Acute effects of docosahexaenoyl-taurine on human lipid digestion – a randomised, crossover, double-blind, placebo-controlled trial in healthy males

Elevated plasma triglyceride (TG) concentration dose-dependently increases the risk of cardiovascular disease (CVD). High doses of omega-3 fatty acids (n3-FA) are recommended for treatment of hypertriglyceridaemia (plasma TG ≥ 2 mmol/l). The molecular mechanisms underlying the beneficial effects of n3-FAs on plasma TG are not fully understood. An n3-FA metabolite, docosahexaenoyl-taurine (DHA-T), was found to reduce TG absorption from an oil meal in mice, like long-term n3-FA supplementation in humans. In this exploratory randomised, double-blinded, placebo-controlled, crossover study, we investigated how acute, oral administration of DHA-T affects postprandial serum TG in 19 healthy men (age 18–30, body mass index 18.5–25, non-smokers). The participants underwent a high-fat mixed meal test (HF-MMT) with DHA-T (2 mg/kg) or placebo. During the HF-MMT, blood samples and gallbladder volume measurements were collected. The trial took place at the Center for Clinical Metabolic Research at Gentofte Hospital, Hellerup, Denmark. Whereas DHA-T did not significantly reduce the primary endpoint of postprandial TG concentration, it was absorbed and peaked at 10.5 (95% CI: 7.2–13.7) µmol/l, with no reported adverse effects. DHA-T unexpectedly increased serum concentration of taurine-conjugated bile acids (iAUC: placebo: 124 (95% CI: 89–158) µmol/l × min vs. DHA-T: 161 (95% CI: 114–207) µmol/l × min, p = 0.02). This is the first study to directly test the effects of an N-acyl taurine (NAT) in humans. DHA-T did not reduce postprandial serum TG concentration. Importantly, DHA-T is orally available, and no adverse events were reported in this small, exploratory study. We observed an interplay between DHA-T, conjugated bile acids, and endogenous NATs. The study provides novel insights into the physiological roles of NATs and demonstrates that consumption of DHA-T at 2 mg/kg is well-tolerated in healthy young men. The trial was retrospectively registered at ClinicalTrials.gov (TRN: NCT05953064) during recruitment (June 20th, 2023).