BTD encodes the protein biotinidase, an enzyme crucial for biotin use throughout the human body. Biotin, or vitamin B7, is an essential nutrient that must be acquired from the diet. Biotin has been shown to have a range of biological functions, including a role in maintaining hair health. BTD polymorphisms can lead to a failure in biotin utilization, which can also cause hair loss conditions such as alopecia. Some companies have suggested that BTD can be used to predict hair loss treatment efficacy, citing studies investigating genetic variation in BTD. This article will explore how relevant BTD is to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What is BTD?

The BTD gene encodes the protein biotinidase, which plays a crucial role in the biotin cycle. Biotin, otherwise known as vitamin B7, cannot be synthesized by the human body, meaning it must be acquired via the diet. However, diet-acquired biotin is often bound to other proteins, forming larger compounds such as biocytin, which prevent the biotin from being used. Biotinidase functions by breaking down these larger compounds, freeing up the biotin so that it can be utilized by the body. After use, biotinidase also helps to recycle any biotin that remains in the body, ensuring that it can be used again.^[1]Leon‐Del‐Rio, A. (2019). Biotin in metabolism, gene expression, and human disease. Journal of Inherited Metabolic Disease, 42(4), 647-654. Available at: https://doi.org/10.1002/jimd.12073

Biotin has a great many roles throughout the body, including the regulation of metabolism, regulation of gene expression, and supporting normal immune function. ^[2]Leon‐Del‐Rio, A. (2019). Biotin in metabolism, gene expression, and human disease. Journal of Inherited Metabolic Disease, 42(4), 647-654. Available at: https://doi.org/10.1002/jimd.12073 Biotin is known to have roles in protein synthesis and, specifically, keratin production, which is a key component of the hair.^[3]Patel, D. P., Swink, S. M., & Castelo-Soccio, L. (2017). A review of the use of biotin for hair loss. Skin appendage disorders, 3(3), 166-169. Available at: https://doi.org/10.1159/000462981

Biotin metabolic pathways are also enriched in bacteria of the healthy scalp vs that which is producing dandruff, further suggesting a role for biotin in the maintenance of hair health.^[4]Saxena, R., Mittal, P., Clavaud, C., Dhakan, D.B., Hegde, P., Veeranagaiah, M.M., Saha, S., Souverain, L., Roy, N., Breton, L. and Misra, N. (2018). Comparison of healthy and dandruff scalp … Continue reading

Yet stronger evidence is presented by observing the symptoms of patients who are biotin deficient (they lack biotin) or biotin-dependent (their body requires an abnormally high amount of biotin to function normally). Affected individuals experience a range of symptoms, including hair abnormalities and the development of conditions such as alopecia.^[5]Bhattarai, D., Banday, A. Z., Sadanand, R., Arora, K., Kaur, G., Sharma, S., & Rawat, A. (2021). Hair microscopy: an easy adjunct to diagnosis of systemic diseases in children. Applied … Continue reading

Furthermore, one study was conducted with 541 women to determine how many women with self-perceived hair loss also had a biotin deficiency. It was found that 38% of these women had a biotin deficiency; however, it was also found that 11% of these women had health factors that greatly elevated their risk of developing a deficiency in the first place. One interesting finding, however, was that if a woman had hair loss, biotin deficiency, and seborrheic dermatitis, then biotin supplementation may help to improve hair loss outcomes (Figure 1).

What is the Evidence for Targeting BTD for Hair Loss?

Collectively, a significant amount of evidence suggests that biotin is important in maintaining hair health, but how does that link to BTD?

It is well-documented that biotinidase deficiency is a leading cause of biotin deficiency and dependency, leading to symptoms such as hair loss. Biotinidase deficiency is caused by mutations and polymorphisms in the BTD gene, which can partially or completely impair biotinidase activity. Clinically, BTD polymorphisms and biotinidase deficiency should be identified as early as possible, given the profound harm that it can cause to development and overall health. Biotinidase deficiency is typically detected early in life, either by newborn screening or due to the array of symptoms it causes. Still, some individuals may go into adult life undiagnosed.^[7]Zempleni, J., Hassan, Y. I., & Wijeratne, S. S. (2008). Biotin and biotinidase deficiency. Expert review of endocrinology & metabolism, 3(6), 715-724. Available at: … Continue reading

Fortunately, it is possible to prevent, slow, and even reverse the symptoms associated with biotinidase deficiency. Affected individuals are given oral biotin supplements, provided in the free-from (thus not requiring biotinidase), which they must continue to take for life. The supplement is extremely effective and, among other benefits, hair growth has been shown to return in children who suffered from alopecia due to their condition.^[8]Wolf, B. (2012). Biotinidase deficiency: “if you have to have an inherited metabolic disease, this is the one to have”. Genetics in Medicine, 14(6), 565-575. Available at: … Continue reading

Some companies have stated that the rs13078881 polymorphism in BTD can be used to predict the efficacy of treatment with biotin for hair loss. A study conducted on 19 children showed that the rs13078881 CG and CC genotype biotinidase deficiency.^[9]Swango, K. L., Demirkol, M., Hüner, G., Pronicka, E., Sykut-Cegielska, J., Schulze, A., & Wolf, B. (1998). Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase … Continue reading

This does serve as an indication that biotin supplementation could benefit people with this polymorphism. However, as the study was conducted in children, the results may not represent how the polymorphism affects adults. Supporting this point, a separate study found that adults with the rs13078881 polymorphism exhibited biotinidase deficiency, but they did not present with any symptoms.^[10]Wolf, B., Norrgard, K., Pomponio, R.J., Mock, D.M., Secor McVoy, J.R., Fleischhauer, K., Shapiro, S., Blitzer, M.G. and Hymes, J., 1997. Profound biotinidase deficiency in two asymptomatic adults. … Continue reading

The contrasting results presented by these studies suggest that the underlying mechanisms of biotinidase deficiency and how it causes the associated symptoms are yet to be truly understood. More importantly, in the context of this article, neither of the above studies mentions hair loss. Owing to these points, it is not possible to accurately determine how the rs13078881 polymorphism may influence hair loss treatments.

Consideration of the wider literature does lend itself to the conclusion that biotin supplementation may be beneficial for those with both hair loss and biotinidase deficiency. At the time of writing, there is a lack of evidence showing that biotin supplementation in healthy individuals with a hair loss disorder is beneficial.^[11]Patel, D. P., Swink, S. M., & Castelo-Soccio, L. (2017). A review of the use of biotin for hair loss. Skin appendage disorders, 3(3), 166-169. Available at: https://doi.org/10.1159/000462981

What Do Your Genetic Results Mean?

Your Result	BTD (rs13078881)
	Variant 1 – CC genotype	Variant 2 – CG genotype	Variant 3 – GG genotype
What it means	Associated with partial biotinidase deficiency	Associated with normal biotinidase levels – but are a carrier for the gene mutation	Associated with normal biotinidase levels
The Implication	May benefit from biotin supplementation	May not benefit from biotin supplementation	May not benefit from biotin supplementation

What Relevance Does BTD Have for Hair Loss Treatment?

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies. 

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

Yes. Studies have shown that biotinidase deficiency may lead to hair loss, and this gene polymorphism can lead to partial biotinidase deficiency. (score = 1)

• Does the totality of evidence implicate BTD as a causal agent for hair loss? (1 point)

While biotinidase deficiency may lead to hair loss, there is no evidence implicating this polymorphism in BTD in hair loss. (score = 0)

• Does the totality of evidence implicate BTD as a predictive factor for hair loss treatment responsiveness? (2 points)

No. There is no evidence to suggest that BTD polymorphisms will affect treatment responsiveness. (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

Since BTD fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

Individuals who have both biotinidase deficiency and hair loss may well benefit from biotin supplementation. However, while there is significant evidence that genetic variation in BTD is associated with hair loss, which may affect the efficacy of biotin supplementation, the evidence is insufficient to make definitive treatment recommendations based solely on genotype. Larger, more robust studies are required to better understand how biotin supplementation benefits hair loss in those with biotinidase deficiency and/or BTD polymorphisms and the healthy population.