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Food and health

Effects of dietary macronutrients on liver fat content in adults: a systematic review and meta-analysis of randomized controlled trials

European Journal of Clinical Nutrition volume 75, pages 588–601 (2021)Cite this article

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Abstract

Dietary macronutrient composition may affect hepatic liver content and its associated diseases, but the results from human intervention trials have been equivocal or underpowered. We aimed to assess the effects of dietary macronutrient composition on liver fat content by conducting a systematic review and meta-analysis of randomized controlled trials in adults. Four databases (PubMed, Embase, Web of Science, and COCHRANE Library) were systematically searched for trials with isocaloric diets evaluating the effect of dietary macronutrient composition (energy percentages of fat, carbohydrates, and protein, and their specific types) on liver fat content as assessed by magnetic resonance techniques, computed tomography or liver biopsy. Data on change in liver fat content were pooled by random or fixed-effects meta-analyses and expressed as standardized mean difference (SMD). We included 26 randomized controlled trials providing data for 32 comparisons on dietary macronutrient composition. Replacing dietary fat with carbohydrates did not result in changes in liver fat (12 comparisons, SMD 0.01 (95% CI −0.36; 0.37)). Unsaturated fat as compared with saturated fat reduced liver fat content (4 comparisons, SMD −0.80 (95% CI −1.09; −0.51)). Replacing carbohydrates with protein reduced liver fat content (5 comparisons, SMD −0.33 (95% CI −0.54; −0.12)). Our meta-analyses showed that replacing carbohydrates with total fat on liver fat content was not effective, while replacing carbohydrates with proteins and saturated fat with unsaturated fat was. More well-performed and well-described studies on the effect of types of carbohydrates and proteins on liver fat content are needed, especially studies comparing proteins with fats.

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Fig. 1: Flowchart of included randomized controlled trials in meta-analysis on dietary macronutrient composition in relation to liver fat.
Fig. 2: Difference between effects of a low-carbohydrate high-fat diet (LCHF) and a high-carbohydrate low-fat (HCLF) on liver fat content in studies included in meta-analysis: a random-effects model.
Fig. 3: Difference between effects of a diet high in saturated fats (SFA) and a diet high in unsaturated fat (UFA) on liver fat content in studies included in meta-analysis: a fixed-effects model.
Fig. 4: Difference between effects of a low-protein high-carbohydrate (LPHC) diet and a high-protein low-carbohydrate (HPLC) diet on liver fat content in studies included in meta-analysis: a fixed-effects model.

Data availability

Data used in the manuscript, code book, and analytic code will be made available to editors upon request.

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Acknowledgements

We thank P.K. Luukkonen, S. Haufe, and M.R. Mensink for providing additional data for our analyses. We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE). This research was in part financed by the Ministry of Economic Affairs and Climate Policy by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships and by Unilever R&D Vlaardingen.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

    Esther Winters-van Eekelen, Inge Verkouter, Babette G. de Roos, Frits R. Rosendaal, Olaf M. Dekkers & Renée de Mutsert

  2. Unilever Research and Development, Vlaardingen, the Netherlands

    Harry P. F. Peters, Marjan Alssema & Peter L. Zock

  3. Department of Radiology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, 6200, Maastricht, the Netherlands

    Vera B. Schrauwen-Hinderling

  4. Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands

    Kay H. M. Roumans & Patrick Schrauwen

  5. Walaeus Library, Leiden University Medical Center, Leiden, the Netherlands

    Jan W. Schoones

  6. Department of Endocrinology, Leiden University Center, Leiden, the Netherlands

    Olaf M. Dekkers

  7. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark

    Olaf M. Dekkers

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Contributions

EW-vE, IV, RdM, MA, HP, PZ, FR, VS-H, and PS designed research, EW-vE, IV, BdR, RdM, HP, MA, JS and KR conducted research, EW-vE, IV, BdR, and OD analyzed data, EW-vE, IV, BdR, RdM, HP, and MA wrote paper, EW-vE and RdM had primary responsibility for final content. All authors read and approved the final manuscript.

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Correspondence to Esther Winters-van Eekelen.

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MA, HP, and PZ were employees of Unilever R&D Vlaardingen at the time of this study. The other authors declare no conflict of interest.

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Winters-van Eekelen, E., Verkouter, I., Peters, H.P.F. et al. Effects of dietary macronutrients on liver fat content in adults: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 75, 588–601 (2021). https://doi.org/10.1038/s41430-020-00778-1

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