by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
As I enjoyed my Saturday night watching the Discovery channel and reading through my PDR, it occurred to me that an article on reductase inhibitors would be a good idea. (And here you guys thought scientists don’t have fun!) It seems like every guy I know is popping Saw palmetto or something else to prevent benign prostatic hyperplasia (BPH) while they try every Andro product on the market. Avoiding BPH is a good idea, but taking any old thing with those prohormones is not. Sure inhibiting 5-alpha-reductase and blocking the conversion of testosterone (T) to DHT (see Elevating Free testosterone) sounds like a good idea. The problem is that if you only block the production of DHT, you send more T into the loving arms of aromatase. This can lead to elevated estrogen levels. Now if you are taking prohormones, which also elevate estrogen levels, you wind up shutting your nuts down as fast as closing the lid on a bomb container.
Quick Review Course
After our testes produce T, it can go through a number of biochemical changes. Testosterone can be aromatized or converted into estradiol, converted into androstenedione, bind to receptors inside cells, get metabolized by the liver, and some of it we convert into DHT using the enzyme 5 alpha reductase (5AR). Part of the sales pitch that numerous supplement companies have claimed is that you need to take agents like Saw palmetto or Pygeum africanum in order to control DHT production and prevent problems with your prostate. I read through a ton of studies and in almost every single case the info in ads about using plant extracts to control DHT levels or prevent BPH was wrong. What follows is a laundry list of agents and what they can or cannot do.
A Trip through The Local Health Food Store
When I walk through a health food store, I always like to take a look at the newest products on the shelves. Normally, I head straight to the section of prosexual aids, not for me of course, but for a friend, really. I don’t pay much attention to the prostate-protection type of products because I don’t have any prostate problems. Lately, I have been bombarded with questions from guys showing me bottles of various herbal extracts. Some of this stuff was down right scary. I complied a little list of the various ingredients that I saw in these products. What you are about to read will certainly give you something to think about.
Artocarpus incisus
Some science-type guys, realizing that there really aren’t that many well known naturally occurring reductase inhibitors, decided to travel to New Guinea to test extracts from some trees [1]. It must be nice to have the kind of funding that allows you to travel so far just for ball protection. Personally, my research interests would take me to Hawaii or Jamaica and involve lots of beautiful women, something that I’m pretty sure that New Guinea doesn’t have. I mean, someone has to do this type of research. Anyway, they found that two isolated ingredients, namely chlorophorin and artocarpin, were effective at inhibiting the 5-alpha reductase enzyme from rats. This would be really great except that they didn’t test the tree extracts against other enzymes. We would just call this a lack of enzyme specificity data. You wouldn’t want to take this stuff and then find out it inhibits other enzymes, like those needed to make testosterone. The concentrations used appeared higher than what one might expect physiologically. There is also no data on these extracts and prostate cells. But hey, next time you take a trip to Papua New Guinea, be sure to stock up on some of the local heartwoods, because maybe down the road it will be useful. For now, let the natives try it first.
Azelaic acid
Azelaic acid is a naturally occurring dicarboxylic acid. It is fairly safe based on cell studies done so far. It functions as an anti-fungal agent as well as an anti-cancer agent. It inhibits mitochondrial and DNA enzymes in cancer cells, yet does not affect normal cells at similar dosages and times of exposure [2]. It can be administered topically, focally, orally, intravenously, intra-arterially, and intralymphatically, without side effects and is metabolized without producing harmful by-products. Its effectiveness can be increased by taking it with B6 and zinc [3]. The major problem I see so far is that human studies need to be done where they look at the effects on hormone levels and the prostate. Most of the work so far has focused on 5-alpha-reductase in skin and not prostate. These may be two different forms of the same enzyme. I can see this product being useful in a topical formula for treating acne and preventing hair-loss. This reminds me - I better go put some on my head!
Brosimum rubescens and Dalbergia cochinchinensis
The B. rubescens tree is found in Peru where the locals call it “palo de sangre,” or “palisangre,” or “palo negro.” It can also be found in Brazil where those guys call it “muirapiranga.” Now that you got your daily dose of culture and foreign language instruction, let’s get right to the important information, or as I like to call it in this case, “the nutcracker.” The active agents in these trees are called palodesangrens. Now some prostate protector products contain extracts of Brosimum rubescens, which are high in the active agents above. Using prostate tissue from rats, it was found that the palodesangrens bind to the DHT receptor, causing androgen dependent diseases [4]. Dalbergia cochinchinensis also contains active agents, which bind to DHT receptors & form complexes that result in androgen diseases [5]. Let’s think about this. Taking this product prevents androgens from binding to the androgen receptors. If you have prostate cancer, sure this may be an option to consider, but if you don’t have any prostate problems, stay far away from this stuff.
Cactus flower (Opuntia)
Cactus flower is used in foreign countries to counteract BPH. So far there isn’t any published information regarding its clinical effects in patients or on the mechanism of its biological activity. A fairly recent study evaluated the ability of cactus flower extracts to inhibit lipid peroxidation, androgen aromatization, and testosterone reduction [6]. These are the biochemical events that occur in BPH. So if you can reduce these events, maybe you can prevent the prostate from growing to the size of a grapefruit. The extracts inhibited aromatase and 5-alpha-reductase activity in cultured foreskin cells. They also inhibited the enzymes in blenderized human placenta and prostate. The findings were somewhat impressive and indicated that at least in cell cultures and tissue preparations, cactus flower extracts may be useful as a defense against BPH. Seems promising, but we need some human studies to validate it works in people.
Other Agents Found In Products With Limited Support Against 5AR
There are lots of naturally occurring agents that have been reported to inhibit 5AR in cells. Epilobium parviflorum contains the ellagitannins oenothein A and oenothein B [7]. A close cousin of E. parviflorum is E. angustifolium. Extracts from this plant administered to rats decrease sexual organ weight [8]. Impatiens balsamina L. contains the bisnaphthquione derivative named impatienol [9]. Phytoestrogens alter brain 5AR levels in rats [10]. A flower pollen extract inhibits prostate cell growth [11]. Pinocembrin isolated from Populus nigra had strong 5AR inhibitory activity [11]. Riboflavin [12], tea [13], and zinc [14] also inhibit 5AR. While it may seem appealing to try some of these agents, there is limited research on their ability to inhibit 5AR in people, so you might want to hold off until we know more about them.
Commercially Available Products
You have to be wondering at this point if anything works and has been tested in people. There are a number of products, mostly from Germany, that have been studied. The first is Harzol. This is a plant extract of Hypoxis rooperi. It doesn’t appear to bind to the androgen receptor or bind to 5AR [15]. It may have value as an antitumor agent. Tadenan is an extract of Pygeum africanum. While clinical trials indicate it is safe and effective in the treatment of BPH [16], it also decreases luteinizing hormone and testosterone in rats [17]. Prostagutt, Remigeron, Talso, and Strogen Forte are all extracts of Sabalis serrulatae. They not only inhibit 5AR, but they also inhibit 3BHSD (3-beta-hydroxy steroid dehydrogenase) and interfere with iron absorption [18]. Since 3BHSD is involved in making testosterone, you wouldn’t want to take this stuff unless you really needed to. Permixon is probably the most widely used and widely copied commercially available product. It is an extract of Saw palmetto (Serenoa repens). Various studies report beneficial results of Permixon on BPH symptoms [19]. Cell studies indicate that it can inhibit both isoforms of 5AR, the binding of androgens to the androgen receptor [20], and sperm motility [21].
My Take On All Of This
I haven’t found a naturally occurring DHT inhibitor that I would take all the time, so there isn’t anything I can recommend at this point. While some of the agents listed do have potential, there isn’t enough to warrant their use yet. If something comes up, I will be sure to let you know.
References:
1. Shimizu, K., et al., The 5 alpha-reductase inhibitory components from heartwood of Artocarpus incisus: structure-activity investigations. Planta Medica, 2000. 66(1): p. 16-9.
2. Breathnach, A.S., Azelaic acid: potential as a general antitumoural agent. Medical Hypotheses, 1999. 52(3): p. 221-6.
3. Stamatiadis, D., M.C. Bulteau-Portois, and I. Mowszowicz, Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. British Journal of Dermatology, 1988. 119(5): p. 627-32.
4. Shirota, O., et al., Antiandrogenic natural Diels—Alder-type adducts from Brosimum rubescens. Journal of Natural Products, 1997. 60(10): p. 997-1002.
5. Pathak, V., et al., Antiandrogenic phenolic constituents from Dalbergia cochinchinensis. Phytochemistry, 1997. 46(7): p. 1219-23.
6. Jonas, A., et al., Cactus flower extracts may prove beneficial in benign prostatic hyperplasia due to inhibition of 5alpha reductase activity, aromatase activity and lipid peroxidation. Urological Research, 1998. 26(4): p. 265-70.
7. Ducrey, B., et al., Inhibition of 5 alpha-reductase and aromatase by the ellagitannins oenothein A and oenothein B from Epilobium species. Planta Medica, 1997. 63(2): p. 111-4.
8. Hiermann, A. and F. Bucar, Studies of Epilobium angustifolium extracts on growth of accessory sexual organs in rats. Journal of Ethnopharmacology, 1997. 55(3): p. 179-83.
9. Ishiguro, K., H. Oku, and T. Kato, Testosterone 5alpha-reductase inhibitor bisnaphthoquinone derivative from Impatiens balsamina. Phytothery Research, 2000. 14(1): p. 54-6.
10. Weber, K.S., et al., Brain aromatase and 5alpha-reductase, regulatory behaviors and testosterone levels in adult rats on phytoestrogen diets. Proceedings of the Society for Experimental Biology and Medicine, 1999. 221(2): p. 131-5.
11. Habib, F.K., et al., In vitro evaluation of the pollen extract, cernitin T-60, in the regulation of prostate cell growth. British Journal of Urology, 1990. 66(4): p. 393-7.
12. Nakayama, O., et al., Riboflavin, a testosterone 5 alpha-reductase inhibitor. Journal of Antibiotics, 1990. 43(12): p. 1615-6.
13. Liao, S. and R.A. Hiipakka, Selective inhibition of steroid 5 alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate. Biochemical & Biophysical Research Communications, 1995. 214(3): p. 833-8.
14. Om, A.S. and K.W. Chung, Dietary zinc deficiency alters 5 alpha-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. Journal of Nutrition, 1996. 126(4): p. 842-8.
15. Rhodes, L., et al., Comparison of finasteride (Proscar), a 5 alpha reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5 alpha reductase inhibition. Prostate, 1993. 22(1): p. 43-51.
16. Breza, J., et al., Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe. Current Medical Research & Opinion, 1998. 14(3): p. 127-39.
17. Muntzing, J., et al., Direct and indirect effects of docosanol (IK.2), the active principle in Tadenan, on the rat prostate. Investigative Urology, 1979. 17(3): p. 176-80.
18. Toth, I., et al., In vitro inhibition of testicular delta 5-3 beta-hydroxysteroid dehydrogenase and prostatic 5 alpha-reductase activities in rats and humans by strogen forte extract. International Urology & Nephrology, 1996. 28(3): p. 337-48.
19. Plosker, G.L. and R.N. Brogden, Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia. Drugs & Aging, 1996. 9(5): p. 379-95.
20. Carilla, E., et al., Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate. Journal of Steroid Biochemistry, 1984. 20(1): p. 521-3.
21. Ondrizek, R.R., et al., Inhibition of human sperm motility by specific herbs used in alternative medicine. Journal of Assisted Reproduction & Genetics, 1999. 16(2): p. 87-91.
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