Calcium Modulation of Hypertension and Obesity: Mechanisms and Implications

AbstractRegulation of intracellular calcium plays a key role in hypertension and obesity. Dysregulation of calcium homeostasis appears to be a fundamental factor linking these conditions. Regulation of intracellular calcium in key disease-related target tissues by calcitrophic hormones provides the opportunity to modulate disease risk with dietary calcium. Overall, sub-optimal calcium intakes contribute to the etiology of salt-sensitivity and hypertension. High salt diets exert a calciuretic effect, serving to exacerbate the physiological consequences of sub-optimal calcium diets. Among these are increases in 1,25-dihydroxyvitamin D, which increases vascular smooth muscle intracellular calcium, thereby increasing peripheral vascular resistance and blood pressure. Dietary calcium reduces blood pressure in large part via suppression of 1,25-dihydroxyvitamin D, thereby normalizing intracellular calcium. The practical relevance of this approach has been confirmed in the DASH (Dietary Approaches to Stop Hypertension) trial, which demonstrated that increasing low-fat dairy product and fruit and vegetable consumption exerted profound blood pressure-lowering effects. The magnitude of this effect among hypertensives was comparable to that typically found in pharmacological trials of mild hypertension. 1,25-dihydroxyvitamin D also stimulates calcium influx in human adipocytes, resulting in stimulation of lipogenesis, inhibition of lipolysis and expansion of triglyceride stores. Accordingly, suppression of 1,25-dihydroxyvitamin D by dietary calcium has been identified as a target, which may contribute to the prevention and management of obesity. Indeed, laboratory, clinical and population data all indicate a significant anti-obesity effect of dietary calcium, although large-scale prospective clinical trials have not yet been conducted to definitively demonstrate the scope of this effect. Thus, available evidence indicates that increasing dietary calcium intakes may result in reductions in fat mass as well as in blood pressure.Keywordsblood pressurecalciumhypertensionobesity Key teaching points: • Calcitrophic hormones, including 1,25-dihydroxyvitamin D, regulate intracellular calcium levels in vascular smooth muscles cells and in adipocytes. This presents an opportunity to influence hypertension and metabolic disease risk using dietary calcium to modulate 1,25-dihydroxyvitamin D levels.• Increasing dietary calcium attenuates salt-sensitivity and lowers blood pressure, especially in hypertensive individuals.• A food pattern that emphasizes low-fat dairy products (3–4 servings daily) and fruits and vegetables (8 servings) exerts significant antihypertensive effects. These effects are comparable in magnitude to pharmacological management of mild hypertension.• 1,25-dihydroxyvitamin D stimulation of calcium influx in adipocytes results in increased lipogenesis, inhibition of lipolysis, and expanded triglyceride stores. Conversely, reducing 1,25-dihydroxyvitamin D levels by increasing dietary calcium results in reduction of fat mass and augmentation of weight and fat loss during caloric restriction. Key teaching points: • Calcitrophic hormones, including 1,25-dihydroxyvitamin D, regulate intracellular calcium levels in vascular smooth muscles cells and in adipocytes. This presents an opportunity to influence hypertension and metabolic disease risk using dietary calcium to modulate 1,25-dihydroxyvitamin D levels.• Increasing dietary calcium attenuates salt-sensitivity and lowers blood pressure, especially in hypertensive individuals.• A food pattern that emphasizes low-fat dairy products (3–4 servings daily) and fruits and vegetables (8 servings) exerts significant antihypertensive effects. These effects are comparable in magnitude to pharmacological management of mild hypertension.• 1,25-dihydroxyvitamin D stimulation of calcium influx in adipocytes results in increased lipogenesis, inhibition of lipolysis, and expanded triglyceride stores. Conversely, reducing 1,25-dihydroxyvitamin D levels by increasing dietary calcium results in reduction of fat mass and augmentation of weight and fat loss during caloric restriction.NotesPresented in part at Ross Products Research Conference on Medical Issues, "Synergy in Medical and Nutritional Therapy," November 6–8, 2000, Key Largo, Florida.