OBJECTIVE:To examine long-term safety and efficacy for weight loss of an herbal Ma Huang and Kola nut supplement (90=192 mg=day ephedrine alkaloids=caffeine). DESIGN: Six-month randomized, double-blind placebo controlled trial. SUBJECTS: A total of 167 subjects (body mass index (BMI) 31.8 AE 4.1 kg=m 2 ) randomized to placebo (n ¼ 84) or herbal treatment (n ¼ 83) at two outpatient weight control research units. MEASUREMENTS: Primary outcome measurements were changes in blood pressure, heart function and body weight. Secondary variables included body composition and metabolic changes. RESULTS: By last observation carried forward analysis, herbal vs placebo treatment decreased body weight ( 7 5.3 AE 5.0 vs 7 2.6 AE 3.2 kg, P < 0.001), body fat ( 7 4.3 AE 3.3 vs 7 2.7 AE 2.8 kg, P ¼ 0.020) and LDL-cholesterol ( 7 8 AE 20 vs 0 AE 17 mg=dl, P ¼ 0.013), and increased HDL-cholesterol ( þ 2.7 AE 5.7 vs 7 0.3 AE 6.7 mg=dl, P ¼ 0.004). Herbal treatment produced small changes in blood pressure variables ( þ 3 to 7 5 mmHg, P 0.05), and increased heart rate (4 AE 9 vs 7 3 AE 9 bpm, P < 0.001), but cardiac arrhythmias were not increased (P > 0.05). By self-report, dry mouth (P < 0.01), heartburn (P < 0.05), and insomnia (P < 0.01) were increased and diarrhea decreased (P < 0.05). Irritability, nausea, chest pain and palpitations did not differ, nor did numbers of subjects who withdrew. CONCLUSION: In this 6-month placebo-controlled trial, herbal ephedra=caffeine (90=192 mg=day) promoted body weight and body fat reduction and improved blood lipids without significant adverse events.