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.

Bofu-Tsusho-San: Ephedrine Based Kampo Kitchen Sink Fat Burner Cuts 10kg Body Weight, Boosts Metabolism by +15% & Reduces Insulin of Diet-Resistant Woman by 50%

Is there a Japanese  weight loss wonder supplement not even Dr. Oz knows about? And could it be more effective than Oz's raspberry ketones?

Sometimes the most inconspicuous articles turn out to be the most interesting ones. I mean, who would have guessed that a case report titled "Japanese herbal medicine for weight loss in a morbidly obese patient: A case report" would make it into the SuppVersity news? Being as heavy as tall, in this case 154.8 kg distributed not very proportional on a 157 cm frame with an 155cm waist, is - as unfortunate as that may seem - not exactly uncommon these days - even for a 22-year old woman. The words "japanese herbal medicine" and the line "her resting metabolic rate (RMR) increased from 2260 to 2440 kcal/day" (Haruta. 2013) the abstract mentions right after discussing her 10kg weight loss peaked my interest.

How bad off was the subject?

The subject had obviously been yoyo-dieting for years, when she was as hospitalized in the researchers' department for the purpose of weight loss.

"Her heart rate was approximately 100 beats per minute and her blood pressure was 156/108 mm Hg. Upon initial admission, we performed blood work, abdominal ultrasonography (US), and a head computed tomography (CT) to exclude secondary adiposis."

A biochemical examination of her blood yielded

To eat or to diet, what's worse? Some people argue that "dieting just makes you fat" and we all know about the yoyo effect, but is that (a) true and (b) what effects does it have on your over and metabolic health? (learn more)

• marginally elevated ALT levels;
• marginally elevated uric acid, but 
• normal creatinine and BUN levels;
• low HDL levels (bottom of the range), and 
• high-normal LDL levels;
• elevated HbA1c and fasting blood glucose levels,
• highly elevated insulin levels (2.7x), and
• highly elevated (5.5x) CRP levels
• normal cortisol, normal growth hormone, but 
• slightly elevated ACTH levels
• slightly elevated testosterone levels, but 
• otherwise normal endocrine function

Although the  elevation of ALT was marginal and the other parameters of liver health appeared in range, a fatty liver and a left ovarian tumor were detected by abdominal ultrasound.Unfortunately both not exactly uncommon in subjects with full blown metabolic syndrome, which is - according to International Diabetes Federation criteria - defined as having...

• hypertension, blood pressure>130/85 mm Hg, 
• abdominal circumference > 80 cm

• HDL-C < 50 mg/dL, and 
• plasma glucose>100 mg/dL

The doctors at the Department of Psychosomatic Internal Medicine of the Kagoshima University Graduate School of Medical and Dental Sciences in Kagoshima, Japan, prescribed a reasonable exercise program and a calorically restricted diet containing 2,000kcal and thus ca. 12% less than the subjects resting metabolic rate (measured by respiratory exchange ratio; 2260 kcal/day). That did help her to lose ~5kg during her stay at the hospital, but at 150kg the weight loss stalled until....

Things changed, when the scientist prescribed bofu-tsusho-san

Bofu-tsusho-san  has been used in Kampo, the Japanese study and adaptation of Traditional Chinese medicine (TCM), for decades and though I have to admit I had not heard about it before, there is actually existing evidence for its efficiacy as a weight loss adjuvant:

Figure 1: Bofu-tsusho-san (BTO) does what you expect from a potent weight loss helper. It keeps your metabolic rate up - and even better BTO even increases it on a per lbs of body mass basis (Hioki. 2004)

• higher body fat loss, greater weight loss, no reduction in BMR + improved insulin response and lower homa-IR in 40 Japanese women (body mass index (BMI) 36.5 +/- 4.8 kg/m2) with IGT and insulin resistance (IR), who had been treated with a low-calorie diet (5016 kj/day: 1200 kcal) and an exercise regimen (1254 kj/day: 300 kcal) compared to 40 women in the placebo group (Hioki. 2004).

• blunts the weight gain patients on anti-psychotics (Zyprexa = olanzapine) often experience (Yamamoto. 2009).
   
• works by three distinct pathways, i.e. via the inhibition of triglyceride synthesis in the liver, and the enhancement of lipolysis in adipocytes and of thermogenesis in brown adipose tissue. At least that's what early studies in rodents suggest (Morimoto. 2001). 

The preparation has an overall favorable safety profile, with a tolerable intake of 2g/kg in rodents and thus ~325mg/kg in humans. Nevertheless, Bofu-tsusho-san is not totally devoid of side effect, there are two case reports of pneumonitis that occured after ~1 months of treatment with the drug and went away when the herbal was discontinued (Masushima. 2002; Suzuki. 2004).

For the subject in the study at hand, it may yet eventually turn out to be a life saver. After all the fat that had been coming back for more after each and every diet kept melting away, even after her stay at the hospital and when she reported back for the last examination before the paper was written, she had lost 10kg. That left her still morbidly obese, but with the initially mentioned +8% in resting metabolic rate (+15% if you express that relative to her body weight), improved fasting glucose levels (-31%) an HbA1c of 5.5.% (-17%) and immuno reactive insulin levels of 27.9 mU/mL (-45%!) she may not have been on her way to the cover of Shape, but (and this may be even a contrast) to a non-life-threatening body weight.

Let's look at the formula: Some old acquaintances in here

Did you know... that ephedrine HCL is not just a beta agonist, but also a potent anti-inflammatory? According to the results a group of scientists presents in the latest issue of Cellular & Molecular Biology, ephedrine HCL is "a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection"!? This conclusion is based on the observation that EHCL increases the levels of the anti-inflammatory interleukin-10 (IL-10) and decreases the release of proinflammatory cytokines (IL-6, TNF-alpha, IL-12 and IL-1beta) in immune cells that are stimulated with a component of the cell walls of gram-positive bacteria (Zheng. 2013)

Bofu-tsusho-san has also been shown (in vitro; Katoh. 2009) to inhibit beta-estradiol 3-glucuronidation, which is yet probably only a problem if you ingest it in very high amounts, an undertaking that could pose other problems even before you realize that its blocking your estrogen metabolism due to the sympathetic overactivation caused by ingredient #1 on the list below:

• Ephedrae herba (EH; contains ephedrine),
• Glycyrrhizae radix (GR; contains licoricidin), 
• Forsythiae fructus (FF; contains D-pinoresinol), and
• Schizonepetae spica (SS; inhibits phosphodiesterase enzymatic activities).

Looks pretty much as if it came right from the labs of an innovative supplement company, who've been following the SuppVersity news and articles pretty closely, right? Ok, everybody knowas about the beta-agonist qualities of ephedrine that may not have been important, but the fat-loss prowess of licorice (cf. "All about cortisol"), as well as the potential application of phosphodiesterase inhibitors to alleviate insulin resistance and promote fat loss (cf. Jansson. 2010; Murdolo. 2012) Carl and I mentioned on one of the past episodes of the Science Round Up would be something they may have picked up, here...

"Enough of the bragging, Adel!"

Ok, ok. I have to admit that it would have required some research on their part to come up with the additional Forsythiae fructus extract and the

• antihyperglycemic (Wikul. 2012), 
• antihypertensive (Greeneway. 2011),
• antifungal (Hwang. 2010) and 
• antioxidant effects - particularly in the gut (Jung. 2010; During. 2012) 

of its D-pinoresinol glycosoids, to come up with this ingenious invention, if it had not already been invented by an unknown Japanese Kampo practitioner decades ago, I should say ;-)

---

The Kitchen Sink Approach to fat loss is surprisingly effective(learn more)

Bottom line: While I believe nobody will be arguing that the ephedra part of the formula is probably the most effective ingredient, it's interesting to see that traditional medicine has already come up with "drugs", or rather herbals, that make use of synergies such as the weight loss benefits of PDE inhibtors, the Western allopathic medicine starts to understand, only now.

That these synergies can do the trick in commercially available supplements, as well, is something we have seen about a week ago, with the "Kitchen Sink Fat Burner" (learn more).

And still, not knowing which of the ingredients are actually responsible for the observed benefits is an unquestionable downside. A downside due to which I can't tell you if the classic E+C stack would be as, less or even more effective than the "kambo version of ECA". What I can tell you, though, is that the addition of Schizonepetae spica to the legendary "fat loss classic" makes sense. The same would go for Glycyrrhizae radix and Forsythiae fructus, which appear to make particularly good match as the latter will counter potentially blood pressure elevations due to the former.

References:

• During A, Debouche C, Raas T, Larondelle Y. Among plant lignans, pinoresinol has the strongest antiinflammatory properties in human intestinal Caco-2 cells. J Nutr. 2012 Oct;142(10):1798-805.
• Greenway F, Liu Z, Yu Y, Gupta A. A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension. Altern Med Rev. 2011 Dec;16(4):338-47. 
• Hioki C, Yoshimoto K, Yoshida T. Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clin Exp Pharmacol Physiol. 2004 Sep;31(9):614-9.  
• Hwang B, Lee J, Liu QH, Woo ER, Lee DG. Antifungal effect of (+)-pinoresinol isolated from Sambucus williamsii. Molecules. 2010 May 14;15(5):3507-16.
• Jansson PA, Murdolo G, Sjögren L, Nyström B, Sjöstrand M, Strindberg L, Lönnroth P. Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes. Diabetologia. 2010 Oct;53(10):2205-8. doi: 10.1007/s00125-010-1819-4. Epub 2010 Jun 10. 
• Jung HW, Mahesh R, Lee JG, Lee SH, Kim YS, Park YK. Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia. Neurosci Lett. 2010 Aug 23;480(3):215-20.
• Katoh M, Yoshioka Y, Nakagawa N, Yokoi T. Effects of Japanese herbal medicine,
  Kampo, on human UGT1A1 activity. Drug Metab Pharmacokinet. 2009;24(3):226-34.
• Lee MY, Shin IS, Seo CS, Kim JH, Han SR, Shin HK. Subchronic oral toxicity
  studies of the traditional herbal formula Bangpungtongseong-san in Crl: CD (SD)
  rats. J Ethnopharmacol. 2012 Dec 18;144(3):720-5.
• Matsushima H, Takayanagi N, Ubukata M, Tokunaga D, Mori S, Sato N, Kurashima K, Yanagisawa T, Sugita Y, Kawabata Y, Kanazawa M. [A case of pneumonitis induced by Bofu-tsusho-san]. Nihon Kokyuki Gakkai Zasshi. 2002 Dec;40(12):955-9.
• Morimoto Y, Sakata M, Ohno A, Maegawa T, Tajima S. [Effects of bofu-tsusho-san, a traditional Chinese medicine, on body fat accumulation in fructose-loaded rats]. Nihon Yakurigaku Zasshi. 2001 Jan;117(1):77-86.
• Murdolo G, Sjöstrand M, Strindberg L, Lönnroth P, Jansson PA. The selective phosphodiesterase-5 inhibitor tadalafil induces microvascular and metabolic effects in type 2 diabetic postmenopausal females. J Clin Endocrinol Metab. 2013 Jan;98(1):245-54. 
• Suzuki S, Tanaka A, Arai T, Adachi M. [Case of interstitial pneumonitis induced by a Chinese herbal medicine, bofu-tsusho-san]. Nihon Kokyuki Gakkai Zasshi. 2004 Aug;42(8):777-81. Japanese.
• Yamamoto N, Inada T. Bofu-tsusho-san effectively attenuates the weight gain
  observed after receiving olanzapine. Psychiatry Clin Neurosci. 2008
  Dec;62(6):747.
• Wikul A, Damsud T, Kataoka K, Phuwapraisirisan P. (+)-Pinoresinol is a putative hypoglycemic agent in defatted sesame (Sesamum indicum) seeds though inhibiting α-glucosidase. Bioorg Med Chem Lett. 2012 Aug 15;22(16):5215-7.
• Zheng Y, Yang Y, Li Y, Xu L, Wang Y, Guo Z, Song H, Yang M, Luo B, Zheng A, Li P, Zhang Y, Ji G, Yu Y. Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3β pathway. Cell Mol Immunol. 2013 Apr 22.

Science Round-Up Seconds: Does the Paleo Diet Ruin Your Lipid Profile? Plus: Liver Health & Hepatitis - Milk Thistle & Beyond. Libido Boosters & Real PDE-5 Inhibitors. "Fake" Cinnamon, Coumarin, Bloodthinning & Carcinogenic Cereals.

Is the Paleo Diet unhealthy for healthy individuals? A recent thesis would suggest just that. Learn more about and make up your mind based on the last installment of the Science Round-Up and today's Seconds (img informedhealth.com.au)

I hope you did not miss that the SuppVersity Science Round-Up will as of now always be starting early(-ier) at 12PM EST. If so, don't worry, you can still download the show and listen to Carl and me talking about the things you may be missing, the ones you get extra and those you would rather not have in your supplements and foods. Let's take silymarin, for example, as you have learned on the show, not all "liver assist", "liver clense" or "liver health" products are created equal. Most intriguingly, their ability to scavenge free radicals, as measured by the trolox assay, is not singularly dependent on the actual silymarin content, but will - as the data from the study Anthony et al. conducted (Anthony. 2013) - vary largely, depending on where the milk thistle was grown, how it was processed and thus what else, aside from the purportedly active ingredient is in it.

There is more to natural products than a single active ingredient

If you will, the "there is more to it" was a golden thread that ran through the whole show, but before we follow it up to the next topic, I want to provide you at least an excerpt from the actual data Anthony et al. produced.

Table 1: Selected products tested in the study ordered by their anti-oxidant activity in the TROLOX essay; products with highest TROLOX and anti hepatitis C viral activity highlighted in green and violet, respectively (Anthony. 2013)

As you can see my selection of the 45 products, the scientists bought and tested, reflects what you have already heard on the show: The silymarin content varies largely. In essence, the actual silymarin content may yet not even be that important. If you focus solely on their TROLOX equivalents (TROLOX is a vitamin E like antioxidant and it is used to quantify the anti-oxidant activity in a standardized way - more or less like the meter is used to quantify the length of an object or seconds are used as a standard timespans are expressed in).

More about Liv-52: Actually, the Himalaya(R) product is one of the few OTC supplements with not just one, but more than 20 studies to back its hepatoproctective and antioxidant effects. One thing to keep in min about the research is though that it was - despite being mostly published in peer-reviewed journal - in large parts conducted by scientists who work either for or with the company. As I've pointed out previously, this does not mean that the data is flawed, but it puts observations such as the improved glucose uptake (213%) , the 50% reduction in triglyceride content (anti-NAFLD effect), the 790% increase in glutathione, as well as the decreased TNF-α (-51%) and IL-8 (-550%) and concomitant -65% and -69% reductions of lipid oxidation and DNA fragmentation, respectively, Vidyashankar et al. observed in a recent in-vitro study somewhat into perspective (Vidyashankar. 2012).

If you are looking for the most potent among the readily available products in my selection the most potent "liver protectant" would actually be the PED user's first choice Liv-52, which does not even contain silymarin but is based on an undisclosed amount of  capers (Capparis spinosa), wild chicory (Cichorium intybus), arjuna (Terminalia arjuna), negro coffee (Cassia occidentalis), yarrow (Achillea millefolium) and tamarisk (Tamarixgallica). Bio Silymarin by Advanced Beta Glucon Therapy, on the other hand, is a close second with an almost identical TROLOX value (9.4 vs. 9.5 for Liv-52), is based on silymarin; plus, it exerts 77% more pronounced hepatitis C virus (HCV) antiviral activity than the Himalaya product which lists "viral hepatitis" as the #1 indication on the corresponding website.

As far as these anti-HCV effects, which were standardized against the results the scientists observed in cultures that were treated with 100 U/mL interferon-α, are concerned another Source Natural's Silymarin Plus, emerged as the most potent product. With the "plus" signaling the addition of choline, inositol, vitamin C+E, this observation confirms that antioxidant activity and anti-viral activity are two pairs of shoes - even when the active ingredient (silymarin) is the same.

Apropos active ingredient

You are yet by no means at the mercy of milk thistle and silymarin, when you want to protect your liver from harm. Spices like

• Tumeric (curcumin)
• Coriander

• Garlic
• Red chili
• Black pepper

bust also coffee and green tea, and fruits and vegetables such as

• carrots
• ivy guard
• sweet corn
• soy (for the glycine in it)

• grapes
• custard apples
• Indian gooseberries
• pomegrenade
• sea buckthorn

have potent anti-oxidant and antiproliferative activities (Shukla. 2013)

OTC libido boosters - more than just an alternative

Now that we are talking about alternatives, let's get straight to the next one: The "alternative" to viagra, cialis & co. Honestly, I would hope that you will never have to use one of these (I suggest you take a peak at yesterday's post "The '20 / 30 Principle' Sheds 15% Body Fat in 6 Months, Boosts Testosterone & Sexual Performance in Overweight Men. Plus: Six Signs You're Doing Too Much, Already."; read more), but in the unfortunate case you do, you may be surprised how effective the majority of them actually is.

Figure 1: Categorial breakdown of the adulterated majority of the 91 products from the Campbell study (Campbell. 2013)

A brief glance at the data in figure 2 does yet suffice to see that this is not another case of the "nature knows best principle", but simply a consequence of the fact that the majority of these products do contain either sildenafil and/or taldalfil or some sort of molecular cousin ("analogs" in figure 2). Moreover, in 18 out of these products the dosage was >110% of what would be legit on a per serving base for the prescription varieties (I suspect this is 20mg).

Also mentioned in this context: Saw palmetto is a PDE-5 inhibitor (cf. Yang. 2013). Although the evidence is from a rabbit study, it's pretty likely that there will be at least some discernible effects of saw palmetto on PDE-5 activity an iNOS activity in the human corpus cavernosum, as well.

Coumarin: Carcinogenic & blood thinning cereals

Table 2: Coumarin content in mg/100g of the samples from the Wang study

As unfortunate as it may seem, the chance that the cinnamon you consume with pre-packaged food is "real" (=verum) and from the inner bark of Cinnamomum verum are close to zero. Since this is however the only variety, where you can be almost 100% sure that you don't consume blood thinning and pro-carcinogenic coumarin, it does actually not come as a surprise that cinnamon apple sauce or a cinammon roll bought from the local supermarket contain 0.64 and 2.1mg of this agent on a per serving basis.

If you take a closer look at the rest of the data Wang et al. collected for their latest study (Table 2; cf. Wang. 2013), you may be surprised to see that regular bread, generally unsuspicious oats and purportedly healthy granola bars contain coumarin in amounts that will have you easily surpass the daily uptake limit of 0.1 mg/kg body weight, which was established by the European Food Safety Authority (EFSA) right after it became clear that coumarin is a potential carcinogen... *yamyoll*

Nedless to say that the consumption of respective supplements, which are currently heavily marketed as healthy anti-diabesity agents, could do more harm then good, when the producers play it cheap and put the next best "Cinnamomum XY" they can get their hands on into the caps.

Neither viagra nor cinnamon caps are "paleo", yet still...

E. Trexler titled his recently published thesis "Paleolithic Diet is Associated With Unfavorable Changes to Blood Lipids in Healthy Subjects", which would suggest that the paleo diet is similarly unhealthy as the consumption of "fake", coumarin-loaden cinnamon or high amounts of isolated cholorogenic acid (story is discussed in detail in the podcast; cf. Mubarak. 2013).

Figure 2: Lipid profile (left; values expressed in % of reference levels), fitness and body fat level (right) before and after the Paleo + Crossfit interention (calculated based on Traxel. 2013)

If you take a closer look at the abstract and the actual "side effects" (figure 2), the 10-weeks of paleo dieting + CrossFit-based, high-intensity circuit training exercise program had on the body composition and fitness levels, I personally cannot but ask the following question:

 "What is the significance of the elevations in LDL and minor reductions in HDL in a scenario that produces exactly what has just been shown to be at the heart of the 'Obesity Paradox' and lipid values that are still within the ever-narrowing 'normal' or 'optimal' range?"

I'll leave it up to you to answer this question and decide whether it can really be so bad to rid yourself of all modern, processed foods including any form of processed sugar, soft drinks, and coffees, while fueling your life and workout related energy by increasing your consumption of lean meat, fish, eggs, nuts, fruit, and vegetables. Have a nice weekend!

References:

• Anthony K, Subramanya G, Uprichard S, Hammouda F, Saleh M. Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements. Antioxidants. 2013; 2(1):23-36.
• Campbell N, Clark JP, Stecher VJ, Thomas JW, Callanan AC, Donnelly BF, Goldstein I, Kaminetsky JC. Adulteration of Purported Herbal and Natural Sexual Performance Enhancement Dietary Supplements with Synthetic Phosphodiesterase Type 5 Inhibitors. J Sex Med. 2013 May 1. 
• Mubarak A, Hodgson JM, Considine MJ, Croft KD, Matthews VB. Supplementation of a high-fat diet with chlorogenic Acid is associated with insulin resistance and hepatic lipid accumulation in mice. J Agric Food Chem. 2013 May 8;61(18):4371-8. 
• Shukla SK, Kumar V. Bioactive Foods and Supplements for Protection against Liver Disease. In: Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease. Elsevier. 2013. 
• Trexler, E. Paleolithic Diet is Associated With Unfavorable Changes to Blood Lipids in Healthy Subjects Honors Research Thesis. Ohio State Univeristy. May 2013.
• Vidyashankar S, Sharath Kumar LM, Barooah V, Sandeep Varma R, Nandakumar KS, Patki PS. Liv.52 up-regulates cellular antioxidants and increase glucose uptake to circumvent oleic acid induced hepatic steatosis in HepG2 cells. Phytomedicine. 2012 Oct 15;19(13):1156-65.
• Yang S, Chen C, Li Y, Ren Z, Zhang Y, Wu G, Wang H, Hu Z, Yao M. Saw Palmetto Extract Enhances Erectile Responses by Inhibition of Phosphodiesterase 5 Activity and Increase in Inducible Nitric Oxide Synthase Messenger Ribonucleic Acid Expression in Rat and Rabbit Corpus Cavernosum. Urology. 2013 Apr 23. doi:pii: S0090-4295(13)00169-6.

Fat From Serotonin, MS Despite Vitamin D, DHA & DPA in Your Cell Walls. Weightloss Obstacle Late Lunch?

Yet another reason why calorie counting is not good for your sanity: The "average" sexual intercourse burns only 14 kcal more than watching TV.  and significantly less than a fast paced walk on the inclined treadmill. Luckily weight loss & maintenance is more complex than calories in vs. out, anyway ;-)

"14" that's the SuppVersity figure of the number of extra calories you will expend when you and your significant other decide to have sex instead of sitting on the couch watching TV tonight. I got that figure from a paper my buddy Sean Casey from CasePerformance has brought to my attention. Published in the latest issue of the prestigious New England Journal of Medicine (Casazza. 2013), it discusses the 7 most commonly held "false and scientifically unsupported beliefs about obesity" the scientists identified in a thorough analysis of popular media and scientific literature.

"The scientific community needs some more honesty"

While the sex-myth, which originally states that you would burn at least 100kcal, with a little more action" even 300kcal per intercourse, is obviously my favorite, there are also a couple of  less sexy "presumptions about obesity" (e.g. simply eat more veggies and fruit and you lose weight) and "facts about obesity" (e.g.  the scientists dug up and debunked in a paper that ends with the wise words:

"While we work to generate additional useful knowledge, we may in some cases justifiably move forward with hypothesized, but not proved, strategies. However, as a scientific community we must always be open and honest with the public about the state of our knowledge and should rigorously evaluate unproved strategies." (Casazza. 2013)

Actually the term "the state of our knowledge" is an ideal segue to what follows - the "short" news! Originally the On Short Notice column was actually intended as a very brief overview of what has been going on in the "community" as of late. And since we are talking about honesty, I must admit that I have failed miserably in the past installments as far as the tiny word "short" in the column's title is concerned.

The new short news are short again ;-)

So, as of now, I will be doing my very best to bring the On Short Notice column back on the short track, so to say. I guess, we will see in a couple of paragraphs, how successful my efforts will be ;-)

• Does serotonin make you fat? It's pro-fat storage effects would suggest so
  
  

  

  If 5-HT can make you fat and creatine blunts its increase PWO (learn more), what does that tell us about creatine? Nothing, but it leaves room for speculations.

  (Gres. 2013) -- If you trust in TV wisdom the reason women eat chocolate, whenever they feel sad or alone is it's ability to boost serotonin (5-HT). The latter is yet not the reason Sandra Grès et al. say that serotonin could make you fat. Rather than that, it's the ability of 5-HT to stimulate the obesogenic peroxisome proliferator-activated receptor γ (PPAR-γ, learn more), on adipose cells, which will increase fat storage and the recruitment of new fat cells from the stem cell reservoir.
  
  These effects happen in the periphery (vs. the brain) and are totally unrelated to the centrally mediated effects of serotonin.

• MS patients benefit from the sun, not vitamin D
  
  (Zivadinov. 2013) -- Where is your vitamin D supposed to come from? From your skin, right. And where does your skin get it from? From tablets? No. It manufactures it from the "bad" cholesterol when it's  exposed to the "bad" sunlight.
  
  

  

  In the upper left of this image you see, where the magic is - the rest is just a nice bonus.

  With all those supposedly bad, but in fact, vital things being important for much more than vitamin D synthesis it is therefore not surprising that a recently published paper on the associations of sun-exposure and/or vitamin D with MRI measures in multiple-sclerosis patterns revealed that
  

  "[...] sun exposure was associated with increased grey matter volume (GMV, r_p=0.16, p=0.019) and whole brain volume (WBV, r_p=0.20, p=0.004)" (Zivadinov. 2013).

  ...and that totally irrespective of whether the subjects had high or low vitamin D levels. If you wanted to say it fancily, you'd say the beneficial effects of sun exposure on the brain volume in MS patients was found to be disassociated from the effect the sun has on vitamin D levels (suggested read: Vitamin D, Epstein Bar & MS)

• If you want to up the omega-3 levels in your tissue, pick DHA and / or its precursor DPA over EPA
  
  

  

  Figure 1: Incorporation various lipid fractions in different tissues (Kaur. 2013)

  (Kaur. 2013) -- According to a very recent rodent study docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) are much more readily incorporated into two of your most vital organs, namely your brain and liver and likewise the preferred phospholipid in the cell walls of your kidneys and muscle tissue. Only your fat cells don't really like these long(est) chain omega-3s the incorporation of which was ~50% lower than that of oleic acid (OA; that's the mono-unsaturated fatty acid in olive oil), which was used as a "neutral" control.
  
  The one question I would still like to have an answer to is how beneficial it actually is if the phospholipids (PL, figure 1) in your cell membranes are full of easily oxidizable fatty acids.
  
  Also, what do we make of the other lipid fractions? Cholesterol (CHOL), diacylglycerol (DGL) and NEFAs + triglycerides (NE+TG)? Where do we actually want those good omega-3 fatty acids to accumulate? ... just some food for thought for your DPA and DHA lovin' brains ;-)

• 
  On a side note: If you like GMO, you won't have to eat fish any longer to get your omega-3 PUFAs
  
  (Petrie. 2012) -- Researchers from the CSIRO Food Futures National Research Flagship have already engineered the first GMO brassica species with a higher DHA yield >11% than fish. The invention is hailed as "a breakthrough in the development of sustainable alternative sources of DHA as this technology should be applicable in oilseed crops" (Petrie. 2012)

• When late eating (spec. lunch) and certain genes come together weight loss can become pretty difficult - reasons still not fully understood, though
  
  (Garaulet. 2013) -- Late lunch and certain genotypes appear to make weight loss difficult for some. And the relation holds even after possible confounding factors like energy intake and even appetite hormones, were measured.
  

  

  Skipping breakfast. Yay or Nay? (read more)

  "Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups." (Garaulet. 2013)

  While this is not a general argument against intermittent fasting, skipping breakfast and the like, it does still go to show you that we are not all created exactly equal and any cookie cutter approach to weight loss, therefore, counter-indicated. 

• Show me your wrist and I'll tell you something about your glucose metabolism.
  
  (Nudeh. 2013) -- A study that was published in the latest issue of the The Journal of Clinical Endocrinology & Metabolism reveals: Wrist circumference is a significant predictor of diabetes in both genders of the adult population.

  

  Figure 2: Incidence of diabetes during 8.8 years of follow-up in different tertiles of baseline
  wrist circumference among male and female populations (significant trend in both genders; Noudeh. 2013)

  What's particularly interesting is that this association which was observed in a cohort of 6393 subjects (2716 males and 3677 females), who had been subjected to a standard 2-hour post challenge plasma glucose, test holds independent of BMI and waist circumference - allegedly for women, only. 

• Sildenafil Citrate Attenuates the Deleterious Effects of Elevated Ammonia
  
  (Arafa. 2013) -- You will probably remember the problems with ammonia accumulation due to huge BCAA and protein intakes (learn more). If you trust the latest results of two Egyptian researchers from the Zagazi University it would look as if a solution to that problem (which shouldn't be one, if your liver is healthy and you don't go overboard on pro-ammonia foods, anyway) would already exist: Sildenafil citrate aka Viagra can help.
  
  In their study, the researcher administered 10mg/kg sildenafil to rats that were treated with a daily intraperitoneal (i.p.) injection of ammonium chloride (100 mg/kg body weight) for eight weeks. This treatment resulted in a significant reduction in serum liver enzymes, lipid profile and - maybe most importantly - brain lipid peroxidation and caspase-3 mRNA. It also increased the nitric oxide (NO) levels in the blood and lead to a significant increase in cGMP, antioxidants and endothelial nitric oxide synthase (eNOS) gene expression in the brains of hyperammonemic rats.
  

  

  List of various foods and their ammonia content (Rudnan. 1973)

  "Our results showed that sildenafil exerts a protective effect on the brain by reversing oxidative stress during hyperammonemia and this could be due to (i) cytoprotective, antioxidant and anti-apoptotic effects ii) increasing cGMP and enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus preventing oxidative damage in the brain."

  Until now, the scientists cannot tell how exactly the human equivalent of 1.62mg/kg sildenafil citrate work, but its modulatory effect on the NO/cGMP pathway is the most likely candidate. That these effects are of real world significance has incidentally been shown, already. In 2003, for example, the learning abilities of rats with hyperammonemia was restored by a similar regimen (Erceg. 2003) 

• Acetyl cysteine - don't swallow, but rub it... onto your skin, if you have acne
  
  (

  

  The comedo count is a measure of the number of comedones, i.e. the open black "pores" like those on the forehead of the person shown on this photo

  Montes. 2012) -- According to a study published in the latest issue of Skinmed, the application of a 5% acetylcysteine topical gel proved to be "significantly superior to placebo (P = .04)" in reducing the comedo counts. The results were comparable in male and female participants and would suggest that "acetylcysteine is an effective therapeutic option for the treatment of mild to moderate acne". Whether it is an alternative to the retinoid based standard drugs, is yet still questionable.
  
  By the way, the latter, or rather the most prescribed of these retinol-like drugs, namely tretinoin has only recently been found to synergize with Aloe vera for even better results (Saeedi. 2013).

• Brazilian propolis ethanol extract promotes glucose uptake and translocation of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle
   
  

  

  In the unfortunate case, you missed the news: The commonly ignored BCAA Isoleucine also boosts GLUT4 (read more)

  (Ueda. 2013) I guess you will have heard about the miracles "royal jelly" is supposed to work on your health, right? Well, the cheap "packaging" material bees use to seal the smaller gaps in their hives (the larger ones are usually filled with beeswax) seems to have similarly outstanding - and in this case scientifically backed effects.
  
  When propolis was administered at a human equivalent dose of 20mg/kg to mice, those rodents saw increases in both PI3 and AMPK modulated increase in the glucose transporter 4 activity and skeletal glucose uptake.
  
  The main active polyphenols were artepillin C, coumaric acid, and kaempferide. All of them promoted GLUT4 translocation in a subsequent ex-vivo analysis using L6 myotubes, but kaempferide, which can also be found in avocado seeds (Pahua-Ramos. 2012) and cardia sinensis aka grey-leaved saucer berry extracts (Martinetti. 2010), was the most potent one.

Now you are surprised, right? Me too. Nine individual items and all of them still qualify as "short news". I guess in view of the sheer abundance of news you won't need anything else till tomorrow, but in case you do, I have a couple of suggestions to check out on the SuppVersity Facebook Wall:

• Lycopene works as an anti-cancer agent, because some of it's metabolites "look" like retinol (vitamin A) and dock to the retinol receptor (read more)
  
• Curcumin is a hormetic agent (learn more about hormesis), but not all curcuminoids are created equally effective (read more)
• White poison!? Low sugar diet does not improve insulin sensitivity but decreases glucose levels in obese subjects (read more)
• Myostatin knockout mice have increased brown fat - Does this mean that myostatin suppression will increase browning of fat in man, as well? The recent SuppVersity article on PGC-1A4 already confirmed that (read more) 
• Fish oil for alcohol withdrawal - Only three weeks on low dose EPA (60 mg/day) and high dose DHA (252 mg/day) supplement yielded significant decreases in distress symptoms and basal cortisol secretion in abstinent alcoholics (read more)
• SuppVersity Suggested Read: The Hunter-Gatherer Within: Health and the Natural Human Diet - "Don't get your food from the same place your car does" (read more)

There are going to be a couple of more news before the official next SuppVersity post will be posted in ~24h - so "like" the SuppVersity on Facebook and make sure you don't miss any of them. Have a nice weekend!

References:

• Arafa MH, Atteia HH. Sildenafil Citrate Attenuates the Deleterious Effects of Elevated Ammonia. Toxicol Mech Methods. 2013 Jan 23. 
• Casazza K, Fontaine KR, Astrup A, Birch LL, Brown AW, Bohan Brown MM, Durant N, Dutton G, Foster EM, Heymsfield SB, McIver K, Mehta T, Menachemi N, Newby PK, Pate R, Rolls BJ, Sen B, Smith DL Jr, Thomas DM, Allison DB. Myths, presumptions, and facts about obesity. N Engl J Med. 2013 Jan 31;368(5):446-54.
• Erceg S, Monfort P, Hernández-Viadel M, Rodrigo R, Montoliu C, Felipo V. Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology. 2005 Feb;41(2):299-306.
• Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Jan 29.
• Grès S, Canteiro S, Mercader J, Carpéné C. Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells. Mol Nutr Food Res. 2013 Feb 6.
• Jahangiri Noudeh Y, Hadaegh F, Vatankhah N, Momenan AA, Saadat N, Khalili D, Azizi F. Wrist Circumference as a Novel Predictor of Diabetes and Prediabetes: Results of Cross-Sectional and 8.8-Year Follow-up Studies. J Clin Endocrinol Metab. 2013 Feb;98(2):777-84.
• Kaur G, Molero JC, Weisinger HS, Sinclair AJ. Orally administered [14C]DPA and [14C]DHA are metabolised differently to [14C]EPA in rats. British Journal of Nutrition. 2013; 109, pp 441-448. 
• Martineti V, Tognarini I, Azzari C, Carbonell Sala S, Clematis F, Dolci M, Lanzotti V, Tonelli F, Brandi ML, Curir P. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus. Phytother Res. 2010 Sep;24(9):1302-8.
• Montes LF, Wilborn WH, Montes CM. Topical acne treatment with acetylcysteine: clinical and experimental effects. Skinmed. 2012 Nov-Dec;10(6):348-51.
• Pahua-Ramos ME, Ortiz-Moreno A, Chamorro-Cevallos G, Hernández-Navarro MD, Garduño-Siciliano L, Necoechea-Mondragón H, Hernández-Ortega M. Hypolipidemic effect of avocado (Persea americana Mill) seed in a hypercholesterolemic mouse model. Plant Foods Hum Nutr. 2012 Mar;67(1):10-6.
• Petrie JR, Shrestha P, Zhou XR, Mansour MP, Liu Q, Belide S, Nichols PD, Singh SP. Metabolic engineering plant seeds with fish oil-like levels of DHA. PLoS One. 2012;7(11):e49165. 
• Rudnan D, Smith RB 3rd, Salam AA, Warren WD, Galambos JT, Wenger J. Ammonia content of food. Am J Clin Nutr. 1973 May;26(5):487-90.
• Ueda M, Hayashibara K, Ashida H. Propolis extract promotes translocation of glucose transporter 4 and glucose uptake through both PI3K- and AMPK-dependent pathways in skeletal muscle. Biofactors. 2013 Jan 28.
• Zivadinov R, Treu CN, Weinstock-Guttman B, Turner C, Bergsland N, O'Connor K, Dwyer MG, Carl E, Ramasamy DP, Qu J, Ramanathan M. Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Feb 5.

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.

Pomegranate for Statin Users, Magnesium for Cancer-Free Colons, Cialis for Diabetic & Healthy Women and Protein Supplementation for 0.81kg More Muscle & 13.5kg More Strength Gains Than Placebo (Data From Meta-Analysis)

As the data in the graphs at the bottom shows, only vigorous physical activity (right), yet not moderate (middle), let alone light physical activity (left) will help kids to stave off the bad visceral body fat, which increases their waist line from year to year. The photo in the background was by the way taken in 1989 on Orchard Beach, in the Bronx. If I remember correctly that's 6 years before the release of Nintendo's first "Game Boy". And yeah, I got one and it really doubled if not tripled my sedentary time!

7 minutes! That's the SuppVersity figure of the week and a number that should actually ring a bell with everyone of you who is following my advice and pays a daily visit to the SuppVersity Facebook Wall. "Seven minutes" that's what scientists from the University of Alberta and their Canadian colleagues believe would be the amount of "vigorous physical activities" our kids should get (Hay. 2012). I am not sure, if those scientists are still youths, but assuming they are not, I wonder if they cannot remember the amount of "vigorous activity" (which was back in the day simply called "play") they themselves or at least their parents or grand parents got, in the days when you still had to physically kick a ball, if you wanted to play soccer with your friends.

I mean, it's already bad enough that today's kids spend 70% of their time with sedentary activity, only 23% with light activity (like walking from the sofa to freezer ;-), 7% with modest and only 0.6% with vigorous physical activity, wouldn't it be wise then, to rather shoot for the stars and work towards a much higher amount of vigorous activity? After all, even Hay's own study shows that only vigorous activity was associated with a reduced waist circumference and lower markers of metabolic disease (see illustration on the right).

Even if the kids don't make it to the moon, but over to the neighbor's basketball hoop or a public playground that would be a major improvement over the 'exhausting' walks from the Playstation to the fridge and back, wouldn't it?

• Pomegranate the better statin? Adding pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) to a statin and reduce adipose tissue ROS production by a whopping 73%!  In their most recent paper Mira Rosenblat, Nina Volkova, Michael Aviram report that the administration of Simvastatin (15 μg/ml) to macrophages in the petri dish did only only "modestly decreased macrophage reactive oxygen species (ROS)" (Rosenblat. 2012), the presence of punicalagin (15 or 30 μM) almost 'extinguished the fire' cutting back inflammation dose-dependently by another 61% or 79%.
  
  

  

  As a regular here at the SuppVersity yo will still be aware that Pomegranate does also contain a potent plant version of CLA, called CLnA, no? Well then go back and read the full article!

  Intriguingly, β-sitosterol alone showed had minor pro-oxidant activity, when it was administered to the J774A.1 macrophages cell line the researchers from The Lipid Research Laboratory in Haifa (Israel) were analyzing,
  

  "the combination of simvastatin, β-sitosterol and punicalagin, clearly demonstrated a remarkable 73% reduction in ROS production."

  So what's the use of the statin, then? After all the scientists also found (but rather not mention in their abstract) that the combination of β-sitosterol and punicalagin actually suppressed macrophage cholesterol synthesis as effectively as low dose Simvastin or high dose Pravastatin (Click here to read about pomegranate in the SuppVersity news)
• Organo-Magnesium stops colon cancer in its tracks by inhibiting inflammation, and the findings a group of researchers from the Gifu University Graduate School report in a soon-to-be published paper are not surprising. After all many epidemiological studies studies like Folsom & Hong (2006), for example, have already shown that there is a -23% reduced risk of developing colon cancer for 55-65 year-old Swedish women in the highest vs. lowers quantile of magnesium intake. Earlier this year Wark et al. conducted a randomized trial and meta-analysis of the hitherto published studies and found:
  

  "Our findings support the hypothesis that higher intakes of dietary magnesium are associated with lower risk of colorectal tumors. The consumption of magnesium-rich foods may be a new avenue to explore further in the search for cancer-prevention strategies." (Wark. 2012)

  Tabs or capsules? A 2010 study has the answer to the question which form of supplemental minerals is the best for you. Roswitha Siener and her colleagues from the University of Bonn in Germany found that magnesium oxide from effervescent tablets is better absorbed than from capsules and you can be pretty sure that similar results will be found for other forms of magnesium. My advice would yet be: Save the money and just go for plain magnesium citrate powder.
  The meta analysis yielded 13% lower risk of colorectal adenomas and 12% lower risk of colorectal cancer for every additional 100mg of magnesium per day. This does yet not mean that by eating pounds of magnesium you could render yourself 'cancer proof', but it is good evidence to make sure to get at least the into the 380-500mg range. And if you want to supplement, you really won't need the organ-magnesium Kuno et al. produced by mixing magnesium oxide (0.22 g), citric acid (0.55 g), malic acid (0.55 g), and glycine (0.22 g) - unless you can't tolerate it, cheap magnesium citrate will do just as well.
  
• Taldalafil for insulin resistant and healthy post-menopausal women?! (Murdolo. 2012) A group of European scientists have found that the administration of 10mg of Taldalfil (the notorious PDE-5 inhibitor in Cialis) to both diabetic and healthy controls led to
  
  • an increase in permeability surface area product for glucose , and
  • skeletal muscle interstitial lactate levels r
  The forearm glucose uptake, as well as the arterial lactate levels showed differential responses, while there was a trend for increased glucose uptake in the healthy controls, the latter was absent in the diabetic group. The profound decrease in arterial lactate levels in the diabetic patients, on the other hand, was not present in the healthy controls, whose lactate levels had already been in the normal range (see figure 1).
  
  

  

  Figure 1: Effects of 10mg of Taldalafil on arterial and intramuscular lactate concentration (Murdolo. 2012). The increase in intramuscular glucose oxidation (evidenced by the lactate that is generated during this process) could even be of interest to healthy women (and men?).

  Based on these findings, Guiseppe Murdolo and his colleagues argue that the results would suggest that acute Tadalafil administration can increase the capillary recruitment and nonoxidative glucose metabolism, without having consistent effects on forearm blood flow and regional lipolytic rate. However...
  

  "[...] notwithstanding the lack of measurable changes on forearm glucose uptake, the microvascular response to tadalafil emerged as an independent predictor of muscle glucose disposal in both T2D patients and insulin-sensitive controls."

  Well, and if those effects don't reach statistical significance, maybe 'others' will. After all a 2003 study by Caruso et al. suggests that Taldalafil can also increase "the frequency of sexual fantasies and of sexual intercourse, and enjoyment" (Caruso. 2003) in a group of  53 pre-menopausal women (age 22–28) years affected by arousal disorders. Maybe we should simply put Taldalfil into the drinking... ah, I am just kidding ;-)
• Finally! Scientists determine 'exactly'*rofl* how much more muscle you can gain with supplemental protein (Cermak. 2012). I hope I do not have to point you towards the irony in the headline of this On Short Notice item. If this ain't your first visit to the SuppVersity you should by now be aware that calculations like add 1g of protein per day and gain x-amounts of lean muscle mass per month, year or whatever timespan are nonsensical and will provide, if anything, a very general orientation.
  
  That said, it is still interesting to see the actual results Naomi M Cermak et al.'s quantitative meta-analysis of 22 studies, of which 77% were conducted with untrained individuals (64% with young trainees) produced. Most studies, which had a duration of 6-24 weeks (median: 12 weeks), used 3-5 x whole body workouts / splits coupled with milk (mostly whey) protein supplementation in amounts that ranged from 10g to 106g - keep that in mind when you think about how 'exact' the following figures can actually be:
  

  • 

    Size-wise and even more so strength-wise Arnold could still benefit from a protein shake after a workout. When it comes to the increases in type I and type II fiber CSA, his age could however put a spoke in his wheel.

    Fat free and fat mass - Compared with the placebo, protein supplementation significantly augmented the gain in FFM during prolonged resistance-type exercise training (weighted mean difference: 0.69 kg). A subgroup analysis for age showed that protein supplementation was beneficial for both the young and the old trainees, but that the total effect size in terms of fat free mass gains were ~1.7x higher in the young subject (+0.81 kg) than in the older ones (+0.48 kg;) subjects.
    
    What I find particularly surprising is that the subgroup analysis also revealed that training status had no significant and what's more, if anything a beneficial effect on the effect sizes in the young untrained (+0.75 kg) and trained subjects (+0.98 kg), respectively.
    
    As far as fat loss is concerned the scientists did not record any statistical significant differences compared to placebo and that despite the fact that the placebo in most of the 22 studies was a sugary carbohydrate drink.
  • Muscle fiber cross sectional area - As the gains in lean mass already suggest, the cross sectional area (CSA) of the muscle fibers increased: By ~ 212µm² in the type I fibers and 291µm² in type II fibers. Unfortunately, both the increases in type I and type II fibers were statistically significant only in the young trainees.
  • 1-RM Strength - The performance for the one-rep maximum (1RM) on the leg press improved across the board (+13.5kg more than in placebo) and that did work almost equally well for younger (+14.4kg) and older trainees (+13.1kg).
  I will leave it up do you what you want to do with this data and whether you think that studies like this are actually useful for the individual practitioner who does not - contrary to way too many dietitians - have to be convinced of the benefits of protein supplementation on top of the low 0.8g per body weight the dietary guidelines recommend.

That's it another saturdaily installment of On Short Notice and in case you feel that you could use some more educative news, tomorrow is another day ;-)

References:

• Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, cross-over, placebo-controlled study. BJOG. 2001 Jun;108(6):623-8.
• Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012 Nov 7.
• Folsom AR, Hong CP. Magnesium intake and reduced risk of colon cancer in a prospective study of women. Am J Epidemiol. 2006 Feb 1;163(3):232-5.
• Hay J, Maximova K, Durksen A, Carson V, Rinaldi RL, Torrance B, Ball GD, Majumdar SR, Plotnikoff RC, Veugelers P, Boulé NG, Wozny P, McCargar L, Downs S, Lewanczuk R, McGavock J. Physical Activity Intensity and Cardiometabolic Risk in Youth. Arch Pediatr Adolesc Med. 2012 Sep 10:1-8. doi: 10.1001/archpediatrics.2012.1028.
• Kuno T, Hatano Y, Tomita H, Hara A, Hirose Y, Hirata A, Mori H, Terasaki M, Masuda S, Tanaka T. Organo-Magnesium Suppresses Inflammation-Associated Colon Carcinogenesis in Male Crj: CD-1 Mice. Carcinogenesis. 2012 Nov 3.
• Murdolo G, Sjöstrand M, Strindberg L, Lönnroth P, Jansson PA. The Selective Phosphodiesterase-5 Inhibitor Tadalafil Induces Microvascular and Metabolic Effects in Type 2 Diabetic Postmenopausal Females. J Clin Endocrinol Metab. 2012 Nov 1.
• Rosenblat M, Volkova N, Aviram M. Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis. Available online 31 October 2012.
• Siener R, Jahnen A, Hesse A. Bioavailability of magnesium from different pharmaceutical formulations. Urol Res. 2011 Apr;39(2):123-7.
• Wark PA, Lau R, Norat T, Kampman E. Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis. Am J Clin Nutr. 2012 Sep;96(3):622-31. doi: 10.3945/ajcn.111.030924. Epub 2012 Aug 1.