The aim of this systematic review and meta-analysis is to summarise the effects of intermittent energy restriction on weight and biological markers in long term intervention studies of >6 months duration. An electronic search was performed using the MEDLINE, EMBASE and the Cochrane Library databases for intervention trials lasting 6 months or longer investigating the effects of intermittent energy restriction. A total of nine studies were identified as meeting the pre-specified criteria. All studies included an intermittent energy restriction arm, with six being directly compared to continuous energy restriction. A total of 981 subjects were enrolled and randomised, with weight loss observed in all intermittent energy restriction arms regardless of study duration or follow up length. Eight interventions in six trials were used for the meta-analyses, with results indicating neither intermittent or continuous energy restriction being superior with respect to weight loss, 0.084 ± 0.114 (overall mean difference between groups ± standard error; p = 0.458). The effects of intermittent energy restriction in the long term remain unclear. The number of long term studies conducted is very limited, and participant numbers typically small (less than 50 completers), indicating the need for larger, long term trials of 12 months or more, to be conducted in order to understand the impact of intermittent energy restriction on weight loss and long term weight management. Blood lipid concentrations, glucose, and insulin were not altered by intermittent energy expenditure in values greater than those seen with continuous energy restriction.

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Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

Fibroblast growth factor-21 (FGF-21), is a protein involved in cell growth and differentiation, development, wound repair and metabolism. Research looking at the impact of weight loss on FGF-21 levels is limited. The objective of this exploratory study was to determine changes in serum FGF-21 levels following weight loss induced by either continuous energy restriction or intermittent energy restriction. A sub cohort of participants who completed a 12-month dietary intervention trial following continuous energy restriction, or a week-on week-off energy restriction pattern, were selected for analysis. FGF-21 levels were not altered by weight loss and were not correlated with body weight or BMI at baseline or 12 months. Weight loss after 12 months either through continuous energy restriction or intermittent energy restriction was −5.9 ± 4.5 and −4.9 ± 3.4 kg, respectively. There was no change in FGF-21 levels, 0.3 ± 0.9 and 0.04 ± 0.2 ng/mL (p = 0.2). In conclusion, weight loss in healthy overweight or obesity subjects did not affect FGF-21 levels.