Nutritional Supplements to Treat Skin and Hair Aging: A Review of Current Information

With today’s increasing life expectations, the desire to look youthful plays a more important role than ever; thus the appearance of skin and hair becomes even more relevant. Even-toned, supple skin with a healthy glow and silky, shiny hair establish an individual’s image and self-perception. In humans, the association of nutrition with changes in skin and hair was first made by James Lind in 1747 with the confirmation of an empirical link between scurvy and vitamin C.1

Nutritionals for the body and mind have been marketed for decades, first as medicines and later as food supplements. Skin and hair traditionally have been treated topically since they are located on the outermost areas of the body. However, since the penetration of ingredients into and through the skin is limited, research has attempted to reach the skin and its appendages through systemic means. Thus, the concept of “beauty from within” developed, and in turn, supplements for both dermocosmetic and dermatologic applications.

Yet, uncertainty remains among caregivers and consumers regarding the capabilities of such preparations. While not exhaustive, this review examines select data on nutritional supplements in relation to skin and hair benefits, to examine the potential for nutritionals to treat skin and hair aging.

Aging in Skin and Hair

Aging is the accumulation of genetically programmed changes in an organism over time. In humans, this refers to a multidimensional process of physical, psychological and social changes.2 Hair aging comprises weathering of the hair shaft and aging of the hair follicle. The first, weathering of the hair shaft, involves the progressive degeneration of the hair fiber from the root to the tip; for example, the tip of a long hair may be three years older than the root. The second, aging of the follicle, manifests as a decrease in melanocyte function, or graying, and a decrease in hair production, especially in the case of androgenetic and senescent alopecia.3

Skin aging, which also includes the scalp, is induced by two processes that are well-characterized: intrinsic and extrinsic aging.4, 5 Intrinsic aging, also known as natural aging or chronological aging,6 is inevitable and genetically controlled. In hair, it leads to cutaneous alterations and familial premature greying or androgenetic alopecia.3

Extrinsic aging is induced by external factors that often fortify one other, in turn aging the skin prematurely and contributing to approximately 80–90% of overall skin changes.7, 8 External aging factors include photoaging, unbalanced diet, air pollution, smoking, sedentary lifestyle, psychological stress, etc.

Among these external factors, the most important contributor to aging is photoaging, which refers to aging caused by pronounced and unprotected sun exposure and the subsequent production of reactive oxygen species (ROS)—a process often referred to as oxidative stress.9

Oxidative stress is a condition in which the production of ROS exceeds the natural antioxidative defense capacities of the organism. Oxidative stress also plays a role in intrinsic aging since it is associated with reactions of ROS formed in the respiratory chain, together with a natural decrease in antioxidative defense mechanisms.10 Women, in particular, suffer a decline in antioxidant protection due to age-related estrogen loss.

Due to the role of ROS in the aging process, most strategies aim either to prevent the induction of ROS (i.e., UV absorption), or act against its formation (i.e., antioxidants), or repair the damage caused by it (i.e., repair enzymes, anti-inflammatory agents, etc.)9, 10 Controlling the level of oxidation of the sulfur pool is another strategy.11, 12

One could write volumes on the plethora of compounds found in recent years that exhibit some positive effect on skin and/or hair aging. Those that have gained recent attention are briefly discussed here.

Food Supplements

Some tissues are capable of selectively accumulating micronutrients to use them for specific functions.13 Such is the case for the skin as well. For instance, it is known that the accumulation of β-carotene in skin provides considerable antioxidative protection—and β-carotene is only one of the many antioxidants that can be detected in the skin. Carotenoids, tocopherols, vitamin C, vitamin B6, flavonoids and other polyphenols, as well as lipoic acid, contribute to the physiological defense of an organism and may contribute to endogenous skin and hair antiaging benefits.9, 10, 14, 15

Carotenoids: As plant pigments, carotenoids protect plants against excess light.16 Major carotenoids in the human organism include β-carotene, α-carotene, lycopene, phytoene and phytofluene, xanthophylls lutein, zeaxanthin and α- and β-cryptoxanthin.17 β-carotene is a ROS-scavenger and precursor of vitamin A, and as such it helps to maintain natural vitamin A homeostasis.15 β-carotene also inhibits free radical and singlet oxygen-induced lipid peroxidation in the biologic system, and is thought to quench photochemical reactions in the epidermis induced by UVB exposure.15 In addition, lutein and zeaxanthin are potent antioxidants that, after UV irradiation, have been shown to be depleted.18, 19

Various intervention studies have been conducted with carotenoids. Dietary intervention with 40 g/day of tomato paste (corresponding to 16 mg/day of lycopene) during 10 weeks led to elevated serum levels of lycopene and amounts of carotenoids in the skin. No significant protective effect was found at week 4 but after 10 weeks of treatment, erythema formation after standardized UV irradiation was significantly lower in the group consuming the tomato paste than in the controls.20

Dietary supplementation with carotenoids has shown a photoprotective effect at doses of at least 12 mg/day for at least seven weeks of treatment.9 The photoprotective effect of β-carotene alone (24 mg/day) was compared with that of a carotenoid mixture consisting of β-carotene, lutein and lycopene (8 mg each/day) and after 12 weeks of supplementation, the intensity of UV-induced erythema was diminished to a similar extent in both groups receiving carotenoids;21 however, it should be noted that β-carotene is limited and could potentially increase the risk of lung cancer in heavy smokers.

Further human studies confirmed the photoprotective abilities of dietary supplementation with lutein and zeaxanthin; these effects could be reinforced by concomitant topical administration22 in accordance with earlier publications.23 Lycopene safety (from Blakeslea trispora) as novel food ingredient also was recently reviewed by the European Food Safety Authority and found to be as safe as lycopene from other sources, whereas an acceptable daily intake (ADI) of 0.5 milligrams per kilogram of body weight per day (mg/kg bw/d) should be respected.24

Vitamins: The antiaging effects of vitamins E and C are believed to be due to their antioxidant properties; both act together with vitamin A against ROS. Vitamin C is necessary for the production of collagen fibers and for the regeneration of vitamin E from the tocopheryl radical.25, 26 The combined oral application of α-tocopherol at 2 grams/day (g/d) with ascorbate at 3 g/d over a period of 50 days showed greater efficacy than separate but equivalent doses of the individual compounds, and led to significant protection against UV radiation.27 Some protection also was observed via high level, co-supplemented doses of vitamins E and C after a short period of time.28 Similarly, the co-application of vitamin E with β-carotene also improved the antiaging efficacy over β-carotene alone but not at a level of statistical significance.29 The application of single compounds did not yield significant protection.9

Also, the combined supplementation of antioxidants including β-carotene, lycopene, lutein, α-tocopherol and selenium has been shown to improve parameters related to skin structure such as skin density, thickness, roughness and scaling after 12 weeks of supplementation.30 Similar results were observed after oral application of a combination of vitamins C and E, carotenoids, selenium and proanthocyanidins.31 Furthermore, combinations of oral antioxidant supplements with concomitant topical antioxidative treatments were tested and showed superiority over single topical treatments.32

The inclusion of vitamin B6 (pyridoxine) in micronutrient supplements is justified by the contribution of this vitamin to preserve an adequate glutathione/oxidized glutathione (GSH/GSSG) balance. Recent findings have shown that, in human kidneys, a deficiency in vitamin B6 is accompanied by increased peroxidation of polyunsaturated fatty acids (PUFAs) and a decrease in both the levels of vitamin E and in the GSH/GSSG ratio33—changes that affect skin health.

Brzezinska-Wcislo34 showed that daily intramuscular supplementation of vitamin B6 for a period of 20 to 30 days, and repetition of this regimen six months later, improved the condition of hair as well as reduced hair loss in women with chronic telogen effluvium (CTE). Biotin, a water-soluble vitamin of the B complex, has often been discussed in relation to hair and hair loss. Dietary supplementation with biotin has been shown to improve the clinical condition of brittle nails;35 however, no known studies have confirmed its effects on androgenetic alopecia. Supplementing the diet with biotin is unlikely to harm a patient but no data exists suggesting that it reduces hair loss.36

Finally, it can be concluded that the combined administration of vitamins is always more effective than administering vitamins alone, which shows that they all play an important role for antioxidative protection together.

Polyphenols: Polyphenolic compounds are secondary plant metabolites characterized by the presence of more than one phenol group per molecule. They are major constituents of the diet and comprise a large variety of structurally different molecules subdivided into phenolic acids, flavonoids, stilbenes and lignans. Some of these are among the strongest antioxidants known. Considerable amounts of polyphenols are found in cocoa, tea and red wine.37, 38 The majority of investigated polyphenols belong to the group of flavonoids. Most ingested flavonoids are not absorbed; they largely are degraded by the intestinal microflora and conjugated into glucuronides and sulfates. Once absorbed generally as phenolic acids, flavonoids continue to exert an antioxidative effect, possibly based on mechanisms other than redox reactions.15

Flavonoids may themselves be divided into six subclasses as a function of the type of heterocycle involved:38 flavonols, flavones, isoflavones, flavanones, anthocyanidins and flavanols (catechins and proanthocyanidins). Proanthocyanidins—also known as oligomeric proanthocyanidins (OPC), pycnogenol, leucocyanidin and leucoanthocyanin—are oligomeric flavonoids. They are dimers or oligomers of catechin and epicatechin and their gallic acid esters.37, 38

• Soy isoflavones: Soy isoflavones are considered to have beneficial effects on the skin such as preventing lipid oxidation of the skin tissue, stimulating fibroblast proliferation, reducing collagen degradation, and inhibiting 5α-reductase39 and UV-induced matrix metalloproteinase-1 (MMP-1) expression and thus, subsequent collagen degradation.40 These effects are derived from the aglycone part of the isoflavones, which also shows better bioavailability. In a double blind, placebo-controlled trial of 13 female volunteers in their late 30s and early 40s, the effect of 40 mg/d soy isoflavone aglycone oral intake was evaluated and revealed a statistically significant improvement in fine wrinkles at week 12, compared with a placebo.39 Among the soy isoflavones-aglycones genistein was the strongest; its activity is attributed to its potent antioxidant capacity.41 Thus, soy isoflavones aglycones could improve the skin of middle-aged women.

• Oligomeric Pinus pinaster (Pycnogenol): Some confusion exists regarding pycnogenol since it is both the synonym for natural OPCs from different origins, as noted above, but also in reference to a commercial extracta from the bark of the French maritime pine, Pinus pinaster.42 This OPC mixture is one of the most powerful antioxidants known42 and has been used as a health supplement for years since it shows efficacy in protecting human skin against solar-radiation induced erythema.7 The material appears to provide biological activities beyond free-radical scavenging, making it an interesting antiaging agent.43

In human intervention studies, doses of polyphenols ranging from 75 mg up to 200 mg daily were administered for three months.44 Among the various clinical indications studied, melasma and UV light sensitivity were two particular skin-related interventions. While the clinical data is significant, more longer-term clinical trials are required. Concerning safety, OPCs are generally viewed as safe; however, no comprehensive information is available for populations at risk, such as pregnant women or children.45

• Red orange extract: Standardized red orange extract (ROE) with phenolic molecules as its main active components, including anthocyanins, flavanones and hydroxycinnamic acids, and ascorbic acid (vitamin C), shows antioxidant and photoprotective activity in different in vitro cell-free experimental models and protects human skin-derived cells against iron-induced lipid peroxidation. Furthermore, when administered orally, ROE was able to increase the level of circulating thiol in humans.46

Another extract, grape seed extract (GSE), is rich in OPCs. It is registered by the US National Center for Complementary and Alternative Medicine (NCCAM) as an herbal nutritional complement47 for cancer prevention and wound healing.

• Green tea polyphenols: Green tea polyphenols (GTPs) have gained considerable attention in recent years due to their antimutagenic and anticarcinogenic properties.48, 49 It has been reported that oral administration or topical application of GTPs protects against UV radiation-induced erythema, carcinogenesis and immunosuppression in humans and animals.48-52 Among the GTPs, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epicatechin (EC), (+)-gallocatechin and (+)-catechin are the major components.38, 50

EGCG has been identified as the major constituent responsible for the biological effects of GTPs.48-50, 52 In vitro studies using ex vivo cultured hair follicles have shown positive effects of EGCG on hair growth,53 corresponding with its proliferative effect on dermal papilla cells that has been shown in vitro and in vivo. Supplementation with GTP of rodents suffering from spontaneous hair loss induced hair regrowth in 33% of the cases during six months of treatment versus no effects in the control group.54

However, although the majority of evidence shows remarkable benefits from the intake of GTPs in general, and EGCG in particular, little data has been published on human effects, and remarkable discrepancies exist between animal and human data.52, 55-57 Nevertheless, green tea is registered by the NCCAM as an herbal nutritional complement to protect skin against sun damage.58 Green tea is considered to be safe in adults when consumed in moderate amounts,57-58 although a limiting factor is its caffeine content.55-58

• Resveratrol: Resveratrol is a polyphenol found in the skin of red grapes, nuts, fruits and red wine. It attracted scientific attention years ago as a possible explanation for the “French Paradox”—i.e., the low incidence of heart disease found among the French, who tend to eat a relatively high fat diet; however, this connection has not consistently been proven.48, 49, 59

In vitro, resveratrol is a potent antioxidant with strong anti-inflammatory and antiproliferative properties. It shows oestrogen-receptor binding activity, featuring agonist or antagonist properties.59 Resveratrol stimulates collagen synthesis and inhibits dermal matrix-degrading enzymes, which makes this material a potential antiaging agent for skin care.48, 49, 59 On the other hand, these activities have also been observed in vitro in cell-free assays or in cell cultures at concentrations that are unlikely to be attained in vivo.59

Probiotics

Probiotics are defined as viable microorganisms that exhibit a beneficial effect on the health of the host when they are ingested. More recently, non-viable microorganisms also have been included in the definition.60 Strains of the genera Lactobacillus and Bifidobacterium are the most common probiotics used for human consumption. They have been shown to exert various positive effects on human health after oral application; e.g., reduction of cholesterol levels, re-balancing intestinal flora, immuno-modulation, etc. The oral administration of either a viable or a non-viable lactococcal strain (H61) on senescence-accelerated mice (SAM) was associated with the suppression of skin ulcers and a reduction in hair loss, compared with controls.60

Ω-3 Long-chain PUFAs

Ω3 Long-chain polyunsaturated fatty acids (Ω3-LCPUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) recently have gained interest due their potential benefits for consumers. EPA and DHA often are referred to as “marine-derived” fatty acids since they are present in oils from cold seawater fish including cod, herring, mackerel, salmon, menhaden and sardines.61 These Ω3-LCPUFAs are involved in diverse physiological processes such as visual and cognitive functions and neuronal development. DHA is also the most abundant Ω3 fatty acid in cell membranes.61, 62

With regard to the skin, Ω3-LCPUFAs have been shown to influence the intrinsic processes of aging in general—collagen remodelling in particular—by inhibiting matrix metalloproteinases (MMPs).63 In addition, Ω3-LCPUFAs modulate key mediators of skin inflammation related to UV exposure.64 In fact, an increase of the Ω3-LCPUFA concentration in skin following supplementation leads to a definitive increase in the MED.49 Several human intervention studies have investigated the consequences of dietary Ω3-LCPUFA supplementation on deleterious effects of UV light in skin (see Table 1).

In regard to the effects of Ω3-LCPUFAs on hair, strong animal data supports the role of PUFA deficiency in hair loss; however, there is limited evidence from human data.71 Dietary supplementation with Ω3-LCPUFA is generally considered to be safe.72

Trace Elements

Iron: Iron is an important nutrient in the human body. Besides its function in the transport and metabolism of oxygen, iron plays a relevant role in the growth and maintenance of skin and its appendages.73 Epidermal cells, hair papillae, nail plate epithelia, apocrine and sebaceous glands, and dermal macrophages are particularly sensitive to iron deficiencies. Severe iron deficiency is associated with general fatigue, eczema, pruritus, skin irritation and hair loss. Furthermore, increased vulnerability to infections and impaired wound healing can also be related to iron deficiency.73

Although iron requirements for hair growth likely vary with age, race, sex and skin color, blood ferritin levels of 40 μg/L or greater are considered ideal for “normal’’ hair growth.73 In one study, 20% of patients showing diffuse hair loss exhibited iron deficiency without obvious anaemia.74 The changes were transitory and iron supplements restored normal hair growth. Also, in 22 women challenged by CTE, which increases hair shedding, Rushton et al.71 demonstrated a 39% decrease in hair shedding after six months of treatment with a daily iron (Fe 72 mg) and L-lysine (1.5 g) supplement. The same was confirmed by a double-blind, placebo controlled study with the same supplement.1

On the contrary, too much iron is detrimental for healthy hair as has been seen in patients with haemochromatosis.75 The high level of iron in these cases likely affects the trace metal balance that is necessary for normal hair growth.73 And although the human body should contain 3-5 g of iron, it is likely that the minimal levels necessary for the “normal’’ functioning and appearance of hair and skin is quite low.73

Zinc: Currently there is no evidence to support the popular belief that low serum zinc concentrations cause hair loss.1, 76, 77

Silicon: Silicon (Si) is a ubiquitous element present in various tissues in the human body including the hair and nails (1–10 ppm).78 It is present in beverages (e.g., beer) and water in the form of orthosilicic acid (OSA). Physiological concentrations of OSA recently were found to stimulate the synthesis of collagen type I in skin fibroblasts.79

A stabilized form of OSA, choline-stabilized OSA (ch-OSA), was found to have high bioavailability in humans.80 Supplementation of animals with low doses of ch-OSA complexes resulted in higher collagen concentration in the skin.81 In humans, the oral intake of ch-OSA during a 20-week study in women with photoaged skin resulted in significant positive effect on the skin surface and mechanical properties in skin,82 accompanied by an improvement in hair brittleness, in comparison with a placebo group. More recently, the effect of oral administration of 10 mg Si/d (in the form of ch-OSA) on hair tensile strength and morphology in women with fine hair was compared with a placebo in a double-blind, randomized clinical trial, and it was shown that the ch-OSA supplements reduced loss in hair elasticity and strength while improving hair thickness.78

Others

L-Cystine, dexpanthenol: L-cystine is the oxidized form of the amino acid L-cysteine, which is a key hair component. Animal intervention studies demonstrated that concomitant oral administration of L-cystine with vitamin B6 prevented environmental cigarette smoke-induced alopecia in mice.83 Dexpanthenol, L-cystine and miliacin each demonstrated positive effects on the proliferation and metabolic capacity of keratinocyte monocell cultures, effects that were amplified by the combination of these three substances.84 Furthermore, in two controlled (one placebo controlled, one comparative) interventional clinical trials with 60 or 72 women, combinations of nutritional supplements including thiamine, calcium pantothenate, medicinal yeast, cystine, keratin and PABA improved hair quality and hair density and retarded hair loss.85, 86 Conversely, oral daily doses of 100 mg calcium pantothenate for 4–5 months did not show positive effects.

Taurine: Taurine is a sulfur amino acid that is present in large amounts in almost all tissues including the skin87 and is produced during methionine and cysteine metabolism. In vitro trials have shown that taurine promoted hair survival;88 however, no published clinical trials demonstrating its efficacy in humans have been found.

Saw palmetto: Saw palmetto or Serenoa repens, is an herbal remedy processed from fruits of the American dwarf pine tree. Due to its ability to inhibit the enzyme 5α-reductase without affecting testosterone levels in men, and because of its partial antagonistic effect on testosterone receptors, it is used as hair loss remedy.36 However, the efficacy of saw palmetto has not been proven in clinical trials comparing single saw palmetto to placebos.

Alpha-lipoic-acid: Alpha-lipoic-acid is a strong antioxidant that directly neutralizes a large array of ROS, thus protecting human keratinocytes against UV-induced oxidative damage. Its activity makes it useful for increasing the modulating effect of carotenoids or preventing the negative effects of vitamin C or E deficiency.89 It also acts on the metabolism of adipocytes, facilitating their elimination.15, 90

Conclusion

The concept of influencing endogenous skin and hair antiaging has gained tremendous interest recently, as the described studies illustrate. The aging process, both intrinsic and extrinsic, is believed to be influenced mainly by the formation of free radicals, also known as ROS. The use of antioxidants, particularly in combination, seems to be the most efficacious strategy to prevent skin aging. The combination of nutritional supplements, such as vitamins and amino acids or plant extracts, seems to best support antiaging benefits in hair.

From this review, it becomes clear that nutritional factors may positively influence the skin and its appendices, protecting against oxidative stress and ameliorating their function. However, most data available tends to originate from in vitro and animal trials or small human clinical studies. Larger, double-blind, randomized, crossover studies are urgently needed to further investigate the appropriate dose regimens of the various nutrients and thus increase confidence in the significance of food supplements for prevention and treatment of skin and hair aging.

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