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IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

Esther Boelsma1 and Joris Kloek2*

Author affiliations

1 TNO Quality of Life, Business unit Biosciences, P. O. Box 360, 3700 AJ, Zeist, the Netherlands

2 DSM Biotechnology Center, P. O. Box 1, 2600 MA, Delft, the Netherlands

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Citation and License

Nutrition Journal 2010, 9:52  doi:10.1186/1475-2891-9-52

Published: 8 November 2010



Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH) on reducing blood pressure (BP) as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II.


We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP), MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP), or placebo (containing cellulose) for 4 weeks.


In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080) and diastolic BP by 2.3 mm Hg (P = 0.0065) compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II.


MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP.

Trial registration NCT00471263