Effects of refined carbohydrates on immune markers after weight loss on a very-low-carbohydrate diet: A randomized controlled feeding trial

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This study explored the effects of three diets differing in the amount and type of carbohydrates on peripheral immune markers. After a 15% weight loss with a very-low-carbohydrate diet (VLCD), participants were randomized to isocaloric diets: VLCD, high-carbohydrate diet with high starch content (HC-Starch), or high-carbohydrate diet with high sugar content (HC-Sugar). Changes in peripheral immune markers were assessed in 44 participants using multimodal analyses before randomization and after 10 weeks on the diet. In HC-Starch, cytometry by time of flight (CyTOF) revealed significant shifts in proportions of circulating natural killer (NK) cells and increased activation markers in NK cells, monocytes, T cells, dendritic cells, and neutrophils. In agreement, transcriptomics showed upregulation of immune and metabolic pathways with HC-Starch but reductions with HC-Sugar. Cytokine analysis and mouse experiments suggested that increased adipsin and complement activation could underlie these changes. Following weight loss with VLCD, starch-rich diets serve as an unrecognized driver of inflammation. This study was registered at ClinicalTrials.gov: NCT03394664.