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 ;-)
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