Detrimental Role of High Dietary Phosphate Intake on Skeletal Muscle ATP Synthesis in Healthy Humans

Abstract

Background Inorganic phosphate (Pi) is found in large quantities in processed food to increase palatability and longevity on the shelf. Prior work from our group using animal models suggests that increased dietary Pi is associated with lower resting metabolic rate as well as downregulation of fatty acid oxidation and upregulation of carbohydrate metabolism. We hypothesized that higher dietary Pi would be associated with lower resting mitochondrial function as measured by in-vivo, 31P MR spectroscopy. Methods The study sample included participants from the Dallas Heart Study without history of cardiovascular vascular disease or kidney disease. Dietary Pi (in mg/kcal/day) was measured from a 24-hour dietary recall (ASA24®). 31P MR spectroscopy (7T, Philips) was used for the assessment of ATP synthesis production at rest in the calf muscle using wideband inversion transfer technology. We calculated the correlation coefficient (Pearson's) to quantify the association between both dietary Pi intake normalized to total energy intake (mg/Kcal/day) and urinary Pi (mg/gram of creatinine, Cr) with resting ATP synthesis (mM/min). Results We studied 12 individuals (46% female) with a mean age and BMI of 59 and 28, respectively. Within this population, 15% were African American and 46% were non-white. Hypertension was present in 46% and diabetes in 23%. All but one participant had normal renal function (mean GFR 80 mL/min). The average dietary Pi intake was 1408 mg and the average urinary Pi was 44 mg/L. Results are shown in figure 1 and 2. Figure 1 demonstrates an inverse association between dietary Pi and resting ATP synthesis (r = -0.62, p= 0.03). We observed a directionally similar pattern of association between urinary Pi/Cr and resting ATP synthesis (Figure 2). Conclusions Our study suggests a deleterious role of inorganic phosphate on resting ATP synthesis in skeletal muscle. Given the importance of muscle mitochondrial function for exercise capacity, these data suggest that excess dietary Pi intake, associated with the Western diet, may explain reduced physical activity, which may predispose the general population to increased cardiovascular risk.