Sweet, But Not Innocent!? The Fattening Effects of the Non - Nutritive Sweeteners Erythritol & Aspartame Are On Par With Equally Sweet Sugar Water

I just hope that today's SuppVersity article is not going to cause scenes like this, because when it all said and done it may be less likely, but not impossible that it is (for whatever vexed reason) still aspartame that caused the negative effects observed in the study at hand.

It is one of the recurring motifs here at the SuppVersisty and at the same time one of the most popular issues of dispute in the health and fitness community: The Obesogenic Effects of Artificial Sweeteners. Or, in plain English, the question  

"Can I use Sucralose, Aspartame and Acesulfam-K without taking the risk of getting fatter - not leaner, as I actually intended?"

For all three of the explicitly mentioned agents human studies clearly suggest that the answer is "Yes, you can!" And I will now dare saying that the of the most recent study from the Oita University in Japan are not going to change that - as long as you use them instead of carbs in your diet the said zero-calorie sweetener are going to help not block weight loss.

So why did the mice in the Mitsutomi study get obese then?

By anticipating the most important conclusion, I have made things easy for us, after all the only questions we still have to answer are:

• Why did the mice in the Mitsutomi study get obese?

• Is it possible that this is an erythritol-specific effect?

It would appear as it it could not be all too difficult to answer the first question. It was after all part of the research interests of the Japanese scientists, so that you would expect it to be answered in the discussion of their result. Well, let's see then, ...

Exactly what the energy drinks promise, the sugar water got the rats "on sucrose" going: They were >40% more active than their peers - without caffeine as you may notice (Mitsotomi. 2013)

"Compared with sucrose supplementation, NNS supplementation decreased the serum glucose level. Interestingly, compared with the control treatment, NNS supplementation increased the serum insulin level in mice with DIO. In addition, NNS administration influenced glucose tolerance compared to controls.

These observations suggest that NNS supplementation induced insulin resistance by increase of tissue triglyceride, although some NNSs are used to control hyperglycemia.

NNS supplementation increased the WAT leptin level in DIO mice in the present study.

It is possible that the high leptin level was related to body adiposity. Indeed, NNS administration increased the weight of epididymal fat. Thus, it is possible that the high leptin level was related to the influence on body adiposity." (Mitsotomi. 2013)

No, I don't see an explanation, rather a concise summary of the results, that tells us that the addition of plain sugar (33%)  to the drinking water did - as the scientists already expected - lead to a decrease in food intake and an increase in obesity and its nasty unhealthy side effects.

Figure 1: Differences in food intake & body composition of mice with 33% sucrose and 4% erythritol + aspartame in the drinking water (left) expressed relative to control w/ plain water, histology of lover (top) and white adipose tissue (WAT, bottom) of mice with regular (control) and sucrose respectively NNS drinking water (Mitsotomi. 2013)

Much to their own surprise, Mitsotomi et al. did also observe that the group that received the "non-nutritive sweeteners" as a 4% solution (99% of which were erythritol and 1% was aspartame) in their drinking water got exactly as fat (see Figure 1), had a slightly less pronounced increase in adipocyte size, and experienced a similar fatty acid deposition in the liver (NAFLD). And as if that had not been bad enough, there were also pathological changes in the "fat burning brown adipose tissue" (BAT) of the rodents in the NNS group - a physiological deterioration, Mitsotomi et al. observed exclusively in the erythritol + aspartame goup.

Figure 2: Leptin resistance (in WAT) and the major downregulation in UCP-1 (in BAT; both left) are candidates of which the researchers believe that they were responsible for the visible defect (right) in the BAT architecture (Mitsotomi. 2013)

Let's be honest, if you take another look at the BAT histology in Figure 2 (right) even you as a non-expert will see that there is a major difference between the meshed BAT in the rodents on the control diet and the messy BAT of the NNS group, compared to which the brown fat cells of the sugar guzzlers still look very healthy.

Remember: All this mess happened in the absence of an increase in calorie intake

Just to make this clear: This is not the first study to show that artificial sweeteners can have obesogenic effects in rodent models. In contrast to Naismith et al. (1995) and Blundell & Hill (1986) who observed a "pradoxical effects" of  artificial sweeteners on the appetite of their lab rodents, the rats in the study at hand did not overeat, though! They also moved about as much as their peers in the control group and still got fat and sick.

Want to change your "Fat-o-type"? Work out! | read more

In other words, the weight gain the Japanese researchers recorded was neither a result of a mismatch between energy intake and expenditure nor the consequence of a promotional effect of artificial sweeteners on the "sweet tooth" of the rodents. Rather than that it was either brought about or accompanied and promoted by the impairment of the thermogenic capacity of the brown adipose tissue, of which you can argue, based on histologies in Figure 2 that the brown adipose tissue of the furry "subjects" of this study was not just functionally, but also structurally compromised by the ingestion of the non-nutritive sweeteners.

The defective brown adipose tissue (BAT) and the correspondingly reduced UCP 1 expression (UCP increases mitochondrial uncoupling in BAT and burns off energy to increase the body temperature), led to a significant reduction in oxygen consumption. With the latter being a direct marker of fatty acid oxidation the it is difficult to say which came first, the defect in BAT or the onset of obesity. What we can say for sure, though, is that the defective BAT had its share in the rapid weight gain and the corresponding metabolic deterioration.

This could be an erythritol specific effect

Despite the fact that Mitsotomi et al. did not address the potential influence the type of artificial sweetener they used, it is not unlikely that the use of erythritol, of which I have seen dozens of toxicity studies, but no long(er) term feeding studies in a potentially obesogenic diet scenario, could explain the unexpected study outcome. So: "Is this an erythritol specific effect?"

An advantage of erythritol is that it has almost the same sweetness profile as sugar (sucrose), but is 30-40% less sweet (de Cock. 2012)

Without further studies, it is obviously not possible to answer this question, it does however not appear to be unlikely that it were the 99% of erythritol in the commercial erythritol + aspartam mixture the researchers used in their study that's to blame for the obesogenic effects. If this was a general NNS effect, a similar impairment of the brown adipose tissue and corresponding increases in body, muscle and liver fat should after all have been observed in previous studies, already. To my knowledge these studies do not exist - specifically not for aspartame. Without speculating about unpredictable interactions within the two we are thus left with erythritol as out only culprit.

While erythritol has only 60% to 70% of the sweetness of sucrose (comparing 10% solutions in water; this means you need much more of it to achieve a similar sweetness) it has an almost identical sweetness profile (no "off" tastes; cf. de Cock. 2012). This is not the only reason both scientists and the food industry are fond of the low-calorie sweetener. It's rather the combination of its gut- and tooth-friendliness that makes it such a valuable addition to everything sweet. So, despite the fact that it does share the the anti-caries effects with sugar alcohols like xylitol, it is so easy on the gut that its use is not restricted to chewing gums and other "food" items that need only marginal amounts of sweeteners to achieve the desired degree of sweetness. If you want to sweeten larger amounts of foods / beverages, erythritol is thus the sugar alcohol of choice

There is evidence that suggests aspartame reduces insulin - at least during workouts | learn more

Why don't you suspect aspartame? The reason that I am scrutinizing erythritol and not aspartame is simple. Despite or rather because of all the hoopla around potential toxic effects of aspartame it is one of the best researched artificial sweeteners and evidence for obesogenic effects in the absence of increases in food intake are simply non-existent. It may thus make this article more popular among the high number of aspartame haters out there, but it would not help us understand the experimental results,if I started lamenting about how Coke and Pepsi are trying to kill us.

If you take a peak at the Wikipedia article and many scientific papers, you will learn that erythritol has been shown to be mostly (90%) absorbed before the chyme enters the colon (Bernt. 1996). The non-negligible rest of the erythritol  (10%), on the other hand, is said to pass through the short and long intestine, where it is generally believed not to fermented by the gut bacteria (Arrigoni. 2005).

The cholesterol increase scientists observed in response to a high sucralose diet is another of the many yet not fully understood side effects of artifical sweeteners | learn more

In view of a more recent study by Beards et al. (2010) it is however more than questionable that this assumption for which researchers usually cite the in vitro results Arrigoni et al. presented in a 2005 paper is accurate.

Beards and her colleagues from the University of Reading in the UK were after all able to show that erythritol is not simply excreted undigested. Rather than that it is fermented and leads to changes in the bacterial composition and a 6.25x increase in acetate production.

In view of the beneficial effects of SFCA (acetate, propionate and butyrate) on the production of satiety hormones this certainly appears to be a good thing. From studies by Patil et al. we do however know that chronically high SCFA levels and decreased relative bacteroides levels are characteristic of features of human obesity (Patil. 2012; see Angelakis. 2012, as well).

If we include the comparatively short timespan (24h) in the course of which the said changes in the bacterial composition and acetate production in the Beards study occured and assume that this may, after days of constant erythritol exposure have destabilized the previous "ecosystem" in the gut, it does not appear too far fetched to assume that the rodents may have suffered from weight gain and all sorts of metabolic deterioration as a consequence of the potential lactobacilli + Atopobium overgrowth in response to the erythritol in their drinking water.

By now it should no longer appear totally odd to assume that neither artificial sweeteners per se, nor the "bad bad" aspartame are to blame for the "fat effects" the researchers observed in the study at hand, right? I mean, of all the three short chain fatty acids, butyrate, acetate and propionate, acetate is the one with the weakest antiobesogenic effects (Lin. 2012) and in view of the fact that it is preferentially used as a substrate for de novo lipogenesis (=deposition of fat) in colonocytes, hepatocytes and adipocytes (Samuel. 2008), both the fatty liver and the 172% increase in body fat could be explained by the constant influx of acetate from a dysbiotic gut - right?

Suggested Read + Podcast: "he Pro-Insulinogenic Effect of Artificial Sweeteners + Mechanisms & Consequences" | read more

Reason to be afraid - yes or no?"It could be possible...", these are the four little words that would have to go before each and every of the sentences in this conclusion. It could be possible that the interaction of erythritol with the gut microbiome of the rodents drove the accumulation of lipids in the liver, which would in turn have lead to the development of insulin and leptin resistance and could have compromised the function of the "fat burning brown adipose tissue" of our furry friends. The latter could have sped up the weight gain and may eventually explain why the mice in the "non-nutritive sweetener" group were by no means better off than their similarly obese peers in the sucrose group.

Despite the fact that it could also be possible that similar negative effects on the accumulation of liver and whole body fat would be observed in humans, the failure of the brown adipose tissue wouldn't be much of a problem for us, a species that has long lost most of its brown fat stores (learn more). Against that background and in view of the fact that I'd hope that no one of you follows a 60% fat, 20% carbohydrate diet and tries to sooth his / her sweet tooth with 2-3l of erythritol + aspartame sweetened water per day, I'd suggest you refrain from freaking out until we do have more compelling evidence that the stress hormones you will be producing are not more harmful than the few mg of sugar alcohols in your protein bars.

References:

• Angelakis E, Armougom F, Million M, Raoult D. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012 Jan;7(1):91-109.
• Arrigoni E, Brouns F, Amadò R. Human gut microbiota does not ferment erythritol. Br J Nutr. 2005 Nov;94(5):643-6. 
• Beards E, Tuohy K, Gibson G. Bacterial, SCFA and gas profiles of a range of food ingredients following in vitro fermentation by human colonic microbiota. Anaerobe. 2010 Aug;16(4):420-5.
• Bernt WO, Borzelleca JF, Flamm G, Munro IC. Erythritol: a review of biological and toxicological studies. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S191-7. Review.
• Blundell JE, Hill AJ. Paradoxical effects of an intense sweetener (aspartame) on appetite. Lancet 1986;1(8489):1092–3.
• de Cock P. Erythritol. In "Sweeteners and Sugar Alternatives in Food Technology". 2nd edition. Ed. O'Donnell & Kearsley. Wiley. 2012.
• Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240. 
• Mitsutomi K et al. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism. Oct. 2013 [ahead of print]
• Naismith DJ, Rhodes C. Adjustment in energy intake following the covert removal of sugar from the diet. J Hum Nutr Diet 1995;8:167–75.  
• Patil DP, Dhotre DP, Chavan SG, Sultan A, Jain DS, Lanjekar VB, Gangawani J, Shah PS, Todkar JS, Shah S, Ranade DR, Patole MS, Shouche YS. Molecular analysis of gut microbiota in obesity among Indian individuals. J Biosci. 2012 Sep;37(4):647-57.
• Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16767-72.
• Sell H, Deshaies Y, Richard D. The brown adipocyte: update on its metabolic role. Int J Biochem Cell Biol 2004;36: 2098–104.

Inflammation Is a True Fat Burner: BSO-Induced Glutathione Depletion Wards off Fat Gains on Hypercaloric Diet

Image 1: This little bugger obviously has too little inflammation going on ;-)

Are you "on fire"? Inflammation has been implicated as the root cause of almost all modern disease: obesity, diabetes, heart disease, cancer, you name it. Soothing the flames via natural and supplemental anti-oxidants has thusly been proposed and marketed as a solution for many of the aforementioned health problems.

Yet, despite tons of vitamins, anti-oxidants and all the other "healthy" stuff we are taking and consuming on a daily basis, the number of morbidly obese people, diabetics and heart attack patients appears to be ever-increasing... how can that be?

A possible answer to that question comes from scientists from the Saha Cardiovascular Research Center at the University of Kentucky College of Medicine in Lexington, Kentucky, US (Findeisen. 2011) - we simply got everything wrong! The observation that insulin resistance and beta-cell dysfunction usually occur in the presence of large amounts so-called reactive oxygen specimen (ROS) lead scientists to propose that there was a causative relationship between these two events, of which the data only shows that they are corollary.

Image 2: Whenever there is a fire, the firefighters are not far away, but does this correlation indicate that all firefighters are firebugs? (img texarkanagazette.com)

Despite the fact that the distinction between correlation and causation should be obvious, correlations have a long history of being mistaken as causative factors in the history of science. The corollary elevation of total cholesterol in heart disease patients, for example, is the reason that millions of well-educated people world-wide still believe that cholesterol would cause heart disease - an erroneous conclusion for which my friend, Carl Lenore, has coined a very fitting analogy (actually the analogy spans all those "corollary causation"): When there is a fire in down-town New York, it won't take long until the place is packed with firefighters, nevertheless, no sane observer would get the idea that the corollary appearance of firefighters on the scene would be the reason for the fire.

Here, at the SuppVersity, you have already learned that a group of researchers from Germany has invested a lot of work into research on the beneficial effects of inflammation (Ristow. 2010). Now, with the data from Hannes M. Findeisen (who unquestionably is a German or has German ancestors, as well ;-) et al., evidence begins to accumulate that the role of reactive oxygen specimen in glucose homeostasis could in fact be a beneficial and not a detrimental one. After all, Findeisen and his colleagues were able to show that the pharmacological depletion of glutathion, our natural broadband fire-extinguisher, made mice resistant to diet-induced obesity, increased energy expenditure and enhanced insulin sensitivity.

If you have listened to all the installments of the Amino Acids for Super Humans Series on Carl Lenore's Super Human Radio, you will already have heard me mention that a methionine/cysteine-free diet has been shown years ago to have profound fat-burning, or I should say, weight-reducing effects on mice - no wonder, with methionine and cysteine being essential substrates for mammalian gluthation production, a lack of these dietary sulfur-amino acids induced a similar glutathion depletion as the addition of 30mmol/l BSO to the drinking water of the mice in the Findeisen study (for more on the glutathion depleting effects of BSO, cf. Skapek. 1998; Mira. 2002; Cattan. 2008)

Even before the works of Ristow et al. and now Findeisen et al., it has been well-established that reactive oxygen specimen, the purported villains of the 21st century, enhance cellular signaling (Veal. 2007). About a year ago, Chang and Chang  reported that H2O2, in particular, is a potent activator of protein signaling pathways, including insulin signaling and can even mimic insulin's effects by the inhibition of oxidation-sensitive protein tyrosinases (Chang. 2010). With glutathion being the primary H2O2 scavenger in mammalian tissue, it is thus not surprising that the BSO treated and thusly glutathion depleted mice in the Findeisen study displayed a more favorable response to a glucose tolerance test after 6 weeks of treatment with BSO and a 45%(high)-fat diet (cf. figure 1).

Figure 1: Glucose levels in mg/dl after oral glucose tolerance test in mice after 6 weeks on a high-fat diet (47% fat) with or without 30mmol/L BSO in their drinking water (data adapted from Findeisen. 2011)

These results are surprising, also because the daily food and water intake of the mice was identical. The latter cannot be said of their calorie-expenditure, daily activity level (cf. figure 2) and the activity of the "fat burning" uncoupling protein UCP2 (+100%), the elevation of which increases thermogenesis and energy expenditure.

Figure 2: Relative changes in energy expenditure and daily activity due to BSO induced glutathion depletion in mice on a high fat diet compared to non-treated control (data calculated based on Findeisen. 2011)

Now, most importantly for you, as a physical culturist, may be that glutathione depleted mice did not simply fail to thrive or shrivel away - they were, as Findeisen points out...

completely protected from diet-induced obesity, despite similar food intake and water consumption. Analysis of body composition in mice fed a HFD diet confirmed significantly decreased fat mass in BSO-treated mice without significant differences in lean body mass, indicating that the difference in body weight was due to reduced fat mass in BSO-treated mice.

If you don't believe the words, I suggest you take a look at the data in figure 3 - while the control mice had a body fat percentage of whopping 32% the mice on BSO with their ~16% body fat were well within the normal range for lab-mice.

Figure 3: Fat and lean mass (in g) of mice from the control group and the glutathion-depleted group after 6 weeks on a hypercaloric high fat diet (data adapted from Findeisen. 2011)

Even the researchers appeared to be surprised by the profound effects glutathion depletion had on the rodent's ability to accumulate body fat. As far as the underlying reasons are concerned, they speculate that it was ...

[...] possible  that  the  observed  increase in the expression of UCP-2 and UCP-3 in BSO-treated mice induced  mitochondrial  uncoupling [...] Alternatively, the enhanced energy expenditure in BSO-treated mice  might  be  the  result  of  increased  locomotor  activity.  In skeletal muscle, ROS are necessary for optimal contractile function, force production, and exercise-induced adaptations. Furthermore, particularly H2O2 is increasingly recognized as
a potent neuromodulator. It is therefore conceivable, that glutathione depletion may lead to activity-stimulating changes in the redox environment of muscle or brain.

Now, it is however questionable in how far any of these three phenomena would occur in human beings, as well. While the lack of large amounts of UCP-sensitive brown adipose tissue would decrease the UCP induced thermogenic response to glutathione depletion, locomotor activity is something that appears to be completely blocked in the modern couch potato, anyways. It would thus warrant further research (and studies into the general safety of this approach) before it would appear warranted that you take a spoon of BSO with every meal to counter the negative effects of your last binge ;-)

Ephedrine, Exercise or Diet? Ephedra Modulates Substrate Utilization, but Exercise Melts Body Fat & Builds Muscle

Image 1: Twinlabs' made a fortune on their line of ephedra containing fat burners.

For many people ephedrine, the "E" in the infamous ECA stacks and the alkaloid from the mua huang on which Twinlab and co. made a fortune in the late 1990s, was the first and only truly working fat-burner on the supplement market. "Legendary", "unique", "unparalleled", these are the attributes by which they like to refer to their old-school fat burner. What's missing from most of these stories, though, are the hardships, the hours of intense training and weeks of radical dieting that may have become more bearable, yet by no means obsolete with the use of respective products.

A 2012 look at diet, exercise and ephedrine

In a soon to be published paper, Nikki Sclotum and her colleagues from GlaxoSmithKline, the North Caroline State University and the Purdue University report on the results of an experimental comparison of ephedrine, diet and exercise based weightloss regimen in a mouse model of diet induced obesity (Slocum. 2012). The pre-fattened mice in the study were either ...

• given 18mg/kg of ephedrine, orally (human equivalent: 1.5mg/kg, or 117mg for an 80kg adult),
• forced to do steady-state-cardio at 10m/min on a treadill for 1h per day, or
• kept on a caloric deficit that was -26% below their maintenance food intake

And the results of the 7-day experiment confirm that many of those "magical weight loss effects of ephedrine" were actually rooted in the dietary and exercise regimen of the former ephedrine consumers and, if anything, simply augmented by the drug. The non-existence of statistically significant differences in body weight and body fat loss clearly supports this notion; and while the relative body-fat changes in the ephedrine group reached borderline significance, it should be mentioned that rodents who carry significant amounts of metabolically active brown fat on their small bodies, are way more susceptible to the beta receptor mediated thermogenic effects of ephedrine and co., than human beings - a good reason to meet all the study outcomes in the ephedrine group with some skepticism (this includes the increased UCP expression discussed later).

Figure 1: Changes in total body weight (g) and body composition (%) after 7 days (data adapted from Slocum. 2012)

The reduction in body weight and, more importantly, body fat levels in the exercise group, on the other hand, are not only (more or less) independent of the thermogenic potential of brown adipose tissue, they are also quite impressive and speak to the validity of my repeatedly propounded hypothesis that exercise is the #1 body recompositioning agent. Contrary to dietary restriction (and ephedrine), it does namely not just burn off body fat, but builds muscle as well - true "recompositioning", if you will, and an investment in "metabolic currency" (TM of my friend Carl Lanore ;-), of which you can draw for the rest of your life.

"So what? Is ephedrine totally useless, then?"

Figure 2: Respiratory exchange ratio of the animals in the control, diet, exercise and ephedrine groups on day 7 of the experiment (adapted directly from Slocum. 2012)

These observations alone would clearly raise the question if ephedrine, the "one true fat burner" as which it is still touted, was in fact similarly useless as its many successors. And I guess, if it were not for another very interesting finding of the study the answer would be "YES!". With its profound effects on the so-called respiratory exchange ratio, i.e. the amount of CO2 the animals exhaled per volume unit of O2 they consumed, it does yet exhibit a "substrate repartitioning" effects. With higher VCO2 : VO2 ratios indicating greater carbohydrate and lower fatty acid oxidation and lower VCO2 : VO2 ratios  indicating lower carbohydrate and higher fatty acid oxidation rates, a brief glance at the graph in figure 2 should suffice to see that the ephedrine group derived a significantly higher amount of energy from fatty acids than their comrades in crime, whose RERs of almost 1 would suggest that their small bodies ran primarily on glucose for fuel in the dark period, which is the time of the day, when rodents exhibit the highest activity level.

Ephedrine can increase the fat and thus decrease the carbohydrate oxidation. It cannot actively "burn" fat.

In other words, on a "calorie per calorie" base, the rodents on ephedrine used more fat than any of their peers. Due to the comparably small increase in UCP1 activity (~2x for ephedrine;  ~4x for exercise),a marker of increased increased fatty acid oxidation, as well as the lower overall energy expenditure (compared to the exercise) and greater caloric intake (compared to the diet group), their metabolic advantage of being "fat adapted" did yet not translate into statistically significant decreases in body fat let alone weight - most of the fat that was liberated by the ephedrine induced norepinephrine rush was, if you will, simply restored (or replaced) to (or in) the adipose tissue from which it had been liberated.

Ephedrine can help, when it is combined with exercise and/or diet!

In view of the fact that neither exercise, nor diet had comparably significant influence on the respiratory exchange ratio, it does still stand to reason that the almost legendary "fat burning" effect of ephedra- or mua-huang-based fat-burners was achieved by combining the shift towards fat and away from carbohydrate oxidation with the exercise induced increase in energy expenditure in the presence of and otherwise constant or moderately decreased energy intake, which often was a direct result of the anorexic effects of the plant alkaloid.

Warning: The supplement industry is well aware of the legendary reputation of the "good old ECA stacks" and tries to fool customers by loading their mostly caffeine based "fat burners" with "ephedra extracts", "ephedra leaf extracts" or similar ingredients, which may come from plants that belong to the same family, but do not contain any of the active alkaloids!

If we discard those appetite reducing effects, which are probably a side effect of greater fatty acids availability and reduced dependence on glucose as a main fuel source, this confirms the afore-made statement that ephedrine is more of an "energy substrate modulator" than a "fat burner" in the literal sense.

Ditch the ECA, embrace the DECaS stack

And while the addition of caffeine another "substrate modulator" amplified this effect, the effects of A, for aspirin, which was supposed to prolong the activity of E and C, ward off high blood pressure and other CVD related side effects and even prevent the habituation effect which come with the longterm use of every stimulant as a mere physiological result of the downregulation of (in this case) the beta-adrenergic receptors  have never been scientifically validated (it is also interesting to note that, in the study at hand, the brown adipose tissue beta receptor expression was reduced, but the reduction did not reach statistical significance over this short time span).

Bottom line: With the ban of (real, see red box above) ephedra based "fat burners" you may thus have a small disadvantage compared to the "veterans from the good old days", the ban did yet not effect the fundamental rules of body recompositioning: Train hard, don't cut your calories too extreme and, by all means, get enough and restful sleep... and if that is somewhat of a relief, with the DECa (=Diet, Exercise, Sleep and Caffeine) stack, restful sleep becomes significantly easier ;-)

BCAA Ward Off Body Fat Gain on Hypercaloric High Fat Diet: Branch-Chained Amino Acid Feeding Triggers Favorable Metabolic Changes in Diet-Induced Obese Mice.

When it comes to BCAA products,
stick to the basics. There is a reason nature
has them in the 2:1:1 ratio.

Science is more and more beginning to realize that the oversimplified "calories in vs. calories out" concept is hardly able to explain weight gain and loss in the ever-increasing number of obese individuals throughout the world. The findings of a relatively recent study from Oita University, Japan (Arakava. 2011) underline the importance of a paradigm-shift in nutritional counseling from dietary advice that is based on caloric value towards concepts accounting for the different signaling cascades various macro- (protein, fats, carbohydrates) and micro-nutrients (vitamins, minerals, polyphenols, etc.) trigger.

What the scientists found was that mice, who were fed a hypercaloric high fat (45%) diet for 6 weeks, gained significantly less weight, if their drinking water was enriched with BCAAs in the course of the last 2 weeks.

The BCAA-treated group gained almost 7% less body weight and had less epididymal adipose tissue (WAT) mass than the control group (p<0.05). BCAA supplementation also reduced the hepatic and skeletal muscle triglyceride (TG) concentrations (p<0.05).

The reason for this "anti-obesity" effect of BCAAs, the scientists speculate, is the increase of hepatic PPAR-alpha and uncoupling protein (UCP) 2, and PPAR-alpha and UCP3 in the skeletal muscle, respectively. While the upregulation in PPAR-alpha would be responsible for the reduction in blood (& muscle) triglycerides (other than total cholesterol a reliable risk factor of heart disease & diabetes), the increases in uncoupling protein (put simply) render the mitochondrial wall more permeable for protons and thus increases the dissipation of energy as heat. In consequence of these BCAA-triggered adaptations, the mice spent more energy and "burned" more fat.

Figure 1: Glucose, Insulin, Triglycerides and Free Fatty Acids in Control and BCAA treated DIO mice
(data adapted from Arakava. 2011)

If you have a closer look at the data I plotted in figure 1 you will further notice that a) the decrease in serum triglycerides is only modest (note: the decrease in liver triglycerides may be of greater importance, anyways) and b) BCAA supplementation also had a direct effect on insulin secretion, the reduction of which may well contribute to the reduced fat accumulation Arakava et al. observed in the BCAA group.

Despite the fact that applicability of the results of rodent studies to human beings (and I am referring to thermogenic effects, in particular) is still questionable, the take home message of this study is to look into the physiological effects of individual nutrients rather than into their energy equivalent in calories to evaluate their use and usefulness in weight loss and weight gain (remember BCAAs are a promising adjunct to cancer therapy and other conditions associated with muscle loss and/or wasting, as well, cf. Tazi. 2010).

I-Force Dexaprine Ingredient Write-Up.

Figure 1: I-Force Nutrition's
newest fat burner Dexaprine

Just received an email from the marketing guys @I-Force Nutrition informing me that "Dexaprine is finally here...". Well, to be honest, I had not been waiting for it, but the email intrigued me and I would like to give you a brief rundown on the ingredients, which are "guaranteed to give you more energy, increased appetite suppression, and insane mood enhancement than you have ever experienced!" - I don't know about you, but I think I have heard similar claims before ;-)

Ok, here we go: One bottle of Dexaprine, which is 39.99 (pre-order offer @ I-Force webshop) has 60 servings (serving size 1 capsule) of the "thermogenic powerhouse" (I love these advertisment guys) @ 600mg of the following ingredients

• Thermophoric Amine Mood Enhancing Complex,
  which is basically just synephrine (from citrus aurantium) + geranamine (which is also known as 1,3-dimethylamylamine, 4-methyl-2-hexylamine, or as I-Force has it on the label 1,3-dimethylpentylamine)
  
• Extended Release Energy Complex,
  which is a combination of caffeine and theophylline, with the latter having identical beneficial (stimulant, beta receptor agonism, etc.) as well as detrimental (e.g. temporary insulin resistance in muscle tissue, cf. Colnes. 2010, adrenal problems due to long term (over-)use etc.) effects on perceived energy and weight loss, but a longer half-life, which is even prolonged by the concomittant admistration of caffeine (Jonkman. 1991)
  
• Anabolic Protein Synthesis Enhancing Complex,of which I think that it is completely mislabeled, because it is a combination of the two diiodo-L-Thyronines (also known as T2s), 3,3'-T2 and 3,5-T2, of which I have already written in a paper for a German BodyBuilding and fitness magazine (click here for Google-translation) that their impact on metabolic rate (in non-hypothyroid individuals) is probably negligible and would - according to the mice studies that are presently available - require much higher doses than those present in current "thyroid stimulating" products to up-regulate UCP significantly above "normal" levels.

So, overall this does leave us with a probably relatively long lasting stimulant that will enable you to work harder and thus burn more calories and subsequently more fat. Not bad, but nothing new or even revolutionary here.

On a side note: As it is quite often the case in the supplement industry, Dexaprine is deliberately named to sound similar to a potent drug, the synthetic amphetamine Dexedrine (has up to 15 mg dextro-Amphetamin per cap). This practice is about as shabby as calling a product XYZ-"drol". The latter, i.e. the "drols", have incidentally been banned by bodybuilding.com - good idea, guys ;-)