We reviewed all randomized weight loss studies performed in adults with overweight or obesity (BMI ≥ 25 kg/m) that involved a comparison of IMF to CER. Studies included in the review were ≥8 weeks in duration, and the IMF paradigm prescribed ≥60% energy restriction on “fast” days, with intervening “fed” days of ad libitum intake or intake at or above daily energy needs (see Table 1 ). We did not include studies that utilized ≤60% energy restriction on fast days to remain consistent with prior definitions of IMF in the literature [ 15 ]. Interventions of less than 8 weeks were not included because 8 weeks is not a sufficient duration to provide meaningful, clinically relevant information in regard to weight loss. Eleven studies met our criteria and are summarized in Table 1 . Because there are no commonly accepted definitions and terminology used to describe the various IMF paradigms, a description of each intervention is provided in the table. Harvie et al., 2011 [ 40 ]; Harvie et al., 2013 [ 41 ]; Carter et al., 2016 [ 42 ]; Carter et al., 2018 [ 43 ]; Schübel et al. [ 44 ]; Conley et al. [ 45 ]; and Sundfør et al. [ 46 ] all evaluated various forms of the 2DW IMF diet (either 25% [ 40 44 ] or 30% [ 41 ] of energy intake (EI) or specific calorie goals on 2 restricted days per week [ 42 46 ], with no restriction on the other 5 days). Catenacci et al. [ 25 ] evaluated zero-calorie alternate day fasting (100% energy restriction on fast days alternating with ad libitum intake on fed days), while Varady et al. [ 47 ], Trepanowski et al. [ 48 ], and Hutchison et al. [ 49 ] evaluated alternate day modified fasting (ADMF) (25% [ 47 48 ] and 37% [ 49 ] of energy requirements on fast days alternating with either ad libitum intake on fed days [ 47 ] or the provision of 100–145% [ 48 49 ] of EI on fed days). These studies generally enrolled participants who were physically inactive or engaged in light or low amounts of physical activity at the baseline. All studies had a majority of female participants, with the exception of Schübel et al. [ 44 ] and Sundfør et al. [ 46 ], both of which included 50% males, and Conley et al. [ 45 ], which included only older male war veterans. Four studies—Varady et al. [ 47 ], Catenacci et al. [ 25 ], Trepanowski et al. [ 48 ], and Hutchison et al. [ 49 ]—provided meals to study participants during some or all of the intervention; all other studies gave energy intake goals but allowed participants to eat their own food.

p

Overall, the available evidence suggests that IMF paradigms produce equivalent weight loss when compared to CER, with 9 out of 11 studies reviewed showing no significant differences in weight or body fat loss between IMF and CER groups. Our findings are consistent with a recent systematic review and meta-analysis conducted by Harris et al. [ 51 ] that included four studies comparing IMF to CER published through November 2015. We excluded two studies included in that systematic review and meta-analysis (Hill et al. [ 52 ] and Viegener et al. [ 53 ]) due to the fact that the regimens did not include intervening days of ad libitum food intake, but alternated periods of significant (600–900 kcal/day) with moderate (1200–1500 kcal/day) energy restriction. In the Harris et al. review, the authors found no significant difference between IMF and CER (−1.03 kg, 95% CI −2.46 kg to 0.40 kg). In the present review, the only studies that showed differences in weight or body fat loss were Harvie et al., 2013 [ 41 ] and Hutchison et al. [ 49 ]. The Harvie et al., 2013 study included a 2DW IMF regimen which required two consecutive days/week of either a low-carbohydrate diet (70% energy restriction and 40 g carbohydrate) or a less restrictive low-carbohydrate 2DW IMF diet that allowed ad libitum protein and monounsaturated fatty acids. The 2DW IMF diets were compared to an isocaloric 25% CER Mediterranean-type diet. While there was no significant difference in weight loss between the groups, there was a greater loss of body fat (measured using bioimpedance) with both 2DW regimens compared to CER over 3 months: mean change in body fat was −3.7 kg (95% CI −2.5, −4.9) for the low-carbohydrate 2DW group, −3.7 kg (95% CI −2.8, −4.7) for the low-carbohydrate 2DW plus ad lib protein group, and −2.0 kg (95% CI −1.0, 3.0) for the CER group. The Hutchison et al. [ 49 ] study included an ADMF group that was provided a diet at 70% of the calculated baseline energy requirements per week (ADMF 70), an AMDF diet at 100% of the calculated baseline energy requirements per week (ADMF 100), and a CER group at 70% of the calculated baseline energy requirements daily (CER). The two ADMF groups were provided meals on their fed days (~100% energy requirements for ADMF 70 and ~145% energy requirements for ADMF 100) and were asked to consume breakfast (32% of energy requirements for ADMF 70 and 37% in ADMF 100) before 8 am on 3 nonconsecutive fast days per week, followed by a 24 h fast until 8 am the following day. ADMF 70 produced greater weight loss (−5.4 ± 0.5 kg) and fat loss (−3.9 ± 0.4 kg) compared to both CER (−3.9 ± 0.4 kg; −2.8 ± 0.4 kg) and ADMF 100 (−2.7 ± 0.5 kg; −2.3 ± 0.4 kg). Importantly, both the ADMF 100 and ADMF 70 groups ate less than provided on fed days, resulting in an overall average weekly deficit of ~9% and ~2% more than prescribed, respectively, such that energy restriction in ADMF 70 was greater than CER. This spontaneous energy restriction on fed days was also observed in Harvie et al., 2013 [ 41 ] and Trepanowski et al. [ 48 ], and has been hypothesized to be a benefit of IMF [ 54 ]. Schubel et al. [ 44 ] showed a trend toward greater weight loss with 2DW IMF compared to CER (log relative weight change −7.1 ± 0.7% vs. −5.2 ± 0.6%,= 0.053). Five studies (Harvie et al., 2013 [ 41 ], Catenacci et al. [ 25 ], Schubel et al. [ 44 ], Trepanowski et al. [ 48 ], and Sundfør et al. [ 46 ]) included maintenance and/or follow-up phases, with relatively minimal contact with participants for 4–26 weeks. In general, there was no difference in weight regain between IMF and CER groups over these follow-up periods.