The Science behind Revivogen One of our users takes a look at the science behind Revivogen.

Random Reflections on Revivogen
Author: Bryan Shelton
Email: bryan@airmail.net

There's been a fair amount of interest in Revivogen lately. I share this interest, and I'm posting this article to express my own personal views and opinions about it. Any comments or contrary opinions are certainly welcome!

The folks at Revivogen are saying that the most important part of this product is the novel use of fatty acids (gamma Linolenic acid, alpha Linolenic acid, Linoleic acid, and a few others) which are supposed to be potent inhibitors of 5AR. They base this on studies done in the 1990's by Liang and Liao; you can see these studies here in the HairlossTalk Resource Library under the "DHT Inhibition" section. But reading these studies almost immediately raised a red flag in my mind: there was no mention made of whether or not these fatty acids inhibit the all-important 5AR type 2, or just type 1 (or *both*, for that matter). I rolled my eyes and wondered if this was going to turn out to be another "azelaic acid" type thing, where the evidence is non-specific and shows inhibition of 5AR, but doesn't break it down into type 1 vs. type 2 (this is a good topic for another post). I resolved to retrieve the full articles and find out what they had to say.

Well, I went two-for-three: I got the first and third articles here on HairlossTalk.com, but the medical library didn't have the more obscure second one, which was published in the Journal of the Formosan Medical Association. However, I made up for this by finding a paper by a completely different group, writing on the same subject: "Inhibition of Steroid 5alpha- Reductase Activity by Aliphatic Fatty Acids", Niederprum, Schweikert, Thuroff, and Zanker, Annals of the New York Academy of Sciences 1995 September 30; 768:227-30. This study is also in HairlossTalk's Resource Library under the "DHT Inhibition" section. To make a long story a little shorter: these studies *do* establish that these fatty acids (or at the very least, gamma- Linolenic acid) inhibit *both* types of 5AR equally well.


DHT Inhibition in Revivogen

How well do they inhibit them? Let's look at "Growth Suppression of Hamster Flank Organs by Topical Application of Gamma-Linolenic and Other Fatty Acid Inhibitors of 5alpha-Reductase" by Liang and Liao. (Also in the Resource Library). Hamster flank organs have long been used to test the effects of both androgens and antiandrogens; these organs and obviously their sebaceous glands and the hair growing over them, are all very androgen- sensitive. Liang and Liao found in one test that 1 mg of gamma-Linolenic acid (I'll call it GLA from now on) applied topically to these organs once a day reduced their testosterone-stimulated growth by about 50%. In another similar test, the figure was about 66%. Still another test using 2-4 mg a day of GLA produced 60% to 70% inhibition. Please keep in mind that these are NOT the percentage reductions in DHT, but the percentage reductions in an actual measured androgen-sensitive biological effect! There were also suppression effects in the growth of sebaceous glands and hair (keep in mind that this is *body* hair, so this is the expected effect), although they didn't supply numerical data for these parameters.

So how does this compare to other topical antiandrogens? I found two studies that tested the effects of Spironolactone, potassium canrenoate (the main metabolite of Spironolactone), and the powerful Cyproterone acetate, all applied topically on these same hamster flank organs; plus, another study that tested *injected* Spironolactone. The first found about a 30% reduction in the testosterone-stimulated increase in flank organ size, about a 27% reduction in sebaceous gland size, and a modest 13% reduction in the diameter of hairs, all from 0.4 mg/day of topical Spiro. The second found a 39.3% flank organ reduction with 0.3 mg/day of topical Spiro., 29.5% from 3 mg/day of topical Spiro., and about an average of 35% from 0.3 mg/day of topical Cyproterone acetate. Sebaceous gland reductions were about 33% for both doses of Spiro., and a more modest 20% for the Cyproterone acetate. The third study found 40% and 51% reductions in sebaceous gland cross-sectional area by daily *injections* of 0.5 mg and 2.0 mg, respectively. The results of these similarly-conducted studies, all performed on hamster flank organs, seem to show a superiority of GLA over the established antiandrogens Spironolactone and Cyproterone acetate. 1 mg GLA produced flank organ reductions of somewhere between 50% and 66%, while the drugs produced a remarkably consistent average of about 35%. Equally important, there seemed to be no more extra response from increasing doses of Spironolactone!

I'm impressed by these numbers. A beneficial dietary fatty acid turns out to be more effective at inhibiting certain androgen-dependent biological effects than a couple of powerful synthetic drugs, at least in this animal model! I have no reason not to believe that this would translate over similarly for those of us who use topical Spironolactone for hair-loss. Attempting to translate from hamsters to humans: if 1 mg is sufficient for part of the back area of a hamster, I'm guessing that, oh, 10 mg for my baldspot and another 10 mg along my front hairline (for preventive maintenance) should be sufficient. This would be 1/2 ml of a 2% GLA alcohol solution in the back, and another 1/2 ml in front. I suspect that this might well be able to take over the antiandrogen duty of our regimens.


Revivogen in combination with Spironolactone

One newsgroup user raised an interesting and appropriate question: isn't Spironolactone more cost-effective than Revivogen? For every bottle of Revivogen that you buy, can't you buy a few bottles of ready-made Spiro. solution, or at least make your own? Yes, but remember that in these experiments there appeared to be a limit of effectiveness of Spiro. It seemed not to do any better above a certain dosage, and this level of effectiveness was lower than what was obtained with the GLA. If this is also true for human use for balding, then the use of Revivogen *might* be indicated for people who can't get the required level of antiandrogenicity through the usual means. However, to be fair to Spiro., there might be a reason for its relatively poor showing in these tests: all of these substances were given to the animals once a day. Spiro. is rather rapidly converted into its metabolite, canrenone, a *much* weaker antiandrogen. What if flank organs and sebaceous glands (and hair follicles) require a more continuous exposure to antiandrogens to get the desired effect? What if a fatty acid hangs around a lot longer, but Spiro. is metabolized and dissipated more quickly, requiring *twice* a day application? Would that mean that topical Spiro. at the proper dosage and used the proper way, could still be as effective as GLA? I frankly don't know the answer to that question, but I have to admit that it's a possibility. I don't have the data to say, either way.

But this leads me now to what I consider to be the *ideal* way to use Revivogen: use it along with topical Spironolactone! Disregarding the saw palmetto content of Revivogen for the moment, consider that GLA and the other fatty acids have no effect on the androgen receptors of hair follicles. Conversely, Spironolactone has no effect on 5AR; it does not block it at all. Think of the one-two punch you could have by combining *both* substances, and stopping or reducing activity on *both* sides of the 5AR enzyme! I feel that this combination is even more likely to serve successfully as a topical substitute for finasteride (Propecia), for those of us who are looking for such an alternative.

I'll have more Revivogen comments a bit later.

Bryan