Ile-Pro-Pro and Val-Pro-Pro Tripeptide-Containing Milk Product has Acute Blood Pressure Lowering Effects in Mildly Hypertensive Subjects

Abstract

Casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) lower blood pressure (BP) in long-term clinical studies. Their acute effects on BP and vascular function, important for daily dosing scheme, were studied in a placebo-controlled double-blind crossover study using a single oral dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro as well as plant sterols. Twenty-five subjects with untreated mild hypertension received in random order 250 g of study product (25 mg peptides and 2 g plant sterols) or placebo. Ambulatory BP was monitored for 8 h post-dose and arterial stiffness measured by pulse wave analysis at 2, 4, and 8 h. Blood and urine samples were analyzed for markers of the renin-angiotensin system (RAS) and endothelial function. Baseline adjusted treatment effect for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial BP was −2.1 mmHg (95% CI: −4.1 to −0.1, p = 0.045), −1.6 mmHg (95% CI: −3.1 to −0.1, p = 0.03), and −1,9 mmHg (95% CI: −3–3 to −0.4, p = 0.0093), respectively, in favor of the active treatment for 8 h post- dose. No significant differences between the treatments were seen in brachial or aortic augmentation index, pulse wave velocity, or markers of RAS. Urinary excretion of cGMP, the second messenger of endothelial nitric oxide, was higher in the active group vs. placebo (p = 0.01). The results indicate that a single dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols acutely lowers brachial SBP and DBP in mildly hypertensive subjects.

• bioactive milk peptides
• Ile-Pro-Pro
• Val-Pro-Pro
• blood pressure
• vascular function
• human

ACKNOWLEDGMENTS

We sincerely thank Petri Silfverberg and Elina Lausvaara for planning and preparing the study products. The staff at Charite Research Organisation is acknowledged for professionally conducting the study. The authors are grateful to the subjects for co-operation.

Declaration of interest: Anu Turpeinen and Riitta Korpela are/were employees of Valio R&D, Helsinki, Finland. Heikki Vapaatalo is a member of the Scientific Advisory Board of MSD Finland Ltd., Santen Ltd., Finland, a leader of a Valio milk protein project, and PI of a Valio milk protein project on cardiovascular health. The study was funded by the Finnish Funding Agency for Technology and Innovation.