Rajani Katta, MD1 and Sophia Huang, BSc2

1McGovern Medical School at The University of Texas Health Sciences Center at Houston, Houston, TX, USA
2Rice University, Houston, TX, USA

Conflict of interest:
Rajani Katta: advisory board member for Vichy Laboratories and author of a book for the general public on diet and dermatology. Sophia Huang has no conflicts to declare.

Abstract
Dermatology supplements, often marketed as “skin, hair, and nail” supplements, are becoming increasingly popular. However, many consumers lack an understanding of the science of dietary supplements or the specifics of the supplement industry. While certain supplements at the right dose in the right population may prove beneficial, the evidence is sparse for many supplements. In addition, the use of some supplements has resulted in serious adverse effects. From a regulatory standpoint, the US FDA recognizes dietary supplements as foods. This distinction has multiple ramifications, including the fact that manufacturers do not need to prove efficacy, safety, or quality prior to sale. Therefore, physicians and consumers must evaluate each supplement ingredient and formulation individually. This article outlines an evidence-based approach to assess dermatology supplements. As a starting point, all supplements should be evaluated for PPIES: purity, potency, interactions, efficacy, and safety.

Key Words:
beauty supplements, evidence-based approach, hair, interactions, nails, potency, purity, skin, supplement safety

Background

While consumers used to seek out “hope in a jar”, many now turn to “hope in a capsule”, as global consumer interest in dietary supplements continues to rise. According to a 2017 Council for Responsible Nutrition Survey, 76% of adults in the United States take dietary supplements.1 Among dietary supplements, the category of “beauty” supplements in particular has experienced a surge in popularity. On social media and in retail stores, these are marketed using a large variety of descriptive terms, such as “age defying”, “for thinning hair”, “for skin, hair, and nails”, and others.

Beauty supplements are big business. While some of this growth is due to increasing consumer interest, another major contributing factor is the lack of oversight and regulation. Without any need to demonstrate safety or efficacy prior to sales, manufacturers continue to enter the market. According to a report by Goldstein Research, in 2016 the global beauty supplement market was valued at about $3.5 billion, and by the end of 2024 this market is estimated to reach $6.8 billion.2

Although extremely popular, many consumers do not understand the science of dietary supplements or the specifics of the supplement industry. Certain supplements at the right dose in the right population may indeed be potentially beneficial. One example is encouraging research on the use of nicotinamide in the prevention of non-melanoma skin cancer (NMSC) in high-risk patients.3 However, the evidence is sparse for most supplements. In fact, while evidence of harm from dietary supplements is extensive and well-documented, evidence of benefit is much more limited. It is therefore extremely important to examine the use of supplements with an evidence-based approach.

The evidence-based evaluation of skin, hair, and nail supplements presents a number of challenges. The sheer number of available supplements is a major concern. It is extremely challenging for physicians, let alone consumers, to have extensive knowledge of available supplement ingredients, not to mention the safety, efficacy, and potential interactions of each. According to an analysis in 2010 by Consumer Reports, the independent organization Natural Medicines Comprehensive Database listed over 54,000 supplements.4 Of these, 12% were associated with safety or quality concerns.

Even more concerning is that many supplements simply lack information on safety and effectiveness. In the same analysis, about two-thirds of the listed substances lacked any information on safety and efficacy as supported by scientific evidence.4 This underscores the challenges facing physicians when advising patients, especially as they seek definitive recommendations on whether certain supplements are safe and effective for their skin concerns. Physicians must emphasize that our answers are only as good as the evidence that is available. Given the limited research on many supplements, recommendations must often be limited as well.

In this article, we review an evidence-based approach to the evaluation of dermatology supplements. It is important to evaluate each supplement from the standpoint of PPIES: purity, potency, interactions, efficacy, and safety (Table 1). It is also important, when recommending supplementation, to suggest specific brands, as a large variation in quality has been demonstrated. Finally, consumers must be cautioned that supplements have to be used carefully and only when recommended, due to the potential for side effects and drug interactions.

PPIES – Purity, Potency, Interactions, Efficacy, and Safety

Purity –

Multiple reports have described adulteration of supplements, as well as contamination with microbes and heavy metals. In one FDA report, out of the supplements surveyed, 776 were identified as adulterated with prescription medications.9-11

Potency –

Potency involves two main issues: 1) accurate dosing, which includes consistency in dosage from bottle to bottle and ensuring that the dose stated on the label is accurate and 2) the correct dosage for the intended purpose.12 In one study of melatonin supplements, 71% of bottles examined misreported the correct dosage, with some containing over four times the dose represented on the label.23

Interactions –

Many supplements may interact with foods, medications, and other supplements. However, this information is not required on the label. In a literature review of interactions between medications and herbs and dietary supplements, over 1400 unique interactions with over 200 herbs and supplements were identified.13

Efficacy –

Determining efficacy of supplements is very complex. Since manufacturers are not required to prove efficacy, there is limited evidence regarding the efficacy of supplements. For supplements such as biotin, research has only demonstrated efficacy for a narrow indication or in a narrow population.14

Safety –

Even when safety studies are done, they may focus solely on short-term safety. There is a notable lack of research on the long-term safety of supplements. In one large study of beta-carotene supplements, researchers found that while male smokers tolerated these supplements well in the short-term, over a median interval of 6.1 years they exhibited an increased risk of lung cancer.3

Table 1: PPIES: An approach to supplements.

Definition

The category of dietary supplements is extremely large. From a regulatory standpoint, the FDA recognizes dietary supplements as foods.5 From a practical standpoint, this category includes such varied substances as vitamins, minerals, and herbs. It also includes plant or food extracts, such as beta-carotene supplements or fish oil capsules. It also includes live microorganisms, as in probiotics. It may include hormones, such as melatonin. It may include protein powders, enzymes, or glandular extracts. It also includes combinations of all of the above.

Many different formulations and delivery vehicles may be utilized. These include tablets, capsules, liquids, powders, softgels, timed-release tablets, chewables, gummies, and others.

Regulation of Manufacturing and Marketing

Despite their remarkable popularity, there is a notable lack of oversight and scientific rigor in the manufacturing and marketing of supplements. Much of that is due to the regulatory framework around dietary supplements.

There is a stark difference in the laws governing pharmaceutical medications versus those governing supplements. In the case of pharmaceuticals, manufacturers must provide evidence of both safety and efficacy to the FDA before approval for sale. In the case of supplements, it is almost the polar opposite.

In 1994, the Dietary Supplement Health and Education Act (DSHEA) was passed.6 The DSHEA legally recognized dietary supplements as foods, as opposed to drugs. This distinction has multiple ramifications. To begin with, supplement manufacturers do not need to confirm safety, efficacy, or quality before selling to the public. Supplements which include a combination of multiple ingredients do not need to demonstrate a lack of interactions between ingredients.

While manufacturers are expected to utilize current good manufacturing practices, no confirmatory pre-market testing is required. In fact, the FDA is only able to inspect a small fraction of manufacturing facilities, and reports reveal frequent noncompliance. As information received under the Freedom of Information Act revealed, the FDA inspected only 583 dietary supplement manufacturing facilities in 2016, with 61.5% of inspected facilities in the US receiving citations of noncompliance.7 Consumer Lab, an independent testing organization, has reported multiple quality issues with supplements. Their results indicate that overall about 1 in 5 supplements are considered poor quality, with herbal products even higher at 39%. Documented issues range from poor quality ingredients to little or no ingredient, to inadequate disintegration of pills.8

Evaluating Individual Supplements

The evaluation of a specific supplement requires several distinct considerations. The first relates to the primary active ingredient, such as vitamin D. It is also important to consider the particular supplement formulation, which encompasses the delivery vehicle (e.g., capsule, tablet, gummy), inactive ingredients, and any other active ingredients (e.g., multivitamin, combination supplement). Finally, the specific brand must be evaluated.

With every supplement, we recommend the PPIES approach. It is important to evaluate each specific supplement for its purity, potency, interactions, efficacy, and safety.

Purity is a major concern, as multiple reports have described contamination with microbes or heavy metals, as well as adulteration with prescription medications.9-11 In terms of potency, concerns include variability of doses from bottle to bottle, as well as doses that are either much higher or lower than stated on the label.12 Another concern is determining a safe and effective dose. In terms of interactions, many supplements have the potential to interact with foods, drugs, or other supplements, and such information is not required on the label.13 Issues of efficacy are very complex. Manufacturers do not need to prove efficacy, and therefore research studies evaluating supplements are limited. When present, some define efficacy for only a narrow indication in a narrow population,14 while others have methodological limitations.15 Finally, safety is a major concern. Consumers often mistakenly assume that “natural” supplements are entirely safe, despite evidence of harm from such natural substances as vitamin A, iron, beta-carotene, vitamin B6, and many others.16-18

Table 2 provides a brief summary of these important issues that patients must take into account when considering supplement use.

Advice to Patients

    • Treat every supplement with the same level of caution that you would use with a pharmaceutical medication. Just like FDA-approved drugs, many supplements have the potential for side effects and interactions.
    • Supplements are not “FDA-approved”, because the FDA does not require proof of safety, effectiveness, or quality prior to sale.
    • Do you want to know about a supplement’s safety or effectiveness? Then you need to ask questions and review the evidence. When it comes to pharmaceuticals, the FDA and its panel of experts have asked these questions for you. When it comes to supplements, it is up to the manufacturer to ask these questions. Unfortunately, many have not.
    • When it comes to asking questions, think PPIES. Look for information on purity, potency, interactions, effectiveness, and safety.
    • Evaluate all ingredients in the supplements. Evaluate specific brands also, because there may be large differences in quality.
    • While independent laboratory verification can attest to a branded supplement’s purity and potency, such “seals of approval” do not provide any information on overall efficacy, potential for interactions, or safety.

Table 2: Summary of key points for patients to consider.

Purity

Purity of supplements is an important consideration, as reported issues have ranged from microbial contamination to adulteration.

Contamination with both microbes and heavy metals is a concern. Bacterial contamination has been demonstrated in both liquid19 and herbal supplements9. Bacterial contamination has also been described in “whole foods” or “greens” powders and pills, such as those made from wheat grass or leafy vegetables,20 while contamination with pathogenic fungi was documented in children’s probiotics.21

In terms of heavy metals, one-fifth of Ayurvedic medicines purchased via the internet (both US-manufactured and Indian-manufactured) contained detectable lead, mercury, or arsenic.10

Adulteration with other ingredients is a concern as well. Over the span of 9 years, the FDA identified 776 adulterated supplements. Most were in the categories of weight loss, sexual enhancement, and muscle building, and the most common adulterants included sildenafil, sibutramine, and synthetic steroids.11

Potency

In terms of potency, two main issues exist. The first is ensuring that the supplement contains the dose specified on the label, and that doses are consistent in all packages. The second concern is determining the correct dose, in terms of efficacy and safety, for a particular medical indication.

Ensuring accuracy and consistency of dosing is a major consideration, as many reports have documented serious errors. In one case, a patient consumed more than 1,000 times the labeled dose of vitamin D, due to serious manufacturing and labeling errors in a US-manufactured supplement.22 In a case series, a multivitamin contained as much as 200 times the intended dose of selenium, leading to an FDA warning describing patients with “significant hair loss, muscle cramps, diarrhea, joint pain, and fatigue.”12 In another study, 71% of melatonin supplement bottles misreported the actual amount. Some contained over four times the amount of melatonin represented on the label.23

Another issue is that of the correct dose for the patient. With micronutrient supplementation, more is not necessarily better. Rather, the “right” dose is better. It is well known that many micronutrients must be maintained within a defined therapeutic window. Iron supplements, for example, can lead to iron overload even at low doses, if taken for a long period of time.16 Even the dosing of “natural” antioxidants (AOs) can be a concern, as in male smokers who exhibited higher rates of lung cancer after beta-carotene supplementation.17

The research regarding AOs is particularly instructive on the difficulties inherent in supplement research. This research initially appeared very promising, as multiple animal and laboratory studies found that AO supplements reduced carcinogenesis. In human studies, populations with a higher intake of AO-rich fruits and vegetables demonstrated lower rates of certain cancers.24

However, human studies of high dose AO supplements (as opposed to dietary intake of AOs) have shown that these do not help and in fact may even promote carcinogenesis in some cases.25 One possible explanation is centered on “the Goldilocks principle”. In other words, AO intake should be maintained within an ideal range, not too low but also not too high. This is due to the fact that the process of oxidation and anti-oxidation is a finely balanced process, and at high doses some AOs may exhibit pro-oxidant effects.25

Physicians, therefore, should advocate an individualized approach to keep levels within an optimal range. This approach includes a consideration of dietary sources and may include laboratory testing. For many nutrients, baseline status is an important consideration, and evaluation may be recommended prior to supplementation. For example, vitamin D supplementation in patients with AD and low serum vitamin D levels may be helpful, but has not consistently shown efficacy in those with baseline normal levels.26 It has also been noted that patients consuming adequate dietary selenium may easily exceed the recommended upper limits of intake if also supplementing with selenium.12 This is of concern as selenium is a frequent component of “hair loss supplements”.27

Interactions

It is well documented that supplements may interact with medications, foods, and other supplements. As described in one review of herb-drug interactions, concurrent use may “mimic, magnify, or oppose the effect of drugs.”13 Therefore, all patients considering supplements require a thorough medication review, including all prescription and over-the-counter medications as well as all supplements.

In a literature review of documented interactions between medications and herbs/dietary supplements, the authors identified a total of over 1,400 unique pairs of interactions involving over 200 herbs and supplements. The greatest number of documented interactions involved magnesium, calcium, iron, St. John’s wort, and Ginkgo biloba.28 Particular caution must be exercised in patients on medications that impact bleeding time or in those who have a history of cardiac conduction issues. For example, saw palmetto, found in some hair loss supplements, has been reported to increase bleeding time.29 In one study evaluating supplement use among older adults, it was found that many patients are at risk for such interactions: 63% of subjects used dietary supplements, and approximately 15% were considered at risk for a potentially major drug-drug interaction between prescription medications, over-the-counter medications, and supplements.30 Examples included increased risk of bleeding with warfarin and omega-3 fish oils or garlic.

Another potential interaction is with lab testing. Biotin has been found to interfere with a number of lab tests, including troponin (used in the diagnosis of myocardial infarction) and tests for thyroid function.31

Efficacy

Efficacy can be extremely challenging to determine when it comes to dietary supplements. It is important to emphasize to patients that our recommendations are only as strong as the evidence available. In the case of supplements, some have little to no published scientific research. While others have been the subject of scientific research, many of these studies have important limitations, ranging from poor methodology to a lack of generalizability.

To begin with, supplements that have worked in animal or laboratory studies may not work in human populations, as in the case of multiple randomized placebo controlled trials of high-dose AOs showing no efficacy in the prevention of NMSC.25

Even when human studies are available, there are multiple considerations. For all research studies, it is critical to consider the source and quality of the evidence. For some supplements, human research studies have been conducted, but run the risk of bias, as in collagen supplement studies that have no placebo15 or that are sponsored by the manufacturer.32 Even publication in a peer-reviewed medical journal does not equate to high quality evidence. For example, one supplement containing “green coffee bean extract” became very popular for weight loss, with results from a “randomized, double blind, placebo controlled study” published in a peer-reviewed journal.33 However, later investigations highlighted major concerns: the study included only 16 subjects, and all data was collected in India and then sent to a US researcher paid by the manufacturer to write the article.34 Two years later, the article was retracted as “the sponsors of the study cannot assure the validity of the data.”35

In the case of supplements such as biotin, efficacy has only been shown in research performed for a narrow indication (brittle nails)14 or in a narrow population (those with hair loss and inherited or acquired biotin deficiencies).36 Unfortunately, success in limited areas is often mistakenly assumed to indicate efficacy in other situations. Despite a lack of evidence for other indications, many “beauty” supplements contain biotin and advertise its use for “skin, hair, and nails”.

In a related issue, manufacturers often rely on “deficiency-state” outcomes to support supplementation in normal populations, without evidence. For example, hair loss supplements often contain ingredients such as vitamin A. While those deficient in vitamin A may experience hair loss, there is no evidence that it is useful in individuals with normal levels. In fact, high levels of vitamin A can actually trigger hair loss.27

Finally, little research has compared the efficacy of supplementation to dietary change. While it may be tempting to reach for a capsule, beneficial dietary changes typically have many benefits beyond a single micronutrient. Research to date has simply not demonstrated that, outside of deficiency states, supplements are consistently better than dietary change.

Safety

Since warning labels are not legally required on most supplements, the consumer must beware. Even when of high-quality and delivered in appropriate doses, many “natural” supplements have well-known and documented side effects, ranging from allergic reactions to gastrointestinal upset to sedation and more.

While some research studies have evaluated short-term safety, many lack information on long-term safety. This is a concern, as even supplements exhibiting few side effects in short-term studies can result in long-term damage. One of the best examples is that of beta-carotene supplements. Although these were tolerated well in the short-term, male smokers who took these supplements for a median interval of 6.1 years had an increased risk of lung cancer.37 In another example, the long-term use of high-dose vitamin B6 and B12 supplements, at doses commonly used in individual supplements, was associated with an increased lung cancer risk in men,18 with smokers who took high-dose B6 supplements over 10 years demonstrating a three-fold increased risk.

It is also important to consider the patient population. Little research has been done to ensure safety in pregnant or breastfeeding women. One well-known example is the risk of birth defects following ingestion of high-dose vitamin A. Similar concerns would arise in children, the elderly, and those with impaired liver or renal function.

Another major concern is the proliferation of multi-ingredient supplements. If considering such a supplement, it is important to ask what studies have been done to ensure that these ingredients may be safely combined.

Resources

In terms of purity and potency, the use of third-party independent investigative laboratories provide the most straightforward evidence. If these seals are found on the bottle, then an independent laboratory has affirmed the accuracy of the label. The supplement contains the ingredients specified, at the doses listed. Such seals also affirm that the product is not contaminated with microbes or heavy metals.

Independent labs providing these verifications include Consumer Lab, US Pharmacopeia, NSF International (National Sanitation Foundation), and UL (Underwriters Laboratories).53

Unfortunately, when evaluating interactions, efficacy, and safety, there is no such “seal of approval”. Every supplement must be approached on an individual basis. Considerations include the active ingredient, the formulation, all inactive ingredients, and the specific brand. It is also important to consider the dose, the patient population for whom it is under consideration, and the medical indication.

For more information on interactions, one subscription service that provides a large, searchable database is the Natural Medicines Comprehensive Database (www.NaturalDatabase.com).54 The subscription service ConsumerLab.com is another useful resource. This website publishes comparisons of different brands, with information on purity, potency, and cost. The service also provides reviews of the scientific research behind specific supplements.

Table of dermatology supplements
Table 3: A selection of dermatology supplements for which further research may be indicated, with important considerations.
AD = atopic dermatitis; AE = adverse event; AO = antioxidant; MI = myocardial infarction; NMSC = non-melanoma skin cancer; RCT = randomized controlled trial; RDBPC = randomized, double-blind, placebo-controlled
Click here to enlarge table.

Conclusion

Despite the increasing popularity of skin, hair, and nail supplements, many consumers are unaware of the potential concerns associated with their use. As manufacturers do not need to provide any evidence of safety, efficacy, or even quality prior to sale, it is imperative that consumers approach all supplements with caution. An evidence-based approach to the use of an individual supplement should include research on PPIES: purity, potency, interactions, efficacy, and safety.

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