Evaluation of the Safety and Effectiveness of Nutritional Supplements for Treating Hair Loss
A Systematic Review
Lara Drake, JAMA Dermatol. Published online November 30, 2022.
Key Points
Question Are nutritional supplements or dietary interventions safe and effective for patients with hair loss?
Findings In this systematic review of 30 studies of nutritional interventions, the highest-quality evidence suggests the potential effectiveness of Viviscal, Nourkrin, Nutrafol, Lamdapil, Pantogar, Capsaicin and isoflavone, omega 3 and 6 with antioxidants, apple nutraceutical, total glucosides of paeony and compound glycyrrhizin tablets, zinc, tocotrienol, and pumpkin seed oil. No data for dietary interventions were identified.
Meaning The findings of this systematic review indicate that nutritional interventions may benefit select patients with hair loss, and although few adverse events were reported, physicians should engage in shared decision-making with patients given the lack of federal oversight of these regimens.
Abstract
Importance Despite the widespread use of nutritional supplements and dietary interventions for treating hair loss, the safety and effectiveness of available products remain unclear.
Objective To evaluate and compile the findings of all dietary and nutritional interventions for treatment of hair loss among individuals without a known baseline nutritional deficiency.
Evidence Review The MEDLINE, Embase, and CINAHL databases were searched from inception through October 20, 2021, to identify articles written in English with original findings from investigations of dietary and nutritional interventions in individuals with alopecia or hair loss without a known baseline nutritional deficiency. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Outcomes of interest were disease course, both objectively and subjectively measured. Data were evaluated from January 3 to 11, 2022.
Findings The database searches yielded 6347 citations to which 11 articles from reference lists were added. Of this total, 30 articles were included: 17 randomized clinical trials (RCTs), 11 clinical studies (non-RCT), and 2 case series studies. No diet-based interventional studies met inclusion criteria. Studies of nutritional interventions with the highest-quality evidence showed the potential benefit of Viviscal, Nourkrin, Nutrafol, Lamdapil, Pantogar, capsaicin and isoflavone, omegas 3 and 6 with antioxidants, apple nutraceutical, total glucosides of paeony and compound glycyrrhizin tablets, zinc, tocotrienol, and pumpkin seed oil. Kimchi and cheonggukjang, vitamin D3, and Forti5 had low-quality evidence for disease course improvement. Adverse effects were rare and mild for all the therapies evaluated.
Conclusions and Relevance The findings of this systematic review should be interpreted in the context of each study’s design; however, this work suggests a potential role for nutritional supplements in the treatment of hair loss. Physicians should engage in shared decision-making by covering the potential risks and benefits of these treatments with patients experiencing hair loss. Future research should focus on larger RCTs with active comparators.
Introduction
Although nutritional supplements—vitamins, nutraceuticals, and botanicals—for hair loss are common, data around their effectiveness and adverse effects are highly variable.1 Complementary medications are commonly used for the treatment of alopecia areata (AA) and androgenic alopecia (AGA); a study found that in a hair loss clinic, 81% of patients used supplements.2-4 The most common hair loss supplements were found to be biotin, vitamin B12, and B-complex multivitamin.5 Although the benefit of nutritional interventions is unknown, their use can be expensive, lead to toxic effects in high doses, and interact with medications and test results.1 Given the frequency of supplement use in hair loss patients, we aimed to evaluate the data behind supplements and dietary changes among patients with no known baseline nutritional deficiency.
Methods
This systematic review was exempted from institutional review board approval and informed consent because all data came from previously published studies. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.6
Information Sources and Search
A health sciences librarian (C. H.) performed a search of MEDLINE, Embase, and CINAHL databases, from inception through October 20, 2021. The strategy combined diet or nutrition therapy and hair loss, using keywords and subject headings for each. The search was limited to publications in English and excluded animal studies using the Cochrane limit for studies in humans.7 Investigators scanned reference lists of relevant reviews to supplement database searches. The full search strategy is available in the eMethods in the Supplement.
Eligibility Criteria
Included studies contained original data that evaluated diet and nutritional interventions in adult and/or child participants with hair loss. We excluded studies of animals or nonhumans; hair loss secondary to a nutritional deficiency, medication, toxin exposure, or underlying disease; treatments accompanied by behavioral interventions; and published in a language other than English. We included articles with relevant outcomes, such as disease course and adverse effects; randomized clinical trials (RCTs); clinical studies (non-RCTs); prospective and retrospective cohort studies; and case series and case reports.
Study Selection and Quality Assessment
Initially, the search yielded 6347 citations. After review of the references and other resources, 11 articles were added. Ultimately, 30 articles met our criteria and were included in the analysis: 17 RCTs, 11 clinical studies, and 2 case series (Figure). After initial screening of the titles and abstracts, reviews of the full texts were performed by 3 independent reviewers (L. D., S. R. H., J. M.). A fourth reviewer (A. M.) mediated disagreement and reviewed final articles for inclusion. Quality assessment of included articles was performed independently by 2 reviewers (L. D., S. R. H.) using the Oxford Centre for Evidence-Based Medicine criteria (Table 1).8 Data were evaluated from January 3 to 11, 2022.
Results
We reviewed the study design, nutritional intervention, and outcomes of each of the 30 included articles (eTables 1 and 2 in the Supplement). Table 29-38 provides a list of ingredients for each nutritional supplement.
Safety and Effectiveness of 5-α Reductase Inhibitors
The enzyme 5-α reductase (5AR) converts testosterone to dihydroxytestosterone (DHT), a mediator of AGA. Finasteride, currently approved by the US Food and Drug Administration (FDA) for the treatment of AGA in men, inhibits 5AR.
Saw Palmetto
Serenoa repens, commonly known as saw palmetto, is a botanical compound hypothesized to inhibit 5AR. Clinical studies of S repens have shown efficacy for androgen-dependent conditions (eg, benign prosthetic hyperplasia), which like AGA are also mediated by DHT.9,39
An RCT of active oral lipidosterolic extract of S repens use in 19 males with mild-to-moderate AGA showed 60% investigator-assessed improvement in the intervention group compared with 11% in the placebo group after 5 months, although it was not a statistically significant difference.9 Another comparative effectiveness trial of S repens and oral finasteride in 100 men with mild-to-moderate AGA found finasteride more effective at improving hair loss, while S repens stabilized hair loss after 24 months.10 Adverse events reported were mild and included nausea, diarrhea, and constipation.
These findings suggest that S repens may stabilize hair loss, although its effect is likely less than that of finasteride. Sexual dysfunction, an adverse effect associated with finasteride, was also seen with S repens but to a lesser extent.9,10,39 Physicians should be aware that in men using S repens, there may be a theoretical risk of missing early detection of prostate cancer given that 5AR inhibition been associated with reduced levels of prostate cancer markers.10,40
Pumpkin Seed Oil
Pumpkin seed oil has shown effectiveness in treating benign prosthetic hyperplasia given its 5AR inhibition and antiandrogenic properties.41,42 An RCT of pumpkin seed oil capsule use among 76 men with AGA demonstrated significantly superior hair growth and patient-reported satisfaction among the intervention vs the control group; adverse events (ie, pruritus and abdominal pain) were similar in both groups. Pumpkin seed oil may be a potential alternative to finasteride for treatment of AGA; however, to our knowledge, no comparative study has been performed.11
Forti5
Forti5 (Q-SkinScience) is a nutritional supplement designed to target AGA using antioxidants, melatonin, cholecalciferol, soy phytoestrogens, and botanical 5AR inhibitors. A prospective case series of Forti5 use among 10 adults with AGA showed investigator-assessed improvement in 80% of participants at 24 weeks, with significantly increased hair mass index.12 Despite favorable results with no adverse effects, the study was limited by its small sample size and lack of control group.
Safety and Effectiveness of Micronutrients
Micronutrients play a key role in the normal functioning of the hair follicle. Many types of alopecia are characterized by lower levels of micronutrients compared with controls.
Vitamin D
Lower or deficient levels of vitamin D have been associated with AA, AGA, and telogen effluvium (TE) in some studies.43-45 A single-arm prospective study13 that assessed oral vitamin D3 supplementation in 40 women with TE observed that at 6 months, 82.5% of the patients had improved results on hair pull test and 85% reported being satisfied; no adverse effects were reported. Given the self-resolving course of TE, lack of control group, and lack of baseline vitamin D assessment, these findings should be interpreted with caution.
Zinc
Zinc deficiencies can cause TE, hair breakage, and hair thinning. Lower serum zinc levels have inconsistently been identified in patients with AA compared with controls.46-48 The association between AA and zinc use is hypothesized to be its role in copper and/or zinc superoxide dismutase, with decreased levels resulting in tissue oxidative damage.47
A nonrandomized, double-blind, placebo-controlled study14 of zinc sulfate use in 38 participants with AA, alopecia totalis, and alopecia universalis with normal baseline zinc levels demonstrated no improvement in hair outcomes at 3 months, while another crossover study16 of zinc sulfate capsule use in 67 patients with AA and baseline normal zinc levels showed significant hair regrowth after 3 months of zinc supplementation. Larger, more rigorous studies are needed to evaluate the association of zinc supplementation with AA. An additional 4-arm comparative effectiveness study15 of zinc sulfate and calcium pantothenate, zinc sulfate, calcium pantothenate, and 2% topical minoxidil use in 73 women with self-reported hair loss showed increased hair thickness and density in all groups, with the largest increase in density among the minoxidil group and in thickness among the calcium monotherapy group at 4 months; no adverse effects were reported. The study’s limitations included using self-perceived hair loss data and the lack of a control group.
B Vitamins
The B vitamins include B7 (biotin) and B12. To our knowledge, biotin monotherapy for alopecia has not been studied but it is a component of other nutritional supplements in this review. Biotin use is widely advertised for improving hair growth.49 The FDA has warned against biotin supplementation because it can interfere with some laboratory testing such as troponin and hormonal tests.50
Vitamin B12 is important for DNA synthesis and has been proposed to be beneficial for proliferating hair cells.46 A prospective study evaluated the use of oral B12 daily and injection monthly in 10 participants with TE with dysesthesia17 (a subcategory of TE with itch, pain, soreness, and/or burning) and normal baseline B12 levels. At 4 months, all participants had experienced decreased or absent shedding, and 90% reported decreased or absent dysesthesia, with no adverse effects. However, given the self-resolving course of TE and lack of control group, these findings should be interpreted with caution.
Antioxidants
Oxidative stress has been suggested in the pathogenesis of AA, AGA, and TE.51-53 Antioxidants—eg, selenium, carotenoids, and vitamins A, C, and E—are commonly included in supplements. Excessive supplementation has been linked to toxic effects and hair loss.54,55 An expert-blinded RCT18 of fish oil, blackcurrant seed oil, vitamin E, vitamin C, and lycopene supplementation compared with no supplementation among 118 women with Ludwig stage 1 AGA showed significantly increased hair density and thickness in the intervention group at 6 months. Another RCT evaluated mixed tocotrienols (vitamin E family)19 in 35 patients with unspecified hair loss showed significantly more hairs in the intervention group at 8 months. There were no adverse events reported in either of these studies, and their limitations included a lack of defined hair loss in the inclusion criteria and small sample sizes.
Safety and Effectiveness of Immunomodulators
A subset of alopecia types, such as AA, are autoimmune conditions. Therefore, it has been hypothesized that substances with immunomodulating properties may affect hair regrowth. Total glycosides of paeony (TGPC) and compound glycyrrhizin tablets (CGT) are Chinese herbal plant extracts that have been shown to regulate T-cell activation.20 A comparative effectiveness study of TGPC, CGT, and vitamin B2 vs CGT alone20 in 117 children with severe AA showed a reduction in AA severity score compared with the baseline in both groups, and a significantly better response among the TGPC and CGT group compared with the CGT monotherapy group at 12 months. Adverse events were mild and included abdominal pain and increased stool frequency.
Safety and Effectiveness of Amino Acids
Keratin is a structural fibrous protein that makes up hair; it has large amounts of the sulfur-containing amino acid cysteine. Supplementation with sulfur-containing amino acid was initially investigated in sheep, in which it increased wool production.56 An L-cystine deficiency makes hair thin, brittle, dry, and fragile, and ultimately results in hair loss.
Pantogar (Merz Pharma) is a hair growth supplement that contains L-cystine and keratin among other ingredients. An RCT of Pantogar use in 30 adult women with TE21 showed significantly increased anagen hair rates but no significant change in hair count, density, and diameter in the intervention group compared with baseline at 6 months. Adverse events included gastrointestinal symptoms, weight gain, and transient elevation of pancreatic enzymes. Limitations included a small sample size and short time course that mimicked the natural resolution of TE.
Safety and Effectiveness of Probiotics
Probiotics are hypothesized to improve blood flow to the scalp.22,57 A study of use of Mogut (Coenbio Co), a kimchi and cheonggukjang (fermented soybean paste) probiotic product, among 23 men and 23 women with AGA22 showed significant improvement in hair thickness and/or hair count in 93% of patients at 4 months with no adverse effects reported. Limitations included small sample size and lack of a control group.
Safety and Effectiveness of Growth Hormone Modulators
Insulin growth factor-1 (IGF-1) plays an important role in hair follicle development and in the hair growth cycle.58 Modulated by growth hormone, deficiencies in either IGF-1 and/or growth hormone have been associated with several causes and types of hair loss, including alopecia and TE.59
Capsaicin and Isoflavones
Capsaicin is used as a topical analgesic and as a food additive to provide a spicy flavor and a burning sensation. Isoflavones are naturally occurring phytoestrogens of the bean and legume family. Both topical capsaicin and isoflavones may increase dermal IGF-1 production,60 which is involved in hair growth. An RCT of capsaicin and isoflavone use in 48 adults with either AGA or AA23 showed significantly more hair growth in the capsaicin and isoflavone group at 5 months; no adverse effects were reported. Limitations were its small sample size and the inclusion of various types of alopecia.
Miliacin Encapsulated by Polar Lipids
Miliacin is the main compound in millet, a type of small-seeded grass, which is hypothesized to modulate IGF-1.61 An RCT of miliacin encapsulated by polar lipids capsule use in 65 women with TE24 showed no difference between the intervention and placebo groups at 12 weeks; no adverse effects were reported. Limitations included the small sample size and the short time frame that mimicked the natural resolution of TE.
Safety and Effectiveness of Marine Protein-Based Supplements
Nutraceuticals containing marine protein supplements (MPS) have been hypothesized to decrease hair loss by providing essential nutrients to nourish thinning hair.29 Compounds with MPS as the primary component have been assessed in several clinical trials for efficacy in treating hair loss.
Viviscal
Viviscal (Lifes2good Inc) is an oral supplement that primarily contains the AminoMarTM marine complex, a proprietary blend of extracellular matrix components from sharks and mollusks.62 Use of Viviscal and its formulation, Viviscal Man, were studied in men with AGA and showed significant improvements in hair counts.25,26 Viviscal and other formulations were also examined in women with self-perceived hair thinning; they showed increased terminal hair counts and reduced shedding.27-30 Adverse effects included mild bloating and stomach discomfort in both the placebo and intervention groups. The limitations of these studies included the subjective inclusion criteria of self-perceived hair thinning, no baseline nutritional status or definition of the hair loss pattern, small sample sizes, and funding by the product’s manufacturer.
An additional RCT31 studied use of Hairgain (later marketed as Viviscal) in 60 adults with hair loss; there was a significant increase in hair counts among the intervention group at 12 months and no adverse effects. Limitations included a small sample size and inclusion of patients with various types of alopecia. All Viviscal formulations are summarized in eTable 2 in the Supplement.
Nourkrin
Nourkrin (Pharma Medico) is another MPS. Dysregulated proteoglycan metabolism plays a mediatory role in the causes of hair loss. It has been hypothesized that Nourkrin acts as proteoglycan replacement therapy in treating hair loss.63 An RCT of Nourkrin use in 51 men and 4 women with unspecified hair loss32 showed significantly increased hair counts in the intervention group compared with the placebo group at 12 months; no adverse effects were reported. Limitations included the low number of female patients and a lack of specific hair loss inclusion criteria.
Safety and Effectiveness of Multi-Ingredient Supplements
The nutritional supplements in this section are composed of multiple ingredients, each with unique mechanisms of action. Their ingredients and proposed mechanisms in combating alopecia were reviewed.
Nutrafol
Nutrafol (Nutraceutical Wellness Inc) contains the patented Synergen Complex, which is composed of plant-based active compounds with anti-inflammatory, antioxidant, and DHT-inhibitory properties.33 Nutrafol and its formulations were studied in women with self-perceived thinning hair33,34; the results showed significantly increased hair counts and decreased shedding; adverse effects, included nausea, bloating, and diarrhea, were reported among the intervention group. Limitations of these studies included subjective inclusion criteria of self-perceived hair thinning with no baseline nutritional status and funding by the product’s manufacturer. A case series study of 4 African American women with AGA, hair thinning, and traction alopecia who used Nutrafol demonstrated hair regrowth in 2 months to 2 years, with no adverse effects reported.35 Lack of control, blinding, and inclusion of different types of hair loss limited the generalizability of this study’s findings.
Omni-Three
Omni-Three (Omninutrition) is a patented nutritional supplement containing plant extracts that have demonstrated anti-inflammatory and antioxidant properties in vitro and in vivo.64-66 A prospective study of Omni-Three36 use in 27 adults with TE demonstrated nonsignificant improvement for hair growth at 3 months; no adverse effects were reported. Limitations included a small sample size, lack of statistical significance, lack of a control group, and a short time course that mimicked the natural resolution of TE.
Apple Nutraceutical
Topical procyanidin B2 has demonstrated efficacy in hair growth in prior human trials.67 Procyanidins increase the anagen growth phase, ultimately leading to increased hair density and terminal hair formation.68,69 An apple variety of the Apple Fruits of Annurca family has high procyanidin B2 content.70 A comparative study of use of 2 extract formulations from the Apple Fruits of Annurca37 variety in 250 adult participants with AGA showed significant increases in hair density, weight, and keratin content, from baseline in both groups at 8 weeks; no adverse effects were reported. Limitations included a short duration and the lack of a control group.
Lambdapil
Lambdapil (Isdin SA) is a food supplement composed of L-cystine (keratin protein synthesis), S repens (5AR inhibitor), silicon derived from Equistem arvense (for hair resilience), and other ingredients.71 An RCT of Lambdapil treatment in 35 men with AGA and 35 women with TE showed a significant improvement in results of the hair pull test in the Lambdapil group compared with placebo group of women with TE, and a significant increase in the anagen to telogen ratio compared with baseline in men with AGA at 6 months.38 Adverse effects included bloating in the active treatment group. Limitations included nonclinically relevant outcomes and a small sample size.
Discussion
This systematic review highlights the safety and effectiveness of several nutritional interventions for patients with hair loss. Twelve of the 20 nutritional interventions had high-quality studies suggesting objectively evaluated effectiveness (Table 1). These findings should be interpreted in the context of each study’s methods and limitations—the quality of study design and the size of each study varied considerably. No studies of dietary interventions qualified for inclusion in this review.
Currently, dietary supplements are categorized as food; however, the FDA does not govern their safety or effectiveness of nutritional supplements before consumer marketing.72 Given the ubiquitous use and substantial financial burden of nutritional supplements, it is imperative that both physicians and patients be aware of the lack of FDA oversight and be vigilant when selecting a supplement. Despite these limits, some patients with hair loss may benefit from nutritional supplementation, and shared decision-making with dermatologists should be encouraged to review risks and benefits of each treatment.
Limitations
Nonstandardized inclusion criteria, hair loss definitions, and outcome assessments restricted comparisons between studies and limits generalizability to all patients with hair loss. Additionally, many studies were funded by their manufacturers, introducing potential biases.
Conclusions
This systematic review of nutritional supplementation and dietary interventions for hair loss found that few studies reported adverse events; however, adequately powered RCTs are warranted to further assess the safety and effectiveness of these treatments. Additionally, because finasteride and minoxidil are FDA-approved first-line treatments for many types of alopecia, nutritional interventions should be evaluated as alternative or adjunct treatments by future trials.