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  • Advances in Age-Defying Skincare: The Vitamin B3 Story

    We’re all familiar with hyped skin care ingredients that promise the moon—or at least subliminally suggest that we’ll look as if constantly bathed in moonlight with regular usage. Of course, some superhero ingredients, like retinol, stand the test of time. Others, like vitamin C derivatives SAP and MAP, have improved tremendously over their earlier versions thanks to excellent research and development. And others, like peptides, excited formulators at first, then disappointed once it became obvious that they weren’t living up to their original promise. Still others, like plant stem cells, were silly from the get-go—we are not plants, so it’s unclear how plant stem cells (undifferentiated cells that foster new cell growth) are supposed to improve mammalian skin. Plants and animals don’t even belong to the same Kingdom, so it’s a stretch.

    But there is one ingredient we’ve just rediscovered and, based on a host of recent studies, it turns out that it’s been doing superhero work all along. We are just beginning to understand the wide range of its good deeds, as well as how it works to deliver such excellent results. Ladies and gentlemen (gentlemen take note, as a couple of its talents have special applications for you), it is our great pleasure to (re)introduce to you: niacinamide—also known as vitamin B3.

    A new look at an old friend

    Original studies showed that [1] niacinamide (aka nicotinamide) was useful in the treatment of a wide range of dermatological conditions, including autoimmune blistering disorders, acne, rosacea, aging skin and atopic dermatitis.

    But we are discovering that its benefits are far more extensive. New studies show niacinamide’s positive impact on:

    Photoprotection

    Sun protection starts with sunscreen, but these days it doesn’t end there. Faced as we are with higher temperatures and more sunny days, additional strategies are needed to ensure protection against the mutagenic and immune suppressive effects of sunlight. Nicotinamide, which has little or no toxicity even at high doses, “has photoprotective effects against carcinogenesis and immune suppression in mice, and is photoimmunoprotective in humans when used as a lotion or orally.” [2]

    Chemoprevention

    In addition to photoimmune protection, niacinamide is chemopreventive, due to its ability to enhance DNA repair of cells damaged by UV light. The pathway, as explained in the paragraph below, is that nicotinamide, a precursor of nicotinamide adenine dinucleotide (NAD), replenishes the energy lost in skin cells due to UV irradiation. [3]

    “Photodamaged DNA is rapidly repaired in the presence of normal DNA repair mechanisms, but this process is highly energy-intensive. UV radiation not only damages DNA, but also depletes cellular ATP at this time of greatest energy demand. As a precursor of nicotinamide adenine dinucleotide (NAD+), nicotinamide is an essential cofactor in ATP production. Nicotinamide replenishes cellular ATP levels in human keratinocytes after UV exposure, largely by enabling glycolysis to occur at a rate similar to that of unirradiated cells. This energy-replenishing effect is thought to be a key mechanism by which nicotinamide enhances DNA repair.” [4]

    Men’s Skin Health

    The photoprotective/chemopreventive aspects of nicotinamide have made it the focus of a very interesting study which indicates that men are more susceptible to UV-induced immunosuppression than women, and that topical nicotinamide may help to provide protection from immunosuppression.

    “Men were immunosuppressed by ssUV (solar simulated ultraviolet light) at doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression.” [5]

    Age Spots

    In addition to providing photoprotection, enhancing DNA repair, reducing susceptibility to immunosuppression, and boosting cellular energy, other studies [6] show that nicotinamide reduces actinic keratoses. [7] This is good news for those of us wanting to address age spots for cosmetic reasons but remember—they are considered pre-cancerous lesions as well. Again, men are more likely than women to leave such spots untended, providing yet another explanation for the higher rates of skin cancer among men.

    Aging Skin

    Studies reporting improvement in aging skin via topical vitamin B3 were in the literature long before this summary report published in 2005. [8] “Analyses of the data revealed a variety of significant skin appearance improvement effects for topical niacinamide: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing). In addition, elasticity (as measured via cutometry) was improved.

    The latest developments are even more promising

    Kristina Holey and I have used niacinamide as part of our sensitive/reactive skin care protocol for a long time. Its anti-inflammatory properties have made it a mainstay in the atopic dermatitis, adult acne treatment categories as well. Now, new studies prompt me to add three more groups to the list of niacinamide beneficiaries—people in the 50+ age group, men (especially those exposed to large amounts of sunlight on a daily basis) and people who live in areas like Australia where the ozone layer is depleted or absent. (If you fall into all three categories, this is a no-brainer.) This is because niacinamide addresses:

    Fibrillar collagen

    For all of you who responded so enthusiastically to the collagen blog post—this is for you. It turns out that niacin derivatives, in particular nicotinamide, stimulate elastin and fibrillin in fibroblasts and inhibit MMP (matrix metalloproteinases are enzymes that break down collagen) or elastase (an enzyme that breaks down elastin) activity. “Overall, the niacin derivatives, more so nicotinamide and 2,6-dihydroxynicotinamide, have anti-skin aging potential through the stimulation of elastin and fibrillin, and the direct inhibition of the extracellular matrix proteolytic enzymes.” [9] This is the type of collagen building our laudable vegans can jump on board with.

    Mitochondrial Protection

    Mitochondria are structures located in the cell’s cytoplasm outside the nucleus. They are responsible for energy production; besides converting nutrients into energy they also perform many other specialized tasks. Mitochondria are of particular importance to cell health, as they function primarily to produce adenosine triphosphate (ATP), the energy of the cell. You can compare them to the lungs of the cell, in that they drive cell respiration.

    We are just beginning to appreciate the enormous importance of normal mitochondrial function when it comes to staying healthy into older age, and luckily, some attention is also being focused on what happens to the skin. As we age, our skin suffers from a decline in mitochondrial function that is especially pronounced in epidermal keratinocytes. “A study on the age-dependency of the mitochondrial network in young and old volunteers revealed that keratinocytes in old skin establish a significantly more fragmented network with smaller and more compact mitochondrial clusters than keratinocytes in young skin.” [10]

    Normal mitochondrial function also produces ROS (reactive oxygen species or free radicals) and skin care companies have been using the antioxidants known to scavenge ROS such as L-ascorbic acid, tocopherol and polyphenols for a number of years. But we haven’t paid as much attention to mitochondrial ROS. This is where niacinamide springs into action, superhero style.

    “Niacinamide is a coenzyme precursor for important redox coenzymes—nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+)—and their reduced forms, NADH and NADPH, respectively. These coenzymes play important roles in many enzymatic reactions, which at least partially explains the exceptionally broad spectrum of effects that topical niacinamide exhibits on skin. Among those multiple effects, niacinamide has been shown to decrease ROS production by mitochondria and to extend the replicative lifespan of fibroblasts, an effect that points to the boosting of mitochondrial function and the protection of the mitochondrial genome.” [11]

    In other words, skin care products containing niacinamide protect mitochondria and boost their function. This results in increased skin cell protection, longer cell life, improved barrier function and a more robust ECM (extracellular matrix)—all of which leads to a healthier, more youthful looking skin.

    Internal supplementation

    Beyond its topical application, there is buzz around internal supplementation—so much so that the Scientific American deemed it the “Anti-aging NAD fad.” [12] Author David Stipp says: “Recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD (nicotinamide adenine dinucleotide).” He goes on to say:

    “NAD boosters might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging. Elysium (one of the companies manufacturing a NAD supplement) is banking on this potential synergy—its NR -containing (NR=nicotinamide riboside) supplement includes a resveratrol-like substance called pterostilbene (pronounced tero-STILL-bean), which is found in blueberries and grapes.”

    He finishes with a caution: “But the paucity of human data gives me pause. Nobel laureates notwithstanding, I plan to wait until more is known before jumping up from the supper table to run out for some NR. Besides, it probably won’t be long before more data come out given the growing buzz about NAD.”

    Well, some data is coming in, and it’s looking good for NAD [13] — and by extension, looking good for older folks. What I infer from the Nature article is that it doesn’t hurt to take it, and it might just help—and in this case, I’m following my own advice. At my age it’s all about the mitochondria.

    Supplement with niacinamide if:

    1. You need extra sun protection. This includes men and people who are exposed to a lot of UV rays, like athletes, outdoor sportspeople and those who live in ozone-depleted locations. Remember that niacinamide is “photoimmunoprotective in humans when used as a lotion or orally.” For best protection, do the following:

      Topically: Layer a niacinamide serum (like our Soothing B3 Serum which is 10% niacinamide in a hyaluronic acid base) under sunscreen before you go out. After a day in the sun, make the serum a part of your night time routine.

      Orally: Take up to 1500 mgs of Vitamin B3 (as niacinamide, not niacin) daily. Also take a B vitamin complex to ensure you don’t become deficient in the other Bs. Many studies support this finding: “Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight.” [14]

    2. You’re in the 50+ age group looking for mature skin support, you’re a vegan who wants a collagen boost from a vegan source, you want to diminish age spots/hyperpigmentation.

      Topically: Use a niacinamide lotion (like our Soothing B3 Serum which is 10% niacinamide in a hyaluronic acid base) twice daily, in the morning under sunscreen, and in the evening layered with your other products. It can be used in conjunction with whatever retinoid serum you are using; in fact it is recommended, as it works synergistically with retinol. It is also safe to layer a niacinamide serum with a vitamin C serum, but you may not want to use a serum that contains both vitamin C and niacinamide—they do not play all that well together.

      Orally: look for NAD+ supplements containing nicotinamide riboside plus an antioxidant like resveratrol or pterostilbene. Use according to directions on the container.

     

    References

    1. ^ Australas J Dermatol. 2014 Aug;55(3):169-75. doi: 10.1111/ajd.12163. Epub 2014 Mar 17. Nicotinamide and the Skin
    2. ^ Photoprotective effects of nicotinamide Damian, DL; https://www.ncbi.nlm.nih.gov/pubmed/20354654
    3. ^ https://www.skincancer.org/publications/the-melanoma-letter/spring-2016-vol-4-no-1/nicotinamide.
    4. ^ Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Surjana D, Halliday GM, Damian DL. Carcinogenesis. 2013 May;34(5):1144-9. doi: 10.1093/carcin/bgt017. Epub 2013 Jan 24. https://www.ncbi.nlm.nih.gov/pubmed/23349012
    5. ^ Damian DL, Patterson CRS, Stapelberg M, Park J, Barnetson RS, Halliday GM. Ultraviolet radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J Invest Dermatol 2008; 128:447-54.
    6. ^https://core.ac.uk/download/pdf/82104818.pdfg
    7. ^ Moloney FJ, Vestergaard ME, Radojkovic BL, Damian DL. Randomised, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses. Br J Dermatol 2010; 162:1138-9.
    8. ^ Niacinamide: A B vitamin that improves aging facial skin appearance. https://www.ncbi.nlm.nih.gov/pubmed/16029679
    9. ^ Stimulation of the Fibrillar Collagen and Heat Shock Proteins by Nicotinamide or Its Derivatives in Non-Irradiated or UVA Radiated Fibroblasts, and Direct Anti-Oxidant Activity of Nicotinamide Derivatives, Cosmetics 2015, 2(2), 146-161; doi:10.3390/cosmetics2020146Article
    10. ^Fragmentation of the mitochondrial network in skin in vivo, Daneil Mellem ,et al Published: June 23, 2017 https://doi.org/10.1371/journal.pone.0174469
    11. ^ https://www.the-dermatologist.com/content/mitochondria-and-skin
    12. ^ https://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad/
    13. ^ Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults, Christopher Martens et al https://www.nature.com/articles/s41467-018-03421-7
    14. ^ Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Yiasemides E1, Sivapirabu G, Halliday GM, Park J, Damian DL.