1. In this randomized controlled trial, 4:3 intermittent fasting was associated with significantly greater weight loss compared with daily caloric restriction.
2. Overall caloric intake was lower in the 4:3 IMF group, although both groups remained below the target weekly energy deficit.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Although daily caloric restriction (DCR) remains a mainstay for weight loss, many patients struggle with diet adherence and weight regain. Intermittent fasting (IMF) has been proposed as an alternative, but most studies have only examined a 5:2 (2 fast days) paradigm, with little difference in weight loss compared with DCR. This study aimed to compare the effects of 4:3 IMF, a more restrictive strategy, with DCR on weight loss in overweight patients and patients with obesity. The results showed that 4:3 IMF was associated with significantly greater weight loss compared with DCR. Further, more than twice as many patients in the 4:3 IMF group lost at least 10% of their weight than in the DCR group. Both groups showed improvements in cardiometabolic markers such as systolic blood pressure, total and low-density lipoprotein (LDL) cholesterol, triglyceride, and hemoglobin A1c outcomes. While most estimates numerically favored 4:3 IMF to DCR, the study was underpowered to detect statistically significant differences in these endpoints. The strategy of 4:3 IMF resulted in greater caloric restriction overall, but both groups were below the weekly calorie deficit target. No adverse events were reported in either group. The generalizability of this study is limited by the lack of power to detect differences in secondary outcomes, a high dropout rate, and an underrepresentation of males and Black individuals in the study population. Nevertheless, this study suggested that 4:3 IMF could be an effective alternative to DCR.
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In-Depth [randomized controlled trial]: This randomized controlled trial aimed to compare weight loss in participants undergoing 4:3 IMF versus DCR. Eligible patients had a starting body mass index (BMI) of 27 to 46 kg/m2 and did not have a history of diabetes, cardiovascular disease, eating disorders, or use of anti-obesity medications, among others. The 4:3 IMF method involved 3 non-consecutive fasting days per week, with a targeted weekly calorie deficit of 34.3%, while DCR participants were given a daily calorie goal that would allow for the same level of calorie deficit. The study included 165 randomly assigned participants, 84 of whom were assigned to 4:3 IMF and 81 to DCR; the mean age was 42 years (standard deviation [SD], 9 years), the mean BMI was 34.1 kg/m2 (SD, 4.4 kg/m2), and 73.9% participants were female. At 12 months, the 4:3 IMF group saw significantly greater weight loss (-7.7 kg [95% CI, -9.6 to -5.9 kg] vs. -4.8 kg [95% CI, -6.8 to -2.8 kg]; p = 0.040) and a higher percentage change in body weight (-7.6% [95% CI, -9.5% to -5.7%] vs. -5.0% [95% CI, -6.9% to -3.1%]) compared with the DCR group. Weight loss of at least 5% was achieved by 58% (n = 50) of 4:3 IMF participants compared with 47% (n = 27) of DCR participants; weight loss of at least 10% was achieved by 38% (n = 26) of 4:3 IMF participants compared with 16% (n = 9) of DCR participants. Overall, this study highlighted the effectiveness of 4:3 IMF for weight loss.
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