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Abstract
Very-low-carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno-nutritional intervention study enrolling healthy volunteers. We show that ketone bodies profoundly impact human T-cell responses. CD4+, CD8+, and regulatory T-cell capacity were markedly enhanced, and T memory cell formation was augmented. RNAseq and functional metabolic analyses revealed a fundamental immunometabolic reprogramming in response to ketones favoring mitochondrial oxidative metabolism. This confers superior respiratory reserve, cellular energy supply, and reactive oxygen species signaling. Our data suggest a very-low-carbohydrate diet as a clinical tool to improve human T-cell immunity. Rethinking the value of nutrition and dietary interventions in modern medicine is required.