Abstract
Next to smoking, obesity is the second leading preventable risk factor for cancer, but increasing rates of obesity and overweight are estimated to overtake smoking as the leading preventable cancer risk factor. Few research studies have investigated the dysregulated endocrine metabolism of dietary phosphate as a potential mediating factor in the association of obesity with cancer. Phosphate toxicity, the accumulation of excess phosphate in the body from dysregulated phosphate metabolism, is associated with tumorigenesis. High levels of hormones that regulate phosphate metabolism, such as parathyroid hormone and fibroblast growth factor 23, are also associated with obesity, providing a potential link between obesity and phosphate toxicity. Increased dietary intake of inorganic phosphate is linked to excessive consumption of foods processed with phosphate additives, and consumption of ultra-processed foods is associated with an increase in the incidence of obesity. Sugar-sweetened beverages provide the single largest source of sugar and energy intake in the U.S. population, and colas containing phosphoric acid are associated with tumorigenesis, suggesting another potential connection between obesity and cancer. Furthermore, dietary phosphate is positively correlated with increases in obesity, central obesity, and metabolic syndrome. The present perspective article proposes that dysregulated dietary phosphate potentially mediates the association of obesity with cancer.
Highlights
A higher bodyweight has been associated with reduced cancer risk—an obesity paradox that some researchers suggest may be related to selection bias from reliance on body mass index (BMI), which does not measure fat mass and fat-free mass [5]
A recent prospective cohort study showed that consumption of ultraprocessed foods was associated with a 79% increase in the incidence of obesity measured by BMI and a 30% increase in the incidence of abdominal obesity measured by waist circumference (WC) [49]
The evidence presented in this paper supports an endocrine pathway in which dysregulated dietary phosphate potentially mediates the association of obesity with cancer
Summary
The dietary mineral phosphorus, often found in chemical combination with oxygen as phosphate (PO4 ), is an essential micronutrient with a dietary reference intake (DRI) of. 700 mg/day for adults [10]. Bones and teeth contain 85% of total body phosphate. Inorganic phosphate (Pi) forms hydroxyapatite with calcium, which mineralizes the extracellular matrix of bone. The lipid bilayers of cell membranes contain phosphate, and phosphate is a component in nucleic acids, deoxyribonucleic acid (DNA), and ribonucleic acid (RNA). Energy is derived from the metabolism of adenosine triphosphate (ATP) and adenosine diphosphate (ADP). Phosphate acts as a urinary buffer, and many enzymatic reactions involve inorganic phosphate
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