title":"Small Molecule Antagonists of NAADP-Induced Ca2+ Release in T-Lymphocytes Suggest Potential Therapeutic Agents for Autoimmune Disease","seo_title":"Blocking NAADP Calcium Release in T-Cells: A New Approach to Autoimmune Disease","publication_title":"https://pure.mpg.de/rest/items/item_3047247/component/file_3048996/content","publication_url":"https://pure.mpg.de/rest/items/item_3047247/component/file_3048996/content","pmid":null,"date":"2021-09-16","publication_year":2018,"description":"Ca2+ is one of the major ways that cells communicate and is involved in the regulation of many important cellular processes from proliferation to apoptosis. Ca2+ regulation is involved in many autoimmune conditions and nicotinic acid (niacin) and is key to this signaling.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"ca2","name":"Ca2+"},{"slug":"nad","name":"NAD+"},{"slug":"t-cell","name":"T-cell"}],"conditions":[{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"},{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":94,"slug":"studies-on-tryptophan-niacin-metabolism-in-streptozotocin-diabetic-rats","title":"Studies on Tryptophan-Niacin Metabolism in Streptozotocin Diabetic Rats","seo_title":"How Diabetes Disrupts the Tryptophan-to-Niacin Conversion Pathway","publication_title":"Studies on Tryptophan-Niacin Metabolism in Streptozotocin Diabetic Rats","publication_url":"https://doi.org/10.2337/diab.23.12.977","pmid":null,"date":"2023-05-14","publication_year":1974,"description":"Rats where split into 2 groups, one group was injected with a single does of  streptozotocin at a dose of 60 mg/kg body weight, which is a chemical that is used to induce diabetes. After 12 weeks it was found that the diabetes group was only able to convert half as much tryptophan to niacins as the control group. The rats in the diabetic group had twice  the excretion of xanthurenic acid in their urine. Xanthurenic acid is a waste product that is produced when tryptophan is not converted into niacin.","body_markdown":null,"study_type":"animal","model":"rat","sample_size":null,"duration":"12 weeks","blinded":null,"intervention":"tryptophan","route":"intraperitoneal","dose_reported":"60 mg/kg streptozotocin (single injection to induce diabetes)","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"negative","effect_size":"diabetic rats converted half as much tryptophan to niacin vs control","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"tryptophan","name":"tryptophan"}],"conditions":[{"slug":"diabetes","name":"diabetes"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":95,"slug":"supplementation-of-nicotinic-acid-and-its-derivatives-up-regulates-cellular-nad-level-rather-than-nicotinamide-derivatives-in-cultured-normal-human-epidermal-keratinocytes","title":"Supplementation of nicotinic acid and its derivatives up-regulates cellular NAD+ level rather than nicotinamide derivatives in cultured normal human epidermal keratinocytes","seo_title":"Nicotinic Acid Raises Skin Cell NAD+ More Than Nicotinamide Does","publication_title":"Supplementation of nicotinic acid and its derivatives up-regulates cellular NAD+ level rather than nicotinamide derivatives in cultured normal human epidermal keratinocytes","publication_url":"https://www.researchsquare.com/article/rs-2481861/v1","pmid":null,"date":"2023-03-26","publication_year":2023,"description":"In cultured skin cells, nicotinic acid supplementation 1.3-fold up-regulated intracellular NAD+ level significantly and its metabolites nicotinic acid mono nucleotide also increased NAD+ level by 1.5-fold with 100 μM application. Surprisingly, NAM and its derivatives could not up-regulate cellular NAD+ levels in keratinocytes.","body_markdown":"## Overview\n\nThis preprint (Research Square, 2023) tested whether different forms of vitamin B3 can raise NAD+ levels in human skin cells — specifically, normal human epidermal keratinocytes. The key finding: **nicotinic acid (niacin) significantly raises NAD+ levels in skin cells, while niacinamide (nicotinamide/NAM) and its derivatives do not**.\n\nThis has direct relevance for anyone supplementing for skin health, psoriasis, or anti-aging: the NAD+-boosting effect in skin tissue appears specific to nicotinic acid, not the more popular niacinamide form.\n\n## Key Findings\n\n- **Nicotinic acid at 100 μM**: 1.3-fold increase in intracellular NAD+ levels (statistically significant)\n- **Nicotinic acid mononucleotide (NaMN)**: 1.5-fold increase in NAD+ at 100 μM application\n- **Niacinamide (NAM) and its derivatives**: Could **not** up-regulate cellular NAD+ levels in keratinocytes\n\nThis is a striking result. The supplement industry widely promotes niacinamide for skin health, but if the mechanism involves NAD+ restoration in skin cells, this study suggests niacinamide is the wrong compound.\n\n## Why This Matters for Skin\n\nNAD+ is essential for cellular energy production, DNA repair, and the activity of sirtuins — enzymes involved in cellular aging and stress response. Keratinocytes (the primary cells of the outer skin layer) are metabolically active and undergo rapid turnover. Low NAD+ in keratinocytes has been associated with impaired skin barrier function and inflammatory conditions.\n\nThe GPR109A receptor — activated by nicotinic acid, not niacinamide — is also expressed in skin cells and keratinocytes. Separate research shows GPR109A activation has anti-inflammatory effects in the skin, which is one proposed mechanism for niacin's benefit in psoriasis. This study adds another mechanism: direct NAD+ elevation.\n\n## The Nicotinic Acid vs. Niacinamide Distinction\n\nBoth compounds are marketed as \"niacin\" or \"vitamin B3,\" but they are pharmacologically distinct:\n\n| Property | Nicotinic Acid | Niacinamide |\n|----------|----------------|-------------|\n| GPR109A activation | Yes | No |\n| Niacin flush | Yes | No |\n| NAD+ in keratinocytes | Yes (this study) | No (this study) |\n| Typical use | Lipid management, research | Skincare serums |\n\nThis confusion between the two forms is one reason the niacin research literature is difficult to interpret. Studies on skin health that use niacinamide may be missing the effects specific to nicotinic acid.\n\n## Limitations\n\nThis is an in vitro study using cultured cells. Whether the same dose-response relationship holds in vivo — in intact skin of living humans — requires clinical research. Cell culture conditions can differ significantly from tissue conditions in the body. Nonetheless, the finding is mechanistically plausible and consistent with other research showing tissue-specific NAD+ metabolism.","study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":"100 uM","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"1.3-fold NAD+ increase (nicotinic acid); 1.5-fold (NaMN); no increase (niacinamide)","mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"}],"conditions":[{"slug":"dermatitis","name":"dermatitis"},{"slug":"psoriasis","name":"psoriasis"},{"slug":"aging","name":"aging"}],"pathways":[{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":96,"slug":"the-covid-19-burden-or-tryptophan-syndrome-autoimmunity-immunoparalysis-and-tolerance-in-a-tumorigenic-environment","title":"The COVID-19 Burden or Tryptophan Syndrome: Autoimmunity, Immunoparalysis and Tolerance in a Tumorigenic Environment","seo_title":"Niacin and Long COVID: Tryptophan Disruption May Drive COVID Symptoms","publication_title":"https://clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-195.php?jid=jide","publication_url":"https://clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-195.php?jid=jide","pmid":null,"date":"2021-09-16","publication_year":2021,"description":"Long covid is due to changes in the metabolism of tryptophan and the lack of niacin (NAD/NADH+). Tryptophan has its metabolism altered by the lack of intestinal absorption due to internalization of ACE-2 and hypoxemia and inflammation, diverting its products to the formation of toxic Kynurenine metabolites. The longer time under hypoxemia, the less niacin and the more tryptophan will deviate to Kynurenine in an inflamed environment","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"neutral","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadh","name":"NADH"},{"slug":"tryptophan","name":"tryptophan"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"},{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":97,"slug":"the-effect-of-melatonin-on-thrombosis-sepsis-and-mortality-rate-in-covid-19-patients","title":"The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients","seo_title":"Melatonin Reduces Thrombosis and Mortality in COVID-19 Patients","publication_title":"https://www.sciencedirect.com/science/article/pii/S1201971221007980","publication_url":"https://www.sciencedirect.com/science/article/pii/S1201971221007980","pmid":null,"date":"2021-10-24","publication_year":2021,"description":"Single-center, open-label, randomized clinical trial done on Covid patients in Iraq to study melatonin supplementation for Covid treatment. All 158 patients got standard care, 82 of those patients ate 10mg melatonin each night. Thrombosis and sepsis developed significantly less in melatonin group. 13 patients in control group died vs 1 person in the melatonin group.","body_markdown":null,"study_type":"rct","model":"human","sample_size":158,"duration":null,"blinded":null,"intervention":"melatonin","route":"oral","dose_reported":"10 mg/night","dose_mg_kg":null,"dose_absolute_mg":10,"dose_human_equiv_g":0.01,"outcome":"positive","effect_size":"13 deaths in control vs 1 in melatonin group","mechanisms":[{"slug":"nf-kb","name":"NF-kB"},{"slug":"tnf-alpha","name":"TNF-alpha"}],"conditions":[{"slug":"sepsis","name":"sepsis"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions"}]},{"id":98,"slug":"the-importance-of-“folic-acid”-in-rations-low-in-nicotinic-acid","title":"The Importance of \"Folic Acid\" in Rations low in Nicotinic Acid","seo_title":null,"publication_title":"The Importance of \"Folic Acid\" in Rations low in Nicotinic Acid","publication_url":"https://www.sciencedirect.com/science/article/pii/S0021925817416036/pdf?md5=97a21b4e592bfa627e2bee3b64c63ab1&pid=1-s2.0-S0021925817416036-main.pdf","pmid":null,"date":"2022-12-21","publication_year":1945,"description":"Dogs with severe niacin deficiency required folic acid to be administered in tandem with niacin in order to recover and avoid death.","body_markdown":null,"study_type":"animal","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"combination","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"pellagra","name":"pellagra"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":99,"slug":"the-isolation-and-identification-of-the-anti-black-tongue-factor","title":"The isolation and identification of the anti-black tongue factor","seo_title":"Anti-Black Tongue Factor: 1937 Study Identified Niacin as Vitamin B3","publication_title":"The isolation and identification of the anti-black tongue factor","publication_url":"https://www.jbc.org/article/S0021-9258(18)74164-1/pdf","pmid":null,"date":"2021-09-12","publication_year":1937,"description":"A study from 1937 showing supplementing niacin cures black tongue in dogs just as well as feeding them liver. Other studies from the time are also mentioned such as one that shows rats supplementing nicotinic acid (niacin) lived longer.","body_markdown":"## Overview\n\nThis landmark 1937 paper by Elvehjem, Madden, Strong, and Woolley (Journal of Biological Chemistry) established that nicotinic acid — niacin / vitamin B3 — is the \"anti-black tongue factor\" that cures black tongue disease in dogs. The paper confirmed that synthesized nicotinic acid, not liver extract, was the active compound responsible for the curative effects long associated with liver supplementation.\n\n## What Is Black Tongue Disease?\n\nBlack tongue in dogs was a well-characterized nutritional deficiency disease in the 1930s, analogous to pellagra in humans. Affected dogs developed inflamed, dark lesions on the tongue and oral mucosa (hence \"black tongue\"), along with salivation, gastrointestinal inflammation, and eventual death if untreated. For years it was known that feeding dogs raw liver cured the condition, but the active component was unknown.\n\n## The Isolation\n\nThe 1937 paper describes systematic fractionation of liver and yeast to isolate the active compound. The researchers identified it as **nicotinic acid** — a molecule already known to chemists as a derivative of pyridine, but not previously recognized as a vitamin. They demonstrated that pure synthetic nicotinic acid at small doses cured black tongue as effectively as liver.\n\nThis was a pivotal moment: nicotinic acid was established as the vitamin responsible for preventing pellagra in humans and black tongue in dogs, and could now be synthesized and given in pure form.\n\n## The Rat Longevity Note\n\nThe paper also references a separate study showing that rats supplemented with nicotinic acid lived significantly longer than unsupplemented controls — an early data point suggesting niacin's effects extend beyond simple deficiency correction.\n\n## Historical Significance\n\nThe isolation of the anti-black tongue factor as nicotinic acid is one of the foundational discoveries in vitamin history. It opened the research path to understanding niacin's pharmacology at therapeutic doses — doses far above the nutritional requirement — including its effects on lipid metabolism, GPR109A activation, and inflammatory modulation.\n\n**Note on naming:** The term \"niacin\" is used loosely for both nicotinic acid (the compound isolated in this paper) and niacinamide (nicotinamide). The anti-black tongue factor was specifically nicotinic acid. The two forms have distinct pharmacological profiles and are not interchangeable for all purposes.","study_type":"animal","model":"n/a","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"pellagra","name":"pellagra"}],"pathways":[{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":100,"slug":"the-lifespan-extension-ability-of-nicotinic-acid-depends-on-whether-the-intracellular-nad-level-is-lower-than-the-sirtuin-saturating-concentrations","title":"The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations","seo_title":"Niacin Extends Lifespan Only When NAD+ Levels Are Below Sirtuin Saturation","publication_title":"The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations","publication_url":"https://europepmc.org/article/PMC/PMC5435603","pmid":null,"date":"2022-06-18","publication_year":2017,"description":"Cultural cell study indicates the lifespan extension ability of niacin depends on whether the intracellular NAD+ level was lower than the sirtuin-saturating concentration.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"}],"conditions":[{"slug":"aging","name":"aging"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":101,"slug":"the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation","title":"The NAD + precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation","seo_title":"Niacin Improves DNA Integrity in Blood Cells After Radiation Exposure","publication_title":"https://pubmed.ncbi.nlm.nih.gov/28216063/","publication_url":"https://pubmed.ncbi.nlm.nih.gov/28216063/","pmid":"28216063","date":"2021-09-14","publication_year":2017,"description":"Peripheral blood mononuclear cells (diverse mix of highly specialized immune cells) supplemented with nicotinic acid (niacin) and then blasted by x-ray radiation showed increased NAD+ levels, improved DNA repair efficiency and enhanced genomic stability compared to control.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"dna-repair","name":"DNA-repair"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":102,"slug":"the-niacin-butyrate-receptor-gpr109a-suppresses-mammary-tumorigenesis-by-inhibiting-cell-survival","title":"The Niacin/Butyrate Receptor GPR109A Suppresses Mammary Tumorigenesis by Inhibiting Cell Survival","seo_title":"GPR109A Receptor Suppresses Breast Tumor Growth via Niacin and Butyrate","publication_title":"The Niacin/Butyrate Receptor GPR109A Suppresses Mammary Tumorigenesis by Inhibiting Cell Survival","publication_url":"https://cancerres.aacrjournals.org/content/74/4/1166","pmid":null,"date":"2021-09-16","publication_year":2014,"description":"The expression of niacin receptor GPR109A is decreased by over 70% in breast cancer samples. It's reduced in early stages, and almost undetectable in advanced stages. Increasing expression of GPR109A seems to act as a tumor suppressor in breast tissue, but interestingly can also acts as tumor protective in other tissues like skin, mechanism of differentiation unknown.","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"GPR109A expression decreased >70% in breast cancer samples","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"apoptosis","name":"apoptosis"},{"slug":"butyrate","name":"butyrate"}],"conditions":[{"slug":"cancer","name":"cancer"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"},{"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit"}]},{"id":103,"slug":"the-oxidative-stress-induced-niacin-sink-osins-model-for-hiv-pathogenesis","title":"The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis","seo_title":"HIV Causes Niacin Deficiency via Oxidative Stress — The OSINS Model Explained","publication_title":"The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis","publication_url":"https://pubmed.ncbi.nlm.nih.gov/19857540/","pmid":"19857540","date":"2021-09-14","publication_year":2009,"description":"Talks about how intracellular niacin depletion along leads to tryptophan depletion as the body attempts to compensate by synthesizing niacin from tryptophan. And how this imbalance impairs the immune system in HIV.","body_markdown":null,"study_type":"mechanistic","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"neutral","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nadph","name":"NADPH"},{"slug":"parp","name":"PARP"},{"slug":"tryptophan","name":"tryptophan"},{"slug":"t-cell","name":"T-cell"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis"}]},{"id":104,"slug":"the-treatment-of-migraines-and-tension-type-headaches-with-intravenous-and-oral-niacin-nicotinic-acid-systematic-review-of-the-literature","title":"The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature","seo_title":"Niacin for Migraines: Systematic Review of IV and Oral Nicotinic Acid","publication_title":"The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature","publication_url":"https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC548511/","pmid":null,"date":"2021-09-16","publication_year":2003,"description":"An overview of the evidence for using niacin to treat headaches. Mechanisms explored are vasodilation, improvement of mitochondrial energy metabolism, improved oxygenation, lowering of lactic acid.","body_markdown":null,"study_type":"review","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"atp","name":"ATP"},{"slug":"prostaglandin","name":"prostaglandin"}],"conditions":[{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"},{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"}]},{"id":105,"slug":"the-β-hydroxybutyrate-receptor-hca2-activates-a-neuroprotective-subset-of-macrophages","title":"The β-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages","seo_title":null,"publication_title":"The β-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages","publication_url":"https://www.nature.com/articles/ncomms4944","pmid":null,"date":"2022-12-21","publication_year":2014,"description":"Nicotinic acid mimics the effect of a ketogenic diet in activating HCA2, which induces a neuroprotective phenotype in bone marrow-derived macrophages that infiltrate the brain and that this results in an improved outcome in a mouse model of stroke.","body_markdown":null,"study_type":"animal","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"macrophage","name":"macrophage"},{"slug":"pgd2","name":"PGD2"}],"conditions":[{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":106,"slug":"treatment-of-arthritis-by-nicotinic-acid-and-nicotinamide","title":"Treatment of Arthritis by Nicotinic Acid and Nicotinamide","seo_title":"Niacin and Niacinamide as Early Treatments for Arthritis: Historical Evidence","publication_title":"Treatment of Arthritis by Nicotinic Acid and Nicotinamide","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831040/pdf/canmedaj00811-0022.pdf","pmid":null,"date":"2022-09-24","publication_year":1943,"description":"Reports of patients successfully managing or curing various forms of arthritis via nicotinic and/or nicotinamide supplementation. A daily dosage of about one gram per 50 lb. body weight is necessary.","body_markdown":null,"study_type":"case-report","model":"human","sample_size":null,"duration":null,"blinded":null,"intervention":"combination","route":"oral","dose_reported":"~1 g per 50 lb body weight per day","dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"arthritis","name":"arthritis"},{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}],"pathways":[{"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":107,"slug":"treatment-of-asthma-by-nicotinic-acid","title":"Treatment of Asthma by Nicotinic Acid","seo_title":"Niacin as an Early Treatment for Asthma: Historical Evidence","publication_title":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2282923/pdf/brmedj03990-0011.pdf","publication_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2282923/pdf/brmedj03990-0011.pdf","pmid":null,"date":"2022-11-27","publication_year":1944,"description":"Relief of the asthma attacks was obtained in 21 out of 30 cases with niacin either via intravenous injection (16 out of 21 patients relieved) or orally (5 out of 9 patients relieved). A series of 50 or 100 mg doses used. Relapse was common once niacin was discontinued.","body_markdown":null,"study_type":"case-report","model":"human","sample_size":30,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":"50 or 100 mg doses","dose_mg_kg":null,"dose_absolute_mg":100,"dose_human_equiv_g":0.1,"outcome":"positive","effect_size":"21 out of 30 cases relieved (70%)","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"prostaglandin","name":"prostaglandin"}],"conditions":[{"slug":"asthma","name":"asthma"},{"slug":"inflammation","name":"inflammation"}],"pathways":[{"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect"},{"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem"}]},{"id":108,"slug":"trpv4-stimulation-induced-melatonin-secretion-by-increasing-arylalkymine-n-acetyltransferase-aanat-protein-level","title":"TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level","seo_title":"AANAT Enzyme: How TRPV4 Stimulation Boosts Melatonin Secretion","publication_title":"TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level","publication_url":"https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5412331/","pmid":null,"date":"2021-10-23","publication_year":2017,"description":"The role of TRPV4 channel present in human ciliary body epithelial cells in AANAT  production was studied. AANAT, Aralkylamine N-acetyltransferase seems to be the key enzyme involved in producing melatonin from serotonin. In rodents, transcriptional activation of aanat gene is the classical mechanism to induce melatonin biosynthesis. TRPV4 is present in the human ciliary body and ciliary body epithelial cells. Activating TRPV4 channel increases the expression of AANAT, which elevates the concentration of NAS and melatonin","body_markdown":null,"study_type":"in-vitro","model":"cell-line","sample_size":null,"duration":null,"blinded":null,"intervention":"none","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":null,"mechanisms":[{"slug":"ca2","name":"Ca2+"},{"slug":"melatonin","name":"melatonin"}],"conditions":[],"pathways":[]},{"id":109,"slug":"vitamin-b3-and-seborrheic-dermatitis-a-phase-iv-clinical-study-of-fda-data","title":"Vitamin b3 and Seborrheic dermatitis - a phase IV clinical study of FDA data","seo_title":"Vitamin B3 for Seborrheic Dermatitis: Analysis of FDA Clinical Data","publication_title":"Vitamin b3 and Seborrheic dermatitis - a phase IV clinical study of FDA data","publication_url":"https://www.ehealthme.com/ds/vitamin-b3/seborrheic-dermatitis/","pmid":null,"date":"2023-03-26","publication_year":2023,"description":"Study of 4,269 people that take niacin or have Seborrheic dermatitis finds no cases of Seborrheic dermatitis in people who take niacin.","body_markdown":null,"study_type":"ecological","model":"human","sample_size":4269,"duration":null,"blinded":null,"intervention":"nicotinic-acid","route":"oral","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"positive","effect_size":"0 cases of seborrheic dermatitis among niacin users (n=4269)","mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"dermatitis","name":"dermatitis"}],"pathways":[{"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor"}]},{"id":110,"slug":"wallerian-degeneration-is-executed-by-an-nmn-sarm1-dependent-late-ca2-influx-but-only-modestly-influenced-by-mitochondria","title":"Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca2+ Influx but Only Modestly Influenced by Mitochondria","seo_title":"NMN and SARM1 Drive Nerve Fiber Degeneration — NMN Is Not Always Beneficial","publication_title":"Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca2+ Influx but Only Modestly Influenced by Mitochondria","publication_url":"https://www.cell.com/cell-reports/fulltext/S2211-1247(15)01347-9","pmid":null,"date":"2023-03-11","publication_year":2015,"description":"Nicotinamide mononucleotide (NMN) accumulation in the extra cellular environment contributes to the breakdown of axons (nerve fibers).","body_markdown":null,"study_type":"mechanistic","model":"mouse","sample_size":null,"duration":null,"blinded":null,"intervention":"NMN","route":"n/a","dose_reported":null,"dose_mg_kg":null,"dose_absolute_mg":null,"dose_human_equiv_g":null,"outcome":"negative","effect_size":null,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"ca2","name":"Ca2+"}],"conditions":[{"slug":"neuroinflammation","name":"neuroinflammation"}],"pathways":[{"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease"},{"slug":"counter-evidence","title":"What the Evidence Doesn't Show"}]}],"mechanisms":[{"id":18,"slug":"adiponectin","name":"adiponectin","description":null},{"id":13,"slug":"ampk","name":"AMPK","description":null},{"id":22,"slug":"apoptosis","name":"apoptosis","description":null},{"id":25,"slug":"atp","name":"ATP","description":null},{"id":10,"slug":"butyrate","name":"butyrate","description":null},{"id":29,"slug":"ca2","name":"Ca2+","description":null},{"id":27,"slug":"cox-2","name":"COX-2","description":null},{"id":12,"slug":"dna-repair","name":"DNA-repair","description":null},{"id":1,"slug":"gpr109a","name":"GPR109A","description":null},{"id":26,"slug":"hdac","name":"HDAC","description":null},{"id":5,"slug":"il-10","name":"IL-10","description":null},{"id":19,"slug":"il-18","name":"IL-18","description":null},{"id":24,"slug":"il-6","name":"IL-6","description":null},{"id":9,"slug":"macrophage","name":"macrophage","description":null},{"id":11,"slug":"melatonin","name":"melatonin","description":null},{"id":28,"slug":"mtor","name":"mTOR","description":null},{"id":2,"slug":"nad","name":"NAD+","description":null},{"id":17,"slug":"nadh","name":"NADH","description":null},{"id":16,"slug":"nadph","name":"NADPH","description":null},{"id":6,"slug":"nf-kb","name":"NF-kB","description":null},{"id":21,"slug":"p53","name":"p53","description":null},{"id":7,"slug":"parp","name":"PARP","description":null},{"id":8,"slug":"pgd2","name":"PGD2","description":null},{"id":15,"slug":"prostaglandin","name":"prostaglandin","description":null},{"id":3,"slug":"sirt1","name":"SIRT1","description":null},{"id":23,"slug":"t-cell","name":"T-cell","description":null},{"id":20,"slug":"tnf-alpha","name":"TNF-alpha","description":null},{"id":4,"slug":"treg","name":"Treg","description":null},{"id":14,"slug":"tryptophan","name":"tryptophan","description":null}],"conditions":[{"id":14,"slug":"aging","name":"aging","description":null},{"id":27,"slug":"alzheimers","name":"alzheimers","description":null},{"id":4,"slug":"arthritis","name":"arthritis","description":null},{"id":6,"slug":"asthma","name":"asthma","description":null},{"id":8,"slug":"atherosclerosis","name":"atherosclerosis","description":null},{"id":1,"slug":"autoimmune","name":"autoimmune","description":null},{"id":25,"slug":"brain-tumor","name":"brain-tumor","description":null},{"id":11,"slug":"cancer","name":"cancer","description":null},{"id":29,"slug":"ckd","name":"CKD","description":null},{"id":3,"slug":"colitis","name":"colitis","description":null},{"id":23,"slug":"colorectal-cancer","name":"colorectal-cancer","description":null},{"id":18,"slug":"depression","name":"depression","description":null},{"id":17,"slug":"dermatitis","name":"dermatitis","description":null},{"id":15,"slug":"diabetes","name":"diabetes","description":null},{"id":7,"slug":"dyslipidemia","name":"dyslipidemia","description":null},{"id":21,"slug":"fertility","name":"fertility","description":null},{"id":19,"slug":"gulf-war-illness","name":"gulf-war-illness","description":null},{"id":24,"slug":"hearing-loss","name":"hearing-loss","description":null},{"id":10,"slug":"inflammation","name":"inflammation","description":null},{"id":28,"slug":"insulin-resistance","name":"insulin-resistance","description":null},{"id":9,"slug":"liver","name":"liver","description":null},{"id":13,"slug":"me-cfs","name":"ME-CFS","description":null},{"id":5,"slug":"multiple-sclerosis","name":"multiple-sclerosis","description":null},{"id":12,"slug":"neuroinflammation","name":"neuroinflammation","description":null},{"id":22,"slug":"obesity","name":"obesity","description":null},{"id":20,"slug":"parkinsons","name":"parkinsons","description":null},{"id":16,"slug":"pellagra","name":"pellagra","description":null},{"id":2,"slug":"psoriasis","name":"psoriasis","description":null},{"id":26,"slug":"sepsis","name":"sepsis","description":null}],"pathways":[{"id":1,"slug":"gpr109a-immune","title":"Nicotinic Acid and the GPR109A Receptor","description":"How nicotinic acid activates GPR109A to promote regulatory T cells and suppress inflammation.","weight":1,"category":"mechanism","status":"hypothesis","body_markdown":"## The receptor hypothesis\n\nNicotinic acid binds GPR109A (also called HCA2 or HCAR2), a G-protein-coupled receptor expressed on immune cells — macrophages, dendritic cells, neutrophils, and colonic epithelial cells. This binding triggers a signaling cascade that shifts the immune system toward anti-inflammatory regulation.\n\nThe key steps: GPR109A activation → prostaglandin D2 release → promotion of regulatory T cells (Treg) → increased IL-10 (an anti-inflammatory cytokine) → suppression of NF-kB-mediated inflammation.\n\nThis pathway is specific to nicotinic acid. Niacinamide does not activate GPR109A. Neither does NR or NMN. This specificity is the strongest argument that nicotinic acid's immune effects operate through GPR109A rather than through NAD+ metabolism alone.\n\n## Evidence in the gut\n\nThe most robust evidence comes from colitis models. Multiple studies demonstrate that GPR109A activation by nicotinic acid (or its endogenous agonist butyrate) suppresses colonic inflammation and carcinogenesis. Knockout mice lacking GPR109A lose the protective effect entirely.\n\nIn a striking human study, 26 patients with moderate ulcerative colitis unresponsive to conventional treatment received daily niacin enemas for 6 weeks. 92.3% responded positively and 88.5% achieved clinical remission — mediated through prostaglandin D2 and the D prostanoid receptor 1 pathway.\n\n## Evidence in the brain\n\nGPR109A is expressed in microglia and macrophages in the central nervous system. Niacin treatment reactivates myeloid cells in brain tumor models, reducing tumor size and prolonging survival. Separate evidence shows GPR109A-dependent neuroprotection through the β-hydroxybutyrate receptor pathway, activating a protective subset of macrophages.\n\nFor Parkinson's disease, niacin supplementation may operate through three concurrent GPR109A-related mechanisms: reduced neuroinflammation, increased dopamine production via NADPH, and improved mitochondrial function.\n\n## Evidence in the skin\n\nPsoriatic skin shows decreased expression of GPR109A. Topical sodium butyrate (another GPR109A agonist) can restore receptor expression. This suggests a feedback loop: chronic inflammation downregulates the receptor that would help resolve it, and exogenous GPR109A agonists can break the cycle.\n\n## Evidence in macrophage function\n\nActivated GPR109A inhibits chemoattractant-mediated macrophage migration via the Gβγ/PKC/ERK1/2 pathway. Niacin shifts macrophages from proinflammatory to anti-inflammatory phenotypes — a mechanism with implications across multiple autoimmune conditions.\n\nInflammation itself upregulates GPR109A expression in adipose tissue and macrophages, suggesting a built-in amplification loop: the more inflamed the tissue, the more responsive it becomes to nicotinic acid signaling.\n\n## What remains unknown\n\n- **Human dose-response**: Most GPR109A evidence comes from animal models. The dose at which GPR109A-mediated immune effects become clinically significant in humans is poorly characterized.\n- **Tissue-specific activation**: GPR109A is expressed differently across tissues. Whether systemic nicotinic acid supplementation activates the receptor sufficiently in all relevant tissues (gut, brain, skin, joints) is unclear.\n- **Duration effects**: Long-term GPR109A activation patterns are unstudied. Does the receptor desensitize? Does the immune shift persist after discontinuation?\n- **Interaction with other pathways**: GPR109A effects overlap with NAD+ metabolism effects. Isolating the receptor-specific contribution from the metabolic contribution remains difficult.","study_count":40,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"il-10","name":"IL-10"},{"slug":"treg","name":"Treg"},{"slug":"pgd2","name":"PGD2"},{"slug":"macrophage","name":"macrophage"}],"conditions":[{"slug":"colitis","name":"colitis"},{"slug":"psoriasis","name":"psoriasis"},{"slug":"neuroinflammation","name":"neuroinflammation"},{"slug":"autoimmune","name":"autoimmune"}]},{"id":2,"slug":"nad-depletion","title":"NAD+ Deficiency as a Driver of Autoimmune Disease","description":"NAD+ as master regulator: how depletion through the Preiss-Handler pathway connects to immune dysfunction.","weight":2,"category":"mechanism","status":"hypothesis","body_markdown":"## NAD+ as master regulator\n\nNicotinamide adenine dinucleotide (NAD+) is a coenzyme present in every living cell. It is essential for energy metabolism, DNA repair, gene expression, and cell signaling. Over 500 enzymatic reactions depend on it.\n\nNicotinic acid feeds NAD+ synthesis via the Preiss-Handler pathway — a three-step conversion that is distinct from the salvage pathway used by niacinamide or NR. This distinction matters: the Preiss-Handler pathway may have tissue-specific advantages that explain why nicotinic acid produces effects that other NAD+ precursors do not.\n\n## The depletion hypothesis\n\nNAD+ levels decline with age and chronic inflammation. PARP enzymes consume NAD+ during DNA repair. SIRT1 and other sirtuins consume NAD+ to deacetylate proteins that regulate inflammation and metabolism. Under conditions of chronic immune activation, NAD+ consumption can exceed synthesis, creating a deficit.\n\nThis deficit has cascading effects: impaired DNA repair (genomic instability), reduced sirtuin activity (loss of anti-inflammatory regulation via SIRT1), compromised energy metabolism (mitochondrial dysfunction), and weakened immune homeostasis.\n\n## Evidence\n\nNAD+ homeostasis disruption is documented in multiple disease states. In adult-onset mitochondrial myopathy, systemic NAD+ deficiency was confirmed and high-dose niacin (750-1000mg/day) improved muscle performance by rescuing NAD+ levels.\n\nIn congenital malformation research, NAD+ deficiency during pregnancy causes multiple organ malformations in mice, preventable by niacin supplementation. This demonstrates that NAD+ availability is not merely metabolic but structurally developmental.\n\nCoronavirus infection and PARP expression dysregulate the NAD+ metabolome, suggesting that acute immune challenges can rapidly deplete NAD+. This positions NAD+ depletion as both a chronic aging phenomenon and an acute infection response.\n\nPharmacological doses of niacin increase bone marrow poly(ADP-ribose) — the PARP substrate — and extend the latency of carcinogenesis. Niacin requirements for genomic stability suggest that the RDA is optimized for preventing pellagra, not for maintaining DNA repair capacity.\n\n## The sirtuin connection\n\nNicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway. SIRT1 requires NAD+ as a substrate. By raising NAD+ levels, nicotinic acid fuels the very enzyme that suppresses inflammatory gene expression.\n\nThe lifespan extension ability of nicotinic acid depends on whether intracellular NAD+ levels are below sirtuin-saturating concentrations — suggesting that supplementation benefits are greatest when there is an existing deficit.\n\n## Beyond metabolism\n\nNAD+ depletion affects the gut microbiome. Bacteria boost mammalian host NAD+ metabolism by engaging the deamidated biosynthesis pathway (the same Preiss-Handler pathway that nicotinic acid feeds). This creates a gut-liver-immune axis where microbiome health directly influences NAD+ availability.\n\nNuclear de novo NAD+ synthesis via histone dynamics influences DNA repair during cellular senescence. This epigenetic dimension means NAD+ levels affect gene expression patterns, not just metabolic rates.\n\n## What remains unknown\n\n- **Measurement**: NAD+ levels are difficult to measure in living humans. Most evidence for depletion is indirect or from animal models.\n- **Optimal levels**: What NAD+ concentration is \"sufficient\" for immune homeostasis? The answer likely varies by tissue and disease state.\n- **Pathway specificity**: Whether the Preiss-Handler pathway (nicotinic acid) produces qualitatively different NAD+ distribution than the salvage pathway (niacinamide/NR) in humans.\n- **Dose to replete**: How much nicotinic acid is needed to meaningfully raise NAD+ in depleted individuals? The RDA is clearly insufficient for therapeutic purposes, but the optimal therapeutic range is undefined.","study_count":41,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"},{"slug":"parp","name":"PARP"},{"slug":"dna-repair","name":"DNA-repair"},{"slug":"ampk","name":"AMPK"}],"conditions":[{"slug":"autoimmune","name":"autoimmune"},{"slug":"aging","name":"aging"},{"slug":"cancer","name":"cancer"},{"slug":"diabetes","name":"diabetes"},{"slug":"neuroinflammation","name":"neuroinflammation"}]},{"id":3,"slug":"gut-immune-axis","title":"Butyrate, GPR109A, and the Gut-Immune Circuit","description":"How dysbiosis reduces butyrate, impairs GPR109A signaling, and how niacin bypasses the broken microbiome.","weight":3,"category":"mechanism","status":"hypothesis","body_markdown":"## The circuit\n\nButyrate is a short-chain fatty acid produced by gut bacteria from dietary fiber. It is the primary endogenous agonist of GPR109A in the colon. When gut bacteria produce sufficient butyrate, GPR109A signaling maintains immune tolerance in the gut — promoting regulatory T cells, suppressing inflammatory cytokines, and maintaining epithelial barrier integrity.\n\nWhen this circuit breaks — through dysbiosis, antibiotic use, poor diet, or chronic illness — butyrate production drops, GPR109A signaling weakens, and gut immune regulation fails. The resulting inflammation further damages the microbiome, creating a self-reinforcing cycle.\n\nNicotinic acid is an exogenous GPR109A agonist. It can activate the same receptor that butyrate would, bypassing the broken microbiome entirely.\n\n## Evidence for the circuit\n\nActivation of GPR109A by both niacin and butyrate suppresses colonic inflammation and carcinogenesis in multiple studies. The mechanism requires GPR109A — knockout models show no benefit.\n\nDeficient butyrate-producing capacity in the gut microbiome is documented in ME/CFS patients and is associated with fatigue symptoms. This connects microbiome dysfunction to a specific immune-mediated condition through a measurable metabolite.\n\nBacterial PNCa (nicotinic acid-converting enzyme) improves diet-induced fatty liver in mice by enabling the transition from nicotinamide to nicotinic acid — showing that the gut microbiome itself participates in niacin metabolism and GPR109A signaling.\n\n## The melatonin connection\n\nGut melatonin — produced by enterochromaffin cells in quantities far exceeding pineal production — is a potent modulator of gut immune function. Gut dysbiosis dysregulates central and systemic homeostasis via decreased melatonin and suboptimal mitochondrial functioning.\n\nMelatonin alleviates titanium nanoparticle-induced osteolysis via activation of the butyrate/GPR109A signaling pathway, directly linking melatonin to the same receptor that nicotinic acid activates.\n\nTRPV4 stimulation induces melatonin secretion, and nicotinic acid is a common regulator of heat-sensing TRPV1-4 ion channels. This creates an unexpected connection: nicotinic acid may influence gut melatonin production through TRPV channel regulation.\n\n## The COVID-19 intersection\n\nIntestinal flora was identified as a potential strategy against SARS-CoV-2 infection, with butyrate-producing bacteria and GPR109A signaling implicated in immune defense. Network pharmacology analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets.\n\nCoronavirus infection depletes NAD+ through PARP dysregulation, while simultaneously disrupting the gut microbiome — attacking both sides of the niacin-GPR109A-immune axis simultaneously.\n\n## What remains unknown\n\n- **Dose to substitute for butyrate**: How much oral nicotinic acid produces equivalent GPR109A activation in the colon compared to endogenous butyrate production?\n- **Microbiome restoration**: Does nicotinic acid supplementation help restore butyrate-producing bacteria, or does it merely substitute for their absence?\n- **Route matters**: The ulcerative colitis study used niacin enemas (direct colonic application). Whether oral niacin reaches the colon in sufficient concentration for local GPR109A activation is unclear.\n- **ME/CFS connection**: The butyrate deficiency in ME/CFS is documented, but whether nicotinic acid supplementation improves ME/CFS symptoms through GPR109A compensation has not been tested.","study_count":15,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"butyrate","name":"butyrate"},{"slug":"treg","name":"Treg"},{"slug":"il-10","name":"IL-10"},{"slug":"melatonin","name":"melatonin"}],"conditions":[{"slug":"colitis","name":"colitis"},{"slug":"me-cfs","name":"ME-CFS"},{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}]},{"id":4,"slug":"autoimmune","title":"Why Nicotinic Acid Helps Autoimmune Conditions","description":"Connecting the threads: GPR109A + NAD+ → specific autoimmune conditions.","weight":4,"category":"mechanism","status":"hypothesis","body_markdown":"## The synthesis\n\nThree mechanisms converge to explain why nicotinic acid specifically (not niacinamide, not NR, not NMN) helps autoimmune conditions:\n\n1. **GPR109A activation** — directly promotes regulatory T cells and anti-inflammatory cytokines\n2. **NAD+ repletion** — fuels SIRT1-mediated suppression of NF-kB inflammatory signaling\n3. **Gut-immune bypass** — substitutes for deficient butyrate signaling in the dysbiotic gut\n\nNo other niacin form activates all three simultaneously. Niacinamide feeds NAD+ but does not activate GPR109A. NR and NMN feed NAD+ through a different pathway and do not activate GPR109A. Only nicotinic acid operates on both the receptor and the metabolic level.\n\n## Condition-specific evidence\n\n**Colitis**: The strongest human evidence. 88.5% remission in treatment-resistant ulcerative colitis with niacin enemas. Mechanism: GPR109A → PGD2 → D prostanoid receptor 1. Supported by multiple animal studies showing GPR109A-dependent suppression of colonic inflammation.\n\n**Psoriasis**: Psoriatic skin shows decreased GPR109A expression. Topical butyrate restores it. Plasma melatonin levels are altered in psoriasis, connecting to the gut-melatonin-GPR109A axis. Clinical evidence is limited but the mechanistic case is strong.\n\n**Arthritis**: Direct clinical evidence from early studies of nicotinic acid and nicotinamide treatment. The mechanism likely operates through both SIRT1-dependent anti-inflammatory signaling and GPR109A-mediated immune regulation.\n\n**Multiple sclerosis**: Niacin-mediated rejuvenation of macrophages and microglia enhances remyelination in the aging central nervous system. GPR109A activation in the CNS promotes a neuroprotective macrophage subset. Animal evidence is compelling; human trials are needed.\n\n**Asthma**: Historical treatment evidence with nicotinic acid. Mechanism likely involves GPR109A-mediated suppression of inflammatory cytokines in airway macrophages.\n\n## The NF-kB convergence\n\nMost autoimmune conditions involve NF-kB pathway overactivation. Nicotinic acid suppresses NF-kB through two independent routes: SIRT1-mediated deacetylation (NAD+-dependent) and GPR109A-mediated signaling. This dual suppression may explain why nicotinic acid produces broader anti-inflammatory effects than either pathway alone would predict.\n\nNiacin attenuates the production of pro-inflammatory cytokines in macrophages by HCA2-dependent (GPR109A-dependent) mechanisms. Nicotinic acid inhibits vascular inflammation via SIRT1-dependent signaling. These are distinct pathways converging on the same inflammatory master switch.\n\n## The calcium channel dimension\n\nNicotinic acid is a common regulator of TRPV1-4 ion channels, and NAADP-induced Ca2+ release in T lymphocytes suggests potential therapeutic targets for autoimmune disease. These calcium signaling mechanisms represent a third dimension of nicotinic acid's immune effects, distinct from both GPR109A and NAD+ pathways.\n\n## What remains unknown\n\n- **Which conditions respond best**: The evidence base varies enormously by condition. Colitis has human data. Psoriasis has strong mechanistic data. MS has animal data. Most others have only indirect evidence.\n- **Dose optimization**: Different autoimmune conditions may require different doses, routes, and durations.\n- **Combination effects**: Whether nicotinic acid combined with standard immunotherapy produces additive or synergistic effects.\n- **Biomarkers**: No reliable biomarker exists to predict which autoimmune patients would benefit most from nicotinic acid supplementation.\n- **The chicken-and-egg**: Does NAD+ depletion drive autoimmunity, or does autoimmune inflammation deplete NAD+? Likely both — but the causal direction matters for treatment timing.","study_count":10,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"},{"slug":"treg","name":"Treg"},{"slug":"il-10","name":"IL-10"},{"slug":"nf-kb","name":"NF-kB"}],"conditions":[{"slug":"autoimmune","name":"autoimmune"},{"slug":"psoriasis","name":"psoriasis"},{"slug":"colitis","name":"colitis"},{"slug":"arthritis","name":"arthritis"},{"slug":"multiple-sclerosis","name":"multiple-sclerosis"},{"slug":"asthma","name":"asthma"}]},{"id":5,"slug":"form-specificity","title":"Nicotinic Acid vs. Niacinamide vs. NR vs. NMN: Why Form Matters","description":"Only nicotinic acid activates GPR109A. The form determines the mechanism.","weight":5,"category":"practice","status":"established","body_markdown":"## The forms\n\nFour common niacin-related supplements exist, each with different properties:\n\n| Form | GPR109A activation | NAD+ pathway | Flush | Typical dose |\n|------|-------------------|-------------|-------|-------------|\n| **Nicotinic acid** (niacin) | Yes | Preiss-Handler | Yes | 500mg-3g |\n| **Niacinamide** (nicotinamide) | No | Salvage | No | 500mg-1.5g |\n| **NR** (nicotinamide riboside) | No | Salvage → NMN | No | 250-500mg |\n| **NMN** (nicotinamide mononucleotide) | No | Direct to NAD+ | No | 250-500mg |\n\nThis distinction is not a minor detail. It is the central fact that determines whether supplementation can activate immune regulatory pathways through GPR109A.\n\n## Why the form matters\n\nNicotinic acid is the only form that activates GPR109A. This receptor is the mechanism behind:\n- Regulatory T cell promotion\n- Anti-inflammatory macrophage polarization\n- Prostaglandin D2-mediated immune signaling\n- The niacin flush itself (which is GPR109A-mediated)\n\nIf a niacin supplement does not cause a flush, it is not activating GPR109A. This is not a side effect to be avoided — it is the signal that the immune-regulatory pathway is being activated.\n\n## NAD+ pathway differences\n\nNicotinic acid enters NAD+ synthesis via the Preiss-Handler pathway (nicotinic acid → NaMN → NaAD → NAD+). All other forms use the salvage pathway or direct conversion.\n\nSupplementation of nicotinic acid and its derivatives shows that nicotinic acid up-regulates cellular NAD+ levels more effectively than nicotinamide derivatives in cultured human epidermal keratinocytes. This may reflect tissue-specific differences in pathway enzyme expression.\n\nBacteria in the gut can convert nicotinamide to nicotinic acid via PNCa, improving liver function in mouse models — suggesting that the gut microbiome mediates some form conversion. But this conversion is unreliable and microbiome-dependent.\n\n## The \"flush-free\" problem\n\nSustained-release niacin formulations and \"flush-free\" versions (often inositol hexaniacinate) were developed to avoid the flush. A direct comparison study showed that sustained-release niacin caused hepatotoxicity in 52% of patients while immediate-release niacin caused 0% liver toxicity.\n\nThe flush-free versions likely have reduced GPR109A activation — which is precisely the mechanism relevant for immune effects. They trade the therapeutic signal for comfort.\n\n## What remains unknown\n\n- **Relative immune potency**: No head-to-head trial has compared nicotinic acid vs. niacinamide vs. NR for autoimmune outcomes in humans.\n- **Gut conversion rate**: What fraction of oral niacinamide is converted to nicotinic acid by gut bacteria in a typical human?\n- **NR immune effects**: NR may have immune effects through NAD+ repletion alone, without GPR109A. Whether these are clinically meaningful is untested.\n- **Combination potential**: Whether nicotinic acid (for GPR109A) combined with NR (for efficient NAD+ repletion) produces additive benefits.","study_count":11,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"},{"slug":"sirt1","name":"SIRT1"},{"slug":"pgd2","name":"PGD2"}],"conditions":[{"slug":"autoimmune","name":"autoimmune"},{"slug":"inflammation","name":"inflammation"}]},{"id":6,"slug":"dose-response","title":"Vitamin or Drug? The Dose-Response Problem","description":"RDA is 14-18mg. Therapeutic range is 100-1000x that. The pharmacological implications.","weight":6,"category":"practice","status":"data","body_markdown":"## The scale problem\n\nThe Recommended Dietary Allowance (RDA) for niacin is 14-18mg per day. This prevents pellagra.\n\nTherapeutic doses in the research literature range from 500mg to 3,000mg per day — 30x to 200x the RDA. Hoffer's clinical practice used approximately 3g/day. Lipid-lowering protocols use 1-3g/day.\n\nAt these doses, nicotinic acid is not functioning as a vitamin. It is functioning as a drug: activating GPR109A at pharmacological concentrations, raising NAD+ beyond baseline homeostasis, and producing measurable systemic effects.\n\n## Animal-to-human dose scaling\n\nMost niacin studies use animal models. Converting animal doses to human-equivalent doses requires FDA allometric body surface area (BSA) scaling:\n\n| Model | BSA factor | Example: 500 mg/kg in animal |\n|-------|-----------|------------------------------|\n| Mouse | ÷ 12.3 | 500 ÷ 12.3 × 75 ÷ 1000 = **3.0g** human equivalent |\n| Rat | ÷ 6.2 | 500 ÷ 6.2 × 75 ÷ 1000 = **6.0g** human equivalent |\n\nMany animal studies use doses that translate to 1-6g human equivalent — squarely in the range Hoffer used clinically.\n\n## Evidence by dose range\n\n**14-18mg (RDA)**: Prevents overt pellagra. No immune effects documented.\n\n**100-500mg**: Niacin reduces abdominal fat in a pilot study. Modest cardiovascular effects. The fifteen-year mortality follow-up of the Coronary Drug Project found long-term benefit from niacin at these doses.\n\n**500mg-1g**: Effectiveness of niacin supplementation for type 2 diabetes documented in meta-analysis. Effects on blood sugar. Testicular structure and function improvements in diabetic rats at equivalent doses.\n\n**1-3g**: Niacin cures systemic NAD+ deficiency and improves muscle performance in mitochondrial myopathy (750-1000mg/day). Lipid-modifying effects well-characterized. Hoffer's clinical range.\n\n**3g+**: Gulf War Illness pilot RCT used a niacin-containing regimen. Animal study human-equivalent doses at this range show robust immune and anti-cancer effects. Pharmacological doses increase bone marrow poly(ADP-ribose) and extend cancer latency.\n\n## The genomic stability threshold\n\nNiacin requirements for genomic stability suggest a threshold above the RDA: the amount of niacin needed to maintain optimal DNA repair via PARP is higher than the amount needed to prevent pellagra. The NAD+ precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation.\n\nHigh dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots — a real-world observation that higher niacin intake protects against DNA damage.\n\n## Hepatotoxicity is form-dependent, not dose-dependent\n\nThe concern about high-dose niacin hepatotoxicity applies specifically to sustained-release formulations, not to immediate-release nicotinic acid. The comparison study found 52% hepatotoxicity with sustained-release versus 0% with immediate-release at equivalent doses.\n\n## What remains unknown\n\n- **Optimal immune dose in humans**: No dose-finding study has been conducted for autoimmune outcomes.\n- **Upper bound**: At what dose do diminishing returns begin? Is there a ceiling for GPR109A activation?\n- **Individual variation**: NAD+ status, microbiome composition, and genetic variation in GPR109A expression likely create wide inter-individual dose-response curves.\n- **Duration to effect**: How long at a given dose before immune effects manifest? The flush diminishes over weeks, suggesting receptor adaptation — does the immune effect similarly change?","study_count":33,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"},{"slug":"parp","name":"PARP"},{"slug":"sirt1","name":"SIRT1"}],"conditions":[{"slug":"autoimmune","name":"autoimmune"},{"slug":"inflammation","name":"inflammation"},{"slug":"cancer","name":"cancer"},{"slug":"dyslipidemia","name":"dyslipidemia"}]},{"id":7,"slug":"the-flush","title":"The Niacin Flush: Signal, Not Side Effect","description":"PGD2-mediated, GPR109A-dependent. Flush intensity correlates with inflammatory state.","weight":7,"category":"practice","status":"hypothesis","body_markdown":"## What the flush is\n\nThe niacin flush — warmth, redness, tingling of the skin, typically face, neck, and upper body — occurs within 15-30 minutes of taking nicotinic acid. It is mediated by prostaglandin D2 (PGD2) released through GPR109A activation.\n\nThis is not an allergic reaction. It is not histamine-mediated (though histamine may contribute). It is a specific pharmacological response to GPR109A signaling in Langerhans cells and dermal dendritic cells.\n\n## Why the flush matters\n\nThe flush is the observable signal of GPR109A activation. If you take a niacin supplement and do not flush, GPR109A is not being activated at a meaningful level. This means:\n\n- \"Flush-free\" niacin formulations may not deliver immune-regulatory benefits\n- The intensity of the flush may indicate the degree of GPR109A activation needed\n- Flush diminishment over time suggests receptor adaptation or reduced inflammatory signaling\n\nClinical observation consistently reports that people with higher inflammatory states experience more intense initial flushing. As inflammation resolves, flush intensity decreases. This is consistent with increased GPR109A expression in inflamed tissue — more receptors means more PGD2 release means more flush.\n\n## The PGD2 pathway\n\nGPR109A activation → arachidonic acid release → COX-1/COX-2 conversion → prostaglandin D2 → vasodilation (flush) and immune modulation.\n\nPGD2 is not merely a vasodilator. It promotes regulatory T cell differentiation and has anti-inflammatory properties in its own right. The niacin-induced PGD2 release may be part of the therapeutic mechanism, not merely a byproduct.\n\nThe ulcerative colitis remission study explicitly identified the PGD2-mediated D prostanoid receptor 1 pathway as the mechanism of action — the same pathway that produces the flush.\n\n## Flush management\n\nThe flush typically diminishes over 1-3 weeks of consistent use. Common strategies:\n- Start at low dose (100-250mg) and titrate up\n- Take with meals (slows absorption, reduces peak)\n- Consistent daily use (receptor adaptation)\n\nAspirin blocks the flush by inhibiting COX — but this also blocks PGD2 production, which may reduce the immune-regulatory signal. The trade-off is not well characterized.\n\n## What remains unknown\n\n- **Flush as biomarker**: Can flush intensity be quantified and used to track inflammatory state over time?\n- **Aspirin interaction**: Does aspirin's COX inhibition meaningfully reduce GPR109A-mediated immune benefits?\n- **Tolerance mechanism**: Does flush diminishment represent GPR109A desensitization, reduced inflammation, or downstream PGD2 receptor adaptation?\n- **Individual variation**: Why do some people flush intensely at 100mg while others tolerate 1g with minimal flush? Is this genetic (GPR109A polymorphisms), inflammatory, or metabolic?","study_count":7,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"pgd2","name":"PGD2"},{"slug":"prostaglandin","name":"prostaglandin"}],"conditions":[{"slug":"inflammation","name":"inflammation"},{"slug":"autoimmune","name":"autoimmune"}]},{"id":8,"slug":"subclinical-pellagra","title":"The Subclinical Pellagra Hypothesis","description":"Pellagra's 4 Ds map to the exact conditions in these studies. The RDA prevents overt pellagra, not optimal function.","weight":8,"category":"mechanism","status":"speculative","body_markdown":"## The classical disease\n\nPellagra is the disease of severe niacin deficiency. Its four Ds: dermatitis, diarrhea, dementia, and death. It was epidemic in the early 20th-century American South, killing thousands before the anti-black tongue factor was identified as nicotinic acid.\n\nThe RDA of 14-18mg/day was established to prevent overt pellagra. It succeeds at this. Clinical pellagra is now rare in developed countries.\n\n## The subclinical hypothesis\n\nBut what if the threshold for preventing pellagra and the threshold for optimal immune function are different? What if a significant fraction of the population has niacin levels sufficient to prevent the 4 Ds but insufficient for optimal NAD+ status, GPR109A-mediated immune regulation, or DNA repair?\n\nThis would look like: mild skin conditions, subtle gut inflammation, low-grade neuroinflammation, and increased susceptibility to autoimmune dysfunction — exactly the conditions that nicotinic acid supplementation appears to address.\n\n## Evidence\n\n**Skin**: Dyssebacia (abnormal sebum production) is identified as an early cutaneous marker of niacin deficiency — appearing before overt pellagra. Acne vulgaris is proposed as a special clinical type of pellagra. These conditions are common and typically treated symptomatically rather than as nutritional deficiencies.\n\n**Tryptophan competition**: Iron deficiency reduces the efficacy of tryptophan as a niacin precursor. Since tryptophan is the primary dietary pathway to niacin (tryptophan → NAD+), iron deficiency — common worldwide — may create functional niacin insufficiency even with adequate dietary tryptophan.\n\n**Brain barrier**: Effects of Huntington's and Alzheimer's on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier suggest that neurodegenerative conditions may impair niacin delivery to the CNS, creating localized deficiency even with adequate systemic levels.\n\n**The COVID connection**: The tryptophan syndrome model for COVID-19 suggests that infection depletes tryptophan (and therefore niacin/NAD+), creating acute subclinical pellagra during illness.\n\n## The autoimmune epidemic connection\n\nAutoimmune diseases have increased dramatically over the past 50 years. Dietary changes over the same period include: reduced whole grain consumption (a major niacin source), increased processed food (stripped of B vitamins), increased antibiotic use (disrupting butyrate-producing gut bacteria), and increased tryptophan competition from chronic inflammation.\n\nIf subclinical pellagra is real, these dietary and microbiome shifts could contribute to the autoimmune epidemic by chronically undermining niacin-dependent immune regulation.\n\n## Historical context\n\nThe politics of pellagra in the early 20th century demonstrate how nutritional diseases can be misattributed for decades. Pellagra was blamed on infection, genetics, and moral failure before its nutritional basis was accepted. The subclinical pellagra hypothesis asks whether a similar misattribution is happening now — this time mistaking mild deficiency for idiopathic autoimmune disease.\n\n## What remains unknown\n\n- **Prevalence**: No population-level survey of subclinical niacin status exists. NAD+ levels are not routinely measured.\n- **Diagnostic criteria**: What biomarker would distinguish subclinical niacin insufficiency from adequacy?\n- **Causation vs. correlation**: Does niacin insufficiency cause autoimmune susceptibility, or does autoimmune inflammation deplete niacin?\n- **Other B vitamins**: Pellagra often co-occurs with other B vitamin deficiencies. The subclinical version may similarly involve multiple micronutrient insufficiencies.","study_count":18,"mechanisms":[{"slug":"nad","name":"NAD+"},{"slug":"tryptophan","name":"tryptophan"}],"conditions":[{"slug":"pellagra","name":"pellagra"},{"slug":"dermatitis","name":"dermatitis"},{"slug":"inflammation","name":"inflammation"},{"slug":"depression","name":"depression"},{"slug":"neuroinflammation","name":"neuroinflammation"}]},{"id":9,"slug":"sourcing","title":"Not All Nicotinic Acid Is Created Equal","description":"Manufacturing methods, pharmaceutical grading, and COA interpretation for gram-scale use.","weight":9,"category":"trust","status":"data","body_markdown":"## Why sourcing matters at scale\n\nAt the RDA of 14-18mg, the quality of a niacin supplement is nearly irrelevant — even a low-purity product delivers a negligible absolute amount of contaminants.\n\nAt 1-3 grams per day, you are consuming 100-200x more. Manufacturing contaminants, heavy metals, filler quality, and dissolution profiles all scale proportionally. A supplement that is 99% pure at 15mg delivers 0.15mg of impurities. The same product at 3g delivers 30mg of impurities daily.\n\n## Grading\n\n**USP (United States Pharmacopeia)**: Independently verified to meet standards for identity, strength, purity, and dissolution. USP-verified products carry the USP mark. This is the gold standard.\n\n**USP-grade (claimed)**: Manufacturer claims USP standards but has not undergone independent verification. Common and often legitimate, but unverified.\n\n**Food grade**: Meets FDA requirements for food additives. Lower purity standards than pharmaceutical grade. May contain higher levels of heavy metals and processing residuals.\n\n**Reagent grade**: Laboratory use. High purity but not tested for oral consumption safety.\n\n## Certificate of Analysis (COA)\n\nA COA should specify:\n- **Identity**: Confirms the product is nicotinic acid (not niacinamide)\n- **Purity**: ≥99% for gram-scale use\n- **Heavy metals**: Lead, arsenic, mercury, cadmium levels\n- **Microbial**: Yeast, mold, E. coli, Salmonella testing\n- **Testing lab**: Independent third-party, not manufacturer's own lab\n\nRequest the COA for the specific lot number you're purchasing. Reputable suppliers provide this without hesitation.\n\n## Form factors\n\n**Powder**: Most economical for gram-scale dosing. Requires a scale for accurate measurement. Best for titration.\n\n**Tablets (immediate-release)**: Convenient, pre-measured. Ensure they are immediate-release — not \"sustained-release,\" \"extended-release,\" or \"flush-free.\"\n\n**Capsules**: Similar to tablets. Check for immediate-release formulation. Some capsules contain niacinamide mislabeled or marketed interchangeably with niacin.\n\n## The sustained-release warning\n\nSustained-release niacin formulations carry documented hepatotoxicity risk — 52% of patients in one comparative study developed liver toxicity markers. Immediate-release formulations showed 0% hepatotoxicity at equivalent doses. This is the single most important sourcing distinction.\n\n## What remains unknown\n\n- **Country-of-origin effects**: Whether manufacturing origin (China, India, Europe, US) meaningfully affects purity for reputable suppliers with independent COA testing.\n- **Long-term contaminant accumulation**: No studies track contaminant accumulation from daily gram-scale niacin supplementation over years.\n- **Dissolution profiles**: Whether dissolution speed of immediate-release formulations varies enough between manufacturers to affect GPR109A activation patterns.","study_count":0,"mechanisms":[],"conditions":[]},{"id":10,"slug":"counter-evidence","title":"What the Evidence Doesn't Show","description":"Hepatotoxicity, AIM-HIGH, negative studies. Including them makes the positive evidence credible.","weight":10,"category":"trust","status":"data","body_markdown":"## Why this page exists\n\nA research project that only presents positive findings is advocacy, not investigation. The negative evidence, contradictions, and limitations are what make the positive evidence worth trusting.\n\n## The AIM-HIGH trial\n\nThe Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides (AIM-HIGH) trial was a large randomized controlled trial testing niacin added to statin therapy. It was stopped early because niacin showed no additional cardiovascular benefit over statins alone.\n\nAIM-HIGH had a chilling effect on niacin research and clinical use. However, its relevance to niacin's immune effects is limited:\n- It tested cardiovascular endpoints, not immune or autoimmune outcomes\n- Participants were already on statins, which have their own anti-inflammatory effects\n- The dose (1.5-2g/day extended-release) and formulation may matter\n- It tells us nothing about GPR109A-mediated immune regulation\n\nThe AIM-HIGH result is often cited as evidence that \"niacin doesn't work.\" This is a category error — it showed that niacin doesn't add cardiovascular benefit on top of statins, not that niacin has no biological effects.\n\n## Hepatotoxicity\n\nSustained-release niacin formulations cause hepatotoxicity in a significant fraction of users (52% in one comparative study). This is a real and serious adverse effect — but it is form-specific, not molecule-specific. Immediate-release nicotinic acid showed 0% hepatotoxicity at equivalent doses in the same study.\n\nThe mechanism: sustained-release formulations deliver niacin slowly through the portal circulation, overwhelming hepatic first-pass metabolism. Immediate-release creates a brief spike that the liver processes normally.\n\n## Missing human evidence\n\nThe most significant limitation of the niacin-autoimmune thesis is the lack of human randomized controlled trials specifically designed to test immune outcomes. Most immune evidence comes from:\n- Animal models (mouse and rat)\n- In vitro studies (cell lines)\n- Observational data\n- Small case series\n- One human colitis study (n=26, no placebo control)\n\nThis evidence gap does not invalidate the hypothesis — it means the hypothesis is unproven, not disproven. The mechanistic evidence is strong. The human clinical evidence is thin.\n\n## Negative and mixed study results\n\nNot every study shows benefit. Some studies show neutral outcomes for specific conditions at specific doses. These are catalogued in the database and can be filtered via the API.\n\nThe pattern in negative results tends to be: wrong form (niacinamide instead of nicotinic acid), insufficient dose, wrong endpoint (cardiovascular rather than immune), or confounded by concurrent therapies.\n\n## Methodological limitations across the corpus\n\n- **Publication bias**: Positive results are published more readily. The true proportion of negative niacin studies is unknown.\n- **Animal model translation**: Mouse and rat immune systems differ from human. The allometric dose scaling is approximate.\n- **Dose heterogeneity**: Studies use widely varying doses, making cross-study comparison difficult.\n- **Duration**: Most studies are short-term. Long-term effects of gram-scale nicotinic acid on immune function are essentially unstudied.\n\n## What this means for the reader\n\nThe evidence for nicotinic acid's immune effects is mechanistically compelling but clinically incomplete. The receptor mechanism (GPR109A) is well-characterized. The downstream immune effects are documented in models. The translation to human autoimmune treatment is plausible but unproven by rigorous clinical standards.\n\nThis is an active investigation, not a settled conclusion.","study_count":1,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"nad","name":"NAD+"}],"conditions":[{"slug":"dyslipidemia","name":"dyslipidemia"},{"slug":"atherosclerosis","name":"atherosclerosis"},{"slug":"liver","name":"liver"}]},{"id":11,"slug":"why-not-mainstream","title":"Why Your Doctor Doesn't Know About This","description":"Off-patent economics, the flush barrier, cholesterol framing, and the AIM-HIGH chilling effect.","weight":11,"category":"trust","status":"established","body_markdown":"## The structural barriers\n\nNicotinic acid is a naturally occurring molecule that cannot be patented. This single fact explains most of its absence from mainstream autoimmune treatment.\n\n## Economic structure\n\nPharmaceutical development follows patent-protected molecules. A drug company can spend $1 billion on clinical trials for a patentable compound and recoup the investment through exclusivity. No company will spend $1 billion proving that an off-patent vitamin treats autoimmune disease — there is no exclusivity to recoup.\n\nThis means: no Phase III trials, no FDA indication for autoimmune use, no pharmaceutical sales force educating physicians, no insurance coverage for therapeutic doses, no continuing medical education modules.\n\nThe evidence does not advance through the standard pipeline because the standard pipeline requires patent protection to function.\n\n## The cholesterol framing\n\nFor decades, niacin was known primarily as a cholesterol drug. It was the first substance shown to reduce cardiovascular mortality (the Coronary Drug Project, 1975, with benefits persisting at the fifteen-year follow-up). But it was framed entirely through the lipid lens.\n\nWhen AIM-HIGH showed niacin didn't add cardiovascular benefit on top of statins, the medical community concluded \"niacin doesn't work\" — meaning niacin doesn't add lipid benefit to statins. The GPR109A receptor wasn't discovered until after niacin was already categorized as a cholesterol drug. Its immune effects were never part of the mainstream narrative.\n\n## The flush barrier\n\nDoctors avoid prescribing medications with uncomfortable side effects. The niacin flush is uncomfortable for patients unfamiliar with it. Sustained-release formulations were developed to eliminate the flush — but these carry hepatotoxicity risk and likely reduce GPR109A activation.\n\nThe irony: the mechanism that makes nicotinic acid uncomfortable (GPR109A → PGD2 → flush) is the same mechanism that makes it therapeutically interesting for autoimmune conditions. Eliminating the flush may eliminate the benefit.\n\n## The supplement stigma\n\nIn evidence-based medicine, \"take a vitamin\" is not a serious treatment recommendation. The association with supplement culture, health food stores, and alternative medicine creates a credibility barrier that prevents serious investigation.\n\nThis stigma is partly earned — the supplement industry makes many unsubstantiated claims. But it also prevents investigation of legitimate mechanisms like GPR109A activation that happen to involve a vitamin-class molecule.\n\n## The research gap\n\nThe result of these structural barriers: a molecule with a well-characterized receptor mechanism, documented immune effects in animal models, and 50 years of clinical observation data has essentially zero randomized controlled trial evidence for autoimmune outcomes in humans.\n\nThis is not because the hypothesis is weak. It is because the economic incentive structure does not fund the trials that would test it.\n\n## What could change this\n\n- **Academic-funded trials**: University-based RCTs testing nicotinic acid for specific autoimmune conditions (colitis has the strongest starting evidence)\n- **Repurposing programs**: Government-funded drug repurposing initiatives that don't require patent protection\n- **Patient-reported outcomes**: Large-scale observational data from patients self-supplementing\n- **GPR109A drug development**: Pharmaceutical companies developing patentable GPR109A agonists — which would indirectly validate the nicotinic acid mechanism\n\nUntil one of these pathways opens, the evidence will remain in the state it is: mechanistically strong, clinically underexplored.","study_count":2,"mechanisms":[{"slug":"gpr109a","name":"GPR109A"},{"slug":"pgd2","name":"PGD2"}],"conditions":[{"slug":"autoimmune","name":"autoimmune"},{"slug":"dyslipidemia","name":"dyslipidemia"}]}],"relationships":{"study_mechanisms":[{"study_id":1,"mechanism_id":6},{"study_id":2,"mechanism_id":2},{"study_id":3,"mechanism_id":1},{"study_id":3,"mechanism_id":16},{"study_id":3,"mechanism_id":2},{"study_id":3,"mechanism_id":17},{"study_id":4,"mechanism_id":2},{"study_id":5,"mechanism_id":2},{"study_id":5,"mechanism_id":9},{"study_id":6,"mechanism_id":6},{"study_id":6,"mechanism_id":18},{"study_id":6,"mechanism_id":1},{"study_id":7,"mechanism_id":1},{"study_id":7,"mechanism_id":9},{"study_id":7,"mechanism_id":6},{"study_id":8,"mechanism_id":1},{"study_id":8,"mechanism_id":19},{"study_id":8,"mechanism_id":5},{"study_id":8,"mechanism_id":4},{"study_id":8,"mechanism_id":10},{"study_id":9,"mechanism_id":1},{"study_id":9,"mechanism_id":19},{"study_id":9,"mechanism_id":5},{"study_id":9,"mechanism_id":4},{"study_id":9,"mechanism_id":10},{"study_id":9,"mechanism_id":9},{"study_id":10,"mechanism_id":1},{"study_id":10,"mechanism_id":19},{"study_id":10,"mechanism_id":4},{"study_id":10,"mechanism_id":10},{"study_id":11,"mechanism_id":1},{"study_id":11,"mechanism_id":18},{"study_id":11,"mechanism_id":20},{"study_id":11,"mechanism_id":9},{"study_id":12,"mechanism_id":18},{"study_id":12,"mechanism_id":9},{"study_id":12,"mechanism_id":6},{"study_id":13,"mechanism_id":2},{"study_id":13,"mechanism_id":15},{"study_id":13,"mechanism_id":8},{"study_id":14,"mechanism_id":2},{"study_id":14,"mechanism_id":14},{"study_id":15,"mechanism_id":2},{"study_id":16,"mechanism_id":2},{"study_id":17,"mechanism_id":2},{"study_id":18,"mechanism_id":1},{"study_id":18,"mechanism_id":9},{"study_id":19,"mechanism_id":7},{"study_id":19,"mechanism_id":2},{"study_id":20,"mechanism_id":21},{"study_id":20,"mechanism_id":22},{"study_id":21,"mechanism_id":1},{"study_id":21,"mechanism_id":10},{"study_id":21,"mechanism_id":23},{"study_id":22,"mechanism_id":1},{"study_id":22,"mechanism_id":2},{"study_id":23,"mechanism_id":10},{"study_id":24,"mechanism_id":2},{"study_id":25,"mechanism_id":2},{"study_id":25,"mechanism_id":16},{"study_id":27,"mechanism_id":6},{"study_id":27,"mechanism_id":5},{"study_id":27,"mechanism_id":20},{"study_id":27,"mechanism_id":24},{"study_id":27,"mechanism_id":10},{"study_id":28,"mechanism_id":2},{"study_id":29,"mechanism_id":2},{"study_id":30,"mechanism_id":2},{"study_id":30,"mechanism_id":16},{"study_id":31,"mechanism_id":2},{"study_id":31,"mechanism_id":1},{"study_id":32,"mechanism_id":1},{"study_id":33,"mechanism_id":2},{"study_id":35,"mechanism_id":2},{"study_id":36,"mechanism_id":1},{"study_id":36,"mechanism_id":6},{"study_id":36,"mechanism_id":20},{"study_id":36,"mechanism_id":24},{"study_id":36,"mechanism_id":9},{"study_id":36,"mechanism_id":15},{"study_id":36,"mechanism_id":8},{"study_id":37,"mechanism_id":2},{"study_id":37,"mechanism_id":1},{"study_id":38,"mechanism_id":10},{"study_id":38,"mechanism_id":2},{"study_id":38,"mechanism_id":3},{"study_id":38,"mechanism_id":25},{"study_id":39,"mechanism_id":14},{"study_id":39,"mechanism_id":11},{"study_id":40,"mechanism_id":2},{"study_id":40,"mechanism_id":7},{"study_id":40,"mechanism_id":12},{"study_id":41,"mechanism_id":2},{"study_id":41,"mechanism_id":7},{"study_id":41,"mechanism_id":3},{"study_id":41,"mechanism_id":12},{"study_id":41,"mechanism_id":26},{"study_id":41,"mechanism_id":21},{"study_id":42,"mechanism_id":1},{"study_id":42,"mechanism_id":6},{"study_id":42,"mechanism_id":9},{"study_id":42,"mechanism_id":20},{"study_id":42,"mechanism_id":24},{"study_id":43,"mechanism_id":10},{"study_id":43,"mechanism_id":6},{"study_id":43,"mechanism_id":5},{"study_id":43,"mechanism_id":23},{"study_id":43,"mechanism_id":4},{"study_id":44,"mechanism_id":1},{"study_id":44,"mechanism_id":18},{"study_id":45,"mechanism_id":2},{"study_id":46,"mechanism_id":13},{"study_id":46,"mechanism_id":3},{"study_id":46,"mechanism_id":2},{"study_id":47,"mechanism_id":2},{"study_id":47,"mechanism_id":3},{"study_id":48,"mechanism_id":1},{"study_id":48,"mechanism_id":10},{"study_id":48,"mechanism_id":6},{"study_id":49,"mechanism_id":6},{"study_id":49,"mechanism_id":22},{"study_id":49,"mechanism_id":20},{"study_id":49,"mechanism_id":24},{"study_id":50,"mechanism_id":2},{"study_id":50,"mechanism_id":17},{"study_id":50,"mechanism_id":25},{"study_id":51,"mechanism_id":16},{"study_id":52,"mechanism_id":6},{"study_id":53,"mechanism_id":27},{"study_id":53,"mechanism_id":15},{"study_id":54,"mechanism_id":25},{"study_id":55,"mechanism_id":2},{"study_id":56,"mechanism_id":2},{"study_id":56,"mechanism_id":17},{"study_id":56,"mechanism_id":3},{"study_id":56,"mechanism_id":7},{"study_id":56,"mechanism_id":6},{"study_id":56,"mechanism_id":13},{"study_id":57,"mechanism_id":2},{"study_id":57,"mechanism_id":3},{"study_id":58,"mechanism_id":1},{"study_id":58,"mechanism_id":6},{"study_id":58,"mechanism_id":20},{"study_id":58,"mechanism_id":24},{"study_id":58,"mechanism_id":2},{"study_id":58,"mechanism_id":23},{"study_id":58,"mechanism_id":9},{"study_id":58,"mechanism_id":7},{"study_id":59,"mechanism_id":18},{"study_id":60,"mechanism_id":1},{"study_id":60,"mechanism_id":8},{"study_id":60,"mechanism_id":15},{"study_id":60,"mechanism_id":9},{"study_id":61,"mechanism_id":1},{"study_id":61,"mechanism_id":9},{"study_id":61,"mechanism_id":2},{"study_id":61,"mechanism_id":6},{"study_id":61,"mechanism_id":5},{"study_id":61,"mechanism_id":20},{"study_id":62,"mechanism_id":6},{"study_id":62,"mechanism_id":1},{"study_id":62,"mechanism_id":20},{"study_id":62,"mechanism_id":24},{"study_id":62,"mechanism_id":9},{"study_id":63,"mechanism_id":1},{"study_id":63,"mechanism_id":8},{"study_id":63,"mechanism_id":15},{"study_id":63,"mechanism_id":9},{"study_id":64,"mechanism_id":1},{"study_id":64,"mechanism_id":20},{"study_id":64,"mechanism_id":24},{"study_id":64,"mechanism_id":6},{"study_id":64,"mechanism_id":9},{"study_id":65,"mechanism_id":2},{"study_id":65,"mechanism_id":3},{"study_id":65,"mechanism_id":7},{"study_id":66,"mechanism_id":1},{"study_id":66,"mechanism_id":13},{"study_id":67,"mechanism_id":1},{"study_id":67,"mechanism_id":2},{"study_id":68,"mechanism_id":1},{"study_id":68,"mechanism_id":2},{"study_id":68,"mechanism_id":3},{"study_id":68,"mechanism_id":7},{"study_id":68,"mechanism_id":6},{"study_id":69,"mechanism_id":28},{"study_id":69,"mechanism_id":22},{"study_id":69,"mechanism_id":2},{"study_id":70,"mechanism_id":1},{"study_id":70,"mechanism_id":18},{"study_id":71,"mechanism_id":2},{"study_id":71,"mechanism_id":6},{"study_id":72,"mechanism_id":2},{"study_id":72,"mechanism_id":7},{"study_id":72,"mechanism_id":21},{"study_id":72,"mechanism_id":12},{"study_id":73,"mechanism_id":9},{"study_id":73,"mechanism_id":1},{"study_id":74,"mechanism_id":1},{"study_id":74,"mechanism_id":9},{"study_id":74,"mechanism_id":2},{"study_id":75,"mechanism_id":22},{"study_id":75,"mechanism_id":2},{"study_id":76,"mechanism_id":3},{"study_id":76,"mechanism_id":6},{"study_id":76,"mechanism_id":12},{"study_id":77,"mechanism_id":29},{"study_id":77,"mechanism_id":15},{"study_id":78,"mechanism_id":2},{"study_id":78,"mechanism_id":3},{"study_id":79,"mechanism_id":1},{"study_id":79,"mechanism_id":18},{"study_id":80,"mechanism_id":2},{"study_id":80,"mechanism_id":17},{"study_id":80,"mechanism_id":16},{"study_id":80,"mechanism_id":7},{"study_id":80,"mechanism_id":3},{"study_id":80,"mechanism_id":22},{"study_id":81,"mechanism_id":2},{"study_id":81,"mechanism_id":7},{"study_id":81,"mechanism_id":21},{"study_id":81,"mechanism_id":12},{"study_id":82,"mechanism_id":6},{"study_id":82,"mechanism_id":9},{"study_id":83,"mechanism_id":2},{"study_id":83,"mechanism_id":25},{"study_id":84,"mechanism_id":2},{"study_id":84,"mechanism_id":7},{"study_id":84,"mechanism_id":12},{"study_id":85,"mechanism_id":1},{"study_id":85,"mechanism_id":11},{"study_id":85,"mechanism_id":18},{"study_id":86,"mechanism_id":1},{"study_id":86,"mechanism_id":9},{"study_id":87,"mechanism_id":11},{"study_id":88,"mechanism_id":2},{"study_id":89,"mechanism_id":2},{"study_id":89,"mechanism_id":7},{"study_id":89,"mechanism_id":12},{"study_id":89,"mechanism_id":21},{"study_id":90,"mechanism_id":2},{"study_id":90,"mechanism_id":16},{"study_id":90,"mechanism_id":12},{"study_id":91,"mechanism_id":1},{"study_id":91,"mechanism_id":2},{"study_id":91,"mechanism_id":6},{"study_id":92,"mechanism_id":1},{"study_id":92,"mechanism_id":2},{"study_id":93,"mechanism_id":29},{"study_id":93,"mechanism_id":2},{"study_id":93,"mechanism_id":23},{"study_id":94,"mechanism_id":2},{"study_id":94,"mechanism_id":14},{"study_id":95,"mechanism_id":2},{"study_id":95,"mechanism_id":3},{"study_id":96,"mechanism_id":2},{"study_id":96,"mechanism_id":17},{"study_id":96,"mechanism_id":14},{"study_id":96,"mechanism_id":6},{"study_id":97,"mechanism_id":6},{"study_id":97,"mechanism_id":20},{"study_id":98,"mechanism_id":2},{"study_id":99,"mechanism_id":2},{"study_id":100,"mechanism_id":2},{"study_id":100,"mechanism_id":3},{"study_id":101,"mechanism_id":2},{"study_id":101,"mechanism_id":7},{"study_id":101,"mechanism_id":12},{"study_id":102,"mechanism_id":1},{"study_id":102,"mechanism_id":22},{"study_id":102,"mechanism_id":10},{"study_id":103,"mechanism_id":2},{"study_id":103,"mechanism_id":16},{"study_id":103,"mechanism_id":7},{"study_id":103,"mechanism_id":14},{"study_id":103,"mechanism_id":23},{"study_id":104,"mechanism_id":2},{"study_id":104,"mechanism_id":25},{"study_id":104,"mechanism_id":15},{"study_id":105,"mechanism_id":1},{"study_id":105,"mechanism_id":9},{"study_id":105,"mechanism_id":8},{"study_id":106,"mechanism_id":2},{"study_id":106,"mechanism_id":6},{"study_id":107,"mechanism_id":1},{"study_id":107,"mechanism_id":15},{"study_id":108,"mechanism_id":29},{"study_id":108,"mechanism_id":11},{"study_id":109,"mechanism_id":1},{"study_id":109,"mechanism_id":2},{"study_id":110,"mechanism_id":2},{"study_id":110,"mechanism_id":29}],"study_conditions":[{"study_id":1,"condition_id":7},{"study_id":2,"condition_id":19},{"study_id":3,"condition_id":20},{"study_id":3,"condition_id":12},{"study_id":3,"condition_id":10},{"study_id":4,"condition_id":21},{"study_id":5,"condition_id":17},{"study_id":5,"condition_id":16},{"study_id":5,"condition_id":7},{"study_id":6,"condition_id":10},{"study_id":6,"condition_id":22},{"study_id":7,"condition_id":10},{"study_id":7,"condition_id":8},{"study_id":8,"condition_id":3},{"study_id":8,"condition_id":23},{"study_id":8,"condition_id":10},{"study_id":9,"condition_id":3},{"study_id":9,"condition_id":23},{"study_id":9,"condition_id":10},{"study_id":9,"condition_id":8},{"study_id":10,"condition_id":3},{"study_id":10,"condition_id":23},{"study_id":10,"condition_id":10},{"study_id":11,"condition_id":10},{"study_id":11,"condition_id":8},{"study_id":11,"condition_id":22},{"study_id":12,"condition_id":10},{"study_id":12,"condition_id":8},{"study_id":12,"condition_id":22},{"study_id":13,"condition_id":8},{"study_id":13,"condition_id":10},{"study_id":14,"condition_id":18},{"study_id":15,"condition_id":10},{"study_id":16,"condition_id":9},{"study_id":16,"condition_id":22},{"study_id":17,"condition_id":24},{"study_id":17,"condition_id":14},{"study_id":18,"condition_id":25},{"study_id":18,"condition_id":11},{"study_id":19,"condition_id":10},{"study_id":20,"condition_id":11},{"study_id":21,"condition_id":2},{"study_id":21,"condition_id":10},{"study_id":21,"condition_id":17},{"study_id":22,"condition_id":26},{"study_id":22,"condition_id":10},{"study_id":23,"condition_id":13},{"study_id":23,"condition_id":10},{"study_id":24,"condition_id":9},{"study_id":24,"condition_id":22},{"study_id":25,"condition_id":9},{"study_id":25,"condition_id":10},{"study_id":26,"condition_id":17},{"study_id":26,"condition_id":16},{"study_id":27,"condition_id":10},{"study_id":27,"condition_id":3},{"study_id":28,"condition_id":27},{"study_id":28,"condition_id":12},{"study_id":30,"condition_id":21},{"study_id":30,"condition_id":15},{"study_id":31,"condition_id":15},{"study_id":31,"condition_id":7},{"study_id":32,"condition_id":14},{"study_id":33,"condition_id":7},{"study_id":34,"condition_id":28},{"study_id":34,"condition_id":15},{"study_id":35,"condition_id":15},{"study_id":35,"condition_id":28},{"study_id":36,"condition_id":12},{"study_id":36,"condition_id":27},{"study_id":36,"condition_id":20},{"study_id":36,"condition_id":5},{"study_id":37,"condition_id":8},{"study_id":37,"condition_id":7},{"study_id":38,"condition_id":10},{"study_id":38,"condition_id":1},{"study_id":39,"condition_id":10},{"study_id":40,"condition_id":11},{"study_id":41,"condition_id":11},{"study_id":41,"condition_id":14},{"study_id":42,"condition_id":10},{"study_id":43,"condition_id":10},{"study_id":44,"condition_id":22},{"study_id":44,"condition_id":28},{"study_id":45,"condition_id":16},{"study_id":46,"condition_id":7},{"study_id":46,"condition_id":8},{"study_id":47,"condition_id":21},{"study_id":48,"condition_id":10},{"study_id":49,"condition_id":10},{"study_id":50,"condition_id":11},{"study_id":50,"condition_id":10},{"study_id":50,"condition_id":14},{"study_id":51,"condition_id":10},{"study_id":52,"condition_id":22},{"study_id":52,"condition_id":10},{"study_id":53,"condition_id":10},{"study_id":54,"condition_id":27},{"study_id":54,"condition_id":20},{"study_id":54,"condition_id":12},{"study_id":55,"condition_id":21},{"study_id":56,"condition_id":14},{"study_id":56,"condition_id":11},{"study_id":56,"condition_id":12},{"study_id":56,"condition_id":10},{"study_id":57,"condition_id":21},{"study_id":57,"condition_id":14},{"study_id":58,"condition_id":10},{"study_id":59,"condition_id":7},{"study_id":59,"condition_id":8},{"study_id":60,"condition_id":3},{"study_id":60,"condition_id":10},{"study_id":61,"condition_id":10},{"study_id":61,"condition_id":1},{"study_id":62,"condition_id":26},{"study_id":62,"condition_id":10},{"study_id":63,"condition_id":10},{"study_id":64,"condition_id":10},{"study_id":65,"condition_id":10},{"study_id":65,"condition_id":9},{"study_id":66,"condition_id":22},{"study_id":66,"condition_id":9},{"study_id":66,"condition_id":28},{"study_id":67,"condition_id":9},{"study_id":67,"condition_id":10},{"study_id":68,"condition_id":27},{"study_id":68,"condition_id":20},{"study_id":68,"condition_id":12},{"study_id":69,"condition_id":11},{"study_id":69,"condition_id":10},{"study_id":70,"condition_id":22},{"study_id":70,"condition_id":7},{"study_id":71,"condition_id":9},{"study_id":72,"condition_id":11},{"study_id":73,"condition_id":8},{"study_id":73,"condition_id":10},{"study_id":74,"condition_id":5},{"study_id":74,"condition_id":12},{"study_id":74,"condition_id":14},{"study_id":75,"condition_id":25},{"study_id":75,"condition_id":11},{"study_id":76,"condition_id":10},{"study_id":76,"condition_id":8},{"study_id":77,"condition_id":10},{"study_id":78,"condition_id":18},{"study_id":79,"condition_id":7},{"study_id":79,"condition_id":8},{"study_id":80,"condition_id":10},{"study_id":80,"condition_id":11},{"study_id":81,"condition_id":11},{"study_id":82,"condition_id":10},{"study_id":83,"condition_id":12},{"study_id":84,"condition_id":11},{"study_id":85,"condition_id":22},{"study_id":85,"condition_id":28},{"study_id":86,"condition_id":18},{"study_id":86,"condition_id":12},{"study_id":87,"condition_id":2},{"study_id":87,"condition_id":1},{"study_id":88,"condition_id":16},{"study_id":89,"condition_id":11},{"study_id":90,"condition_id":10},{"study_id":91,"condition_id":10},{"study_id":92,"condition_id":29},{"study_id":92,"condition_id":10},{"study_id":93,"condition_id":1},{"study_id":94,"condition_id":15},{"study_id":95,"condition_id":17},{"study_id":95,"condition_id":2},{"study_id":95,"condition_id":14},{"study_id":96,"condition_id":10},{"study_id":96,"condition_id":1},{"study_id":97,"condition_id":26},{"study_id":97,"condition_id":10},{"study_id":98,"condition_id":16},{"study_id":99,"condition_id":16},{"study_id":100,"condition_id":14},{"study_id":101,"condition_id":10},{"study_id":101,"condition_id":11},{"study_id":102,"condition_id":11},{"study_id":103,"condition_id":10},{"study_id":103,"condition_id":1},{"study_id":104,"condition_id":10},{"study_id":105,"condition_id":12},{"study_id":106,"condition_id":4},{"study_id":106,"condition_id":10},{"study_id":106,"condition_id":1},{"study_id":107,"condition_id":6},{"study_id":107,"condition_id":10},{"study_id":109,"condition_id":17},{"study_id":110,"condition_id":12}],"study_pathways":[{"study_id":1,"pathway_id":6},{"study_id":1,"pathway_id":5},{"study_id":1,"pathway_id":7},{"study_id":2,"pathway_id":6},{"study_id":2,"pathway_id":7},{"study_id":3,"pathway_id":1},{"study_id":3,"pathway_id":2},{"study_id":4,"pathway_id":2},{"study_id":4,"pathway_id":8},{"study_id":5,"pathway_id":8},{"study_id":5,"pathway_id":5},{"study_id":6,"pathway_id":1},{"study_id":7,"pathway_id":1},{"study_id":8,"pathway_id":1},{"study_id":8,"pathway_id":3},{"study_id":9,"pathway_id":1},{"study_id":9,"pathway_id":3},{"study_id":10,"pathway_id":1},{"study_id":10,"pathway_id":3},{"study_id":11,"pathway_id":1},{"study_id":12,"pathway_id":1},{"study_id":13,"pathway_id":1},{"study_id":13,"pathway_id":7},{"study_id":14,"pathway_id":2},{"study_id":14,"pathway_id":8},{"study_id":15,"pathway_id":3},{"study_id":15,"pathway_id":5},{"study_id":16,"pathway_id":3},{"study_id":16,"pathway_id":5},{"study_id":17,"pathway_id":2},{"study_id":18,"pathway_id":1},{"study_id":19,"pathway_id":2},{"study_id":20,"pathway_id":5},{"study_id":21,"pathway_id":1},{"study_id":21,"pathway_id":3},{"study_id":22,"pathway_id":1},{"study_id":22,"pathway_id":6},{"study_id":23,"pathway_id":3},{"study_id":23,"pathway_id":8},{"study_id":24,"pathway_id":6},{"study_id":25,"pathway_id":6},{"study_id":26,"pathway_id":8},{"study_id":27,"pathway_id":3},{"study_id":27,"pathway_id":6},{"study_id":27,"pathway_id":1},{"study_id":28,"pathway_id":5},{"study_id":29,"pathway_id":6},{"study_id":30,"pathway_id":6},{"study_id":31,"pathway_id":6},{"study_id":32,"pathway_id":1},{"study_id":32,"pathway_id":6},{"study_id":33,"pathway_id":6},{"study_id":34,"pathway_id":3},{"study_id":35,"pathway_id":6},{"study_id":36,"pathway_id":1},{"study_id":36,"pathway_id":4},{"study_id":37,"pathway_id":6},{"study_id":37,"pathway_id":11},{"study_id":38,"pathway_id":3},{"study_id":38,"pathway_id":2},{"study_id":39,"pathway_id":3},{"study_id":40,"pathway_id":6},{"study_id":40,"pathway_id":2},{"study_id":41,"pathway_id":2},{"study_id":42,"pathway_id":1},{"study_id":43,"pathway_id":3},{"study_id":44,"pathway_id":1},{"study_id":44,"pathway_id":6},{"study_id":45,"pathway_id":8},{"study_id":46,"pathway_id":6},{"study_id":46,"pathway_id":2},{"study_id":47,"pathway_id":2},{"study_id":48,"pathway_id":1},{"study_id":48,"pathway_id":3},{"study_id":49,"pathway_id":4},{"study_id":50,"pathway_id":2},{"study_id":51,"pathway_id":4},{"study_id":52,"pathway_id":4},{"study_id":53,"pathway_id":4},{"study_id":54,"pathway_id":2},{"study_id":55,"pathway_id":2},{"study_id":56,"pathway_id":2},{"study_id":56,"pathway_id":4},{"study_id":57,"pathway_id":2},{"study_id":58,"pathway_id":1},{"study_id":58,"pathway_id":2},{"study_id":59,"pathway_id":7},{"study_id":59,"pathway_id":6},{"study_id":60,"pathway_id":1},{"study_id":60,"pathway_id":3},{"study_id":61,"pathway_id":1},{"study_id":61,"pathway_id":2},{"study_id":62,"pathway_id":1},{"study_id":63,"pathway_id":1},{"study_id":64,"pathway_id":1},{"study_id":65,"pathway_id":2},{"study_id":66,"pathway_id":1},{"study_id":66,"pathway_id":6},{"study_id":67,"pathway_id":1},{"study_id":67,"pathway_id":2},{"study_id":68,"pathway_id":1},{"study_id":68,"pathway_id":2},{"study_id":68,"pathway_id":8},{"study_id":69,"pathway_id":2},{"study_id":69,"pathway_id":6},{"study_id":70,"pathway_id":1},{"study_id":70,"pathway_id":6},{"study_id":71,"pathway_id":2},{"study_id":71,"pathway_id":6},{"study_id":72,"pathway_id":2},{"study_id":72,"pathway_id":8},{"study_id":73,"pathway_id":1},{"study_id":74,"pathway_id":1},{"study_id":74,"pathway_id":2},{"study_id":75,"pathway_id":2},{"study_id":76,"pathway_id":1},{"study_id":76,"pathway_id":2},{"study_id":77,"pathway_id":7},{"study_id":77,"pathway_id":1},{"study_id":78,"pathway_id":8},{"study_id":78,"pathway_id":6},{"study_id":79,"pathway_id":6},{"study_id":80,"pathway_id":2},{"study_id":80,"pathway_id":8},{"study_id":81,"pathway_id":2},{"study_id":81,"pathway_id":6},{"study_id":82,"pathway_id":8},{"study_id":82,"pathway_id":6},{"study_id":83,"pathway_id":2},{"study_id":83,"pathway_id":5},{"study_id":84,"pathway_id":2},{"study_id":84,"pathway_id":6},{"study_id":85,"pathway_id":1},{"study_id":85,"pathway_id":6},{"study_id":86,"pathway_id":1},{"study_id":86,"pathway_id":8},{"study_id":87,"pathway_id":4},{"study_id":88,"pathway_id":8},{"study_id":88,"pathway_id":11},{"study_id":89,"pathway_id":2},{"study_id":89,"pathway_id":5},{"study_id":90,"pathway_id":2},{"study_id":90,"pathway_id":5},{"study_id":91,"pathway_id":1},{"study_id":91,"pathway_id":6},{"study_id":92,"pathway_id":1},{"study_id":92,"pathway_id":2},{"study_id":92,"pathway_id":6},{"study_id":93,"pathway_id":4},{"study_id":93,"pathway_id":1},{"study_id":94,"pathway_id":2},{"study_id":94,"pathway_id":8},{"study_id":95,"pathway_id":5},{"study_id":95,"pathway_id":2},{"study_id":96,"pathway_id":2},{"study_id":96,"pathway_id":8},{"study_id":96,"pathway_id":4},{"study_id":97,"pathway_id":4},{"study_id":98,"pathway_id":8},{"study_id":98,"pathway_id":6},{"study_id":99,"pathway_id":8},{"study_id":100,"pathway_id":2},{"study_id":100,"pathway_id":6},{"study_id":101,"pathway_id":2},{"study_id":102,"pathway_id":1},{"study_id":102,"pathway_id":3},{"study_id":103,"pathway_id":2},{"study_id":103,"pathway_id":8},{"study_id":104,"pathway_id":7},{"study_id":104,"pathway_id":2},{"study_id":105,"pathway_id":1},{"study_id":106,"pathway_id":5},{"study_id":106,"pathway_id":6},{"study_id":107,"pathway_id":7},{"study_id":107,"pathway_id":6},{"study_id":109,"pathway_id":1},{"study_id":110,"pathway_id":2},{"study_id":110,"pathway_id":10}],"pathway_mechanisms":[{"pathway_id":1,"mechanism_id":1},{"pathway_id":1,"mechanism_id":5},{"pathway_id":1,"mechanism_id":4},{"pathway_id":1,"mechanism_id":8},{"pathway_id":1,"mechanism_id":9},{"pathway_id":2,"mechanism_id":2},{"pathway_id":2,"mechanism_id":3},{"pathway_id":2,"mechanism_id":7},{"pathway_id":2,"mechanism_id":12},{"pathway_id":2,"mechanism_id":13},{"pathway_id":3,"mechanism_id":1},{"pathway_id":3,"mechanism_id":10},{"pathway_id":3,"mechanism_id":4},{"pathway_id":3,"mechanism_id":5},{"pathway_id":3,"mechanism_id":11},{"pathway_id":4,"mechanism_id":1},{"pathway_id":4,"mechanism_id":2},{"pathway_id":4,"mechanism_id":3},{"pathway_id":4,"mechanism_id":4},{"pathway_id":4,"mechanism_id":5},{"pathway_id":4,"mechanism_id":6},{"pathway_id":5,"mechanism_id":1},{"pathway_id":5,"mechanism_id":2},{"pathway_id":5,"mechanism_id":3},{"pathway_id":5,"mechanism_id":8},{"pathway_id":6,"mechanism_id":1},{"pathway_id":6,"mechanism_id":2},{"pathway_id":6,"mechanism_id":7},{"pathway_id":6,"mechanism_id":3},{"pathway_id":7,"mechanism_id":1},{"pathway_id":7,"mechanism_id":8},{"pathway_id":7,"mechanism_id":15},{"pathway_id":8,"mechanism_id":2},{"pathway_id":8,"mechanism_id":14},{"pathway_id":10,"mechanism_id":1},{"pathway_id":10,"mechanism_id":2},{"pathway_id":11,"mechanism_id":1},{"pathway_id":11,"mechanism_id":8}],"pathway_conditions":[{"pathway_id":1,"condition_id":3},{"pathway_id":1,"condition_id":2},{"pathway_id":1,"condition_id":12},{"pathway_id":1,"condition_id":1},{"pathway_id":2,"condition_id":1},{"pathway_id":2,"condition_id":14},{"pathway_id":2,"condition_id":11},{"pathway_id":2,"condition_id":15},{"pathway_id":2,"condition_id":12},{"pathway_id":3,"condition_id":3},{"pathway_id":3,"condition_id":13},{"pathway_id":3,"condition_id":10},{"pathway_id":3,"condition_id":1},{"pathway_id":4,"condition_id":1},{"pathway_id":4,"condition_id":2},{"pathway_id":4,"condition_id":3},{"pathway_id":4,"condition_id":4},{"pathway_id":4,"condition_id":5},{"pathway_id":4,"condition_id":6},{"pathway_id":5,"condition_id":1},{"pathway_id":5,"condition_id":10},{"pathway_id":6,"condition_id":1},{"pathway_id":6,"condition_id":10},{"pathway_id":6,"condition_id":11},{"pathway_id":6,"condition_id":7},{"pathway_id":7,"condition_id":10},{"pathway_id":7,"condition_id":1},{"pathway_id":8,"condition_id":16},{"pathway_id":8,"condition_id":17},{"pathway_id":8,"condition_id":10},{"pathway_id":8,"condition_id":18},{"pathway_id":8,"condition_id":12},{"pathway_id":10,"condition_id":7},{"pathway_id":10,"condition_id":8},{"pathway_id":10,"condition_id":9},{"pathway_id":11,"condition_id":1},{"pathway_id":11,"condition_id":7}]}}