Objective: Increasing 1, 25‐dihydroxyvitamin D in response to low‐calcium diets stimulates adipocyte Ca²⁺ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans.Research Methods and Procedures: We performed a randomized, placebo‐controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high‐calcium diet (standard diet supplemented with 800 mg of calcium/d), or high‐dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo).Results: Patients assigned to the standard diet lost 6.4 ± 2.5% of their body weight, which was increased by 26% (to 8.6 ± 1.1%) on the high‐calcium diet and 70% (to 10.9 ± 1.6% of body weight) on the high‐dairy diet (p < 0.01). Fat loss was similarly augmented by the high‐calcium and high‐dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 ± 7.9% of total fat loss on the low‐calcium diet, and this fraction was increased to 50.1 ± 6.4% and 66.2 ± 3.0% on the high‐calcium and high‐dairy diets, respectively (p < 0.001).Discussion: Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.

Dietary calcium plays a pivotal role in the regulation of energy metabolism; high calcium diets attenuate adipocyte lipid accretion and weight gain during periods of overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Intracellular Ca²⁺ has a key role in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca²⁺ resulting in stimulation of lipogenic gene expression and lipogenesis, suppression of lipolysis, and increased lipid filling and adiposity. Moreover, we have recently demonstrated that the increased calcitriol released in response to low calcium diets stimulates Ca²⁺ influx in human adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a human-like pattern) respond to low calcium diets with accelerated weight gain and fat accretion, while high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, while high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. These findings are further supported by clinical and epidemiological data demonstrating a profound reduction in the odds of being obese associated with increasing dietary calcium intake. Notably, dairy sources of calcium exert a significantly greater anti-obesity effect than supplemental sources in each of these studies, possibly due to the effects of other bioactive compounds, such as the angiotensin converting enzyme inhibitor found in milk, on adipocyte metabolism, indicating an important role for dairy products in the control of obesity.

Dietary calcium plays a pivotal role in the regulation of energy metabolism because high-calcium diets attenuate adipocyte lipid accretion and weight gain during the overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, which thereby markedly accelerates weight loss. Intracellular Ca²⁺ plays a key regulatory role in adipocyte lipid metabolism and triacylglycerol storage; increased intracellular Ca²⁺ results in the stimulation of lipogenic gene expression and lipogenesis and the suppression of lipolysis, which results in increased lipid filling and increased adiposity. Moreover, the increased calcitriol produced in response to low-calcium diets stimulates adipocyte Ca²⁺ influx and, consequently, promotes adiposity, whereas higher-calcium diets inhibit lipogenesis, inhibit diet-induced obesity in mice, and promote lipolysis, lipid oxidation, and thermogenesis. Notably, dairy sources of calcium markedly attenuate weight and fat gain and accelerate fat loss to a greater degree than do supplemental sources of calcium. This augmented effect of dairy products relative to supplemental calcium is likely due to additional bioactive compounds, including the angiotensin-converting enzyme inhibitors and the rich concentration of branched-chain amino acids in whey, which act synergistically with calcium to attenuate adiposity. These concepts are confirmed by epidemiologic data and recent clinical trials, which indicate that diets that include ≥3 daily servings of dairy products result in significant reductions in adipose tissue mass in obese humans in the absence of caloric restriction and markedly accelerate weight and body fat loss secondary to caloric restriction compared with diets low in dairy products. These data indicate an important role for dairy products in both the prevention and treatment of obesity.