Daily ingestion of the tablets containing powdered fermented milk with L. helveticus CM4 in subjects with high-normal blood pressure or mild hypertension reduces elevated blood pressure without any adverse effects.

Casein hydrolysate, prepared with Aspergillus oryzae protease, contains angiotensin I-converting enzyme inhibitory peptides, such as Val-Pro-Pro and Ile-Pro-Pro. We conducted a randomized, double-blind, placebo-controlled study to evaluate the effect of casein hydrolysate on the blood pressure of 144 subjects with high-normal blood pressure (n = 104) and mild hypertension (n = 40). Subjects were randomly assigned to two groups for a 12-week intake period. In the test group, both systolic (SBP) and diastolic (DBP) blood pressure decreased significantly compared with the placebo group: SBP/DBP significantly decreased from 138.2 +/- 6.5/84.4 +/- 5.3 mm Hg at week 0 to 132.3 +/- 7.3 (P < .001)/81.2 +/- 4.8 mm Hg (P < .001) at week 12. In the stratified analysis, the test product showed an antihypertensive effect in both the subject group with high-normal blood pressure and that with mild hypertension. No side effect was observed in any subjects in this study. These results demonstrate that the casein hydrolysate, prepared with A. oryzae protease, produced a significant reduction in blood pressure in a population of subjects with high-normal blood pressure or mild hypertension without an adverse event.

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BackgroundLactobacillus gasseri CP2305 (CP2305) is a strain of Lactobacillus isolated from a stool sample from a healthy adult that showed beneficial effects on health as a paraprobiotic. In a previous study, we demonstrated that CP2305-fermented heat-treated milk modified gut functions more than artificially acidified sour milk. Thus, the regulatory activity of the former beverage was attributed to the inactivated CP2305 cells.ObjectiveThe aim of this study was to elucidate the contribution of non-viable paraprobiotic CP2305 cells to regulating human gut functions. We thus conducted a randomized, placebo-controlled, double-blinded parallel group trial.DesignThe trial included 118 healthy participants with relatively low or high stool frequencies. The test beverage was prepared by adding 1×1010 washed, heat-treated, and dried CP2305 cells directly to the placebo beverage. The participants ingested a bottle of the assigned beverage daily for 3 weeks and answered daily questionnaires about defecation and quality of life. Fecal samples were collected and the fecal characteristics, microbial metabolite contents of the feces and composition of fecal microbiota were evaluated.ResultsThe number of evacuations and the scores for fecal odors were significantly improved in the group that consumed the CP2305-containing beverage compared with those of the group that consumed the placebo (p=0.035 and p=0.040, respectively). Regarding the fecal contents of microbial metabolites, the level of fecal p-cresol was significantly decreased in the CP2305 group relative to that of the placebo group (p=0.013). The Bifidobacterium content of the intestinal microbiota was significantly increased in the CP2305 group relative to that of the placebo group (p<0.008), whereas the content of Clostridium cluster IV was significantly decreased (p<0.003). The parasympathetic nerve activity of the autonomic nervous system became dominant and the total power of autonomic activity was elevated in the CP2305 group (p=0.0401 and p=0.011, respectively).ConclusionsThe continuous ingestion of heat-treated CP2305 cells clearly affected intestinal functionality. This is the first report of sterilized Lactobacillus cells having a significant impact on the environment and functions of the intestinal tract. The observed effects might be due, at least in part, to the brain–gut interaction.

Inflammation of adipose tissue triggers the metabolic syndrome, atherosclerosis and CHD. In the present study, we investigated whether the milk casein-derived tripeptide valine-proline-proline (VPP) has an anti-inflammatory effect on the adipose tissue of high-fat diet (HFD)-fed mice. Male C57BL/6J mice (7 weeks of age) were fed ad libitum with either a HFD and plain tap water (HFD group) or a HFD and water containing 0·3 mg VPP/ml (HFDþVPP group) for 10 weeks. The results showed that the expression level of CD18 in the peripheral blood monocytes of the HFDþ VPP group was significantly decreased compared with the level observed in those of the HFD group. Activated monocytes and pro-inflammatory macrophages were accumulated in the stromal vascular fractions of the adipose tissue from HFD-fed mice, which were significantly decreased in those supplemented with VPP. The formation of crown-like structures rich in pro-inflammatory macrophages was also significantly reduced in the adipose tissue of mice administered with VPP. Real-time PCR analysis revealed that the expression of monocyte chemoattractant protein-1 and that of the pro-inflammatory cytokine IL-6 in adipose tissue tend to be lower in the HFDþ VPP group than in the HFD group. These observations indicate that oral administration of VPP exerts an anti-inflammatory effect on the adipose tissue of HFD-fed mice, which may eventually lead to the primary prevention of chronic inflammation-related diseases.Key words: Casein-derived tripeptides: Inflammation: High-fat diet: Adipose tissue: Macrophages Lifestyle-related metabolic disorders such as hypertension, diabetes and dyslipidaemia play a crucial role in the development of atherosclerosis and CVD. Low-grade, but chronic inflammation is considered to be involved in the development of metabolic disorders. Among these, inflammation of adipose tissue is associated with obesity and directly promotes systemic low-grade inflammation and metabolic dysfunction (1 -3) . It has been reported that two naturally existing milk caseinderived bioactive tripeptides, isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), produced during lactic acid bacteria fermentation or in casein hydrolysates, inhibit angiotensin-converting enzyme activity (4,5) , and foods containing these peptides reduce blood pressure in several clinical trials (6,7) . VPP and IPP have also been shown to induce the production of vasodilative substances including NO in human umbilical vein endothelial cells and isolated rat arterial vessels (8) . Several recent clinical trials have shown that intake of casein hydrolysate containing VPP and IPP for 1 week improved vascular endothelial dysfunction without affecting systemic blood pressure in subjects with untreated stage-I hypertension (9) . Moreover, an 8-week intervention using the same regimen has been shown to decrease central systolic blood pressure and arterial stiffness (brachial -ankle pulse wave velocity and carotid arterial compliance) (10,11) .Animal studies have revealed th...