Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial

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.     

The effect of dietary linoleic acid on blood pressure and erythrocyte sodium transport

The influence of an increase in the polyunsaturated fat linoleic acid on blood pressure and erythrocyte membrane sodium transport was investigated in normotensive first degree relatives of hypertensive patients and controls by the double blind administration of safflower oil or paraffin oil (placebo) capsules for four weeks separated by a four week washout period. Systolic blood pressure fell in the controls with linoleic acid supplementation but there was no significant change in total sodium efflux rate constant. When the pattern of response was compared the changes in supine systolic blood pressure, plasma renin activity, total and ouabain-sensitive sodium efflux rate constant were significantly different in the controls compared to the relatives. These results show that dietary linoleic acid supplementation may have effects on ionic fluxes across cell membranes and cause a modest fall in blood pressure. In addition, since the response to the change in fat intake was different in the relatives and the controls, this provides further evidence of differences in the physicochemical structure of the plasma membrane in hypertensive subjects and their offspring.     

Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study

High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.     

The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain

OBJECTIVE: The incidence of obesity and overweight in the US has increased considerably during the past two decades and currently affects 65% of the adult population. Research has indicated that small, yet irreversible, gains during the holiday season contribute to increases in weight during adulthood. Conjugated linoleic acid (CLA), a naturally occurring dietary fatty acid, has been found to reduce weight gain and dramatically decrease fat mass in animals. Although research in humans has shown inconsistent results, most studies have been of insufficient duration or have utilized body composition methods that are less accurate than the currently accepted criterion. DESIGN: Randomized, double-blind, placebo-controlled study of 3.2 g/day CLA for 6 months. SUBJECTS: Forty healthy, overweight subjects (age: 18-44 years; body mass index: 25-30 kg/m(2)). MEASUREMENTS: Body composition by the four-compartment model, resting metabolic rate (RMR) by indirect calorimetry, self-reported physical activity and dietary intake, and blood chemistries were determined at baseline and after 6 months. Body weight was measured monthly during the pre-holiday season (August-October), holiday season (November-December) and post-holiday season (January-March). Adverse events were assessed monthly. RESULTS: Compared to CLA, the placebo group showed a greater rate of weight gain during the holiday season (P=0.01). Within the placebo group, holiday weight change was significantly greater compared to the pre-holiday period (August-October) (P=0.03). Six-month change in body composition was improved with CLA compared to placebo (P=0.02), and body fat was significantly reduced within the CLA group (-1.0+/-2.2 kg, P=0.05). CLA had no effect on RMR, physical activity or dietary intake. The rate of reported negative emotions decreased significantly with CLA, although there was no difference in any other category of adverse event. In comparison to the placebo, CLA did not affect insulin resistance, blood lipids and markers of liver function or markers of inflammation, with the exception of a significant decrease in a biomarker of endothelial dysfunction. CONCLUSION: CLA supplementation among overweight adults significantly reduced body fat over 6 months and prevented weight gain during the holiday season. Although no adverse effects were seen, additional studies should evaluate the effect of prolonged use of CLA.     

Low dose bendrofluazide (1.25 mg) effectively lowers blood pressure over 24 h: results of a randomized, double-blind, placebo-controlled crossover study.

Previous studies indicate that low dose bendrofluazide (1.25 mg/day) has no deleterious effect on insulin sensitivity in contrast to conventional doses. To evaluate the antihypertensive effect of 1.25 mg bendrofluazide across 24 h, we studied 12 subjects in a randomized, double blind, cross-over trial, comprising 8 weeks of either 1.25 mg/day bendrofluazide or placebo. Twenty-four-hour blood pressure averages were significantly lower after bendrofluazide compared with placebo (systolic 125 +/- 4 v 136 +/- 3 mm Hg, P < .005; diastolic: 78 +/- 2 v 85 +/- 2 mm Hg, P < .01). Trough:peak ratios were 0.67 +/- 0.07 for systolic and 0.72 +/- 0.15 for diastolic blood pressure reduction. In conclusion, 1.25 mg bendrofluazide daily produced a useful antihypertensive effect across the full 24-h period.     

Effect of trans fatty acid intake on abdominal and liver fat deposition and blood lipids: a randomized trial in overweight postmenopausal women

Background:

Intake of industrially produced trans fatty acids (TFAs) is, according to observational studies, associated with an increased risk of cardiovascular disease, but the causal mechanisms have not been fully elucidated. Besides inducing dyslipidemia, TFA intake is suspected to promote abdominal and liver fat deposition.

Objective:

We examined the effect of a high intake of TFA as part of an isocaloric diet on whole-body, abdominal and hepatic fat deposition, and blood lipids in postmenopausal women.

Methods:

In a 16-week double-blind parallel intervention study, 52 healthy overweight postmenopausal women were randomized to receive either partially hydrogenated soybean oil providing 15.7 g day⁻¹ of TFA or a control oil with mainly oleic and palmitic acid. Before and after the intervention, body composition was assessed by dual-energy X-ray absorptiometry, abdominal fat by magnetic resonance (MR) imaging, and liver fat by ¹H MR spectroscopy.

Results:

Compared with the control fat, TFA intake decreased plasma high-density lipoprotein (HDL)-cholesterol by 10%, increased low-density lipoprotein (LDL)-cholesterol by 18% and resulted in an increased LDL/HDL-cholesterol ratio (baseline adjusted mean (95% CI) difference between diet groups 0.41 (0.22; 0.60); P<0.001). TFA tended to increase the body fat (0.46 (−0.20; 1.17) kg; P=0.16) and waist circumference (1.1 (−0.1; 2.4) cm; P=0.08) more than the control fat, whereas neither abdominal nor liver fat deposition was affected by TFA.

Conclusion:

The adverse effect of dietary TFA on cardiovascular disease risk involves induction of dyslipidemia, and perhaps body fat, whereas weight gain-independent accumulation of ectopic fat could not be identified as a contributory factor during short-term intake.     

The effect of alcohol and gender on ambulatory blood pressure: results from the Baseline Double Exposure study

BACKGROUND: Research has demonstrated that psychosocial and lifestyle factors are associated with sustained increases in blood pressure (BP). METHODS: Using post-hoc analyses from the Baseline Double Exposure cohort study, alcohol consumption and gender were examined as to their association with ambulatory BP (ABP) in participants with normal or elevated and untreated BP. RESULTS: The current study included 248 subjects, 135 (54.4%) of whom were women, with a mean age (+/- SD) of 50.8 +/- 6.6 years. The main effects model, which included BMI, multiple regression analysis with 24 h systolic BP as the dependent variable found that alcohol consumption (P = .033), male gender (P = .004), and age (P = .039) were significant variables associated with higher systolic BP, whereas exercise (P = .037) was associated with lower systolic BP. From the regression analysis, the independent effect of alcohol consumption (> or = 10 drinks per week) on systolic BP was 4.4 mm Hg for all subjects during 24 h and 7.1 mm Hg during spousal contact, whereas in women with this degree of alcohol consumption the effect on systolic BP was 8.4 mm Hg during 24 h and 11.4 mm Hg during spousal contact. When the interaction term of gender by drinking status was added to the same regression model, the term was not significant for systolic BP during 24 h, but was significant during spousal contact time (P = .047). CONCLUSIONS: The current study demonstrates an association between alcohol with higher systolic BP, more pronounced in women than men, particularly during spousal contact time. This is the first time that the interaction of alcohol and gender with ABP has been demonstrated.     

Eating dark and milk chocolate: a randomized crossover study of effects on appetite and energy intake

Objective:

To compare the effect of dark and milk chocolate on appetite sensations and energy intake at an ad libitum test meal in healthy, normal-weight men.

Subjects/methods:

A total of 16 young, healthy, normal-weight men participated in a randomized, crossover study. Test meals were 100 g of either milk (2285 kJ) or dark chocolate (2502 kJ). Visual-analogue scales were used to record appetite sensations before and after the test meal was consumed and subsequently every 30 min for 5 h. An ad libitum meal was served 2 h after the test meal had been consumed.

Results:

The participants felt more satiated, less hungry, and had lower ratings of prospective food consumption after consumption of the dark chocolate than after the milk chocolate. Ratings of the desire to eat something sweet, fatty or savoury were all lower after consumption of the dark chocolate. Energy intake at the ad libitum meal was 17% lower after consumption of the dark chocolate than after the milk chocolate (P=0.002). If the energy provided by the chocolate is included in the calculation, the energy intake after consumption of the dark chocolate was still 8% lower than after the milk chocolate (P=0.01). The dark chocolate load resulted in an overall energy difference of −584 kJ (95% confidence interval (−1027;−141)) during the test period.

Conclusion:

In the present study, dark chocolate promotes satiety, lowers the desire to eat something sweet, and suppresses energy intake compared with milk chocolate.     

Comparative effects of diltiazem sustained-release and captopril on blood pressure control and plasma lipoproteins in primary hypertension: a randomized, double-blind, crossover study

We compared the effects of sustained-release diltiazem and captopril on blood pressure control and lipid profile. Forty-eight patients with primary hypertension were included in this randomized, double-blind, crossover study and 43 completed the trial. Following a two-to four-week placebo run-in period, each patient initially received either diltiazem (60-180 mg twice daily) or captopril (25-75 mg twice daily) for 16 weeks and then crossed over to the other drug after an interim placebo washout period. Both drugs significantly reduced systolic (SBP) and diastolic (DPB) blood pressure compared to baseline. However, supine (P less than 0.01), sitting and standing (P less than 0.05) DPB was lower with diltiazem than with captopril. Moreover, BP control (sitting DBP less than 90 mmHg) was achieved in a greater proportion of patients treated with diltiazem (63 vs 44%). Heart rate was significantly reduced (P less than 0.001) with diltiazem in all positions but was unchanged with captopril. Lipid, lipoprotein and apolipoprotein concentrations were not modified with either treatment. We conclude that both diltiazem and captopril are effective antihypertensive agents without deleterious effects on lipid metabolism. However diltiazem provides a better prolonged control of BP and may offer some advantages for patients in whom a slower heart rate would be beneficial.     

Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study.

AIMS: To evaluate the effects of simvastatin on serum lipids and insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia. METHODS: A double-blind, randomized, placebo-controlled and two-period crossover study. After a 2-month run-in, 19 eligible Type 2 diabetic patients with hypercholesterolaemia were randomized to receive either simvastatin or placebo for 3 months, exchanging their treatment thereafter for another 3 months. Blood samples were taken in month 0 and at monthly intervals to measure serum lipids and indices of glycaemic control. An euglycaemic insulin clamp was performed in months 0, 3 and 6 to assess change of insulin sensitivity. The amount of glucose infused during 90-120 min of the clamp (M), and the mean values of serum insulin during 90-120 min (I) were measured. The M and M/I ratio were used to represent the in vivo insulin sensitivity of the subject. RESULTS: Simvastatin significantly reduced serum total cholesterol (TC) by 23+/-18% and low density lipoprotein-cholesterol (LDL-C) by 30+/-26%. It did not alter glycaemic control. The M-values and M/I ratios were similar in both groups in each period and no drug effect on insulin sensitivity could be identified. CONCLUSIONS: Simvastatin significantly reduced the serum TC and LDL-C levels without alteration of insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.     

The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials

BACKGROUND: An increased intake of magnesium might lower blood pressure (BP), yet evidence from clinical trials is inconsistent, perhaps as a result of small sample size or heterogeneity in study design. METHODS: We performed a meta-analysis of randomized trials that tested the effects of magnesium supplementation on BP. Twenty trials meeting the inclusion criteria were identified. Random effects models and meta-regression methods were used to pool study results and to determine the dose-response relationship of magnesium to BP. RESULTS: The 20 studies included 14 of hypertensive and 6 of normotensive persons totaling 1220 participants. The doses of magnesium ranged from 10 to 40 mmol/day (median, 15.4 mmol/day). Magnesium supplementation resulted in only a small overall reduction in BP. The pooled net estimates of BP change (95% confidence interval [CI]) were -0.6 (-2.2 to 1.0) mm Hg for systolic BP and -0.8 (-1.9 to 0.4) mm Hg for diastolic BP. However, there was an apparent dose-dependent effect of magnesium, with reductions of 4.3 mm Hg systolic BP (95% CI 6.3 to 2.2; P < .001) and of 2.3 mm Hg diastolic BP (95% CI 4.9 to 0.0; P = .09) for each 10 mmol/day increase in magnesium dose. CONCLUSIONS: Our meta-analysis detected dose-dependent BP reductions from magnesium supplementation. However, adequately powered trials with sufficiently high doses of magnesium supplements need to be performed to confirm this relationship.     

The effect of 6 months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese

BACKGROUND: Contradicting results have been published regarding the effect of conjugated linoleic acid (CLA) on insulin resistance. However, only a few studies have used the euglycemic hyperinsulinemic clamp method, which is considered the standard for measuring insulin resistance. OBJECTIVE: To evaluate if CLA as a mixture of the main isomers trans-10 cis-12 and cis-9 trans-11 affects the insulin resistance in healthy overweight and obese male and female adults. DESIGN: The main study was a randomized, double-blind, placebo-controlled trial with change in body composition as primary end point comprising 118 subjects receiving supplementation with either placebo (olive oil) or CLA (Clarinol) for 6 months. A sub-population of 49 subjects agreed additionally to participate in an euglycemic hyperinsulinemic clamp study at baseline and after 6 months of supplementation with study drug. The primary outcome was the change in glucose uptake (M) as measured by the hyperinsulinemic euglycemic glucose clamp method. Secondary outcomes were the correlates between insulin resistance and changes in body composition or blood chemistry parameters. Forty-one subjects completed the clamp test at both time points. RESULTS: The median M of the CLA group was 11.0 mg min(-1) lean body mass (lbm)(-1) (n=24) at baseline, 10.3 mg min(-1) lbm(-1) (n=24) after 6 months, and the median difference was +0.21 mg min(-1) lbm(-1) (n=24). The median M of placebo group was 8.4 mg min(-1) lbm(-1) at baseline and 9.3 mg min(-1) lbm(-1) after 6 months and the median difference was -0.22 mg min(-1) lbm(-1) (n=17). No significant (P<0.05) differences were found within groups or between groups. Likewise, the glucose uptake insulin concentration ratio during clamp (M/I) was independent of treatment and time. Homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index derived from fasting glucose and insulin were also independent of treatment and time, and HOMA for the clamp population (n=49) corresponded well with HOMA for the per protocol population (n=83). Correlation analysis showed that changes in M were inversely correlated to changes in glucohemoglobin (P=0.002), but did not correlate with changes in either glucose, insulin, insulin c-peptide, leptin, adiponectin or percent body fat. CONCLUSIONS: CLA does not affect glucose metabolism or insulin sensitivity in a population of overweight or obese volunteers.     

Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells

Conjugated linoleic acid (CLA) is a collective term referring to the positional and geometric isomers of linoleic acid. This novel fatty acid has been shown to have a number of beneficial actions, including immunomodulatory, anticarcinogenic, and antiatherogenic effects. Tight junctions of epithelial cells determine epithelial membrane integrity and selective paracellular permeability to ions and macromolecules. Occludin and ZO-1 are integral structural components of the tight junction, which are involved in the biogenesis and functional integrity of the epithelial monolayer. This study investigated the effects of two isomers of CLA (cis-9 and trans-10 isomers) on Caco-2 cell transepithelial resistance (TER) development, paracellular epithelial permeability, and occludin and ZO-1 expression. Caco-2 cells were grown in media supplemented with 0.05 mM linoleic acid, cis-9 CLA, or trans-10 CLA for 21 days. The trans-10 CLA isomer delayed Caco-2 cell TER development, which is an in vitro measure of epithelial cell integrity, and increased paracellular epithelial permeability. Immunofluorescent staining of Caco-2 cell epithelial monolayers grown in media supplemented trans-10 CLA showed that the trans-10 CLA isomer altered distribution of occludin and ZO-1. The trans-10 CLA isomer delayed the acquisition of transepithelial resistance and altered the cellular distribution of occludin, which have important implications in relation to epithelial permeability.     

Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial.

BACKGROUND: Some studies have suggested reductions in blood pressure (BP)with statin treatment, particularly in persons with hypertension. Randomized trial evidence is limited. METHODS: We performed a randomized, double-blind, placebo-controlled trial with equal allocation to simvastatin, 20 mg; pravastatin sodium,40 mg; or placebo for 6 months. Nine hundred seventy-three men and women without known cardiovascular disease or diabetes mellitus, with low-density lipoprotein cholesterol screening levels of 115 to 190 mg/dL, had assessment of systolic and diastolic BP (SBP and DBP, respectively). Blood pressure values were compared for placebo vs statins by intention-to-treat (ITT) analysis. Additional analyses were performed that (1) were confined to subjects with neither high baseline BP (SBP>140 mm Hg or DBP>90 mm Hg) nor receiving BP medications, to exclude groups in whom BP medications or medication changes may have influenced results, and (2) separately evaluated simvastatin and pravastatin (vs placebo). The time course of BP changes after statin initiation and the effect of stopping statins on BP were examined. RESULTS: Statins modestly but significantly reduced BP relative to placebo,by 2.2 mm Hg for SBP (P=.02) and 2.4 mm Hg for DBP (P<.001) in ITT analysis. Blood pressure reductions ranged from 2.4 to 2.8 mm Hg for both SBP and DBP with both simvastatin and pravastatin, in those subjects with full follow-up, and without potential for influence by BP medications (ie, neither receiving nor meriting BP medications). CONCLUSIONS: Reductions in SBP and DBP occurred with hydrophilic and lipophilic statins and extended to normotensive subjects. These modest effects may contribute to the reduced risk of stroke and cardiovascular events reported on statins. Trial Registration clinicaltrials.gov Identifier: NCT00330980.     

Hydroxyhydroquinone-free coffee: a double-blind, randomized controlled dose-response study of blood pressure

Background and aimCoffee is rich in chlorogenic acids (CGA), whose metabolites may have beneficial effects such as anti-hypertensive effects. However, trial results concerning the effects of coffee on blood pressure (BP) are not consistent. A recent study suggested that hydroxyhydroquinone (HHQ), produced by the roasting of green coffee beans, inhibits the effect of CGA. In the present study, the dose–response for CGA in HHQ-free coffee on BP were investigated in mildly hypertensive men and women.Methods and resultsThe trial design was a double-blind, randomized controlled trial, with five study groups including, control, zero-dose, low-dose, middle-dose and high-dose. The control beverage was identical to ordinary coffee. The others contained reduced HHQ levels, compared to ordinary coffee, and the CGA were adjusted in target concentration. A total of 203 subjects were randomly allocated. Each subject drank one cup of coffee per day. The study involved a screening and a baseline observation period of 6 weeks and an intervention period of 4 weeks. BP response showed CGA has an anti-hypertensive effect in a dose-dependent manner in HHQ-free coffee, and ordinary coffee showed almost no effect. As a result, a significant correlation between BP change and the three dose–response patterns was observed (p < 0.001).ConclusionsThis study demonstrates a dose-dependent decrease in BP for CGA in HHQ-free coffee.