Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study

Background & aims

Citrulline increases protein synthesis during refeeding in rodents with short bowel syndrome, aging and malnutrition, and improves nitrogen balance in fed healthy humans. The aim of the current study therefore was to determine whether citrulline had affected protein metabolism in healthy volunteers.

Methods

In a randomized, double-blind, cross-over study, 12 healthy adults received a 5-h intravenous infusion of L-[1-¹³C]-leucine in the post-absorptive state, after a 7-day oral supplementation with 0.18 g/kg/day citrulline, or an iso-nitrogenous placebo. Treatment order was randomized, treatment periods were separated by 13-day wash out. Leucine appearance rate (Ra) was determined from plasma [1-¹³C]-keto-iso-caproate enrichment and leucine oxidation from expired ¹³CO₂, and nitrogen balance was estimated from 6-h urinary urea excretion.

Results

Compared with placebo, oral citrulline supplementation increased plasma citrulline, arginine and ornithine concentrations, but failed to affect albumin, transthyretin, free insulin and insulin-like growth factor (IGF)-1 plasma concentrations, urinary nitrate excretion, or nitrogen balance. Citrulline supplementation did not alter leucine Ra, leucine oxidation, nor whole-body protein synthesis.

Conclusion

In healthy, well nourished volunteers, oral citrulline increases plasma citrulline and arginine availability but does not affect whole-body protein kinetics in the post-absorptive state.