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.

BackgroundDue to the increasing evidence of their health benefits, whole grains are recommended for consumption worldwide. Such recommendations are, however, rarely quantitative. Our aim was to perform a quantitative evaluation of the relationship between whole grain consumption and the occurrence of type 2 diabetes (T2D) to support a recommendation on the daily consumption of whole grains.Methods and FindingsWe conducted a systematic review by searching three bibliographic databases. We included human studies addressing the relationship between whole grain consumption and T2D occurrence, and providing quantitative information on daily intake of whole grains. A dose-response meta-regression analysis between whole grain intake and T2D occurrence was performed, using a hierarchical mixed least square linear regression model. Eight observational studies were included (all but one prospective), with a total of 15,573 cases of T2D among 316,051 participants. Quantitative meta-regression demonstrated a significant linear inverse relationship between whole grain intake and T2D occurrence (P<0.0001), with an overall absolute reduction of 0.3% in the T2D rate for each additional 10 g of whole grain ingredient consumed daily. The association persisted when adjusted on sex, age, country, study design, follow up duration, and mode of report of whole grain intakes (as foods or ingredients).ConclusionsThe meta-regression model made it possible to estimate the decrease in T2D risk corresponding to various changes in whole grain intakes, and the results contribute to setting up quantitative recommendations. For instance, consuming three servings of whole grain foods (45 g of whole grain ingredients) daily would induce a 20% relative reduction in the T2D risk as compared to consuming a half serving (7.5 g of whole grain ingredients). These results should be considered for future recommendations, by considering the actual whole grain intake of the concerned populations. The systematic review protocol was published on the PROSPERO register (CRD42013006925).

BackgroundThe 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 FindingsEligible 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.ConclusionsResults 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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