Mercury, From Fish to Toenail; Less Testosterone Needed W/ TRT + Tongkat Ali; R,R-Monatin the Next Stevia From South Africa! Plus: Magnesium Protects Mitochondria from LPS & Caffeine Arteries from HIIT Induced Platelet Activity!

Image 1: Looks like the Terminator was concerned about "bone" health, maybe he should consider Tonkgat ali as an addition to his TRT... or whatever regimen;-)

If you want to, you can call today's news a special installment of "On Short Notice", I have already had a couple of interesting news and before I am piling up another truckload, I thought I could make at least some of you happy and put a handful of them out before the Super Human Radio & SuppVersity Science Round-Up on Thursday (you better make time to listen live, Thursday, 12PM/EST and download the first installment if you haven't done so, already ;-) and the "official" Saturdaily installment of "On Short Notice", here at the SuppVersity.

So let's see what we have here: Contrary to the order in the headline we will check out your toenails later, after all, I don't know what they look like and don't want to kill your appetite so that you cannot fully appreciate the findings of Fry et al. who discuss the potential application of an extract from the bark of Sclerochiton ilicifolius A.Meeuse as an all natural sweetener that's probably at least as, if not sweeter than stevia and - you guessed it - 100% calorie free! The same, i.e. being calorie free is obviously true for magnesium aspartate... whatever, in view of its potent protective effects against lipopolysaccharide induced mitochondrial damage and decay, you should not care about that, anyways.  And despite the fact that I would hope that the same goes for the minor pro-thrombotic effects of interval training, there may be one or another of the SuppVersity readers who's having issues with platelet activity already and will therefore be relieved to hear that a cup of coffee before your workout will not increase, but rather decrease the risk of thrombosis in response to the post-exercise increase in platelet activity.

You don't want to miss this week's installment of the joint Super Human Radio + SuppVersity
Science News Roundup - the show airs each Thursday, 12PM/EST (tune in live!)

The latter, i.e. the risk of thrombosis would by the way be even higher, if you were one of Xun et al.'s study participants who consumes one or more servings of fish per day. This would place you at greater risk of having high toenail mercury levels and with those being representative of whole body and tissue mercury levels you would already have higher baseline platelet activity than Mr. or Mrs. Healthy Average Joe, which would probably be a reason for your doctor to tell you that he cannot, by any means, put you on TRT (testosterone replacement therapy) - and that even if you were about as hypogonadal as the castrated rats in the Saadiah Abdul Razak study from the latest issue of Evidence Based Complementary Medicine. A study by the way you could print, show it to your doctor and say: "Look, I don't want to lose my muscle and break my bone, so let's do this you give me a script for low dose TRT and I get myself some quality Eurycoma longifolia extract and we will see how my values look like in 6 weeks from now." 

You see, as usual, even doctors can learn something, here at the SuppVersity so let's not put them on the rack for another paragraph or two and start right with our first item for today:

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  Image 2: Could the bark of these twigs from a spiny-leafed, hardwood shrub from South Africa hold a likewise natural stevia alternative?

  Is R,R-Monatin the new stevia? I know you all love your stevia, but there are people who simply hate the taste and still don't want to resort to any of the dubious sugar alcohols let alone the 100% artificial sweeteners, who may be interested that John C. Fry and a couple of other researchers published ad paper on a novel all natural sweetener from the bark of a South African spiny-leafed, hardwood shrub that goes by the name of  Sclerochiton ilicifolius A.Meeuse (Fry. 2013).
  According to the Fry et al., the compound has a potency above 3000 at 5% sucrose equivalent, which would make it (theoretically) even sweeter than stevia. Since the latter hit the market, we do yet all know how unrealiable these theoretical values are so that we will probably have to wait until the first monatin-based sweeteners become available - and you as a SuppVersity would be the first to know what's in there ;-)
  If we assume that there are no hitherto undisclosed health issues with monatin and it does in fact taste sweet and not disgusting, metallic or whatever, it is also likely that we are going to see new "proprietary" blends of stevia + monatin, similar to their artificial counterparts you still see in Coke Zero & Co - the quasi "natural" way to get as close as possible to the "true sugar taste", people are still craving, these days... if they don't hurry, I do yet doubt that there will be a market for products like that very long, as we are more or less trained to crave the "real sugar" taste, but this would be the topic for another blogpost ;-)

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  Figure 1: Effect of different doses of pre-supplementation with magnesium aspartate on markers of LPS induced mitochondrial decay, antioxidant activity and oxidative damage (data calculated based on Ahmed. 2013)

  250mg/day magnesium counter the metabolic derangements from lipopolysaccharide (LPS) intoxication When Lamiaa A. Ahmed added 20mg/kg or 40mg/kg (~125mg or 250mg in human equivalents) of magnesium aspartate to the chow mice that were pretreated with LPS injections, the researcher from the Faculty of Pharmacy at the University of Cairo found that this regimen restored body temperature (low dose) and heart rate (high dose) of the profoundly inflamed to normal, restored the lowered glutathione levels (both doses) and reduced (low dose) and normalized (high dose) the elevated creatine kinase (marker of cell damage) and thiobarbituric acid reactive substances (TBARS; marker of oxidative damage) levels that had been elevated by the lipopolysaccharide treatment (Ahmed. 2013).
  The ATP:ADP ratio, the activity of the sodium potassium pumps and the creatine phosphate levels (CrPh protects the cell wall from damage as you remember from a previous installment, right?) were not completely restored to, but the pathological changes were minimized dose-dependently. In conjunction with the normalization of the lactate to pyruvate ratio, a sign of either exertional exercise or - if it occurs at rest, as it does here - mitochondrial failure, these observations indicate that Mg therapy could be a reliable protective agent in LPS-induced cardio- and general myotoxicity. In that it should be noted that higher, but not exorbitantly high (250mg is roughly 2/3 of what you should aim to get from our diet everyday, anyway) doses were more effective in reducing cell membrane damage as well as in improving the intracellular acidosis, energy production, oxidative stress and Na+,K+-ATPase activity and corresponded with a better perseverance of the mitochondrial ultrastructure.
  And while Ahmed sees the main application of Mg aspartate therapy in "critically ill" patients, I would say that the large group of patients (and non-patients) with other pathologies such as a leaky gut would benefit as well, since the defective gut barrier opens the door for the "excrements" of your gut bacteria, to induce all sorts of pathologies including mitochondrial damage and decay, but also depression, obesity, diabetes, etc. (Maes. 2008; Musso. 2010)... and before I forget to mention it is not unlikely that cheap magnesium citrate (if tolerated) would do the job just as well - maybe in a slightly higher dosage of say 300mg per day (best taken in divided doses with food).

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  Image 3: Coffee is full of wonders ;-)

  Antithrombotic effects of caffeine blunt platelet activity in response to interval training The use of 3mg/kg (equiv. to ~1 large cup of strong coffee or 2 smaller cups of regular coffee) of caffeine as an ergogenic aid during aerobic interval training cannot just improve your performance, it will also prevent the pro-thrombotic platelet function activation that occurs during exercise. That's the somewhat surprising finding of the one of the latest studies from the Health Innovations Research Institute at the School of Medical Sciences on the campus of the RMIT University in Melbourne, Australia (Whittaker. 2013).
  Whether this effect is of any importance to you certainly depends on your personal health. Personally, I would say that it is negligible for the vast majority of people who engage in strenuous athletic activities, if you belong to a risk group where platelet function is either high (risk of developing thromboses) or low (risk of bleeding) you may want to keep these results in mind.
  And if you don't care about platelet function, you may be considering to have another cup of coffee, when I tell you that ~3 cups per day appear to offer some protection against skin cancer, parkinson's and non-alcoholic-fatty-liver disease (click on the links to read the full stories on the SuppVersity Facebook Wall).

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  Image 4: Remember last week's post on the mercury in fish and how it's not simply excreted with the selenium, let alone the cysteine it's bound to? It looks like the toenails of young Americans would confirm those lab results.

  Something fishy about toenail mercury levels I guess all of you will remember my "shocking" post about the mercury toxicity from fish (cf. "Mercury in Fish NOT Harmless, Regardless of Cysteine, Selenium, EPA or DHA!"), this one could actually go as sort of a follow up post, as it deals with the real-world consequences of mercury exposure and the subsequent deposition of the heavy metal in the toe nails of the 4,344 American male and female participants (age 20–32y) in the CARDIA Trace Element Study researchers from the Gillings School of Global Public Health and School of Medicine at the University of North Carolina have recently examined (Xun. 2013).
  I know, it may sound gross, but toenails have, among the various biological specimens you could theoretically analyze, the advantage of providing a relatively reliable long-term measure of Hg exposure (from a few months to a year), are easily collected, transported,stored, and cleaned and are relatively sheltered from environmental contaminants and less likely to be contaminated by shampoo, hair treatments, and medication (Morris. 1983, He 2011).

  

  Image 5: Who would have thought that your toenails provide a way better measure of the toxic load you have accumulated than your hair, for example? Just looking at them is yet not enough for a thorough analysis

  Since the Hg levels in toenails also have relatively high correlation with both mercury intake (r = 0.54; Ohno. 2007) and the mercury deposition in critical organs (spec. in the brain - r = 0.65 ; Bjorkman. 2007), it should be obvious that the association between toe nail mercury levels and fish intake in all, but those participants who lived in Oakland and had the lowest (0.45 servings per day) fish intake per day could have a significant impact on the health of the subjects that consume more than one serving of fish per day and have a 76% higher beta coefficient of the natural logarithm of toenail Hg level than those who consume fish / seafood less than once per day (this mean that the mercury in the toenails of daily fish eaters increases 75% more rapidly towards that level than in those who eat 0.35 to 1.03 servings). Interestingly this was particularly true for the Caucasian men in the study, where the beta coefficient was another 45% higher (beta = 0.64 vs. beta = 0.44).
  Despite the fact that these results seem to confirm that eating one dose of untested canned tuna (which would probably go as way more than one serving in the eyes of the scientists) is not necessarily the best idea. It does however not mean that you cannot have you once or even twice a weak salmon steak or sushi - just keep your diet more versatile and don't make fish (or any other single foodstuff your only "allowed" source of protein or fat.

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  Figure 2: Weight of castrated rats on TRT, TRT (50% dose) + Eurycoma longifolia  (EL) or Eurycoma longifolia, alone, at the end of the 6-week supplementation phase, ratio of bone building osteocalcin to CRX a marker of bone resorption and actual bone strength, as measure by maximal tolerable load and Young's Modulus; all data expressed relative to sham operated (=intact) rats (data calculated based on Saadiah Abdul Razak. 2013)

  Low dose testosterone + long jack better than TRT alone? The results Saadiah Abdul Razak et al. present in the latest issue of Evidence Based Complementary Medicine don't actually look like they were interesting for muscle heads, I mean "androgen dependent osteoporosis", where are the word hypertrophy, skeletal muscle, or at least ripped & jacked? And I have to admit that of these only "skeletal muscle" makes its appearance somewhere in the introductory remarks of the discussion and only in the context of the "auxiliary functions" of testosterone as a growth hormone and IGF-1 booster and muscle builder. I do still believe that the data in the figure 2 on the right is going to get your attention - after all, the combination treatment of testosterone + Eurycoma longifolia did not "just" restore the balance of the "bone builder" osteocalcin to the "bone eater" ORX (actually it's just a marker of bone resorption) to normal (=sham levels), it did also effectively build the strongest bones, with the highest maximal load in Newton and the greatest elastic stability, as measured by the Young's Modulus.
  What's interesting, as well, is that all treatments were equally effective in restoring normal body weight - who knows maybe 15mg/kg/day (HED: 2.4mg/kg; ~170-250mg/day) of Eurycoma longifolia (EL) extract would even make a valuable stand alone (no pun intended ;-) testosterone booster for mild cases of real hypogonadism (not the one where your diet is shitty, your training sucks and it's your "low T" that you believe is to to blame that you make no gains), or an adjunct to HRT that would allow you to use only half the regular dose (this was done in the study at hand) and see similar results!? That it's good for sperm quality and testosterone, when it's administered in ~13x higher dosages in rodents (Chan. 2009) and for sperm health in men (at about the dosage used here; cf. Tambi. 2010) has already been established.
  And still, the "major gap" of which Bhat et al. postulated that it existed "in [sic!] providing scientific base for commercial utilization and clearance of the Tongkat Ali products with regard to consumer's safety" is still in existence. Moreover, the same could be said about our knowledge with respect to the individual effects of the potentially biologically active component(s) in the plant and respective extracts. Before those issues are not solved, the "extract" you may buy could be anything from uberpotent to simply toxic... although I suspect that it is still most likely that it will simply be ineffective.

What? That went too fast? Don't worry, it's just two days to the Thursdaily Science News Roundup on SHR, four days to the next official installment of "On Short Notice" and just one click away from a handful of additional up-to-the-minute news on the SuppVersity Facebook Wall such as

• the correlation of low growth hormone levels with NAFLD (= non-alcoholic fatty liver disease), 
• a study on how digestion potentates the antimicrobial activity of coconut oil,
• a potential successor to metformin that triples muscular glucose uptake in the absence of insulin 

and all the other interesting tidbits I have already and am still going to post there even before the next SuppVersity news is going to be published right here, tomorrow! Ah,... and by the way it's not prohibited to share articles you like on Facebook and other social media outlets ;-)

References:

• Ahmed, L.A., Protective effects of magnesium supplementation on metabolic energy derangements in
  lipopolysaccharide-induced cardiotoxicity in mice. Eur J Pharmacol. 2013.
• Bhat R, Karim AA. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia. 2010 Oct;81(7):669-79. Epub 2010 Apr 29. 
• Bjorkman L, Lundekvam BF, Laegreid T, Bertelsen BI, Morild I, Lilleng P, Lind B, Palm B, Vahter M. Mercury in human brain, blood, muscle and toenails in relation to exposure: an
  autopsy study. Environ Health. 2007; 6:30 
• Chan KL, Low BS, Teh CH, Das PK. The effect of Eurycoma longifolia on sperm quality of male rats. Nat Prod Commun. 2009 Oct;4(10):1331-6. 
• Fry JC, Yurttas N, Biermann KL, Lindley MG, Goulson MJ. The Sweetness Concentration-Response of R,R-Monatin, a Naturally Occurring High-Potency Sweetener. J Food Sci. 2013 Aug 27.  
• He K. Trace elements in nails as biomarkers in clinical research. Eur J Clin Invest. 2011;  41(1):98–102.
• Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.
• Morris JS, Stampfer MJ, Willett WC Dietary selenium in humans: toenails as an indicator. Biol Trace Elem Res. 1983; 5:529–537.
• Ohno T, Sakamoto M, Kurosawa T, Dakeishi M, Iwata T, Murata K. Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function. Environ Res. 2007;103(2):191–1.
• Saadiah Abdul Razak H, Shuid AN, Naina Mohamed I. Combined Effects of Eurycoma
  longifolia and Testosterone on Androgen-Deficient Osteoporosis in a Male Rat Model. Evid Based Complement Alternat Med. 2013;2013:872406. Epub 2013 Aug 9.
• Whittaker JP, Linden MD, Coffey VG. Effect of Aerobic Interval Training and Caffeine on Blood Platelet Function. Med Sci Sports Exerc. 2013 Aug 29.
• Xun P, Liu K, Morris JS, Jordan JM, He K. Distributions and determinants of mercury concentrations in toenails among American young adults: the CARDIA Trace Element Study. Environ Sci Pollut Res Int. 2013 Aug 25.

Tongkat Ali - Malaysian Viagra W/ Anti-Belly Effect: More Than 30% Reduced Omental Fat Pad Size + Corresponding Increases in Testosterone W/ Human Equiv. of 4g+/Day

It's efficacy in situations like this has more scientific back-up than any of the muscle building of fat burning promises some Tongkat Ali supps come with.

By now, most of you should have read the article on the testosterone "boozing" effects of alcohol and realized that the post workout Margarita probably comes off second best, when we compare it to whey and may - at least until we don't know otherwise - actually be pathological (=the result of a disturbance of the normal hormone metabolism in the liver). That being said, we better go back the "tried(!) and proven(?)" stuff. I mean a herb that goes by the name "Long Jack" does already sound way more promising than a "Blood Mary" doesn't it?

"Long Jack? ;Malaysian viagra? Ok, I am in!"

As the popular name already implies, the root of Eurycoma longifolia Jack, an evergreen plant that belongs to the family Simaroubaceae has a long (all puns intended) tradition in folk medicine. For which purposes? Well, in Malaysia, where people obviously like it a little more explicit, it's called "Tongkat Ali" (TA) and means (literally translated) "Ali's walking stick"... if that ain't explicit enough for you, just call it the "bushman's viagra", or whatever you like.

What's interesting and important to know though is that medicinal value highly of the root extract depends on the soil the plant was grown on. Tongkat Ali from the Malaysian Peninsular, for example, has higher concentrations of phytochemical compounds, such as eurycomaride, tannins, high molecular weight polysaccharides, glycoproteins, mucopolysaccharides and alkaloids of the quassinoid group, than TA from Thailand, Vietnam or Indonesia (Jiwajinda. 2001; Miyake. 2009). This is an important fact to keep in mind, when you buy your TA and a potential reason why you (a) may require way higher dosages than science would suggest to see any effect or (b) may not experience any of the benefits you may have hoped for (e.g. raging libido, increased testosterone and, as you are about to learn in today's article, loss of belly fat).

"Did I hear fat loss?" Yeah, you did!

I have to concede, the hitherto unrecognized fat loss effects Solomon et al. report in their latest paper that's about to be publishe in the peer reviewed journal andrologia were actually the main reason the 14-day rodent experiment the South African researchers conducted eventually made it into the SuppVersity news. The meager testosterone increase of +30% alone doesn't give me a kick, at all. I mean there are way more potent natural testosterone boosters out there that don't exert any beneficial downstream effects on your physique. So why should we bother?

Figure 1: Relative (in % of pre values) body weight, testes weight, prostate weight, weight of the epididymal and omental fat pads, the gastrocnemius muscle and the testosterone levels of the rodents after 14 days on the high or low dose of the extract (

And in fact, the 5.7% reduction in body weight the rodents in both the low (200mg/kg) and high dose (800mg/kg) arm of the study experienced would be quite the opposite of what you'd usually expect as a downstream effect of increased testosterone levels in otherwise healthy rodents. With a statistically significant increase in sperm vitality in the low dose and a less pronounced statistically non-significant increase in sperm vitality in the high dose group, as well as the highly significant increases in sperm count in both groups, it is yet very unlikely that the already small amount of body weight the rodents lost in the course of the 14-day experiment was a sign of toxicity or whatever.

What's more likely is that the overall weight loss effect is simply the result of the highly significant -31.9% reduction in omental and probably other not explicitly measured body fat (not the epididymal fat, i.e. the fat around the reproductive organs, though).

"How much of this stuff do I need?"

Don't be fooled: The testosterone and libido boosting effects we see in the study at hand is something dozens of other herbs can do as well, thin of the study on Nigella Sativa from one of the past installments of "On Short Notice", for example.

Provided you can get your hands on a correspondingly potent extract, it probably would not be necessary, and certainly a waste of valuable ressources to take more than the low dose regimen (HED 4g/day) , which is, compared to what we have hitherto seen in human trials, still hilariously much.

For the fertility part of the equation, way smaller doses of as little as 300mg of a freeze dried water extract from TA (brandname Physta(R)) have shown quite astonishing results in a group of 30-55 year old male subjects who achieved a 44.4% higher sperm motility, 18.2% higher semen volume and subjectively improved erectile performance after 12-weeks on this commercially available product (Ismail. 2013).What you should at least keep in mind though is the fact that financing of the study was provided by Biotropics Malaysia Berhad, the producer of Physta.

Similar fertility related results were also reported by Tambi et al. in 2010 (another "proprietary extract" ;-) and a handful of older and in some cases non-peer reviewed studies. As far as more physical culture related effects are concerned, a recent review by Chen et al. concludes that

"Eurycoma longifolia Jack, or 'tongkat ali', has not appeared to elicit any ergogenic effect on endurance performance in a limited number of studies of these herbs. However, future studies of this herb are definitely warranted because there might be a dose-dependent response and the supplementation duration of the previous studies might have been too short." (Chen. 2013)

It would therefore appear as if TA was more of "classic" libido & testosterone booster than an ergogenic. Something like tribulus and maca and just as those two probably of very dubious usefulness for young athletic men in the prime of their reproductive years.

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Bottom line: That being said, Long Jack could be worth a try for everyone with already (or temporarily ;-) reduced testosterone levels, at least if we trust the judgement of Tami et al. who conclude their 2013 study into the effects of 1 month on 200g of a water-soluble TA extract with the words: "The standardised water-soluble extract of Tongkat ali proved to be a suitable herbal supplement in overcoming symptoms of LOH [late onset hypogonadism]." (Tambi. 2013)

The veterans among the SuppVerity readers may remember that I also covered the 2013 study by Tambi et al. on the usefulness of TA for men hypogonadal men (learn more)

If you still insist to try it, you should keep an eye on the eurycomanone and 13α(21)-dihydroeurycomaone content of whatever product you are buying, because these are the two fractions which will increase LH and FSH production and are thus probably responsible for jacking up your testosterone and sperm production (Low. 2013).

What? You cannot find a product that's standardized for those? Not even a supplement producer losing a word about their existence? Well, that's how this business works. Cite the studies and discard all the nasty details you don't like...


References:.

• Chen CK, Muhamad AS, Ooi FK. Herbs in exercise and sports. J Physiol Anthropol. 2013 Mar 8;31:4. doi: 10.1186/1880-6805-31-4. Review.
• Ismail SB, Wan Mohammad WM, George A, Nik Hussain NH, Musthapa Kamal ZM, Liske E. Randomized Clinical Trial on the Use of PHYSTA Freeze-Dried Water Extract of Eurycoma longifolia for the Improvement of Quality of Life and Sexual Well-Being in Men. Evid Based Complement Alternat Med. 2013;2013:429268.
• Jiwajinda S, Santisopasri V, Murakami A, Hirai N, Ohigashi H. Quassinoids from Eurycoma longifoliaas plant growth inhibitors.Phytochemistry. 2001; 58:959–962
• 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. 2013 Feb 13;145(3):706-14.
• Miyake K, Tezuka Y, Awale S, Li F, Kadota S.Quassinoids fromEurycoma longifolia. J Nat Prod. 2009; 72:2135–2140. 
• Solomon MC, Erasmus N, Henkel RR. In vivo effects of Eurycoma longifolia Jack (Tongkat Ali) extract on reproductive functions in the rat. Andrologia. 2013 Mar 6.
• Tambi MI, Imran MK. Eurycoma longifolia Jack in managing idiopathic male infertility. Asian J Androl. 2010 May;12(3):376-80. doi: 10.1038/aja.2010.7. Epub 2010 Mar 29.
• Tambi MI, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia. 2013 May;44 Suppl 1:226-30.