Effect of Oral Ketone Body Intake on Human CD8+ T-Cell Immunometabolism.

Ketone salt (KS) supplementation produced a short-lived increase in plasma BHB concentrations followed by increased BHB uptake in immune cells.

• The plasma BHB elevation from KS was described as 'short-lived' rather than sustained.
• Increased intracellular BHB accumulation was detected in immune cells following KS supplementation.
• The intervention lasted three weeks in healthy volunteers.
• This pattern differed from ketone ester supplementation in terms of intracellular uptake.

Ketone ester (KE) supplementation led to more sustained plasma BHB levels but without detectable intracellular BHB accumulation in immune cells.

• KE supplementation produced 'more sustained plasma BHB levels' compared to KS.
• Despite higher or more prolonged circulating BHB, no intracellular BHB accumulation was detectable in immune cells.
• This contrasts with the KS condition, where intracellular BHB uptake was observed.
• The intervention period was three weeks in healthy volunteers.

Neither ketone salt nor ketone ester supplementation affected CD8+ T-cell cytokine production, functional capacity, or mitochondrial energy metabolism.

• CD8+ T-cell cytokine secretion was measured and showed no change with either KS or KE intervention.
• Functional responses of CD8+ T cells were analyzed and remained unaltered.
• Mitochondrial energy metabolism was assessed and did not differ between conditions.
• These outcomes were consistent across both supplementation types despite differing pharmacokinetic profiles of plasma BHB.

Combining ketone salt supplementation with a carbohydrate-restricted, non-ketogenic diet also did not alter CD8+ T-cell immunometabolic parameters.

• A subgroup received KS supplementation combined with a carbohydrate-restricted, non-ketogenic diet.
• This combined intervention was tested to explore whether partial dietary modification could enhance the effects of supplementation.
• No changes in CD8+ T-cell immunometabolic parameters were observed even with this combined approach.
• The diet was explicitly described as non-ketogenic, distinguishing it from a full ketogenic diet.

The ketogenic diet has been shown to exert beneficial effects on human immunity by enhancing cytotoxic T lymphocyte function through metabolic reprogramming.

• This background finding motivated the study's investigation into whether exogenous ketone supplements could replicate KD effects.
• The mechanism described involves metabolic reprogramming of CD8+ T cells.
• Strict dietary restrictions of the KD limit adherence and complicate clinical use, driving interest in supplement alternatives.
• Exogenous ketone supplements were promoted as a 'more feasible alternative to elevate ketone body levels without the need for dietary changes.'

Broader metabolic adaptations beyond transient BHB elevation are likely required to reproduce the immunometabolic effects of a ketogenic diet.

• The authors conclude that 'transient elevation of circulating ketone body levels through supplementation seems insufficient to reproduce the immunometabolic effects of a KD.'
• The KD likely requires 'broader metabolic adaptations' that are not achieved by supplementation alone.
• The impact of exogenous ketones on adaptive immunity in healthy individuals is characterized as 'limited.'
• This conclusion is supported by the null findings across all measured CD8+ T-cell parameters in both supplementation conditions.