Do the Lactotripeptides Isoleucine–Proline–Proline and Valine–Proline–Proline Reduce Systolic Blood Pressure in European Subjects? A Meta-Analysis of Randomized Controlled Trials

BACKGROUND The milk-derived peptides isoleucine-proline-proline (IPP) and valine-proline- proline (VPP) have been shown to reduce systolic blood pressure (SBP). This decrease is convincingly shown in subjects of Asian origin, but less consistent results have been obtained in European populations. METHODS A meta-analysis was conducted in accord with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) requirements, to assess the effect of IPP and VPP on SBP in Europeans, and to explore some determinants of this effect. RESULTS Ninety-one publications on the effect of IPP and VPP on SBP in Europeans were identified, and 14 trials with 15 sets of data (n = 1,306) met the inclusion criteria for the meta-analysis. A random-effects model (using the restricted maximum likelihood (REML) estimator) was used for the analysis. Although not all individual trials showed a statistically significant effect of IPP or VPP in reducing SBP, the combination of all data for the two peptides yielded a statistically significantly greater effect for IPP/VPP than for placebo. The decrease in SBP with IPP/VPP was 1.28mm Hg (95% CI, -2.09 to -0.48, P = 0.0017) and the decrease in diastolic BP (DBP) was 0.59mm Hg (95% CI, -1.18 to -0.01, P = 0.047). There was no evidence in the meta-analysis of any publication bias or of heterogeneity (P = 0.13). Among other features, a significant effect was seen for age, with each additional year of age reducing the effect on SBP by 0.09mm Hg. This might be related to isolated systolic hypertension, a condition often encountered in the elderly, who may be poorly responsive to first-line treatments for hypertension. CONCLUSION The peptides IPP and VPP are effective in moderately reducing SBP in European subjects, as is known for Asian populations. These two peptides could therefore have a role in controlling blood pressure (BP), a prospect that merits their further study.