Tuesday, October 30, 2012

Capsaicin or Plant Oxysterol 28-Homobrassinolide (28-HB) - Two Candidates for a Natty Test Booster that Works?

In am not sure if people got afraid that I rip their papers apart by pointing with a figure at the non-existent real-world significance of their revolutionary findings about the testosterone boosting effects of herb X from the deepest jungle in Y. What I do know however, is that for whatever reason studies like these have become rare as of late. I have still been able to pick up two of them, to do what Carl usually calls the SuppVersity Sniff Test on Capsaicin *achoo!* ... sorry! And the oxysterol 28-Homobrassinolide, which is present in miniscule amounts in Chinese cabbage, for example.

Capsaicin: The hotter, the better?

The first of the two studies we are going to tackle, today, comes right from the Department of Histology & Embryology at the Faculty of Veterinary Medicine of the University of Uludag in Turkey... and yes, the fact that it comes from the "Department of Histology & Embryology at the Faculty  of Veterinary Medicine" is in fact a first indicator that some of the initially mentioned "sniffing" and an appropriate amount of healthy skepticism are probably indicated. But let's not make any hasty judgments; after all, this study is not about herb X from the deepest jungle in Y, but a simple investigation into the effects of capsaicin on the morphology of rodent testes.

While capsaicin seems to be better used topical as a fat burner, here is a serious warning: Don't rub any capsaicin based fat burner onto your scrotum  in the false hope to turn it into a test booster ;-)
As a SuppVersity student you will be aware that capsaicin, the "hot stuff" in hot peppers, is quite a remarkable substance (e.g. "Capsaicin Cream for Topical Fat loss?").

Aside from topical (and at least in rodents) systemic effects on fat loss and the metabolic syndrome, there have also been several reports linking capsaicin to improvements in testicular morphology in diabetic and otherwise sick animals. Others report direct stimulative effects of capsaicin on testicular development and modulatory effects on the local and systemic expression of ghrelin, which has been shown to exert inhibitory effects of testosterone secretion in the testes (Tena-Sempere. 2005).

The latter, i.e. the connection between capsaicin, ghrelin and testicular morphology, development and function was obviously what Ilhan and Erdost must have had in mind, when they devised an experiment in the course of which they treated adolescent and adult mice with capsaicin (CAP) hoping to observe a change in the local expression ghrelin and subsequent changes in gonadal testosterone production.
"The animals were divided into two age groups: puberty and adult. Control groups for both age groups were fed with standard diet and experimental groups were fed with a diet containing 0.02% CAP. Testes were collected quickly after sacrifice. After dehydration, the specimens were embedded in paraffin and 5 μm sections were cut, and Crossman's triple staining and immunohistochemical staining for ghrelin were applied." (Ilhan. 2012)
The immunohistochemical stains of the testicular tissue the scientists conducted revealed that ghrelin was present in the testosterone producing Leydig and Sertoli cells of all animals. It was yet not expressed in any of the spermatogenic cells of either the adolescent or adult rodents.

The capsaicin treatment, on the other hand, reduced the immunoreaction in both groups - a clear sign of a local reduction in ghrelin.

Against that background and the previously cited findings by Tena-Sempera (as well as similar studies), it is not surprising that these local reductions in ghrelin went hand in hand with statistically significant increases in serum testosterone levels in both experimental groups, yet especially in adults (see figure 1).
Figure 1: Ghrelin and testosterone levels in response to control or capsaicin supplemented diet (base on Ilhan. 2012)
Since the increase in circulating testosterone took place in presence of an increase in systemic ghrelin levels, it is obvious that capsaicin does not block the release of ghrelin, but rather it's local effects - the exact mechanism, however has still to be elucidated.

The same goes for the beneficial effects of which is probably a "side effect" of the increase in testosterone, since any amelioration of the local inhibition of spermatogenesis in the the spermatogenic cells would require the presence of the "hunger hormone" in this cells. And, as mentioned above, the immunostaining did not reveal any significant amounts of ghrelin in the testes of both the treated and untreated animals.

Right, right, I don't bother about mechanisms as long as it works - So how much do I need?

Figure 2:  Capsaicin content (mg/100g) of different varieties of pepper fruits (Supalkova. 2007)
In view of all of these "may bes" and "could bes" the researchers conclusion that capsaicin "appears to enhance testicular cell proliferation and can affect the release of ghrelin and testosterone directly or indirectly" (Ilhan. 2012) is not very satisfying. If we do yet simply discard that we don't know why capsaicin boosts testosterone and further assume that the results will translate to human beings, capsaicin certainly sounds like an easy and cost-effective way to boost both testosterone and fertility, after all, the human equivalent of those 0.02% capsaicin amounts to no more than 200-300mg per day!

What may yet sound like a very reasonable for a good reason not achievable by eating peppers alone and could in fact burn right through your stomach lining. 

It stands out of question 200mg , that does not sound much, but if you take a closer look at the data in figure 2 you will be able to estimate that it will "taste" or rather "burn" like too much, already. After all, you would have to consume at least 100g of the ovaries  of the hottest variety of peppers the group of Czech researchers could find, when they did the analysis on which the data in figure 2 is based
Ovaries in a pepper? Are you serious? The "ovaries" are the parts inside a pepper on which the seeds are sitting... yeah, the stuffy you usually throw away, because you can't stand how "hot" it is (the illustration on the left a slightly modified version of figure 2 in Supalkova. 2007).
That said, milder varieties are obviously even less suitable, after all, you would need 1kg or even 10kg of the ovaries of those... Not exactly something anybody would expect to yield great health benefits, anyways, right?
So what about those  28-homobrassinolides, then? Those must be great, right?

I guess most normal people will immediately think of their touted cholesterol lowering effects, when they hear about "plant sterols". Not the average muscle-head, though for him (and mostly it's just "him" who falls for this idea) their structural resemblance to steroid hormones is what counts and their ability to totally mess up your own endocrine system is what is ignored as soon as the "Big T" is mentioned (click here to read all about the role of testosterone in building muscle). No wonder the "T-word" is also at the heart of the bro-scientific sales pitches the companies who are bottling respective products will have their reps propagate on the bulletin boards of the bodybuilding and fitness world. The scientific perspective is slightly different, though and the truth is probably, as so often, anywhere in the middle. And in this regards the recent study on possible pro-androgenic effects of 28-homobrassinolides (28-HB) that was founded on the rationale that 28-HB has been shown to ameliorate high blood glucose levels, while the latter have been shown to compromise testicular function and testosterone production is no exception.
Figure 3: Effect of 28-HB on lipid peroxidation, superoxide dismutase activity and catalase activity in rat testis (based on Premalata. 2012)
"Studies investigating the effects of 28-homobrassinolide (28-HB) on diabetic male rats indicated antihyperglycemic potency in this phytohormone. Since hyperglycemia was known to suppress testicular and ovarian steroidogenesis in the rat, it provided a basis for evaluating the biopotency of this oxysterol in rat testicular steroidogenesis. The present study was designed to elucidate the effects of 28-HB on testicular steroidogenesis in normal and streptozotocin (STZ)-induced diabetic rats." (Premalath. 2012)
Fortunately, though the researchers had a normal control group which received the same dose of 50µg of 28-HB in 50mL of 50% ethanol per day in their study. This gives the otherwise very artificial data at least some significance for the average, hopefully non-diabetic trainee as well.

A plant sterol that's obviously not for diabetics only

As the data in figure 3 shows all the expected beneficial effects on the streptozotocin-induced downregulation of superoxide dismutase (SOD) and catalase activity (CAT, as well as a reduction in reduced glutathione; not shown in figure 3) and partial reversal of the increase in lipid peroxidation were present in the diabetic rodents. And even in the healthy control, the ratio of anti- to pro-oxidant factors improved significicantly.
Figure 4: Changes in the levels of ABP and StAR protein, as well as testosterone in the testis of 28-homobrassinolide-treated rats (Premalatha. 2012)
The corresponding, or I should say "corollary" changes in steroidogenic acute regulatory protein (StAR), and androgen-binding protein (ABP) expression, but even more so increase in intratesticular (not(!) serum!) testosterone levels you see in figure 4 do however raise the question, whether what we are seeing here - specifically in the diabetic rodents - is actually (still) healthy or not (see figure 4).

To potent to be healthy?

In this regard it may also be worthwile to take into account what the scientists say about the enzymatic conversion of cholesterol to testosterone and how it may and does figure in this context:
"It is known that the synthesis of T in animal tissues is under the influence of 3b- and 17b-hydroxy steroid dehydrogenases. Increase in the activities of 3b- and 17b-HSD observed in the present study was suggestive of the active involvement of these enzymes in rat testicular steriodogenesis. Elevated 17b-HSD activity due to 28-HB was noted in relation to the elevated StAR content in normal rat testicular tissue. However, elevated 17b-HSD activity did not correlate with the StAR content of diabetic rat testis, suggestive of a disproportionate link between HSD activity and StAR content in the diabetic rat testis probably influenced by 28-HB. [...] It is reported that androgens reduced T biosynthesis in adult Leydig cells and in Leydig cell lines in an autoregulatory man-ner through receptor-mediated inhibition of StAR expression under normal physiological conditions. On the contrary, the increase in StAR protein level along with the relatively high level of T (figure 4) detected in the testis of male rats used in this study is due to the specific effect of the phytooxysterol 28-HB. Even though StAR and ABP were positively regulated by administered 28-HB, the observed increase in testicular
T content in diabetic rat is to be considered excessive." (Premalatha. 2012)
My gut feeling is that the attribute "excessive" Premalatha et al. use in their paper is absolutely spot on. And this goes despite the fact that similar yet way less pronounced effects effects have been observed in the absence of 28-HB administration simply as a result of streptozotocin administration in previous studies in both male and female rodents (Ho. 1991; Leaming 1982). These short term effects are probably a result of a skewed negative feedback at the level of the hypothalamus, where the increased circulating testosterone levels should actually lead to a corresponding decrease in gonadotropin-releasing hormone (GnRH). This regulatory mechanism, however does not work correctly in the early phase of STZ-induced diabetes, so that it take up to 120-140 days until a new "normal" and in this case supra-physological (= low testosterone) steady state is achieved.

Both, the questionable mechanism, as well as the "overshoot" in testicular testosterone levels and the absence of respective information on the levels of circulating testosterone -- what if it simply accumulated in the testis (remember the difference in systemic and local ghrelin in the capsaicin study!)? -- make the usefulness and even the safety of 28-HB as a test booster more than questionable.

Looking for more promising alternatives? Check out my previous post on "+180% Testosterone w/ Taurine"
Bottom line: If we go back to the original question whether one of the two supps could be the long-awaited breakthrough "natural" testosterone booster everyone expect me appears to be waiting for (what is "natural" about eating 100g+ of red pepper ovaries or using plant sterol extracts, by the way?), it appears as if none of the two would qualify.

Whether dihydrocapsiate, which has been pimped by Ajinomoto as a more potent, and safer fat burner than capsaicin and could be a more tolerable alternative to capsaicin, would even have the same effects on the testis is about as questionable as its value as a fat burner, of which Galgani and Ravussin found in 2010, already, that the <50kcal/day increase in energy expenditure in response to 1 month of supplementation with 9mg/day of the said capsiate "is in the range of day-to-day RMR variability" (Galgani. 2012) and therefore negligible.

Anyhow, in the unlikley case that some mad or sane scientists find non-negligible effects of supplementation with either dihydrocapsiate (or another more tolerable variety of capsaicin, such as a nano-encapsulated  for example) or 28-homobrassinolide in a future human trial, you know that the SuppVersity is the place to go to read about those results first, right?

References:
  • Galgani JE, Ravussin E. Effect of dihydrocapsiate on resting metabolic rate in humans. Am J Clin Nutr. 2010 Nov;92(5):1089-93.
  • Ho SM. Prostatic androgen receptor and plasma testosterone levels in streptozotocin-induced diabetic rats. J Steroid Biochem Mol Biol. 1991;38(1):67-72.
  • Ilhan T, Erdost H. Effects of capsaicin on testis ghrelin expression in mice. Biotech Histochem. 2012 Sep 27.
  • Kwon DY, Kim YS, Ryu SY, Cha MR, Yon GH, Yang HJ, Kim MJ, Kang S, Park S. Capsiate improves glucose metabolism by improving insulin sensitivity better than capsaicin in diabetic rats. J Nutr Biochem. 2012 Sep 28. pii: S0955-2863(12)00213-6.
  • Leaming AB, Mathur RS, Levine JH. Increased plasma testoster-one in streptozotocin-diabetic female rats.Endocrinology.1982; 111(4):1329-1333.
  • Premalatha R, Jubendradass R, Rani SJ, Srikumar K, Mathur PP. A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats. Reprod Sci. 2012 Sep 25.
  • Supalkova V, Stavelikova H, Krizkova S, Adam V, Horna A, Havel L, Ryant P, Babula P, Kizek R. Study of Capsaicin Content in Various Parts of Pepper Fruit by Liquid Chromatography with Electrochemical Detection. Acta Chim. Slov. 2007, 54, 55–59.
  • Tena-Sempere M. Ghrelin: novel regulator of gonadal function. J Endocrinol Invest. 2005;28(5 Suppl):26-9.

9 comments:

  1. "Don't rub any capsaicin based fat burner onto your scrotum in the false hope to turn it into a test booster"

    Else there will be much involuntary screaming and thrashing about!

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    1. *lol* I thought I better copy McDonald's "watch out your hot coffee could be hot"-warning just in case... I mean, you know how people are, when it comes to means of boosting testosterone. Some will literally do anything (funnily some of the "some" who would probably even rub capsaicin on their scrotum will tell you that they would never do TRT, because that's dangerous... and that after years of messing up their endocrine system with "harmless natural testosterone boosters")

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  2. Don't know how it is where you guys live, but here in Belgium you can't even obtain pharmaceutical preparations of capsaicin beyond a 3% resin (so you couldn't even purify your own higher concentration out of it). You could always dismantle your weaponized pepperspray, which contains 10-12% capsaicin, and that should really tell you you don't want to get this stuff anywhere. I know this because I once tried obtaining a pure capsaicin to devise a 2% benzyl alcohol localized delivery system.

    Having said that, was there any mention of how capsaicin did what it did ? Potentially via the vanilloid receptor ? If that were the case there are other alternatives of course like evodiamine.

    I personally am a very big fan of spicy, to the point where i can easily consume 50-100g of raw peppers, but trust me, these aren't the very hottest peppers (they aren't mild either, I grow them myself, they will burn off your pallate) and I couldn't do this every day. Even one such session can be fairly disastrous on your stool. Doing this twice a day for any span of time would wreck havoc, not just on your body, but on your household.

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    1. unfortunately the study is not exactly comprehensive and there was no investigation into the MOA, but it's unlikely that this is mediated by a receptor of which I have not heard it is expressed anywhere else than in the gut (I must admit, I did not check the literature, though; would not expect anybody probing this, anyways.

      But evodiamine is at least from a mechanistic perspective exactly NOT what you want to use
      "The stimulatory effect of forskolin on testosterone release in TICs was prevented by administration of evodiamine [...] evodiamine reduces testosterone secretion in rat TICs via a mechanism involving reduced activity of cAMP-related pathways and 17beta-hydroxysteroid dehydrogenase (17beta-HSD)." (Lin. 1999)

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  3. Are there ANY effective natural T-boosters? Taurine?

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    1. Sleep is most natural T-booster, though hardest to obtain in modern times. ;)

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    2. well said, Maxim.

      Taurine just as any of the other working test boosters appears quite nice to get test from the low back to the (upper) normal range, but that effect is mostly mediated by general health effects (antioxidant etc.)

      and it has little effect on you ability to build muscle (it does however seem to work (synergize with a healthy diet + exercise) for fertility - see Pround Daddy's N=1 experience in the comment to the taurine post here > http://tinyurl.com/d9dgmkg

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  4. I really need to apologize. While the facts of Mrs. ProudDaddy's pregnancy and my having started taurine are true, I just used your article as an excuse to brag about my siring a child at age 71. The Mrs. has endometriosis, we're clinically diagnosed as an infertile couple, and our first child was conceived via IVF. This miracle, ten years later, was more likely due to the elimination of most processed foods from our diet and regular workouts. How else does one explain a yearly coupling resulting in conception? Then again, maybe it WAS the taurine!

    (The last was again said tongue-in-cheek - my T levels have always been slightly above average, although quite high now when age-adjusted.)

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  5. Here is a great place to get more information:

    http://examine.com/supplements/Capsaicin/

    ReplyDelete