Twenty trials were included in the assessment of weight loss and eight in the assessment of athletic performance. It was unclear how many trials were RCTs or CCTs, or how many participants were included. A total of 117 studies were included in the review of adverse events: 52 controlled trials and 65 case reports or case series.
Weight loss.
Trials of ephedrine or ephedra for weight loss involved up to 6 months of treatment.
Five trials, which received quality scores between 1 and 3, compared ephedrine with placebo. The pooled estimate of the rate of weight loss was an effect size of -0.50 (95% confidence interval, CI: -0.85, -0.15), which translated to a monthly weight loss of 1.3 pounds more for ephedrine than for placebo. An analysis including only high-quality trials found a pooled estimate significantly lower than the main analysis (effect size -0.20, P=0.049). No statistical heterogeneity was identified (P=0.185).
Twelve trials compared ephedrine plus caffeine with placebo, of which six had a quality score of 3 or more. The pooled estimate of the rate of weight loss was an effect size of -0.85 (95% CI: -1.1, -0.61), which translated to a loss of 2.2 pounds more in the treatment group than in the placebo group. The results of the sensitivity analyses were not significantly different from the main analysis. There was no evidence of publication bias. The P-value from the chi-squared test for heterogeneity was 0.073, although the directions of the effect sizes of the individual trials were consistent.
Three trials compared ephedrine plus caffeine with ephedrine alone, and the quality scores were between 1 and 3. The pooled estimate of the rate of weight loss for the combined group was an effect size of -0.31 (95% CI: -0.60, -0.02), which equated to a weight loss of 0.8 pounds per month more for ephedrine plus caffeine compared with ephedrine alone. No statistical heterogeneity was identified (P=0.966).
Two trials compared ephedrine with another active weight loss therapy. There were no statistically significant differences between the groups in either trial.
One trial, which received a quality score of 4, compared ephedra with placebo. This trial found a weight loss rate of 1.8 pounds per month greater in the ephedra group than in the placebo group (95% CI: -2.7, -1.0).
Four trials compared ephedra plus caffeine-containing herbs with placebo; two of the trials received a quality score of 5 and two received a score of 2. The pooled estimate of the rate of weight loss was an effect size of -0.81 (95% CI: -1.12, -0.51), which translated to a weight loss of 2.1 pounds more in the treatment group than in the placebo group. There was no evidence of publication bias and no statistical heterogeneity was identified (P=0.689).
The meta-regression across all trials showed that all effect sizes for each comparison were significantly different from zero (i.e. all treatments were associated with significantly increased weight loss compared with placebo), with ephedrine plus caffeine and ephedra plus caffeine-containing herbs being somewhat more effective for weight loss than ephedrine alone.
Athletic performance.
Six small trials (with fewer than 24 participants) compared the effects of synthetic ephedrine with or without caffeine to caffeine and placebo on exercise parameters in healthy males. One of these trials assessed strength training and found a significant improvement in muscle endurance during the first of three repetitions. No other statistically significant differences were identified. One trial assessed the effects of ephedrine versus placebo or no treatment on 21 healthy young men. No statistical differences in athletic performance were identified.
Adverse events.
The pooled estimates showed that the treatment groups experienced significantly higher rates of psychiatric symptoms (8 trials; OR 3.64, 95% CI: 1.91, 7.31), autonomic hyperactivity (13 trials; OR 3.37, 95% CI: 2.19, 5.31), heart palpitations (11 trials; OR 2.29, 95% CI: 1.27, 4.32) and upper gastrointestinal symptoms (10 trials; OR 2.15, 95% CI: 1.39, 3.38).