British Journal of Nutrition

Research Article

Antihypertensive effect of casein hydrolysate in a placebo-controlled study in subjects with high-normal blood pressure and mild hypertension

Seiichi Mizunoa1, Keiichi Matsuuraa1, Takanobu Gotoua1, Shingo Nishimuraa1, Osami Kajimotoa2, Mitsuharu Yabunea2, Yoshitaka Kajimotoa2 and Naoyuki Yamamotoa1 c1

a1 Food Research Laboratory, Calpis Co. Ltd. Sagamihara, Kanagawa, Japan

a2 Soiken Inc., Toyonaka, Osaka, Japan


We describe a clinical trial to study the efficacy of a casein hydrolysate, prepared using an Aspergillus oryzae protease, containing the major angiotensin-I-converting enzyme inhibitory peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) in a single-blind, placebo-controlled study. A total of 131 volunteers with high-normal blood pressure and mild hypertension were randomly divided into four groups (n 32 or 33 in each group). Each volunteer was given two tablets containing four different dosages of VPP and IPP (VPP+IPP: 0, 1·8, 2·5 and 3·6 mg), daily for 6 weeks. A significant decrease in systolic blood pressure was observed at 6 weeks in the active group receiving 1·8 mg (P<0·01) VPP and IPP; in the active groups receiving either 2·5 mg or 3·6 mg, systolic blood pressure was decreased at both 3 weeks (P<0·05 and P<0·05) and 6 weeks (P<0·001 and P<0·0001) compared with systolic blood pressure measured before treatment. Changes in the systolic blood pressure after 6 weeks of treatment in the four groups were −1·7, −6·3, −6·7 and −10·1 mmHg, and these effects were dose dependent. In addition, a significant difference in systolic blood pressure between the placebo group and the VPP and IPP group receiving 3·6 mg was observed (P<0·001) by two-way ANOVA. The antihypertensive effect was greater in mildly hypertensive subjects (n 20 or 21 in each group) than in any of the other subjects. No significant change of diastolic blood pressure was observed for all the test groups, and no differences in diastolic blood pressure in the test sample groups compared with the placebo group were observed during the test period.

(Received April 29 2004)

(Revised January 06 2005)

(Accepted January 10 2005)


c1 *Corresponding author: Dr Naoyuki Yamamoto, fax +81 042 769 7810, email