The antihypertensive effect of fermented milk in individuals with prehypertension or borderline hypertension. A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure. Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects. Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men.
Fermented milk (FM) with putative antihypertensive effect in humans could be an easy applicable lifestyle intervention against hypertension. The mode of action is supposed to be through active milk peptides, shown to possess in vitro ACE-inhibitory effect. Blood pressure (BP) reductions upto 23 mm Hg have been reported in spontaneously hypertensive rats fed FM. Results from human studies of the antihypertensive effect are inconsistent. However, many studies suffer from methodological weaknesses, as insufficient blinding and the use of office BP measurements. We conducted a randomised, double-blind placebo-controlled study of the antihypertensive effect of Lactobacillus helveticus FM in 94 prehypertensive and borderline hypertensive subjects. The participants were randomised into three treatment groups with a daily intake of 150 ml of FM, 300 ml of FM or placebo (chemically acidified milk). The primary outcome was repeated 24-h ambulatory BP measurements. There were no statistically significant differences in the outcome between the groups (systolic BP (SBP), P=0.9; diastolic BP (DBP), P=0.2). However, the group receiving 300 ml FM had reduced BP across the 8-week period in several readings, which could be compatible with a minor antihypertensive effect. Heart rate and lipids remained unchanged between groups. Hence, our study does not support earlier studies measuring office BP-measurements, reporting antihypertensive effect of FM. Based on straight performed 24-h ambulatory BP measurements, milk fermented with Lactobacillus helveticus does not posses significant antihypertensive effect. Angiotensin-converting enzyme (ACE; EC 3.4.15.1) plays a dual role in the regulation of hypertension: it catalyzes the production of the vasoconstrictor angiotensin II and it inactivates the vasodilator bradykinin. By inhibiting these processes, ACE inhibitors have antihypertensive effects. Peptides derived from milk proteins can have ACE-inhibiting properties and may thus be used as antihypertensive components.
                We evaluated the long-term blood pressure-lowering effect of milk fermented by Lactobacillus helveticus LBK-16H in hypertensive subjects.
                In a randomized placebo-controlled study, 39 hypertensive patients received 150 mL/d of either L. helveticus LBK-16H fermented milk or a control product for 21 wk after a 2-wk run-in period. During the run-in period, the average baseline diastolic and systolic blood pressure values were 155 and 97 mm Hg, respectively, in the test product group and 152 and 96 mm Hg, respectively, in the control group. After the run-in period, blood pressure was measured at home on the same day every week with the use of an automatic blood pressure recorder.
                There was a mean difference of 6.7 +/- 3.0 mm Hg in systolic blood pressure (P = 0.030) and of 3.6 +/- 1.9 mm Hg (P = 0.059) in diastolic blood pressure between the test product and control groups. Demographic factors had no significant effect on the responses.
                L. helveticus LBK-16H fermented milk containing bioactive peptides in normal daily use has a blood pressure-lowering effect in hypertensive subjects. The present study was carried out to evaluate the blood pressure (BP)-lowering effect and the safety aspects of Lactobacillus helveticus LBK-16H fermented milk with high tripeptide doses on hypertensive subjects using 24-h ambulatory measurements (ABPM).
                In a randomized, double blinded placebo-controlled parallel group study, 94 hypertensive patients not receiving any drug treatment were given 150 mL twice daily of either L. helveticus LBK-16H fermented milk with a high concentration of tripeptides (Ile-Pro-Pro 7.5 mg/100 g and Val-Pro-Pro 10 mg/100 g) or a control product, for 10 weeks after a 4-week run-in period. Twenty-four-hour ABPM were taken at the beginning and at the end of the intervention period. The average baseline systolic and diastolic BP values were 132.6 +/- 9.9/83.0 +/- 8.0 mm Hg in the L. helveticus group and 130.3 +/- 9.6 /80.2 +/- 7.0 mm Hg in the control group.
                There was a mean difference of -4.1 +/- 0.9 mm Hg in systolic (P = .001) and a -1.8 +/- 0.7 mm Hg in diastolic BP (P = .048) between the L. helveticus group and the control group. There was no difference in the sum of the adverse events (P = .820).
                Lactobacillus helveticus LBK-16H fermented milk containing bioactive peptides, in daily use, does have a BP-lowering effect in hypertensive subjects and is thus a potential for the dietary treatment of hypertension. Angiotensin-converting enzyme (ACE) is important in the regulation of blood pressure (BP). Two tripeptides that inhibit ACE, isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have been isolated from certain sour milks. The aim of the study reported was to evaluate the effect on BP in subjects with mild hypertension of a new sour milk containing tripeptides. The initial number of subjects was 60 (36 men, 24 women). Among the criteria for inclusion in the study were systolic BP (SBP) between 140 and 180 mmHg and/or diastolic BP (DPB) between 90 and 110 mmHg, without antihypertensive drug therapy. There were two study periods with a washout period between. All subjects were given 1.5 dl per day of a placebo (regular sour milk) or of the active product, a milk that had been fermented with Lactobacillus helveticus bacteria and contained 2.4-2.7 mg of Ile-Pro-Pro and 2.4-2.7 mg of Val-Pro-Pro per 1.5 dl. In the first phase, SBP fell 16 mmHg from baseline in the active group, 2 mmHg more than in the placebo group (P=0.0668) and no difference in DBP (P=0.92). There was a statistically significant downward trend both in SBP and DBP (P=0.0001). During the second phase, SBP fell 11 mmHg in the active group (P=0.008). The reduction in SBP was significantly larger in active than placebo group (P=0.012). In the crossover analysis combining both phases, SBP fell on average 2.6+/-15.9 mmHg more on the active product compared with the placebo product, but this difference was not statistically significant (P=0.3111). The difference in DBP, 1.0+/-8.3 mmHg between the two test products was not significant either (P=0.4431). In conclusion, the ingestion of sour milk fermented by L. helveticus bacteria and that containing ACE inhibitory tripeptides seems to lower BP modestly. The effect of fermented milk supplemented with whey protein concentrate on the serum lipid level of rats was investigated. The serum total cholesterol level for the group fed fermented milk with both Lactobacillus casei TMC0409 and Streptococcus thermophilus TMC 1543 was significantly lower than that of the control group (P<0.05) in rats. Furthermore, the effect of the longterm intake of this fermented milk on the serum lipid level of twenty healthy adult men was investigated. During the 8-wk study, the volunteers consumed 200 ml of fermented milk or placebo in the morning and evening. Blood samples were drawn for analysis three times, just before taking the experimental diet, and after 4 wk and 8 wk of consumption. After 8 wk, the high density lipoprotein cholesterol level for the fermented milk group showed a significant rise after 4 wk (P<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The triglyceride level for the fermented milk group lowered significantly after 4 wk (<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The atherogenic index [(total cholesterol - high density lipoprotein cholesterol)/high-density lipoprotein cholesterol] for the fermented milk group decreased significantly from 4.24 to 3.52 (P<0.05). The systolic blood pressure lowered significantly by the intake of fermented milk (P<0.05) On the other hand, such effect was not observed in the placebo group (P>0.05). These results indicate potential of the development of fermented milk with multiple therapeutic effects. To study the effect of a new fermented milk product containing GABA (FMG) on the blood pressure (BP) of patients with mild hypertension.
                A randomized, placebo-controlled, single-blind trial.
                The study was carried out at the outpatient clinic of the Cardiovascular Disease Center, Tokyo Metropolitan Police Hospital, Japan.
                The study population comprised 39 mildly hypertensive patients (16 women and 23 men) aged 28-81 y (mean, 54.2 y).
                The study consisted of a 12-week period of daily intake of FMG or placebo (weeks 1-12) followed by 2 weeks of no intake (weeks 13 and 14). We measured the peripheral BP and heart rate of seated patients at weeks 0, 2, 4, 8, 12 and 14. Routine blood study and urinalysis were performed before and after the intake.
                There was a significant decrease of BP within 2 or 4 weeks, and it remained decreased throughout the 12-week intake period. For the FMG recipients, the mean decrease after 12 weeks was 17.4+/-4.3 mmHg in the systolic BP (SBP) and 7.2+/-5.7 mmHg in the diastolic BP (DBP). Both of these values differed statistically from baseline levels (P<0.01), and the SBP of the FMG group differed from the placebo group (P<0.05). Heart rate, body weight, hematological and blood chemistry variables, and urinalysis results (glucosuria and proteinuria) did not vary both groups throughout the study.
                FMG may contribute to lowering BP in mildly hypertensive people. A placebo-controlled study was conducted to test the effect of Calpis (Calpis Food Industry Co, Ltd, Tokyo, Japan) sour milk, i.e., a milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae, on the blood pressure of 30 elderly hypertensive patients, most of whom were taking antihypertensive medication. Subjects were randomly assigned to two groups. One group ingested daily 95 mL of the sour milk for 8 wk, and the other group ingested the same amount of artificially acidified milk as a placebo for 8 wk. In the sour-milk group, systolic blood pressure decreased significantly 4 and 8 wk after ingestion, by 9.4 +/- 3.6 mm Hg (mean+/- SE, P < 0.05) and 14.1 +/- 3.1 mm Hg (P < 0.01), respectively. The diastolic blood pressure also decreased significantly, by 6.9 +/- 2.2 mm Hg (P < 0.01), by 8 wk after ingestion of the sour milk began. No significant changes in blood pressure were observed in the placebo group. The decrease in systolic and diastolic blood pressure in the sour-milk group tended to be greater than in the placebo group. No marked changes were observed in other indexes, including pulse rate, body weight, and blood serum variables in both groups. Several placebo-controlled clinical studies suggest that products containing isoleucyl-prolyl-proline and valyl-prolyl-proline are able to lower blood pressure without adverse effects. The most efficient way of producing high concentrations of these lactotripeptides (LTPs) is enzymatic hydrolysis of dairy protein (casein) with the use of a mixture of several enzymes derived from the nongenetically modified organism Aspergillus oryzae, including proteases and peptidases. To date, no large studies of the blood pressure-lowering properties of enzymatically produced LTP (ELTP) powder in European populations have been published.
                This study was performed to evaluate the hypothesis that consumption of ELTP in a yogurt beverage for 8 wk significantly lowers blood pressure.
                In this multicenter, double-blind, parallel, placebo-controlled trial, office blood pressure was evaluated in 275 Dutch hypertensive subjects. Blood pressures and body weight were measured on several days at baseline and at weeks 4 and 8 of the intervention between 2.5 and 3 h after intake of the test product. Twenty-four-h urine samples were collected at baseline and at the end of the intervention for urinalysis of sodium, potassium, creatinine, and microalbumin excretion.
                The results showed that 10.2 mg ELTP/d does not lead to a reduction in systolic blood pressure (P = 0.66) or diastolic blood pressure (P = 0.72) compared with placebo.
                This study showed no effect of an ELTP-enriched yogurt beverage on blood pressure in hypertensive subjects in a fairly large study. A double-blind randomized controlled trial was carried out to assess the effect of sour milk, containing two tripeptides (valine-proline-proline and isoleucine-proline-proline), on blood pressure (BP).
                A total of 46 borderline hypertensive men aged 23 to 59 years were recruited at their workplace for this trial. Subjects were randomly allocated into two groups; sour milk drink group (S-group, n = 23) and placebo (acidified milk) drink group (P-group, n = 23) for 4 weeks. Blood pressure was measured twice at each occasion by a physician, at the health center of the company, with a mercury at baseline, 2 and 4 weeks. Statistical analysis was performed by SPSS 10.0J.
                The S-group and P-group showed no significant difference in baseline systolic BP (mean [SD], S: 147.6 [9.6], P: 145.3 [13.0]) or diastolic BP (S: 95.3 [9.9], P: 91.5 [9.6]). In the S-group, change in systolic BP at 2 and 4 weeks were -4.3 mm Hg (95% confidence interval [CI] -8.3 to -0.4; P = .032) and -5.2 mm Hg (95% CI -10.1 to -0.3; P = .039), both statistically significant. Diastolic BP showed change from -1.7 mm Hg (95% CI -5.4 to 2.0) at 2 weeks and -2.0 (95% CI -5.4 to 1.5) at 4 weeks, respectively. In the P-group, change in systolic BP were -0.5 (95% CI -5.8 to 4.8) at 2 weeks and -3.7 (95% CI -8.3 to 0.9) and change in diastolic BP were -0.6 (95% CI -4.7 to 3.6) and -0.3 (95% CI -3.9 to 3.3), which were not statistically significant.
                This trial demonstrated the beneficial effect of sour milk on BP in borderline hypertensive men who were not taking antihypertensive medication.
                Copyright 2004 American Journal of Hypertension, Ltd.
The review does not support an effect of fermented milk on blood pressure. Despite the positive effect on SBP the authors conclude, for several reasons, that fermented milk has no effect on blood pressure. The effect found was very modest and only on SBP, the included studies were very heterogeneous and several with weak methodology. Finally, sensitivity and subgroup analyses could not reproduce the antihypertensive effect. The results do not give notion to the use of fermented milk as treatment for hypertension or as a lifestyle intervention for pre-hypertension nor would it influence population blood pressure.