Ephedrine/Caffeine Research Papers

Title: Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise.

Author: Bell DG; Jacobs I; Zamecnik J
Source: Eur J Appl Physiol, 77(5):427-33 1998 Apr

This study investigated the effects of acute ingestion of caffeine (C), ephedrine (E) and their combination (C+E) on time to exhaustion during high-intensity exercise. Using a repeated-measures, double-blind design, eight male subjects exercised on a cycle ergometer at a power output that led to exhaustion after about 12.6 min during a placebo (P) control trial. They did this 1.5 h after ingesting either C (5 mg x kg[-1]), E (1 mg x kg[-1]), C+E, or P. Trials were separated by 1 week. Venous blood was sampled before and during exercise. The mean (SD) times to exhaustion were 12.6 (3.1) (P), 14.4 (4.1) (C), 15.0 (5.7) (E) and 17.5 (5.8) (C+E) min. Only the C+E treatment significantly increased time to exhaustion compared to P. Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE) and the respiratory exchange ratio (RER) were similar during exercise for all trials. Heart rate during exercise was significantly increased for the C+E and C trials compared to P. Subjective ratings of perceived exertion during exercise were significantly lower after C+E compared to P. All treatments significantly increased lactate levels. Free fatty acid (FFA) levels were significantly increased by C ingestion. Glycerol levels were increased by C+E and C ingestion. Glucose levels were also higher with the drug treatments compared to P. Increased monamine availability after C+E treatment was suggested by measurements of catecholamines and dopamine. In conclusion, the combination of C+E significantly prolonged exercise time to exhaustion compared to P, while neither C nor E treatments alone significantly changed time to exhaustion. The improved performance was attributed to increased central nervous system stimulation.


Title: Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine/caffeine mixture.

Author: Toubro S; Astrup AV; Breum L; Quaade F
Source: Int J Obes Relat Metab Disord, 17 Suppl 1():S69-72 1993 Feb

In a randomized, placebo-controlled, double blind study, 180 obese patients were treated by diet (4.2 MJ/day) and either an ephedrine/caffeine combination (20mg/200mg), ephedrine (20mg), caffeine (200mg) or placebo 3 times a day for 24 weeks. 141 patients completed this part of the study. All medication was stopped between week 24-26 in order to catch any withdrawal symptoms. From week 26 to 50, 99 patients completed treatment with the ephedrine/caffeine compound in an open trial design, resulting in a statistically significant (p = 0.02) weight loss of 1.1kg. In another randomized, double-blind, placebo-controlled 8 week study on obese subjects we found the mentioned compound showed lean body mass conserving properties. We conclude that the ephedrine/caffeine combination is effective in improving and maintaining weight loss, further it has lean body mass saving properties. The side effects are minor and transient and no withdrawal symptoms have been found.


Title: Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice.

Author: Breum L; Pedersen JK; Ahlstrøm F; Frimodt-Møller J
Source: Int J Obes Relat Metab Disord, 18(2):99-103 1994 Feb

In previous separate studies, dexfenfluramine (DF) and ephedrine/caffeine (EC) have been shown to promote weight loss in obese patients as compared with placebo. 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), supplementary to a 5 MJ/day diet. Forty-three patients from the DF group and 38 from the EC group completed the study. After 15 weeks of treatment, the DF group (n = 43) had lost 6.9 +/- 4.3 kg and the EC group (n = 38) had lost 8.3 +/- 5.2 kg (mean +/- s.d., P = 0.12). 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. Twenty-three patients in the DF group (43%) and 27 in the EC group (54%) complained of side-effects. Central nervous system side-effects, especially agitation, were more pronounced in the EC group (P < 0.05), whereas gastro-intestinal symptoms were more frequent in the DF group (P < 0.05). The side-effects declined markedly during the first month of treatment in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Title: The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans.

Author: Toubro S; Astrup A; Breum L; Quaade F
Source: Int J Obes Relat Metab Disord, 17 Suppl 3():S73-7; discussion S82 1993 Dec

This paper describes a 24-week open follow-up trial with reduced obese patients all receiving an ephedrine/caffeine combination (20 mg/200 mg) three times a day. The study was a continuation of a previous 24-week double-blind placebo-controlled study where the ephedrine/caffeine mixture had shown superior weight-reducing properties when compared with either ephedrine alone (20 mg) or caffeine alone (200 mg) three times a day. The medication was stopped between weeks 24-26 in order to evaluate withdrawal symptoms. The follow-up period was from weeks 26 to 50. Of 127 patients included, 99 completed the follow-up treatment, which resulted in an additional weight loss of 1.1 kg (P = 0.02). Adverse drug reactions were all minor and temporary. We conclude that the ephedrine/caffeine combination is safe and effective in long-term treatment in improving and maintaining weight loss. The side-effects are minor and transient and no clinically relevant withdrawal symptoms have been observed.


Title: Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man.

Author: Astrup A; Toubro S
Source: Int J Obes Relat Metab Disord, 17 Suppl 1():S41-3 1993 Feb

To develop an appropriate combination of ephedrine and caffeine consisting of clinically relevant doses, we examined the acute thermogenic, metabolic, and cardiovascular effects of different doses of caffeine (C) and ephedrine (E) given separately and in combination to normal subjects. The thermogenic effect after E+C (20 mg/200mg) was larger than that of any other combinations, and E and C exerted a supra-additive synergism on thermogenesis and systolic blood pressure, while being without effect on diastolic blood pressure. The combination also had pronounced effects on glucose metabolism by increasing plasma glucose, insulin and C-peptide concentrations. During chronic treatment the effect of E+C on energy expenditure is maintained, while side effects subside because tolerance develops to its hemodynamic and metabolic effects. During dietary energy restriction E+C promotes fat loss and preserves fat-free mass, which may contribute to its chronic effect on energy balance. In conclusion, the hemodynamic and side effects to E+C are transient during chronic treatment, while the effect on energy expenditure persists. The compound also possesses repartitioning properties, which may be useful in the treatment of obesity.


Title: 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.

Author: Astrup A; Breum L; Toubro S; Hein P; Quaade F
Source: Int J Obes Relat Metab Disord, 16(4):269-77 1992 Apr

The sympathomimetic agent ephedrine has potent thermogenic and anti-obesity properties in rodents. The effect is markedly enhanced by caffeine, while caffeine given alone has no effect. This study was undertaken to find out if a similar weight reducing synergism between ephedrine and caffeine is present in obese patients. In a randomized, placebo-controlled, double blind study, 180 obese patients were treated by diet (4.2 MJ/day) and either an ephedrine/caffeine combination (20mg/200mg), ephedrine (20 mg), caffeine (200 mg) or placebo three times a day for 24 weeks. Withdrawals were distributed equally in the four groups, and 141 patients completed the trial. Mean weight losses was significantly greater with the combination than with placebo from week 8 to week 24 (ephedrine/caffeine, 16.6 +/- 6.8 kg vs. placebo, 13.2 +/- 6.6 kg (mean +/- s.d.), P = 0.0015). Weight loss in both the ephedrine and the caffeine groups was similar to that of the placebo group. Side effects (tremor, insomnia and dizziness) were transient and after eight weeks of treatment they had reached placebo levels. Systolic and diastolic blood pressure fell similarly in all four groups. We conclude, that in analogy with animal studies, the ephedrine/caffeine combination is effective, while caffeine and ephedrine separately are ineffective for the treatment of human obesity.

Title: Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity.

Author: Daly PA; Krieger DR; Dulloo AG; Young JB; Landsberg L
Source: Int J Obes Relat Metab Disord, 17 Suppl 1():S73-8 1993 Feb

The safety and efficacy of a mixture of ephedrine (75-150mg), caffeine (150mg) and aspirin (330mg), in divided premeal doses, were investigated in 24 obese humans (mean BMI 37.0) in a randomized double blind placebo-controlled trial. Energy intake was not restricted. Overall weight loss over 8 weeks was 2.2kg for ECA vs. 0.7 kg for placebo (p < 0.05). 8 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 (p = 0.036). 6 subjects continued on ECA for 7 to 26 months. After 5 months on ECA, average weight loss in 5 of these was 5.2 kg compared to 0.03 kg gained during 5 months between studies with no intervention (p = 0.03). The sixth subject lost 66 kg over 13 months by self-imposed caloric restriction. 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 doses is thus well tolerated in otherwise healthy obese subjects, and supports modest, sustained weight loss even without prescribed caloric restriction, and may be more effective in conjunction with restriction of energy intake.