- Objectives: To study efficacy and safety of capsicum extract capsule in lowering LDLcholesterol, total cholesterol and triglyceride, and increasing HDL-cholesterol levels of dyslipidemic patients. Methods: This study had 2 parts, consisting of capsicum extract capsule production, to meet with standardized quality and have appropriate amount of capsaicin as an active ingredient, and phase 1 – 4 of prospective, double-blind, randomized, parallelgroup, placebo-controlled study. Phase 1 was for safety assessment of 2-week capsaicum extract capsule use in healthy volunteers, while phase 2 – 4 were to evaluate efficacy and safety of capsaicum extract capsule in decreasing LDLcholesterol and triglyceride levels of patients with hyperlipidemia. . Results: Capsicum extract tablet was firstly formulated with weight variation, thickness, hardness, and disintegration time, which was within 3 minutes, were complied with acceptance criteria. The amount of capsaicin was 2.9 – 3.1 + 0.2 mg in each 2-mg tablet. For placebo-controlled safety study, 9 and 3 healthy volunteers were randomized to capsaicin extract tablet and placebo group, respectively. Both groups took one tablet with meal twice day for 2 weeks. Unfortunately, 5 persons (55.6 %) of active group stopped taking tablets sooner secondary to moderate to severe gastrointestinal side effects, such as abdominal pain, nausea, vomiting and diarrhea, while all in placebo group had continued taking tablets for 2 weeks. To resolve the gastrointestinal disturbances and to prevent throat burning sensation due to rapid dispersion of the tablet, the investigators reformulated capsaicum extract in capsule, taken twice daily with meals. Again, 9 of 10 volunteers (90 %) could not tolerate nausea, vomiting, heartburn, and diarrhea symptoms from taking capsicum extract capsules. Only one with 120 kg body weight, in active group, finshed his 2- week study. He might receive 2 times lower capsacin dose than others with normal weight. The gastrointestinal toxicity of this capsaicin dose made the study stopped. Thus, phase 2 – 4 of the study were not initiated.