Supplementation of nicotinic acid and its derivatives up-regulates cellular NAD+ level rather than nicotinamide derivatives in cultured normal human epidermal keratinocytes

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.

Overview

This 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.

This 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.

Key Findings

• Nicotinic acid at 100 μM: 1.3-fold increase in intracellular NAD+ levels (statistically significant)
• Nicotinic acid mononucleotide (NaMN): 1.5-fold increase in NAD+ at 100 μM application
• Niacinamide (NAM) and its derivatives: Could not up-regulate cellular NAD+ levels in keratinocytes

This 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.

Why This Matters for Skin

NAD+ 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.

The 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.

The Nicotinic Acid vs. Niacinamide Distinction

Both compounds are marketed as “niacin” or “vitamin B3,” but they are pharmacologically distinct:

Property	Nicotinic Acid	Niacinamide
GPR109A activation	Yes	No
Niacin flush	Yes	No
NAD+ in keratinocytes	Yes (this study)	No (this study)
Typical use	Lipid management, research	Skincare serums

This 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.

Limitations

This 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.