A catalyst is a chemical entity that increases the rate of a chemical reaction but remains unchanged at the end of the process. Many biochemical reactions are driven by catalysts. One such catalyst is Nicotinamide Adenosine Dinucleotide (NAD for short), which carries electrons in biochemical processes leading to energy production, such as glycolysis, citric acid cycle and fatty acid metabolism, as well as oxidative phosphorylation and other reactions. When DNA is damaged by agents such as ionizing radiation, ultraviolet radiation or dimethyl-sulfate, NAD serves as substrate (that is, no longer as a catalyst!) for poly-ADP-ribosylation, a reaction that facilitates DNA repair. At the end of this reaction cellular NAD can be all used up. In this case, the cells cannot produce energy anymore, they die and trigger the inflammatory process, the single most efficient mechanism known to accelerate skin aging.

Early Attempts in Skin Care

The inflammatory process consequent to DNA damage in UV-exposed skin provokes the so-called solar erythema. When I was working with L’Oréal, I envisioned to fight solar erythema by applying NAD to the skin after the exposure to solar radiation. Since NAD carries two negative charges, it is expected not to penetrate cell membranes, and therefore it was encapsulated into liposomes. The results were extremely interesting: 20 mM (~1.2%) NAD in liposomes was as effective as indomethacine in reducing erythema, whereas neither NAD free in buffer nor empty liposomes had any anti-erythemal effect.¹ My colleagues from the Department of Chemistry and I were granted US patent 5250290 as well as EU patent EP 0484199 for the topical use of NAD in liposomes as an anti-erythemal agent.

NAD is a very interesting molecule that is quite expensive and needs encapsulation to penetrate epidermal cells where it can exert its activity. This is perhaps the reason why those patents were never put to work. But those patents and the papers describing the work performed aroused the curiosity of those scientists who remembered that vitamin B3 is a precursor of NAD and tested the effects of topical application of vitamin B3 (in the amide form). It was observed that the topical application of vitamin B3 on human skin after exposure to ultraviolet radiation increases the level of NAD, enhances the production of energy, reduces the UV-induced depression of the cutaneous immune response and boosts DNA repair.^2,3,4 In addition to this, daily oral supplementation of nicotinamide has been shown in human volunteers to decrease by 20% the incidence of basal-cell carcinoma and by 30% that of squamous cell carcinoma as well as by 11% the number of actinic keratoses.⁵

For some mysterious reason, in the skin care arena, vitamin B3 has never reached the popularity level of other vitamins used in cosmetics, such as vitamins C (ascorbic acid), A (retinol) and E (a-tocopherol). My guess is that many cosmetic scientists, aware that the acidic form of vitamin B3 (nicotinic acid, aka niacin) is a powerful vasodilator and provokes intense erythema upon topical application, might consider all forms of vitamin B3 as unwelcome ingredients in skin care products.

Where Do We Stand Today?

Aging has been defined as accumulation of damage. NAD is used up because it is necessary in the process of removing DNA damage and, therefore, can be considered an anti-aging factor. Since nicotinamide is a precursor of NAD, it deserves consideration as an anti-aging ingredient, at least as far as skin is concerned. A botanical extract is presently advertised as being able to boost the enzymes committed to the synthesis of NAD and can be technically considered to be an anti-aging ingredient, too.

Because of its role in many vital biochemical reactions, NAD is being dubbed “the” longevity molecule. One might therefore infer that NAD precursors or a booster of its synthesis, are longevity molecules too. Is this legitimate?

One might spend a minute or two in thought before answering the question. Paradoxically, one could point out that ingredients with anti-aging properties might even be antinomic to fostering longevity: the best way not to grow old is to die young, isn’t it? Another way to look at things, in skin care, is that when a basal keratinocyte in human epidermis does duplicate, one of the daughter cells enters the differentiation process while the other will duplicate again 24 hours later, and this for up to, or more than, 120 years, thus making the need to boost keratinocyte longevity quite unessential.

As far as the longevity of human individuals is concerned, it is fair to say that the lack of NAD will shorten their lifespan, as it is indicated by the story of the discovery of vitamin B3, whose absence provokes the “4 D” outcomes: dermatitis, diarrhea, dementia and death. If a molecule whose absence causes the death of the individual can be called a longevity molecule, then we could say that water is a longevity molecule, couldn’t we?  

References

1. Jacobson EL, Giacomoni PU, Roberts MJ, Wondrak GT, Jacobson MK (2001) Metabolic effects of solar radiation and enhancers of energy metabolism. In: Sun Protection in Man (PU Giacomoni editor) Elsevier, Amsterdam, pages 677-690
2. Park, J, Halliday, GM, Surjana D, Damian DL (2010) Nicotinamide prevents ultraviolet radiation-induced cellular energy loss. Photochem. Photobiol. 86, 942-948
3. Sivapirabu G, Yiasemides E, Halliday GM, Parg J, Damian DL (2009) Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against UV-induced immunosuppression in humans. Br. J. Dermatol. 161 : 1357-1364
4. Surjana D, Halliday GM, Damian DL (2013) Nicotinamide enhances repair of UV radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 34 : 1144-1149
5. Chen AC, Martin AJ, Choy B, Fernandez-Peñas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, et al (2015) A Phase 3 randomized Trial of Nicotinamide for Skin Cancer Chemoprevention. The New England J. of Med. 373 : 1618-1626

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Paolo Giacomoni, PhD
Insight Analysis Consulting
[email protected]
516-769-6904
 
Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as Executive Director of Research at Estée Lauder and was Head of the Department of Biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents. He is presently Head of R&D with L.RAPHAEL—The science of beauty—Geneva, Switzerland.