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.