5-MTHF improves portal pressure reduction with propranolol in cirrhosis patients

Treatment with 5-methyltetrahydrofolate (5-MTHF) significantly enhances the effect of propranolol in reducing hepatic venous pressure gradient (HVPG) in patients with cirrhosis and portal hypertension, a recent study has shown.

“This effect appears to be mediated by improved nitric oxide bioavailability in the hepatic microcirculation,” the investigators said.

Under double-blind conditions, 60 patients with cirrhosis and HVPG ≥12 mm Hg were randomly assigned to receive either 5-MTHF plus propranolol or placebo plus propranolol for 90 days. The investigators again measured HVPG and markers of nitric oxide bioavailability (tetrahydrobiopterin [BH4], asymmetric dimethylarginine [ADMA], and homocysteine [tHcy]) at the end of treatment.

Baseline clinical and haemodynamic data and nitric oxide bioavailability markers were comparable between the two groups. Patients in both groups achieved a reduction in HVPG, but those treated with 5-MTHF plus propranolol had a significantly greater decrease compared to those on placebo (percentage decrease, 20 vs 12.5; p=0.028), with no difference in hepatic blood flow.

Treatment with 5-MTHF plus propranolol, compared with placebo, also resulted in higher BH4 (1,101.4 vs 517 pg/ml; p<0.001), lower ADMA (109.3 vs 139.9 μmol/L; p=0.027), and lower tHcy (11.0 vs 15.4 μmol/L; p=0.010) plasma levels.

“5-MTHF can prevent oxidative loss of BH4, a cofactor for endothelial nitric oxide synthase coupling,” the investigators said. “It also converts tHcy into methionine and enables the degradation of ADMA, an inhibitor of endothelial nitric oxide synthase.”