Alternate-day fasting elicits larger changes in fat mass than time-restricted eating in adults without obesity - A randomized clinical trial.

Background & Aims Intermittent fasting (IF) is a popular nutritional strategy for weight control and improved metabolic health, however it is unclear which type of intermittent fasting is most effective. This randomized trial directly compared short-term alternate-day fasting (ADF) and time-restricted eating (TRE) with controls in adults with overweight or a high normal weight. The aim was to compare the effects of ADF and TRE versus controls regarding whole-body fat mass loss, weight control and cardiometabolic health. Methods In this 4-week, parallel-arm, randomized clinical trial (February 2021-May 2022), participants aged 18-40 years with a body mass index between 23 and 30 kg/m2 were assigned to ADF (alternating fasting and ad libitum eating days), to TRE (eating only between 12:00-20:00), or control (no change in eating times). The primary outcome was change in total fat volume (assessed by whole-body magnetic resonance imaging). Secondary outcomes were subcutaneous and visceral fat mass, body weight, resting metabolic rate, biochemical markers, energy intake, activity energy expenditure and health-related quality of life. Results Seventy-six participants (mean [standard deviation (SD)] age, 29.6 [5.6] years; body mass index, 25.8 [2.2] kg/m2; 34 [44 %] female) were randomized to ADF (n = 26), TRE (n = 26), or control (n = 24). Seventy-five participants completed the trial (25 in ADF, 26 in TRE, 24 in control). ADF led to a greater reduction in total fat volume than control (mean difference -1059.8 cm3, 95 % CI: -1380.0 cm3 to -739.6 cm3, p < 0.001) and TRE (-695.7 cm3, 95 % CI: -1013.9 to -377.6 cm3, p < 0.001). TRE also reduced total fat volume compared to control (-364.0 cm3, 95 % CI: -621.3 cm3 to -106.7 cm3, p = 0.007). Energy intake was reduced by 34 % [18 %] in ADF, 15 % [21 %] in TRE and 3 % [22 %] in control. ADF, but not TRE, reduced visceral fat mass, resting metabolic rate, triiodothyronine and non-HDL cholesterol compared to controls. Only ADF increased activity energy expenditure and health-related quality of life. No serious adverse events occurred. Conclusions In this randomized clinical trial, ADF was more effective in reducing energy intake than TRE which has subsequent effects on fat mass and body weight. Only ADF improved several cardiometabolic risk factors. Registration https://clinicaltrials.gov/study/NCT04732130; Unique identifier: NCT04732130.