We hypothesized that negative energy balance by a systematic procedure (TAIslim® System) with increasing metabolic rate through physical activity and use of dietary supplement, TAIslim (containing indigestible dietary fiber, L‐phenylalanine, N‐acetyl‐L‐tyrosine, tea extract and Lycium barbarum) b.i.d., and decreasing caloric intake by consuming fiber‐containing meal replacement (TAIslim SHAKE) b.i.d. and chew (TAIslim SKINNY) t.i.d. would be successful to lose weight in obese humans. Randomized, double‐blind, placebo‐controlled human clinical studies have shown that TAIslim System significantly reduced body weight by 9.2±0.8 (SEM)% compared to pre‐intervention or placebo group (1.1±0.6%) in 2 months. Other metabolic syndrome markers, such as waist circumference, total body fat, blood pressure, and fasting blood glucose level, were also significantly reduced by TAIslim System in a range of 5.8–10% compared to pre‐intervention or placebo (−0.2–1.9%). Postprandial Energy Expenditure was significantly increased by TAIslim System compared to placebo and baseline levels for more than 4 h post‐intake. TAIslim System also significantly suppressed appetite, measured by subjective visual analogue scale, by 39% compared to the baseline (11% reduction in the placebo). These results suggest that negative energy balance caused by the TAIslim System may be an effective body weight management procedure.