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

Abstract

BACKGROUNDThe 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.METHODSA 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.RESULTSNinety-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.CONCLUSIONThe 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.

Effects of 12 weeks of treatment with fermented milk on blood pressure, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind placebo-controlled study

“…A metaanalysis of the data from 15 studies showed a small effect on SBP, but no effect on DBP, as mentioned previously (4). Similarly, a recent meta-analysis of 14 studies assessing the BP-lowering effect of the peptides isoleucine-prolineproline and valine-proline-proline exclusively in European subjects has shown a small decrease in SBP and DBP of 1.28 and 0.59 mmHg respectively (21). It cannot be ruled out that the use of BP-lowering medication, ACE/AT2 blockers in our study might have influenced the results; however, we do not find this likely as both dose and type of antihypertensive medication were kept constant during the study period.…”

Impact of non-starter lactobacilli on release of peptides with angiotensin-converting enzyme inhibitory and antioxidant activities during bovine milk fermentation

“…Among these, lacto-tripeptides valine-proline-proline (VPP) and isoleucine-proline-proline (IPP) are resistant to GI digestion and can cross the mucosal barrier, resisting to digestion by serum peptidases (Foltz et al, 2008). VPP and IPP have been shown to reduce systolic blood pressure in hypertensive subjects (Boelsma and Kloek, 2010;Nakamura et al, 2011;Cicero et al, 2013), due to inhibition of angiotensin-converting enzyme (ACE), stimulation of vasodilator production, and modulation of sympathetic nervous activity (Usinger et al, 2010). In addition to antihypertensive effects, milk-derived peptidic fractions have been demonstrated to exert radical scavenging functionalities and prevent oxidative stresses associated with numerous degenerative chronic diseases, including cardiovascular ischemia, reperfusion, and atherosclerosis (Kudoh et al, 2001;Virtanen et al, 2007).…”

The role of nutrition and nutraceutical supplements in the treatment of hypertension

“…Milk peptides which contain both caseins and whey proteins are a rich source of ACEI peptides. Val-Pro-Pro and Ile-Pro-Pro given at 5 to 60 mg/d have variable reductions in BP with an average decrease in pooled studies of about 1.28-4.8/0.59-2.2 mmHg [71,100,[104][105][106][107] . However several recent meta-analysis did not show significant reductions in BP in humans [106,108] .…”

“…Bovine casein-derived peptides and whey protein-derived peptides exhibit ACEI activity [102][103][104][105][106][107][108][109][110][111] . These components include B-caseins, B-lg fractions, B2-microglobulin and serum albumin [102][103][104]111] .…”