Abstract
BACKGROUND: The milk casein-derived biologically active tripeptides, isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have documented antihypertensive effect probably related to reduced angiotensin formation. It has been suggested that these tripeptides may reduce arterial stiffness and improve endothelial function. Our aim was to evaluate whether the milk-based drink containing Ile-Pro-Pro and Val-Pro-Pro influence arterial stiffness, measured as augmentation index (AIx), and endothelial function in man. METHODS: In a double-blind parallel group intervention study, 89 hypertensive subjects received daily peptide milk containing a low dose of tripeptides (5 mg/day) for 12 weeks and a high dose (50 mg/day) for the following 12 weeks, or a placebo milk drink to titrate the dose-response effect. Arterial stiffness was assessed by pulse wave analysis at the beginning and end of each intervention period. Endothelial function was tested by examining pulse wave reflection response to sublingual nitroglycerin and salbutamol inhalation. Blood pressure was measured by using office and 24-h ambulatory blood pressure measurement. RESULTS: At the end of the second intervention period, AIx decreased significantly in the peptide group compared with the placebo group (peptide group -1.53% (95% confidence interval (CI) -2.95 to -0.12), placebo group 1.20% (95% CI 0.09-2.32), P=0.013). No change in endothelial function index was observed (peptide group 0.02 (95% CI -0.06 to 0.08), placebo group 0.04 (95% CI -0.04 to 0.12), P=0.85). There were no statistically significant differences between the effects of the peptide and placebo treatment on office and 24-h ambulatory blood pressure. CONCLUSIONS: Long-term treatment with Lactobacillus helveticus-fermented milk containing bioactive peptides reduces arterial stiffness expressed as AIx in hypertensive subjects.