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marylin monroe
Showing posts with label testosterone. Show all posts
Showing posts with label testosterone. Show all posts

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.

Natural Sildenafil & Testosterone Alternatives: Pedalium Murex & Paederia Foetida +150% Testosterone and +200% Erectile Function. Plus: Icariin, Aromatase & Stronger Bones. Probiotics, Phytosterols & Thyroid Activity.

If the Aliens have seen these Bugarash apocalypse pilgrims, they have probably turned tail and fled ;-)
I guess the SuppVersity figure of the week was a date "12/21/2012", I mean this is a once in a life-time event! Or do you really believe there will be another chance for mankind to be snatched from the jaws of extinction?

Ok, enough of the sarcasm, the world is still there and the SuppVersity is still operating, so let's get to the not so short On Short Notice items for today.

If there had been more room in the headline I would probably have labeled it "Endocrine Special" and I guess once you have gone through the posts, you will agree that this would certainly have made sense.

  • Traditional treatment of osteopenia with Epimedium brevicornum works, 'cause it's a potent aromatase promoter (Yang. 2012) -- When a group of researchers from the Chengdu Institute of Biology, Chinese Academy of Sciences and the School of Chinese Pharmacy, Chengdu University of Traditional Chinese Medicine in Chengdu, China, set out to investigate the mechanism behind the anti-osteoporotic effects of the dried leave extract from Epimedium brevicornum, they already suspected that it would probably be related to some sort of endocrine modulation.

    Figure 1: In vitro effect of Forskolin and Icariin on aromatase expression in KGN cells (Yang. 2012)
    With estrogen deficiency being the major cause of osteoporosis, a disease which does by the way affect over 200 million people worldwide (Riggs. 1998), being their the most likely mechanism behind the bone building and bone mineral density (BMD) protective effects, it was obvious to study, whether there was some sort of interaction between the extract and the data in figure 1 shows that Yang et al. were right to do so (note: the cell line used in the study was a KGN granulosa cell that's closely associated with the developing female oocyte, so effects could vary from one tissue to the other)

    Now all that certainly sounds as if this was bad stuff no sane male human being should be taking. Luckily, for many of you, my fellow men, who may have been exposed to Epimidium / Icariin from various supplements, this is not the case. Why? Simply because estrogen is not the enemy and Epimidium has not only been found to have anti-aging effects (whole extracts; Yan. 2009), it also prevents neurotoxicity from beta-amyloid plague the key feature of Alzheimer's and similar diseases (Zeng. 2010; listen to Thursday's Science Round-Up for other amyloid beta inhibitors / protectant's) and the neurotoxic effects of excess corticosteroids (Liu. 2011). In addition, Epimidium pubescen flavenoids have been shown to reverse the negative effects even passive exposure to cigarette smoke may have on the bone mineral density of male rats (Gao. 2012) and Icariin the common denominator in all of the members of the Epimidium family exerts direct proliferative and thus pro-fertility effects on the sertoli cells in male rodents (Nan. 2012).

    Table 1: Analysis of Chinese Epimidium species (MDida. 2010)
    Ah, and last but not least the beneficial effect Horny Goat Weed (likewise one of the members of the Epimidium family) has on male libido are likely partly a result of the increased aromatase activity, as well. If it works for you, your estrogen levels are probably pretty low to begin with (this reasoning is based on the profound beneficial effects of estrogen on male libido in men expressing little to no aromatase enzyme; Carani. 1999).

  • Pedalium murex Linn. fruits may not be as potent acute libido and erectile performance enhancers as sildenafil, but the effects accumulate and persist just as its unique testosterone boosting effects (Sharma. 2012) -- In case taking a potential proestrogenic compound like Horny Goat is nothing you feel would do anything good for your libido, you may want to use some Pedalium murex Linn. in traditional Indian medicinea herb that has been used in traditional Indian medicine for centuries to treat male sexual dysfunction and impotency.
    Figure 2: Effects of different doses of an ethanolic extract from Pedalium murex (P.m.) and Sildenafil citrate (5mgkg) on penile erection scores and post ejaculatory interval (time it takes to be able to have sex again) exrpessed relative to saline treated control (based on Sharma. 2012)
    As the data in figure 2 shows, its effects on erectile performance are slightly less pronounced than those of sildenafil citrate, but at an appropriate dosage and after some time, it will probably do its job sufficiently for most men with respective problems. What's really exiting though, is that the data in figure 3 clearly shows that it does so not by simple nitric oxide effects (P. murex at 10 mg/
    ml exhibited a relative nitric oxide release of 15.3 mM as compared to a nitric oxide release of 39.3472.7 mM with sildenafil citrate), but probably (also) by boosting testosterone levels. 

    Figure 3: Serum testosterone levels during and after Pedalium murex or Sildenafil citrate administration expressed relative to saline control (Sharma. 2012)
    Since the testosterone levels remained elevated for 14 days after the treatment was seized these observations make P. murex a potential candidate for the next best natty test booster.to be powered by advertisement lines like "up to 125% increase in testosterone that last for more than 2 weeks" even when you take some time off. I guess, the only serious downside here is the close relation of P. murex to the notoriously useless Tribulus, which does also contain furostanol glycosides. Luckily Magnle and Jolley found another potentially active ingredient in P. murex fruit. The compound goes by the name diosgenin and appears to be a direct precursor for the synthesis of sex hormones including testosterone (Mangle. 1998).

    Since I don't think you will have to wait very long until the first major players in the supplement business will jump on this bandwagon - you know that a single rodent study is enough to make fortune until people realize that this stuff does not work, at all - you will probably soon be able to test it on yourself. In case you intend to do that, you should certainly look for a standardized ethanolic extract with ~20%+ of diosgenin (that was the content of the extract Sharma et al. used) and a serving size of 16.2mg/kg per body weight, the HED of the 100mg/kg group (that would be 1,300mg /day of the extract for an 80kg adult).

  • Paederia foetida Linn. (P. foetida) yet another Indian libido and testosterone boosting herb (Soni. 2012) -- If you like the appeal of exclusiveness a climbing plant found in the Central and Eastern Himalayas, at elevations of up to 5000 ft, you may prefer the an ethanol extract of Paederia foetida Linn. (P. foetida) leaves over the previously discussed Pedalium murex fruit extract.

    Figure 4: Penile erection index and testosterone levels of rats after 15 and 28 days on P. foetida, data expressed relative to saline control (Soni. 2012)
    According to a recent study from the same group of Indian scientists (yet a different lead author), the effects of P. foetida and P. murex are in fact virtually identical. While the general protocol was very similar (in this done on rat, not mice) the positive control was not Sildenafil citrate, as in the previously mentioned experiment, but an intramuscular injection of 0.5 mg/kg body weight of testosterone suspension in arachis oil twice a week. It's actually a pity the scientists didn't measure the actual testosterone levels in the animals in the testosterone group. I would be curious how the 2.5x increase in the high dose group (200mg/kg, human equivalent ~2,600mg/day) would compare. When it comes to the erection quality, it did at least easily top the results of injectable testosterone (see figure 4), which is yet allegedly not the best erection booster, anyway. And if we went by the data on body weight and the weight of the testes, seminal vesicles, prostate glands and epididymis, it even appears to be more anabolic than testosterone; after all the body weight gain in the PF groups were 15%. 23% and 34% higher than in the control group and comparable if not higher to those that were induced by testosterone (+29%).

    And for all the supplement producers and fans of stacks it may be important to know that the leaves of P. foetida, which is also used as carminative, antiinflammatory, astringent, spasmolytic, antidiarrhoeal, diuretic and antilithic do contain a whole host of well- and lesser known compounds, e.g. iridoid glycosides, sitosterol, stigmasterol, campesterol, ursolic acid, hentriacontane, hentriacontanol, ceryl alcohol, palmitic acid and methyl mercaptan, but no diosgenin. So Ayurvedabol (TM) or whatever name ending on -bol, -drol or -ripp-off has not been used by the creepy competition, already, could benefit from having both Paederia foetida and Pedalium murex in it ;-)

  • Combination of probiotics and phytosterols ramps up thyroid function and (re-)establishes a healthy lipid profile (Awaisheh. 2012) -- While I could offer you a minimum of two additional libido enhancing, potentially pro-anabolic testosterone booster, I know that not all of you are into these products (am I right ladies?), so I thought it prudent to close this installment of On Short Notice with a study on thyroid metabolism, which could be is of interested for all of you.

    Which phytosterols are there and where can I find them? The major phytosterols in the human diet are sitosterol (high in nuts, amaranth, avocados, grape leaves), stigmasterol (high in coriander, chocolate and soy), campesterol (high in various vegetable oils, spec. conola / rapeseed) and brassicasterol (high in cabbage, broccoli, other brassica, but also coriander, seafood and rapeseed oil).
    Contrary to some previous studies and anecdotal reports on the Internet, a recent paper by scientists from the Department of Food Science at the Al-Balqa Applied University, in Salt, Jordan, suggest that phytosterols don't have thyroid inhibiting, but promoting effects.

    In their latest study Awaisheh et al. investigated the effects of a probiotic stack containing two strains of each of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus reuteri and a phytosterol supplement on the lipid metabolism in rodents. Their results show that the addition of the phytosterol supplement promoted the already pronounced effects the probiotics had on the hypercholesterolemia of the rodents who were fed with a high-fat-high-cholesterol basal diet for 8 weeks. In addition, the phytosterols, yet not the probiotics alone, elevated the levels of serum total thyroxine (TT4), total triiodothyronine (TT3), and free triiodothyronin (fT3), which could have exerted additional benefits on the non-measured triglyceride levels.

    These results do actually come as a surprise and I would like to see more research - specifically in human trials - before I would buy products from producers who seize the scientists suggestion that this renders probiotics and phytosterols potential candidates for "functional foods" - I mean, let's be honest ever since the first "functional foods" hit the market people have been getting sicker: Do you really believe that's because they don't eat the "good" cholesterol lowering margarine instead of their beloved Kerrygold butter? I don't think so.

That's it for today.. well, aside from the promise to include the other testosterone and libido boosting herb studies in another SuppVersity post and a selection of the latest  SuppVersity Facebook News, of course:
  • Iron deficiency makes H Pylori go on a rampage - Iron deficiency enhances H. pylori virulence and increases risk of gastric cancer (read more)
  • Danish folk medicine for depression? Not really, but there are a couple of promising natural MAO-A inhibitors the Danes have been using for centuries (read more)
  • Strength training equally heart healthy as aerobics - 6-weeks of strength training show particular beneficial effects in African American men (read more)
Since I it's still pretty early and I am certainly not going to the city, before the shops close and all the people who believed they wouldn't need Christmas presents this year, since the world would *put whatever apocalyptic catastrophe you like here*, have gone home, I may be adding some more news later. Until then, I hope you have some fun with what's already there and are looking forward for the 2nd installment of the "Making HIIT a Hit" series that will be published tomorrow.

    References:
    • Awaisheh SS, Khalifeh MS, Al-Ruwaili MA, Khalil OM, Al-Ameri OH, Al-Groom R. Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats. J Dairy Sci. 2012 Nov 22.
    • Carani C, Rochira V, Faustini-Fustini M, Balestrieri A, Granata AR. Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency. Clin Endocrinol (Oxf). 1999 Oct;51(4):517-24.
    • Gao SG, Liu H, Li KH, Liu WH, Xu M, Jiang W, Wei LC, Zhang FJ, Tian J, Xiao WF, Yang Y, Song Y, Lei GH. Effect of Epimedium pubescen flavonoid on bone mineral density and biomechanical properties of femoral distal end and femoral diaphysis of passively smoking male rats. J Orthop Sci. 2012 May;17(3):281-8.
    • Liu B, Zhang H, Xu C, Yang G, Tao J, Huang J, Wu J, Duan X, Cao Y, Dong J. Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons. Brain Res. 2011 Feb 23;1375:59-67. 
    • Mangle MS, Jolley CI. HPTLC studies on Tribulus terrestris (Chota ghokru) and Pedalium murex (Bada ghokru). Indian Drugs. 1998; 35:189–194.
    • MDidea Extracts Professional. Horny Goat Weed or Epimedium Herb: Botanical Origin, Archeology, Traditional and Pharmacological findings of Epimedium species, fractions and isolated components. 08th, Oct. 2010. < http://www.mdidea.net/products/herbextract/icariin/data10.html > retrieved on 12/21/2012. 
    • Nan Y, Zhang X, Yang G, Xie J, Lu Z, Wang W, Ni X, Cao X, Ma J, Wang Z. Icariin stimulates the proliferation of rat Sertoli cells in an ERK1/2-dependent manner in vitro. Andrologia. 2012 Nov 7.
    • Riggs BL, Khosla S, Melton LJ 3rd. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998 May;13(5):763-73. 
    • Sharma V, Thakur M, Dixit VK. A comparative study of ethanolic extracts of Pedalium murex Linn. fruits and sildenafil citrate on sexual behaviors and serum testosterone level in male rats during and after treatment. J Ethnopharmacol. 2012 Aug 30;143(1):201-6.
    • Soni DK, Sharma V, Chauhan NS, Dixit VK. Effect of ethanolic extract of Paederia foetida Linn. leaves on sexual behavior and spermatogenesis in male rats
    • Yan S, Wu B, Lin Z, Jin H, Huang J, Yang Y, Zhang X, Shen Z, Zhang W. Metabonomic characterization of aging and investigation on the anti-aging effects of total flavones of Epimedium. Mol Biosyst. 2009 Oct;5(10):1204-13.
    • Zeng KW, Ko H, Yang HO, Wang XM. Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology. 2010 Nov;59(6):542-50.

    Science Round-Up Seconds: Nicotine's Effect on Brain Aromatase & the Consequences, 2D:4D Digit Ratio Predicts Testosterone Response to Sprinting and All the Anti-Obesity & Pro-Brain Effects W/ Just 2 Cups of Coffee per Week?

    Wallaby Lachie Turner (left), Greg Inglis (centre) & Jarryd Hayne (Stuff.co.nz) - who would have thought that the relative length of their 2nd and 4th digit could predict their testosterone response after the sprint? Not you? Well, then you got to check out the first of the short-items at the bottom.
    Those of you who have listened to yesterday's installment of the SuppVersity Science Round-Up on Super Human Radio, will have realized that the show did - as usual - take a somewhat different direction than originally planned. Before I get to the actual SuppVersity Round-Up Seconds, of which there actually weren't all too many I consider absolutely newsworthy and appropriate for a written format, I thought I would briefly mention the paper on which I based the hypothesis (remember: this is nothing certain) that there may be a link between the calcium-influx into the muscle and the strength and hypertrophy effects of performance enhancing drugs (spec. those with a high anabolic : androgenic effect ratio) - for those of you who may want to follow up on this hypothesis or think Carl and I were just making things up ;-) 

    The study I refer to shortly after the last break (download the podcast), was conducted by a group of researchers from the Instituto de Ciencias Biomedicas at the Universidad de Chile in Santiago de Chile, dealt with the modulatory effects of testosterone (and aldosterone) on intracellular calcium response in skeletal muscle cell cultures and not the subsequent consequences on contractile force of hypertrophy and could thus only serve as a point of departure for future investigations to either confirm or refute this idea (Estrada. 2010).

    Nicotine exposure, brain aromatase and gender-specific implications

    With the advent of new technologies, esp. the direct observation of aromatase activity in primate brains (Lidstrom, 1998; Kim, 2009; Biegon, 2010), our understanding of the peripheral effects of certain substances on hormone metabolism, one of the latest such insights pertains to the effects of nicotine exposure on the expression of the aromatase enzyme in the brain.
    Figure 1: Effect of nicotine on brain aromatase availability in the female baboon. Representative baseline PET image coregistered with MRI at baseline and following injection of low dose (0.015 mg/kg) or high dose (0.03 mg/kg) nicotine. PET images show averaged frames acquired between 52.5 and 90 min after tracer injection, pseudocolored using the rainbow spectrum, with purple indicating the lowest density and red indicating the highest density of radioactivity (from Biegon, 2010).
    In a recently published paper scientists from the Brookhaven National Laboratory Upton in New York did now connect the dots between the previously observed direct inhibitory effects on the central expression of the CYP19a mediated expression of the aromatase enzyme of nicotine and (potentially) other tobacco alkaloids. Thus, Anat Biegon, Nelly Alia-Klein and Joanna S. Fowler are not only able to explain, why women are more susceptible to the addictive effects of the nicotinic acetylcholine receptor agonist, which accumulates in the leaves of several members of the Solanaceae (nightshade) family, than men, but observations such as the early onset of menopause and lower plasma estrogen levels and correspondingly higher osteoporosis risk in female smokers compared to their non-smoking peers, as well (Daniell. 1972; MacMahon. 1982; Nusbaum. 2000; Pant. 2008; Korkor. 2009).

    Table 1: Comparison of the effects of nicotine exposure and the effects of an aromatase inhibitor (at different time points in life) on sexual behavior, anxiety and depression, hot flashes, and weight gain in men and women (Biegon. 2012)
    The scientists also list a couple of other ascertained side-effects pertaining which are equally important to men and women: The sexual behavior for example has been shown to drop both in response to prenatal, as well as acute nicotine exposure in male mammals - something those of you who happen to have a prescription for an aromatase inhibitor as an adjunct to their TRT regimen and did not hit the sweet spot between too much and too little estrogen, will certainly be aware of. While anecdotal evidence clearly points into that direction the scientific consensus on the negative impact of aromatase inhibitors on male libido in men (not male rodents), is however not yet clear. Personally, I believe this is partly due to the fact that pertinent studies usually deal with subjects who reduce their estrogen levels to normal, which could in fact lead to increased testosterone and DHT level in the absence of any negative side effects on the patients' libido.

    If you take a look at the overview in table 1, you will however realize that other effects as the anxiolytic effects of acute nicotine exposure in adult women or the weight loss effect (which is certainly another reason women like to smoke) stand in direct opposition to the hypothesis that the majority of nicotines beneficial and negative side-effects were mediated by its effects on the aromatase enzyme. Fortunately, for most smokers, this appears to apply to the pro-Alzheimer's effects of low brain aromatase (Hiltunen. 2006), as well - at least, if we go by the conflicting results of the latest epidemiological studies, which contradict earlier findings that did even suggest that smokers would have a lower risk of Alzheimer's disease.

    Alzheimer's, dementia, etc. are yet only examples of the far reaching effects brain aromatase and its regulation by nicotine and other substances such as aromatase inhibiting drugs, but also all sorts of environmental toxins with endocrine side-effects could have - so you can easily expect more interesting study results in the future.

    Other news that did not make it into the show

    As I have mentioned in the introduction, we did cover a hell lot of ground, so that most of the other studies are directly related to the luteinizing hormone negative feedback and thus no real "news" - I skipped discussing those, since I though that everyone listening will get the main message and did not want to bore those of you who are not interested in this topic with a show solely on the effects of nutrient deprivation and exercise on the endocrine milieu. But enough of the excuses, there is still more:
    • Right-left digit ratio (2D:4D) predicts testosterone response to exercise in 79 professional Rubgy players (Kilduff. 2012) - In the analysis, researchers from the Swansea University at the Sports Science, Talbot Building in Singleton Park,  Swansea, UK, found that despite significant differences in basal testosterone levels, the 2D:4D ratio, which is generally regarded as an indicator of in-utero androgen exposure was significantly associated with a lower testosterone response to repeated sprint-agility tests in the 25 subjects who participated in the active arm of the study.
    • Caffeine prevents weight gain and cognitive impairment by high fat diet (Moy. 2012) - This is not news? Just read on, you will soon realize that it is news! Firstly, the scientists from the University of Albany identified an ameliorative effect of caffeine on the diet-induced reduction of hippocampal expression of the brain-derived neurotrophic factor (BDNF) as the underlying mechanism behind it's neuroprotective effect (the same stuff that's also increased by exercise, by the way).

      Figure 2: Assuming this is not a mistake in the study caffeine once a week would be enough to boost the BDNF levels of junk-food and normal eaters alike (Moy. 2012)
      And secondly, the rodents received only a single, weekly intraperitoneal injection that would be equivalent to ~250mg in a human being (I double checked, the study says: "All animals received either caffeine (20 mg/kg) or saline (volume-matched), i.p., once weekly."; my emphasis in Moy. 2012). If that's not a mistake, chronic caffeine consumption may not even be necessary to see a hell-lot of the anti-diabetes and anti-neurological damage effects of coffee - just 2 cups once per week that's it!

      And if you look closely at the data in figure 2 you see that even "normal" people may benefit from this regimen.
    Since tomorrow is an official installment of "On Short Notice" due, I will leave you on that flabbergast caffeine study and just remind you that there is - as everyday (guaranteed even on Christmas ;-) tons of interesting new stuff on the SuppVersity Facebook Wall, as well - let's see what we have today:
    • Insulin has anti-Alzheimer's effect - Yeah you read me right. It reduces the formation of ameliod beta plague (read more)
    • Yet more plant extracts with natural anti-cancer activity: Chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L known in TCM as Rui Xiang Lang D (read more)
    • Want to father a Nobel Laureate and in your early to late 30s? Than its about time you procreate! Study finds U-shaped curve for father's age and intellectual abilities of the offspring peaking at 32-37 years or so (read more
       
    • ...plus the rest I did not mention (read all)
        I guess with the podcast to listen to and some food for thought on once-weekly caffeine administration (on a side note, injecting into the intraperitoneal cavity is, for most substances, only minimally different from oral ingestion and done only to assure that the animals don't spit whatever you want them to ingest back out) you will survive the next couple of hours until the facebook news will receive another update and the next installment of "On Short Notice" is going to be published? If not, complain in the comment area ;-)
         
        References:
        • Biegon A, Kim SW, Alexoff DL, Jayne M, Carter P, Hubbard B, King P, Logan J, Muench L, Pareto D, Schlyer D, Shea C, Telang F, Wang GJ, Xu Y, Fowler JS. Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole. Synapse. 2010 Nov; 64(11):801-7. 
        • Biegon A, Alia-Klein N, Fowler JS. Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain. Front Pharmacol. 2012;3:185.
        • Daniell HW. Osteoporosis and smoking. JAMA. 1972 Jul 31;221(5):509.
        • Estrada M, Liberona JL, Miranda M, Jaimovich E. Aldosterone- and testosterone-mediated intracellular calcium response in skeletal muscle cell cultures. Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E132-9.
        • Hiltunen M, Iivonen S, Soininen H. Aromatase enzyme and Alzheimer's disease. Minerva Endocrinol. 2006 Mar;31(1):61-73.
        • Korkor AB, Eastwood D, Bretzmann C. Effects of gender, alcohol, smoking, and dairy consumption on bone mass in Wisconsin adolescents. WMJ. 2009 Jul;108(4):181-8.
        • MacMahon B, Trichopoulos D, Cole P, Brown J. Cigarette smoking and urinary estrogens. N Engl J Med. 1982 Oct 21;307(17):1062-5.
        • Moy GA, McNay EC. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF. Physiol Behav. 2012 Dec 6.
        • Nusbaum ML, Gordon M, Nusbaum D, McCarthy MA, Vasilakis D. Smoke alarm: a review of the clinical impact of smoking on women. Prim Care Update Ob Gyns. 2000 Sep 1;7(5):207-214.
        • Pant S, Shapiro CL. Aromatase inhibitor-associated bone loss: clinical considerations. Drugs. 2008;68(18):2591-600.
        • Roselli CE, Abdelgadir SE, Ronnekleiv OK, Klosterman SA. Anatomic distribution and regulation of aromatase gene expression in the rat brain. Biol. Reprod. 1998; 58, 79–87.
        • Roselli CE, Resko JA. Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance. J. Steroid Biochem. Mol. Biol. 2001; 79, 247–253.
         

        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.

          Licorice More Estrogenic Than Estradiol: Some of the Flavonoids in Glycyrrhiza Glabra Roots Turn Out to Be Superinductors of the Estrogen-α & -β Receptors

          Image 1: In view of the fact that most confectionary licorice contains no more than ~3% of the roots of the licorice plant, I would rather bother about the tricks the ~74g of carbohydrates (on a 100g base) of this treat may play on your insulin levels than about any potential negative effects the consumption of a few or even a whole bunch of these licorice wheels may have on your testosterone levels or overall manliness ;-)
          You probably have heard about licorice, the root of Glycyrrhiza glabra, a legume with a slightly sweet taste and one of the ingredient of the eponymous candy being a potent adrenal "revitalizer" that is used and advocated my many naturopathic doctors. If you frequent any of the major health and fitness boards on the Internet, you will yet also be familiar with some of its unwanted side-effects, first and foremost its scientifically validated anti-androgenic (specifically testosterone reducing) effects (Zamansoltani. 2009). While Zamansoltani et al. yet still speculated, whether the reduction in serum testosterone they observed as a result of administration of 150-300mg/kg of licorice extract (HED ~ 40-80mg/kg; 3.2-6.4g for a 80kg human) to male rats still speculated, whether these reduction were the result of "[i]ncreas[es] in T metabolism, down-regulation of androgen receptors or activation of oestrogen [sic!] receptors", a recent study that was published in the Annals of Bioanalytical Chemistry shows that the latter, i.e. the (profound!) activation of both types of estrogen receptors probably was the underlying cause of the emasculation of the licorice treated bucks (Simons. 2011).

          Estrogen receptor superinductors were not invented by Dr. Spock

          In a pretty meticulous analysis, Rudy Simons et al. found that several fractions of an ethyl acetate extract from licorice root displayed estrogenic activities at either the estrogen-alpha or estrogen-beta receptor that were more pronounced than the ones of the reference "drug", estradiol (E2).
          Figure 1: Relative estrogenic activity (in % of estradiol = E2) of 51 fractions that were isolated from an ethyl acetate extract from licorice root (data adapted from Simons. 2011).
          If you take a closer look at the 51 fractions the scientists identified by liquid chromatography-massspectrometry and analyzed for their activity by the means of yeast estrogen bioassays, you will recognize that not just one or two, but a whole host of these "fractions", which themselves were complex mixtures of similar compounds, exhibit partly profound estrogenic activity. In that it is particularly noteworthy that the superinduction (activity >E2=100%) was not caused by a post-translational stabilization of the firefly luciferase reporter enzyme, which would have disqualified these results as shortcomings of the yeast essay Simons et al. had used - a effect which has been previously described for genistein, one of the phytoestrogens in soy and soy products.
          Figure 2: Relative content and estrogenic activity of individual fractions F1-F5, F6-F21 and F22-F51 from the ethyl acetate extract from licorice root used in the study (calculated based on Simons. 2011).
          Of all the fractions, the scientists isolated from the licorice extract, which was supplied by Frutarom US, fraction 41 (F41) with an estrogen-alpha receptor activity of 159.9% at the low (3µg/ml) and 186.9% at the high (10µg/ml) concentrations was by far the 'worst offender'. In view of the fact that we do not know how much of these flavonoids actually make it into the bloodstream, the 103.1, 97.9, 95.5, 74.6, 68.7, 57.2 and 57.3% estrogen-beta activity of fractions F24-F30 at a much lower concentration of 0.3µg/ml is probably more of a concern and most likely the underlying cause of the anti-androgenic effects of licorice, which have also been established in a human study on seven 22-24 year old healthy male subjects by Decio Armanini et al. in 1999 (Armanini. 1999):
          Figure 3: Changes in testosterone, androstenedione and 17-hydroxy-progesterone levels (ng/dl) in 7 healthy men upon oral adminstration of 7g of a commercial licorice preparation (data based on Armanini. 1999)
          As you can see in figure 3, the 7 g of a commercial preparation of licorice (containing 0.5 g of glycyrrhizic acid) the men in the Amanino study received in the form of tablets (Saila, Bologna, Italy) on a daily basis had an immediate and pretty profound anti-androgenic effect (-44% total testosterone within 2 days!) resulting from the negative feedback of the phytoestrogenic components from Glycyrrhiza glabra. The levels of androstenedione and 17-hydroxy-progesterone on the other hand did not change.
          Image 2: Licorice could help with menopause symptoms such as hot flashes, but it has potential corticosteroid-like side effects you should keep an eye on.
          Update: Evelyn from CarbSane asked in the comment section whether licorice would not make a good addition to any natural menopause treatment. In fact, she is right that the very estrogenicity of the licorice extracts that is detrimental to men could be of great use for women going through menopause. A cursory search of the databases (how else could it be in view of the fact that you cannot patent licorice) does yet reveal that no one appears to be willing to invest serious money into studies on the effects of licorice / licorice extracts in menopausal women. Nevertheless, there is evidence for estrogen-like bone-building effects (Somjen. 2004) and a -2.4% reduction in the dreaded hot flashes over placebo (Nahidi. 2011).

          Moreover, licorice appears to act as an SSRI (selective serotonine reuptake inhibitor) and may thus also help with moodswings and neurotransmitter-imbalances (Ofir. 2003), which can also cause sugar cravings and thusly induce weight gain. If you add to that the growth-inhibitory action the glabridins in licorice exhibit on breast-cancer cells (Tamir. 2000), it may be well worth to try to alleviate menopause symptoms with licorice. In that, it is yet important to know that the glycyrrhetinic acid in licorice has mineralocorticoid-like side effect (i.e. it works like cortisol), which can become problematic especially if licorice is taken as part of one of the typical pharmacological protocols conventional doctors tend to prescribe to their patients (e.g. Inada. 2007). My advice would thus be to carefully monitor your reaction, Ladies ;-)
          Against the background of the results of both the initially mentioned rodent study by Zamansoltani et al. (Zamansoltani. 2009), as well as the certainly more relevant data from the 1999 study by Armanini et al. (Armanini. 1999) the 'test-tube' findings by Simons et al. gain a degree of practical significance many of the likewise bio-essay based studies, the manufacturers of purported (!) testosterone boosters like to cite to underline the scientific validity of their products, are lacking... you may want to keep that in mind before you try to counter the unwanted side-effects of a licorice-based "adrenal optimizer" by popping a few servings of the latest and greatest "scientifically proven testosterone booster" ;-)

          The Acute & 24h Effects of 3 Types of High Intensity Circuit Training on Testosterone & Cortisol in Young Trained Men.

          It's obviously to have the 24h effects on testosterone and cortisol than only those measured after the workout , but can we make solid conclusions based on the additional data?
          In spite of the fact that the acute testosterone and cortisol response to exercise appears to have little direct effects on the overall training outcome (Schoenfeld. 2013), acute increase in cortisol and reductions in testosterone, i.e. a decrease in the testosterone:cortisol ratio is a classic feature of overtraining and can very well blunt, if not reverse the beneficial effects of exercise on your health and body composition.

          Against that background a recent experiment that was conducted by researchers from the University of Chieti-Pescara in Italy could be of great interest to everyone who is performing high intensity interval training on a regular basis. Why?

          Well, in contrast to previous studies, Blasio et al. investigated both the acute and 24h effects of a high intensity interval resistance training regimen in trained young men.
          Learn more about building muscle and strength at www.suppversity.com

          Tri- or Multi-Set Training for Body Recomp.?

          Alternating Squat & Blood Pressure - Productive?

          Pre-Exhaustion Exhausts Your Growth Potential

          Exercise not Intensity Variation for Max. Gains

          Battle the Rope to Get Ripped & Strong

          Study Indicates Cut the Volume Make the Gains!
          To characterize the effects on heart rate and hormonal responses the subjects, eight trained, healthy trained men (28.61 ±3.51 yrs), performed three different workouts which had the same exercises, the same load and number of repetitions for each exercise, but different exercise order, recovery and speed of execution.
          • RANDOM workout: the assigned goal was to complete the assigned repetitions respecting only two duties. The first one was don’t stop until all of the repetitions were completed; the second was that there were no assigned order of execution of exercises and no assigned consecutive repetitions to complete.

            Participants were thus free to choose both the order of exercises and number of consecutive repetitions for each exercise (i.e. 2 repetitions of kettlebell swing, 10 repetitions of medicine ball slam, 20 repetitions of squat, 4 repetitions of spin with Bulgarian bag, etc.).

            No recovery period was assigned
            , except the time necessary to move from a station to another, and no speed of execution of exercises was assigned: participants were free to choose the preferred speed. 
          • LADDER workout: respecting the following order of execution, kettlebell swing, medicine ball slam, spin with Bulgarian bag, squat, pull-up, burpee, participants had to complete the total repetitions according to a pyramidal scheme (e.g. 1st lap 10 repetitions at each exercise, 2nd lap 9 repetitions at each exercise) until the total number of repetitions of each exercise was executed.

            Each lap of the circuit was followed by 1 minute of recovery. No speed of execution of exercises was assigned: participants were free to choose the preferred speed. 
          • AS SOON AS POSSIBLE (ASAP) workout : respecting the following order of execution, kettlebel swing, medicine ball slam, spin with Bulgarian bag, squat, pull-up, burpee, participants had to complete the total volume in six laps executed as soon as possible.

            During each lap participants had to complete the sixth part of total number of repetitions of each exercise without rest among exercises. Each lap of the circuit was followed by 1 minute of recovery.
          Salivary samples were collected before and after each workout, at 11:00 p.m. and at 7:00 a.m. of the following day. Salive was also collected during a non-training day. Similarly, before and after the workout, plasma lactate was measured while a beat-to-beat heart rate recording was executed during each workout. Cortisol (C) and testosterone (T) were measured in salivary samples.

          2h before the workouts the subjects who had to abstain from sexual intercourse, stimulants and alcohol from 2 days before to the experimental days and until 9:00 a.m. of the following day, consumed a standardized meal that was lower to 400 and consisted of 33 cl of water, 35 cl of orange juice and two 30 g energy bars (Power Sport Double Use, Enervit, Milan, Italy).

          Let's look at the results

          While the protocols elicited the same heart rate response (the major part of each workout was spent between 80 and 100% of maximal heart rate, confirming the high cardiovascular intensity of the workouts), they elicited different hormonal and lactate variations with the LADDER workout producing the lowest lactate increase and the RANDOM workout eliciting the highest lactate, cortisol and testosterone increases.
          Figure 1: Relative changes in hormone and lactate concentration in response to the workouts (Di Blasio. 2014)
          When C was considered in ratio with T no significant differences have been shown among workouts-induced variations. Results of the analysis of covariance, executed on significantly modified variables, confirmed that basal hormonal and lactate values did not influence their variations.

          When they studied the effects of workouts on prolonged hormones production (i.e. until the morning following the morning, di Blasio et. al. found that observed that observed that
          "C had both time (F=179.723; p < 0.001) and group × time effect (F=10.942; p < 0.001): while during non-training day there is a physiological decline of C production at 11:00 p.m., during training days its decline is not present but seems to have a continuous increase from 7:00 p.m. to 7:00 a.m." (Di Blasio. 2014)
          For the testosterone production the authors found both time (F=443.340; p < 0.001) and group × time effect (F=3.254; p=0.008) even if the group × time effect seems determined by the samples collected at 7:00 p.m., so that the effects cannot be ascribed fully / exclusively to the workout.
          Figure 2: 23h hormone profile after the RANDOM, LADDER, ASAP workouts on a control day (di Blasio. 2014)
          What is most interesting, though, is the cortisol to testosterone ratio. It shows the greatest inter-group differences and could potentially be of great physiological relevance (Crowley. 1996). In that, the LADDER workout has the most negative effect, as it will totally blunt the natural decline of the C:T ratio at noon.
          In case you're planning to incorporate circuit training into your schedule, make sure to have a huge chunk of beef after your workouts ;-) - "Post-Workout Steak "Supplementation" (135g of Lean Beef) Augments Improvements in Body Composition In Response to 8 Weeks of Circuit Resistance Training" | more
          Bottom line: As usual, it is difficult to interpret the results in order to make concrete practical recommendations. The lactate and hormonal data does yet suggest that the "random" order, i.e. a training that involves a self-selected exercise order and rep speed, as well as little to no rest between exercises is the least, the ladder training, with its decreasing 10, 9, ... rep numbers and one minute rest between each lap of the curcuits is the most metabolically demanding workout.

          Whether and to which extend this translates into an increased risk of overtraining, let alone increased muscle and strength gains, on the other hand, remains to be seen. In view of the overall effect on lactate levels and the C:T ratio, though, the study does suggest that you better be careful with high intensity circuit / interval resistance training sessions and give your body adequate time to rest and recover | Comment on Facebook!
          References:
          • Crowley, Michael A., and Kathleen S. Matt. "Hormonal regulation of skeletal muscle hypertrophy in rats: the testosterone to cortisol ratio." European journal of applied physiology and occupational physiology 73.1-2 (1996): 66-72. 
          • Schoenfeld, Brad J. "Postexercise hypertrophic adaptations: a reexamination of the hormone hypothesis and its applicability to resistance training program design." The Journal of Strength & Conditioning Research 27.6 (2013): 1720-1730.

          Intermittent Thoughts on Intermittent Fasting - Programing Success: Building Muscle Begins With Losing Body Fat.

          Image 1: Arnold does the "double bicep" + vacuums. If you want to look like a bodybuilder, muscle alone is not enough.
          First, I want to thank Jahed, Pablo, RF, Angimal, Garrett and Rudolf for their patience. After all, it has been two weeks now since you have submitted your (meta-)goals, which were all more related to building muscle and increasing performance, then to losing body fat, which was the topic the last installment of the Intermittent Thoughts dealt with. Yet although, at first sight, both topics have little (to nothing) to do with each other, there are are at least three important factors by which a reduction in body fat is very well related to increased muscularity and skeletal muscle hypertrophy. Let's get back to the "Peter Griffin" type of chubby person from the last installment, for a few seconds. Imagine "Peter" has packed on, say 10lbs of lean muscle and now stands in front of you, does the "double bicep" and vacuums, just like Arnold does in image 1... what? Why are you laughing?

          Do you want muscles? Or do you want to look muscular?

          Now, obviously the first intersection of bodyfat and muscularity (in a broader sense) relates to the question whether or not your body fat level is low enough for any increases in skeletal muscle mass to be visible. I mean +10lbs on the ripped frame of a 202lbs (now 212lbs) bodybuilder look absolutely freekish. On our Peter Griffin, a gain of 10lbs of lean muscle tissue will probably go completely unrecognized - this also puts "chubby" beginners at risk of neglecting the strength training component of their exercise regimen, because, from a mere "cosmetic" stand point, each gram of body fat they drop will make a significant difference in terms of the way they look. Building muscle beneath the thick layers of adipose tissue, on the other hand, initially appears to have little value... but remember: looks are deceptive, and I hope that my elaborations in the last installment made it quite clear "building a bigger metabolic engine" and not starving the latter away on a low-calorie diet, is the cornerstone of maintainable reductions in body fat levels.
          Figure 1: Where are you on the fat/muscle mass (FFMI = weight/height[in m]²) continuum? *indicates age-group 20-29 in the NHANES dataset (data based on data from Hattori. 1999; Picket. 2005; CDC, NHANES data from 2010)
          Interestingly enough, being lean, or, I should say, the metabolic and endocrine consequences of being lean actually have way more profound implications on "building muscle", than the mere advantage of the immediate visibility of the newly acquired lean body tissue. On "the boards" (meaning bulletin boards like bodybuilding.com, anabolicminds, etc.) it is a recurrent topic whether you should "bulk" (people there interpret that mainly as "eat to gain" and often as "overeat to gain") or "cut" (meaning lose fat) first. And while the answer obviously depends on where you are starting from, it stands out of question that the average American male (aged 27-62) who gets fatter and fatter every year and currently has a body fat percentage of 24.9% (Rohrmann. 2011) would be ill-advised to even think about the word "bulking".
          Image 2: Just to put the 24.9% body fat of the average American male into perspective. The average bodyfat percentage of a sekitori sumo wrestler is 28.6%
          (Hattori. 1999)!
          Please note, that the "no bulk with high body fat percentage" rule does also apply to the female physical culturists out there. The reason that I am mainly addressing the male faction of my readership here, is that women are not so stupid to think, they would have to down 2-3 portions of "weight gainers" (these products are exactly what they are called, they will make you gain weight, not muscle) and 4-5 protein shakes in addition to a hypo-caloric (junkfood-)diet in order to build a muscular physique, anyways. Things would be different, though if the physique of a sekitori sumo wrestler (one of the higher ranked sumos, cf. image 2), is what you are aspiring. In that case you can start "bulking" with weight gainers and all the other "high class" products the industry has to offer... I mean the average sekitori sumo has 109kg of lean muscle tissue hidden somwhere beyond the 45.4kg of fat he is carrying around the dohyo.
          If you want to "program success" and your "motivational elevator pitch" from part one of this part of the Intermittent Thoughts Series contains sentences like "look like a cover model." (Garrett; November 14, 2011 3:05 AM) or "[building] a stronger body, bodyfat below 8%" (RF, November 7, 2011 12:22 PM) or my favorite one which obviously nobody was dared to say, yet 90% of the Men's Health readers probably have on their minds "build muscle just to look good at the beach / impress the ladies", it is imperative that you lose your love handles first! Not to (just) to be able to see the gains you are making, but to set yourself up for optimal lean muscle gains (in essence, this is also related to the assumption Jahed Momand's assumption made in his "motivational elevator pitch" that leaning out prior to building his maximal clean and jerk and snatch to compete at 85kg probably is the smartest way to go, after all a low body fat percentage is obligatory if you want to be competitive in the lower weight classes).

          The endocrine advantage of low(er) body fat percentages

          The first and often overlooked advantage of a decent degree of leanness (cf. "active American", figure 1) is a hormonal one. According to the findings of the latest (published) NHANES data (National Health and Nutrition Examination Survey III; Rohrmann. 2011) there is a direct correlation between body-fatness as measured by BMI, waist circumference and body fat levels, on the one hand, and total and free testosterone and estrogen levels and their binding globulin SHBG:
          Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend < 0.05). 
          Further statistical analysis of the data reveals that a body fat increase of one-quartile (e.g. from the lower 1/4 of the study population to the next fatter quartile) goes hand in hand with a decreases in sex hormones into the next lower quartile (e.g. from the highest into the next lower quartile). A sample calculation for a 50 year old white non-smoker revealed that for each 5.2cm increase in body waist circumference or +2.7% increase in body fat, the free testosterone level decreased by 2%. With an increase of "only" +3.7cm or +1.8% in waist circumference or body-fatness, respectively you can however bump up your estrogen levels by 2%.
          Figure 2: Relative free testosterone and free estradiol levels in men from the NHANES study; data expressed relative to serum levels of "lean" men with <84.9cm ~ 33.4" waist circumference; values above the bars are the differences between relative testosterone vs. estradiol levels compared to "lean" men (calculated based on Rohrmann. 2011)
          In view of the differential response of androgenic and estrogenic free (i.e. "active") hormones to changes in body-fatness (cf. figure 2), it is no wonder that we see a characteristic and in terms of lean muscle gains highly unfavorable pattern in the "fatter" quartiles of the study population, with maximal  free estradiol levels (1.08pg/ml; +30% vs. min) and minimal free testosterone levels (0.097ng/ml; -13% vs. max) in the "fattest" quartile of the study population (I deliberately selected waist circumference over "body fat levels" which were measured by bio-impedence, as my body fat marker of choice). Even if you as a SuppVersity reader should by now be aware that testosterone alone does not "build muscle", its highly facilitative effect on exercise induced increases in lean body tissue is significantly blunted by the fat-induced reduction in free testosterone and the (by the way fat promoting) increase in free estradiol in "chubby" men.

          The endocrine factor: By leaning out first you set the hormonal scene (a higher testosterone to estrogen ratio) for optimal lean muscle gains.

          The metabolic advantage of lower body fat levels

          While testosterone and estrogen levels obviously figure large in the orchestrate that determines whether the nutrients you ingest (remember no one of you eats "calories") end up being stored as body fat, used as "fuel" or building block for lean muscle tissue, insulin, the "most anabolic agent in the world" (a quote from steroids.com; obviously a very questionable statement), may play an even greater role, when it comes to building muscle, not fat. Those of you have have listened to Dr. Layne Norton's and Dr. Connelly's dissertations on the largely misunderstood role of insulin in relation to the protein synthetic response to exercise, as well as its highly undesirable effects on fat storage during the last episodes of BodyRX Radio, will be aware that the often touted idea that "insulin is the most anabolic agent in the world" applies, above all else, to adipose tissue.

          Image 3: "Insulin the most anabolic agent in the world"!? Correct, if we are talking about fat,  not muscle tissue ;-)
          While "broscience" and the producers of sugary "weight gainers" and "post-workout recovery formulas" still maintain the myth of the "muscle building insulin spike" the (post-workout) ingestion of large amounts of fast-acting carbohydrates would provide, a recent study from Stuart Phillips lab at McMasters University into the purported benefits of the "insulin spike" produced by the co-ingesting 50g of carbohydrates with your 25g of whey protein post-workout found neither an increase in muscle protein synthesis, nor decreases in muscle protein breakdown, which are often cited as another benefit of increased insulin levels (Staples. 2011). More specifically, the additional +1,250% (!) increase in insulin (over +400% with whey alone) did not have any additional effect on protein synthesis, or, in other words: With insulin some (here 5x above fasted baseline) appears to be good, more, on the other hand is not only not better, it is in fact worse.

          That being said, the improvements in insulin sensitivity which go hand in hand with reductions in body fat levels (increases in leptin sensitivity, reductions in inflammation, etc.) will decrease your basal, as well as your postprandial insulin levels, because your body will simply need less of the storage hormone to get the job done. This, in turn, will allow you to fuel your workouts with appropriate (not exorbitant) amounts of carbohydrates without running the risk of storing additional body fat. This is particularly true, in view of the fact that the "type of insulin sensitivity" you acquire when you selectively lose body fat (not muscle) favors the storage of blood sugar as muscle glycogen over its conversion to triglycerides and subsequent storage in adipose tissue (note that the latter happens both in obese and insulin resistant, as well as in "reduced obese" individuals, who have lost a lot of body mass, not fat, on prolonged calorie restricted diets).

          The metabolic factor: By reducing your body fat levels first (leaning out vs. just losing weight) you decrease the risk that (superfluous) carbohydrates (and other nutrients) get stored as body fat.

          The anti-livelong-obesity advantage of lower body fat levels

          Image 4: There are two ways to get fat, adipose tissue hypertrophy and adipose tissue hyperplasia. While you obviously want to avoid both, only the latter is potentially irreversible (Otto. 2005).
          The third and maybe most far-reaching  advantage of lowering your body fat level before bulking up is actually related to the leeway you have in terms of the unavoidable fat gain that is part of every "bulk" no matter how "clean" it may be (see also red box below). It should be obvious that just as the myonuclei in your skeletal muscle have a limited capacity to "grow" (also to hypertrophy, i.e. to simply increase their size /we will discuss the three pathways of muscle growth in one of the upcoming installments in more detail), your fat cells can only store a finite amount of lipids before they begin to "burst from the seams" (some scientists even believe that this is part of what triggers the detrimental inflammatory cascade in obese individuals). When that is about to happen, the only way your body can protect itself from suffocating in glucose and triglycerides that can neither be burned as fuel nor stored in the bristling adipocytes is to generate new fat cells (adipocyte hyperplasia).
          My definition of a clean bulk: You may now be shocked to hear that even a "clean bulk" will necessarily also increase the amount of body fat you are carrying. That, and this is a very important point, does yet not mean that your body fat % must necessarily increase. A "clean bulk" by (my) definition is a bulk where you add more muscle than fat tissue to your frame. Now, even if you you were an absolute zero in math, you should recognize that this implies that your body fat percentage would actually drop, although your overall body fat levels may increase. Keep that in mind, whenever you are trying to gain muscle. Your goal should never be to cut fat (reduce overall fat mass) and build muscle (increase lean muscle tissue) at the same time - if you try that you program stagnancy, not progress!
          Now, the unfortunate truth is that it is pretty easy to "empty" those cells again (you can do this in weeks), yet uncertain on which time-scales (if at all) and by which means (other than surgery) you can get rid of newly acquired adipocytes ever again.
          An infant usually has about 5 to 6 billion fat cells, the number of which naturally increases during early childhood and puberty, so that the average healthy adult ends up with 25 to 30 billion fat cells. If those 30 billion adipocytes are already filled up when you start bulking, chances are that your body feels compelled to increase its storage capacity, so that - in the worse case - you end up with the roughly 75 billion fat cells, the typical overweight adult is carrying around on his "chubby" frame. If you still insist that you are not "big" enough and continue to eat whatever you can grab, the number of fat cells can increase up to 250, even 300 billion... it stands to reason that even when you emptied all of those, you would still be "fat".

          The anti-obesity factor: By leaning out first, you reduce the risk of a (potentially irreversible) increase in adipocyte number that may set you up for lifelong weight problems.

          An intermittent conclusion on the first step of programming skeletal muscle hypertophy

          Image 5: After a handful of unsuccesful bulking efforts, SuppVersity Student Duong Nguyen eventually made it right - he leaned out first. If you are interested in his subsequent bulk, check out his blog!
          As you may notice, I (once again) went off on a tangent. I hope you don't mind that you have not yet learned about effective ways measure your progress, about how to improve your gains by setting realistic, but challenging goals and about the often-overlooked impact the mind-muscle will (not could!) have on the real world outcomes of your efforts in the gym, in this installment of the Intermittent Thoughts.

          But hey! For (hopefully) a minority of you the "time to bulk" may not have come anyways ;-) So, if you have not achieved a degree of leanness comparable to that of the "average active American" (cf. figure 1), I suggest you re-read last week's installment on setting yourself up for body-fat loss and thusly take appropriate measures to increase the effectiveness of your first or next "bulk" and decrease the propensity of doing permanent "aesthetic" or even metabolic damage.

          As for the rest of you, I would hope that you could at least gain a few new insights into the challenges your not so lean friends are facing when they are trying to gain muscle without adding another inch to their waistlines.