Chronic High Dose BCAA Supplementation Reduces Endurance Performance by 43% Plus: How Ammonia, Glutamine, Arginine & Low Carb Could be Involved

Tired, exhausted, had to cut your workout short today? Is it the flu, or just too much BCAAs?

When some is good and more is better, even more is not necessarily going to be 'betterer' - and that's not simply due to the fact that there is no comparative to an adjective that's already in the comparative. Therefore it is actually not surprising that a team of researchers from the Department of Food and Experimental Nutrition at the Faculty of Pharmaceutical Sciences, the Department of Nutrition at the School of Public Health and the Department of Physiology and Biophysics at the Institute of Biomedical Sciences of the University of Sã o Paulo in Brazil has just published the results of a study (Falavigna. 2012) which demonstrates that there is an upper limit to the benefits of BCAA supplementation. What I guess will be surprising at least for some not so regular SuppVersity visitors, is that there is more than just a saturation effect: Too much BCAAs can actually have ergolytic (= anti-ergogenic) effects - at least under certain circumstances.

Another chapter in the book of good things that turn against you, when taken in excess

In their latest paper that has just been published in nutrients, Gina Falavigna and her colleagues analyzed effects of chronic BCAA supplementation on exercise performance in male Wistar rats. Based on previous animal and human data and the still widely supported, though actually experimentally non-validated (cf. Meeusen. 2007) theory that BCAAs would work their non-hypertrophy specific, endurance enhancing magic via the blockade of exercise induced 5-HT (serotonin) accumulation in the brain, the researchers speculated that ...

"[...] chronic BCAA supplementation (through the diet, using different BCAA  concentrations) would increase performance in rats subjected to a swimming exhaustion  test." (Falavigna. 2012)

To verify this hypothesis, Flavigna et al. randomized their rats to three different groups receiving either the standard AIN-93M diet for the maintenance of adult rodents (control group) or the same diet with additional additional 3.57% (group S1) and 4.76% (group S2) BCAAs at a ~2:1:1 ratio of lecine : valine : isoleucine (the BCAAs were manufactured by the Brazilian branch of Ajinomoto). The rodents in the S1 and S2 groups did thus receive 50% and 100% more branched-chain amino acids than the rodents in the control group which had to contend themselves with the BCAAs in the casein fraction of their diets (see figure 1, right). In order to assure that the diets would be isocaloric, an amount of starch equivalent to the amoung of BCCAs that had been added to the chow was removed from the supplemented diets.

Overall, the study lasted for six weeks. During this time the rodents were subjected to a 1h/day weight bearing swimming protocol five times a week. In the first two weeks, the rats were ...

"[...] adapted to the water medium and exercised with increasing overloads attached to the tail until an overload corresponding to 5% of total body weight was reached. This final overload was used until the end of the training protocol [...] The overloads were corrected weekly according to the variations in animal weight.  The efficiency of the training protocol was assessed on the basis of maximum activity of the enzyme citrate synthase in the soleus muscle, with a group of sedentary animals being used as the control for this parameter." (Falavigna. 2012)

Neither the overall amount of food nor the body weight gain of the rodents in the control, and the two exercise groups showed any statistically significant difference. The latter cannot be said about the exercise performance, as well as the accumulation of ammonia, though (see figure 1):

Figure 1: Exercise duration and plasma ammonia levels during / after swmming test (left) and macronutrient composition of the experimental diets (right; based on Falavigna.. 2012)

While the rodents in the +50% BCAA group (S1) do show the expected increase in endurance (+37%) their peers in the high dose (+100%) BCAA group (S2) experienced an even more pronounced drop in endurance performance (-43% vs. control), which went hand in hand with a profound increase in blood ammonia (+34%).

"Ammonia is a ubiquitous metabolic product producing multiple effects on physiological and biochemical systems. Its concentration in several body compartments is elevated during exercise, predominantly by the increased activity of the purine nucleotide cycle in skeletal muscle. Depending on the intensity and duration of exercise, muscle ammonia may be elevated to the extent that it leaks (diffuses) from muscle to blood, and thereby can be carried to other organs. The direction of movement of ammonia or the ammonium ion is dependent on concentration and pH gradients between tissues. As such, ammonia can also cross the blood-brain barrier, although the rate of diffusion of ammonia from blood to brain during exercise is unknown. It seems reasonable to assume that exhaustive exercise may induce a state of acute ammonia toxicity which, although transient and reversible relative to disease states, may be severe enough in critical regions of the central nervous system (CNS) to affect continuing coordinated activity. Regional differences in brain ammonia content, detoxification capacity, and specific sensitivity may account for the variability of precipitating factors and latency of response in CNS-mediated dysfunction arising from an exercise" stimulus, e.g., motor incoordination, ataxia and stupor. There have been numerous suggestions that elevated ammonia is associated with, or perhaps is responsible for, exercise fatigue, although evidence for this relies extensively on temporal relationships." (Falvigna. 2012; my emphasis)

Mark the last words of the previously cited paragraph: "[E]vidence for [the role of ammonia] in exercise fatigue relies extensively on temporal relationships". It is thus - as for now - a solely corollary, not yet a causative association, of which I do however feel that it would be very likely to turn into a causal one if someone actually measured the influx of ammonia into the brain during a workout.

Wait, ammonia? But ain't it more likely that the BCAAs block the uptake of tryptophan?

What's for sure is that another hypothesis, which relates to the blockade of tryptophan uptake can be ruled out as an underlying reason of the differences. After all the scientists who argue that ...

"[t]he increased synthesis of serotonin during exercise may be related to the development of central fatigue, because this neurotransmitter has several physiological functions, since it operates by  mood, lethargy, individual behavior, regulation of sleep, body temperature and blood  pressure, appetite suppression and changes in perceived exertion." (Falavigna. 2012)

...actually measured the 5-HT levels and observed no differences between the dietary groups. Overall, the study results to thus clearly indicate that both, medium nor high dose "chronic BCAA supplementation was not effective in improving the main parameters indicative of central fatigue" (Falavigna. 2012) - well, at least as long as we still stick to the hypothesis that the latter is induced by the accumulation of 5-HT in the brain.

Forget about tryptophan and serotonin, focus on ammonia

The fact that neither the high, nor medium dose of BCAAs did exert any effects on the serotonin levels in the brain does yet not explain why the medium dose supplementation regimen produced ergogenic, while the high dose regimen induced ergolytic effects.

The occurrence of direct toxic effects due to (too) high amounts of branched-chain amino acids can be ruled out based on previous studies in which the administration of more than 10g/kg body weight of BCAAs (the human equivalent would be 130g+ per day), as well as dosages of 2.5g/kg body weight chronically did not entail any toxic side effects (Shimomura.  2004). The same is true for other confounding variables, such as the citrate synthase activity, a measure of the general efficiency of the training protocol, bood glucose, insulin,free fatty acids, and lactate levels, as well as liver and muscle glycogen content, which were virtually identical in both groups. This leaves us with the increase in plasma ammonia as our 'last resort' to explain the -58% shorter swimming time in the high (S2) vs. medium (S1) dose BCAA group (-43% lower vs. non-supplemented control).

Figure 2: The reduced performance of the high BCAA group could well be related to peripheral and/or central ammonia build-up as a results of increased BCAA oxidation, camparably low glutamine intakes and the rate-limited enzymantic conversion and recycling of gluatmine (illustration originally from Earrante. 2003). Studies by Snow (2000) and Carvalho-Peixoto (2007) suggest: Both carbohydrate & glutamine supplements could help.

Based on what we know about the mammalian body, the increased build-up of ammonia in the high BCAA group could be a result of the unfortunate combination of temporary energy shortage and learned wastefulness' in a situation, where the otherwise sparse BCAAs are available in abundance. Furthermore, with a glutamine content of only 9-13% in the casein fraction of their diets (Swails. 1992), the rodents in the high BCAA group did ingest more than 2.6-3.8 times more BCAAs than glutamine; a fact which may have contributed to a temporary glutamine deficiency as a result of its increased use in the detoxification of the ammonia that's generated when the BCAAs are oxidized. The resulting peripheral and possibly central ammonia build-up (see figure 2) could then have begun to intoxicate liver and brains of the rodents and thus hampered gluconeogensis (normal levels stimulate, high levels of ammonia hamper gluconeogensis; cf. Fritz. 1988) and induced central fatigue (Wagenmakers. 1990; Nybo. 2004) -- and that not despite, but rather due to the chronic "high dose" BCAA supplementation (HED ~50g/day).

So do I have to drop my BCAAs now or what? Whether these results are relevant for you will probably depend on a whole host of parameters, which include

• the type, intensity and duration of exercise you do, 
• the ratio of BCAAs to glutamine in your diet,
• the amount of arginine, which acts as a substrate for the urea cycle and is therefore necessary to for the excretion of ammonia by the kindeys (Schaefer. 2002),
• the amount of carbohydrates in your diet (with more = less amino acid oxidation = lower ammonia and very low carb = you are in trouble; e.g. Czarnowski. 1995; Snow. 2000; Carvalho-Peixoto. 2007), 

... and those factors I will probably have forgotten to mention now. Unless you don't forget that you can neither lifve from BCCAs and protein alone, but accept the neflglected truth that too much protein is about as bad a too little protein, you can file this post under "show your stupid friends" and get back out, when they complain about feeling sick, bloated and fat "despite" eating a BCAA supplemented high protein, low carb (and often even low fat) diets.

References:

• Carvalho-Peixoto J, Alves RC, Cameron LC. Glutamine and carbohydrate supplements reduce ammonemia increase during endurance field exercise. Appl Physiol Nutr Metab. 2007 Dec;32(6):1186-90.
• Errante LD, Petroff OA. Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations. Seizure. 2003 Jul;12(5):300-6.
• Falavigna G, de Araú jo Junior JA, Rogero MM, de Oliveira Pires IS, rio Graç a Pedrosa R, Martins Junior E, Alves de Castro I, Tirapegui J. Effects of Diets Supplemented with Branched-Chain Amino Acids on the Performance and Fatigue Mechanisms of Rats Submitted to Prolonged Physical Exercise. Nutrients 2012. 4; 1767-1780.
• Fritz S, Bohnensack R. Stimulation of alanine metabolism in rat liver by ammonia. Biomed Biochim Acta. 1988;47(12):923-32.
• Meeusen R, Watson P. Amino acids and the brain: do they play a role in "central fatigue"? Int J Sport Nutr Exerc Metab. 2007 Aug;17 Suppl:S37-46.
• Nybo L, Dalsgaard MK, Steensberg A, Møller K, Secher NH. Cerebral ammonia uptake and accumulation during prolonged exercise in humans. J Physiol. 2005 Feb 15;563(Pt 1):285-90. Epub 2004 Dec 20. 
• Schaefer A, Piquard F, Geny B, Doutreleau S, Lampert E, Mettauer B, Lonsdorfer J. L-arginine reduces exercise-induced increase in plasma lactate and ammonia. Int J Sports Med. 2002 Aug;23(6):403-7.
• Shimomura, Y.; Murakami, T.; Nakai, N.; Nagasaki, M.; Harris, R.A. Exercise promotes BCAA catabolism:  Effects  of BCAA supplementation on skeletal muscle during exercise.  J. Nutr.  2004, 134, 1583S–1587S.
• Snow RJ, Carey MF, Stathis CG, Febbraio MA, Hargreaves M. Effect of carbohydrate ingestion on ammonia metabolism during exercise in humans. J Appl Physiol. 2000 May;88(5):1576-80.
• Swails WS, Bell SJ, Borlase BC, Forse RA, Blackburn GL. Glutamine content of whole proteins: implications for enteral formulas. Nutr Clin Pract. 1992 Apr;7(2):77-80.
• Wagenmakers AJ, Coakley JH, Edwards RH. Metabolism of branched-chain amino acids and ammonia during exercise: clues from McArdle's disease. Int J Sports Med. 1990 May;11 Suppl 2:S101-13.

TTA + Fish Oil Revisited - Increased Intramuscular Omega-3 Levels Compromise Heart and Skeletal Muscle Performance: -40% Endurance & -54% Total Work Capacity in 9 Weeks

Image 1: It is hilarious this picture was probably shot and (ab-)used to propagate the unhealthy message that you could never get enough omega-3 fatty acids from your diet, because that would mean you had to eat such nasty stuff as fish - pah, better pop some pills, I mean we are in the 21st century right!?

I guess you will remember my previous blogpost,  "TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants?", on the 2012 study by Vigerust et al. which did show that TTA could ameliorate the hepatoxic side effects of fish oil, which, when it is administered in amounts higher than 1-2g per day over an extended time period, begins to accumulate in the liver (see also "Too Much of a Good(?) Thing: When Fish Oil Starts Clogging Your Arteries and Fattening Up Your Liver"). Moreover, the addition of ~912.4mg (human equivalent) TTA to the "long-term fish oil = fatty liver"-equation turned produced a pretty potent fat burning and anti-obesity stack. Based on previous reports on the unwanted side effects of TTA-based fatburners in the past, I deliberately selected the subtitle "Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run" and explicitly cautioned against the (over-)use of this fat loss combo for an extended period of time - as one of the most recent article in the journal Lipids in Health and Disease suggests, more than rightly so (Strand. 2012)!

TTA a can save your liver, but it will exasperate the shift of n-3 into your heart

Image 2 (Knuuti. 2008): a globally, well-perfused and (top) a compromised heart with a maximum perfusion of 1.3 ml/g/min (bottom)

As the data the scientists from the Haukeland University Hospital in Bergen, Norway, collected clearly suggest. A similar combination of fish oil and TTA of which Vigerust et al. found that it ramps up fatty acid oxidation in the liver and clears your most important detoxification organ from long-chain polyunsaturated fatty acid junk (not or incompletely oxidized omega-3s) fails to elicit similar effect in the heart of 8-10 weeks old male Wistar rats, who were kept for 50(!) weeks on one the following four 25% fat diets which differed only in terms of their individual fatty acid composition:

• control diet - 23% lard, 2% soybean oil
• TTA - 0.375% TTA, 22.6% lard, 2%
• fish oil - 10.4% fish oil (42% EPA / 21% DHA), 12.6% lard
• TTA & FO - 0.375% TTA, 10.4% FO, 12.2% lard, 2% soy

With both, fish oil and TTA being potent peroxisome-proliferator receptor (PPAR) agonists the scientists were mainly interested in the long-term effects of this touted "anti-diabesity" (i.e. countering diabetes and obesity) agents on the deposition and distribution of different fatty acids in various tissues. A special focus was on the heart and the downstream effects of fatty acid metabolism and myocardial function and performance.

N-3 accumulation in the heart? Wait that's a good thing, right? NO!

For the laymen who has been bamboozled by the fish oil craze this may initially sound counterintuitive, but the profound accumulation of omega-3 fatty acids in the myocardium (heart) of the rodents (see figure 1) is about as bad as it can get for the critters heart health.

Figure 1: PUFA composition (wt%) in heart of rats after 50 weeks of diet administration (Strand. 2012)

Similar to what we have seen for Zinc (cf. "Zinc: 15mg Are Plenty - After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome") and alpha lipoic acid (cf. "Lean & Muscular With Alpha Lipoic Acid? You Could Be Just as Lean, But More Muscular W/out 'Nutrient Repartitioner'!"), the PPAR-agonists fish oil and TTA, both of which have been shown to exert beneficial effects in certain sick (as of yet still sub-)groups of the population, like diabetics (e.g. Khalid. 2011) and patients with dilated cardiomyopathy (e.g. Nodari. 2011), exert diametrically opposed effects in a rodent model that is probably more accurate for the average healthy human being than his/her sedentary, obese and metabolically deranged peers.

Keep away from your obese neighbors' supplement stash, damn it!

Independent analyses such as a 2009 paper by Dijkstra et al. do not support the commonly held conviction that fish oil or a higher intake of omega-3 fatty acids was beneficial for the general non-diabetic public anyway (Dijkstra. 2009). And it does not take all too long to find numerous reports of in parts serious side effects from the consumption of high-dosed TTA-based fat-burners in the archives of popular fitness and bodydbuilding boards, before the respective supplement producers got scared and pulled them voluntarily and under the pre-text that they had found more effective formulations off the market.

Figure 2: Enzyme activity (nmol/min/mg) in heart of rats after 50 weeks of diet administration (based on Strand. 2012)

Probably a smart move if you look at the combined increases in enzymes that oxidize (ACOX) and enzymes that synthesize and store  fatty acids (FAS and GKAT) in the heart muscles of the rodents in figure 2. Together the synergy of increased storage and increased oxidation could create a perfect storm, which due to the overall "limited capacity of heart to metabolize the poorly oxidizable n-3 PUFA compared to SFA [...] might altogether indicate a reduction in cardiac efficiency" (Strand. 2012).

Reduced cardiac efficacy = reduced muscular efficacy

It's quite funny that we could actually have known that all along, after all, one of my favorite "holy omega-3 vs. bad omega-6" studies by K.J. Ayre and A.J. Hulbert was published in 1997 already. Ayre and Hulbert wanted to elucidate the effects of different dietary fatty acid compositions on the exercise capacity of rodents and found (way before the fish oil craze and therefore not so much to their surprise) that compared to a coconut (EFA deficient) or sesame oil (high omega-6) the n-3 enriched test diet led to a profound decrease in exercise capacity (see figure 3)

Figure 3: Endurance and total work capacity (left) and soleus and EDL fatty acid composition (right) of rats after 9 weeks on diets containing almost no essential fatty acids , a high n-6 or a high n-3 content (Ayre. 2012)

Similar to the detrimental effects on the efficacy of the heart muscle, the decreases in endurance -40% and -54% in endurance and work capacity in the n-3 group went hand in hand with profound increases in the soleus and extensor digitorum longus omega-3 content.

In view of the fact that TTA appears to increase the existing fatty acid recompositioning effects of an overload of dietary omega-3 fatty acids in the diet, and against the background that the observed negative side effects came about in no more than 9 weeks and were not reversed after 6 weeks on standard chow, it appears more than questionable if the few lbs of body fat you may be able to shed with the aforementioned TTA+fish oil double whammy over say 4-8 weeks are actually worth taking the risk of permanent or at least only slowly reversible changes in the intracellular fatty acid composition of your heart and skeletal muscle.

"And what about fish oil supplementation alone?"

Aside from the fact that the usefulness of fish oil caps in healthy individuals is questionable (Dijkstra. 2009) and anything beyond 1-2g of fish oil per day could well lead to increased not decreased oxidative damage in athletes and physical culturists (cf. "Omega-3 Fatty Acids Pro-Inflammatory in Athletes"; Filaire. 2010), you don't necessarily have to throw away your fish oil. After all, I would hope that no one here is getting 50% of his/her daily fat intake from fish oil caps - which was basically what Strand et al. fed their rodents to make sure that the shift in myocardial fatty acid levels would be profound enough. Still the Ayre study, where the n-3 content of the diets was much lower (16% of total fat intake, ~8.8g of fish oil if you consumed 2,000kcal/day), does indicate that the intramuscular changes in fatty acid composition can be profound and not without detrimental consequences even without the addition of TTA and in response to amounts of omega 3 fats of which we all know that thousand of supplement junkies still believe would be nothing but beneficial for their health.

Image 3 (woschie): What would these guys say, if everything they caught was a handful of fish oil caps? "Look! I have caught the best part of the fish. lucky me, so I don't have to take it, squeeze it and bath it in all sorts of chemicals to separate the good fats from the bad protein I would then have to process to fish meal!"

In the end, it all comes, as so often, by the way, back to two very common motifs here at the SuppVersity motif A which I have already implied in one of the subheadings is the simple truth that what has been show to work for the obese type II diabetic does not necessarily work for a healthy human being, let alone such an extraordinary specimen as you are ;-) And that does in fact segue perfectly into motif B which revolves around the notion of balance and is basically the foundation of my repetitive advice to always prefer real foods over supplements, where the latter is possible - and contrary to creatine of which even a meal-loving carnivore like myself could never get enough from his diet to see any of the scientifically well-established benefits, eating fish spending a couple of extra-bucks on grass-fed beef from time to time and simply avoiding the omega-6 laden vegetable oils will make the use of those nasty fish oil caps obsolete, anyways.

References:

1. Ayre KJ, Hulbert AJ. Dietary fatty acid profile affects endurance in rats. Lipids. 1997 Dec;32(12):1265-70.
2. Dijkstra SC, Brouwer IA, van Rooij FJ, Hofman A, Witteman JC, Geleijnse JM. Intake of very long chain n-3 fatty acids from fish and the incidence of heart failure: the Rotterdam Study. Eur J Heart Fail. 2009 Oct;11(10):922-8.
3. Filaire E, Massart A, Portier H, Rouveix M, Rosado F, Bage AS, Gobert M, Durand D. Effect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletes. Int J Sport Nutr Exerc Metab. 2010 Dec;20(6):496-506.
4. Khalid AM, Hafstad AD, Larsen TS, Severson DL, Boardman N, Hagve M, Berge RK, Aasum E. Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2116-22. Epub 2011 Mar 18.
5. Knuuti J, Bengel FM. Technology and guidelines: Positron emission tomography and molecular imaging. Heart 2008;94:3 360-367
6. Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, Gheorghiade M: Dei Cas L: Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol 2011, 57:870–879.
7. Strand E, Bjørndal B, Nygård O, Burri L, Berge C, Bohov P, Christensen BJ, Berge K, Wergedahl H, Viste A, Berge RK. Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat. Lipids Health Dis. 2012 Jun 27;11(1):82.
8. Vigerust NF, Cacabelos D, Burri L, Berge K, Wergedahl H, Christensen B, Portero-Otin M, Viste A, Pamplona R, Berge RK, Bjørndal B. Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks. J Nutr Biochem. 2012 Jan 3.

Study Confirms Antioxidants (C+E) Are Bad For Healthy People Who Train, But in Some Subjects C+E Increase the Fat Loss Effects of HIIT + HIT by a Whopping 60%

The anti-long-term health, but pro short term fat loss effects of vitamin C + E

I must admit that I filed the study by Paulsen et al. (2014; accepted manuscript) under "further evidence that high doses of anti-oxidants do more harm than good to active individuals" the very moment I posted the information from the corresponding press release in the SuppVersity Facebook News (read it!).

A couple of days ago, I wanted to cite the paper in a different context and took a closer look at the actual results (yeah, even I sometimes only read the abstract) and as it turns out,...

...the scientists left out some information, you may be interested in, ...

...even though it may not be relevant from a statistical perspective. How I know things about your interests?Based on the visitor statistics of the SuppVersity. I just have to take a brief look at them to know that the vast majority of you will be intrigued to hear that the "daily vitamin C and E supplementation" (1000mg vitamin C and 235mg vitamin E per day), although it may have "attenuated increases in markers of mitochondrial biogenesis following endurance training", led to an albeit non-significant, but highly conspicuous 60% increase in body fat reduction.

Figure 1: Pre- & post-levels of body fat mass (left, in kg) and relative changes in type I and type II muscle fiber size (right; in % of baseline) in the subjects in the vitamin C + E and placebo arm of the study (Paulsen. 2014)

Yes, I know. The inter-group difference did not reach statistical significance. If you look at the exact figures, though you will have to concede that the intra-group difference did. In other words: While the subjects who took the anti-ergogenic anti-oxidants lost a significant amount of body fat, those who took the placebo did not. This is because the fat loss in the supplementation groups was much more evenly distributed than in the placebo group (the corresponding standard deviations were "only" 1.6x, not 3.6x (placebo) higher than the average fat loss of -5.3kg).

Table 1: Overview of the exercise component of the study (Paulsen. 2014)

Due to the minimal loss or marginal gain of lean body mass (and fiber size; see Figure 1) in the vitamin and placebo group, respectively, the relative difference of the change in body fat % (-4.6% in the vitamin and -2.0% in the placebo group) is even more pronounced.

This does not mean that these effects on the body composition are "real", i.e. actually due to the provision of vitamin C + E. What it does mean, though is that the occurred, although there was no visible training effect on the mitochondrial capacity and thus in the absence of any visible / measurable training effects.

The fat loss effects are not significant and my ad hoc hypothesis to explain them merely speculative. Therefore I still advice against the use of high dose "kamikaze" antioxidants (mere ROS-scavenger) like vitamin C + E - not just in the vicinity of a workout, but in general.

The absence of structural changes and the corresponding long-term health benefits that will always outweigh those of temporary reductions of body fat, should be reason enough to understand that someone who is not sick and chronically inflamed as the animals and human subjects in the studies you will see referenced in the write-ups of the supplement industry not to consume copious amounts of vitamin C, vitamin E or NAC.

Bottom line: I am certainly no advocate of high dose vitamin supplements and there is accumulating and in my humble opinion convincing evidence that they blunt the adaptive response to exercise training - including the potentially life-saving changes in mitochondrial capacity.

Still, the data from the Paulsen study does also support the conventional wisdom that a high level of baseline inflammation hampers the loss of body fat and that in spite, or rather because of the fat-burning prowess of IL-6, of which Knudsen et al. (2014) have recently been able to show that it is responsible for the exercise induced increase in UCP1 expression in subcutaneous white adipose tissue that will have your love handles melt away.

That does not make sense? Well, maybe it does. If you think about it as a vitamin-induced alleviation of the IL-6 analog to insulin resistance that allows the fat cells to finally "see" the IL-6 again and would thus propel the loss of body fat in those of the 14 women and 13 men in the supplement arm of the study who had a high baseline inflammation and correspondingly low "IL-6 sensitivity", this would be similar to the beneficial effects of ALA on weight loss int he obese and their absence in lean people.

References:

• Knudsen, Jakob G., et al. "Role of IL-6 in Exercise Training-and Cold-Induced UCP1 Expression in Subcutaneous White Adipose Tissue." PloS one 9.1 (2014): e84910.
• Paulsen, G, et al. "Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized control trial." Journal of Physiology (February 2014; accepted manuscript).