Tuesday, October 22, 2013

Versatile Resveratrol Part 2: The ultimate skin care ingredient?

What would the ideal anti-aging skin care product look like? To begin with, it would need to provide protection against sun damage from UV exposure.[i] Of course any sunscreen does that, so what we really want is something that can help reverse the effects of UV exposure, which include mutations in the DNA of skin cells. This is where the idea of working at a molecular level comes into play. While many products talk about “DNA repair” the evidence for a role for resveratrol is particularly strong. There are several ways that resveratrol functions in this regard, the best known of which is its powerful antioxidant effects.

Healthier DNA means not only more attractive skin but a lower risk of skin cancers. The use of antioxidants such as resveratrol to lower risk of skin cancer is known as chemoprevention. There is evidence that it may help prevent many other types of cancer as well.

Another measure of aging has to do with integrity of sequences on the ends of the chromosome known as telomeres[ii]. Each time a cell replicates, the DNA must “unzip” to provide a template for the chromosomes in the new cell. It is prevented from unraveling by telomeres, which are sort of like the caps on shoelaces, but with each cycle the telomeres get shorter.. Restoring telomeres is a major effort in anti-aging, and it appears that resveratrol may activate the enzyme that restores telomeres (telomerase), thereby improving cellular health and longevity.

Nothing will magically undo every DNA mutation or the visible manifestations of them in the skin (such as discoloration, wrinkles, and other blemishes) so our ideal product should help with those too. One way that resveratrol improves skin is by inhibition of the enzyme that makes pigment, which results in lightening of dark spots and overall brightening[iii] of the skin.

Facial redness[iv] is another manifestation of the type of inflammation associated with accelerated aging. Resveratrol has also been shown to reduce facial redness with a twice daily application for 6 weeks, and continued improvement beyond that.

We all know that good skin is built by good collagen and elastin (a type  of collagen.) These proteins are constantly being rebuilt by enzymes known as matrix metalloproteinases, referred to as “MMP’s.” Regulation of MMP activity is critical to skin health and aging. It should come as no surprise then that resveratrol is implicated in regulation of MMP via SIRT activation[v], improving the skin’s stress response to UV exposure. This translates into healthier collagen and more elastic skin.

Sometimes however collagen rebuilding is overly exuberant, resulting in thickened scars. An extreme form of scarring is keloid, and treatment of keloids remains a challenge for plastic surgeons. An effective weapon   may be found in resveratrol, which has been shown to inhibit the cells (fibroblasts) that are overly active in keloids, while having no adverse effect on normal fibroblasts.[vi]

Acne is another common problem, and not one limited to teenagers. While there are effective treatments for acne such as benzoyl peroxide and tretinoin (Retin-A), these can cause irritation. Resveratrol is proving to be a useful adjunct to acne treatment,[vii] with more than one mode of action: It is antibacterial with specific effects on the type of bacteria associated with acne, while its anti-inflammatory properties reduce the redness and irritation.

A later life issue is changes in the skin with menopause. These include thinning due to lowered collagen production, dryness due to lessened moisture retention, and others. Given the controversies with estrogen replacement therapy, the need for a product providing estrogen-like effects in the skin is substantial. Resveratrol is one of the few ingredients capable of stimulating collagen production through estrogen-like effects.[viii]

If resveratrol is going to accomplish all of these anti-aging feats in a skin care product, it has to permeate the skin and reach the cells active in regeneration (bioavailability.) resveratrol is uniquely suited to traverse the barrier of hardened surface cells known as the stratum corneum because of a few features. One is the small size of the molecule, probably the smallest of the antioxidant polyphenols; the other is that it is hydrophobic, meaning that it is more comfortable in lipids (fatty molecules.) These types of molecules are able to penetrate better.

[i] Nichols JA, Katiyar SK. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res. 2010 Mar;302(2):71-83
[ii] Xia L, Wang XX, Hu XS, Guo XG, Shang YP, Chen HJ, Zeng CL, Zhang FR, Chen JZ. Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol. 2008 Oct;155(3):387-94.
[iii] Park J, Boo YC. Isolation of Resveratrol from Vitis Viniferae Caulis and Its Potent Inhibition of Human Tyrosinase. Evid Based Complement Alternat Med. 2013;2013:645257
[iv] Ferzil G, Patel M, Phrsai N, Brody N. Reduction of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine. J Drugs Dermatol. 2013 Jul 1;12(7):770-4.
[v] Lee JS, Park KY, Min HG, Lee SJ, Kim JJ, Choi JS, Kim WS, Cha HJ. Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue. Exp Dermatol. 2010 Dec;19(12):1060-6.
[vi] Ikeda K, Torigoe T, Matsumoto Y, Fujita T, Sato N, Yotsuyanagi T. Resveratrol inhibits fibrogenesis and induces apoptosis in keloid fibroblasts. Wound Repair Regen. 2013 Jul-Aug;21(4):616-23.
[vii] Fabbrocini G, Staibano S, De Rosa G, Battimiello V, Fardella N, Ilardi G, La Rotonda MI, Longobardi A, Mazzella M, Siano M, Pastore F, De Vita V, Vecchione ML, Ayala F. Resveratrol-containing gel for the treatment of acne vulgaris: a single-blind, vehicle-controlled, pilot study. Am J Clin Dermatol. 2011 Apr 1;12(2):133-41.
[viii] Giardina S, Michelotti A, Zavattini G, Finzi S, Ghisalberti C, Marzatico F. [Efficacy study in vitro: assessment of the properties of resveratrol and resveratrol + N-acetyl-cysteine on proliferation and inhibition of collagen activity]. Minerva Ginecol. 2010 Jun;62(3):195-201.

Friday, October 4, 2013

Versatile resveratrol: the ultimate skin care ingredient?


Part 1
Recently I was honored to join Professors David Sinclair of Harvard and Joseph Vercauteren of the University of Montpelleir at an anti-aging symposium at the invitation of Mathilde Thomas of Caudalie in Paris. Caudalie has been using wine extracts (and specifically resveratrol) in their products for more than 15 years, after Vercauteren identified it in wine grape vines. Sinclair has become well known for his work identifying the role of sirtuin (SIRT) genes in anti-aging, and resveratrol as a natural sirtuin activator. While much remains to be proven, it is fair to say that science is finally beginning to have an impact on skin care. With an increasing understanding of what causes aging in skin cells and how botanical antioxidants such as resveratrol work at a molecular level, there is no excuse to use anti-aging skin care products that don’t multitask.

Before delving into the potential benefits of resveratrol in skin care, it may help to review how resveratrol came into the spotlight in the first place. By just about any measure, moderate wine consumption is among the most potent anti-aging lifestyle habits known. And although resveratrol is present in only small amounts in wine, it is the best known source; coupled with an impressive array of anti-aging properties identified in laboratory conditions, resveratrol has been offered as the mediator of wine’s benefits. Sales of resveratrol supplements have soared. (One study noted that 2/3 of people who take supplements include resveratrol.)
Wine drinkers do enjoy healthier skin. For example, a study from Australia (where skin damage from sun exposure is a big deal) found that wine drinkers had a 27% lower risk of developing premalignant lesions known as actinic keratoses (AK’s.) Another study, from Germany, found that wine consumption – but not topical application of wine to the skin – reduced the redness from controlled exposure to UV light; in other words, a sunscreen you can drink.
From here the picture gets a bit more complicated, so bear with me for a moment. Topically applied resveratrol confers protection against damage from UV light in skin, just as it provides a handy explanation for why wine drinkers have healthier hearts and brains, and live longer. But remember that there isn’t enough resveratrol in wine to produce the effects seen under lab conditions without consuming enormous amounts, and supplements of resveratrol have a problem with what is known as “bioavailability.” That means that enough of it has to be absorbed into the circulation and distributed to the target tissue (in our case, skin) before being metabolized. Our digestive systems are pretty efficient at disposing of resveratrol (or at least metabolizing it into other compounds), and there is a high degree of variability between people.
To make matters even more confused, there is the issue of a phenomenon known as hormesis. This refers to paradoxical effects from the same thing in different amounts. Resveratrol has demonstrated hormesis in several cancer types wherein it promotes growth at low levels but inhibits at higher ones; the opposite may occur with Alzheimer’s and osteoporosis. Balancing these opposing effects is a considerable challenge, even if predictable levels of resveratrol in target tissues could be achieved.
The upshot is that if you are looking for the effects of resveratrol in the skin, it may be best to just put it there in the first place. Fortunately, there is good evidence that resveratrol is absorbed into the skin when applied topically. In Part 2 of this post I will detail the ways in which resveratrol functions as the ideal anti-aging skin care ingredient.