Response to: “Rethinking biotin therapy for hair, nail, and skin disorders”

To the Editor: We applaud Dr Lipner for her relevant critique and commentary in her recent article, "Rethinking biotin therapy for hair, nail, and skin disorders," regarding the popularized use and promotion of biotin for improvement in hair and nails by media and physicians alike despite a lack of evidence to support routine use.1Lipner S.R. Rethinking biotin therapy for hair, nail, and skin disorders.J Am Acad Dermatol. 2018; 78: 1236-1238Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar We also recognize the trends of increasing consumer purchasing of biotin and physician recommendation of its use as alarming considering the warnings from the US Food and Drug Administration, as up to 20% of Americans consume some form of biotin, which may not be disclosed to physicians.1Lipner S.R. Rethinking biotin therapy for hair, nail, and skin disorders.J Am Acad Dermatol. 2018; 78: 1236-1238Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 2Samarasinghe S. Meah F. Singh V. et al.Biotin interference with routine clinical immunoassays: understand the causes and mitigate the risks.Endocr Pract. 2017; 23: 989-998Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 3Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and Its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academies Press (US), Washington DC1998Google Scholar Although we agree that biotin supplementation should be recommended with caution or avoided altogether when limited evidence suggests benefit for hair, in select dermatologic conditions biotin may be beneficial and further evidence would be immensely valuable.4Walth C, Wessman LL, Wipf A, Bertin AC, Hordinsky MK, Farah RS (2018). Literature-based evaluation of biotin use for alopecia. Poster presented at: 2018 American Hair Research Summit. May 14-16, 2018; Orlando, FL.Google Scholar In our response to the author, we attempt to amplify the influence of her article by highlighting the fact that although there are hair conditions reported in the literature that may respond favorably with biotin, the majority of publications are case reports and there remains a definite lack of controlled, randomized studies to support routine use of biotin. Furthermore, the nonspecific language of several of the case reports renders them difficult to interpret and more information is needed. It is also our intent to emphasize that, to our knowledge, in multiple databases no published studies exist to suggest that biotin should be used for healthy, typical hair growth and distribution. We further aim to underscore the fact that future studies regarding biotin use both in healthy hair and with hair pathology are necessary. As part of a comprehensive literature review in May 2018, we compiled and presented evidence for use of biotin in hair disease.4Walth C, Wessman LL, Wipf A, Bertin AC, Hordinsky MK, Farah RS (2018). Literature-based evaluation of biotin use for alopecia. Poster presented at: 2018 American Hair Research Summit. May 14-16, 2018; Orlando, FL.Google Scholar Articles published after 1979 were obtained via the PubMed database (Table I).4Walth C, Wessman LL, Wipf A, Bertin AC, Hordinsky MK, Farah RS (2018). Literature-based evaluation of biotin use for alopecia. Poster presented at: 2018 American Hair Research Summit. May 14-16, 2018; Orlando, FL.Google Scholar Of the 30 articles, 28 were case reports or case series with patients ranging in age from 2 months to 54 years. The overwhelming majority involved infants and children. Many diagnoses were nonspecific, listed as hair loss or alopecia. Follow-up ranged from weeks to 2 years and improvement in hair conditions (alopecia, telogen effluvium, uncombable hair syndrome, etc) was reported in 30 cases. However, it is difficult to determine whether conditions would have resolved with time regardless of supplementation. Biotin dosing in the trials ranged from 2.5 to 20 mg/d.Table ILiterature review on efficacy of biotin in hair disease and alopeciaSourceTime periodPopulationClinical indicationDoseResultsCase report Thoene J, Baker H, Yoshino M, et al. N Engl J Med. 1981;14:817-820.1 y2-y-old female, multiple carboxylase deficiencyAlopecia universalis10 mg/dComplete regrowth Charles BM, Hosking G, Green A, et al. Lancet. 1979;2:118-120.18 d10-mo-old male, possible defect in absorption of biotinDermatitis and alopecia5 mg bidHair regrowth Sweetman L, Surh L, Baker H, et al. Pediatrics. 1981;68:553-558.1.5 y of observation11-y-old male, dietary deficiency of biotin and multiple carboxylase deficiencyAlopecia totalis1 mg/dNoticeable regrowth of hair within 1 mo Coulter DL, Beals TF, Allen RJ. Develop Med Child Neurol. 1982;24:634-644.n/a11-mo-old female, multiple carboxylase deficiencyHair loss10 mg/dComplete regrowth of hair Coulter DL, Beals TF, Allen RJ. Develop Med Child Neurol. 1982;24:634-644.n/a14-mo-old male, biotin absorption deficiencyTrichorrhexis nodosa10 mg bidRegrowth and increased hair strength McClain CJ, Baker H, Onstad GR. JAMA. 1982;247:3116-3117.3 mo36-y-old male with Crohn's disease receiving total parenteral nutrition, possible biotin deficiencyAlopecia with loss of hair color60 μg/dRegrowth of hair Innis SM, Allardyce DB. Am J Clin Nutr. 1983;37:185-187.6 mo2 adults receiving parenteral nutrition, possible biotin deficiencyHair loss60 - 100 μg/dHalted hair loss at 1 wk; regrowth of healthy hair at 2 mo Khalidi N, Wesley JR, Thoene JG, et al. JPEN J Parenter Enteral Nutr .1984;8:311-314.7 wk54-y-old female receiving total parenteral nutrition, biotin deficiencyComplete hair loss10 mg/d for 3 wk, then 5 mg/d IV for 4 wkNew hair growth observed Mock DM, Baswell DL, Baker H, et al. J Pediatr. 1985;106:762-769.n/a3 pediatric patients receiving total parenteral nutrition, 1 with serum-confirmed biotin deficiencyAlopecia100 μg/dImproved dramatically Shelley WB, Shelley ED. J Am Acad Dermatol. 1985;13:97-102.4 mo18-mo-oldUncombable hair syndrome0.3 mg tidDecreased hair loss, fragility, and pluckability Campana G, Valentini G, Legnaioli MI, et al. Ophthalmic Paediatr Genet. 1987;8:125-129.1 y7-y-old male, multiple carboxylase deficiencySevere alopecia10 mg/dComplete regrowth of hair; noticeably thickened hair Colamaria V, Burlina AB, Gaburro D, et al. Epilepsia. 1989;30:573-578.n/aInfant, low serum biotinidase activitySparse hair on scalp5 mg bidDramatic symptom improvement, unclear if this included changes in sparse hair McVoy JRS, Levy HL, Lawler M, et al. J Pediatr. 1990;116:78-83.2 mo6-mo-old maleOccipital hair loss10 mg/dHair growth markedly thicker Higuchi R, Noda E, Koyama Y, et al. Acta Paediatr. 1996;85:872-874.2 mo11-mo-old male, low serum biotinAlopecia of scalp/eyebrows1 mg/dComplete hair regrowth on scalp and eyebrows Ananth N, Praveen Kumar GS. Indian J Clin Biochem. 2003;18:23-26.6 mo3-mo-old male, biotinidase deficiencyAlopecia10 mg/dComplete resolution of hair loss Hou J. Chang Gung Med J. 2004; 27:129-133.2 y2-y-old female, multiple carboxylase deficiencySparse hair, eyelashes, and eyebrows10 mg/dSymptoms normalized, unclear if includes sparse hair, eyelashes, and eyebrows Fujimoto W, Inaoki M, Fukui T, et al. J Dermatol. 2005;32:256-261.1 mo5-mo-old male, low serum biotinDiffuse alopecia on back of head1 mg/dRegrowth of scalp hair Boccaletti V, Zendri E, Giordano G, et al. Pediatr Dermatol. 2007;24:E14-16.2 y2-y-old maleUncombable hair syndrome5 mg/dNormal combability; thicker hair Dahiphale R, Jain S, Agrawal M. Indian Pediatr. 2008;45:77-779.6 mo3-mo-old male, low biotinidase activityAlopecia10 mg/dMarked improvement after only days, hair regrowth Komur M, Okuyaz C, Ezgu F, et al. Eur J Paediatr Neurol. 2011;15:551-553.6 mo3-y-old female, biotinidase deficiencyHair loss10 mg bidComplete hair regrowth Munnich A, Saudubray JM, Cotisson A, et al. Eur J Pediatr. 1981;137:203-206.12 mo2 pediatric patients, low plasma biotinTotal alopecia10 mg/dImproved Rajendiran A, Sampath S. BMJ Case Rep. 2011; doi:10.1136/bcr.07.2011.4494.8 mo2-mo-old male, biotinidase deficiencyAlopecia of scalp/eyebrows, lack of hair pigmentation10 mg bidComplete regrowth of normally pigmented hair on scalp and eyebrows Mukhopadhyay D, Das MK, Dhar S, et al. Indian J Dermatol. 2014;59:502-504.6 wk3-y-old male, low serum biotinidase level/multiple carboxylase deficiencyDiffuse alopecia30 mg/dFull head of noticeably thickened hair Grootens KP, Hartong EGTM. J Clin Psychiatry 2017;78:e838.3 moMiddle-aged female receiving valproic acidTelogen effluvium10 mg/dNormalized Benke PJ, Duchowny M, McKnight D. Pediatr Neurol. 2018;79:61-64.n/a10-y-old female with autismVery poor hair and nail growth25 mg/dHair and nails began to growCase series/review Forbes GM, Forbes A. Nutrition. 1997;13:941-944.n/aPatients receiving parenteral nutritionHair lossIV n/aSymptom resolution Karimzadeh P, Ahmadabadi F, Jafari N, et al. Iran J Child Neurol. 2013;7:47-52.3-6 mo8 patients (1.5-52 mo), biotinidase deficiencyAlopecia; hair hypopigmentation5-20 mg/dComplete resolution of symptoms Gannavarapu S, Prasad C, DiRaimo J, et al. Mol Genet Metab 2015;116:146-151.n/a5-y-old female, partial biotinidase deficiencyAlopecia10 mg/dSymptom resolution Desai S, Ganesan K, Hegde A. Pediatr Radiol. 2008;38: 848-856.4 mo4 patients with biotinidase deficiencySparse hair on scalpn/aPossible improvementTrial Schulpis KH, Karikas GA, Tjamouranis J, et al. Epilepsia. 2001;42:1359-1362.n/aChildren (9 patients with biotinidase deficiency) receiving valproic acidHair loss10 mg/dUnclear number with improvement Castro-Gago M, Perez-Gay L, Gomez-Lado C, et al. J Child Neurol 2011;26:1522-1524.3 mo3 children receiving valproic acidAlopecia due to valproic acid10 mg/dResolution of symptoms with biotinBiotin is the only therapy mentioned in all of the studies except in the following: Benke et al (2018), which mentions acetazolamide; Innis and Allardyce (1983) and Forbes and Forbes (1997), which mention a multivitamin added to parenteral nutrition; and Schulpis et al (2001), Castro-Gago et al (2011), and Grootens (2017), which mention patients receiving biotin in response to valproic acid therapy.bid, Twice a day; IV, intravenously; tid, 3 times a day. Open table in a new tab Biotin is the only therapy mentioned in all of the studies except in the following: Benke et al (2018), which mentions acetazolamide; Innis and Allardyce (1983) and Forbes and Forbes (1997), which mention a multivitamin added to parenteral nutrition; and Schulpis et al (2001), Castro-Gago et al (2011), and Grootens (2017), which mention patients receiving biotin in response to valproic acid therapy. bid, Twice a day; IV, intravenously; tid, 3 times a day. In select hair diseases biotin may be useful. Additional large-scale, double-blinded, randomized clinical trials are necessary to define optimal patient demographics, dosing schedules, and side effect monitoring. Biotin has not been shown to be beneficial for normal, healthy hair or in individuals with no biotin deficiency. In addition, a distorted view of biotin as a wonder drug for hair growth prevails in modern culture, notwithstanding the very real hazards of interfering in clinical testing and diagnosis, as cautioned by Dr Lipner.1Lipner S.R. Rethinking biotin therapy for hair, nail, and skin disorders.J Am Acad Dermatol. 2018; 78: 1236-1238Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Therefore, our conclusion supports that of Dr Lipner: there is little to no reason to believe that biotin supplementation should be recommended for individuals with healthy hair and its use should be limited to select, evidence-based clinical situations after careful consideration and discussion with patients of the risks and benefits of its use. Rethinking biotin therapy for hair, nail, and skin disordersJournal of the American Academy of DermatologyVol. 78Issue 6PreviewBiotin (vitamin B7 or H) is an essential cofactor for mammalian carboxylase enzymes that are involved in important metabolic pathways in humans.1-3 It is acquired from food sources, including egg yolks, milk, nuts, grains, supplementation, and synthesis by intestinal bacteria. The importance of biotin was first observed when rats without biotin in their diets developed neuromuscular dysfunction, alopecia, and dermatitis.4 Biotin deficiency is quite uncommon in humans, and results in similar findings to that seen in rats. Full-Text PDF Reply to: "Response to 'Rethinking biotin therapy for hair, nail, and skin disorders'"Journal of the American Academy of DermatologyVol. 79Issue 6PreviewTo the Editor: I thank Walth et al1 for their interest in my commentary,2 in which I reviewed data supporting the conclusion that biotin treatment for dermatologic conditions is either unfounded or largely based on case reports or small case series. I also highlighted a recent US Food and Drug Administration warning based on reports of biotin consumption interfering with laboratory tests. Full-Text PDF