Correspondence (letter to the editor): Hypophosphatemia Also Increases the Risk

In addition to hyperphosphatemia, hypophosphatemia also increases the cardiovascular risk (1). Low serum concentrations reduce the eNOS activity and lead to insulin resistance, ATP deficiency, and—via lowered 2,3-diphosphoglycerate—to chronic tissue hypoxia causing endothelial damage. Risk factors such as diabetes or obesity are often associated with hypophosphatemia (1, 2).

The causes of clinically relevant phosphate deficiency are not only hypophosphatemic osteomalacia, malnutrition, and sepsis—as mentioned in the section entitled “The risks of hypophosphatemia” – but, in addition to poorly controlled diabetes, also chronic alcohol misuse, major surgery, infections (for example, legionellosis, malaria), COPD, long-term hemodialysis, and treatment with antacids, diuretics, catecholamines, imatinib, and others.

Since serum phosphate accounts for less than 1% of the total phosphate in the body, substantial intracellular phosphate deficiency may exist even in the presence of a normal or even raised serum concentration. Phosphate homeostasis is subject to very complex regulation, whose mechanics have been understood only rudimentarily, which is affected not only by FGF-23, parathormone, and vitamin D, but also by pH, insulin, growth hormone, estrogens, stress hormones, calcium, and magnesium. The cardiovascular risk is probably determined more by an impaired phosphate metabolism than by the very low amount of extracellular phosphate alone. Children, for example, often have much higher serum phosphate concentrations than adults but none the less do not have an increased risk, and in a recent osteoporosis study (3), hypercalcemia was confirmed as a cardiovascular risk factor whereas hyperphosphatemia was not.

The serum concentrations of people with healthy kidneys correlate only minimally with the phosphate content of the ingested food (2); besides, because of their circadian rhythm they fluctuate widely over the course of the day in the individual, and consequently serum phosphate readings, which are usually taken only once a day, are not always representative for the average serum concentration over 24 hours.

It is possible that for a healthy diet, the absolute phosphate content of foodstuffs is less important than, for example, the ratio of calcium to phosphate in the interaction with magnesium and vitamin D.