Studies have shown that minoxidil sulfotransferase converts minoxidil into minoxidil sulfate, and the latter stimulates hair growth.(1,2) Furthermore, when animal studies analyzed hair growth in relation to minoxidil application, in the presence of drug inhibitors of sulfation or sulfotransferase, (acetaminophen which is a sulfate scavenger, and diethylcarbamazine, a deworming medication, which inhibits sulfotransferase), minoxidil sulfate was not created, and hair growth stimulation did not occur.(1)

The Essential Enzyme

The enzyme which catalyzes this reaction is essential to the process, and absence of the enzyme ensures that the active ingredient, minoxidil sulfate can not be formed. Scalp biopsies of patients on topical minoxidil, reveal those with low or no minoxidil sulfotransferase are non-responders to the medication.(1)

Therefore, if a patient's hair follicle tests negative for the presence of minoxidil sulfotransferase, a patient will know they will not respond to hair growth stimulation effects of topical minoxidil.

Aspects of the Sulfation Process

Without minoxidil sulfotransferase, you cannot form minoxidil sulfate, and you will not be a responder.  However, there are other aspects of the sulfation process with the potential to interfere with the ability to form minoxidil sulfate from minoxidil, even in the presence of adequate enzyme. 

To understand what these potential aspects or interference points are, realize that in addition to the minoxidil sulfotransferase enzyme, there are two other essential components of the sulfation process in humans in order for the conversion of minoxidil to minoxidil sulfate, to occur. 

• First of all, the substance 3’phosphoadenosine, 5’ phosphosulfate (PAPS), is synthesized within cells, provides the sulfonate group for sulfation to occur and is a required substrate for the sulfation reaction in humans. Because PAPS is synthesized in cells and not stored, the rate of synthesis determines the rate of sulfation and is a rate limiting variable in the ability to convert minoxidil to minoxidil sulfate. Formation of PAPS requires ATP and inorganic sulfate. ATP is made in the cells, while inorganic sulfate is supplied in the diet, in part from sulfur containing amino acids such as cysteine and methionine, which are products of protein consumption and metabolism. 
  
  Sulfate levels can also vary with certain physiologic states, for example sulfate levels are higher in fetuses and young children, and lower in female menopause—the latter presumably related to decreased kidney absorption. Decreased concentrations of inorganic sulfates have also been observed in certain disease states, such as patients with rheumatoid arthritis. Therefore, any physiologic condition which creates limitations of these substances could potentially impede the rate of synthesis of PAPS, and limit the sulfation reaction (3).
  
  As previously mentioned, the commonly used pain killer, acetaminophen (Tylenol), attracts and reduces available sulfate in the cells and was shown to inhibit the formation of minoxidil sulfate and associated hair growth in hair follicles.(1-3) Other substances including salicylamides and phenols can reduce the availability of sulfate, and have been shown to reduce the ability of the cells to convert minoxidil into minoxidil sulfate. Medications and supplements that require sulfation for activation/deactivation may also prove to reduce available sulfate for minoxidil activation, however, human clinical studies to document an interference of clinical response to minoxidil have not been performed.
  


• Cellular ATP may be in short supply in patients with certain medical conditions, such as lactic acidosis.  This condition may occur in diabetic ketoacidosis, as well as in liver or kidney disease. Some forms of medication, such as phenformin, an antidiabetic medication, as well as some anti-retroviral medications used to treat HIV, can cause this too. Additionally, heavy metals, such as arsenic or molybdenum interrupt ATP formation, as do pesticides such as the organophosphates.
  

As mentioned, there are no clinical studies to confirm the degree to which sulfate and ATP supplies may impact the conversion of minoxidil to minoxidil sulfate in humans, however, in vitro models indicate this can occur.

1. Minoxidil sulfate is the active metabolite that stimulates hair follicles.  Buhl, A.; Waldon, D.; Baker, C.; Garland, A.; Journal of Investigative Dermatology, November 1990, pp553-557
2. Enzymatic and non-enzymatic sulfation mechanisms in the biological actions of minoxidil, Meisheri, K.; Johnson, G;, Puddington, L.;  Biochemical Pharmacology, Vol 45, No 2, 1993, pp271-279
3. Sulfation and sulfotransferases 5: the importance of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the regulation of sulfation. Klaasen, C.D.; Boles, J.W.; FASEB, 1997, pp 404-418