Why is Minoxidil Sulfate a Bad Idea?
Very often I receive questions asking why I do not recommend minoxidil sulfate in a hair regrowth product. Perhaps they've read somewhere minoxidil sulfate works better than minoxidil.
Here I explain why I do not recommend minoxidil sulfate. The structure of real minoxidil sulfate is shown in the Figure below. It is the active metabolite that stimulates hair follicles. Minoxidil applied to the scalp is automatically converted into minoxidil sulfate by sulfotransferase in the scalp (see article 1 below). Yeah, you got it. First of all, it is not necessary because minoxidil will be converted to minoxidil sulfate by the enzymes in your body. Not only is it unnecessary to use minoxidil sulfate, but it is also impractical to include minoxidil sulfate into a solution, because minoxidil sulfate is unstable. It is hydrolyzed back into minoxidil in a few days (See article 2).
Furthermore, the price of minoxidil sulfate is so prohibitively expensive that nobody can afford to add minoxidil sulfate to hair regrowth solutions. I am not aware of any supplier with a large enough stock of minoxidil sulfate with which to make a hair regrowth product. There are some suppliers that offer only in milligrams quantity. The price is about 100 US dollars per 5 milligrams. In a 60 ml hair growth solution with12% minoxidil sulfate, it has 7.2grams of minoxidil sulfate, which will cost more than 100,000 US dollars to procure the minoxidil sulfate for one bottle (one month supply). Clearly no one would put that much minoxidil sulfate in the solution. So what happens? The answer is that the manufacturers of hair growth products who they say they have minoxidil sulfate in their products, either never check the raw material they procure, or they just want to fool customers.
Let me show you what I mean. I bought some minoxidil sulfate a few years back for research purpose. The price was surprisingly lower than minoxidil. It was hard to believe the price was so low given that the synthesis of the minoxidil sulfate is a lot more complicated than minoxidil. Therefore I decided to send the sample to a chemical lab to test the material. The results showed the material had two molecules in it: (1) minoxidil and (2) sulfuric acid, shown as in main image of this blog. To make the "minoxidil sulfate" in the main image of this blog is quite easy. You can get it by simply mixing minoxidil with sulfuric acid. But the product is not real minoxidil sulfate. It is simply a mixture of minoxidil and sulfuric acid. These two molecules are not covalently bonded together. This is different from the real minoxidil sulfate, in which minoxidil is covalently bonded with sulfuric acid to make one single molecule.
Someone people asked me if the "Minoxidil sulfate" they bought online is real or not. They believe it is real because it dissolves in water so it cannot be minoxidil (minoxidil is not water soluble). It is true that minoxidil itself is not very soluble in water, but that changes when sulfuric acid is present. Minoxidil is a weak base, it will be protonated when an acid is presented and it become a positively charged ion and very soluble in water. That is the exact reason why the fake minoxidil sulfate is very soluble in water because it has both minoxidil and the acid sulfuric acid.
Using the fake "minoxidil sulfate" shown in the main image in a hair growth product will only make the product less effective than minoxidil. Why? First of all, there is less minoxidil in the product. Let's say you add 5 grams of the "minoxidil sulfate" to your product, you actually only have 3.2 grams of minoxidil in it. In addition, sulfuric acid is a strong acid, which will protonize minoxidil and make it positively charged. It is well known that skin absorbs lipid or non-charged molecules much more effectively than charged molecules. That means, the presence of sulfuric acid in the product made of "minoxidil sulfate" as shown in Figure 2 will only slow down the absorption.
In summary, a product with minoxidil sulfate does not work any better than minoxidil. If there is any difference, it probably will work less effectively than minoxidil. Minoxidil sulfate is purely a marketing gimmick.
An important step in understanding minoxidil's mechanism of action on hair follicles was to determine the drug's active form. We used organ-cultured vibrissa follicles to test whether it is minoxidil or its sulfated metabolite, minoxidil sulfate, that stimulates hair growth. Follicles from neonatal mice were cultured with or without drugs and effects were assessed by measuring incorporation of radiolabeled cysteine in hair shafts of the treated follicles. Assays of minoxidil sulfotransferase activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate. Inhibiting the formation of intracellular PAPS with chlorate also blocked the action of minoxidil but not of minoxidil sulfate. Acetaminophen, a potent sulfate scavenger blocked cysteine incorporation by minoxidil. It also blocked follicular stimulation by minoxidil sulfate apparently by directly removing the sulfate from the drug. Experiments with U-51,607, a potent minoxidil analog that also forms a sulfated metabolite, showed that its activity was inhibited by both chlorate and diethylcarbamazine. These studies show that sulfation is a critical step for hair-growth effects of minoxidil and that it is the sulfated metabolite that directly affects hair follicles.
The 100,000 g supernatant fraction of rat liver homogenate contains a sulfotransferase activity which catalyzes the sulfation of minoxidil. Synthetic minoxidil N-O sulfate and the enzyme synthesized product had identical chromatographic characteristics on high pressure liquid chromatography. Minoxidil sulfate, which yields minoxidil when treated with sulfatase, was slowly hydrolyzed in water. Several N-oxides of other heterocycles, including several other pyrimidines, triazines and imidazoles, were also substrates for this sulfotransferase.
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