Fat Burning Grains? Japanese Study Says: The Peppery "Grains of Paradise" Actually Qualify as True Thermogenics

If you are as cool as the subject on the right (no black dots in the neck and trap area = no BAT activity) you don't have to keep thinking about BAT thermogenesis (img from Sugita.2013)

"Grains are the root of all our problems." It would be nice if it really were that simple... what would be even better is if they turned out to be the solution, as well. Wouldn't that be paradise?

It would. And what's more, it could! At least if the Grains of Paradise, i.e. the seeds of Aframomum melegueta(Rosco) K. Schum.) (GP), Guinea pepper or Alligator pepper would increase thermogenesis a significant amount more than those ~6kcal/h that have been observed in healthy non-obese subjects in a recent study by Jun Sugita and his (or her?) colleagues from the Department of Nutrition at the School of Nursing and Nutrition of the Tenshi Collage in Japan (Sugita. 2013).
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~6 kcal/h in BAT positive subjects that's definitely not enough

The mechanism by which the ingestion of the ginger relative to its high content of pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol increased the resting energy expenditure in the nineteen healthy male volunteers aged 20 – 32 years was via an increase in the thermogenic activity in the brown adipose tissue of those 12 of 19 subjects who had been identified in a previous cold-exposure test to carry a significant amount of metabolically active brown fat. 

Figure 1: Effects of 40mg of grains of paradise extract on resting energy expenditure - absolute change in kcal (left) and time course of energy expenditure after the ingestion (right) in responders (BAT+) and non-responders (BAT-; cf. Sugita. 2013)

As you can see in figure 1, the effect was small and in the subjects without significant brown fat activity the 40mg of the GP extract had the exact opposite effects. Thus I am not willing to agree with the scientists who conclude that their results would

"[...] suggest that GP extract, like capsaicin and capsinoids, may be a potential tool for increasing BAT thermogenesis and decreasing body fat."

As a standalone ingredient, it is not going to do anything and the efficacy of true "thermogenics" (I am not talking about CNS activators, like ephedrine, here) as fat burners has a long history of lab results that don't carry from rodent models to human reality - even if the subjects don't compensate for the extra energy expenditure.

Histidine as a fat loss adjuvant? Laughable? Not for the obese! For lean folks like her? (learn more)

The reason for the repeated failure is simple: Rodents are no little men and unlike us, they are totally reliant on their ability to use metabolically active brown fat to generate heat and keep themselves warm. Intelligent and lazy as we are, we have come up with more than enough means to keep ourselves warm in the course of our evolutionary history not to be in need of this special fat. And the little amount of brown adipose tissue we have when we are born actually atrophies during the first years of our life. Any fat burner that works primarily by increasing the uncoupling proteins and thus the heat production in said tissue is thus not likely to produce visible results. This is the case for the lean and especially for the obese who happen to have even less brown adipose tissue than those of us, who don't schlep ourselves from the sofa to the fridge and back, sweating like crazy.

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Bottom line: These "fake grains" are not going to solve the problems that are partly brought about by their "real" counterparts (i.e. the "healthy grains" in our diet ;-), but that is probably not going to hinder any snake oil vendor to putting it into his latest fat burning supplement. And who knows, when it's called "... grains", even Dr Oz may jump onto this paradise bandwagon. Why? Because there are enough people who'd rather waste thousands of dollars on false promises than spend a couple of bucks and a few hours of their TV time on a gym membership and the purchase and preparation of healthy whole foods.

References: 

• Sugita J, Yoneshiro T, Hatano T, Aita S, Ikemoto T, Uchiwa H, Iwanaga T, Kameya T, Kawai Y, Saito M. Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men. Br J Nutr. 2013 Aug;110(4):733-8.

Fat Burners Don't Work in the Obese!? BAT Activity Almost Zero, Even after the Ingestion of ~290mg Ephedrine!

Do thermogenic fat burners only work if you already look like this? I mean, what would be the sure, then and why did the ECA stack work for overweight people, as well?

I don't know if you have ever thought about the problems mostly involuntarily obese individuals are facing in their everyday lives!? Even if you discard the constant bullying and the subliminal messages they receive from their peers, not fitting into a regular seat in an airplane certainly is more than just an embarrassment. Now what would you say, if I told you that they are discriminated against even, when they shop at their local GNC, or whichever other supplement vendor they may be using? And I am not talking about the lean guys and girls on the labels of the supplements, here! No, I am referring to a discrimination that takes place on a more fundamental level and it happens right in front of the shelf with every overweight person's favorite supplements: The so-called fat burners!

Ok, now that I got everyone's attention, I guess its about time to break the news: Fat burners don't burn fat!

If this does not happen to be your first visit, here, at the SuppVersity you may now be asking yourself how an (unfortunately still not so) common wisdom like this could make it into the news... right? Well, the answer is simple: In addition to the fact that the active fat burning effects of almost all thermogenics are negligible, so that they can - if anything - support your nutritional weight loss efforts by making it easier for you to stick to your diet and training regimen, a recent study by Carey et al. suggests that the minimal effects they do actually have diminish with each pound of superfluous body fat you are carrying around (Carey. 2012).

"Hold on! 2.5mg/kg ephedrine? That's 170mg and 287.5mg ephedrine. That's madness!" Usually I would say "yeah, you are right", but based on previous studies (Nedergaard . 2011), Carey et al. knew that 1.0mg/kg did not elicit any BAT activity, despite significant physiological adrenergic responses (blood pressure and heart rate; cf. Astrup. 1985a,b). I still don't have to tell you not to "try that at home" - and this is more than just a "parenteral advisory" ;-)

In a randomized, double-blinded, crossover trial, the Australian researchers administered 2.5 mg/kg of ephedrine to nine lean (BMI 22±1 kg/m²) and nine obese (BMI 36±1 kg/m²) young men and measured the thermogenic response of their "fat burning" brown adipose tissue (note: BAT burns glucose as well and the activity of the latter is usually measured by [18F]fluorodeoxyglucose, which can be detected via PET-CT imaging).

Figure 1: PET-CT scan of lean (left) and obese (right) individual (Carey. 2012)

As the images in figure 1 clearly shows the actual BAT activity (located in the neck, where humans carry almost all their BAT; cf. Zingaretti. 2009), which has long been hailed as the underlying reason of the real-world effects the administration of ephedrine HCL, ephedra or mua huang, was far from earth-shaking and by no means comparable to what you would expect based on the almost legendary status of ephedrine as "the most potent thermogenic" that ever hit the market.

Keep in mind: There are also inter-individual differences in the amount of BAT people have. Still the differences between lean and obese were so pronounced that you can hardly argue that the results of the study were mere coincidence.

What is even more striking than the overall magnitude of BAT activity the scientists observed is however that the latterw was more or less completely absent in the obese individuals -- and that despite the fact that I am honestly wondering none of them collapsed after ingesting his 287mg of ephedrine (remember the dosages were scaled according to body weight!). When you think about it, the scientists subsequent conclusion that they have...

"[...] demonstrated for the first time that BAT can be activated in the majority of lean, but not in obese humans with a single dose of ephedrine" (Carey. 2012)

could in fact have far reaching consequences that are not simply restricted to the use of respective dietary supplements, but extend into the realms of the development of future anti-obesity drugs and the use and usefulness of "alternative" obesity "treatments", such as cold exposure, as well.The latter for example may be a more potent activator of BAT activity than ephedrine, but it's falling short, when it comes to the centrally mediated effects, of which it is now becoming increasingly clear that they and not the insignificant BAT activity must be responsible for the indisputable real-world weight loss effects, both, lean and overweight individuals, have seen in the past, when they consumed much lower doses of ephedrine, than the subjects in the study at hand.

Figure 2: BAT activity, nor-adrenaline response, changes in systolic (SBP) and diastolic (DBP) blood pressure in response to 2.5mg/kg body weight ephedrine in lean and obese subjects (data based on Carey. 2012)

If we also take into account that ephedrine is probably still one the most potent inducers of BAT activity among the (formerly) OTC thermogenics and most currently available (and recently banned) ingredients are nothing but central nervous system stimulants, the scientists' remark that their "data highlight[s] the poor responsiveness of BAT to systemic adrenergic stimulation compared with that of the cardiovascular system", should actually make it pretty obvious why so many of the purported (and in some cases even factual) thermogenics don't deliver the "fat burning" results their consumers are expecting: At the moment they start to work, the cardiovascular side-effects are already in the "danger zone", so that anything but a negligible increase in thermogeneisis is rare in the lean and - as the study at hand would suggest - probably totally absent in the average obese diet pill junkie.

Thermogenics won't work for you, but you can work with them... not infinitely, though! 

You can't light the candle from both sides and still expect it to last forever. Stims and meditation are like Jing and Jang, and you got to master them both (read more about how meditation can increase telomere length by 50%).

That many of these products do still work and that they do so even in the obese, as long as they are willing to accept that these products are adjuvants to and not replacements for a sound nutrition and exercise regimen, is thus probably more of a result of their ability to keep you training and dieting longer and harder, than due to any real "thermogenenic" effect. That said, I guess, I don't have to tell you that you cannot light the candle from both sides and expect to last it forever, do I?

Oh, I see, ... I would first have to to tell you what that's supposed to mean, right?! Well, basically it means that unless you want to make the acquaintance of "adrenal fatigue", "central fatigue syndrome" and the "athlete's triad", you better restrict the use of respective products to short time periods of max. 4-6 weeks and make sure not to (ab-)use them to simply ignore the physical necessity of rest and recovery! Believe it, or not, both of them are equally, if not more important, when you are trying to get ripped, as they are, when you are trying to get buffed.

References:

• Astrup A, Lundsgaard C, Madsen J, Christensen NJ. En-hanced thermogenic responsiveness during chronic ephedrine treatment in man. Am J Clin Nutr. 1985a; 42:83–94
• Astrup A, Bulow J, Madsen J, Christensen NJ. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol. 1985b; 248:E507–E515
• Carey AL, Formosa MF, Van Every B, Bertovic D, Eikelis N, Lambert GW, Kalff V, Duffy SJ, Cherk MH, Kingwell BA. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia. 2012 Oct 13.
• Nedergaard J, Bengtsson T, Cannon B. New powers of brown fat: fighting the metabolic syndrome. Cell Metab. 2011 Mar 2;13(3):238-40.
• Vosselman MJ, van der Lans AA, Brans B, Wierts R, van Baak MA, Schrauwen P, Lichtenbelt WD. Systemic β-Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans. Diabetes. 2012 Aug 7.
• Zingaretti MC, Crosta F, Vitali A et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J, 2009; 23:3113–3120.

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 ;-)

BAT: Brown Adipose Tissue in Humans - An Update

In the latest edition of Current Opinion in Lipidology we find a mini-summary (COL. 2010) on current findings on the existence and metabolic purpose of brown adipose tissue (BAT) in human beings. These days the previously accepted position that adults have little to no BAT is put into question by the results of PET, where brown fat becomes especially visible upon cold exposure, when its metabolic activity is increased as a result of thermogenesis.

The author points out that adipocytes (fat cells) and myocytes (muscle cells) do not only share the same origin, the metabolically active BAT exhibits other similarities to muscle cells, as well - it is a metabollically active tissue and of particular importance in the context of insulin sensitivity and glucose disposal:

BAT glucose uptake rate is 10-15-fold higher in cold than in normal room temperature. Other factors that may increase the activity of sympathetic nervous system and uncoupling protein 1 are several including the complex network of hormonal and neuronal signals. Preliminary results suggest that BAT resembles skeletal muscle not only by origin but also by the effect of insulin on the tissue.

Doubtlessly, more research has to be done on the issue of BAT vs. WAT (white adipose tissue) and their relation to obesity, diabetes and the metabolic syndrome. In spite of that, even what we know today suggests that a better understanding of this hitherto overlooked remainder from the days when our ancestors ran around naked could help to find a solution for some of the "fat" health problems of the western societies.