Effect on Blood Pressure of Potassium, Calcium, and Magnesium in Women With Low Habitual Intake

Abstract

In populations, dietary intakes of potassium, calcium, and magnesium each have been inversely associated with blood pressure. However, most clinical trials in normotensive populations have not found that dietary supplements of these minerals lowered blood pressure. We tested the hypothesis that normotensive persons who have low habitual intake of these minerals would be particularly responsive to supplementation. Three hundred normotensive women in the Nurses Health Study II (mean age, 39 years), whose reported intakes of potassium, calcium, and magnesium were between the 10th and 15th percentiles, received for 16 weeks’ duration daily supplements of either potassium 40 mmol, calcium 30 mmol (1200 mg), magnesium 14 mmol (336 mg), all three minerals together or placebos. At baseline, mean (±SD) 24-hour ambulatory blood pressures were 116±8 and 73±6 mm Hg systolic and diastolic, respectively, and mean dietary intakes of potassium, calcium, and magnesium were 62±20 mmol/d, 638±265 mg/d, and 239±79 mg/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were significant for potassium, −2.0 (−3.7 to −0.3) and −1.7 (−3.0 to −0.4), but not for calcium, −0.6 (−2.2 to 1.0) and −0.7 (−2.0 to 0.6), or for magnesium, −0.9 (−2.6 to 0.8) and −0.7 (−2.2 to 0.8). The administration of calcium and magnesium with potassium did not enhance the effect of potassium alone; and the changes in blood pressure were not significant −1.3 (−3.0 to 0.4) and −0.9 (−2.2 to 0.4). In conclusion, potassium, but not calcium or magnesium supplements, has a modest blood pressure–lowering effect in normotensive persons with low dietary intake. This study strengthens evidence for the importance of potassium for blood pressure regulation in the general population.

Dietary potassium, calcium, and magnesium have each been inversely associated with blood pressure in populations.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Since these cations exist together in commonly eaten foods such as fruits, nuts, vegetables, cereals, and dairy products, their intakes are highly correlated. This collinearity makes it difficult in epidemiological studies to distinguish which among these dietary cations has a causal role in blood pressure regulation.1 Meta-analysis of clinical trials found a significant blood pressure–lowering effect (−5.9/−3.4 mm Hg) for potassium supplementation in hypertensive but not in normotensive persons.10 16 Meta-analysis suggested that calcium supplementation has a small effect (−1.7 mm) on systolic blood pressure in hypertensive but not normotensive patients.17 18 Magnesium produced inconsistent results in trials of hypertensives,19 20 21 22 23 24 25 26 27 28 and no effect in normotensives.29 30 The lack of effect of mineral supplements in clinical trials of normotensives is inconsistent with the significant associations in epidemiological studies, since normotensive persons comprise the vast majority of the population samples.

One possible explanation for the divergence in findings between the observational epidemiologic studies and the clinical trials in normotensive persons is that a subset of the population that is relatively deficient from low intake of minerals may be particularly responsive to supplementation. Epidemiological studies tend to compare those in the lowest category of intake, which serves as a point of reference, with persons having average or high intake. In contrast, most trials have tested the effect of raising an average intake to a high intake. An alternative explanation is that these minerals work in concert to reduce blood pressure and that they would be more effective when given together. To explore both possibilities, we conducted a clinical trial of potassium, magnesium, and calcium supplements, given singly and together, to participants in the Nurses Health Study II who reported habitually low intakes of these minerals.