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. Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis. Cyclosporine-induced hypertension and decline in renal function in healthy volunteers. Effects of increased consumption of fluid milk on energy and nutrient intake, body weight, and cardiovascular risk factors in healthy older adults. Hemodynamic effects of lactotripeptides from casein hydrolysate in Mediterranean normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, crossover clinical trial.
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. Milk-derived peptides with ACE-inhibiting properties may have antihypertensive effects in humans. We conducted a randomized double-blind placebo-controlled trial to examine the blood pressure lowering potential of 2 ACE-inhibiting lactotripeptides, ie, Isoleucine-Proline-Proline and Valine-Proline-Proline. We included 135 Dutch subjects with elevated systolic blood pressure who were otherwise healthy and who received no current antihypertensive treatment. After a 2-week run-in period on placebo, subjects randomly received a daily dose of 200 mL dairy drink with 14 mg lactotripeptides obtained by concentrating fermented milk, enzymatic hydrolysis, or chemical synthesis, or placebo for 8 weeks, followed by a 2-week wash-out. The primary outcome was 8-week change in office systolic blood pressure. Secondary outcomes were change in diastolic blood pressure, home blood pressure, 24-hour ambulatory blood pressure, plasma ACE-activity, and plasma angiotensin II. Blood pressure at baseline was on average 142/84 mm Hg. Lactotripeptides did not significantly change systolic blood pressure (P=0.46) or diastolic blood pressure (P=0.31) compared with placebo. The mean difference (95%-CI) in systolic blood pressure response between treatment and placebo was 2.8 mm Hg (-2.6;8.2) for concentrated fermented milk lactotripeptides, -0.5 mm Hg (-6.0;5.0) for enzymatic lactotripeptides, and 1.6 mm Hg (-3.9;6.9) for synthetic lactotripeptides. Treatment neither had a significant effect on secondary outcome measures. In conclusion, the present study does not support the hypothesis of a blood pressure lowering effect of the lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline. Probiotics are efficacious for treating and maintaining remission of ulcerative colitis.
                To conduct a randomized placebo-controlled trial of bifidobacteria-fermented milk supplementation as a dietary adjunct in treating active ulcerative colitis.
                Twenty patients with mild to moderate, active, ulcerative colitis randomly received 100 mL/day of bifidobacteria-fermented milk or placebo for 12 weeks with conventional treatment.
                Clinical and endoscopic activity indices and histological scores were similar in the two groups before treatment. Although improvements were significant in both groups, the clinical activity index was significantly lower in the bifidobacteria-fermented milk than in the placebo group after treatment. The post-treatment endoscopic activity index and histological score were significantly reduced in the bifidobacteria-fermented milk, but not the placebo group. Increases in faecal butyrate, propionate and short-chain fatty acid concentrations were significant in the bifidobacteria-fermented milk, but not the placebo group. No adverse effects were observed in either group.
                Supplementation with this bifidobacteria-fermented milk product is safe and more effective than conventional treatment alone, suggesting possible beneficial effects in managing active ulcerative colitis. This is a pilot study and further larger studies are required to confirm the result these preliminary results. To investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine.
                Eighteen healthy volunteers were administered 10 mg/kg CsA or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of lithium (CLi) and sodium (CNa) were measured for 8 h after ingestion of the capsules. Norepinephrine (2 microg/kg per h) was infused intravenously for 1.5 h into nine subjects.
                CsA increased the MAP by 17+/-2 mmHg. The GFR decreased by 18+/-2% (P < 0.001) and the RVR increased by 37+/-4% (P< 0.001) after ingestion of CsA. The CsA-induced increase in MAP preceded the CsA-induced fall in GFR. The rise in MAP was followed by an early 35+/-8/0 increase in CNa (P < 0.001). At the end of the 8 h study period, CNa decreased by 25+/-7% (P < 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of sodium, whereas the late sodium retention was secondary to the CsA-induced fall in GFR. Infusion of norepinephrine increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without CsA having any additional effect.
                It was demonstrated that a single oral dose of CsA caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that renal dysfunction and sodium retention are not the initiating events in CsA-induced hypertension. The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to norepinephrine. To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life.
                Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers.
                Randomized, controlled open trial.
                Advice to increase skim or 1% milk intake by 3 cups per day (n = 101) or to maintain usual diet (n = 103) for 12 weeks after a 4-week baseline period.
                Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels.
                Group-by-time analysis of variance with repeated-measures, chi 2 test.
                Compliance with the intervention was good. Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothenate, calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% at baseline vs 13% at 12 weeks, P < .001) and vitamin B-12 (6% vs 0%, P < .05) and tended to decrease (P < .10) for protein and thiamin (women) and magnesium and vitamin B-6 (men). The milk group gained 0.6 kg more than control group (P < .01); however, weight gain was less than predicted, which suggests some compensation for the added energy from milk. Blood pressure decreased similarly over time in both groups. Total and low-density lipoprotein cholesterol levels, and the ratio of total cholesterol to high-density lipoprotein cholesterol, were unchanged. Triglyceride levels increased within the normal range in the milk group (P = .002). Quality of life scores were high at baseline and remained high throughout.
                Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes. Dietitians can play a key role in disseminating this advice. Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides derived from enzymatic treatment of casein hydrolysate. We carried out a randomized, double-blind, crossover clinical study to investigate the antihypertensive efficacy of a short-term treatment with lactotripeptides in Mediterranean subjects with normal or high-normal blood pressure (BP). We consecutively enrolled 55 untreated subjects (men:women = 30:25), 40.3 ± 9.8 years old, with normal or high-normal BP. After 4 weeks of dietary standardization, they were allocated to treatment with a fruit juice containing 3 mg of added Ile-Pro-Pro/Val-Pro-Pro lactotripeptides or with placebo for 4 weeks. After a 4-week washout period, they were then assigned to the alternative treatment for a further period of 4 weeks. Overall, no significant difference has been observed in office BP comparing baseline data with those posttreatment. Repeating the analysis by basal BP level, a mild but significant reduction in systolic BP (-1.7 ± 2.3 mm Hg; t = 3.5, P = .002) has been observed only in subjects with high-normal BP after treatment with lactotripeptides. With regard to 24-hour BP measurement, after lactotripeptide treatment only, the subjects experienced a significant reduction in diurnal diastolic BP (-1.6 ± 5.4 mm Hg; P = .042), diurnal mean BP (-2.1 ± 5.9 mm Hg; P = .19), and 24-hour (-5.4 ± 14.2 mm Hg; P = .011) and diurnal (-7.1 ± 19.2%; P = .014) diastolic BP value measurements relative to normal values. No modification has been observed in relation to plasma renin activity and aldosteronemia. In conclusion, diurnal diastolic BP is significantly reduced by lactrotripeptide supplementation in untreated Mediterranean subjects with normal or high-normal BP. Office systolic BP is reduced only in subjects with high-normal BP.
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.