Do you remember your mother telling you to eat your carrots? How about your aunt telling you to eat your bread crusts to make your hair curly? Or, the lady at the vitamin store telling you to take your skin vitamins? These suppositions are based on the concept that you can eat your way to healthy skin and beautiful hair. Is this really possible? Certainly, lovely skin and hair are a manifestation of overall health, since the skin is perhaps the first indicator of illness. When family and friends tell you that you look sick, they are really assessing your skin and seeing some visual image that is associated with illness.
These ideas are embodied in the newest skin care, known as the inside/out approach to skin care. The inside/out approach combines nutritional supplements with skin care products. Many times the same ingredient is taken orally and used topically to add marketing impact. While it has generally been assumed that good nutrition is the key to a long healthy life and beautiful skin, no double blind placebo controlled studies have been conducted to verify this concept. Certain essential vitamins are necessary in the diet to allow body functioning, but the concept that ingesting large quantities of these substances or applying them topically to the skin results in enhanced health benefits has never been confirmed. Yet, marketing products with the inside/out philosophy abounds because foodstuff are considered safe, the raw materials are inexpensive, and the concept has widespread consumer appeal.
Most skin vitamins contain vitamins C, E, and A. Vitamin C, also known as ascorbic acid, is used both orally and topically for skin benefits. Topically, ascorbic acid is used in cosmeceuticals for hyperpigmentation because it interrupts melanogenesis by interacting with copper ions to reduce dopaquinone and blocks dihydrochinindol-2-carboxyl acid oxidation. Orally, vitamin formulations utilize vitamin C, in the form of L-ascorbic acid, to function as an antioxidant by scavenging and quenching free radicals and by regenerating vitamin E from its radical form., It is well established that vitamin C is necessary for wound healing, as it is a cofactor for lysyl and prolyl hydroxylase, which stabilize the triple helical structure of collagen. Whether oral or topical supplementation of vitamin C enhances wound healing is controversial.
The value of vitamin C oral supplementation is theoretically to maintain the body reservoir of 1500 mg, which is rapidly depleted when the body is exposed to UV light. Oral vitamin C is necessary to prevent scurvy, a disease with many skin manifestations including skin fragility, gingivitis, and corkscrew hairs. In addition, vitamin C may also promote fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions. These activities are necessary to maintain youthful appearing skin.
Even though much is available in the popular press regarding the merits of topical vitamin C, little has been published in the peer reviewed dermatology literature. Some investigators have demonstrated enhanced cutaneous vitamin C levels following topical application of 10% L-ascorbic acid, however this work was performed on a porcine model. Other human studies have demonstrated a decrease in the minimal erythema dose and less erythema following UVB exposure in subjects treated with topical 10% L-ascorbic acid, but the sample size was limited.
The other antioxidant vitamin besides vitamin C is vitamin E. Vitamin E is the most popular topical vitamin in cosmeceuticals and a common skin vitamin supplement. Vitamin E, like vitamin C, is a naturally occurring endogenous antioxidant. Even though the concentration of vitamin E in the epidermis is extremely small at 1.0 nmol/g, it is the most important lipid-soluble membrane-bound antioxidant in the body. Vitamin E and vitamin C work synergistically, since vitamin E can regenerate its antioxidant capabilities in the presence of vitamin C. The form of vitamin E with the most biologic activity is alpha tocopherol, which functions to terminate lipid radical chain reactions. It stabilizes membranes against damage by phospholipase A, free fatty acids, and lysophospholipids. Vitamin E may also protect membrane proteins containing selenium or sulfur.
Again, the value of topical vitamin E awaits further study. A review of the literature yielded articles that demonstrated alpha-tocopherol could inhibit UVB induced edema and erythema, conferring an SPF of 3, after multiple applications. This is thought to be due to its ability to marginally absorb light and function as a free radical quenching, lipid soluble antioxidant.
Finally, vitamin A is found in most skin vitamins. It is necessary for vision and possesses a well-characterized skin receptor. The amount of vitamin A in an oral supplement is measured in retinol activity equivalents (RAE). Many supplements contain beta-carotene that can be split to yield two active units of vitamin A. Vitamin A is a fat soluble vitamin with the recommended daily allowance of 700 RAE for women and 900 RAE for men.
90% of the body vitamin A reserve is found in the liver with 1% in the plasma. The liver vitamin A level in a well-nourished adult is approximately 100 micrograms/gram. Adequate dietary vitamin A is not only necessary for vision, but also for the prevention of chemical carcinogenesis in the epithelial tissues of the bronchi, trachea, stomach, uterus, and skin. Outside of the retina, 9-cis- and didehydroretinoic acid are more important as they trigger gene expression by binding to nuclear retinoid receptors.
The topical benefit of retinol, the naturally occurring form of vitamin A, has been documented by well-controlled studies. It is commonly felt among dermatologists that retinol is of benefit in improving the appearance of aged skin.,
In summary, it appears that it is possible to eat your way to healthy skin. Certainly adequate endogenous levels of vitamins C, E, and A are an absolute requirement. The question remains, however, as to whether supplementation in the form of skin vitamins is necessary. Little data exists for the value of supplements that provide vitamin levels well above the recommended daily allowance. A healthy diet perhaps is one of the most important factors to achieving healthy skin. Perhaps your mother was right. Eat your carrots.
Man has been searching for the fountain of youth since time began. Wars have been waged over life prolongation technology and this issue still captivates in 2011. Vitamins that are guaranteed to restore vitality and increase health abound. Creams that improve wrinkles are hocked on a daily basis on cable TV. In short, man is obsessed with living longer. In ancient times, the Egyptian pharos were specially embalmed and buried with their servants, animals, and household belongings so they were ready to go in the afterlife. A more modern approach is to use cryogenics and freeze the dead so they too will be preserved for reawakening at a later date. Science fiction movies have popularized the cryogenic approach to time travel outside the galaxy, but this approach to life prolongation remains elusive.
One of the most interesting aspects of life prolongation is the effect of diet on lifespan. Is there some magic food that when consumed would slow or even reserve aging? The answer is theoretically “yes.” Resveratrol is a dietary supplement touted for exactly this purpose. Of course, everyone wants to know if it works. To date, it has worked in prolonging the life of mice, but no human studies have been conducted. This article examines resveratrol and its potential as the modern fountain of youth.
Resveratrol is a compound found in fermented red grapes and Japanese knotweed among 72 other plant sources. Resveratrol is 3,5,4'-trihydrostilbene, a stilbene composed of two aromatic rings joined by amethylene bridge. It is a specific member of the stilbene family known as a viniferins, which contain phytoalexin polymers important in the prevention of plant bacterial and fungal infections.
Resveratrol has been found to affect sirtuins, which remove acetyl groups from proteins. Sirtuins are enzymes characterized as deacetylases/mono-ADP-ribosyltransferases found in both lower and higher organisms. The name sirtuin comes from the Sir2 gene that stands for silent information regulator 2. Sirtuins remove acetyl groups in the presence of
nicotinamide adenine dinucleotide (NAD+) and add it to the ADP-ribose part of NAD+ to form adenosine diphosphate (O-acetyl-ADP). Adenosine diphosphate is a lower energy form of adenosine triphosphate (ATP), the energy source responsible for human life. Thus, sirtuins are linked to energy production, which is also related to the regulation of aging, since less energy production is a hallmark of human aging.
Resveratrol has an effect on specific proteins known as histones. Histones are tiny protein balls on which DNA is wrapped to allow it to within the confines of the cell nucleus. When DNA wraps on the histone, a nucleosome core is formed with 146 base pairs of DNA. For replication to occur, this DNA spool must unwrap. The histones must be acetylated, through the addition of acetic acid, to become active and allow the DNA to unwrap and must be deacetylated for the histones to become less active. When the histones are deacetylated, the condensed DNA does not unwrap and transcription cannot occur.
How does resveratrol fit into this picture? Sirtuins are intiators of histone deacetylation capable of inactivating certain segments of DNA. Sirtuins are activated by resveratrol. Thus, resveratrol turns on the deacetylation process making it an anti-aging and anti-cancer agent. This is the same effect as is observed with caloric restriction, but the exact details are still not well understood.
Resveratrol can also function as a potent antioxidant. It contains two aromatic groups and may function as a better oral antioxidant that vitamins C and E. It is the antioxidant capabilities of resveratrol that may be effective in the reduction of coronary artery disease and may be the rationale behind drinking a glass of red wine high in to inhibit the onset of heart ailments. Resveratrol can inhibit the oxidation of low density lipoproteins (LDL), which are increased in atherosclerosis. Resveratrol may also inhibit platelet aggregation and cause vasorelaxation in endothelium-intact and endothelium-dependent aortic rings by the action of nitric oxide-dependent and nitric oxide-independent mechanisms.
It appears that resveratrol may have an effect on cancer as an antiproliferative arresting the cell cycle. The main mechanism that is used to arrest the cell cycle is apoptosis. Apoptosis is the method used by the body to destroy abnormal cells that might result in cancer formation, if not eliminated. There are two mechanisms in the body associated with the reduction in cell proliferation, activation of the p53 gene and suppression of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Resveratrol may block the inflammatory process by inhibiting NF-κB. The exact mechanism by which resveratrol inhibits NF-κB activation is unknown
Caloric restriction is the only activity that has ever been proven to prolong life in rodents. A human caloric restriction experiment would be impossible to conduct given current IRB requirements. Resveratrol is the best investigated substance for mimicking caloric restriction in humans. It appears to slow down genetic aging by affecting the SIRT1 gene, which is the mammalian analogue of the Sir2 gene. The problem is that no one knows the exact dose to achieve longevity. Most dietary experts have recommended between 100 and 200mg of resveratrol daily. At present, it appears that the fountain of youth remains elusive, but resveratrol is certainly one of the possible candidates.
Carotenoids are derivatives of vitamin A and have found widespread use in cosmeceuticals due to the established topical antiaging benefits associated with the prescription tretinoin. Cosmetic chemists are searching widely for ingredients that can rival the topical effect of tretinoin in terms of collagen production, wrinkle reduction, and pigmentation improvement. Since tretinoin has a poor tolerability profile, due to the unwanted side effects of erythema and peeling, perhaps a lower potency OTC carotenoid could produce some of the same benefits.
The carotenoids are a large family of orange, red, and yellow appearing substances that perform vital antioxidant roles when ingested and are less well established as topical antioxidants. There are over 600 known naturally occurring carotenoids. Carotenoids are found in numerous fruits and vegetables and are consumed in large quantity in the Western diet. The most notable source is tomatoes. Topically, carotenoids are difficult to formulate in creams, since they impart a characteristic color to the product; however, colorless carotenoids have been developed. Removing one double bond in the carotenoid can decrease the color and improve product aesthetics.
This article examines the commonly used topical carotenoids including astaxanthin, lutein, lycopene, mangosteen, and pomegranate. These raw materials are finding their way into moisturizing cosmeceuticals rapidly, since they are relatively inexpensive and have great consumer appeal. It is clear that much of their efficacy data is from ingestion studies, nevertheless, if you can eat it, you can put it on your skin.
Astaxanthin is a pink carotenoid found in high concentration in salmon, accounting for the characteristic pink color of the fish. This is the rationale for antiaging diets recommending the ingestion of a serving of salmon five times weekly. For topical application purposes, astaxanthin is obtained from the marine microalgae Haematococcus pluvialis. The efficacy of astaxanthin is attributed to its cell membrane, composed of two external lipid layers, which has been touted to possess stronger antioxidant abilities than vitamin E. It is both water and oil soluble only being produced by algae when exposed to intense UV radiation.
Few topical studies exist to confirm the topical effect of astaxanthin, but it has been studied extensively as an oral supplement. It is used as a homeopathic treatment for macular degeneration because, unlike canthaxanthin, another carotenoid, it does not crystallize in the eye. It crosses the blood-brain barrier and has been studied in brain dysfunction, to include spinal cord injuries and Parkinson’s disease. Even though other carotenoids, such as beta-carotene, have been proven ineffective in reducing the oxidative stress associated with cardiovascular disease, astaxanthin is currently undergoing further investigation.
Astaxanthin in concentrations of 0.03-0.07% produces a pink colored cream. This limits the concentration that can be used, but no topical adverse reactions have been associated with this carotenoid. The topical antioxidant benefits of astaxanthin have not been established, but it is showing up in boutique creams launched this year.
Another carotenoid found in topical cosmeceuticals is lutein. It is naturally found in green leafy vegetables, such as spinach and kale. Lutein is an antioxidant in the plant kingdom, also being used for blue light absorption. In the animal kingdom, lutein is found in egg yolks, animal fats, and the corpus luteum. It is a lipophilic molecule, not soluble in water, characterized by a long polyene side chain composed of conjugated double bonds. These double bonds are degraded by light and heat, a universal characteristic of carotenoids to a greater or lesser degree.
Lutein is used as a natural colorant due to its orange-red color resulting from the absorption of blue light. Its largest use is as a food supplement for chickens, which results in more vivid yellow yolks. In humans, lutein is concentrated in the macula and has been linked to the prevention of macular degeneration. It has been available as a nutritional supplement since 1996 and can be administered as a sublingual spray for elderly patients with macular degeneration. Most well conducted studies evaluating the benefit of lutein for macular degeneration have been inconclusive. No recommended daily allowance has been established for lutein, but 6mg/day has been published. Most of the lutein used for food additives is derived from marigolds.
The question remains as to whether lutein topically is of value. Again data is lacking, but excess lutein intake can result in carotenodermia and excess topical application results in bronzing of the skin. It may be of interest that lutein fed to chickens results in the characteristic yellow appearance of chicken skin, which is felt to be more attractive than the natural white skin. I am not sure that this would be the case in humans.
Lycopene is a potent carotenoid found in most fruits and vegetables with a red color including, tomatoes, watermelon, pink grapefruit, papaya, gac, red bell pepper, and pink guava. The highest lycopene containing food is ketchup, but lycopene is not an essential human nutrient. The Mayo Clinic website rates the evidence for the use of lycopene as an antioxidant as a C, since is it not clear if lycopene has these effects on the human body. Lycopene oral supplements have been purported to reduce the risk of prostate cancer, but the FDA concludes there is little scientific evidence to support this claim.
Lycopene is a highly unsaturated hydrocarbon containing 11 conjugated and 2 unconjugated double bonds, which makes it a longer molecule than any other carotenoid. This makes its absorption into the skin is doubtful. It undergoes cis-isomerization possible when exposed to sunlight. Even though lycopene was the new oral supplement added to many commercial multivitamins this year, its topical value has never been documented. It is safe for skin application, but may stain the skin in high concentration.
Of all the topical carotenoids, retinol is the best understood, since it is necessary for vision and possesses a well-characterized skin receptor. Prescription retinoids, such as tazarotene and tretinoin, are well studied for their ability to induce the skin changes, however OTC retinoids may demonstrate some of the same effects, to a lesser degree. ,
It is theoretically possible to interconvert the retinoids from one form to another. For example, retinyl palmitate and retinyl propionate, chemically known as retinyl esters, can become biologically active following cutaneous enzymatic cleavage of the ester bond and subsequent conversion to retinol. Retinol is the naturally occurring vitamin A form found in red, yellow, and orange fruits and vegetables. It is the pigment responsible for vision, but is highly unstable. Retinol can be oxidized to retinaldehyde and then oxidized to retinoic acid, also known as prescription tretinoin. It is this cutaneous conversion of retinol to retinoic acid that is responsible for the biologic activity of some of the new stabilized over-the-counter vitamin A preparations designed to improve the appearance of benign photodamaged skin. Unfortunately, only small amounts of retinyl palmitate and retinol can be converted by the skin, accounting for the increased efficacy seen with prescription preparations containing retinoic acid.
The main problem with prescription retinoids is their irritancy. Unfortunately, as the biological efficacy of the retinoid increases, so does the irritancy. This is also the case with the OTC retinoids. Retinol is more irritating than the retinyl esters and also more unstable. It is for this reason that cosmeceutical formulations not manufactured under strict oxygen-free conditions prefer to add retinyl palmitate to moisturizing creams. However, the retinyl palmitate may present to act as an antioxidant for the lipids present in the moisturizer.
The topical benefit of retinol has been documented by well-controlled studies. It is commonly felt among dermatologists that retinol is of benefit, but it is difficult in moisturizer studies that do not include vehicle control to separate the retinol benefit from the moisturizer benefit. Nevertheless, of all the carotenoids available for formulation, retinol has the most evidence to support topical application efficacy.
Carotenoids are an interesting family of substances, of which only a few have been discussed. Many well-controlled studies have tried to show their oral benefit in everything from cardiovascular disease to cancer prevention to brain trauma and their topical application benefit for photodamaged skin. It is interesting to note that all of these studies have been inconclusive to date. Could it be that carotenoids do not have the same antioxidant protective effect in humans as in fruits, vegetables, and algae? Or, is it that the right model or indication for study has not been identified? It seems to make intuitive sense that carotenoids should have some human benefit, but the data has not been forthcoming. Carotenoids are a large part of the Western diet, yet they are not an essential nutrient.
I must admit that my favorite summer time Southern lunch is a freshly picked tomato sliced thinly on a potato flour roll. The tangy bite of the tomato is clearly due to ascorbic acid while the red stain on my white blouse is from the carotenoids. Something so tasty must have some benefit, however, it remains to be proven.
The incorporation of vitamins into products designed for cutaneous benefit is an area of active research within the skin care community. The number of skin care products noting vitamins as an ingredient has more than tripled since 1991. Which vitamins are valuable to the skin for active damage repair? Which vitamins can function when applied topically? What is the stability and biologic activity of topically applied vitamins? These and other questions are important for the dermatologist to ask when considering the usefulness of vitamins for cutaneous benefit.
This article examines what is currently known about vitamins commonly used in over-the-counter preparations designed to enhance skin functioning. Several vitamins have been implicated in the health of the skin: vitamin A, vitamin C, vitamin E, panthenol, niacin, and niacinamide.
Vitamin A, and its precursor beta-carotene, are found in yellow, orange, and green vegetables, egg yolk, liver, butter, and fish oils. Vitamin A is one of a family of natural and synthetic related derivatives collectively known as retinoids. Retinoids are biologic modifiers that produce receptor specific effects within the body, such as improvement in facial wrinkling, decreased tactile roughness, and lightening of solar lentigenes., However, there is no evidence that oral retinoids are photoprotective.
In the plant kingdom, vitamin A (retinol) functions as a free radical scavenger, protecting plants from UV radiation damage. Plants especially high in vitamin A include spinach, carrots, sweet potatoes, squash, and cantaloupe. More recently, it has been recognized that vitamin A can decrease and reverse the signs of cutaneous aging.
The use of retinoids in the reversal and prevention of photoaging was discovered by Albert Kligman, MD, Ph.D., who noted that topical tretinoin improved wrinkling, lentigenes, roughness, and precancerous actinic keratoses. The retinoids have also been shown to improve wound healing and striae distensae. Retinoids are the major prescription agent used for antiaging purposes.
The retinoids are difficult to formulate due to their inherent photo instability. As antioxidants, they degrade immediately upon light exposure to biologically inactive forms. For this reason, vitamin A oral supplements are packaged in amber bottles to prevent UV radiation exposure and prescription retinoids are packaged in opaque metal or plastic tubes. Topical preparations where the retinoid has oxidized turn yellow, an indication that some degradation has occurred.
Even though retinyl palmitate is the easiest retinoid to topically formulate in the over-the-counter market, it is not a biologically active form in the skin. Topical activity of retinyl palmitate is thought to occur following cutaneous enzymatic cleavage of the ester bond and subsequent conversion of retinol to retinoic acid. It is this cutaneous conversion of retinol to retinoic acid that is responsible for the biologic activity of some of the new stabilized over-the-counter retinol preparations. Unfortunately, only small amounts of retinol can be converted by the skin, accounting for the increased efficacy seen with prescription preparations containing retinoic acid.
The active form of vitamin C is L-ascorbic acid, functioning as an antioxidant by scavenging and quenching free radicals and by regenerating vitamin E from its radical form., Vitamin C can also act as an oxidant, however, only when in the presence of transition metal ions, such as iron. It is a water soluble vitamin found in vegetables and citrus fruits.
Vitamin C is necessary for wound healing, as it is a cofactor for lysyl and prolyl hydroxylase, which stabilize the triple helical structure of collagen. Whether oral or topical supplementation of vitamin C enhances wound healing is controversial. Some investigators have demonstrated enhanced cutaneous vitamin C levels following topical application of 10% L-ascorbic acid, however this work was performed on a porcine model. Other human studies have demonstrated a decrease in the minimal erythema dose and less erythema following UVB exposure in subjects treated with topical 10% L-ascorbic acid. Vitamin C has also been purported to produce lightening of skin dyspigmentation in the form of magnesium L-ascorbyl-2-phosphate.
More research is required, however, before the benefits of topical vitamin C in humans can be confirmed. One of the problems in developing topical vitamin C preparations is the inactivation of the molecule on exposure to light, moisture, and oxygen. This occurs in topical formulations, as well as in the skin, where the body reservoir of 1500 mg is rapidly depleted.
Vitamin E includes the tocopherols and tocotrienols, however, the biologically active forms are alpha and gamma tocopherol. These forms function as lipid soluble antioxidants, with alpha tocopherol possessing greater biologic activity than gamma tocopherol. Dietary sources of Vitamin E include vegetables, oils, seeds, corn, soy, whole wheat flour, margarine, nuts, and some meats and dairy products.
Vitamin E is naturally found in the membranes of cells and organelles. It prevents oxidation of the polyunsaturated fatty acids of the phospholipids in the membranes by capturing singlet oxygen species. It also stabilizes the membranes against damage by phospholipase A, free fatty acids, and lysophospholipids. Oral Vitamin E is used medically to decrease clotting of the blood and minimize athlerosclerotic plaques.
The antioxidant capabilities of alpha-tocopherol are due to its ability to function as a lipid radical scavenger able to terminate lipid radical chain reactions. In this reaction, a low energy tocopheroxyl radical is formed, however, this radical cannot function further as an antioxidant. Regeneration can occur in the presence of vitamin C to again allow the vitamin E to function as a radical scavenger. It may also protect membrane proteins containing selenium or sulfur. The vitamin E concentration in the epidermis is about 1.0 nmol/g. Even though its concentration in the body is relatively low, it is the most important lipid-soluble membrane-bound antioxidant in the body.
A variety of claims have been made regarding the topical effects of vitamin E on the skin to include: improved moisturization, increased softness, and better smoothness. Photoprotective effects have been evaluated for both topical and oral preparations. Topically applied alpha-tocopherol has been shown to inhibit UVB induced edema and erythema, conferring an SPF of 3, after multiple applications. This is thought to be due to its ability to marginally absorb light and function as a free radical quenching, lipid soluble antioxidant. However, oral vitamin E was shown to confer no photoprotective effects.
Vitamin E may also have an anti-inflammatory effect on the skin, due to the inhibition of the production and release of chemical mediators, such as histamine. It may also stabilize the membranes of lysosomes by interacting with eicosanoids to reduce prostaglandin E2 synthesis and increase IL-2 production. This produces both anti-inflammatory and immunostimulatory effects. A survey of elderly individuals found that high plasma tocopherol levels predisposed to a lower incidence of both infection and cancer.
Panthenol is the biologically active alcohol form of pantothenic acid, also known as vitamin B5, and is enzymatically converted to pantothenic acid in the skin. It is widely used topically as a skin and hair conditioning agent in moisturizers, shampoos, hair sprays, hair styling aids, etc. Its function is best characterized as a humectant, since it can both hold and attract water. This is important since water is the plasticizing agent naturally found in both skin and hair.
Many vitamin enriched moisturizing creams and lotions contain panthenol in a concentration of 5%, which has been shown to enhance wound healing. As a humectant ingredient, it is able to attract water from the viable epidermis and dermis to the stratum corneum where it must be trapped by an occlusive ingredient, if the barrier to transepidermal water loss is impaired. Under conditions where the ambient humidity exceeds 70%, panthenol could also draw water from the environment. Water that is applied to the skin in the absence of a humectant is rapidly lost to the atmosphere. Humectants may also allow the skin to feel smoother by filling voids between the corneocytes through swelling.
Hair care products utilize panthenol also as a humectant to increase the water content of the hair shaft, thus increasing elasticity. It functions well in rinse off products, since it is substantive for hair keratin and can actually penetrate the hair shaft through voids where the cuticle has been disrupted. This provides increased manageability, better shine, less static electricity, and improved softness.
Niacin is one component of the B vitamin complex, however it can be synthesized in the human body as nicotinic acid. It is an important part of two coenzymes of intermediate metabolism (nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)). It is found in animal protein foods, beans, nuts, whole grains, enriched bread, cereals, coffee, and tea. Severe deficiencies are characterized by dermatitis, diarrhea, and dementia.
Nicotinic acid produces flushing, due to a transient increase in cutaneous blood flow. For this reason, methyl nicotinate is applied topically in noninvasive testing to assess the effect of test formulations on blood flow. Medically, it is used internally for the treatment of hyperlipidemias to increase HDL while lowering VLDL and LDL levels, but flushing is an expected side effect. Niacin is not frequently incorporated into topical preparations, however niacinamide, a derivative of niacin, has been shown to demonstrate some valuable cutaneous benefits.
Niacinamide, also known as nicotinamide, is the pyridine-3-carboxylic acid amide form of niacin. It is a white crystalline solid that is soluble in water and stable to both heat and oxygen. It is found in the body in all metabolically active tissues, including the skin. Niacinamide does not produce the flushing experienced with niacin, nor is it valuable in the treatment of hyperlipidemias. It has no effect on blood pressure, pulse, or body temperature.
Topical 4% niacinamide has been shown to be of dermatologic benefit in the treatment of papular and pustular acne in a 4% gel. It has also been reported to aid in the treatment of bullous pemphigoid, and necrobiosis lipoidica. Other studies have demonstrated the value of oral niacinamide in the prevention of insulin-dependent diabetes mellitus. The antiaging cutaneous effects of niaciniamide include the promotion of antitumor characteristics in keratinocytes and the suppression of UVB photocarcinogenesis.
The beneficial cutaneous effects from the topical application of niacinamide, especially the improvement in photocarcinogenesis and its antitumor characteristics, have led to further research as to the usefulness of niacinamide as a moisturizer additive. It is easy to formulate due to its water solubility and stability in the presence of light and oxygen. Niacinamide is a promising additive in antiaging moisturizer formulations designed to enhance cutaneous functioning.
Formulating topical vitamins properly is the key to preparing a product with true skin benefit. The vitamin must be of cosmetic grade, meaning without contaminants, so that its concentration and purity can be verified. Not only is the amount of vitamin in the product important, but the vehicle must be carefully selected to maintain the biologic activity of the vitamin and promote cutaneous bioavailability. The vehicle must prevent chelation, inactivation, and degradation of the vitamin. Table 2 details the oxygen, light, temperature, acid, and base stability of the vitamins discussed in this article. Furthermore, it must allow the vitamin to enter the skin and escape enzymatic degradation.
Most importantly, the vitamin must reach the target tissue. In some cases this may be the epidermis, which is the active site for the humectant panthenol. In other cases this may be the dermis, which is the site of oxygen radical formation where antioxidants must reside in order to be biologically effective and protect collagen and elastin.
The literature is full of conflicting reports regarding the effects of vitamins on the skin. Are these inconsistencies the result of inaccurate studies or observer bias? Not necessarily. Many studies that achieve differing results and arrive at conflicting conclusions due to the use of dissimilar model systems. For example, irradiating pig skin to evaluate the photoprotective effect of vitamins does not directly translate into human efficacy. Even though pig skin is the closest animal model to human skin, it does not demonstrate the same follicular structures and may not yield accurate photobiology results.
Other laboratory models used to investigate the efficacy of vitamins include the use of skin substrates or human cadaver skin or fresh abdominoplasty skin. Skin substrate is devoid of a stratum corneum, allowing tremendous amounts of vitamin to penetrate, but not duplicating the human model. Human cadaver skin possesses an intact stratum corneum, but is enzymatically inactive. Fresh abdominoplasty skin is probably the best in vitro model, but it too cannot replace clinical studies under actual use conditions.
Clinical trials must be carefully constructed to achieve scientifically accurate results. Vitamins functioning as skin conditioning agents work fairly rapidly and aesthetic data is quickly obtained. However, demonstration of the antioxidant effect of topically applied vitamins requires a much longer observation period and histologic assessment. The power of the study must also be carefully calculated to allow selection of a sample size sufficient to achieve statistical significance.
The important role of vitamins in the health of the skin cannot be disputed, however, much research remains to be conducted. Retinoids have been well studied for their benefit in prescription antiaging formulations. Vitamin C will be studied further to determine how it can be photostabilized. Vitamin E preparations will be redesigned to enhance cutaneous penetration. Newer topical vitamins, such as niacinamide, show promise as over-the-counter ingredients to be explored in skin antiaging products. Future research will emphasize the importance of careful formulation and clinical testing as the key to developing truly useful topical vitamin preparations for the skin.
The term nutricosmetic combines the words nutrition and cosmetic. Many of the new food introductions at the grocery store are nutricosmetics of a sort. For example, yogurt is not vitamin D enriched like milk. A new line of yogurt contains vitamin D and inulin, a nonabsorbable fiber to aid in elimination. A competing yogurt contains probiotic organisms, which are bacteria designed to recolonize the gut resulting in improved elimination and better overall health from the “inside out.” An old food with sagging sales can be reinvigorated in the marketplace with little up front cost. While the oral route is far superior to the topical route, there are functions that topical vitamins perform in cosmeceuticals. Vitamins are frequently used as specialty ingredients in creams due to their excellent safety, low cost, and high consumer acceptance.
Vitamin D is important in skin health because it maintains the bony architecture over which the skin is draped. Vitamins D and A were used in some of the oldest marketed skin care preparations (A&D Ointment) to aid in wound healing. Thus, vitamin D is used both orally and topically, however its topical application is largely for its ability to function as a humectant, which increases the water holding capacity of the skin.
Vitamin D is a fat soluble vitamin manufactured by the body when exposed to sunlight. The inhibition of vitamin D manufacture by sunscreens and sun avoidance has been a controversial topic in the popular media with some advocating discontinuing sunscreen sun and deliberate sun exposure to prevent vitamin D deficiency. Vitamin D deficiency, the cause of rickets in children, was virtually eliminated when milk was enriched with 400 IU vitamin D per quart in the 1930s. One cup of milk supplies 25% of the recommended daily allowance of vitamin D in adults, however, it is probable that the current recommended daily allowances are too low. 200IU are recommended daily from birth to 50 years, 400IU from 51 to 70 years, and 600IU for 71 years and older.
It is important to recognize that only drinking milk is enriched with vitamin D. Cheese, yogurt, and ice cream are not required to include vitamin D enrichment, however a new trend in some of the nutricosmetic yogurts, mentioned previously, is to add vitamin D. Only a few foods are rich in vitamin D, including fatty fish, such as salmon, sardines in oil, and mackerel, and fish oils, such as cod liver oil. Consuming too much vitamin D results in toxicity, since the vitamin is stored in the fat of the body. Toxicity presents as nausea, vomiting, poor appetite, constipation, weakness, and weight loss.
The importance of vitamin D in appearance is the preservation of the facial bones. Vitamin D is necessary to maintain calcium homeostasis promoting bone mineralization. Proper mineralization of the facial bones is necessary. Bone loss with maturity occurs commonly in the gingival bones, especially in edentulous persons. This loss of bone leads to wrinkling of the skin around the mouth and inward turning of the lips. Dermatologists should consider obtaining 1,25-dihydroxy vitamin D on all female patients past 50 to look for deficiency, especially if they are fair complected, petite, and have a family history of osteoporosis. Several vitamin D replacement protocols are available, depending on the degree of deficiency. One commonly used replacement strategy is to take 50,000IU of vitamin D once weekly for one month followed by 50,000IU monthly.
In addition, vitamin D is being studied for its ability to modulate the skin’s immune response. It appears that vitamin D3 may be a major factor in the regulation of canthelicidin expression, which may be abnormally processed to forms that induce cutaneous inflammation in rosacea, producing a cosmetically unattractive red face. Other researchers have linked vitamin D to the regulation of p53, a tumor suppressor protein important in skin cancer. This has led to a speculative relationship between vitamin D deficiency and melanoma. It may be that oral vitamin D supplementation is worthwhile to prevent skin cancer, which is at one end of the cutaneous aging spectrum.
Vitamin C, also known as ascorbic acid, is used both orally and topically for skin benefits. Topically, ascorbic acid is used in cosmeceuticals for hyperpigmentation because it interrupts melanogenesis by interacting with copper ions to reduce dopaquinone and blocks dihydrochinindol-2-carboxyl acid oxidation. Orally, nutricosmetic formulations utilize vitamin C, in the form of L-ascorbic acid, to function as an antioxidant by scavenging and quenching free radicals and by regenerating vitamin E from its radical form., It is well established that vitamin C is necessary for wound healing, as it is a cofactor for lysyl and prolyl hydroxylase, which stabilize the triple helical structure of collagen. Whether oral or topical supplementation of vitamin C enhances wound healing is controversial.
The value of vitamin C oral supplementation is theoretically to maintain the body reservoir of 1500 mg, which is rapidly depleted when the body is exposed to UV light. Some researchers believe that natural dietary sources of Vitamin C, such as vegetables and citrus fruits, are the best method of restoring body reserves, while others feel that the poorly ripened fruits now sold in grocery stores are Vitamin C deficient. These researchers feel that synthetic vitamin supplementation is important, however, vitamin C can function as an oxidant in the presence of iron. Oral vitamin C is necessary to prevent scurvy, a disease with many skin manifestations including skin fragility, gingivitis, and corkscrew hairs. In addition, vitamin C may also promote fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions. These activities are necessary to maintain youthful appearing skin.
Even though much is available in the popular press regarding the merits of topical vitamin C, little has been published in the peer reviewed dermatology literature. Some investigators have demonstrated enhanced cutaneous vitamin C levels following topical application of 10% L-ascorbic acid, however this work was performed on a porcine model. Other human studies have demonstrated a decrease in the minimal erythema dose and less erythema following UVB exposure in subjects treated with topical 10% L-ascorbic acid, but the sample size was limited. Vitamin C has also been purported to produce lightening of skin dyspigmentation in the form of magnesium L-ascorbyl-2-phosphate, but no well-controlled studies exist. The challenge remains for researchers to embark on large scale double-blinded placebo controlled studies to demonstrate the value of topical vitamin C.
Vitamin E is the most popular topical vitamin in cosmeceuticals and a common nutricosmetic. Vitamin E, like vitamin C, is a naturally occurring endogenous antioxidant. Even though the concentration of vitamin E in the epidermis is extremely small at 1.0 nmol/g, it is the most important lipid-soluble membrane-bound antioxidant in the body. Vitamin E and vitamin C work synergistically, since vitamin E can regenerate its antioxidant capabilities in the presence of vitamin C. The form of vitamin E with the most biologic activity is alpha tocopherol, which functions to terminate lipid radical chain reactions. It stabilizes membranes against damage by phospholipase A, free fatty acids, and lysophospholipids. Vitamin E may also protect membrane proteins containing selenium or sulfur.
The body stores of vitamin E are maintained through the intake of vegetables, oils, seeds, corn, soy, whole wheat flour, margarine, nuts, and some meats and dairy products. These stores must be maintained by continuous consumption or lipid peroxidation and collagen cross-linking occur, which become accelerated with aging skin. Oral vitamin E intake has also been linked to IgE levels and the clinical manifestations of atopy.
Again, the value of topical application awaits further study. A review of the literature yielded articles that demonstrated alpha-tocopherol could inhibit UVB induced edema and erythema, conferring an SPF of 3, after multiple applications. This is thought to be due to its ability to marginally absorb light and function as a free radical quenching, lipid soluble antioxidant. However, oral vitamin E was shown to confer no photoprotective effects. Topical vitamin E may also function as a penetration enhancer for other active ingredients by intercalating within the lipid bilayer region of the stratum corneum and altering membrane characteristics.
Of all the topical carotenoids, retinol is the most important, since it is necessary for vision and possesses a well-characterized skin receptor. The amount of vitamin A in an oral supplement is measured in retinol activity equivalents (RAE). Many supplements contain beta-carotene that can be split to yield two active units of vitamin A. Vitamin A is a fat soluble vitamin with the recommended daily allowance of 700 RAE for women and 900 RAE for men. Foods that are high in vitamin A include sweet potatoes, kale, carrots, mango, turnip greens, spinach, and papaya. Low fat and skim milk, margarine, and cereals are commonly enriched with vitamin A.
90% of the body vitamin A reserve is found in the liver with 1% in the plasma. The liver vitamin A level in a well-nourished adult is approximately 100 micrograms/gram. Adequate dietary vitamin A is not only necessary for vision, but also for the prevention of chemical carcinogenesis in the epithelial tissues of the bronchi, trachea, stomach, uterus, and skin. Outside of the retina, 9-cis- and didehydroretinoic acid are more important as they trigger gene expression by binding to nuclear retinoid receptors. The mean concentrations of carotene, retinol, and dehydroretinol in the back skin of healthy subjects were 13, 0.4, and 0.4 micrograms/gram of protein with no difference found with variations in sex and age.
It is theoretically possible to interconvert the retinoids from one form to another. For example, retinyl palmitate and retinyl propionate, chemically known as retinyl esters, can become biologically active following cutaneous enzymatic cleavage of the ester bond and subsequent conversion to retinol. Retinol is the naturally occurring vitamin A form found in red, yellow, and orange fruits and vegetables. It is the pigment responsible for vision, but is highly unstable. Retinol can be oxidized to retinaldehyde and then oxidized to retinoic acid, also known as prescription tretinoin. It is this cutaneous conversion of retinol to retinoic acid that is responsible for the biologic activity of some of the new stabilized over-the-counter vitamin A preparations designed to improve the appearance of benign photodamaged skin. Unfortunately, only small amounts of retinyl palmitate and retinol can be converted by the skin, accounting for the increased efficacy seen with prescription preparations containing retinoic acid.
The topical benefit of retinol has been documented by well-controlled studies. It is commonly felt among dermatologists that retinol is of benefit in improving the appearance of aged skin.,
Essential fatty acids are sometimes referred to as vitamin F in the nutricosmetic and cosmeceutical literature. The essential fatty acids cannot be synthesized by the body and must be consumed in the diet. They are long chain polyunsaturated fatty acids derived from linolenic, linoleic, and oleic acids. The two families of essential fatty acids are Omega-3, derived from linolenic acid, and Omega-6, derived from linoleic acid, with the number indicating the position of the first double bond continuing from the terminal methyl group on the molecule.
The principal Omega-3 fatty acid is alpha linolenic acid, which is converted to eicosapentaenoic acid and then into docosahexaenoic acid. Omega-3 fatty acids are used in the formation of cell walls and deficiency leads to decreased mental abilities, poor vision, diminished immune function, increased triglycerides, increased LDL cholesterol, hypertension, and skin disease resembling eczema. The highest concentration of Omega-3 fatty acids are found in flaxseed oil, but other sources include canola oil, hempseed oil, walnuts, sesame seeds, avocados, salmon, and albacore tuna.
The principal Omega-6 fatty acid is linoleic acid, which is converted into gamma linolenic acid, with combines with eicosapentaenoic acid to form eicosanoids. The foods previously listed are also high in Omega-6 fatty acid, except borage oil and evening primrose oil should be added, which are currently popular topical agents. Borage oil and evening primrose oil are used in homeopathic preparations for inflamed dry skin, based on the skin disease observed in essential fatty acid deficient patients.