Milk-derived peptides with ACE-inhibiting properties may have antihypertensive effects in humans. We conducted a randomized double-blind placebo-controlled trial to examine the blood pressure lowering potential of 2 ACE-inhibiting lactotripeptides, ie, Isoleucine-Proline-Proline and Valine-Proline-Proline. We included 135 Dutch subjects with elevated systolic blood pressure who were otherwise healthy and who received no current antihypertensive treatment. After a 2-week run-in period on

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... subjects randomly received a daily dose of 200 mL dairy drink with 14 mg lactotripeptides obtained by concentrating fermented milk, enzymatic hydrolysis, or chemical synthesis, or placebo for 8 weeks, followed by a 2-week wash-out. The primary outcome was 8-week change in office systolic blood pressure. Secondary outcomes were change in diastolic blood pressure, home blood pressure, 24-hour ambulatory blood pressure, plasma ACE-activity, and plasma angiotensin II. Blood pressure at baseline was on average 142/84 mm Hg. Lactotripeptides did not significantly change systolic blood pressure (Pϭ0.46) or diastolic blood pressure (Pϭ0.31) compared with placebo. The mean difference (95%-CI) in systolic blood pressure response between treatment and placebo was 2.8 mm Hg (Ϫ2.6;8.2) for concentrated fermented milk lactotripeptides, Ϫ0.5 mm Hg (Ϫ6.0;5.0) for enzymatic lactotripeptides, and 1.6 mm Hg (Ϫ3.9;6.9) for synthetic lactotripeptides. Treatment neither had a significant effect on secondary outcome measures. In conclusion, the present study does not support the hypothesis of a blood pressure lowering effect of the lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline. (Hypertension. 2008;51:399-405.)