PURPOSE OF REVIEW: Since the mid-1990s, a number of randomized controlled trials have been published that showed an antihypertensive effect of peptides derived from milk. Research has mainly focused on isoleucine-proline-proline and valine-proline-proline (IPP + VPP), two lactotripeptides that can inhibit the angiotensin-converting enzyme (ACE) in vitro. In Finnish and Japanese subjects with (mild) hypertension, systolic blood pressure (SBP) reductions of approximately 5 mmHg were reported during 4-12 weeks of IPP + VPP supplementation. This review was performed to summarize new data from human intervention studies. RECENT FINDINGS: The effect of lactotripeptides on blood pressure has recently been examined in six double-blind, placebo-controlled trials that involved a total of 780 subjects with high-normal blood pressure or untreated hypertension from the UK and The Netherlands. Intervention periods lasted 4-8 weeks, and IPP + VPP intake ranged from 2 to 10 mg/day. Contrary to earlier trials, there was little evidence for an antihypertensive effect of IPP + VPP. Furthermore, no ACE inhibition was observed in vivo. SUMMARY: Recent data do not support a role for lactotripeptides in blood pressure regulation. However, we cannot exclude a beneficial effect in hypertensive subjects from specific populations (e.g. Finland, Japan). Should this be confirmed, more research is needed on mechanisms other than the renin-angiotensin-aldosterone system that could be involved.
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