Efficacy of 2.5 mg oral biotin versus 5% topical minoxidil in increasing nail growth rate

Abstract

The fingernail growth rate (NGR) is approximately 3 mm/month and varies according to sex, age, labour activities, systemic diseases, seasonality, dominant hand and trauma.1 The slow growth of nails may have functional and cosmetic impact, such as nail fragility and delayed renewal of the nail plate.2 Few studies have evaluated pharmacological interventions to increase NGR. Biotin has been found to increase the thickness of the nail plate;3 however, its action on the NGR has not yet been investigated. Although 5% topical minoxidil has been demonstrated to increase NGR,4 no comparative studies have been conducted with oral biotin or a combination of both drugs. We evaluated the efficacy of 5% topical minoxidil and 2.5 mg oral biotin in increasing the NGR of the fingernails in healthy adults for 28 days, and we correlated the NGR with gender, age and onychophagy. A quasi-experimental, open, controlled study with a factorial design was performed. Thirty-eight adults of both sexes aged between 25 and 45 years were recruited through non-systematic sampling. Pregnant women, active smokers, individuals with fingernail disorders (including fragile nails), users of drugs that may alter nail growth and those who were allergic to the treatments were not included. This study was approved by local IRB and registered in Brazilian Register of Clinical Trials (https://ensaiosclinicos.gov.br/rg/RBR-63hk5w). At inclusion (T-14), all participants had the nail plate on the second and fourth fingernails of both hands marked with a 40 × 1.2 mm needle in two proximal points (reference points), and a measurement of the distance between the reference points and the capillaries from proximal nail fold was taken. Measurements were taken using Heine Delta20 dermatoscope, and high-resolution photographs were captured using a Nikon D5200 camera. The second and fourth fingernails were chosen based on the smallest physiological variation in their growth.1 The measurements were taken proximally, where any fragility could not influence or generate nail breakage, which commonly occurs distally. In the first 14 days, the participants had no interventions. After this period (T0), subjects were enrolled in one of four groups: control (CTRL), minoxidil (MINOX), biotin (BIOT) or the combination of both drugs (MINOX+BIOT). Topical 5% minoxidil (PANT®) spray was applied twice daily, while 2.5 mg biotin capsules (UNTRAL®) were orally administered daily. Local formaldehyde substances and other topical or oral supplements were prohibited during the study. Measurements of the distance between the reference points and the capillaries from proximal nail fold were taken at T-14, T0, T14 and T28. The estimations of nail growth were obtained by subtracting the successive measures. The NGR was obtained as the arithmetic mean of the values calculated through digital image analysis, performed under ImageJ software. This assessment was carried out in millimetres per day. Age, gender, comorbidities, nail biting and the participants’ dominant hand were considered. The data obtained were analysed by a multilevel generalised linear mixed-effects model, and post hoc analysis was performed by sequential Šidák correction. Five hundred and ninety-two nail measurements were performed. No dropouts occurred, and no adverse events were reported. The main characteristics of the sample are displayed in Table S1 (extensive supplement). There were no dropouts nor adverse events. Basal growth (T0) was more pronounced in the dominant hands and among the subjects who reported nail biting (Table S2). NGR (Figure S3) was higher at T14 in all intervention groups when compared to the control group (p < 0.01), which was sustained at T28, but with no difference between T14 and T28 (p > 0.1). At T28, the MINOX group presented a 19% (CI 95%, 16 to 25%) increase in NGR versus 13% (CI 95%, 10 to 17%) in the BIOT group and 14% (CI 95%, 8 to 20%) in the MINOX + BIOT group. MINOX resulted in a higher NGR than BIOT at T28 (p < 0.01) but did not differ to MINOX + BIOT (p = 0.80). A posteriori sensitivity analysis revealed no influence for age (p = 0.75) and gender (p = 0.42) in NGR after the interventions. However, nail biting individuals presented a greater NGR (p < 0.01) at T28, among the participants which used MINOX or BIOTIN. In a previous study, topical 5% minoxidil during eight weeks promoted an increase in the NGR of fingernails, which was higher in the first month compared to the second month of treatment. In this same trial, the treated fingernails had an NGR of 4.27 mm/month, significantly higher than the 3.91 mm/month of untreated nails.4 The mechanism by which minoxidil promotes nail growth stimulation is not entirely clear. It is known that minoxidil could upregulate the expression of vascular endothelial growth factor in hair follicle dermal papillae, which may occur similarly in the nail apparatus and generate an increase of blood flow and supply.4 Conversely, some studies argue that the effect of minoxidil in NGR probably does not depend on vasodilation, but mitotic stimuli directly on the nail matrix cells by over-regulation of the CYR61 and DUSP1 genes.s1 Oral biotin has been reported to be successful in the treatment of brittle nails. The mechanism by which it increases the matrix mitotic rate is unclear, but studies in vitro showed that biotin stimulates epidermal cell differentiation and aids in maintaining epidermal cell growth, which may help to improve NGR. Furthermore, biotin plays a role in increasing the thickness of the nail plate.s2 In a study that evaluated patients with brittle nail syndrome, there was a 25% increase in nail thickness after oral 2.5 mg biotin over six months.s3 In this trial, minoxidil promoted a greater NGR increase when compared to its association with oral biotin. We hypothesise that the simultaneous increase in nail thickness affects the longitudinal nail growth due to a physiological limit to nail matrix production capacity, but this phenomenon should be explored through a specifically designed trial. Trials with biotin are required in order to clarify its significant effects on nail physiology and nail diseases, since the inadvertent use of biotin, stimulated by the pharmaceutical industry and social media, has increased, despite the lack of evidence to support this indication.s4 The main limitation of this study is related to the lack of a nail plate thickness assessment. In addition, subjects were healthy young adults, while most nail complaints come from the elderly, which has NGR decreased by the age.s5 In our sample, the basal NGR was not correlated with age, but we believe that it has occurred due to 90% of our participants aged between 23 and 39 years. Therefore, another studies involving older subjects should be conducted. The short follow-up of the treatments may also have limited the generalisation of the results. However, the predominance of a small range of age and exclusion of brittle nails of individuals increased the homogeneity of the sample and, therefore, the internal validity of the conclusions. Our results cannot be extrapolated to other age groups or comorbidities. However, they provide a perspective from which to study other doses, routes of administration, length of effect after drug suspension and the NGR plateau reached with each treatment. The modification of physiological aspects related to the nail apparatus with interventions that increase NGR may contribute to the treatment of nail diseases that can alter the NGR (such as onychomycosis),s6 recovery after nail surgery or the treatment of nail dystrophies. Topical minoxidil is a low-cost drug, with few adverse events reported, which may be a novel therapeutic strategy to increase the NGR in healthy patients. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Topics & Concepts