Mardinoglu · Cell metabolism 2018 · non-randomized dietary intervention and transcriptomic cohort study · n=?

An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans.

Cited 483 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized dietary intervention with mechanistic multi-omics profiling and an independent biopsy cohort

PubMed 29456073 · doi:10.1016/j.cmet.2018.01.005 · record verified 2026-08-29

What was done

Obese individuals with non-alcoholic fatty liver disease (NAFLD) underwent a short-term intervention with an isocaloric low-carbohydrate diet containing increased protein. The authors used a multi-omics approach to evaluate metabolic parameters and gut microbiota composition. In addition, liver transcriptomic profiling was conducted on biopsy samples from an independent secondary cohort.

What was found

The abstract reports no exact numeric values or statistical measures. Qualitatively, the intervention led to rapid reductions in liver fat and cardiometabolic risk markers. These improvements were accompanied by decreased hepatic de novo lipogenesis, elevated serum beta-hydroxybutyrate levels, and increased abundance of folate-producing Streptococcus alongside higher serum folate concentrations. Liver transcriptomics showed downregulation of fatty acid synthesis and upregulation of fatty acid oxidation and folate-mediated one-carbon metabolism pathways.

Why it matters

This study provides an integrated mechanistic model for how carbohydrate restriction reduces liver fat in NAFLD, linking host lipid metabolism with microbiome-derived folate production.

Limits

The abstract does not state the sample size (n), intervention duration, exact macronutrient breakdown, or quantitative effect sizes. The study design lacks a randomized control group, making it impossible to separate specific macronutrient shifts from study-related lifestyle changes.

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