Science Round-Up Seconds: Follow-Up on Gum Arabic for Fat Loss. DMAA or Schizandra, Which Caused a Stroke in a Young Soldier? Low Doses of Resveratrol Better Than High Ones? Vitamin E Keeps Diabetic Brains Intact.

When it's served like this, Gum Arabic looks more like a healthy snack than a weight loss adjuvant.

I guess everyone who has already listened to the podcast of yesterday's show or was even able to listen live, will have noticed that the audio quality - yet not my German accent - have improved significantly, now that Carl and I did eventually switch to Skype instead of the landline. I know, you have been telling me that all along... be that as it may, unless my Internet connection hangs up for whatever reasons we will continue to do the SuppVersity Science Round-Ups via Skype from now on. Apropos, there will definitely be another show next Thursday (assuming that the world did not collapse by then ;-)

Follow up on Gum Arabic: Dosing & mechanism

In addition to that, I was actually presently surprised how much ground we were able to cover. Allegedly, we have gone way over the scheduled 60min, and I guess I could have said a couple of additional words on the Gum Arabic study and the astonishing fat loss results what I did mention was that it works astonishingly well, what I did not tell you about - or I have forgotten I did (too little caffeine I guess ;-) - is the dosage and the mechanism of action. At least as far as the former is concerned there is no debating that the fat loss magic (-2.1% from ~20% body fat to ~18% in 6 weeks; cf. Babiker. 2012) happened with just 30g of the substance that's derived  from exudates of Acacia senegal or Acacia seyal trees per day. Oher than the diarrhea and bloating, I did already mention on the show, the on average 19-year old perfectly healthy young women in the active arm of the study complained about nausea (82% in the first week) and an  "unfavourable oral viscous sensation" (100% in the first week). The latter is particularly interesting, because it does actually give us a hint on the underyling mechanism which is "not yet fully elucidated, because of a small number of conducted studies" (on its weight loss effects, but could be related to the increase in plasma leptin (without resistance obviously) as well as the increased fatty acid oxidation in muscle tissue in response to viscous fiber ingestion Islam et al. have reported only recently in Obesity (Silver Spring) earlier this year (Islam. 2012). I guess that we are going to see follow up studies on this one pretty soon and you all know that the Science Round Up and of course the SuppVersity news is where you are going to read about them first ;-)

Now that we lost the working weight loss adjuvants behind us, let's get to one which doesn't have any record of helping with weight and was still in each and every fat burner on earth before it was banned: DMAA (1,3 dimethylamylamine) aka geranium oil or geranium extract.

DMAA induced stroke in young soldier!? Or is it maybe the Schizandra that's to blame?

We all know that the job of a soldier is dangerous. A recently published case-report in Military Medicine does yet show that these dangers may not always be due to standing in the line of fire, but can also arise as a consequence of having too much DMAA supplements in your stash (Young. 2012) :

Is schizandra to blame? While the data is in fact scarce and the overall understanding of it's effects would suggest that the TCM herb would rather protect than harm the brain, it is at least worth noting that (a) schizandra has been found enhance the stimulation of the dompaminergic system (Chang. 1991) and (b) that we know that the abuse of cocaine has very similar effects on neurotransmitters (Prakash. 1993) and is associated with an increased risk of hemorrhagic stroke (Kousik. 2012)

"A 26-year-old male was presented to a military treatment facility in Afghanistan shortly after taking a weight-lifting supplement called Jack3d with a severe headache and was subsequently found to have suffered a Dejerine-Roussy variant right thalamic hemorrhagic stroke. Jack3d active ingredients include geranamine, schizandrol A, caffeine, β-alanine, creatine monohydrate, and L-arginine α-ketoglutarate. A literature search revealed case reports suggesting some of the constituent ingredients may predispose to stroke and hemorrhage and also revealed a substantial paucity of data existed regarding schizandrol A, a herb used in traditional eastern medicine." (Young. 2012)

Now, you always have to take case reports like this with an appropriate amount of skepticism - specifically, when the subject has a personal interest of not disclosing all the "supplements" he may have been taking in order not to lose is job. That being said, you know my take on DMAA from the round-table discussion with Patrick Arnold, Kurtis Frank, and one of the guys from Ergo Log. Bottom line: There really isn't any reason to be pissed of by the ban. Even if it's not to prevent stroke, it will prevent the onset of chronic fatigue syndrome in many aspiring physical culturists.

A re-appreciation of vitamin E and resveratrol

"Regular" vitamin E, i.e. alpha tocopherol, has gotten somewhat of a bad rep as of late and whenever resvertatrol is found to produce any the myriad astonishing health effects scientists have identified, it's either these effects occur either in the petri dish or in a rodent model with (often injected) mega-doses you imply couldn't afford taking on a regular basis. In this regard, a recently published paper which reports profound reductions in the fatty acid synthase, and fatty acid oxidation in the livers and adipose tissue of mice in response to a 0.005% resveratrol enriched high fat chow (this would be ~36mg/day for a human) is yet more than only an exception to the rule (Cho. 2012).

Figure 1: Metabolic effects of high fat diet (HFD) or HFD with two different doses of resveratrol; data expressed relative to mice on a standard diet (Cho. 2012)

I mean, take a look at the effects this low dose had compared to the 4x higher dosing in a second group of mice who received the human equivalent of ~142mg/day (see figure 1). Is this really another instance where more does not only yield no additional benefits, but actually reduces the effect (incidentally, de la Lastra et al. have discussed the pro-antioxidant effects of high doses of resveratrol in 2007 already; cf. de la Lastra. 2007)? Or is this just because "mice are no little human beings" and the results are therefore meaningless for us?

If you believe the latter is the case, I suggest you simply scroll down to the overview of some recent facebook news instead of reading how the adminstration of vitamin E to alloxan-induced diabetic rodents (standard model for type II diabetes) did ameliorate the shrinkage of Purkinje cells and apoptosis of cells in the granular layer, the mitochondrial defects, the splitting  of the myelin sheaths and widening axonal spaces, as well as the decrease in the number of GFAP-positive astrocytes (those that still produce a protein, namely GFAP that's responsible to keep their structure intact) in the cerebellar cortex (Mohammed. 2012)

 + + + + + + + + + + + + + +

That's it for today: You know the holiday season is coming so having too many Seconds isn't a particular good idea these days. If you still need something I suggest you pick one of the easily digestible Facebook news, for example...

• GI, GL and cancer risk - While there are statistically significant associations, only the ones for the glycemic load, which adds another quality factor namely GI + carbs per 100g to the equation, appear to have real world significance, though (read more)
• Folic acid in pregnancy - It's not all gold that glitters in ads and carries the letters "RDA". Among the profound epigenetic effects that have been observed in rodent studies, some sound as if they were from a list of the most rampant current pathologies (read more)
• Adiposity will shrink your brain - Leptin resistance is associated with reduced brain volume, associations persist even when they are corrected for BMI (read more)

You know there is more and there is even more to come. So in case the world does not explode within the next hours you know where to go if you are bored waiting for the "Zombie Repopulation" to happen.
 
References:

• Babiker R, Merghani TH, Elmusharaf K, Badi RM, Lang F, Saeed AM. Effects of gum Arabic ingestion on body mass index and body fat percentage in healthy adult females: two-arm randomized, placebo controlled, double-blind trial. Nutr J. 2012 Dec 15;11(1):111. 
• Cho SJ, Jung UJ, Choi MS. Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. Br J Nutr. 2012 Dec;108(12):2166-75.
• de la Lastra CA, Villegas I. Resveratrol as an anti-oxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans. 2007;35:1156–1160.
• Islam A, Civitarese AE, Hesslink RL, Gallaher DD:  Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression  of fat oxidation genes in rats. Obesity (Silver Spring)2012, 20(2):349–355.
• Kousik SM, Napier TC, Carvey PM. The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation. Front Pharmacol. 2012;3:121.
• Prakash A, Das G. Cocaine and the nervous system. Int J Clin Pharmacol Ther Toxicol. 1993; 31:575–581.
• Young C, Oladipo O, Frasier S, Putko R, Chronister S, Marovich M. Hemorrhagic Stroke in Young Healthy Male Following Use of Sports Supplement Jack3d. Military Medicine. December 2012; 177(12): 1450-1454(5).
• Zhang L, Niu X. [Effects of schizandrol A on monoamine neurotransmitters in the central nervous system]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1991 Feb;13(1):13-6.

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

Wallaby Lachie Turner (left), Greg Inglis (centre) & Jarryd Hayne (Stuff.co.nz) - who would have thought that the relative length of their 2nd and 4th digit could predict their testosterone response after the sprint? Not you? Well, then you got to check out the first of the short-items at the bottom.

Those of you who have listened to yesterday's installment of the SuppVersity Science Round-Up on Super Human Radio, will have realized that the show did - as usual - take a somewhat different direction than originally planned. Before I get to the actual SuppVersity Round-Up Seconds, of which there actually weren't all too many I consider absolutely newsworthy and appropriate for a written format, I thought I would briefly mention the paper on which I based the hypothesis (remember: this is nothing certain) that there may be a link between the calcium-influx into the muscle and the strength and hypertrophy effects of performance enhancing drugs (spec. those with a high anabolic : androgenic effect ratio) - for those of you who may want to follow up on this hypothesis or think Carl and I were just making things up ;-) 

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

Nicotine exposure, brain aromatase and gender-specific implications

With the advent of new technologies, esp. the direct observation of aromatase activity in primate brains (Lidstrom, 1998; Kim, 2009; Biegon, 2010), our understanding of the peripheral effects of certain substances on hormone metabolism, one of the latest such insights pertains to the effects of nicotine exposure on the expression of the aromatase enzyme in the brain.

Figure 1: Effect of nicotine on brain aromatase availability in the female baboon. Representative baseline PET image coregistered with MRI at baseline and following injection of low dose (0.015 mg/kg) or high dose (0.03 mg/kg) nicotine. PET images show averaged frames acquired between 52.5 and 90 min after tracer injection, pseudocolored using the rainbow spectrum, with purple indicating the lowest density and red indicating the highest density of radioactivity (from Biegon, 2010).

In a recently published paper scientists from the Brookhaven National Laboratory Upton in New York did now connect the dots between the previously observed direct inhibitory effects on the central expression of the CYP19a mediated expression of the aromatase enzyme of nicotine and (potentially) other tobacco alkaloids. Thus, Anat Biegon, Nelly Alia-Klein and Joanna S. Fowler are not only able to explain, why women are more susceptible to the addictive effects of the nicotinic acetylcholine receptor agonist, which accumulates in the leaves of several members of the Solanaceae (nightshade) family, than men, but observations such as the early onset of menopause and lower plasma estrogen levels and correspondingly higher osteoporosis risk in female smokers compared to their non-smoking peers, as well (Daniell. 1972; MacMahon. 1982; Nusbaum. 2000; Pant. 2008; Korkor. 2009).

Table 1: Comparison of the effects of nicotine exposure and the effects of an aromatase inhibitor (at different time points in life) on sexual behavior, anxiety and depression, hot flashes, and weight gain in men and women (Biegon. 2012)

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

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

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

Other news that did not make it into the show

As I have mentioned in the introduction, we did cover a hell lot of ground, so that most of the other studies are directly related to the luteinizing hormone negative feedback and thus no real "news" - I skipped discussing those, since I though that everyone listening will get the main message and did not want to bore those of you who are not interested in this topic with a show solely on the effects of nutrient deprivation and exercise on the endocrine milieu. But enough of the excuses, there is still more:

• Right-left digit ratio (2D:4D) predicts testosterone response to exercise in 79 professional Rubgy players (Kilduff. 2012) - In the analysis, researchers from the Swansea University at the Sports Science, Talbot Building in Singleton Park,  Swansea, UK, found that despite significant differences in basal testosterone levels, the 2D:4D ratio, which is generally regarded as an indicator of in-utero androgen exposure was significantly associated with a lower testosterone response to repeated sprint-agility tests in the 25 subjects who participated in the active arm of the study.

• Caffeine prevents weight gain and cognitive impairment by high fat diet (Moy. 2012) - This is not news? Just read on, you will soon realize that it is news! Firstly, the scientists from the University of Albany identified an ameliorative effect of caffeine on the diet-induced reduction of hippocampal expression of the brain-derived neurotrophic factor (BDNF) as the underlying mechanism behind it's neuroprotective effect (the same stuff that's also increased by exercise, by the way).
  
  

  

  Figure 2: Assuming this is not a mistake in the study caffeine once a week would be enough to boost the BDNF levels of junk-food and normal eaters alike (Moy. 2012)

  And secondly, the rodents received only a single, weekly intraperitoneal injection that would be equivalent to ~250mg in a human being (I double checked, the study says: "All animals received either caffeine (20 mg/kg) or saline (volume-matched), i.p., once weekly."; my emphasis in Moy. 2012). If that's not a mistake, chronic caffeine consumption may not even be necessary to see a hell-lot of the anti-diabetes and anti-neurological damage effects of coffee - just 2 cups once per week that's it!
  
  And if you look closely at the data in figure 2 you see that even "normal" people may benefit from this regimen.

Since tomorrow is an official installment of "On Short Notice" due, I will leave you on that flabbergast caffeine study and just remind you that there is - as everyday (guaranteed even on Christmas ;-) tons of interesting new stuff on the SuppVersity Facebook Wall, as well - let's see what we have today:

• Insulin has anti-Alzheimer's effect - Yeah you read me right. It reduces the formation of ameliod beta plague (read more)
• Yet more plant extracts with natural anti-cancer activity: Chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L known in TCM as Rui Xiang Lang D (read more)
• Want to father a Nobel Laureate and in your early to late 30s? Than its about time you procreate! Study finds U-shaped curve for father's age and intellectual abilities of the offspring peaking at 32-37 years or so (read more) 
   
• ...plus the rest I did not mention (read all)

I guess with the podcast to listen to and some food for thought on once-weekly caffeine administration (on a side note, injecting into the intraperitoneal cavity is, for most substances, only minimally different from oral ingestion and done only to assure that the animals don't spit whatever you want them to ingest back out) you will survive the next couple of hours until the facebook news will receive another update and the next installment of "On Short Notice" is going to be published? If not, complain in the comment area ;-)
 
References:

• Biegon A, Kim SW, Alexoff DL, Jayne M, Carter P, Hubbard B, King P, Logan J, Muench L, Pareto D, Schlyer D, Shea C, Telang F, Wang GJ, Xu Y, Fowler JS. Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole. Synapse. 2010 Nov; 64(11):801-7. 
• Biegon A, Alia-Klein N, Fowler JS. Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain. Front Pharmacol. 2012;3:185.
• Daniell HW. Osteoporosis and smoking. JAMA. 1972 Jul 31;221(5):509.
• Estrada M, Liberona JL, Miranda M, Jaimovich E. Aldosterone- and testosterone-mediated intracellular calcium response in skeletal muscle cell cultures. Am J Physiol Endocrinol Metab. 2000 Jul;279(1):E132-9.
• Hiltunen M, Iivonen S, Soininen H. Aromatase enzyme and Alzheimer's disease. Minerva Endocrinol. 2006 Mar;31(1):61-73.
• Korkor AB, Eastwood D, Bretzmann C. Effects of gender, alcohol, smoking, and dairy consumption on bone mass in Wisconsin adolescents. WMJ. 2009 Jul;108(4):181-8.
• MacMahon B, Trichopoulos D, Cole P, Brown J. Cigarette smoking and urinary estrogens. N Engl J Med. 1982 Oct 21;307(17):1062-5.
• Moy GA, McNay EC. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF. Physiol Behav. 2012 Dec 6.
• Nusbaum ML, Gordon M, Nusbaum D, McCarthy MA, Vasilakis D. Smoke alarm: a review of the clinical impact of smoking on women. Prim Care Update Ob Gyns. 2000 Sep 1;7(5):207-214.
• Pant S, Shapiro CL. Aromatase inhibitor-associated bone loss: clinical considerations. Drugs. 2008;68(18):2591-600.
• Roselli CE, Abdelgadir SE, Ronnekleiv OK, Klosterman SA. Anatomic distribution and regulation of aromatase gene expression in the rat brain. Biol. Reprod. 1998; 58, 79–87.
• Roselli CE, Resko JA. Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance. J. Steroid Biochem. Mol. Biol. 2001; 79, 247–253.

 

Science Round-Up Seconds: PGC-1 Alpha 4 Unlocks Muscle Growth, Alpha Lipoic Acid & Dietary N-6 Overload, Aspirin & Other NSAIDs Your Liver & Overall Mortality

Myotubes under the microscope - vehicle (top, normal size), clenbuterol (+100% protein content, middle), clenbuterol + PGC1a4 inhibition (+50% protein content, bottom)

Actually I would hope that you have by now already listened to yesterday's installment of the SuppVersity Science Round-Up. If you did, you are one of a group of highly privileged trainees who already knows why not all PGC1-alpha is created equal and how the alpha-4 isoform does appear to be the missing link between myostatin, on the one hand, and IGF-1 on the other. If you have already listened to the show, you may also have noticed that I was pretty excited about the publication of the Ruas paper (Ruas. 2012). Firstly this study has almost everything you could expect from cutting edge science: A in-vitro tudy to elucidate the basic mechanisms, an in-vivo rodent study involving both wild-type and genetically modified mice and - much to my own surprise - an in-vivo exercise part. And secondly, the results provides the missing link I personally have been looking for, when I wrote the Intermittent Thoughts on Building Muscle Series (click here for the summary and overview of the individual parts) - the link between IGF-1 and myostatin and the reason working out will always make you stronger and bigger and not bigger and weaker, as it is the case in the poor myostatin-knockout mice. Ah... I almost forgot: Third- and lastly, the fact that the researchers induced their hypertrophy effects in a specific part of their study by administering clenbuterol, which then did what I have likewise written about before (see "The Clenbuterol Myostatin Connection"), which is decreasing the expression of myostatin and thus producing skeletal muscle hypertrophy, yet as we now know not directly, but rather in consequence to its PGC-1 a4 promoting effects (+400%!) and the respective downstream effects on myostatin, which were non-existent, when the scentsts blocked PGC-1 a4 expresson (see images on the right)... 

I guess, you need to be somewhat geeky to find that exciting, but anyway. If you don't I'd still recommend you take a listen to the show - it's well worth it, even for totally normal exercise enthusiasts ;-)

And now for the actual seconds

Since the Ruas study appeared on my "radar" quasi in the last minute. We did not get to talk about several of the things I have announced and just to make sure you are not going to be disappointed, once you have gone through the following findings, I will address the acidity / alkalinity issue in a separate post in the future. It requires some more detailed elaborations - but the wait is going to be worth it ;-)

ALA rescues the liver from toxic N-6 overload

Actually this item would have fitted in pretty neatly with the things I explained about the different isoforms of PGC-1 alpha and how they appear to be regulated by diet / energy energy intake and expenditure via AMPK, on the one hand, and MAPKs, i.e. 'switches' that are triggered by stress, as the wear and tear of exercise, for example would be one. Now, we have already talked about the latter aspect, so that I guess I can get right to the not so novel, but still intriguing insights a  group of scientists from the Cerrahpaşa Medical Faculty Medical Biology Department at the Istanbul University  bring to the table as far as the former pathway is concerned (Kaya-Dagistanli. 2012).


In their 8-week experiment, Kaya-Dagistanli and her colleagues confirmed two things, of which I don't even know what would be the more important result:

Figure 1: Fibrosis and fatty degeneration scores in the control group (normal diet) and the high omega-6 group w/ and w/out ALA Kaya-Dagistanli. 2012)

1. The administration of a diet that contained 60% fat from safflower oil, 20% kcal carbohydrate and 20% kcal protein (51% of the fat from n-6, n-6:n-3 ratio of 15.4) did produce major changes not only in the GSH levels, a measure of the total antioxidant capacity in the livers of the 24 Wistar rats, the relatively short time span was even enough to increase the fibrosis and fatty degenration scores by ~10x (see figure 1) compared to the rodents on the low fat standard chow in the control group (only 12% fat total, 39.1% n-6, n-6 : n-3 ratio of 9.3).
2. The addition of 35 mg/kg DL-alpha lipoic acid (human equivalent: 5.7mg/kg; ~500mg/day) from week 4 to week 8 reduced both the negative effects of the omega-6 overload on GSH and the pathological degeneration of the liver, but could not fully restore it to normal levels.

Not just in view of the fact that ALA could not totally blunt the detrimental effects of the n-6 diet, but also in view of the fact that rodents on the regular diet did not see any benefits (remember: if you are not fat and metabolically deranged ALA ain't necessary, probably counterproductive; "Lean & Muscular W/ alpha lipoic acid?"), I personally gravitate towards (1), as far as the more significant finding is concerned. After all, it goes to show you that you simply have to the absolute (and relative?) amount of omega-6 fatty acids in your diets and can go without any such supplements as high dose fish oil and/or alpha lipoic acid. Bottom line: Don't bang your head against the wall and you won't need a helmet ;-)

NSAIDs liver cancer, chronic liver disease and other nasty ways to die

It's quite a happy coincidence that the December issue of the Journal of the National Cancer Institute held yet another intriguing study on the potentially beneficial health effects of the use of NSAIDs, which had been addressed in August already, when Jacobs et al. have gotten quite some public attention with their paper on aspirin use and the decrease in all-cause mortality (Jacobs. 2012). The novel paper that's based on prospective data on 300,504 men and women aged 50 to 71 years who had participated in National Institutes of Health-AARP Diet and Health Study and has been written by a group of scientist who actually work at the National Cancer Institute (Sahasrabuddhe . 2012), did not deal with a slightly different research question, i.e. does the use of aspirin and other NSAIDs offer protection against liver cancer (hepatocellular carcinoma) and death due to chronic liver disease, it also offers a slightly more sophisticated analysis of the (a) the frequency of NSAID use and potential interactions. Still, I decided to summarize the main findings of both, also in view of the fact that we are dealing  wih different cohorts (study subjects in the Jacobs paper were 100,139 men and women with no history of cancer in the Cancer Prevention Study II Nutrition Cohort).

Figure 2: Main results (hazard ratios) of two of the latest epidemiological studies into the effects of aspirin and other NSAIDs on liver cancer, death due to chronic liver disease (left) and aspirin alone on all cause mortality (right; data based on Sahasrabuddha. 2012 & Jacobs. 2012)

With the "demarcation lines" being present at 1.0 (meaning normalized risk) it is pretty easy to see that at least with respect to liver health and all-cause-mortality and solely based on epidemiological evidence, aspirin appears to be one of those "miracle drugs" everyone can benefit from. We have to be cautious however, when we compare everyone with ourselves, after all - and pretty much stands out of question - the protective effects of aspirin and the slightly less unambiguous and as far as hepatic cancer goes, even detrimental effects of other NSAIDs are mediated by...

• the modulation of inflammation via inhibition of the COX enzymatic pathways necessary for the synthesis of prostaglandins
• the ensuing decreases in epithelial proliferation and angiogenesis, as well as an
• increased apoptosis (regular cell death) and ameliorations in the inflammatory response and inflammatory cytokines via non-COX mediated pathways

Now, if you remember the previous study about ALA and how useful it can be if you are the kind of person who hammer his head... ah, I mean who still has not gotten the message that the formerly hailed omega-6 PUFAs from the "healthy corn and vegetable oils" are not a bit healthy, on the one hand, and how superfluous (if not detrimental) the same supplement is for someone who does not exhibit exuberant inflammation to begin with, this certainly does put the results into perspective.

---

Apropos perspective, I am not quite sure how you like the perspective that this is it, for today, but I would be pleased if you took that as an incentive to come back tomorrow and check out the next installment of SuppVersity On Short Notice and for the time being, I still have a couple of facebook news, I am sure you will enjoy:

• Scientists from the UK and New Zealand do pretty damn good job pimping the sales of low fat products - learn what the press release does not tell you (read more)
• German scientists find: Bisphenol A clogs calcium channels - don't know if you'd agree with them that the good news is that it appears to be reversible (read more)
• Grazing is for fat cows, only  - women who want to be lean better eat like a human, i.e. three square meals not more that's it - this will also help with blood triglyceride management (read more) 
• more, much more ;-) 

Any you know, facebook is a fast media, so expect more news to be posted even before the official next SuppVersity article will hit the main site ;-)

References:

• Jacobs EJ, Newton CC, Gapstur SM, Thun MJ. Daily aspirin use and cancer mortality in a large US cohort. J Natl Cancer Inst. 2012 Aug 22;104(16):1208-17.
• Kaya-Dagistanli F, Tanriverdi G, Altinok A, Ozyazgan S, Ozturk M. The effects of alpha lipoic acid on liver cells damages and apoptosis induced by polyunsaturated fatty acids. Food Chem Toxicol. 2012 Nov 28.
• Ruas et al. APGC-1aI soform Induced by Resistance Training Regulates Skeletal Muscle Hypertrophy. Cell, December 7, 2012; 151:1319–1331. 
• Sahasrabuddhe VV, Gunja MZ, Graubard BI, Trabert B, Schwartz LM, Park Y, Hollenbeck AR, Freedman ND, McGlynn KA. Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma. J Natl Cancer Inst. 2012 Dec 5;104(23):1808-14.

Science Round-Up Seconds: How Colostrum Turns the Oxidative Downsides of Endurance Exercise into Benefits and Why Cacao is so Much More Than Just Delicious

Looking for a delicious and more creative way than colostrum powered chocolate milk to combine today's seconds? What about Linda Wagner's Chocolate Cherry Bomb Smoothie with Colostrum, Caco, Maca, Acai, almond milk & more?

By now you will probably have listened to yesterday's installment of the SuppVersity Science Round-Up either via the Super Human Network live stream, or after downloading the podcast (the Round-Up starts in the 2nd hour) that has now been available for ~20h. In case you did not have the chance to listen live or listen to the podcast, but have a vested interest in erectile (dys-)function, optimal testosterone levels, the connection between testosterone, DHT, estrogen, insulin resistance, obesity, the health of your liver and longevity or you are simply eager to learn more about the latest research on high intensity interval training, steady state cardio,  everyday activity and the fallacy of the "exercise just makes you hungry hypothesis" (additional suggested read: "Dr. Oz Was Right: Exercise Does not Just Make You Hungry") and their effects on your metabolic health, conditioning and physique there is no way, you want to miss listening to this show, either before or after you devour this week's installment of the SuppVersity Science Round-Up Seconds.

• Colostrum supplementation blunts exercise induced reduction in endogenous anti-oxidants and potentiates its beneficial effects (Appukutty. 2012) --Published on November 22, this paper by Appukutty et al. is only the latest in a long line of articles on the effectiveness or ineffectiveness of colostrum as an ergogenic aid (suggested read: "Ask Dr. Andro: Are Colostrum and Milk Healthy Muscle Builders?). We will get to these differences in a minute, but let's first take a look at the effects the provision of 50mg/kg body weight (human equivalent: 2.4mg/kg) had on the total antioxidant status, lipid oxidation, xanthine oxidase and super oxide dismutase levels in treadmill exercised (30min per day) mice.

  

  Figure 1: Relative levels of total antioxidants, xanthine oxidase and super oxide dismutase in supplemented (COL), exercised (EX) and exercised + supplemented (EX + COL) mice expressed relative to sedentary non-supplemented control (Appukutty. 2012)

  It's not difficult to see that the effects of the colostrum supplement go beyond the mere amelioration of the exercise induced decrease in total anti-oxidant enzymes and super oxide dismutase levels. The human equivalent of only 2.4mg/kg body weight per day did - after 14 days of supplementation the total antioxidant status in the exercised + supplemented rodents was already 5% greater, after 21 days whopping 11% greater than in the supplement only group.
  
  In view of the previously reported benefits of supplemental colostrum you could certainly argue that the obvious parallels to the difference between "training" and "overtraining", with the former having promotive and the latter having compromising effects on the endogenous anti-oxidant system of your body are no coincidence. In view of the about as many studies which found no or at least no significant factually or potentially ergogenic effects in response to supplemental "beast milk", we still have to answer the question I invoked in the introductory paragraph of this sub/item of today's installment of the SuppVersity Science Round-Up Seconds: "How come it works in some, but by no means all studies?" The answer could actually be way more straight forward than you think and reads "Simply because he scientists used different supplements!"
  
  Even the dairy industry has realized that the way they feed their cows and post-process their colostrum, before they eventually feed it to their offspring, renders almost 60% of the maternal colostrum from US dairy farms "inadequate" so that "a large number of calves are at risk of failure of passive transfer or bacterial infections, or both." (Morrill. 2012)
  
  

  

  Not all colostrum is made the same and the beneficial effects of each and every individual product - specifically with respect to the integrity of the intestinal wall - will necessarily depend on its bacteria content and the latter depends on the feed the cows receive as well as the processing the colostrum undergoes.

  If you do still remember my post on the etiology of exericse-induced increased intestinal permeablity and the beneficial effects 'intact' colostrum has on the integrity of the gut you just have to put two and two together and you have your explanation: Just like the efficacy of any artificial supplement depends on he chemicals the producer puts into it, the effectiveness of a food supplement will vary due do both natural (e.g. seasonal, feed dependent, stress andhealth related...) and 'unnatural' fluctuations in its ingredient profile. Heat treatment, which is applied to almost all commercially available colostrum supplements, for example, may leave most of the IgG content intact, but it will reduce not just the total count, but also the diversity of the microbiota in colostrum (only the heat resistant bacteria, mostly gram-positive, will survive; cf. Hayes. 2012) 

• Study shows, cacao phenols protect your gut from inflammation, but there is much more cacao can do for you (Rodríguez-Ramiro. 2012) -- As a recent paper by scientists from the Ciudad Universitaria in Madrid (Spain) goes to show you, colostrum and bacteria are not the only naturally occuring supplements that are good for your gut health. Cacao has just been shown to do a pretty decent job, as well.
  
  

  

  Table 1: Nutritional content of the experimental diets the rodents were fed for 8 weeks with the carcinogen being injected in week 3 and 4 (Rodríguez-Ramiro. 2012)

  In an in-vivo the Spanish observed that a diet that was enriched with 12% cacao powder had astonishing anti-inflammatory effects in a rat model of azoxymethane (AOM)-induced colon carcinogenesis. The rodents had been fed the 12% cacao diets (composition see table 1 to he right), for 8 weeks. In weeks three and four, the scientists injected the procarcinogenic drug azoyxymethane in order to induce intestinal inflammation that would potentially lead to the development of colon cancer.
  
  Compared to the animals on the regular chow, the rats in the cacao group exhibited highly significant decreases the nuclear levels of  NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase, all of which were profoundly upregulated in response to the AOM injections in their peers on the regular diet.
  
  In a subsequent in-vitro experiment on Caco-2 cells, the scientists were also able to confirm that cocoa the cacao polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation.
  
  Now, it does not really appear feasible to eat a 12% cacao powder diet, right? Well, based on the data from table 1 the average food intake and body weigh of the rodents and some mathematical shenanigan, it's actually not difficult to calculate that the human equivalent dose, which would be 150g of cacao powder per day conains no more than 3g of polyphenols and could theoretically be achieved by supplementing with ~15g of chocamine every day. Ok, that would be hilariously expensive, but I assume you don't inject 3.25mg/kg azoyxymethane on a regular basis, right? Well, I guess this would mean that you won't need 15g of chocamine or 150g of cacoa powder to protect your gut either, right?
  
  Moreover, I suspect that most if not all of you will have heard or read about one of the dozens of epidemiological studies which show associations between very moderate intake of dark chocolate and cardiovascular, neuronal and metabolic health. Apropos "metabolic" did I mention that the animals in the cacao group were also 10% leaner than their peers on the regular - probably not a fair comparison with the differences in the macronutrient make-up but it would still be worth adding another bulletin point to a pretty impressive list of scientifically proven health-benefits of cacao consumption (or supplementation with respective extracts), which comprises among other things

  

  Guess how she got in shape? Right! The EDC Program ! EDC? Yeah: "The Female Weight-Loss EDC: The Fat Burning, Waist Reducing Synergy of Exercise, Diet and Dark Chocolate" - click here to  learn more

  • high antioxidant activity
  • improved insulin sensitivity, beta cell function & carbohydrate metabolism
  • improved HDL/LDL ratios
  • inhibition of detrimental byproducts of the arachidonic acid metabolism
  • induction of NO-mediated, endothelium-dependent relaxations
  • reduced incidence of stroke due to hypotensive effects
  • anti-CVD effects via TGF-β_{1 and} decreased tendency of blood to clotting
  • local and systemic TNF-alpha modulation and VGEF suppression => anti-cancer efects
  • immune effects that can protect you from tooth decay
  • protection against UV radiation and rejuvenating effect if its applied to the skin
  • suppressive effect on fatty acid synthesis
  • increases in mitochondrial respiratio
  • ability to boost serotonine (5-HT), improve mood and lower appetite and cravings
  • [...]
  I am not intending to make an all-encompassing list, here. Instead I will conclude with the astonishing insight from one of the most recent meta analysis that the daily consumption of the polyphenol equivalent of 100g of dark chocolate (at least 60-70% cacao content; 500-1,000mg polyphenols) would prevent 85 cardiovascular events per 10,000 capita every year (Zomer. 2012).
  
  Don't get me wrong I am with you with respect to the absurdity of cost-analyses when we are talking about health, but that's unfortunately the way the health business is operating and therefore I won't simply ignore the 50,000$, which is the saving the scientists estimate for every saved life and the corresponding 40$ of which Zomer et al. suggest that they should be spent "per person per year could be devoted to advertising, educational campaigns, or potentially subsidisation of dark chocolate in this high risk population." (Zomer. 2012)

That's  it for this week - at least as far as the SuppVersity Science Round-Up goes

Since Maxim asked "And what about garlic?", here is an addendum summarizing what I maybe did not get across very well at the end of the show, when I was flabbergast that the show was already over: The researchers took 20 male non-athletes (aged 22-26 years, body fat 16-20% and VO2max 38-42 ml/kg/min) randomized them to 700mg garlic or dextrose control  for 14 days and had them work out at 75% VO2max on the treadmill for 30 minutes at the end of the intervention period. Afterwards they analyzed the blood samples and found that (a)the 14 day supplementation alone reduced the basal triglyceride and increased the high density lipoprotein-cholesterol (HDL) increase (P<0.05) and (b) increased the beneficial effects of the exercise bout on acute reductions in LDL and triglycerides (Zekril. 2012)

I hope you enjoyed listening to the show (click here to download the podcast in case you still haven't done so) and satisfied your cravings for more with this installment of the SuppVersity Science Round-Up Seconds: In case you haven't I suggest you browse over to the SuppVersity Facebook Wall and check out the latest news on

• The connection between MS an impaired blood-brain barrier: A leaky brain and the intrusion of fibrinogen (a coagulation protein from the blood) could be the cause of multiple sclerosis (read more)
• Fishing for Omega-3s in Milk: One cup of fish oil enhanced milk yields 432mg of DHA + EPA... and it does not taste or smell fishy (read  more)
• Heart disease may begin even before you are born: Prenatal stress will turn the "probably" before "develop heart disease" into a "most likely" (read more)

When you are done with that and still hungry for more, you may want to check out my, as well as Patrick Arnold's, Kurtis Frank's (examine.com) and Willem Koert's (ergolog.com) contributions to a round-table discussion on the more or less recent ban of DMAA (aka geranium oil) in Australia - I have been so busy that I totally forgot about having done the respective interview weeks ago. Sorry for letting you know so late ;-)


References:

• Appukutty M, Radhakrishnan AK, Ramasamy K, Ramasamy R, Abdul Majeed AB, Ismail MN, Safii NS, Poh KB, Chinna K, Haleagrahara N. Colostrum supplementation protects against exercise - induced oxidative stress in the skeletal muscle in mice. BMC Res Notes. 2012 Nov 22;5(1):649.
• Hayes MM, Hughes TA, Greene AK. Bacterial diversity in dried colostrum and whey sold as nutraceutical products. J Food Sci. 2012 Jul;77(7):M359-63.
• Morrill KM, Conrad E, Lago A, Campbell J, Quigley J, Tyler H. Nationwide evaluation of quality and composition of colostrum on dairy farms in the United States. J Dairy Sci. 2012 Jul;95(7):3997-4005.  
• Rodríguez-Ramiro I, Ramos S, López-Oliva E, Agis-Torres A, Bravo L, Goya L, Martín MA. Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells. Br J Nutr. 2012 Nov 28:1-10. 
• Zekri1 R, Jafari A, Dehghan G.  The concurrent effect of one bout aerobic exercise and short-term garlic supplementation on the lipids profile in male non-athletes. J Shahrekord Univ Med Sci. 2012; 14 (5) :34-41
• Zomer E, Owen A, Magliano DJ, Liew D, Reid CM. The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model. BMJ. 2012 May 30;344:e3657.

Science Round-Up Seconds: Vitamin E Succinate, How It's Extracted from Barley Leaves, Kills Cancer, Ramps up Growth Hormone & Spikes Prolactin. Plus: Testostosterone & Thyroid Hormone Decline Due To Plyometrics & HIIT

Regardless of all the hypocritical hoopla around his persona, Lance Armstrong has always been able to push himself like no one else. No wonder that intense plyometrics were part of his regimen.

If the SuppVersity Science Round Up was a meal, I guess you could say that Carl Lanore and I were sort of gluttonous, yesterday (click here to download the podcast, if you have not already done so). We almost raced from one topic to another and therefore all the good stuff from the list is gone already and I am a bit pressed on time to get some "private life" in, so that I am not psyched about the idea of writing about auxiliary stuff.

Against that background and in view of the fact that I felt that the pace of yesterday's show did not really leave enough room for some important details, I will stick to rehashing and expanding on the stories about Vitamin E succcinate and the detrimental effects of beating the crap out of yourself doing plyometrics or crazy HIIT workouts (too regularly), in today's installment of the SuppVersity Science Round-Up Seconds.

Let's see. Why don't we start at the end of yesterday's show?

• Vitamin E succinate the most potent anti-cancer tocopherol known to man. As you have heard on the show, vitamin E succinate attaches directly to a protein that's preferentially expressed in carcinogenic or pre-carcinogenic cells. It goes by the name α-Tocopherol-associated protein (TAP) and was found to be one of the major α-tocopherol binding proteins in serum, liver, brain and prostate. What has as of yet not been so clear, though, is that the expression of this protein increases with the malignancy of (breast) cancer (Tam. 2012). 
  
  

  

  Figure 1: Effects of alpha tocoperyl succinate alone (TOS), doxorubicin alone (DOX) or both (DOX + TOS) on cell viability in human MB231 breast cancer cells (my edits, original from Tam. 2012) - note: The effect was less pronounced in other cancer cells, so that it is reasonable to assume that the efficacy of the therapy will depend on the exact genotype of the cancer (for those tested in the study it was MB231 > SKBR3 > MCF 10A)

  When alpha tocopherol succinate binds to the protein on the cancer cells, this will either alone, or in combination with chemotherapy trigger apoptosis and cell death. It is as of yet not fully elucidated why vitamin E succinate is highly cancer-specific and leaves the healthy cells intact, but this could be related to the high metabolic rate and exuberant ROS production of cancer cells. There is however some research that would suggest that the cancer cells literally suffocate in their own radical oxygen specimen (ROS), which can no longer be cleared from the cell, due to the alpha-tocopheryl succinate induced displacement of ubiquinone from CII and the subsequent blockade of succinate dehydrogenase (SDH) activity (Dong. 2012).  If this hypothesis holds true it would therefore appear that long-term chronic supplementation with vitamin E succinate cannot be recommended until future studies on its general safety have been undertaken. As an adjuvant to chemotherapy, on the other hand, it could drastically reduce the dosage requirements during chemotherapy in specific types of cancer (see figure 1) and thus minimize side effects.
  
  You see, there is more to it than you can say in two minutes on the radio and this is why I will make sure we don't rush through the items that fast, in the next show. Ah,... of course the dietary source. I had almost forgotten about that one. As mentioned on the show, alpha tocopheryl succinate was originally extracted from Barley leaves. An while this may not be the first paper dealing with this "natural vitamin E analog", the one by Badamchian et al. is probably the one you will be most interested in.
  
  Published in the Journal of Nutritional Biochemistry the paper does not only describe the isolation of vitamin E succinate from green barley leaf extract (BLE)...
  

  "BLE [barley leaf extract] powder (50 mg/mL) was suspended in water and stirred for 1 hr at room temperature. The mixture was then centrifuged at 3000g for 30 minutes using a bench-top centrifuge. The pellet was discarded and the supernatant was pre-filtered through a Millipore DEPTH filter. The filtrate was then filtered through 0.45 I.tM mem- brane and stored at -20 ° C for HPLC or biological assays." (Badamchian. 1999)

  ... it does also shine another spotlight on its potential biological effects, as far as it's ability to increase growth hormone, but (unfortunately?) also prolactin in isolated anterior pituitary cells from female rodents:
  

  

  Figure 2: Prolactin and growth hormone release in anterior pituitary cells of female rodents after incubation with different amounts of green barley extract in which vitamin E succinate had been deterimed as the main ingredient before (based on Badamchian. 1999)

  It's really hard to estimate whether or not one of these effects would translate from a rodent cell in the petri dish to you or me popping a cap with vitamin E succinate everyday. That's particularly true in view of the fact that the underlying mechanism of the increase in GH and the imho more concerning increase in prolactin is neither mediated by increases in intracellular C-AMP, as it would be the case for GRF (old acronym for growth hormone releasing hormone), nor is it induced by the hydrolysis of polyhoshpoinositide, which is the underlying mechanism of the stimulative effect of TRH (thyrotropin releasing hormone). So basically we neither know how it works, nor do we know, whether the oral ingestion of vitamin E-succinate would be sufficient to produce serum concentrations in the pituitary that would be high enough concentrations to make any difference at all (note: the scientists excluded the influence of other components of the extract by testing alpha tocopherol succinate on its own in a separate trial)
  
  Bottom line: Based on roughly one dozen of in-vitro studies there is simply still to little evidence to decide who, outside of people with a history of cancer or someone who is just undergoing chemotherapy would benefit. Therefore, I suggest you wait before you add vitamin E succinate to your list of 'must have' supplements. Is it promising? Sure! Is it exciting, yeah! Is it save for a healthy being to be taken chronically??? I can't tell.
• The detrimental hormonal effects of pushing yourself beyond the tolerable threshold - Hardcore plyometrics and heavy HIIT and their impact on testosterone, cortisol, thyroid hormone and co: I guess you did already get the main message when you listened to the show, but just to give you an idea about the actual quantities, I thought it would be nice to provide you with two graphs as a reference.
  

  

  Figure 3: Comparison of the hormonal responses measured in the plyometrics (left) and the HIIT vs. LISS (right) study (based on Ozen. 2012 and Hackney. 2012)

  If you focus mainly on the differential cortisol responses in the two studies, it would appear likely that we are dealing with two very different forms of 'overtraining' here. While the HIIT protocol (90s at 100-110%, 90s active recovery at 40% matched for workload with steady state jogging at 60-65% of the VO2 max) probably wouldn't be a problem, if the athletes would get adequate rest and nutrition in the days after the session, the 6-weeks of plyometrics (15 session, increasing density, 90-195 reps per session) were enough to send the participants right into the vicious circle of the Athlete's Triad (if you have not done so already, I suggest you read up on that in the eponymous SuppVersity series).
  
  And you know what? Despite, or I should probably rather say due to their compromised hormone levels the guys in the plyometrics study did not lose a single gram of body weight. Good for their muscle, bad for the fat which was likewise preserved by the hormonal shut down, which affected both cortisol and testosterone in a similar way. So is that good or bad news? Well, let me say it this way:. Usually I see people training for a purpose and while the outcome often is stagnation and chronic fatigue, I would suspect that only few of you will have that on their mind, when they are hitting the gym, right?

Apropos viscous circle, and overtraining in order to avoid "overblogging" I will call it a day for today. Come back tomorrow for a couple of wholly new studies from the realms of exercise and nutrition sciences and in case you are planning to drink this evening, I highly suggest you check out the SuppVersity Facebook newspost on the effects of green tea extract on the uptake of alcohol. It may well be that those old fatburner caps of yours can be put to a way better use ;-)

References:

• Badamchian M, Spangelo BL, Bao Y et al. Isolation of a vitamin E analog from green barley leaf extract that stimulates the release of prolactin and growth hormone from rat anterior pituitary cells in vitro. Journal of Nutritional Biochemestry. 1994; 5: 145-150.
• Dong LF, Low P, Dyason JC, Wang XF, Prochazka L, Witting PK, Freeman R, Swettenham E, Valis K, Liu J, Zobalova R, Turanek J, Spitz DR, Domann FE, Scheffler IE, Ralph SJ, Neuzil J. Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene. 2008 Jul 17;27(31):4324-35. Epub 2008 Mar 31.
• Hackney AC, Kallman A, Hosick KP, Rubin DA, Battaglini CL. Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones (Athens). 2012 Jan-Mar;11(1):54-60.
• Ozen, SV. Reproductive hormones and cortisol responses to plyometric training in males. Biol Sport.2012; 29 (3).
• Tam KW, Ho CT, Lee WJ, Tu SH, Huang CS, Chen CS, Lee CH, Wu CH, Ho YS. Alteration of α-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development. Food Chemistry. 2012 [ahead of print]

SuppVersity Science Round Up Seconds: Wheat Gluten Hydrolysates Fail, Exposure to Air Pollutants During Workout Reduces Brain Benefits, Homocysteine, B-Vitamins, Cognitive Impairment and Mortality

Before the profound weight loss (A) you don't see any of the glucose sucking and fad burning brown fat depots (black spots in B) on the neck of the in (B) 'foermerly obese', now only 'overweight' subject (also take a look at how the visceral fat in the abdominal region in (A) is actually pushing the organs upwards; img Vijgen. 2012)

Those of you who have listened to yesterday's show will have noticed that despite its flow the number of things you can discuss in a 1h podcast is simply very limited, to say the least. This is also why these Friday posts are probably never going to be simple summaries of the SuppVersity Science Round Up of the day before. The same is true for today and still I decided not to use the allegedly lame logo I did for the first two installments, but provide you with some 'real science' evidence of the absence of brown adipose tissue on the obese and it's magical reappearance after shedding 100lbs+ subsequent to a gastric bypass operation, instead (see image on the right).

Assuming that you have no idea what this "evidence" is for, I would suspect that you missed the live show yesterday and also did not find the time to download and listen to the podcast, yet -- right? Well, you should either download and listen to the show now and digest the Seconds later, or you read the following paragraphs first and download the podcast later.

What is not an option, however, is to miss one or another - I mean you can hardly want to eat the seconds if you have not had the main dish yet... and after listening to the podcast, I cannot imagine you don't want at least some seconds. Apropos seconds, here are today's seconds...

• Wheat gluten hydrolysate is not the new goto protein supplement - certainly not for female distance runners and probably not for anyone else, either! These are the kinds of studies that really annoy me. Studies that start out with blatant statements like "WGH [Wheat gluten hydrolysate] has been reported to suppress post-exercise rises in serum creatine kinase in male distance runners" (Hirao. 2012).
  
  

  

  Figure 1: CK, AST, ALT response in the "success trial" with men. In women even the miniscule beneficial effect on CK was not there. No reason to even think about buying a gluten hydrolysate as you new go-to protein supplement with only 5.6g of leucine/100g (whey has 50% more) and almost no GSH replenishing cysteine in it (0.9g vs. 3g+ in whey, which is more than +200% more).

  Sentences like that make the null-results of the study they precede look like the exception to the rule and are still nothing but a concession to a bias (let's hope not due to the grant from Nisshin Pharma Inc. which was the manufacturer of the wheat gluten hydrolysate used in this study). A bias, due to which an isolated observation as the slightly blunted increase in CK is blown up as if a slightly lower CK level was what could turn a sedentary pencil pusher into the next Hussein Bolt (Aoki. 2012).
  
  So, even if you are not afraid of the evil in gluten (which I believe not everyone has to), I strongly caution against making the switch from a high EAA protein with ton's of GSH boosting cysteine in it like whey to a mediocre grain protein, which is a potential allergen and contains tons of glutamine your body will readily turn into glucose, once it passes through the portal veign into the liver (I bet a large part won't even make it into systemic circulation).
  
  And as far as the purported "gender difference" goes the study at hand tries to blame the null result on (Hiriao. 2012), I suspect that it is rather the indisputable difference between the long-distance running at a continuous pace the women in the study at hand did, versus the totally different strains the guys in the previous study were exposed to during a soccer training + mini-match, which made the difference.
• Working out next to a street takes away some of the beneficial cognitive effects due to ultrafine particulate matter (UFPM) exposure. "Working out in the fresh air will promote weight loss more than working out inside." You heard me state that in one of the previous installments of the SuppVersity Science Round Up on Super Human Radio. Now this is still correct and based on sientific evidence, but at least as far as the cognitive benefits are concerned, working out outside does also have its downsides - at least for those of you who live in the inner city area.
  
  

  

  You better watch what you breath while you run.

  During a 12-week program the researchers from the Universiteit Brussel, the Hasselt University and the Royal Military Academy measured the improvements in physical performance, changes in serum markers and corresponding ultrafine particulate matter (UFPM) concentrations in the enviromnent in which their 15 previously untrained subjects conducted their aerobic training program thrice a week (Bos. 2012). What Bos et al. found was that the UFPM levels were signfificantly higher in the urban compared to the rural environment and that the higher UFPM exposures correlated with increases in leukocyte counts (p = 0.02), neutrophil counts (p = 0.04), and eNO levels (p = 0.002) that were exclusively observed in the group that trained in the urban environment.
  
  With the latter being markers of inflammation which exert their effects systemically, i.e. not just in the lung or musculature of which you may be thinking now, but also in the brain, it is no wonder that
  

  "reaction times on the Stroop task improved in the rural group (p = 0.001), but not in the urban group" (Bos. 2012). 

  What's comforting, though, is that the physical fitness did increase to a similar extend in both arms of the study.
• Homocysteine levels, mortality, cognitive impairment and which nutrients can offer some protection. I am not sure about what your impression is, but for whatever reason homocystein seems to be 'out of vogue' -- probably no room for it on the research agenda with all the hype surrounding vitamin D. It used to be all the rage in CVD risk research and today's news item is actually ain't about cardiovascular health, either.
  
  What the researchers from China and Taiwan actually were interested in was the correlation of high and low homocysteine levels with cognitive impairment and the corresponding nutrient intakes. In that Xiu et al. paid particular attention to the "B-vitamins" and found the following correlations between the mortality, cognitive status, homocystein levels and nutrient intake of their 1412 study participants (Xiu. 2012):
  

  • 

    Figure 2: Unadjusted mortality in the four quartiles of homocysteine levels (top); mortality according to homocysteine levels in subjects with different degrees of cognitive impairment (based on Xiu. 2012)

    if you go by the unadjusted data in figure 2, it's plain obvious that the all-cause mortality increases linearly from one quartile to the other 
  • this relation between plasma homocysteine levels and all mortality remained statistically significant after adjustments for age, sex, smoking status, BMI, physical function and general health were made
  • of the general foods, the scientists assessed, only regular fish intake had a statistically significant effect on homocysteine levels, with higher intakes being associated with lower homocysteine levels
  • of the b-vitamins choline was the only one with a significant association with plasma homocysteine levels (suggested read "Old School Supplement Choline Could Save Your Live and Liver!") 
  • neither betaine, nor vitamin B1, B2, B3 or B6 intakes did show statistically significant correlations with plasma homocysteine (not even "borderline significant; p > 0.15 for all, most way hither)
  • of the plasma markers, folate showed a highly significant correlation with homocysteine (14.4 nmol/L in the lowest HCY and 8.70 nnmol/L in the highest HCY group)
  • PLP, the active form of vitamin B6, came in close second with 70.3 nmol/l in the lowest HCY quantile and only 44.4 nmol / l in the highest quantile.
  Now, if you consider the fact that higher intakes of B-vitamins are probably not doing much to lower homocysteine levels int he elderly (at least not dose-dependently, when they are already getting enough) oddity #1, another look at the data in figure 2 will reveal oddity #2: The surprisingly high mortality in the lowest homocysteine quartiles in the patients with severe cognitive decline - how come? I mean, with low homocysteine they should not be at risk of having severe cognitive decline, anyway - right?
  
  Actually if you follow this rationale you can almost answer the question yourself. If you have low homocysteine and severe cognitive decline, the severe cognitive decline can hardly be from high homocysteine levels, so it must have another obviously pathological reason, or as the scientists have it
  

  "The joint effects of the 2 variables [homocysteine and cognitive decline] were most pronounced with severe cognitive impairment where mortality HRs ranged from 5- to 18-fold across a wide range of homocysteine concentrations. The findings with hypohomocysteinemia provide some insight into what might be an optimal range for this analyte in peripheral blood and tissues. The low concentrations may be seen with severe illness and malnutrition, and our study population comprises the health-vulnerable aged. For these reasons, we adjusted these associations for BMI (using the World Health Organization chronic energy deficiency category of, 18.5 kg/m 2 ), and we excluded those who died in the first year of follow-up. The findings were unchanged. Because mortality among the very old may have skewed the joint effects, these are presented for those ≤75 years and over, but again with similar findings." (

  A sarcastic person would now probably say: "We all have to go some time!" and just wave his hands at these results. True! And I am the last to advice you to become over-anxious. Yet in the mean time it would appear prudent to make sure to get your homocysteine levels checked from time to time, not to forget that choline is a b-vitamin as well and not to fall for the idea that you cannot overdose on B-vitamins - I don't have to remind you of the negative effects, specifically folic acid supplementation can have on all sorts of cancer (e.g. breast cancer, where a high folic acid intake from foods and supplements is associated with a +30% risk of cancerous growth; cf. Kim. 2006).

In case you are looking for the post on "ammonia accumulation brain-fog, toxicity, liver 'pathologies' and workout performance", yeah it was on the list, but I decided it would be a shame to tackle that within a short two paragraph seconds items. Don't worry I am not going to forget about it, after all its in my humble opinion one of the main reasons the diets and workout regimen of the many ambitious physical culturists fail. If you are still looking for more and have not listened to the podcast, yet, this would be the right moment to download the file from the Super Human Radio Network server (click here to download), otherwise the latest short news on the SuppVersity Facebook Wall may offer some diversion ;-)

References:

• Aoki K, Kohmura Y, Suzuki Y, Koikawa N, Yoshimura M, Aoba Y, Fukushi N, Sakuraba K, Nagaoka I, Sawaki K. Post-training consumption of wheat gluten hydrolysate suppresses the delayed onset of muscle injury in soccer players. Exp Ther Med. 2012 Jun;3(6):969-972. Epub 2012 Apr 3.
• Bos I, De Boever P, Vanparijs J, Pattyn N, Panis LI, Meeusen R. Subclinical Effects of Aerobic Training in Urban Environment. Med Sci Sports Exerc. 2012 Oct 15.
• Cankurtaran M, Yesil Y, Kuyumcu ME, Oztürk ZA, Yavuz BB, Halil M, Ulger Z, Cankurtaran ES, Arıoğul S. Altered Levels of Homocysteine and Serum Natural Antioxidants Links Oxidative Damage to Alzheimer's Disease. J Alzheimers Dis. 2012 Oct 29.
• Guest PC, Urday S, Ma D, Stelzhammer V, Harris LW, Amess B, Pietsch S, Oheim C, Ozanne SE, Bahn S. Proteomic analysis of the maternal protein restriction rat model for schizophrenia: Identification of translational changes in hormonal signalling pathways and glutamate neurotransmission. Proteomics. 2012 Oct 16.
• Hirao T, Koikawa N, Aoki K, Sakuraba K, Shimmura Y, Suzuki Y, Sawaki K. Female distance runners show a different response to post-workout consumption of wheat gluten hydrolysate compared to their male counterparts. Exp Ther Med. 2012 Apr;3(4):641-644.
• Kim YI. Does a high folate intake increase the risk of breast cancer? Nutr Rev. 2006 Oct;64(10 Pt 1):468-75.
• Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012 Jul;97(7):E1229-33. Epub 2012 Apr 24.
• Xiu LL, Lee MS, Wahlqvist ML, Chia-Yu Chen R, Huang YC, Chen KJ, Li D. Low and high homocysteine are associated with mortality independent of B group vitamins but interactive with cognitive status in a free-living elderly cohort. Nutr Res. 2012. Ahead of print.

SVSR: Supplement-Drug Interactions, Exercise & Your Pysche, Running vs. O-Lifting vs. Heart Health, N3-to-N6 Ratios, CYP Enzymes, Cannabinoids & Telomeres

The SuppVersity Science Round-Up every Thursday live on Carl Lanore's Super Human Radio -- tune in live at 1PM (EST=  6PM GMT)!

I hope that most of you have already had a chance to listen to yesterday's installment of the SuppVersity Science Round Up on Super Human Radio. In case you didn't, or have been waiting for me to post the link to the podcast (just a reminder: you can always download the latest show, from the navigation bar on the right, where it says: "Physical Culture for your Ears"), I'd suggest you go and download the podcast either now, or after going through today's SuppVersity Science Round Up Seconds.

The "Seconds" are as the name implies no "leftovers", but actually yet another selection from the selection of god knows how many interesting newsbits I usually pile up for the short 1h show, Carl and I are doing every Thursday. I would therefore encourage everyone to do both, listen to the podcast and read the "Seconds" one day later. After all, the things Carl and I discuss on the air won't reappear here, they are "SHR exclusives", so to say ;-)

Apropos, in yesterday's show, the topics we did cover were

• premature ejaculation, and how only two hormones seem to make a difference,  
• peptides as prostate cancer vaccine, and how Harvard scientists build them from scratch,
• supps vs. medications, and how fatal commonly overlooked interactions can be, and
• copper, and why it may well matter than raw milk has 2-3x more than pasteurized milk

and before we go on with the actual "seconds", I must acquit myself of a promise -- the promise to provide you with more information on #3 on the above list.

Supplemental data: Supplement vs. drug interactions

Figure 1: Important supplement drug interactions based on Tsai (2012)

Those of you who have already listened to the podcast will probably be waiting eagerly for the supplemental material with more information about the potential pitfalls with supplement-drug interactions, Carl and I have been talking about on yesterday's show. With some digging, typing, searching, excerpting and formatting on my part, I have actually come up with a quite comprehensive and for people who are not familiar with all the funky drug names, probably even more understandable version (see figure 1) of the tabular overview H.H. Tsai and colleagues from the China Medical University Hospital and the College of Pharmacy at the University of Illinois at Chicago have included in their latest review of the literature (Tsai. 2012).

What I left out are the two pages (!) part on St. John's wort. With 147 drug (!) interaction ranging from "A" as in "amiodarone" to "W" as in "warfarin" and covering almost every drug type from anti-depressants, protease inhibotors, calcium channel blockers, PDE-5 inhibitors (viagra & co), SERMs, proton pump inhibitors, etc.. In view of the fact that these are only the known interactions, it would be easier to list those drugs with which St John's does not conflict, anyway. So, unless you have a study at hand which conclusively shows that St. John's is no problem, I would rather err on the side of caution, than end up in the ER.

Top 5 of the most frequent interactions observed with medication that act on (ranked by frequency, figure in brackets indicates percentage of all drugs in the study; based on Lin. 2012):

1. nervous system (19.6%)
2. cardiovascular system (17.7%)
3. antiinfectives for systemic use (14.7%)
4. alimentary tract and and immunomodulating agents (12.2%)
5. musko-skeletal system (6.4%)

As far as the supplement list in figure 1 goes, the most frequent potential side effect due to supplement-drug interactions affected drugs / supplements that play a role in blood coagulation. Danshen, evening primrose, gingko, glucosamine, white willow bark, garlic, vitamin E, fish oil to name only the most common ones, they all can increase the risk of bleeding not only, but specifically in patients who are taking warfarin (aspirin, ibuprofen, heparin and others were on the list, as well).

"What’s wrong with telling a patient, 'If you don’t hear from us with your lab results a few days, give us a call'? The answer is plenty, if that patient is receiving warfarin therapy. Because warfarin has a narrow therapeutic range and complex pharmacology, insufficient monitoring or errors in dosing can lead to severe and possibly life-threatening bleeding and clotting in patients receiving it." (Bush. 2002)

In view of the "top 5" above, this certainly sounds counter-intuitive, but we are dealing with a practical research bias here. As I mentioned on the air, there is simply an overabundance of research on potential interaction with warfarin, because finding the right dosage and adapting it appropriately is already hard even when there are no confounding variables, so that a sudden supplement-drug interaction and subsequent increase in the risk of bleeding can potentially be fatal (see the quote in the red box to the right)!

Regardless of what medication you may be on, rules that apply for a healthy individual that does not take any medication chronically (not even 'harmless' NSAIDs), don't apply to you! So please for one, follow the recommendation you find on each and every supplement to "talk to your medical practitioner" before you add another 'harmless' supplement on top of the 'harmless' over-the-counter or prescription drugs you are taking.

The Seconds: Interesting news that have been missing from yesterday's show

After this pretty lengthy addendum, let's get to three other items I had actually planned to have on the show, two of them are exercise, while the third one is a health and supplementation... and, when I come to think about it, obviously also diet related news-item:

• Exercise makes you happy and puts an end to the greed for money! That's not exactly the result of a recently conducted study from the Charité in Berlin (Bothe. 2012), but it is more or less what follows from the differential response Bothe et al. observed in their untrained and highly trained subjects to monetary stimuli after they had completed a standardized running exercise (30 min at 60-70 % VO2max, T) or placebo (P).
  

  

  Who would have thought that: Exercise reduces the anticipatory response to monitary incentive delay (MIT) test (Bothe. 2012)

  "Acute exercise was found to influence gain anticipation. In the P compared to the T group a more pronounced anticipation-related BOLD response was found in mesolimbic and mesocortical dopamine-innervated regions like the VS, hippocampus (Hipp) and subgenual anterior cingulate cortex (sgACC). [...] Additionally, several brain structures potentially associated with motor preparation (primary and supplementary motor areas) as well as structures belonging to the ventral (lingual gyrus) and dorsal (cuneus, precuneus) visual pathway showed stronger BOLD responses to gain anticipation in the P group compared with the T group." (Bothe. 2012)

  Moreover, according to the paper which is going to be published in one of the upcoming issues of Medicine and Science in Sports and Exercise, all 43 healthy men between the age of  20 - 32 years who participated in the study showed similar increases in mood (effect size F=11.70).
  
  With both, the beneficial outcome of the positive and negative affect schedule and the decrease in anticipatory signalling (= the greedy "I am about to win!") in the psychological testing session (the so-called monetary incentive delay) in an fMRI brain scanner, being identical it becomes evident that you don't have to be an athlete to monetize (all puns intended ;-) on the beneficial psychological effects of exercise.

• 

  Figure 1: Changes in total lean mass, aerobic fitness, strength (mind the scaling with x10!), right ventricular mass and end-diastolic volume in subjects in the endurance (runners) and strength training arm (O-lifting) of the 24-week study (based on Spence. 2012)

  Changes to the heart (right ventricular) due to exercise are mild, and if anything more pronounced in response to endurance than resistance training! " Left ventricular (LV) adaptation to exercise training has been the focus of 'athlete's heart' research to-date, information regarding right ventricular (RV) adaptation is sparse, due to its complex structure and imaging technique limitations." (Spence. 2012) So scarce, in fact, that this recent study that has been conducted by researchers form the The University of Western Australia, the University of Leeds, a and the Liverpool John Moore's University is the first to take a closer look at the impact endurance or resistance training have on the morphology of the RV.
  
  For their randomized trial, the researchers recruited twenty-three young untrained men.. The men were assigned to either
  
  • endurance training (E; n = 10)  - consisting of a progressively overloaded program of walking/jogging/running, divided into three training phases over the 24-week period, or
  • resistance training (R; n = 13) - with a focus on periodised R program was Olympic weightlifting with incorporated assistance exercises (e.g. deadlift, squat, bench press, overhead press) to develop overall strength and technique
  for a total timespan of 6 months, in the course of which body composition, aerobic fitness, muscular strength, RV morphology (MRI) and function (speckle tracking echocardiography) were continously monitored.
  
  The results Spence et al. are going to publish in one of the future issues of Medicine and Science in Sports and Exercise refute even two pieces of common "knowledge". Firstly, a still totally benign, right ventricular hypertrophy was exclusively observed in the endurance training group, yet not in the heavy lifters who were doing their squats, deadlifts and military presses (by 2.7g following E and by 1.4 g  following R training). Secondly, both strength and size gains were no prerogative of the lifting weight group. Contrary to the increase in total lean mass (+1.3 kg vs. +2.1 kg), the strength increase of +53.8 kg vs. +35.3 kg was yet much significantly more pronounced in the weight lifters.
  
  On the other hand only the endurance training group saw significant statistically improvements in their aerobic fitness level. This correspondence of endurance exercise, mild ventricular hypertrophy and increased fitness levels is unquestionably telling in terms of "how bad" a physiologically enlarged heart where the ratio of left-to-right ventricular  mass remains intact (which was the case in the study at hand), don't you think so?
• Omega-3s, omega-6s, telomere length, CYP enzymes, endogenous cannabinoid and the liver you need all of them to see the complete picture While the epidemiologists are still debating who will and who won't benefit from omega-3 supplementation, those who still care about how our bodies works and why their colleagues over at the epidemiology department are still debating, have made quite some progress as far as the underlying health benefits of rectifying the omega-3 to omega-6 balance are concerned.
  
  
  Why are endocannabinoids problematic? One of the answers is: "They will make you fat!" Basically we have known that forever, but a recent study which tracked the conversion of dietary linolic acid (n-6) to it's endocannabinoid metabolits, 2-AG and anandamide has recently confirmed not just that, but also that the provision of no more than 1% of the total energy of the diet in form of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) can already make a huge difference (Alvhem. 2012). With the addition of the long-chain omega-3s, the rodents in the study had a 8:1 ratio of linolic acid (LA) to long-chain omega-3 fatty acids in their diets. Still much higher than what you will hear is necessary, but sufficient to reverse the overabundance of arachidonic acid, in the phospholipids of liver and erythroctes, and the +200% increase in endocannabinoid levels that had been brought about, when the researchers had increased the linolic acid content of the diet from 1% to 8% of the total energy intake. In view of the fact that the same goes for the increased food intake, feed efficiency, and adiposity the mice had developed on the 60% fat (total) diet with a high linolic acid content, this study - despite being done on rodents - clearly shows that it does not necessarily have to be a 1:1 ratio to grasp major health benefits.
  
  If you get down from  30:1 to 8:1 you've come a tremendous way, already; and guess what: The easiest way to achieve that is to just cut out all seed and vegetable oils as well as processed foods that contain them.
  In a recent review on the differential effects of fatty acids on human metabolism in the Italian journal Medical and surgical pediatrics G. Caramia emphasizes the role of omega-6 derived endocannabinoids:
  

  "[E]ndocannabinoids like anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol [that arise from the enzymatic conversion of linolic acid by enzymes from the cytochrome P450 family at the liver are] capable of mimicking the pharmacological actions of the active principle of Cannabis sativa preparations such as hashish and marijuana (-)-Delta9-tetrahydrocannabinol. They act as true 'endogenous cannabinoids' by binding and functionally activating one or both [of the] cannabinoid receptor present on nervous and peripheral cell membranes." (Caramia. 2012; my emphases)

  Unfortunately, the same enzymes which are responsible for the generation of those endocannabinoids, are also responsible for the conversion of n-3 PUFAs into more potent metabolites of EPA and DHA, which will actually do most of the the vascular- and cardioprotective magic that is commonly ascribed to "fish oil".
  
  And how does all that relate to telomeres?
  
  These competitive effects in turn segue directly into the observations of a double-blind 4-month trial that involved 106 healthy sedentary overweight middle-aged and older adults. The participants supplemented their diets with capsules containing either (1) 2.5 g/day n-3 PUFAs, (2) 1.25 g/day n-3 PUFAs, or (3) a placebo that mirrored the proportions of fatty acids in the typical American diet.
  
  Now, it's not news that this led to decreases in inflammatory markers. I am not going to bore you with those, don't worry!
  
  What is news, and in my eyes very important, is that neither the provision nor the dosage of additional long-chain omega-3s had an effect on telomere length, the only variable that mattered was were the changes in the n-6:n-3 PUFA plasma ratios, which "helped clarify the intervention’s impact: telomere length increased with decreasing n-6:n-3 ratios (p= 0.02)" (Kiecolt-Glaser. 2012).

That's it as far as today's seconds go... you want more? Man, I could certainly give you more, but you know that gluttony was once considered a sin, right? Tomorrow is another day, and if you can't wait, just head over to the SuppVersity Facebook wall, which is always bursting from the seems with the latest tidbits from the realms of health, exercise and nutrition sciences.  

References:

• Alvheim AR, Malde MK, Osei-Hyiaman D, Hong Lin Y, Pawlosky RJ, Madsen L, Kristiansen K, Frøyland L, Hibbeln JR. Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity. Obesity (Silver Spring). 2012 Oct;20(10):1984-94.
• Bothe N, Zschucke E, Dimeo F, Heinz A, Wüstenberg T, Ströhle A. Acute Exercise Influences Reward Processing in Highly Trained and Untrained Men. Med Sci Sports Exerc. 2012 Oct 10.
• Bush J. Preventing errors in your practice. Reducing risks for patients receiving warfarin. Fam Pract Manag. 2002 Jul-Aug;9(7):35-38.
• Caramia G. [Essential fatty acids and lipid mediators. Endocannabinoids]. Pediatr Med Chir. 2012 Mar-Apr;34(2):65-72.
• Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn E. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav Immun. 2012 Sep 23. pii: S0889-1591(12)00431-X.
• Spence AL, Carter HH, Murray CP, Oxborough D, Naylor LH, George KP, Green DJ. MRI-derived Right Ventricular Adaptations to Endurance versus Resistance Training. Med Sci Sports Exerc. 2012 Oct 15.
• Tsai HH, Lin HW, Simon Pickard A, Tsai HY, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 2012 Nov;66(11):1056-1078.