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Life Extension Magazine June 2010

Optimal Skin Protection with Vitamin D

By Gary Goldfaden, MD and Robert Goldfaden
Skin Repair and Protection

Skin Repair and Protection

What most people know as “the immune system” is actually one of two components of your body’s total immune capacity. Known to scientists as the adaptive immune system, its ability to mount a strong defense against invading microorganisms and then retain protective antibodies for the future is vital to our survival.

Individuals also possess another immune system that serves as the body’s first line of defense against bacteria, viruses, and other pathogens. Located partially in your skin, it is called the innate immune system. Its purpose is to recognize and repel all foreign invaders in a non-specific fashion, regardless of whether the particular pathogen has been encountered before or not. Innate immunity is so important that nature saw fit to preserve it through almost 60 million years of evolution. It is essential that we have an innate response not only to provide an immediate defense against pathogens, but also to reduce the painful inflammation caused by an overreaction of the body’s immune system.

The skin is a crucial component of the body’s innate immune system. The skin’s keratinocytes can metabolize vitamin D to its active metabolites, while the enzymatic machinery of skin cells can help produce vitamin D receptors. Within the skin, vitamin D and its receptors help form an impermeable barrier and promote an innate immune response against foreign microbes.12

An intriguing study demonstrated one mechanism by which vitamin D may participate in innate immunity.15 After a skin wound occurred, keratinocytes surrounding the wound increased the expression of genes coding for antimicrobial receptors and the antimicrobial peptide, cathelicidin. The active form of vitamin D helped induce these gene expression changes, assisting the eradication of infectious invaders at the site of the skin wound. Vitamin D thus helps keratinocytes recognize and respond to microbes and protect wounds against infection.

Topical application of a vitamin D analog has been found to increase expression of the LL-37 antimicrobial peptide in human skin. LL-37 is a prevalent antimicrobial peptide expressed by keratinocytes that plays numerous roles in skin health, including: controlling microbial flora in intact and damaged skin, attracting immune cells, promoting epithelial repair, and supporting angiogenesis needed for skin healing. Decreased expression of numerous antimicrobial peptides has been reported in certain skin conditions such as atopic dermatitis and chronic leg ulcers.16

Together, these findings highlight vitamin D’s crucial role in helping skin cells recognize and respond to invading microorganisms, protecting healing wounds against infection, and promoting skin healing.

Sunlight, Heat, and Skin: The Intricate Process of Vitamin D Production

There are five distinct layers that make up your epidermis. These are (from outer to inner): the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Where vitamin D is concerned, however, it’s the stratum basale and stratum spinosum that are the most important. These two layers contain the highest concentration of a substance called 7-dehydrocholesterol (about 25-50 micrograms for every square centimeter of skin).29 7-dehydrocholesterol absorbs UVB light wavelengths that are present in sunlight.

Ultraviolet-B (UVB) light breaks the B ring of 7-dehydrocholesterol’s chemical structure to form what is called pre-D3. Pre-D3, a thermodynamically unstable molecule, then undergoes a heat-induced rearrangement to form the prohormone vitamin D3 or cholecalciferol.30

From here, vitamin D3 is transported to your liver, where it is combined with the 25-hydroxylase enzyme to form calcidiol (25-hydroxycholecalciferol or 25-hydroxyvitamin D). Once produced, calcidiol is stored in your liver until it is needed. Later calcidiol is released into the blood where it’s transported to the proximal tubules of your kidneys. Here it is hydroxylated by another enzyme, 1-alpha-hydroxylase, to create the biologically active form of vitamin D, 1,25-dihydroxycholecalciferol or calcitriol. Following this conversion, calcitriol is released back into the bloodstream and carried to the various target organs of your body by binding primarily to vitamin D binding proteins (85-88%) and albumin (12-15%).31

Fighting Age-Accelerating Free Radicals in Your Skin

Although your body metabolizes oxygen very efficiently, your cells still get damaged by reactive oxygen species (ROS)—reactive molecules that contain oxygen.17 This happens when an oxygen molecule sacrifices one of its electrons during chemical reactions inside your body. The oxygen molecule is then left with an unpaired electron in its outer orbit, making it highly unstable.18 This oxygen free radical has to reestablish its balance and form an octet (an atom with eight valence electrons), so it steals a neighboring electron from other natural proteins in your skin to regain stability. This sets off chain reactions that result in an aftermath of misshapen and broken molecules. In the end, the structure of your skin is damaged and its cellular structure is weakened.19,20 Free radicals initiate the deterioration of your skin’s structural support and decrease its elasticity, resilience, and suppleness.

Fighting Age-Accelerating Free Radicals in Your Skin

The most common oxygen free radicals are the singlet oxygen, the hydroxyl radical, and the superoxide anion, all of which are normally found in your skin because of its high rate of metabolic oxidation and the availability of fatty acids.21-23 However, other factors such as air pollution, alcohol consumption, cigarette smoke, and stress can increase free radical production as well.24

Stress not only generates potent, destructive free radicals—it also produces adrenaline-related products that restrict blood flow to your skin. Your skin is able to protect itself from this destructive oxidative stress through the use of low molecular weight antioxidants that combat free radicals. Among the most important of these is vitamin D. In fact, vitamin D has been found to be more effective in reducing lipid peroxidation and increasing enzymes that protect against oxidation than vitamin E.25,26

Unfortunately, between the ages of 20 and 70, your skin loses about 75% of its ability to produce vitamin D3—the metabolic precursor of calcitriol, the biologically active form of vitamin D.27 In addition, your skin is the last organ of your body that receives antioxidants from the food and supplements you eat.28 Much of the active vitamin D that your body produces is used to help build and maintain strong bones. However, if antioxidants are applied topically, protection for your skin can be enhanced.


While most people now understand the importance of maintaining optimal vitamin D blood levels for its numerous health benefits, few know of its role in skin protection and rejuvenation. More a hormone than a vitamin, it is integral to the beauty, suppleness, and youthful appearance of skin. The complex process of vitamin D synthesis and utilization yields the active form, calcitriol, a hormone-like compound intrinsic to cellular proliferation and differentiation. Vitamin D thus contributes to skin cell growth, repair and metabolism. It mobilizes the skin’s immune system and helps destroy free radicals that can cause premature aging. Between the ages of 20 and 70, your skin loses about 75% of its ability to produce vitamin D3—the necessary precursor to calcitriol. In conjunction with optimal intake of vitamin D3, topical vitamin D application may enhance its protective and rejuvenating effect on aging skin.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

While most people now understand the importance of maintaining optimal vitamin D blood levels for its numerous health benefits, few know of its role in skin protection and rejuvenation.

1. Available at: Accessed March 8, 2010.

2. Available at: Accessed March 8, 2010.

3. Available at: Accessed March 8, 2010.

4. Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr Rev. 1995 Apr;16(2):200-57.

5. Norman AW. Vitamin D. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition, Washington, D.C.: International Life Sciences Institute ;1996:120-9.

6. Berger U, Wilson P, McClelland RA, et al. Immunocytochemical detection of 1,25-dihydroxyvitamin D receptors in normal human tissue. J Clin Endocrinol Metab. 1988 Sept;67(3):607–13.

7. Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854): 889–95.

8. Olefsky JM. Nuclear receptor minireview series. J Biol Chem. 2001 Oct 5;276(40):36863–4.

9. Available at: Accessed March 9, 2010.

10. Available at: Accessed March 9, 2010.

11. Matsumoto KY, Azuma M, Kiyok M, Okumura H, Hashimoto K, Yoshikawa K. Involvement of endogenously produced 1,25-dihydroxyvitamin D-3 in the growth and differentiation of human keratinocytes. Biochim Biophys Acta.1991 May 17; 1092(3):311–8.

12. Bikle DD. Vitamin D and the skin. J Bone Miner Metab. 2010 Mar;28(2):117-30.

13. Hosl M, Berneburg M. Vitamin D and the skin. Hautarzt. 2008 Sep;59(9):737-42; quiz 743.

14. Oda Y, Uchida Y, Moradian S, Crumrine D, Elias PM, Bikle DD. Vitamin D receptor and coactivators SRC2 and 3 regulate epidermis-specific sphingolipid production and permeability barrier formation. J Invest Dermatol. 2009 Jun;129(6):1367-78.

15. Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest. 2007;117:803-11.

16. Zasloff M. Sunlight, vitamin D, and the innate immune defenses of the human skin. J Invest Dermatol. 2005;125:xvi-xvii. 

17. Available at: Accessed March 9, 2010.

18. Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull. 1993 Jul;49(3):481-93.

19. Fisher GJ, Quan T, Purohit T, et al. Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin. Am J Pathol. 2009 Jan;174(1):101-14.

20. Jung T, Hohn A, Catalgol B, Grune T. Age-related differences in oxidative protein-damage in young and senescent fibroblasts. Arch Biochem Biophys. 2009 Mar 1;483(1):127-35.

21. Meffert H, Diezel W, Sonnichsen N. Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance. Experientia. 1976 Nov 15;32(11): 1397–8.

22. Kovacic P, Somanathan R. Dermal toxicity and environmental contamination: electron transfer, reactive oxygen species, oxidative stress, cell signaling, and protection by antioxidants. Rev Environ Contam Toxicol. 2010;203:119-38.

23. Korkina L, Pastore S. The role of redox regulation in the normal physiology and inflammatory diseases of skin. Front Biosci (Elite Ed). 2009 Jun 1;1:123-41.

24. Moller P, Wallin H, Knudsen LE. Oxidative stress associated with exercise, psychological stress and life-style factors. Chem Biol Interact. 1996 Sep 27;102(1):17-36.

25. Sardar S, Chakraborty A, Chatterjee M. Comparative effectiveness of vitamin D3 and dietary vitamin E on peroxidation of lipids and enzymes of the hepatic antioxidant system in Sprague-Dawley rats. Int J Vitam Nutr Res. 1996;66(1):39-45.

26. Wiseman H. Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS Lett. 1993 Jul 12;326(1):285-8.

27. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.

28. Tavakkol A, Nabi Z, Soliman N, Polefka TG. Delivery of vitamin E to the skin by a novel liquid skin cleanser: comparison of topical versus oral supplementation. J Cosmet Sci. 2004 Mar-Apr;55(2):177-87.

29. Norman AW. Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutr. 1998 Jun; 67 (6): 1108–10.

30. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362–71.

31. Available at: Accessed March 10, 2010.