More Testosterone Boosters: Andrographolide & Quassinoid Rich Fraction from Eurycoma Longifolia. Preview: Science Round-Up - Sesamin, Teas, Muscle Swelling & Growth...

Do you really get along without estrogen when you want to build muscle (read the answer)

You thought I would already have forgotten my promise from last week to tell you about the other potential testosterone & libido (+fertility) boosters? How dare you ;-)! I just wanted to keep thrill of anticipation and in order to prolong that a little further, I will start out - as on every Thursday - with a sneak preview on today's Science Round-Up  (airs on the Super Human Radio Network on 1PM, click here to listen live).

As you may imagine there were not all too many novel papers published since last week. Notwithstanding, I could assemble enough material for the 1h show. According to my current plan, the schedule will look like this:

• the fat burning effects of n-6 sesamin, AA and D-GLA
• the antibacterial effects of raspberry extracts
• fermented green tea and liver protection
• the optimal brewing time for tea depending on your goals
• the futility of using green tea as a "fat burner" in healthy individuals
• muscle swelling and skeletal hypertrophy & training with cuffs
• exercise will make you hungry, you will eat more and still lose weight

... and more if there is still enough time. Ok, I guess you have been waiting long enough, now. So let's take a look at the promised testosterone boosters and their individual effects:

Andrographolide - Never heard of it? The data suggests it may be wort remembering

Don't worry if you have never heard the name "Andrographolide" before, because even if you did, you are probably only aware of the effects the active agent in Andrographis paniculata (Burm. F.) is supposed to have on the gastro-intestinal tract and upper respiratory infections, fever and herpes (Ayurveda), detoxification (TCM) and the prevention and treatment of the common cold (Scandinavia; cf. Mishra. 2007).

Figure 1: Mounting frequency in male rodents receiving 50mg/kg andrographolide (HED: 8.1mg/kg) compared to sildenafi (left) and long-term effects on serum testosterone levels (right; Sattayasai. 2010)

As the data in figure 1 goes to show you it can help you find back your libido and increase your testosterone levels. With the libido effects being not as immediate, but more long-lasting than with sildenafil and the effects on testosterone only after 4 weeks of continuous use, it is yet not a 1:1 alternative for the typical Western immediate satisfaction seeker ;-)

That said, as with all the natural test-boosters the chance that they will translate into muscle gains are pretty slim - and this stuff first has to prove its efficacy in humans.

Eurycoma Longifolia may be worth taking a look at - though for a brief HTPA boost, only

I guess many of you will know "longjack" aka "Tonkat Ali" and who knows some may even have a supplement that was either based on or did at least contain some of a couple of milligrams of it. Now, in case that did not work, the underlying reason may well have been that your extract was devoid or at least low in the active quassinoids the scientists from the School of Pharmaceutical Sciences Universiti Sains Malaysia in Penang, Malaysia, administered to male rats at dosages of 25mg/kg (4mg/kg for a human).

Figure 2: Endocrine effects of different doses of quassinoids from Tonkat Ali (Low. 2012)

As the data in figure 2 goes to show you, this was actually actually the case and the mechanism appears to be mediated by direct effects on the luteinizing hormone release in the hypothalamus.

Now don't get too excited. While previous studies have shown that the change of toxic side-effects is low, the study at hand did also reveal that

Comparing natty test boosters with anabolic agents (read more)

"[...] the over stimulated effect of testosterone production by E. longifolia probably may not be an issue as the peak testosterone level recorded at the first complete spermatogenesis process of 52 days was reduced back to the normal level even though the animals were given a higher dose or prolonged treatment period, due probably to the effect of homeostasis." (Low. 2012)

That said, chances that you will actually gain some muscle mass on this stuff are (as usual with natty test boosters) zero. To give your HPTA a kickstart the LH inducing effect could come handy, though. So if you whacked your natural testosterone production by whatever means, it is worth a try (not as a standalone PCT, however).

That's it for now, so if you want more news, you better don't forget to tune in live to the SuppVersity Science Round-Up on Superhuman Radio at 1PM (EST)

References:

• Low BS, Das PK, Chan KL. Standardized quassinoid-rich Eurycoma longifolia extract improved spermatogenesis and fertility in male rats via the hypothalamic-pituitary-gonadal axis. J Ethnopharmacol. 2012 Dec 19.
• Mishra SK, Sangwan NS, Sanwan RS. Andrographis paniculata(Kalmegh): a review. Phcog. Rev. 2007; 1, 283–298.
• Sattayasai J, Srisuwan S, Arkaravichien T, Aromdee C. Effects of andrographolide on sexual functions, vascular reactivity and serum testosterone level in rodents. Food Chem Toxicol. 2010 Jul;48(7):1934-8.

5-10% Weight Reduction From Set to Set For Hypertrophy, Heavy Leg Workouts for Cyclists, Garlic For 400% Higher Test/Cortisol Ratios & Max(!) 1g Vitamin C for Muscle Gains

7% increase in breast cancer risk for every 500g above "normal" birthweight for Scandinavian women. Weight is yet not all that counts, mommy's gestational diabetes and even a large body size also precipitate to later disease.

7% per 500g that's the increase in breast cancer risk, the female offspring of Scandinavian women will have, if they are born heavier than normal. This figure is the SuppVersity Figure of the Week and comes from a study I came across a couple of days ago (Troisi. 2012). The statistics are based on birth register data of women from Norway, Sweden or Denmark who were subsequently diagnosed with primary, invasive breast cancer (n=51419) and 10 controls for each case from the birth registries matched by country and year of birth (n = 514,190).

Contrary to what you may think, the birth weight does yet not pose as much of a risk to become obese later in life as being larger than "appropriate" for your gestational age does (Eyzaguirre. 2012). If you also consider that gestational diabetes has been linked with increased risk of metabolic syndrome in the offspring (Davis. 2012) and that obesity in itself is an independent risk factor for breast cancer (Patterson. 2012), these should be more than enough good arguments not to surrender to your occasional food cravings and laziness - pregnant or not.

It's not all in your genes, but most in your hands

Although some people would love, if this was the case, because they could blame their own misery on the mistakes other  may have made, our lives and health are not fully determined by our genes and/or the mistakes our mothers may or may not have made. As Poston and Foreyt wrote in 1999, already: "Obesity is an environmental issue." And we are lucky: It is in our hands to change the environment we are exposing ourselves to and thus influence which of our genetic disposals will become active and are  promoted and which of them won't. Now that's obviously not just the case for obesity, muscular hypertrophy would be another example. Irrespective of your genetic make-up your strength and muscle gains stand and fall with the way you train, eat and supplement... and guess what, all of these points will be addressed in today's installment of On Short Notice.

• Experimentally validated: 5-10% drop in weights per set is "optimal" for hypertrophy training (Medeiros. 2012) -- Scientists from the Laboratory of Physiology and Biokinetic at the Faculty of Biological Sciences and Health on the UNIG Campus V at Itaperuna in Brazil find: The average resistance trainee - in this case a young man aged 24.0±4.5 years with a body mass of 78.3±10.2 kg and a height of 177±7 cm - can remain in the hypertrophy range (10-12 reps to failure) for most of his sets, when he reduces the weight by 5-10% after each set.
  
  Whether this will also yield optimal gains was yet not within the scope of this 5-week study. What these results do however tell you is that you are not training hard enough if you perform all your sets with the exact same weight in the exact same rep range - well, unless you don't just like to listen to Super Human Radio, but are actually related to Superman himself ;-)

• 

  Sir Chris Hoy's legs are not as hilarious as those of the German Robert Forstemann (Robert is the right guy), but I am pretty certain their size and strength played a very important part in becoming the most successful Olympic track cyclist of all times (six gold and one silver Olympic Medal + 11 times world champion)

  Heavy leg training could make the difference between victory or defeat at the end of a cycling race (Hansen. 2012) -- In a soon-to-be-published paper, Ernst A. Hansen et al. report that the addition of 12-weeks of heavy resistance training in the form of 4 lower body exercises (3 × 4–10 repetition maximum) which had to be performed twice a week enhanced the cycling performance of highly trained cyclists by 7% compared to the training outcome of the subjects in a control group who simply followed their regular endurance-only, protocols:
  

  "Performance was determined as average power output in a 5-min all-out trial performed subsequent to 185 min of submaximal cycling. The performance enhancement, which has been reported previously, was here shown to be accompanied by improved pedaling efficacy during the all-out cycling. Thus, E+S shortened the phase where negative crank torque occurs by ~16°, corresponding to ~14%, which was more than in E (P = .002)" (Hansen. 2012)

  Since the test was conducted at the end of a 3h cycling session, it should be plain obvious that those 15% increases in torque will catapult the strength trained endurance athlete to the forefront on every final sprint.

• Human dose equivalent of ~0.1g/kg garlic per day could not just boost your testosterone and lower the high protein diet induced increases in cortisol, it could also improve the way your body utilizes dietary protein (Oi. 2012)-- Actually this is not a new study, but since Maxim was not happy with things "so yesterday" as the increases in HDL and LDL the Arabian scientists observed in the garlic study I have been talking about at the end of Thursday's SuppVersity Science Round-Up on SHR, I thought others may be as happy as Maxim will hopefully be to hear that there is more to garlic than "just" its beneficial effects on your heart.
  
  

  

  Figure 1: Higher testosterone levels, an amelioration of the high protein induced increase in corticosteroids and a 40% increase in net protein balance are unquestionably impressive results given the fact that the all those differences were brought about within 28 days and by no more than 0.1g/kg (HED) of "supplemental" garlic in form of heat dried powder that was added to the chow (Oi. 2001)

  In fact, I am almost sure that the >400% increase in the testosterone to cortisol ratio you will see if you take a closer look at the data in figure 1, is probably rather what Maxim would have liked to hear me talk about. Especially in view of the fact that this endocrine effects went hand in hand with a highly significant +60% increase in protein retention (figure 1, top right). Think about it, if only part of he protein that was now no longer excreted in the urine / feces would be used for protein synthesis this would entail exactly those hypertrophy effects you don't see with your average "scientifically proven" herb-based testosterone booster.
  
  Unfortunately, the scientists did only measure the body weight and visceral fat pads, not the actual muscle mass of the rodents,. But if you go by their ratios it is obvious that the high protein + garlic group were not just the heaviest, but also the leanest.
  
  With +11 % vs. +5% in both the medium and high protein diets, the animals on the low protein did yet exhibit the most profound benefits as far as the body weight / visceral fat ratio goes. Against the background that their net protein balance remained the same, this observation does actually suggest that the pro-anabolic effects of garlic are not solely a result of a decreased protein excretion (see figure 1).

  

  Table 1: Principal sulphur compounds of garlic preparations (Hammami. 2012)

  Warning: Don't live on garlic alone! While the provision of 0.8% garlic powder did have beneficial effects on testosterone production in the study at hand, there are a couple of studies which suggest that a diet with 15-30% of crude garlic (Hammami. 2008 & 2009), as well as the administration of Diallyl trisulphide in isolation (Qian. 1986) and raw garlic juice (e.g. 600mg/kg per day for 21 days in Fehri. 1991) can compromise testosterone production and/or testicular function. In view of the difference between 0.8% garlic powder in the diet of the rodents in study at hand and 15-30% of pure garlic in the diet of the animals in the Hamami studies, it is most likely that the effects were dose-depended, but in case you are interested in health benefits of specific sulfor compounds in garlic, the data in table 1 on the left may still come handy to pick "your" preferred form of garlic.
  Rather than that, it appears as if the human equivalent of 0.1g/kg body weight of heat dried garlic powder that contained a total amount of 5.05 mg/g of total diallylsulfide (0.05 mg of monosulfide, 1.0 mg of disulfide, 3.4 mg of trisulfide, 0.6 mg tetrasulfide) had the ability to improve the incorporation of dietary protein into muscles (and other organs).

 

• Study shows: Vitamin C supplementation does reduce skeletal muscle hypertrophy in response to chronic overload (Makanae. 2012) -- Despite the fact that it has not even been published yet, the paper by Yuhei Makanae et al. actually only confirms what more and more scientists have been speculating about within the last couple of years. The provision of high does of active antioxidants, and as it seems in particular vitamin C, blunts the hypertrophy response to skeletal muscle overload.
  
  

  

  Figure 2: 14-day of 500mg/kg  (HED 0.08g/kg) supplemental vitamin C blunt skeletal muscle hypertrophy in rodents (Makanae. 2012)

  As you can see in figure 2 the effect size was relatively small, but statistically highly significant (p < 0.01) and that despite the fact that the supplementation regimen (500mg/kg body weight; HED: 0.08g/kg body weight) was not even that much higher than what some "vitamin C enthusiasts" are taking on a daily basis in the futile (and useless) effort to boost their serum vitamin C levels to a concentrations your body does - probably not without reason - try to counter by increasing renal vitamin C clearance.
  
  As the data in figure 2 shows, the same homeostatic mechanism we know from humans worked in the rodents, as well - well, at least with respect to the serum levels. In the plantaris muscle of the supplemented group, on the other hand, there was a significantly higher accumulation of vitamin C than in the placebo group. This increase went hand in hand with an attenuation of the repressive effects the chronic overload of the muscle had on the expression of the catabolic protein atrogin-1 and the increases in the pro-anabolic protein Erk1/2 (p < 0.01) in the non-supplemented animals. Based on this observations and with reference to the results of previous studies and the fact that neither the water content of the muscle, nor a significant reduction in food intake in the vitamin C group could explain the observed differences, Makanae et al. conclude "that oral vitamin C administration attenuates plantaris muscle hypertrophy induced by chronic mechanical load." (Makanae. 2012).
  
  What the study does not answer, though, is the question whether the effects would be identical in a real-world training scenario, where the temporary, yet more intense wear and tear on the muscle could in fact be sufficient to induce skeletal muscle hypertrophy human despite vitamin C supplementation. But let's be honest in view of the fact that scientific evidence for ergogenic benefits of more than 1g of supplemental vitamin C  per day (in humans) is simply non-existent, the take away message from the study at hand should actually read: Do not escalate your vitamin C beyond the 1g per day, if you don't want to risk compromising the results of all the hard work you are investing into your training.

That's is, another installment of On Short Notice and the first day of the weekend approaching it's peak. If you still have some time before whatever your plan for Saturday night may be and feel like you could use some seconds on today's short news, I suggest you head over to the SuppVersity Facebook Wall and check out the latest news on

• 

  Ever thought about what green tea, grape seed, curcumin, cranberry, and tons of other Super Food have antimicrobial effects? Considering the LPS-influx from the gut turns out to be a major contributor to all sorts of diseases, I am curious about how much of their effects are actually mediated by the gut microbiome.

  The differential role of intramuscular lipids in trained athletes and sedentary slobs and how the difference between performance enhancement and insulin resistance it all comes back to getting your as off the coach (learn more)
• Metformin 2.0? Scientists have developed a hypolipidemic, anti-atherosclerotic, anti-obesity, and glucose lowering agent called ETC-1002 (learn more)
• Confirmed: Grape seed could be the go-to neuroprotector for diabetics - GSE administration was found to be able to ameliorate most of the biochemical altered parameters in diabetic rats (read more)
• Fermenting your own dairy? Just add some catechin rich teas and the lactobacilli will strive. Makes you wonder about the 'internal' probiotic effects of green and black teas, as well. Doesn't it? (learn more)

There will be more, don't worry - so feel free to check for updates either directly on the SuppVersity Facebook Wall or simply by taking a look at the navigation in the right under "SuppVersity Facebook Wall" from time to time. Obviously, you can also simply "like" the SuppVersity on facebook to make sure you don't miss anything.

References:

• Davis JN, Gunderson EP, Gyllenhammer LE, Goran MI. Impact of Gestational Diabetes Mellitus on Pubertal Changes in Adiposity and Metabolic Profiles in Latino Offspring. J Pediatr. 2012 Nov 10.
• Eyzaguirre F, Bancalari R, Román R, Silva R, Youlton R, Urquidi C, García H, Mericq V. Prevalence of components of the metabolic syndrome according to birthweight among overweight and obese children and adolescents. J Pediatr Endocrinol Metab. 2012;25(1-2):51-6. 
• Fehri B, Aiache JM, Korbi S, Monkni M, Ben Said M, Memmi A, Hizaoui B, Boukef K (1991) Toxic effects induced by the repeat administration of Allium sativum L. J Pharm Belg 46:363–374.
• Hammami I, Nahdi A, Mauduit C, Benahmed M, Amri M, Ben Amar A, Zekri S, El May A, El May MV. The inhibitory effects on adult male reproductive functions of crude garlic (Allium sativum) feeding. Asian J Androl. 2008; 10:593–601.
• Hammami I, Amara S, Benahmed M, El May MV, Mauduit C. Chronic crude garlic-feeding modified adult male rat testicular markers: mechanisms of action. Reprod Biol Endocrinol. 2009; 24:57–65.
• Hansen EA, Rønnestad BR, Vegge G, Raastad T. Cyclists Improve Pedalling Efficacy and Performance After Heavy Strength Training. Int J Sports Physiol Perform. 2011 Dec 2. 
• Hammami I, El May MV. Impact of garlic feeding (Allium sativum) on male fertility. Andrologia. 2012 Sep 3.
• Makanae Y, Kawada S, Sasaki K, Nakazato K, Ishii N. Vitamin C administration attenuates overload-induced skeletal muscle hypertrophy in rats. Acta Physiol (Oxf). 2012 Nov 26.
• Medeiros Jr HS, Mello RS, Amorim MZ, Koch AJ, Machado M. Planned Intensity Reduction to Maintain Repetitions Within Recommended Hypertrophy Range. Int J Sports Physiol Perform. 2012 Nov 19. 
• Oi Y, Imafuku M, Shishido C, Kominato Y, Nishimura S, Iwai K. Garlic supplementation increases testicular testosterone and decreases plasma corticosterone in rats fed a high protein diet. J Nutr. 2001 Aug;131(8):2150-6.
• Patterson RE, Rock CL, Kerr J, Natarajan L, Marshall SJ, Pakiz B, Cadmus-Bertram LA. Metabolism and Breast Cancer Risk: Frontiers in Research and Practice. J Acad Nutr Diet. 2012 Nov 2. doi:pii: S2212-2672(12)01426-8.
• Qian YX, Shen PJ, Xu RY, Liu GM, Yang HQ, Lu YS, Sun P, Zhang RW, Qi LM, Lu QH.  Spermicidal effect in vitro by the active principle of garlic. Contraception. 1986; 34:295–302.
• Troisi R, Grotmol T, Jacobsen J, Tretli S, Toft­Sørensen H, Gissler M, Kaaja R,Potischman N, Ekbom A, Hoover RN Stephansson O. Perinatal characteristics and breast cancer risk in daughters: a Scandinavian population­based study. Journal of Developmental Origins of Health and Disease, Available on CJO 2012.

Human Study: OTC Supplement Doubles T-Levels & Boosts Erections More Than Tadalafil - Too Good to Be True?

Just to make sure you don't suffer from withdrawl symptoms until Adelfo posts the next update on his current contest prep, I thought I'd share a photo that shows where he is currently at - not bad for someone of whom a handful of you have been shocked to hear that he eats at least 200g carbs per day and ice-cream almost every evening, right?

It's Thursday and before I'll get to a question on a very recent study I received via the SuppVersity Facebook page, I will brief you on the line-up of today's installment of the SuppVersity Science Round-Up on the Super Human Radio Network. By now, most of you should actually be familiar with the modus operandi: In case you cannot listen live at 1PM EST, you can always download the show ~2h later either from the "Physical Culture for Your Ears" menu in the sidebar of the SuppVersity, or right over at www.superhumanradio.com - obviously, you can also wait for tomorrow's SuppVersity Science Round-Up Seconds, in which I am providing some additional information on things we have discussed and post selected topics that did not make it into the show.

Apropos topics, the first topic we are going to address does actually pertain to the second part of this post and revolves around a recently published paper by Fabrizio Iacono et al. whose results do - just as SuppVersity reader Mark, who pointed me towards this article, says - look "too good to be true".

Now, upon closer scrutiny it turns out that they may well be "true", but are not just as "good" as they may initially look like. From this testosterone-laden topic we are then going to proceed with topics revolving around male and female longevity, optimal workout types and intensities for different trainees,the health effects of garlic, colostrum and chocolate and related topics.

I could mention more, but am afraid that this will just increase the risk of rushing through the items too quickly. Optimally, you just tune in live and pick up the rest in "print" in tomorrow's SuppVersity Science Round-Up Seconds!

200% increase in total and 130% increase in free testosterone

Just a reminder: Taurine has also (rodent) data showing up to 180% increases in testosterone and that's not exclusively in the sick and old.

This subheading sounds as if I was to pimp the "revolutionary new testbooster" by "whatever company" that will get you muscular and ripped in no time, right? Well, in the end it could well be the text of an advertisement, yet not one from any of the usual suspects but rather one for TRADAMIX®, a blend of "three natural substances with an 'anti-aging' effect on the tissues of the male genitourinary apparatus" (Tradapharma Sagl. 2012) - I know, without the usual "-bols", "-diols", or at least some indirect references to illegal anaobolic substances in the product name, this does not sound like it would work, but the +200% increas in total and +130% increase in free testosterone are for real and documented in a peer-reviewed study involving seventy patients (67.3± 3.7 years) with stable marital relations and reduced libido, with or
without erectile dysfunction who received either the infamous PDE-5 inhibitor Tadalafil (5mg/day) or two servings of the aforementioned 'testicular anti-aging supplement' (Iacono. 2012).

But before we even get to the testosterone levels, let's tackle the main problem of these guys and the actual research interest of the scientists from the University “Federico II” of Naples in Italy first. After all, the main outcome of the study at hand were the improvements in sexual desire and erectile function and those were almost identical in both groups - from 16 to 33 and 16 to 31, in the supplement vs. drug groups, respectively. If you go by the results of the international index of erectile function (IIEF) questionnaire (see figure 1, left), on the other hand, the dietary supplement yielded actually outperformed the blockbuster prescription drug by almost 10%:

Figure 1: Results of international index of erectile function (IIEF) questionnaire and RigiScan (device to measure penile tumescence and rigidity continuously that's used to differentiate vascular from psychogenic erectile dysfunction) before and after 2 months of treatment with Tradamixina and Tadalafil (Iacono. 2012).

What's probably even more impressive, though, are the differential effects of Tradamixina vs. Tadalafil on the RigiScale values (see figure 1, right). The RigiScale is an etablished means to differentiate psychogenic from organ-related (vascular) erectile dysfunction (Basar. 2001) and the fact that there was a significant reduction of RigiScale positive subjects in the Tradamixina group does already suggest a possible reason for the initially mentioned 200% increase in total and 130% increase in free testosterone (see figure 2).

Figure 2: Total and free testosterone levels before and after the administration of Tradamaxine (2 servings per day) or Tadalafil (2mg/day) to Seventy patients (67.3± 3.7 years) with stable marital relations and affected by reduced libido for 2 months (data based on Iacono. 2012)

What this underlying reason is? Well, probably reduced systemic inflammation, which leads to reductions in cortisol, blood glucose, insulin resistance, oxidative damage to the testes etc. and thus simply facilitates the restoration of normal testosterone levels.

If you know how google works, it'll take you maybe 5 minutes and a credit card and you'll have a couple of pounds of the ingredients right on the way to your doorstep.
Yep, you heard me right: A boost of +200% just brought those guys who started with 10ng/dl below the already way too broad normal range from 260-1080ng/dl (values may vary from lab to lab) in a quasi hypogonadal state, back to midrange levels of 680ng/dl.

Real world implications for healthy young men: The chance that a healthy, fit individual with normal testosterone levels would see a boost of 200% in his total or 130% in his free testosterone levels is not low, it is simply ZERO!

Notwithstanding, Tradamixina (or rather its ingredients) is actually more than just a cilialis alternative. While the latter is a short term solution to get rid of the symptoms of an underlying disease, the combination of Ecklonia Cava, tribulus, and d-glucosamine + n-acetyl-d-glucosamine could actually tackle the most frequent cause of erectile dysfunction, which is the triad of inflammation, insulin resistance and arteriosclerosis (for more details see info-box to the right).

So how does this stuff work? Although investigations into the mechanism by which the provision of Tradamaxine did work its magic was actually not part of the study, it's actually not difficult to hypothesize what may be the underlying cause of these unquestionably astonishing results. Firstly, the brown algae Ecklonia Bicyclis (better known as Ecklonia Cava!)of which each serving has 150mg has a very high content of sterols, polyphenols and tannins and is probably the main active ingredient of a formula which includes 396mg of tribulus and 144mg of d-glucosamine and n-acetyl-d-glucosamine as a 'support'. The phlototannins 7-phloro eckol and 6,6′-bieckoll that have been isolated from Ecklonia, a marine brown algae which has been used for centuries in traditional medicine in Asia, are more or less unique with respect to the potency of their antioxidant activity (Li. 2009). In conjunction with tribulus, d-glucosamine and n-acetyl-d-glucosamine, which also exhibit a certain degree of anti-inflammatory activity, a decrease in systemic inflammation is the most likely cause of the profound pro-sexual and pro-hormonal effects of this blend, which is yet by no means as unique as the producers would have it.

Bottom line: It is no coincidence that erectile dysfunction has been identified as a "harbinger of cardiovascular clinical events" (Thompson. 2005) and "a sentinel event for CAD [coronary artery disease]" (Irekpita. 2009). So if you are in the unlucky situation to suffer from vascular (and not physogenic) erectile dysfunction, and had the choice between a drug that will ameliorate the symptoms, i.e. Tadalafil, or a supplement that will treat the underyling cause, the decision for the supplement and against the lifestyle drug should be obvious, right?

Still, there is one, ... no, actually there are two things I would like to ask you, before you run all spiked up to the next best supplement shop: Firstly, how accurate would you say is the authors' claim that there was "no conflict of interest", if no one else, but the lead author of the study, has been granted a patent on the formula on April 4th, 2012 (US2012/089722 A1)? And secondly, do you really believe that it is a mere coincedence that the researchers deliberate use the hardly known appellation Ecklonia Bicyclis for a brown algae all of you probably know as Ecklonia Cava (see "Ecklonia Cava Polyphenols Help Shed Weight Even in The Presence of a Slight Caloric Surplus") throughout the whole paper without mentioning once that it is better known as "Ecklonia Cava"? I am well aware that studies are expensive and need to be financed and I am by no means suggesting that the results are - as Mark suspected - "too good to be true" (remember. the men were hypogonadal to begin with), but this paper does still have a somewhat peculiar aftertaste.

References:

• Basar MM, Atan A, Tekdogan UY. New concept parameters of RigiScan in differentiation of vascular erectile dysfunction: is it a useful test? Int J Urol. 2001 Dec;8(12):686-91.
• Iacono F, Prezioso D, Illiano E, Romeo G, Ruffo A, Amato B. Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily. BMC Surg. 2012 Nov 15;12 Suppl 1:S23.
• Irekpita E, Salami TA. Erectile dysfunction and its relationship with cardiovascular risk factors and disease. Saudi Med J. 2009 Feb;30(2):184-90. 
• Li Y, Qian ZJ, Ryu B, Lee SH, Kim MM, Kim SK. Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava. Bioorg Med Chem. 2009 Mar 1;17(5):1963-73.
• Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005 Dec 21;294(23):2996-3002. 
• Tradapahrm Sagl. Tradamix. 2012 < http://www.tradamix.com/en/ > retrieved on 11/29/2012.

4g of Conjugated Linoleic Acid Promote CYP17A1 + Leydig Cell Testosterone Production and Increase Cardio-Mediated Muscle, Strength and Endurance Gains

"That's all the exercise in induced T-response, bro. Now shut up, I got to squat!"

Yes, this is another of those rodent studies of which we simply don't know if the results will eventually translate to humans. In contrast to previous studies on CLA, which dealt with weight loss and produced marvelous results (see "CLA Destroys Body Fat & Increases Endurance!" | read more) which could not be reproduced in human trials.

This very recent paper from Italy deals with CLA's effects on exercise, testosterone, and potential gains in muscle mass and leaves the parameter body fat out of the equation (Barone. 2013).

"Hold on, that's not news, is it?"

When Roy Nelson shot me the link to the pertinent paper by Rosario Barone et al. (2013), the above, i.e. "Hold on, that's not news, is it?" was actually my first thought. After all, I had written about the purported muscle building effects of CLA in the past (see "Review Claims: CLA & Fish Oil Improve "Anabolic" Effects of Exercise - What Does the SuppVersity Sniff Test Say?" | read more). After briefly checking my previous article, I did realize, though: This is news!

The previous article did not discuss the same results. It did however come from the same team of Italian researches and made the claim that CLA & fish oil would be natural anabolics (read it!) - a claim I reviewed and wrote:

"[...] as far as ergogenic and/or anabolic effects are concerned, CLA is unquestionably the more promising fatty acid off the "two" (actually we are talking about four fatty acids, here: DHA + EPA = fish oil and cis-9,trans-11 and trans-10,cis-12 CLA)." (SuppVersity. 2013)

I have to admit, though, that I was thinking of CLA's ability to block the storage of body fat on a bulk, primarily - not so much about its not yet fully, but at least half-way established effects on exercise performance. The testosterone boosting effects, on the other hand, were something I discarded, so that it's about time to look at them more closely.

In vitro + in vivo - that's the way Barone et al. did it

In a first attempt to access the effects of CLA on the testicular androgen production, the scientists from the University and Hospital of Palermo conducted a couple of tests in the petri dish. Usually boring stuff, if it were not for geeks like me (and some of you) who always ask the nasty question: "Why".

Figure 1: The same research group published a paper that showed increased testosterone in young men on a resistance training regimen. It is therefore not totally unlikely that the results do translate to human beings; the figure shows the total testosterone before vs. after a workout in ng/dl (Macaluso. 2012)

In this case, we are lucky, because Barone et al. did not focus solely on the amount of steroids the the leydig tumour cells (don't worry that should work with regular cells, as well) were spilling out. They also tested for enzymatic changes and observed that as 17α-hydroxylase/17,20-lyase (CYP17A1), which converts progesterone into androstenedione and has  been demonstrated to have direct downstream effects on the testosterone production (Svechnikov. 2009; Weisser. 2011).

As every SuppVersity reader knows, the cytochrome P450 enzyme cascade is on of the most powerful and overlooked actors in the steroid orchestrate. While CYP17A1, which does effectively increase the production of testosterone pre-cursors and will thus exert an indirect beneficial effect on the testosterone production, other members of the cytochrome family facilitate the conversion and clearance of testosterone.

Against that background it was sound to expect to observe similar effects in the in-vivo part of the study. The interplay with other enzymes, however, could easily have thwarted the results. Outside of the petri dish the sheer number of variables that could change the outcome of the study makes it more or less impossible to predict the "exact" study outcome and - I want to emphasize this - the latter could well look slightly or completely different from what you see in Figure 2, when you went ahead and tried to support your training efforts with 4g of the patented Tonalin® FFA 80:

Figure 2: Free testosterone and CYP17A1 expression in the supplemented (CLA-) /  unsupplemented (PLA-) mice after 6 weeks of no (SED) or 15-60min (ramp up) of exercise 5x per week (Barone. 2013).

I hope you did notice the important hint I hid in the last sentence above Figure 2, where it says: "Support your training efforts..." If you didn't take a look at Figure 2 ... I guess, it's obvious to see that this short insert is of paramount importance: No training, no CLA bonus!

"The protein expression of CYP17A1 was significantly higher in both the trained groups (PLA-TR and CLA-TR) compared to the sedentary groups (PLA-SED and CLA-SED) (P <0.01). Moreover, CLA supplementation induced a further increase in CYP17A1 protein in the CLA-TR group compared to the PLA-TR group (P < 0.01)" (Barone. 2013)

In other words, training alone is a CYP17A1 powered testosterone booster and CLA is an adjuvant, which has no effect in the absence of 6 weeks with five "cardio" sessions/week at an ever-increasing pace and duration (15-60min and 3.2-4.8m/min from week 1-6).

Figure 4: Body weight gain, and force/body weight gain  (in %; top) and distance traveled relative to SED-PLA group (Barone. 2013)

"Wow that's exciting, isn't it?" Actually no - not really. The increase in testosterone alone would hardly be worth the paper this article is probably never going to be printed on. What is at least borderline exciting, though, are the increase in muscle gains, strength and running distance the rodents covered in a standardized test (see Figure 3).

Yeah, I have to admit: The data does look exciting, but that can be said of the previously referenced study by Macaluso, as well. The said human trial (see Figure 1), however, tells us that it's probably unrealistic to expect similarly pronounced effects with even more CLA (6g in the Macaluso study from 2012) in men.

Personally, I would save the money, but if you want to try it: Go ahead... and tell us if it works ;-)

I, for my part, am missing anecdotal evidence (You can't tell me that there is no one who has tried that already - so where are the "CLA is king, bro!" posts on the various boards?), the confirmation of this or at least similar effects by other scientists and a 'Conflict of Interest' declaration at the end of a paper that puts such an emphasis on the "®" in  Tonalin® FFA 80.

References:

• Barone, R, Macaluso F, Catanese P, Marino Gammazza A, Rizzuto L, et al. Endurance Exercise and Conjugated Linoleic Acid (CLA) Supplementation Up-Regulate CYP17A1 and Stimulate Testosterone Biosynthesis.  PLoS ONE 8(11): e79686.
• Macaluso F, Morici G, Catanese P, Ardizzone NM, Marino Gammazza A, Bonsignore G, Lo Giudice G, Stampone T, Barone R, Farina F, Di Felice V. Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise. J Strength Cond Res. 2012 Jun;26(6):1667-74.
• Svechnikov K, Spatafora C, Svechnikova I, Tringali C, Söder O. Effects of resveratrol analogs on steroidogenesis and mitochondrial function in rat Leydig cells in vitro. J Appl Toxicol. 2009 Nov;29(8):673-80.
• Weisser J, Landreh L, Söder O, Svechnikov K. Steroidogenesis and steroidogenic gene expression in postnatal fetal rat Leydig cells. Mol Cell Endocrinol. 2011 Jul 20;341(1-2):18-24. doi: 10.1016/j.mce.2011.03.008.

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.

40% Increase in Total + 50% Increase in Free Testosterone - Two Not Necessarily Undesirable Side Effects of Sildenafil. Human Study Confirms Direct Effect of PDE-5 Inhibition

Either you buy one of the bazillion OTC test-boosters that will not do anything for your testosterone levels, but may have minimal effects on your libido; or, you get a script for the blue pills and accept that one of the side-effects of these proven libido-boosters is an increase in testicular testosterone production.

If you were all Germans, I would probably be cracking a joke about the lead author's name "Spitzer", but in view of the fact that you aren't and that it would be a saucy one I will stick to the news-piece alone - it's saucy enough, anyways ;-)

Actually you've heard Carl and me talk about the purported testosterone boosting effects of sildenafil aka Viagra on the Science Round Up in the past, but Mr. Spitzer and his colleagues from the Greenfield Health Center are the first to prove the potency of the testosterone response in male subjects who received "an optimized dose" (more on that later) of sildenafil, as well as its "direct action on the testes" in a controlled larger-scale trial (Spitzer. 2013).

More than just "spitz" (engl. "horny")

The data Matthew Spitzer et al. analyzed came from the Testosterone and Erectile Dysfunction Trial in the course of which 140 men, aged 40–70 years with erectile dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free testosterone (<173 pmol/L; 50 pg/mL) over received starting doses of

• 25mg sildenafil, if they were on an alpha-blocker
• 50mg sildenafil, if they never used sildenafil before, and
• 100mg sildenafil, if they were viagra veterans

for  3–7 weeks. The men in the 25mg and 50mg groups had the chance to increase the dosage to up to 100mg "on occasion"; or, in other words, when their sexual desire did not match their physical function.

Figure 1: Changes of testosterone and other hormones rel. to baseline level (Spitzer. 2013)

As you can see in Figure 1 the ingestion of a handful of the infamous blue pills lead to significant increases of in total (+3.6 nmol/L = 103 ng/dL; p<0.001) and free (+110 pmol/L = 31.7 pg/mL; p<0.001) testosterone levels and were accompanied by parallel increases in serum DHT (0.17 nmol/L = 4.9 ng/dL; p<0.001) and oestradiol (14 pmol/L = 3.7 pg/mL; p<0.001) and significant suppression of luteinizing hormone (change 1.3 units/L; p=0.003) levels.

The latter, i.e. the reduced luteinizing hormone levels are what actually suggests that we are dealing with a direct effect at the testicular level and not some weird hyptohalamic feedback. A centrally mediated in crease in testosterone production would after all have gone hand in hand with in- not decreases in luteinizing hormone concentration.

Minimal changes in adrenal hormones

With small, but noticeable increases in androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p=0.011) and 10.7 pmol/L (2.9 pg/mL; p=0.012), Spitzer et al. cannot exclude that the sildenafil induced phosphodiesterase-5 inhibition did also affect the adrenal glands - or, to be precise, "late adrenal androgen synthesis" (Spitzer. 2013):

Gingko = Brain Viagra?

"The adrenal glands are the major site for production of androstenedione, which is converted to oestrone by aromatase. Enzyme 17,20 lyase, which converts 17a-hydroxyprogesterone to androstenedione, is upregulated with sildenafil treatment in rats.

This could explain the increase in serum androstenedione levels in our participants. However, an increase in 17,20-lyase activity should also result in an increase in DHEAS levels, which was not observed. Further investigation is needed to study the effect of sildenafil on adrenal androgens." (Spitzer. 2013)

While the exact mechanism that's responsible for the androstenedione increases must still be determined, it is, as previously mentioned, almost certain that the increase in testosterone levels was mediated by direct effects on the steroidigenic leydig cells in the testes. They are the ones that respond to the luteinizing hormone signalling from the brain have been reported to respond directly to PDE-5 inhibitors in previous studies by Andric et al. from 2007 & 2010, as well as Janjic et al. from 2012.

More sex = more testosterone?

Whether and to which extend the increase in testosterone has also been indirectly promoted by increases in sexual activity, which have been previously reported to lead to increases in testsosterone levels after successful treatment of erectile dysfunction (Aversa. 2013) remains to be seen. The data from the study at hand does at least not support this notion, because a "greater sexual activity did not predict greater change in serum total testosterone" (Spitzer. 2013).

Other studies have associated greater sexual arousal with acute increases in LH and subsequent increases in testosterone production (LaFerla. 1978; Rowland.1987). With decreasing not increasing LH levels being one of the main findings of the study at hand, it is however more or less impossible that the increased sexual desire was the horse, not the cart in the sildenafil-related increases in testosterone levels Spitzer et al. observed in their 140 borderline to full-blown hypogonadal man.

SuppVersity Suggested Read: "Will Sex Before a Competition Hamper Your Performance? Plus: How Can Estrogen, Cortisol, Quail and Muhammad Ali Help Us Answer This Important Question" | read more

Bottom line: It appears to be settled that it is the direct effect of PDE-5 inhibition on testicular testosterone production that's responsible for the Viagra induced increases in testosterone production. What is not settled, though and I guess that is something people tend to forget about, when they hear promising study results like  these is that the benefits were observed in a men whose testosterone production was already impaired.

In fact, the researchers' acknowledgment that "some portion of the observed increases in testosterone occurring during sildenafil administration is almost certainly attributable to regression to the mean" (Spitzer. 2013) would suggest that similarly pronounced effects cannot necessarily be expected in men with normal testosterone levels... but hey, the same goes for 99.9% of the OTC "test boosters" and people still buy them despite the fact that they do not even have produce those "nasty" boners as a side effect ;o)

References:

• Andric SA, Janjic MM, Stojkov NJ, Kostic TS. Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway. Am J Physiol Endocrinol Metab. 2010 Oct;299(4):E544-50.
• Aversa A, Jannini EA, Maggi M, Lenzi A. Effects of testosterone replacement on response to sildenafil citrate. Ann Intern Med. 2013 Apr 2;158(7):569-70.
• Janjic MM, Stojkov NJ, Bjelic MM, Mihajlovic AI, Andric SA, Kostic TS. Transient rise of serum testosterone level after single sildenafil treatment of adult male rats. J Sex Med. 2012 Oct;9(10):2534-43.
• LaFerla JJ, Anderson DL, Schalch DS. Psychoendocrine response to sexual arousal in human males. Psychosom Med. 1978 Mar;40(2):166-72.
• Rowland DL, Heiman JR, Gladue BA, Hatch JP, Doering CH, Weiler SJ. Endocrine, psychological and genital response to sexual arousal in men. Psychoneuroendocrinology. 1987;12(2):149-58.
• Spitzer M, Bhasin S, Travison TG, Davda MN, Stroh H, Basaria S. Sildenafil increases serum testosterone levels by a direct action on the testes. Andrology. 2013 Nov;1(6):913-8.

Cordyceps Sinensis - Another Supplemental Non-Starter: Human Data Shows No Increase in Testosterone, No Strength Gains, No Improvements in Body Composition.

Image 1: As it turns out it's not necessary you start eating parasites (img nepaliproducts.com)

In view of the public attention adaptogens have gotten, ever since everyone is self-diagnosing him- / herself with "Central Fatigue Syndrom", I assume you will be aware that the parasitic fungus, Cordyceps sinensis (CS) that is found on larvae of Lepidoptera, and has been used for centuries in traditional Chines medicine as a tonic, has lately been marketed as powerful modulator of the hypothalamus-thyroid-pituitary axis (HTPA). Extracts from cordyceps have in fact been shown to have various biological and pharmacological actions on the liver, the kideys, the endocrine and the vascular system. It appears to stimulate erythropeoiesis (production of red blood cells) and haemopoiesis (formation of blood cellular compounds), and it exhibits immunomodulatory and anti-tumor activities.

Within the health and fitness community Cordyceps sinensis has yet been touted as "natural HCG" (human chorionic gonadotropin), because, just like the latter, it stimulates the release of luteinizing hormone and thus testosterone secretion in rodent models (mice and rat; cf. Huang. 2001; HSU. 2003; Huang. 2004). Not long ago, scientists have identified cordycepin as the active ingredient in the parasite extract - an ingredient, which, according to Pan et al., does not only stimulate steriodogenesis, but also exhibits anti-cancer effects by inducing apoptosis in MA-10 mouse Leydig tumor cells (Pan. 2011).

Illustration 1: Training protocol the subjects in the study performed  3x à week for a total of 8 weeks.

With its endocrine and haematopoietic effects, cordyceps looks like the perfect substitute for what you may call the "Tour de France performance package", i.e. the combination of testosterone (e.g. Landis) and erythropoietin (e.g. Riis). Consequently, one should expect that an 8-week (3 training sessions per week)randomized double-blind place-controlled study with sixteen previously not resistance-trained young volunteers (male, age: 19-25; BMI: 24kg/m²; body fat: 14.65%), like the one performed by Hsu et al. at the Graduate Institute of Sports Science at the National Taiwan Sports University, should show at least some measurable effects on strength and muscle gains and/or body composition of the subjects.

Figure 1: Muscle strength as maesured by 1RM after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

Figure 1, however, shows no greater strength improvements in the Cordyceps sinensis (6 caps à 400mg of an extract containing 0.33% soluble protein, 5.81% sugars, 5.92µmol/g adenosine derivatives (5.92 µmol/g), 1.23µmol/g cordycepin and 8.81 µmol/g ergosterol) supplemented strength trainees (CS) compared to the subjects in the placebo group (PL). And even the +7% greater increase in 1RM strength on seated rows does not reach statistical significance.

Figure 2: Changes in body composition after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

Similarly, the cordyceps supplement had no measurable beneficial effects on the accrual of lean or the loss of fat mass in the course of the 8-week strength training protocol (cf. figure 2). Although statistically non-significant, the subjects who received the CS supplement did in fact lose some lean mass and gain some fat mass... certainly not what you would have expected from the purchase of a "testosterone boosting adaptogen"!?

Figure 3: Testosterone levels after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

A pros pos "testosterone boosting", as the data in figure 3 clearly shows, there was a "boost", but the latter was identical between groups and - as the body composition data in figure 2 shows - the placebo group, whose baseline testosterone levels were 7% lower than those of the subjects in the CS group, took greater advantage from this probably exercise-induced and in view of the diurnal fluctuations of serum testosterone statistically non-significant increase.

Figure 4: Changes in serum levels of BUN, Creatinine, ALT and AST after 8 weeks of strength training with (CS) and without (PL) Cordyceps sinensis supplementation (data based on Hsu. 2011).

It would be unfair though to say that the ingestion of 2.4g of Cordyceps sinensis was totally pointless. After all there was a non-negligable decrease in the purported "liver values" ALT and AST. Now, as a diligent reader of the SuppVersity you are among the few chosen ones who outsmart 99% of the general practitioners and know that the enzymes ALanine Transaminase (ALT) and ASpartate Transaminase (AST) are by no means "liver values", i.e. liver-specific. In fact, their elevation in hard training athletes is completely normal and an indicator of muscular, not hepatic, damage, as both, ALT and ALT, are expressed in skeletal muscle, as well (Petterrson. 2007). This does not change that - once again - beneficial effects that have repeatedly been observed in rodent studies did not translate to humans, but it could explain why Quinc, senior member on the Mind and Muscle Forum and a true believer in the potency of cordyceps maintains:

I can't say I have noticed any 1RM gains, but I have noticed a quicker recovery time between sets and more endurance. (Quinc. 2011)

In view of the beneficial effects on the amino acid transferase enzymes, it may well be that the scientists just measured the wrong parameters. If their subjects had participated in the Tour de France, it could well be that the CS group had survived a few kilometers more, before they had had to be picked up by one of the team vehicles ;-)