Purpose The energy density (ED) of a diet can be leveraged to prevent weight gain or treat overweight and obesity. By lowering the ED of the diet, energy intake can be reduced while maintaining portion size. However, a reliable meta-analysis of data from randomized controlled trials (RCTs) is missing. Therefore, this meta-analysis synthesized the evidence of ED manipulation on energy intake in RCTs. Methods The systematic literature search of multiple databases according to PRISMA criteria considered RCTs investigating the objectively measured energy intake from meals with different ED (lower ED (median 1.1 kcal/g) versus higher ED (median 1.5 kcal/g)) under controlled conditions. Subgroup analyses for age (children versus adults), meal type (preload versus entrée design), and intervention length (1 meal versus > 1 meal) were performed to achieve the most homogeneous result. Results The meta-analysis of 38 included studies demonstrated that lowering ED considerably reduced energy intake – 223 kcal (95% CI: – 259.7, – 186.0) in comparison to the higher ED interventions. As heterogeneity was high among studies, subgroup analyses were conducted. Heterogeneity decreased in subgroup analyses for age and meal type combined, strengthening the results. An extended analysis showed a positive linear relationship between ED and energy intake. Dietary ED did not affect the amount of food intake. Conclusion Manipulating ED substantially affects energy intake whereas food intake remains constant. Thus, this approach can be regarded as a powerful tool for weight management through nutrition therapy. Registration on 08/08/2021: CRD42021266653.

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