Vitamins and Minerals

Vitamins and minerals have well-established roles in the normal development of hair follicles, and deficiencies in specific substances can cause characteristic alterations to hair production. The role that vitamins and minerals play in the progression or treatment of AGA is less clear and will be examined in this section.

Vitamin A comprises a group of fat-soluble retinoids that are mostly stored in the liver. A balanced diet will generally provide adequate amounts of vitamin A, and overconsumption of vitamin A (> 10,000 IU/day) is associated with hair loss. Additionally, isotretinoin (a vitamin A analog) was found to decrease hair count, density, and percentage of hairs in the anagen phase in patients being treated for acne vulgaris.

The vitamin B complex includes eight water-soluble vitamins—thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12)—of which only B2, B7, B9, and B12 have been associated with hair loss. There are sparse data on vitamin B2 supplementation for hair loss, but deficiency can cause hair loss. Biotin (vitamin B7) is commonly found in supplements for hair, skin, and nails. While signs of biotin deficiency can include hair loss, there are no large-scale studies to support its use as a supplement for hair regrowth in the absence of deficiency. However, lower biotin levels have been noted in a portion of patients with premature hair loss, suggesting biotin may play a part in the multifactorial etiology of AGA. Vitamins B9 and B12 are involved in nucleic acid synthesis and are therefore important in the rapidly dividing cells of the hair follicle. While there is a lack of studies on the supplemental use of these vitamins for hair regrowth, there has been very weak or no association found between folate and vitamin B12 levels and hair loss.

Vitamin C is a water-soluble vitamin that prevents the oxidation of low-density lipoproteins and free radicals, assists in collagen fiber synthesis, and is essential for iron absorption. Oxidative stress and iron deficiency are important factors in hair abnormalities and hair loss; however, there are no correlational studies on vitamin C levels and hair loss.

Vitamin D is a fat-soluble vitamin obtained via the diet or synthesis in the skin, followed by a series of enzymatic reactions in the liver and kidneys to produce the active form, 1,25-dihydroxyvitamin D. In the skin, vitamin D plays a role in keratinocyte maturation, as well as hair follicle proliferation, where there is the highest number of vitamin D receptors. As seen in vitamin D–dependent rickets type 2, vitamin D deficiency can lead to severe alopecia. Vitamin D may also play a role in AGA, as studies have shown that patients with AGA have significantly lower serum vitamin D levels and vitamin D deficiency. Obtaining serum vitamin D levels and vitamin D supplementation in patients with AGA may be a helpful adjunct in combating hair loss.

Vitamin E is important for oxidant/antioxidant balance and helps protect against free-radical damage. Furthermore, oxidant/antioxidant imbalance has been implicated in AGA through various studies, and there is some evidence to suggest that patients with AGA have lower mean serum vitamin E levels than control patients. Therefore adequate vitamin E supplementation may be helpful in attenuating hair loss in patients with AGA.

Several minerals are implicated in hair loss, including iron, selenium, and zinc. Iron deficiency is the most common nutritional deficiency worldwide and tends to affect females more than males due to menstruation. The role iron deficiency plays in hair loss is still debated, with conflicting evidence. However, iron deficiency is a likely contributor to telogen effluvium, whereas the role it plays in AGA is less clear. Selenium is required for synthesis of a variety of proteins and functions as a cofactor in some antioxidant enzymes. Selenium deficiency tends to affect undersupplemented patients receiving total parenteral nutrition or chemotherapy and can lead to hair discoloration and hair loss; however, deficiency in the general population is almost nonexistent. Zinc is a trace element, and deficiency tends to be associated with a variety of inflammatory conditions and other systemic conditions. The role of zinc in AGA is inconclusive, as is the role of zinc supplementation in treating AGA. Zinc supplementation may be helpful as an adjunct treatment in AGA patients; however, oversupplementation may result in zinc toxicity.

Nutraceuticals

Nutraceuticals are a class of beauty products consisting of phytochemicals derived from food and botanicals that have biologically active effects. This emerging frontier is gaining popularity with an inside-out approach to health and beauty that is seen as safer and more natural. Botanicals in the treatment of hair loss target a variety of pathogenic mechanisms including inflammation, DHT, oxidative damage, stress mediators, and intermediary signaling cascades. The scientific basis and evidence of some common nutraceuticals to treat hair loss, including curcumin, ashwagandha, saw palmetto, tocotrienols, and collagen, will be discussed in this section.

Curcumin is derived from turmeric and has been used in Ayurvedic medicine for centuries to treat respiratory and hepatic disease, as well as inflammatory disorders. Curcumin is well recognized for its antiinflammatory and immunomodulatory effects with minimal side effects, which is the basis for its use as a hair loss supplement. Antiinflammatory properties of curcumin include the downregulation of cyclooxygenase-2 (COX-2), lipoxygenase, and inducible nitric oxide synthase. Additionally, curcumin inhibits the nuclear factor-kappa B (NF-κB) transcription factor, decreasing the tumor necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1) cytokines, which are involved in follicular regression. Curcumin also has antiandrogen activity and has been shown to decrease aberrant androgen receptor expression and 5α-reductase activity, both of which are vital in hair loss caused by AGA.

Ashwagandha is a botanical with a wide range of biologic effects, mostly relating to physical and psychiatric stress reduction. Classified as an adaptogen, ashwagandha assists in maintaining homeostasis when taken daily. Ashwagandha contains steroidal lactones (withanolides), sitoindosides, and other alkaloids that interact with the corticosteroid receptor to modulate the stress response and reduce serum cortisol levels. Elevated stress and cortisol levels have been shown to play a role in hair loss pathogenesis, providing the rationale for ashwagandha supplementation to help prevent hair loss. Additionally, withanolides induce endothelial nitric oxide synthase, which may help improve blood flow to the hair follicle and prevent follicle regression.

Saw palmetto extract (SPE) is a botanical that inhibits both isoforms of 5α-reductase, preventing the conversion of testosterone to DHT. SPE has been studied for treating benign prostate hyperplasia and erectile dysfunction, with conflicting data on its efficacy, but it may provide a natural alternative for treating AGA. A 2014 study of males with AGA compared the efficacy of 320 mg SPE versus finasteride 1 mg supplementation for treating hair loss. Significant improvement occurred in 38% of the SPE group and 68% of the finasteride group. Though more effective than SPE as a monotherapy, finasteride has the risk of erectile dysfunction, while SPE may help treat patients with erectile dysfunction via an increase in inducible nitric oxide synthase. Pumpkin seed oil also inhibits 5α-reductase and has demonstrated significantly superior hair growth and patient satisfaction in a randomized controlled trial of patients with AGA. Pumpkin seed oil may have the potential to be an alternative to saw palmetto; however, no head-to-head studies have been performed.

Tocotrienols/tocopherols are constituents of the vitamin E family that help prevent lipid peroxidation of cell walls. Patients with alopecia likely have lower levels of antioxidants such as glutathione and glutathione peroxidase, along with increased signs of lipid peroxidation, providing the basis for oral tocotrienol and tocopherol supplementation. A study compared the effect of supplementation with tocotrienol versus placebo in patients with hair loss and found a mean hair count increase of 34% in the tocotrienol group versus no significant increase in the control group.

Collagen is an essential component of the extracellular matrix, and collagen hydroxylates from marine sources are commonly used in nutraceuticals. When ingested, collagen fragments are delivered to the skin where they both serve as the building blocks and increase the production of extracellular collagen. Additionally, collagen fragments have photoprotective, antioxidant, and immune modulatory effects, and when included in nutraceuticals, they have been shown to help regrow hair in patients with telogen effluvium and AGA. Marine collagen, specifically, is used in popular nutraceutical products for hair regrowth.

Amino acids have also been studied for hair regrowth. Cysteine and other highly sulfonated amino acids have been used in sheep to help increase wool production. Pantogar (Merz Therapeutics) is a supplement that contains keratin, which has high levels of cysteine; it is marketed as a supplement for the treatment of AGA, but there are no data to support its use for this to date. Pantogar has been shown to increase anagen hair rates but not increase anagen hair counts in telogen effluvium.

Marine complex supplement (MCS) (Viviscal, Lifes2good Inc.) is a commercially available hair loss supplement that uses a blend of nutraceuticals and other ingredients to promote hair regrowth. The primary ingredient in Viviscal is a proprietary marine complex of extracellular matrix components derived from sharks and mollusks, along with apple extract and L-cystine. Depending on the formulation, other ingredients that may help treat hair loss include Equisetum arvense (horsetail) extract, flaxseed extract, and zinc. Viviscal has been available since 1990, and several studies have demonstrated its efficacy in treating hair loss in patients with AGA.

Studies have shown that MCS reduces hair shedding, increases hair thickness, increases terminal hair counts/density, and greatly improves self-assessment of hair regrowth in both males and females with AGA. Furthermore, studies have demonstrated efficacy in treating male- or female-only cohorts, Black patients, and patients of a variety of ages. Moreover, studies show hair regrowth at 3 months and further improvement through 6 months. Multiple studies have demonstrated that the vast majority of patients taking MCS show both objective and subjective improvement of their hair.

There are no significant side effects that have been linked to MCS, and there may be additional health benefits to taking the supplement. Of note, all studies have been funded by the drug company.

Nutraceutical supplement (NS) (Nutrafol, Unilever) is another commercially available hair loss supplement combining multiple nutraceuticals with the intention to help regrow hair. The key supplements aiding in hair regrowth include ashwagandha, marine collagen peptides, tocotrienol, curcumin, and saw palmetto, which target different mechanisms in the pathogenesis of AGA. Although NS was released in 2016, the available studies have demonstrated efficacy in treating AGA.

One study demonstrated increased hair counts, hair thickness, and overall hair quality in females with hair thinning through 9 months of treatment, with virtually all females having a positive response to the treatment. Hair counts, density, and coverage have been demonstrated in roughly 80% of patients who take the supplement daily, with improvements through 9 months. These results have been shown in pre- and postmenopausal females, in males, and across different ethnicities.

Importantly, there are no significant side effects associated with NS supplementation. Furthermore, the supplements in NS likely have additional health benefits beyond hair regrowth. Although NS has more ingredients to target additional and specific mechanisms of hair loss compared to MCS, efficacy cannot be adequately compared due to a lack of head-to-head studies.

Another multiingredient supplement for AGA is Nourkrin (Pharma Medico), which is theorized to help replace the lost proteoglycans playing a role in hair loss and has shown promise in increasing hair counts in patients with unspecified hair loss.