Effects of Val-Pro-Pro and Ile-Pro-Pro on Nondipper Patients: A Preliminary Study

Much clinical evidence on the antihypertensive effects of the milk-derived antihypertensive peptides Val-Pro-Pro and Ile-Pro-Pro (lactotripeptides) has been reported. However, circadian rhythm effects determined by ambulatory blood pressure monitoring (ABPM) to eliminate the confounding influence of the white-coat effect have not been fully studied. Twelve hypertensive patients not receiving antihypertensive medication (2 men, 10 women; mean age +/- standard deviation, 63.5 +/- 8.3 years) who had been visiting our clinic for more than 1 year participated in this study. Mean (+/- standard deviation) systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 142.4 +/- 2.6 and 83.5 +/- 6.4 mm Hg, respectively, at the first office visit. After patients ingested a fermented milk product containing antihypertensive peptides (2.53 mg Val-Pro-Pro; 1.52 mg Ile-Pro-Pro) for more than 4 weeks, both office SBP and DBP were significantly reduced to a mean (+/- standard deviation) of 133.3 +/- 7.0 mm Hg and 76.5 +/- 8.4 mm Hg (P<.001 and P<.005 by paired t-test), respectively. The 24-hour SBP and DBP determined by ABPM were reduced from 127.3 +/- 2.4 and 78.7 +/- 2.3 mm Hg to 120.2 +/- 2.4 and 75.0 +/- 2.2 mm Hg (P<.001 and P<.05), respectively. Awake-time SBP (08:00-21:00), night-time SBP (0:00-05:00), and early-morning SBP (06:00-07:00) were reduced from 130.9 +/- 2.4 to 123.3 +/- 2.3 mm Hg, 118.7 +/- 2.9 to 113.2 +/- 3.4 mm Hg, and 132.8 +/- 4.3 to 122.4 +/- 3.9 mm Hg (by paired t-test: P<.001, P<.05, and P<.05), respectively. As seen with DBP measured by ABPM, 24-hour DBP and awake-time DBP were significantly reduced from 78.7 +/- 2.3 to 75.0 +/- 2.2 mm Hg and 82.1 +/- 2.5 to 77.3 +/- 2.2 mm Hg (P<.05 and P<.01), respectively. Office BP and 24-hour blood pressure did not significantly differ between the dipper and nondipper groups at baseline. However, after treatment, night-time and early-morning blood pressure were significantly reduced from baseline in the nondipper group (-8.5 +/- 2.5 and -15.6 +/- 3.7 mm Hg; P<.05 and P<.01, respectively) but not in the dipper group (-2.5 +/- 3.6 and -1.2 +/- 4.7 mm Hg; P not significant), and the reduction in early-morning blood pressure significantly differed between the groups (P<.05). These results suggest that Val-Pro-Pro and Ile-Pro-Pro decrease blood pressure in patients with stage I hypertension and result not only in lower blood pressure at night-time but also in lower early-morning SBP in nondipper patients.