Cutaneous Side Effects of Sports Supplements

Many patients walking into the dermatology outpatient departments (OPDs) nowadays take nutritional supplements. The use of supplements, though not universally advocated, is not generally considered harmful if taken in the correct doses. The casual use of agents that were previously advocated as nutritional or pharmacological ergogenic aids for athletes, among the general population, is a cause of concern for the dermatologist. Massive marketing, promotion by gym instructors, and unrestricted availability of products touted as “safe, healthy and natural,” have led to a spurt in the use of such “sports supplements” among gym enthusiasts and amateur athletes.

Methods

A search was performed on PubMed in January 2023 with the following terms: ergogenic aids, sports supplements, performance-enhancing drugs, whey protein, testosterone boosters, branched-chain amino acids (BCAAs), anabolic steroids “and” cutaneous “or” skin adverse events. From the results obtained, articles written in the last 15 years were included.

Incidence

The prevalence of the use of supplements among adults in various questionnaire-based studies ranged from 35.6% to 76.6%.[1,2] Objectives behind the intake of supplements were healthy lifestyle, muscle building, volitional weight loss, and increased exercise endurance. Aestheticism has also been linked to increased dietary supplement use.[3] We have observed many of our young patients taking supplements not to increase their endurance but rather to gain a buffed appearance or for weight loss. A correlation between supplement use, exercise addiction, appearance anxiety, poor self-esteem, and severe obsessive–compulsive behaviors (body dysmorphic disorder, muscle dysmorphia) has been observed in a cross-sectional study.[4]

Myriad of agents with unproven claims are now available in the market. Various available agents with claimed muscle-building properties include whey proteins and plant-based proteins, BCAAs (leucine, isoleucine, and valine), creatine, beta-alanine, beta-hydroxy beta-methylbutyrate, L-carnitine, glutamine, and conjugated linoleic acid. Agents that claim to boost testosterone include saw palmetto, ashwagandha, fenugreek, D-aspartic acid, and Tribulus terrestris (Indian name: gokhru). Caffeine, nitric oxide, chromium, selenium, and arginine claim to increase exercise capacity. Hormonal supplements, such as anabolic androgenic steroids, dehydroepiandrosterone sulfate (DHEAS), human growth hormones, and insulin-like growth factor-1 (IGF-1), are also freely available.[5]

Although epidemiology is not studied, certain dermatological conditions, such as nodulocystic acne and androgenetic alopecia, clinically serve as markers of inappropriate use of supplements.

Protein Supplementation

One of the most commonly used supplements in our patients is whey protein. Concentrated whey supplements commonly have the same whey content as 6 to 12 liters of milk per serving.[6] Severe and extensive new-onset acne or flare of existing acne[7] [Figure 1], seborrhea, androgenetic alopecia, and hirsutism are known to be associated with whey protein supplementation. “Bulging biceps, spotty skin and hairless heads” seem to be markers of a patient on whey protein for a long time.

Figure 1.

Bulging biceps with spotty skin (acne) in a gym enthusiast on whey protein supplements

Anabolic hormone response, that is, increased levels of growth hormone, insulin, IGF, and testosterone, which is responsible for muscle building, are also implicated in the pathogenesis of linked dermatological conditions [Figure 2].[8]

Figure 2.

Biochemical pathways of cutaneous response to whey and BCAA supplements. BCAA: branched chain amino acid; GIP: glucose-dependent insulinotropic polypeptide; GH: growth hormone; ACTH: adrenocorticotropic hormone; IGF-1: insulin-like growth factor-1; DHEA: dehydroepiandrosterone; 5αR: 5-alpha-reductase; DHT: dihydrotestosterone; MC5R: melanocortin 5 receptor; PI3K: phoshoinositide-3-kinase; mTOR: mammalian target of rapamycin; FOXO1: forkhead box protein O1; S6K1: S6 kinase 1; SREBP1: sterol regulatory element-binding transcription factor 1; AR: androgen receptor; PPARγ: peroxisome proliferator-activated receptor gamma; LXRα: liver X receptor alpha; TLR: toll-like receptor

Acne itself is now considered an early marker of insulin resistance, obesity, and metabolic syndrome. High doses of BCAAs, that is, leucine, isoleucine, and valine, have potentially negative effect on glucose metabolism, higher risk of developing type 2 diabetes,[9] and hence, cutaneous signs of insulin resistance, such as acanthosis nigricans and acrochordons, may be attributable to them. High IGF-1 levels have been linked to an increased risk of cancer.[10]

High whey protein intake has been shown to increase lipid hydroperoxides and advanced oxidation protein products, known as liver oxidative stress markers in rats.[11] High oxidative stress markers could be extrapolated to acceleration of cutaneous aging. Furthermore, multiple reports of elevation of hepatic enzymes on whey protein consumption should alert the practitioner about concurrent use of hepatotoxic drugs, such as isotretinoin and tetracyclines, for the management of acne.

Testosterone, DHEAS, and Anabolic Steroids Supplements

Unfortunately, banned anabolic steroids may be present in certain dietary supplements taken with the intention of muscle building. In a study conducted in the United States of 776 dietary supplements from the US Food and Drug Administration Tainted Supplements database, it was found that 89.1% of “muscle building supplements” were adulterated with steroid-like ingredients or synthetic steroids.[12] Testosterone boosters and oral DHEAS are freely available over the counter.

Cutaneous adverse events due to testosterone abuse include severe nodulocystic acne, acne conglobata, acne fulminans, and pyogenic granulomas. Seborrhea, epidermoid cysts, and sebaceous cysts occur due to sebaceous gland overactivity; recurrent furunculosis and folliculitis, and superficial mycotic infections, such as dermatophytosis and tinea versicolor, are also associated. Striae distensae, extensive keloids, hirsutism and female pattern hair loss (FPHL) in females, gynecomastia and androgenetic alopecia in males, gingival hypertrophy, and icterus due to hepatic enzyme elevation are other known adverse effects.

Rarer events include reports of precipitation of unstable psoriasis, unmasking of latent hereditary coproporphyria, and sudden eruption of new lesions in a patient with familial angiolipomas.[13]

Miscellaneous ingredients along with their potential adverse events, cutaneous and systemic, are described in Table 1.

Table 1.

Commonly available “supplements” and their adverse events

Supplement	Reported adverse events
Beta-alanine, suprapharmacological doses	Paresthesias in the form of itching/tingling sensation
Creatine	Precipitation of renal disease, bipolar disorder, weight gain
Caffeine	Delayed wound healing and epithelization
Selenium	Increased all-cause mortality,[14] linked with type 2 diabetes mellitus, dyslipidemia, and increased risk of cutaneous melanoma[15]
Growth hormone	Coarsening and leathery appearance of the skin, gynecomastia, pedal edema, hypertension, carpal tunnel syndrome, diabetes, and neuropathy
Thyroid hormone	Hyperpigmentation, non-scarring alopecia, nail changes
Spirulina platensis, Aphanizomenon flos-aqua, Chlorella, Echinacea, and alfalfa	Onset and/or flare of autoimmune cutaneous diseases, including dermatomyositis, pemphigus/pemphigoid, and lupus erythematosus[16]
Vitamin E >1200 mg/d	Diarrhea, weakness, blurred vision, and gonadal dysfunction
Vitamin A >100 times the RDA	Skin desquamation, “retinoid dermatitis,” alopecia, cheilitis
Carotene >30mg/day	Yellowish-orange discoloration of the skin
Pyridoxine >500mg/day	Photosensitivity, neurotoxicity, chronic sensory polyneuropathy
Methylcobalamin	Monomorphic acneiform eruptions, allergic and anaphylactic reactions, erythematous, and pruritic injection site reactions after intramuscular injections
Glutathione	Flatulence, nausea, pruritus, maculopapular rash, Stevens–Johnson syndrome/toxic epidermal necrolysis
Collagen	Gastrointestinal disturbance; potential risk of hypersensitivity, hypercalcemia, arrhythmia, and prion transmission[17]

“Designer drugs” are versions of illegal molecules modified to avoid detection in tests while mimicking their functional effect. Designer anabolic androgenic steroids remain easily available for purchase in over-the-counter bodybuilding supplements, and these products appear to be increasingly popular, despite the known health risks associated with their use.[18] The study conducted by Tucker et al. in 2018 identified unapproved pharmaceutical ingredients in 776 dietary supplements; in most cases (757 of 776 [97.6%]), these ingredients were not declared on the label.[12] Dietary supplement use was associated with 23,000 emergency department visits and 2000 hospitalizations in the United States each year (2004–2013).[19]

Supplements may also interact with other drugs. A literature review has documented over 1,400 unique interactions with greater than 200 herbs and supplements.[20] Bacterial and fungal contamination, and presence of heavy metals, such as lead, arsenic, and mercury, as a result of poor manufacturing protocols have also been reported.[21] Excipients added to nutritional supplements are known to cause urticaria, fixed drug eruptions, and anaphylaxis.

Pharmacokinetics of ergogenic aids in children and teenagers is poorly understood. Young adults and adolescents are generally susceptible to fall for marketing and promotional activities. Peer pressure and appearance anxiety among this age-group make them more likely to use irrational supplements. Hormonal alterations during puberty, sudden growth spurts, and altered pharmacodynamics may render higher risk of adverse events. Also, the “gateway hypothesis” invokes the concern of supplement use progressing to anabolic steroids or other illicit substance misuse. “Stacking” is the combining of multiple supplements in a workout regimen.

There is a lack of randomized, double-blinded, placebo-controlled studies; hence, the benefits are unproven, and long-term safety is unknown. There have been cases of renal failure, hepatic failure, and psychotic episodes resulting from certain supplements;[22] yet, these supplements remain on the market.

Judicious use of ergogenic aids should be advocated with increased involvement of healthcare professionals in decision-making. Improved and stricter regulations, inclusion of package inserts detailing adverse event profile, post-marketing surveillance programs, and public awareness and education are need of the hour. Dermatologists are in a unique position to identify inappropriate use of supplements based on cutaneous manifestations and must educate patients and encourage informed decision.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.