stolen-in a Fair Use sort of way from another site:
The Research Looking at Ephedrine / Caffeine / Aspirin and Weight Loss
In a double blind, placebo controlled study, caffeine alone was found to produce thermogenic and lipolytic effects in humans in a dose dependent manner.13 These researchers found that the thermic effect was significantly correlated to plasma triglyceride levels, plasma lactate concentrations and vascular tone. The authors attribute the increase in lactate, triglycerides and enhanced vascular tone to the increased metabolic rate. In a study using caffeine and ephedrine researchers found no difference in the total amount of body weight that was lost over 8 weeks.14 However, they did find significant differences in the source of the weight that was lost. Fourteen obese women were treated with a ~1000 kcal diet and either E + C (20mg E + 200mg C) or placebo three times per day for 8 weeks in a double-blind study. The total weight-lost was not different between groups, but the E + C group lost ~10 lbs. more body fat and ~6 pounds less fat-free mass. This is encouraging news for any bodybuilder. You must bear in mind, however, that these were obese women. Studies have shown that nutrient partitioning is determined in part by your % fat before you diet or before you over eat.15,16 Nevertheless, that is a tremendous effect on fat loss and muscle retention.
Some research has shown that the anti obesity effects of ephedrine are not significant unless caffeine is used in conjunction with ephedrine.17 In fact, most studies exploring the thermogenic effects of ephedrine also look at caffeine as a synergist. In a randomized, placebo-controlled, double blind study, 180 obese patients were treated by a calorie restricted diet and either an ephedrine/caffeine combination (20mg/200mg), ephedrine (20 mg), caffeine (200 mg) or placebo three times a day for 24 weeks. Average weight loss was significantly greater with the combination than with placebo from week 8 to week 24. Weight loss in both the ephedrine only and the caffeine only groups was similar to that of the placebo group. The authors conclude that the effect of either caffeine or ephedrine alone is ineffective in inducing significant weight loss.18,19 Not only is it necessary to combine ephedrine and caffeine to elicit a significant fat burning effect, the two compounds exhibit synergistic effects in certain ratios. By comparing different ratios of ephedrine and caffeine, it was found that 20 mg of ephedrine and 200 mg of caffeine exhibited a supra additive or synergistic effect while no other ratio did.20 This means that ephedrine and caffeine taken in a 1:10 ratio (20 mg ephedrine : 200 mg caffeine) creates effects greater than the sum of the two drugs added together. In other words, 2 + 2 = 5 in this ratio!
So what about aspirin? There has not been as much research done on aspirin in this "stack". Looking first at animals, chronic administration of aspirin to obese mice had no effect on weight loss. Ephedrine given to these mice increased energy expenditure by 9% and reduced body weight and body fat by 18% and 50%, respectively: obesity however, was reduced but the mice still were not comparable to normal controls. When given both ephedrine and aspirin, increase in energy expenditure found during treatment with ephedrine alone was doubled, and the obese group lost greater than 75% of body fat, and obesity essentially was reversed.21 The research done on humans has also been somewhat promising. The effect of ephedrine (30 mg) and aspirin (300 mg) on the acute thermogenic response to a liquid meal (250 kcal) was investigated in lean and obese women (n = 10 each group). Resting metabolic rate (RMR) was measured prior to each of the following treatments: meal only (M), meal plus ephedrine (ME) or meal plus ephedrine and aspirin (MEA). The postprandial rise in metabolic rate, following the MEA treatment compared to the ME, was significantly greater for the obese group but not the lean. It was concluded that aspirin potentiates the stimulatory effect of ephedrine on the thermogenic response to a meal in obese but not lean women.22 One weakness of this study was the small number of subjects. Nevertheless, these findings are not all that surprising considering the fact that decreased thermic effect of food is often seen in the obese.23 In another study24, a mixture of ephedrine (75-150mg), caffeine (150mg) and aspirin (330mg), in divided premeal doses, were investigated in 24 obese participants in a randomized double blind placebo-controlled trial. Energy intake was not restricted. Overall weight loss over 8 weeks was 2.2kg for eca - ephedrine - caffeine - aspirin - ephedrine - caffeine - aspirin vs. 0.7 kg for placebo. Eight of 13 placebo subjects returned 5 months later and received ECA in an unblinded crossover. After 8 weeks, mean weight loss with ECA was 3.2 kg vs 1.3 kg for placebo. Six subjects continued on ECA for 7 to 26 months. Notice that there is no concern about receptor down regulation or trying useless dosing schedules like "2 weeks on and 2 weeks off". Anyway, after 5 months on ECA, average weight loss in five of these was 5.2 kg compared to 0.03 kg gained during 5 months between studies with no intervention. The sixth subject lost 66 kg over 13 months by self-imposed caloric restriction. This sixth subject lost an amazing 150 lbs. By exercising and cutting calories! Can you believe they didn’t encourage the other subjects to diet and exercise? In all studies, no significant changes in heart rate, blood pressure, blood glucose, insulin, and cholesterol levels, and no differences in the frequency of side effects were found. ECA in these participants caused significant weight loss even without caloric restriction. The authors of this study go on to comment that the ECA combination might be more effective with caloric restriction. That kind of conservatism cracks me up!
In one study that really got my attention they compared the effects of ephedrine against the popular prescription drug dexfenfluramine that goes under the brand name Redux.25 In order to compare the efficacy and safety of these two anorectic drugs, 103 patients with 20-80% overweight were included in a 15-week double-blind study in general practice. Patients were randomized to either 15 mg DF twice daily (n = 53), or 20 mg/200 mg ephedrine/caffeine three times a day (n = 50). Subjects went on a 1200 kcal/day diet during the treatment period. After 15 weeks of treatment, the DF group (n = 43) had lost ~15 +/- 9.46 lbs. and the EC group (n = 38) had lost ~18.3 +/- 11.5 lbs. In the subgroup of patients with BMI > or = 30 kg/m2 (n = 59), the mean weight loss was 7.0 +/- 4.2 kg in the DF group (n = 29) and 9.0 +/- 5.3 kg in the EC group (n = 30), P < 0.05. Both systolic and diastolic blood pressures were reduced similarly during both treatments. Central nervous system side-effects, especially agitation, were more pronounced in the EC group, whereas gastro-intestinal symptoms were more frequent in the DF group. The side-effects declined markedly during the first month of treatment in both groups. Not only was the weight loss with ephedrine and caffeine comparable to Redux, it was probably greater! This study did not look at body composition but I bet it would have shown the E/C combination as superior in retaining lean mass.
You may have noticed that most of the studies I have cited have used obese subjects. This is understandable considering it is the obese population that are targeted for drug therapy. It should be noted however, that the thermogenic properties of an ephedrine/caffeine mixture are also demonstrated in lean subjects as well.26 You should expect increased effectiveness in obese people because of underlying problems with metabolic rate. Anytime you increase the metabolic rate in obese individuals you will see large changes in energy expenditure because the relative increase in metabolic rate is greater than in lean individuals.
13. Astrup A, Toubro S, Cannon S, et al. Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. Am J Clin Nutr 1990 May;51(5):759-767
14. Astrup A, Buemann B, Christensen NJ, Toubro S, et al. The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism 1992 Jul;41(7):686-688
15. Girardier L, Control systems in the defense of body fat stores. Int J Obes Relat Metab Disord 1993 Feb;17 Suppl 1:S3-S8
16. Dulloo AG, Jacquet J, Girardier L, Autoregulation of body composition during weight recovery in human: the Minnesota Experiment revisited. Int J Obes Relat Metab Disord 1996 May;20(5):393-405
17. Dulloo AG, Miller DS, The thermogenic properties of ephedrine / methylxanthine mixtures: Human studies. Int J Obes 1986; 10: 467-81
18. Astrup A, Breum L, Toubro S, Hein P, Quaade F, The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. Int J Obes Relat Metab Disord 1992 Apr;16(4):269-277
19. Toubro S, Astrup AV, Breum L, Quaade F. Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine/caffeine mixture. Int J Obes Relat Metab Disord 1993 Feb;17 Suppl 1:S69-S72
20. Astrup A, Toubro S, Cannon S, Hein P, Madsen J. Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study. Metabolism 1991 Mar;40(3):323-329
21. Dulloo AG, Miller DS., Aspirin as a promoter of ephedrine-induced thermogenesis: potential use in the treatment of obesity. Am J Clin Nutr 1987 Mar;45(3):564-569
22. Horton TJ, Geissler CA., Aspirin potentiates the effect of ephedrine on the thermogenic response to a meal in obese but not lean women. Int J Obes 1991 May;15(5):359-366
23. de Jonge L, Bray GA, The thermic effect of food and obesity: a critical review. Obes Res 1997 Nov;5(6):622-631
24. Daly PA, Krieger DR, Dulloo AG, Young JB, Landsberg L Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity. Int J Obes Relat Metab Disord 1993 Feb;17 Suppl 1:S73-S78
25. Breum L, Pedersen JK, Ahlstrom F, Frimodt-Moller J, Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-center trial in general practice. Int J Obes Relat Metab Disord 1994 Feb;18(2):99-103
26. Astrup A; Toubro S; Cannon S; Hein P; Madsen J Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study. Metabolism 1991 Mar; 40(3):323-9
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