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Meta-Analysis
. 2015 Nov 4;10(11):e0142235.
doi: 10.1371/journal.pone.0142235. eCollection 2015.

Influence of the Lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aurelie Chanson-Rolle  1 , François Aubin  2 , Veronique Braesco  1 , Toshimitsu Hamasaki  3 , Masafumi Kitakaze  4
Affiliations
Meta-Analysis

Influence of the Lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aurelie Chanson-Rolle et al. PLoS One. .

Abstract

Background: The lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations, but the size of the effect varies among studies. We performed a meta-analysis including all published studies to evaluate the SBP-lowering effect of IPP/VPP in Japanese subjects more comprehensively.

Methods and findings: Eligible randomized controlled trials were searched for within four bibliographic databases, including two Japanese ones. Eighteen studies (including a total of 1194 subjects) were included in the meta-analysis. A random effect model using the restricted maximum likelihood (REML) estimator was used for the analysis. The analysis showed that consumption of IPP/VPP induced a significant reduction in SBP as compared with placebo in Japanese subjects, with an estimated effect of -5.63 mm Hg (95% CI, -6.87 to -4.39, P<0.0001) and no evidence of publication bias. A significant heterogeneity between series was evident, which could be explained by a significant influence of the baseline blood pressure status of the subjects, the effect of IPP/VPP on SBP being stronger in hypertensive subjects (-8.35 mm Hg, P<0.0001) than in non-hypertensive subjects (-3.42mm Hg, P<0.0001). Furthermore, the effect of IPP/VPP on SBP remained significant when limiting the analysis to series that tested the usual doses of IPP/VPP consumed daily (below 5 mg/d), with estimated effects of -6.01 mm Hg in the overall population and -3.32 mm Hg in non-hypertensive subjects.

Conclusions: Results from this meta-analysis show that IPP/VPP lactotripeptides can significantly reduce office SBP in Japanese subjects with or without overt hypertension, and for doses that can potentially be consumed as an everyday supplement. This suggests that these peptides could play a role in controlling blood pressure in Japanese subjects. The systematic review protocol was published on the PROSPERO register (CRD42014014322).

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Conflict of interest statement

Competing Interests: ACR, VB and FA received payment from Calpis for performing the systematic review. MK received a grant to perform animal and cellular experiments with lactotripeptides under a collaborative research agreement with Calpis. ACR and VB are employed by VAB-nutrition. FA is employed by Venn Life Sciences. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Flow diagram of study selection.
The list of the 27 articles selected for full text evaluation is available in S1 Table, which also describes the outcome of the selection process for each article (including justification for exclusion). BP: blood pressure. IPP: isoleucine–proline–proline. SBP: systolic blood pressure. VPP: valine–proline–proline.
Fig 2
Fig 2. Forest plot of treatment effects of isoleucine–proline–proline/valine–proline–proline in the meta-analysis of 33 series of findings of its effect on systolic blood pressure in Japanese subjects.
FE: fixed effect. HT: hypertensive. NT: normotensive. PHT: pre-hypertensive. RE: random effect. SBP: systolic blood pressure.
Fig 3
Fig 3. Forest plot of treatment effects of isoleucine–proline–proline/valine–proline–proline on systolic blood pressure in the subgroup analysis according to the baseline blood pressure status of the subject.
Data on SBP changes were available separately for NT, PHT and/or HT subjects for all studies except two, which were therefore excluded from this subgroup analysis (Mizushima et al 2004 [33] and Yoshizawa et al 2010 [38]). HT: hypertensive. NT: normotensive. PHT: pre-hypertensive. SBP: systolic blood pressure.
Fig 4
Fig 4. Funnel plot used to explore the potential for publication bias in the meta-analysis of 33 series for the effect of isoleucine–proline–proline/valine–proline–proline on systolic blood pressure in Japanese subjects.
Series numbers are those indicated in Table 2. IPP: isoleucine–proline–proline. SBP: systolic blood pressure. VPP: valine–proline–proline.
See this image and copyright information in PMC

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