Cy Willson wrote:
A few important points that I think people are missing.
1. There is supportive evidence of these compounds being efficacious when it comes to increasing endogenous testosterone production. I'll past some references below.
2. Medline or pubmed is not intended to be a source of "proof" nor is any database which has published studies (peer-reviewed or not). Proof as I've seen it used here does not exist, as it's implying that every last variable has been accounted for. Instead, these studies are there to allow others to view and interpret the data themselves, again, in support of or against a given hypothesis. Coming to a different conclusion from the authors is completely fine provided that there isn't an overwhelming body of evidence which would contradict your own conclusions.
3. The second point is exemplified greatly in the following. In the particular study of a tribulus extract and the finding of no increase of testosterone levels, there are many areas to critique. First, you're talking about a crude plant extract. This has three main problems with it in this situation and in general.
* These extracts are "standardized" which simply means that the manufacturers providing the product give a loose promise that the plant contains no less than a particular percentage of the active constituent(s). As I've pointed out before in a previous articles, when standardized green tea extracts were evaluated for catechin content, every last product failed to meet label claims, the best of which only had around 50% of the label claim. This is not really anyone's fault when you're relying on a standardized products, but it does easily create huge discrepancies when evaluating such products scientifically. This is one reason for isolating and purifying the compounds responsible for said benefits (more on that to follow below). It makes much more sense to use 750 mg of pure active constituents as opposed to 3,000 mg of a plant extract, "standardized" to contain 25% as this eliminates this concern.
* In the pharmaceutical industry and really just as a generally good idea, it's most always preferred to isolate the main active constituent(s) from a plant instead of having crude extracts. Two reasons for this include the idea that many times, a given plant may have other compounds which oppose the actions of the compounds thought to be responsible for the biological effects. The other is of course because many times, plants may also have other compounds which are toxic. There are certainly studies which one can locate which demonstrate a lack of efficacy from a given extract, yet the isolated compound worked, and there are also, again, studies where a given extract has demonstrated toxicity, while the isolated compound has not. Just to name a few, examples would be licorice root, commiphora mukul and cissus quadrangularis.
* Using extracts instead of isolated compounds limits the possibility of improving efficacy, namely in the way of improving pharmacokinetic aspects, specifically oral bioavailability. For example, I know that with the biologically active compounds in eurycoma, oral bioavailability is extremely low due to the high lipophilicity and consequent low absorption of the compounds, resulting in around 1% of a given dose actually reaching the bloodstream. This is why the nanodispersion delivery is used to address such an issue. Along these same lines, the active constituents in tribulus (protodioscin, methylprotodioscin and other similar analogs) also have a similar issue. In fact IV administration of protodioscin in primates was shown to increase LH and testosterone levels. This again goes back to addressing bioavailability issues which is what has been done with Alpha Male. The high sales and anecdotal evidence is hard for me to ignore with Alpha Male. This is what I do know. Alpha Male contains, if I remember correctly, close to 100% pure isolated compounds, thought to be responsible for biological activity. Whereas some companies have figured out how to do the same thing, they simply extract protodioscin, while ignoring its' analogs. They also ignore the issue of low absorption.
Last but not least, I was discussing this with a friend of mine not too long ago, and I don't think many understand the time, cost and effort involved in having a double-blind, placebo-controlled, randomized (with crossover) study performed in those who aren't in a diseased or abnormal state, only to have it published. Recruiting the subjects alone presents a problem. I see that most cynics want weight-trained males who have serious experience and so forth. Well, I think that most would find, when actually recruiting subjects in a given city or town, it's a bit hard to find, let's say 30 such guys who are willing to give up their current supplements, follow a specific weight training and diet routine, take time out of their day to stop at a lab for hours to have blood drawn, body composition assessed, record diet, obtain their pills, all under the premise that they "might" be taking the active compound for 12 weeks. In case they are lucky, they might receive a 25 or 50 dollar stipend.
In the particular case of Biotest, although I'm not the one who makes such decisions, I can see why it doesn't make much sense to invest a limited amount of research dollars in to a product which already has a large following and high sales when one can better invest money on future products.
Koumanov F, Bozadjieva E, Andreeva M, Platonva E, Ankov V. Clinical trial of Tribestan. Experimental Medicine 1982;2?4.
Gauthaman K, Ganesan AP, Prasad RN. ?Sexual effects of puncturevine (Tribulus terrestris) extract (protodioscin): an evaluation using a rat model.? J Altern Complement Med. 2003 Apr;9(2):257-65.
Gauthaman K, Adaikan PG, Prasad RN. ?Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats.? Life Sci. 2002 Aug 9;71(12):1385-96.
Adaikan PG, Gauthaman K, Prasad RNV, Ng SC. Proerectile pharmacological effects of Tribulus terrestris extract on the rabbit corpus cavernosal smooth muscle in vitro. Annals Academy of Medicine, Singapore 2000;29(1):22?6.
Adaikan PG, Gauthaman K, Prasad RNV, Ng, SC. History of herbal medicines with an insight on the pharmacological properties of Tribulus terrestris. Ageing Male 2001;4:163?169.
Adimoelja A, Adaikan PG. Protodioscin from herbal plant Tribulus terrestris L. improves male sexual functions possibly via DHEA. International Journal of Impotence Research 1997;9(1):S64.
Tomova M, Gjulemetova R, Zarkova S, Peeva S, Pangarova T, Simova M. Steroidal saponins from Tribulus terrestris L. with a stimulating action on the sexual functions. International Conference of Chemistry and Biotechnology of Biologically Active Natural Products, Varna, Bulgaria, September 21?26, vol. 3. 1981. p. 298?302.
Gauthaman K, Adaikan PG, Prasad RNV, Goh VHH, Ng SC. Changes in hormonal parameters secondary to intravenous administration of Tribulus terrestris extract in primates. International Journal of Impotence Research 2000;12(Supplement 2):6 (Abstract).
T.K. Kwan, J.M. Saad , O. Farizaturradiah dan B.H. Koh. 1995. The Effect of Eurycoma longifolia on Rat and Human Testicular Steroidogenesis. Posiding Konvensyen Kebangsaan Tumbuhan Ubatan. FRIM. m/s 201-204.
Ali JM and Saad JM (1993); Biochemical effect of Eurycoma Longifolia Jack on the sexual behavior, fertility, sex hormone and glycolysis; Dissertation Paper for Bachelor of Science, Department of Biochemistry, University of Malaya.
Ang HH, Cheang HS. ?Effects of Eurycoma longifolia jack on laevator ani muscle in both uncastrated and testosterone-stimulated castrated intact male rats.? Arch Pharm Res. 2001 Oct;24(5):437-40.
Ang HH, Ikeda S, Gan EK. ?Evaluation of the potency activity of aphrodisiac in Eurycoma longifolia Jack.? Phytother Res. 2001 Aug;15(5):435-6.
Ang HH, Cheang HS, Yusof AP. ?Effects of Eurycoma longifolia Jack (Tongkat Ali) on the initiation of sexual performance of inexperienced castrated male rats.? Exp Anim. 2000 Jan;49(1):35-8.
Ang HH, Ngai TH, Tan TH. ?Effects of Eurycoma longifolia Jack on sexual qualities in middle aged male rats.? Phytomedicine. 2003;10(6-7):590-3.
Ang HH, Lee KL, Kiyoshi M. ?Eurycoma longifolia Jack enhances sexual motivation in middle-aged male mice.? J Basic Clin Physiol Pharmacol. 2003;14(3):301-8.
Ang HH, Sim MK. ?Eurycoma longifolia Jack enhances libido in sexually experienced male rats.? Exp Anim. 1997 Oct;46(4):287-90.
Ang HH, Ngai TH. ?Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia Jack.? Fundam Clin Pharmacol. 2001 Aug;15(4):265-8.
I genuinely appreciate the list of articles and hope it wasn't too much trouble. One thing I noticed was that the majority of them deal with libido and sexual function (in animals). Now that's interesting to me, because from what I have heard anecdotally, that is the strongest value in Trib.
Q for you: in general do endocrine-related studies on animals apply well to humans?