SULT1A1: Can This Gene Predict Hair Regrowth From Minoxidil? | The Evidence

Article Summary

Can your genes predict minoxidil effectiveness? The SULT1A1 gene, which encodes sulfotransferase, might hold the key, at least according to gene testing companies. SULT1a1 codes for an enzyme that activates minoxidil, a common hair loss treatment. While some studies suggest certain SULT1A1 variants might predict treatment response from minoxidil, these studies suffer from small sample sizes and publication in low or no-impact factor journals. In this article, we dive into the science behind SULT1A1 in the context of hair loss treatment responsiveness and provide an overview of whether gene variations could mean someone is a “responder” or “non-responder”.

Full Article

SULT1A1 is a gene that encodes for sulfotransferase, an enzyme that catalyzes various reactions throughout the body. Regarding hair loss, sulfotransferase is crucial for activating minoxidil, which requires sulfonation to exert its effects.

Some studies suggest that measuring sulfotransferase levels may be possible to predict whether minoxidil will be effective. Others have claimed that the expression of a specific variant of the SULT1A1 gene can indicate whether the drug is likely to work.

This article will explore how relevant SULT1A1 is to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What is SULT1A1?

The SULT1A1 gene codes for an enzyme called sulfotransferase 1A1 (SULTS). The SULT family of enzymes catalyzes the transfer of a sulfonate (SO3-) group from the universal donor  3’-phosphoadenosine 5’-phosphosulfate (PAPS) to an acceptor molecule. This reaction is known as sulfation or sulfurylation.^[1]Negishi, M., Pederson, L.G., Petrochenko, E., Shevtsov, S., Gorokhov, A., Kakuta, Y., Pederson, L.C. (2001). Structure and function of sulfotransferases. Archives of biochemistry and biophysics. … Continue reading

These reactions play a crucial role in the metabolism and detoxification of various compounds, including hormones, neurotransmitters, and drugs (including minoxidil which we will get to), increasing their water solubility and facilitating their elimination.^[2]Gamage, N., Barnett, A., Hempel, N., Duggleby, R.G., Windmill, K.F., Martin, J.L., McManus, M.E. (2006). Human Sulfotransferases and Their Role in Chemical Metabolism. Toxicological Sciences. 90(1). … Continue reading 

The SULT1 family in humans consists of at least nine members, including SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, and SULT1E1. Genetic variations in SULT1A1 can influence enzyme activity and have been associated with differences in drug response, toxicity, and disease susceptibility.^[3]National Library of Medicine. (2024). SULT1A1 sulfotransferase family 1A member 1 [Homo sapiens (human)]. NIH. Available at: … Continue reading 

Some studies have found different variants of the SULT1A1 gene, which are associated with different activity levels. The GG variant was associated with high activity, whereas GA and AA variants were associated with low activity.^[4]Ramos, P.M., Gohad, P., McCoy, J., Wambier, C., Goren, A. (2021). Minoxidil Sulfotransferase Enzyme (SULT1A1) Genetic Variants Predicts Response to Oral Minoxidil Treatment for Female Pattern Hair … Continue reading 

So, we know what SULT1A1 is and about the enzyme it codes for. But how relevant is it to hair loss outcomes?

What is the Evidence For Targeting SULT1A1 for Hair Loss?

One crucial piece of evidence for targeting SULT1A1 for hair loss is the link between sulfotransferase and minoxidil. SULT1A1 codes for the sulfotransferase enzyme that catalyzes the conversion of minoxidil (a prodrug that needs activation to exert its effect) to minoxidil sulfate (the activated form of the drug). As such, some studies have evaluated the correlation between minoxidil efficacy and sulfotransferase activity. 

One study was conducted with 34 patients who had been treated with minoxidil alone for a minimum of 6 months.^[5]Goren, A., Castano, J.A., McCoy, J., Bermudez, F., Lotti, T. (2014). Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia. Dermatologic Therapy. 27. 171-173. … Continue reading These patients were evaluated as “responders” or “non-responders” based on global photographic assessment. Hairs in the growing (anagen phase) were plucked from the border between bald and non-bald scalp areas and evaluated for sulfotransferase activity. Each patient’s sulfotransferase activity was measured and compared to their “responder” or “non-responder” status. The researchers found that most “responders” had a higher sulfotransferase activity, whereas most “non-responders” had a lower sulfotransferase activity.

Another study of the same group also measured sulfotransferase activity in 21 women with female pattern hair loss who had been treated with 5% minoxidil for a minimum of 6 months.^[7]Roberts, J., Desai, N., McCoy, J., Goren, A. (2014). Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia. … Continue reading Fifteen “responders” and 6 “non-responders” were identified, with only two not correctly identified after the assay. 

Why Do Some People Have Lower SULT1A1 Activity Levels Than Others?

Well, the SULT1A1*2 variant of the SULT1A is associated with low enzyme activity and thermal stability of SULT1A1.^[8]Raftogianis, R.B., Wood, T.C., Otterness, D.M., Loon, J.A.V., Weinshilboum, R.M. (1997). Phenol Sulfotransferase Pharmacogenetics in Humans: Association of Common SULT1A1 Alleles with TS PST … Continue reading Therefore, it can be reasonably inferred that those with lower sulfotransferase activity might have this gene variant and, therefore, be less responsive to minoxidil.

SULT1A1 Gene Variants & Minoxidil: Clinical Studies

There are two studies that explore different gene variants of SULT1A1 and their effect on minoxidil efficacy. 

In the first study, 17 males and 18 females with androgenic alopecia were included.^[9]Raghad, N.A., Al-Gazally, M.E., Ewahd, W.A. (2017). Assessment the effect of different genotypes of sulfotransferase 1A1 gene on the response to minoxidil in patients with androgenic alopecia. … Continue reading The participants had been using topical minoxidil for at least 3 months before being assessed for response and allocated into “responder” and “non-responder” groups. The participants were then genotyped to determine what allele variant was present in the SULT1A1 gene and compared.

84% of participants who carried the G allele of the SULT1A1 gene were in the “responder” group, compared to only 16% of those with the A allele. 

Furthermore, of those carrying the GG variant, 68.8% were “responders” compared to 15.8% who were “non-responders”. Conversely, 84.2% of “non-responders” had the GA genotype compared to 31.2% of “responders”. 

Interestingly, a higher proportion of “responders” were female (25.7%), indicating a potential for women to respond better to minoxidil (possibly due to more women having the GG allele variation) – however, this would need to be confirmed in further studies.

A further study was conducted in 2020 in which 10 participants with female pattern hair loss were treated with 1 mg oral minoxidil daily for six months.^[13]Ramos, P.M., Gohad, P., McCoy, J., Wambier, C., Goren, A. (2021). Minoxidil Sulfotransferase Enzyme (SULT1A1) genetic variants predict response to oral minoxidil treatment for female pattern hair … Continue reading Hairs were counted within a 2.2 cm2 area, with a minimum 13% increase in hair count considered as a “responder”. Genotyping was conducted alongside this. Participants with the GG allele variant showed a 13.3% average increase in hair count, while participants with the GA allele variant showed a 6.9% average increase.

The researchers concluded that this gene variant can predict response to oral minoxidil treatment, but we see some issues. There are clearly some are some exceptions to the rule (which you can see below).

One person with the GA allele variant showed a 21.8% increase in hair which is a larger increase than nearly all of the GG allele variants! Furthermore, three of the GG variants did not reach the minimum 13% increase in hair count to actually be labeled a “responder”.

To confirm whether the variants actually affect response rates to minoxidil treatment, larger-scale studies are needed.

Can I Get Better Results with Oral Minoxidil?

On the internet, some individuals have mentioned that if you have a variant of SULT1A1, that means you’re less likely to respond to topical minoxidil, then you should take low-dose oral minoxidil. This is because the liver has abundant sulfotransferase activity which can also convert oral minoxidil to its active form. This active form could then circulate through the bloodstream to the scalp and exert its effects that way.

But is this true?

Well, it is true that the liver has high sulfotransferase activity. This suggests that individuals with low sulfotransferase activity in their hair follicles (due to SULT1A1 gene variants) might still benefit from oral minoxidil. However, as you can see above, studies have shown mixed results regarding the efficacy of oral minoxidil in “non-responders”.

Would Switching From Topical to Oral Help?

Switching to oral minoxidil may help some who don’t respond to topical minoxidil. One study by Ramos et al. found that in their study population of female patients, oral minoxidil slightly outperformed topical minoxidil in improving hair density and reducing shedding over 24 weeks.^[15]Ramos, P.M., Sinclair, R.D., Kasprzak, M., Miot, H.A. (2020). Minoxidil 1 mg oral versus minoxidil 5% topical solution for the treatment of female-pattern hair loss: a randomized clinical … Continue reading

Another study, however, found that although topical minoxidil had a better overall effect than 1 mg oral minoxidil, there was no significant difference between the two groups, indicating that switching might actually just lead to the same response.^[16]Asilian, A., Farmani, A., Saber, M. (2023). Clinical efficacy and safety of low-dose oral minoxidil versus topical solution in the improvement of androgenetic alopecia: a randomized controlled … Continue reading

Will Switching Make a Difference?

Not necessarily. It looks like the effectiveness of oral minoxidil can still be influenced by the same genetic factors that affect topical minoxidil response. Additionally, oral minoxidil carried potential safety risks, as it is not FDA-approved for hair loss and may have systemic side effects that need to be carefully managed.

In recent years, genetic testing companies have sprung up that claim to analyze your genotype to help you choose a personalized hair loss treatment. However, concerns remain about the accuracy of their recommendations, privacy issues regarding genetic data, and the potential for overpromising results without comprehensive clinical validation.

These companies often include the SULT1A1 gene as a predictor of responsiveness to minoxidil. So, we collated all of the potential SULT1A1 gene variants that might be relevant to hair loss and recommendations, depending on your genotype.

SULT1A1 genetic variants play a significant role in predicting the effectiveness of minoxidil for hair loss treatment. While the enzyme’s activity in hair follicles can indicate responsiveness to topical minoxidil, switching to oral minoxidil may offer limited additional benefits due to similar genetic influences on enzyme activity. Enhancing sulfotransferase activity through methods like tretinoin application and microneedling has shown promise in improving treatment outcomes for non-responders.

What Do Your Genetic Results Mean?

There are a number of variants that your genetic testing results might tell you that you have. You can see the possible variants that might come up within your own gene testing and reference these tables once you get your results to find out what they mean. 

Your Result	SULT1A1-1 Variant 1	SULT1A1-1 Variant 2	SULT1A1-1 Variant 3
	rs9282861 GG genotype	rs9282861 GA genotype	rs9282861 AA genotype
What it Means	High sulfotransferase activity	Moderate sulfotransferase activity	Low sulfotransferase activity
The Implication	May respond well to topical minoxidil. Recommend treatment.	May respond normally to topical minoxidil.	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.
Your Result	SULT1A1-2 Variant 1	SULT1A1-2 Variant 2	SULT1A1-2 Variant 3
	rs1042028 GG genotype	rs1042028 GA genotype	rs1042028 AA genotype
What it Means	High sulfotransferase activity	Moderate sulfotransferase activity	Low sulfotransferase activity and low thermal stability
The Implication	May respond well to topical minoxidil. Recommend treatment.	May respond normally to topical minoxidil.	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.
Your Result	SULT1A1-3 Variant 1	SULT1A1-3 Variant 2	SULT1A1-3 Variant 3
	rs1042157 TT genotype	rs1042157 CT genotype	rs1042157 CC genotype
What it Means	Low sulfotransferase activity. You may want to try oral minoxidil or an alternative treatment.	Moderate sulfotransferase activity	High sulfotransferase activity
The Implication	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.	May respond normally to topical minoxidil.	May respond well to topical minoxidil. Recommend treatment.
Your Result	SULT1A1-4 Variant 1	SULT1A1-3 Variant 2	SULT1A1-4 Variant 3
	rs6839 GG genotype	rs6839 AG genotype	rs6839 AA genotype
What it Means	Low sulfotransferase activity	Moderate sulfotransferase activity	High sulfotransferase activity
The Implication	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.	May respond normally to topical minoxidil.	May respond well to topical minoxidil. Recommend treatment.

Table 1: Different potential allele variants of the SULT1A1 gene and the implication in terms of hair treatments.

What Relevance Does SULT1A1 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. 

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

Yes. Some studies have shown that people with variations in the SULT1A1 gene may respond differentially to minoxidil. (score = 1)

• Does the totality of evidence implicate SULT1A1 as a causal agent for hair loss? (1 point)

There is no evidence to suggest that SULT1A1 variations cause hair loss (score = 0)

• Does the totality of evidence implicate SULT1A1 as a predictive factor for hair loss treatment responsiveness? (2 points)

Yes. There are a number of studies implicating SULT1A1 as a predictive factor for minoxidil responsiveness. (score =2)

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

No. One paper was published in a journal with a low/no impact factor. The sample sizes were small, and the results where genotyping was actually conducted were variable. (score= 0)

Total Score = 3

How Can I Improve My Sulfotransferase Activity?

So, you have tried minoxidil, but the regrowth hasn’t been as impactful as you hoped, and you find out that this is because your sulfotransferase levels are low. How can you boost it? Well, studies show that combining retinoic acid or tretinoin with minoxidil can increase sulfotransferase activity.

The topical application of tretinoin increases the expression and activity of follicular sulfotransferase enzymes. One study was conducted on 20 participants (10 males and 10 females) with androgenic alopecia.^[17]Sharma, A., Goren, A., Dhurat, R., Agrawal, S., Sinclair, R., Trueb, R., Vano-Galvan, S., Chen, G., Tan, Y., Kovacevic, M., Situm, M., McCoy, J. (2019). Tretinoin enhances minoxidil response in … Continue reading

The participants’ hair follicles were analyzed using the Minoxidil Response Test and determined as “responders” or “non-responders” to minoxidil treatment. The participants then underwent 5 days of treatment with 0.1% topical tretinoin. The average sulfotransferase activity for the whole cohort did not significantly improve after the five days, however, when the cohort was separated into “responders” and “non-responders”, something interesting happened. Those predicted to be “non-responders” to topical minoxidil did show a significant increase in sulfotransferase activity, with a total of 43% of “non-responders” converted to “responders” after five days of application.

Another way to improve sulfotransferase levels and, therefore, minoxidil efficacy is by undergoing microneedling. One study by Sharma et al. investigated the effect of microneedling on follicular sulfotransferase enzymes in male subjects with androgenic alopecia.^[19]Sharma, A., Surve, R., Dhurat, R., Sinclair, R., Tan, Y., Zou, Y., Muller Ramos, R., Wambier, C., Verner, I., Kovacevic, M., Goren, A. (2020). Microneedling improves minoxidil response in … Continue reading Six male subjects underwent 3 weekly sessions of microneedling at 1.5 mm depth on a target area of the scalp. Sulfotransferase enzyme activity was analyzed in the hair follicle at the baseline and at the end of the three weeks. 66% of participants had an increase in sulfotransferase activity compared to the baseline, and 16% of subjects who were previously classified as “non-responders” to topical minoxidil were converted to “responder” status.

Final Thoughts

While some small studies suggest that testing for SULT1A1 variants might help to predict minoxidil efficacy, the evidence is not yet strong enough to make definitive treatment recommendations based solely on genotype. Larger and more robust studies are needed to confirm the true predictive value of genetic testing for SULT1A1 for personalizing hair loss treatments.