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. 2013) 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. 2013). 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. 2013) :

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. 2013)

"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. 2013)

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. 2013).

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. 2013)

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. 2013)

 + + + + + + + + + + + + + +

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. 2013 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. 2013 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)2013, 20(2):349–355.
• Kousik SM, Napier TC, Carvey PM. The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation. Front Pharmacol. 2013;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 2013; 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.

Leucine + Resveratrol - Synergistic Sirtuin Boosters: +118% Fatty Acid Oxidation, 60% Increase In Muscular Glucose Uptake, -30% Visceral Fat & More - To Good to be True?

Image 1: Can you really team up leucine (or HMB) and resveratrol to make tired mitochondria get a move on? NuSirt Sciences says "YES!" And in the dish and rodents it's actually already working.

What happens if you marry a well-known AMPK promoter and exercise mimetic, with an even more prominent exercise adjuvant and nutritional mTOR booster? Will they neutralize each other? Think about it.... ok, now gimme your answer: What happens if you put resveratrol and leucine together? At first it does not really make sense, does it? Right, it doesn't, at least not unless you follow the same train of thought, the researchers from NuSirt Sciences. NuSirt? That rings a bell, hah? Yeah those were the guys who did a study on their 250mg leucine + 30mg vitamin B6 proprietary blend NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More") and actually, the leucine + resveratrol combination is sort of a spin-off of this initial research.

If you put Sirt1 & Sirt1 together, it suddenly makes sense!

In their latest study (and you bet a future product!) Bruckbauer et al. build on their previous research on the agonistic effects HMB, alpha-KIC or leucine have on skeletal muscle Sirt-1 activity (Bruckbauer. 2011) and rationalize that it seems legit to combine one Sirtuin portein promoter with another one in order to achieve an even more pronounced effect - makes sense, right? Resveratrol the proven AMPK-promoter and igniter of the longevity, gene transcription, cell survival and apoptosis regulating Sir2 proteins (=sirtuins) and leucine the mTOR promoting and, as of late, proven Sirt1 agonist, they could actually form a synergistic duo for fat oxidation, glucose management, the reduction of oxidative stress and inflammation and even longevity!

Figure 1: Effects on sirtuin & AMPK expression in muscle and fat cells upon incubation with leucine, HMB and resveratrol and the respective combinations (left) and effects fatty acid oxidation in isolated rat skeletal muscle upon incubation in low and high glucose conditions (data based on Bruckbauer. 2013)

Now, aside from Sirt1, which is mainly expressed in the nucleus of a cell, another one of the Sir2 proteins, Sirt3, which is expressed predominantly in the mitochondria has as of late gathered quite some attention, as mitochondrial dys- or malfunction is one, if not the common denominator of many of the pathological features of the metabolic and neuro-endocrine ailments the Western diabesity society is suffering from: insulin resistance, type II diabetes, Alzheimer's , you name them! No wonder the NuSirt guys (and girls) are striving to find a marketable way to set them both in full gear and if you take a closer look at the data in figure 1 their initially counter-intuitive approach to bath muscle and fat cells in resveratrol  + HMB / leucine solutions yields impressive results:

• resveratrol, leucine and HMB, alone, exerted only weak independent effects on Sirt1, Sirt 3 and AMPK
• resveratrol and leucine or HMB, combined, yielded Sirt1 and Sirt3 activity increases in the ~50% range (p < 0.05) and AMPK increases of +42% and +55% (p < 0.03); particularly noteworthy are the ~125-175% increases (p < 0.02) muscle cells (remember: Sirt3 is expressed in the mitochondria!)
• the ensuing increases in fatty acid oxidation in incubated muscle cells reached statistical significance in the presence of low (5 mM) glucose levels, only, when and 5 µM HMB or  0.5 mM leucine were co-incubated with 200 nM (~18%; p < 0.05), in the high glucose condition, however, all treatments broad about significant increases in fatty acid oxidation, of which those in the leucine- and HMB-resveratrol combination treatments were the most pronounced (118% and 91% stimulation, respectively; p < 0.005)

Especially the last finding, i.e. the increase in fatty acid oxidation in an in-vitro condition that resembles the hyperglycemic state the average type II diabetic who is not popping tons of metformin and/or injecting insulin is constantly in, makes these results particularly interesting, as it appears as if a "non-pharmacological" (what by the way is "pharmacological" and what isn't?) solution to the diabesity problem could already be hidden on the shelves of your GNC right next door (I assume they carry leucine and resveratrol products ;-)!

Outside of the box... ahh, I mean, ... the petri dish!

In view of the fact that 75% of the in-vitro high performers suck in the rodent model already and of those another 75% don't work in human trials you will be pleased to hear that NuScirt Sciences' resveratrol + leucine / HMB combination has already overcome the first of these hurdles: At least in DIO (diet-induced-obese) rodents who on a 6-week high fat diet regimen, the combination works.

Figure 2: Weight gain, visceral adipose volume, PET measured palmitate uptake, respiratory rate (lower levels = higher relative fat oxidation), heat production relative to body weight, food intake; all value expressed relative to DIO mice who were maintained on an unsupplemented control diet (data based on Bruckbauer. 2013)

Now, it's not as if the rodents would have made it to the Mr Olympia stage, but if you take a closer look at the pattern that's emerging here, it's quite clear that the sirtuin booster does its job in this rodent model. Aside from its ameliorative effect on weight gain, the combination of resveratrol and leucine, led to statistically significant improvements in glucose management and improvements in inflammatory markers (including the anti-inflammatory adipokine adiponectin, see figure 2).

Figure 2: Glucose, insulin and HOMA IR levels, muscular glucose uptake (left), C-reactive protein , IL-6, MCP-1 and adiponectin (right) ; all value expressed relative to DIO mice who were maintained on an unsupplemented control diet (data based on Bruckbauer. 2013)

Most importantly, however it effectively cut through the exuberant amount of visceral adipose tissue (>30% reduction), ramped up the palmitate (fatty acid) uptake, oxidation and heat production (=thermogenesis). Despite all these metabolic improvements which took place in the absence of a simple reduction in food intake, there are still a couple of things left to be desired:

What are the human equivalent doses, here? Since I know you would be asking I did the math for you and you will be pleasantly surprised (HED for 80kg humans)

• 12.5mg resv. = 9mg
• 225mg resv. = 136mg
• 2g HMB = 1.1-1.4g
• 10g HMB = 7.2g
• 24g leucine = 14.3g

I am well aware that it must look as if I had the typical poor arithmetic abilities of the average physicist who has totally forgotten how to calculate using figures instead of letters, but the reason for the discrepancies is that I calculated the exact HEDs based on body weight and food intake for each of the groups.

1. Supplementation with the respective human equivalent doses should yield the same astonishing results in humans as it did in the diet-induced obese mice.
2. The protocol should have effects not just in morbidly obese diabetic human beings, but also in overweight and ideally even lean individuals.
3. The supp must work if you don't put it into the chow, but pop it in separate doses (e.g. 3x/day) as a capsule or tablet.

The good news however is that if 1-3 apply, you could start benefiting from this "super supplement" right now! After all, the resveratrol dose of 12.5mg per kilogram of chow (the mice in the study did not consume more than max. 4g(!) per day) is so low that the 10g package I just saw for 20$ over at the webshop of a major bulk supplier would last you literally forever ...

Unfortunately, this is exactly why I don't believe that LeuResSirt, or whatever other stupid name the final product will be given, is going to work - I mean, come on, you can't tell me that there are not already people out there who get 15-20g of leucine everyday and pop resveratrol in 100x the necessary dose of 8-9mg everyday!? And did they turn into a beast, become fast-food resistant or lose fat magically? What? Yeah... that must be Phil Heath secret, right... how come I did not realize that before? ;-)

Bottom line: Regardless of the probably justified skepticism, I will still keep you posted on whether or not NuSirt knocks out another incredible (in the literal sense) human study like the one on NuFit (see "Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize & More"). So stay tuned, you all know that no supplement will ever more ergogenic than your daily dose of SuppVersity news!

References:

• Bruckbauer A, Zemel MB. Effects of dairy consumption on SIRT1 and mitochondrial biogenesis in adipocytes and muscle cells. Nutr Metab (Lond). 2011 Dec 20;8:91.
• Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2013 Aug 22;9(1):77.

Build a Bigger Mitochondrial Engine and Double Your Endurance With Chitooligosaccharides! Glucosamine Mix from Chitosan Acts on Sirt1 & AMPK, Similar to Resveratrol

Figure 1: Glucosamine composition of the chitooligosaccharide used in the study (data adapted from Jeong. 2013).

Usually I try to avoid this term, as it seems to imply that there is, or at least soon will be a pill that would allow you to stay the lazy bastard you are now and still make it into your old age, healthy lean, attractive and vigorous, but in this case the word "exercise mimetic" is unquestionably what describes the effects of 6 weeks of oral supplementation with chitooligosaccharide described in a recently published paper by scientists from the Amorepacific Corporation Research & Development Center and the Kyung Hee University in South Korea best. I have to give props to my friend Carl Lanore the voice (and brain) of Super Human Radio who shot me an email on this issue, yesterday.

A brief glance at the full-text was enough to realize that Carl who likes to pretend he was the idiomatic "blind man" with no scientific degree (I could hardly care less, by the way ;-) who hits upon things like this only perchance was up to something - those who now the show, will be aware that he is smarter than many of the experts he interviews, anyways... but I am getting derailed, here. Where was I? Ah yeah, the study...

COS - What we already know

• Ameliorates weight gain (-15%) and high blood lipids on HFD in mice in the absence of reduced energy intake (Choi. 2013)
• Promotes cytokine release in intestinal epithelial cells (Bahar. 2013)
• Inhibits pancreatic lipase and thus breakdown and subsequent uptake of dietary fat (Kang. 2013)
• Suppresses TNF-alpha induced collagen breakdown in-vitro (Ryu. 2013)
• Has neuroprotective effects (Joodi. 2011)

Promising in vivo rodent + in vitro cell line data: Very promising, but not yet field-tested

Hyun Woo Jeong and his colleagues fed 39 female Sprague-Dawley rats either normal or 0.05% chitooligosaccharide (COS produced by Bioland Korea Co. Briefly from chitosan by enzyme digestion, followed by deacetylation of chitin; cf. Hirano. 1989) enriched rodent chow for 6 weeks.

At the end of the study period, 50% of the rodents had performed an exercise test on the treadmill, in the course of which they had to run at a pace of 20m/min until exhaustion, while the rest of the animals were sacrificed before this final workout to assess their pre-exercise plasma profiles including ALT, AST, triglyceride, total cholesterol, lactate, and free fatty acid levels (none of which showed significant changes over the course of the 6-week study period).

Despite the fact that the scientists did not measure the total lean and fat mass of the rodents, the collective data in figure 2 clearly suggests that the -72% reduction in weight gain was not at the expense metabollically active muscle tissue.

Figure 2: Body weight and energy intake (left) and muscle weight vs. body weight (right) data at the end of the 6-week trial (data adapted from Jeong. 2013).

Despite a statistically non-signficant reduction in food intake (-6%) the chitooligosaccharide treated rodents had heavier soleus (slow twitch, type II fiber dominant muscle) muscles and a more favoreable plantaris (fast twitch, type II-X fiber dominant muscle) to total body weight ratio (indicative of a lower body fat percentage), than their non-supplemented peers. Moreover, a cursory glance at figure 3 does also reveal why this is the case.

Figure 3: Electron microscopic image of muscle tissue (top; small arrows and green areas indicate the presence of mytochondria), mitochondrial density in in-vitro control experiment after exposre to different doses of  resveratrol vs. chitooligosaccharide (bottom, left) and time to exhaustion during treadmill test (adapted from Jeong. 2013)

Even as a non-expert it is easy to see that the chitooligosaccharides had profound "anabolic" effects on the mitochondria of the lab animals.

COS activated AMPK and increased the cellular NAD+ / NADH ratio to induce Sirt1 activation. The activation of AMPK and Sirt1 increased the expression and activity of PGC1 and augmented the expression of mitochondrial genes. As a result of activation of AMPK, Sirt1, and PGC1, COS facilitated mitochondrial biogenesis. In rodents, the administration of COS significantly increased intramuscular mitochondrial content, resulting in enhanced exercise endurance and reduced plasma lipid profiles. (Jeong. 2013)

In the Petri-dish, it may be less potent than resveratrol on a per mg base (figure 3, bottom-left), but the real world effects in terms of both, increased mitochondrial biogenesis (see green mitochondria in the electron microscopic image of skeletal muscle; figure 3, top) and subsequent increases in average running time to exhaustion (+96%; figure 3, bottom right) speak for themselves.

Implications: Other than resveratrol, which has an oral biovailability that is hardly high enough to be quantified (Walle. 2004), chitooligosaccharide could actually be suitable for oral supplementation - at least if we assume similar pharmacokinetics in humans as in rats (which is likely, but not necessarily the case).

• especially sedentary individuals or people who rarely train could benefit from the exercise-mimicking effects 
• in a previous study by Cho et al. chitooligosaccharide lactate has been found to be superior to chitooligosaccharide HCL (Cho. 2010)
• the optimal dosage and, more importantly, whether trained and well-conditioned individuals would benefit to a similar extend / at all, would yet require further studies. 
• the human equivalent dosages for the study at hand would be 600-900mg/day depending on the individuals body weight

Image 1: COS is rather something for the "old" Mr C. than for Adelfo

Aside from the fact that there are (at least to my knowledge) no over-the-counter chitooligosaccharide supplements on the market, so that you would probably have to order a metric ton right from China at Alibaba.com, I would not expect too much from it, anyways. Firstly, the chances that it turns out to be another supplemental non-starter like resveratrol are high. And second- and more importantly, the beneficial effects will be less pronounced for well-conditioned individuals and could even be close to zero (and certainly not practically relevant) for people who go to the gym to train and not to pose, to chat or to flirt. People like you and me and Adelfo Cerame, whose new client Mr. C. is soon going to join the ever-growing community of physical culturists, who don't need a "mimetic" for something they love: Exercise!

References:

• Bahar B, O'Doherty JV, Maher S, McMorrow J, Sweeney T. Chitooligosaccharide elicits acute inflammatory cytokine response through AP-1 pathway in human intestinal epithelial-like (Caco-2) cells. Mol Immunol. 2013 Jul;51(3-4):283-91. Epub 2013 Apr 16.
• Cho SY, Lee JH, Song MJ, Park PJ, Shin ES, Sohn JH, Seo DB, Lim KM, Kim WG, Lee SJ. Effects of chitooligosaccharide lactate salt on sleep deprivation-induced fatigue in mice. Biol Pharm Bull. 2010;33(7):1128-32.
• Choi EH, Yang HP, Chun HS. Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation. Nutr Res. 2013 Mar;32(3):218-28.
• Hirano S, Tsuchida H, Nagao N. N-acetylation in chitosan and the rate of its enzymic hydrolysis. Biomaterials. 1989;10: 574–576.
• Jeong HW, Cho SY, Kim S, Shin ES, Kim JM, Song MJ, Park PJ, Sohn JH, Park H, Seo DB, Kim WG, Lee SJ. Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats. PLoS One. 2013;7(7):e40073.
• Joodi G, Ansari N, Khodagholi F. Chitooligosaccharide-mediated neuroprotection is associated with modulation of Hsps expression and reduction of MAPK phosphorylation. Int J Biol Macromol. 2011 Jun 1;48(5):726-35.
• Kang NH, Lee WK, Yi BR, Park MA, Lee HR, Park SK, Hwang KA, Park HK, Choi KC. Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model. Lab Anim Res. 2013 Mar;28(1):31-8. Epub 2013 Mar 21.
• Ryu B, Himaya SW, Napitupulu RJ, Eom TK, Kim SK. Sulfated chitooligosaccharide II (SCOS II) suppress collagen degradation in TNF-induced chondrosarcoma cells via NF-κB pathway. Carbohydr Res. 2013 Mar 1;350:55-61.
• Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004 Dec;32(12):1377-82. Epub 2004 Aug 27.

Resveratrol from 100l of 1994 Pinot Noir Could Increase Fat Oxidation by 71%, Strength by 18-58% and Endurance by 20% - At Least, If You Could Afford and Drink It Every Day!

Image 1: Itadori (Japanese Knotweed) and selected varieties of red wine are the best yet vastly 'underdosed' sources of resveratrol (see red box, below)

At least in rodents, resveratrol, the red-wine polyphenol, has been shown to act as an exercise mimetic, exerting profound effects on PGC-alpha expression which protect muscle from wasting due to mechanical unloading (also know as extreme couch-potato-ing ;-) and rodents from the negative side-effects of obesogenic diets by directly modulation gene expression, lipid transport and fatty acid oxidation in skeletal muscle (Chen. 2011; Momken. 2011). Still, most of the oftentimes publicly puffed up data on resveratrol comes from in-vitro studies with dosages of which even the researchers often believe that they are not attainable via oral supplementation.

Rodents or petri dishes? Humans would be too expensive...

Compared with the aformentioned in vitro data, the numbers and gene essays in a recently published study by scientists from the University of Alberta are actually of great practical relevance (Dolinsky. 2013), because Dolinsky et al. administered their resveratrol orally* (4g in 1kg chow) to healthy rats and - what's even more important for the average trainee - 50% of those rats were exercised for 60min, 5x per week on a treadmill (10m/min to 20m/min; cf. Fenning. 2003) for 12 weeks.

Figure 1: Resveratrol content of selected red-wines and Itadori (Japanese knotweed) tea (based on Burns. 2005; equivalent consumption based on dose used in Dolinsky. 2013)

*Can I get my resveratrol from wine or food: I cannot emphasize enough that with ~75% of orally administered resveratrol being excreted via feces and urine and an oral bioavailability of resveratrol of almost ZERO (Vitaglione. 2005; Wenzel. 2005), there is no reason whatsoever to cope with any of the ~100 in-vitro studies that are published on a monthly basis hailing resveratrol for this and that and praising it as the god-sent natural remedy for every ailment, except the consistent ignorance towards the profound difference between a cell in a petri dish and a complex organism that is so prevalent among the human lab rats in their white coats, these days. And the data in figure 1 should make it pretty clear that similar benefits as they were observed in the study at hand are not just unlikely, they are simply impossible to be achieved without highly concentrated supplements - or do you want to drink 105+ liters of wine a day to get your daily dose of ~2g of resveratrol?

Let's assume you got the ~350$ for your 2g/day of resveratrol powder** to mix with your food (**calculated based on the current price of >90% pure bulk powder in Europe), what would be the results? Would you lose weight? Unlikely. Would you lose body fat? Possible! Would you gain muscle? Very unlikely. So what's all the fuss about then?

Figure 2: Body weight (in g), time to exhaustion (in min) and distance covered (in m) during a treadmill exercise test at the end of the 12-week study period (based on Dolinsky. 2013)

Much ado about nothing? Not really, no. After all, the ~20% increase in endurance (time to exhaustion and distance covered; cf. figure 2)  did not come out of nowhere and do - and this is actually the main reason this study did actually make it to SuppVersity - add to the benefits of regular training. The "resveratrol rats" had ...

Image 2 (ADAM): Resveratrol has already been shown to prevent pathological hypertrophy of the heart muscle by AMPK / AKT modulation (Chan. 2008)

• greater strength gains +18% tibialis anterior twitch force and +58% and +22% tetanic and twitch force, respectively, in soleus vs. training alone
• improved cardiac function as assessed by statistical significant improvements in left ventricular ejection fraction and decreased isovolumic relaxation time, as well as increased ratio of the peak mitral flow velocity (E-wave) to the peak velocity of the late filling wave of atrial contraction
• decreased cardiac stress due to a -30% reduction in left ventricular wall stress vs. training alone
• higher VO2 ~10% during the active period 
• increased PPAR signalling and fatty acid metabolism in the heart (+8.8% and +10.3% respectively; p < 0.00001)

Sexier than the strength gains and the utterly unsexy (but vitally important) improvements in cardiac performance are yet the statistically significant reduction in triglycerides which should help insulin sensitivity (not measured in the study) and are probably a beneficial downstream effect of the  resveratrol induced shift towards higher fatty acid and lower glucose oxidation (-6% respiratory exchange ratio, RER; cf. figure 3) that went hand in hand with a highly significant +71% increase in fatty acid oxidation:

Figure 1: Triglyceride levels, free fatty acids, respiratory exchange ratio (higher values = lower fat oxidation, higher glucose oxidation) and total fat oxidation at the end of the 12-week study period (all data expressed relative exercised control; based on Dolinsky. 2013)

Along with the +50% increase in AMPK (vs. exercise alone) and the 20% increase in the "mitochondrial builder" PGC1-alpha (cf. "Two days on High Fat Diet Increase the Activity of Irisin Releasing Transcription Factor PGC1-α") it is obvious that, taken at the right dosage, resveratrol is not the supplemental non-starter everyone is let to believe who spent $30 for 60 100mg caps of resveratrol and took a 3-day dose (3x 2g!) spread across a whole month - obviously without the desired outcomes result.

At the moment resveratrol is still an expensive toy for scientists

Table 1: Significant changes in heart muscle gene expression (based on Dolinsky. 2013)

As a tool to study (epi-)genetics and the downstream effects and interactions of reduction of cytokines, such as the inteferon-induced proteins, which regulate immune functions, cell growth and apoptosis (Sen. 2000), increases in mitochondrial uncoupling protein 3 (UCP3) and UCP1, higher expressions of adiponectin and thyroid responsive protein and the steroyl-coenzyme A desaturase-1 enzyme, which converts saturated to mono unsaturated fatty acids and plays an important role in controlling inflammation, preventing atherosclerosis, steatohepatitis (fatty liver) and pancreatic beta cell dysfunction (Brown. 2010) resveratrol is a must have. As one of the most expensive currently available supplement with little to no actual human data from studies on healthy subjects, its usefulness for physical culturists is questionable and its cost-benefit ratio is abysmal, to say the least.

References:

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