Three randomized placebo-controlled clinical trials in mild hypertensives are proposed to assess the hypotensive potential of dietary polyunsaturated fatty acids in fish, oil, and of dietary magnesium, alone and with supplemental potassium. 1. The n-3 (omega-3) fatty acids in fish oil favorably affect the balance between vasodilating and vasoconstricting prostanoids, and hypotensive effects of fish oils have been found in normal volunteers. Therefore, two doses of a highly purified and standardized preparation of n-3 fatty acids, 4g and 8g/d, will be administered to 30 hypertensive patients for three months, and placebo for a third three-month period in a crossover design. 2. Magnesium is primarily an intracellular cation that relaxes smooth muscle in animal models, in part by decreasing the intracellular concentration of the vasoconstrictor, calcium. There is suggestive evidence that, in humans, systemic blood pressure (BP) is lowered by supplemental magnesium. Moreover, since dietary magnesium regulates cellular potassium content, synergism may exist between these two cations for lowering BP. Therefore, 120 untreated mild hypertensives will be randomized into four groups of 30 subjects who will receive daily for six months either 1) magnesium, 375mg, 2) potassium 60mmoles, 3) magnesium and potassium, or 4) matching placebos. To study the hypotensive mechanism of magnesium, changes in intracellular magnesium and free calcium will be determined in the subjects' blood mononuclear cells and related to the changes in BP. 3. A similar trial of magnesium and potassium will be conducted in mild hypertensives who are being treated with diuretics since diuretics deplete Mg and K and the hypotensive effect of oral repletion may be potentiated. Blood pressure will be measured on multiple occasions throughout the study at the clinic and at the subjects' homes to provide an extensive record of treatment effects. Each study will have over 90% power to detect a significant hypotensive effect of treatment over placebo of 4mm systolic and 3mm diastolic BP. Biochemical validation of compliance with each treatment will be obtained. The discovery of an effective dietary supplement to treat mild hypertension would be of great interest and practical importance.
