Potassium supplementation and heart rate: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Increasing the intake of potassium has been shown to lower blood pressure, but whether it also affects heart rate (HR) is largely unknown. We therefore assessed the effect of potassium supplementation on HR in a meta-analysis of randomized controlled trials. METHODS AND RESULTS: We searched PubMed (1966-October 2014) for randomized, placebo-controlled trials in healthy adults with a minimum duration of two weeks in which the effect of increased potassium intake on HR was assessed. In addition, reference lists from meta-analysis papers on potassium and blood pressure were hand-searched for publications. Two investigators independently extracted the data. We performed random effects meta-analyses, subgroup and meta-regression analyses for characteristics of the study (e.g. design, intervention duration, potassium dose and salt type, change in potassium excretion, sodium excretion during intervention) and study population (e.g. gender, age, hypertensive status, pre-study HR, pre-study potassium excretion). A total of 22 trials (1086 subjects), with a median potassium dose of 2.5 g/day (range: 0.9-4.7 g/day), and median intervention duration of 4 weeks (range: 2-24 weeks) were included. The meta-analysis showed no overall effect of increased potassium intake on HR (0.19 bpm, 95% CI: -0.44, 0.82). Stratified analyses yielded no significant effects of potassium intake on HR in subgroups, and there was no evidence for a dose-response relationship in meta-regression analyses. CONCLUSION: A chronic increase in potassium intake with supplemental doses of 2-3 g/day is unlikely to affect HR in apparently healthy adults.

Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study.

We performed a randomised, placebo-controlled, crossover study to examine the effects of sodium and potassium supplementation on blood pressure (BP) and arterial stiffness in untreated (pre)hypertensive individuals. During the study, subjects were on a fully controlled diet that was relatively low in sodium and potassium. After a 1-week run-in period, subjects received capsules with supplemental sodium (3 g d(-1), equals 7.6 g d(-1) of salt), supplemental potassium (3 g d(-1)) or placebo, for 4 weeks each, in random order. Fasting office BP, 24-h ambulatory BP and measures of arterial stiffness were assessed at baseline and every 4 weeks. Of 37 randomized subjects, 36 completed the study. They had a mean pre-treatment BP of 145/81 mm Hg and 69% had systolic BP ⩾140 mm Hg. Sodium excretion was increased by 98 mmol per 24 h and potassium excretion by 63 mmol per 24 h during active interventions, compared with placebo. During sodium supplementation, office BP was significantly increased by 7.5/3.3 mm Hg, 24-h BP by 7.5/2.7 mm Hg and central BP by 8.5/3.6 mm Hg. During potassium supplementation, 24-h BP was significantly reduced by 3.9/1.6 mm Hg and central pulse pressure by 2.9 mm Hg. Pulse wave velocity and augmentation index were not significantly affected by sodium or potassium supplementation. In conclusion, increasing the intake of sodium caused a substantial increase in BP in subjects with untreated elevated BP. Increased potassium intake, on top of a relatively low-sodium diet, had a beneficial effect on BP. Arterial stiffness did not materially change during 4-week interventions with sodium or potassium.

N-6 and n-3 fatty acid cholesteryl esters in relation to incident stroke in a Dutch adult population: a nested case-control study.

BACKGROUND AND AIMS: There are few prospective studies on fatty acid status in relation to incident stroke, with inconsistent results. We assessed the associations of plasma n-6 and n-3 PUFA in cholesteryl esters with the risk of total stroke and stroke subtypes in Dutch adults. METHODS AND RESULTS: We conducted a nested case-control study using data from a population-based cohort study in adults aged 20-65 years. Blood sampling and data collection took place during 1993-1997 and subjects were followed for 8-13 years. We identified 179 incident cases of stroke and 179 randomly selected controls, matched on age, gender, and enrollment date. Odds ratios (OR) with 95% confidence intervals (95%CI) were calculated per standard deviation (SD) increase of PUFA in cholesteryl esters using multivariable conditional logistic regression. Cases comprised 93 ischemic, 50 hemorrhagic, and 36 unspecified strokes. The n-6 PUFA linoleic acid and arachidonic acid contributed ~55% and ~6.5% respectively to total plasma fatty acids, whereas the n-3 PUFA alpha-linolenic acid contributed ~0.5% and eicosapentaenoic acid plus docosahexaenoic acid (EPA-DHA) ~1.3%. After adjustment for confounders, n-6 and n-3 PUFA were not associated with incident total stroke or stroke subtypes. The OR (95% CI) for total stroke was 0.95 (0.74-1.23) per SD increase in linoleic acid and 1.02 (0.80-1.30) per SD increase in arachidonic acid. ORs (95% CI) for total stroke were 0.94 (0.72-1.21) for alpha-linolenic acid and 1.16 (0.94-1.45) for EPA-DHA. CONCLUSION: In the present study, plasma n-6 or n-3 fatty acids were not related to incident stroke or stroke subtypes.

No effects of n-3 fatty acid supplementation on serum total testosterone levels in older men: the Alpha Omega Trial.

The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and docosahexaenoic acid (DHA) has been related to testosterone levels in epidemiological analyses. The aim of this study was to assess whether the n-3 fatty acids affects testosterone levels in post-myocardial infarction (MI) patients, who are at risk of testosterone deficiency. In a double-blind, placebo-controlled trial of low-dose supplementation of n-3 fatty acids, we included 1850 male post-MI patients aged 60-80 years who participated in the Alpha Omega Trial. Patients were randomly allocated to margarines that provided 400 mg/day of EPA-DHA (n = 453), 2 mg/day of ALA (n = 467), EPA-DHA plus ALA (n = 458), or placebo (n = 472). Serum testosterone levels were assessed at baseline and after 41 months using whole day blood samples obtained at the subjects' home or at the hospital. Subjects were on average age of 68.4 (SD 5.3) years old and had baseline mean serum total testosterone of 14.8 (SD 5.6) nmol/L. The four randomized groups did not differ for baseline characteristics. ALA, EPA-DHA, and EPA-DHA plus ALA supplementation did not affect serum total testosterone compared to placebo. Moreover, n-3 fatty acid supplementation did not affect the risk of incident testosterone deficiency (n = 76 with total testosterone <8.0 nmol/L). We conclude that n-3 fatty acids supplementation did not affect serum total testosterone in men who had had a MI.

The effect of conjugated linoleic acid, a natural trans fat from milk and meat, on human blood pressure: results from a randomized crossover feeding study.

Cis-9, trans-11 conjugated linoleic acid (CLA) is a natural trans fatty acid that is largely restricted to ruminant fats and consumed in foods and supplements. Its role in blood pressure (BP) regulation is still unclear. We examined the effect of cis-9, trans-11 CLA on BP compared with oleic acid. A total of 61 healthy volunteers were sequentially fed each of 3 diets for 3 weeks, in random order, for a total of 9 weeks. The diets were identical except for 7% of energy (18.9 g in a diet of 10 MJ day(-1)) that was provided either by oleic acid, by industrial trans fatty acids or by cis-9, trans-11 CLA. We measured BP on two separate days at the end of each intervention period. At baseline, mean BP was 113.8±14.4 mm Hg systolic and 66.3±9.6 mm Hg diastolic. The effect of the CLA diet compared with the oleic acid diet was 0.11 mm Hg (95% confidence interval: -1.27, 1.49) systolic and -0.45 mm Hg (-1.63, 0.73) diastolic. After the industrial trans fatty acid diet, the effect was 1.13 mm Hg (-0.25, 2.51) systolic and -0.44 mm Hg (-1.62, 0.73) diastolic compared with the oleic acid diet. Our study suggests that short-term high intakes of cis-9,trans-11 CLA do not affect BP in healthy volunteers.

Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial.

BACKGROUND: High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking. OBJECTIVE: To investigate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on cognitive performance. METHODS: Double-blind, placebo-controlled trial involving 302 cognitively healthy (Mini-Mental State Examination score > 21) individuals aged 65 years or older. Participants were randomly assigned to 1,800 mg/d EPA-DHA, 400 mg/d EPA-DHA, or placebo capsules for 26 weeks. Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention, sensorimotor speed, memory, and executive function. RESULTS: The mean age of the participants was 70 years, and 55% were male. Plasma concentrations of EPA-DHA increased by 238% in the high-dose and 51% in the low-dose fish oil group compared with placebo, reflecting excellent compliance. Baseline scores on the cognitive tests were comparable in the three groups. Overall, there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo. CONCLUSIONS: In this randomized, double-blind, placebo-controlled trial, we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance.

Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials.

Calcium plays a role in blood pressure (BP) regulation, but the importance of supplemental calcium intake for the prevention of hypertension is still debated. We conducted a meta-analysis of randomized controlled trials to determine the effect of calcium supplementation on BP. A systematic search for randomized trials of calcium supplementation and BP in non-pregnant subjects was performed in Medline from 1966 to June 2003. Seventy-one trials were identified, 40 of which met the criteria for meta-analysis (total of 2492 subjects). Two persons independently extracted data from original publications on changes in calcium intake and BP. In addition, data were collected on subjects' characteristics, that is, age, gender, initial BP and initial calcium intake. A random effects model was used to obtain the effect of calcium supplementation on BP, overall and in predefined population subgroups. Calcium supplementation (mean daily dose: 1200 mg) reduced systolic BP by -1.86 mm Hg (95% confidence interval: -2.91 to -0.81) and diastolic BP by -0.99 mm Hg (-1.61 to -0.37). In people with a relatively low calcium intake (< or =800 mg per day) somewhat larger BP estimates were obtained, that is, -2.63 (-4.03 to -1.24) for systolic BP and -1.30 (-2.13 to -0.47) for diastolic BP. Our study suggests that an adequate intake of calcium should be recommended for the prevention of hypertension. More research on BP in people with calcium-deficient diets is warranted.

Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials.

The objective of the study was to assess the blood pressure response to changes in sodium and potassium intake and examine effect modification by age, gender, blood pressure, body weight and habitual sodium and potassium intake. Randomised trials of sodium reduction or potassium supplementation and blood pressure were identified through reference lists of systematic reviews and an additional MEDLINE search (January 1995-March 2001). A total of 40 sodium trials and 27 potassium trials in adults with a minimum duration of 2 weeks were selected for analysis. Data on changes in electrolyte intake and blood pressure during intervention were collected, as well as data on mean age, gender, body weight, initial electrolyte intake and initial blood pressure of the trial populations. Blood pressure effects of changes in electrolyte intake were assessed by weighted metaregression analysis, overall and in strata of trial population characteristics. Analyses were repeated with adjustment for potential confounders. Sodium reduction (median: -77 mmol/24 h) was associated with a change of -2.54 mmHg (95% CI: -3.16, -1.92) in systolic blood pressure and -1.96 mmHg (-2.41, -1.51) in diastolic blood pressure. Corresponding values for increased potassium intake (median: 44 mmol/24 h) were -2.42 mmHg (-3.75, -1.08) and -1.57 mmHg (-2.65, -0.50). Blood pressure response was larger in hypertensives than normotensives, both for sodium (systolic: -5.24 vs -1.26 mmHg, P < 0.001; diastolic: -3.69 vs -1.14 mmHg, P < 0.001) and potassium (systolic: -3.51 vs -0.97 mmHg, P=0.089; diastolic: -2.51 vs -0.34 mmHg, P=0.074). In conclusion, reduced intake of sodium and increased intake of potassium could make an important contribution to the prevention of hypertension, especially in populations with elevated blood pressure.

Tea flavonoids may protect against atherosclerosis: the Rotterdam Study.

BACKGROUND: Epidemiological studies have indicated a protective role of dietary flavonoids in cardiovascular disease, but evidence is still conflicting. Tea is the major dietary source for flavonoids in Western populations. We studied the association of tea intake with aortic atherosclerosis in a general population. METHODS: The present analysis formed part of the Rotterdam Study, a prospective study of men and women 55 years and older. Dietary intakes were assessed at baseline by a trained dietician who used a semiquantitative food frequency questionnaire. Calcified plaques in the abdominal aorta were radiographically detected after 2 to 3 years of follow-up. Aortic atherosclerosis was classified as "mild," "moderate," or "severe," according to the length of the calcified area (<1 cm, 1-5 cm, and >5 cm, respectively). The association of tea intake with severity of aortic atherosclerosis was studied in 3454 subjects who were free of cardiovascular disease at baseline. Data were analyzed by logistic regression, adjusting for age, sex, body mass index (calculated as weight in kilograms divided by the square of height in meters), smoking, education, and intake of alcohol, coffee, vitamin antioxidants, total fat, and total energy. RESULTS: Multivariable analyses showed a significant, inverse association of tea intake with severe aortic atherosclerosis. Odds ratios decreased from 0.54 (95% confidence interval [CI], 0.32-0.92) for drinking 125 to 250 mL (1-2 cups) of tea to 0.31 (CI, 0.16-0.59) for drinking more than 500 mL/d (4 cups per day). The associations were stronger in women than in men. The association of tea intake with mild and moderate atherosclerosis was not statistically significant. CONCLUSION: This study indicates a protective effect of tea drinking against ischemic heart disease.

Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study.

BACKGROUND: Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease. OBJECTIVE: We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population. DESIGN: The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression. RESULTS: Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E. CONCLUSION: The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI.