Phosphorus is an abundant mineral that exists primarily as phosphate, a charged particle necessary for numerous biological processes. Phosphate is a structural component of adenosine triphosphate (ATP), the body’s main energy currency, making it integral to energy production. This mineral is also essential for the structure of cell membranes and nucleic acids. Approximately 85% of the body’s total phosphorus is stored within the bones and teeth. Low phosphorus in the blood, called hypophosphatemia, is defined in adults as a serum phosphate concentration below 2.5 milligrams per deciliter (mg/dL). The body maintains phosphate levels through a complex interplay between the gut, the bones, and the kidneys.
Low Phosphorus Due to Poor Intake or Absorption
The simplest cause of low phosphorus is an insufficient supply, either from a lack of consumption or a failure to absorb the mineral in the digestive tract. Since phosphorus is widely present in many common foods, a simple dietary deficiency is uncommon in otherwise healthy individuals. However, severe malnutrition, chronic alcoholism, or prolonged periods of starvation can deplete the body’s phosphate reserves over time.
Phosphate absorption in the small intestine relies heavily on the active form of Vitamin D. A deficiency in Vitamin D impairs this absorption, reducing the amount of phosphate entering the bloodstream. Certain gastrointestinal disorders can also physically impede the absorption process. Conditions like Crohn’s disease, celiac disease, or chronic diarrhea damage the intestinal lining, preventing the mineral from entering circulation.
The ingestion of certain substances can chemically block absorption within the gut. Phosphate binders, which are designed to treat high phosphate levels, work by binding to dietary phosphate in the intestine. This forms an insoluble complex that is then excreted in the feces, effectively lowering the amount of phosphate available to the body. Overuse of aluminum-containing antacids can similarly bind phosphate, leading to poor intestinal absorption and hypophosphatemia.
Low Phosphorus Due to Increased Urinary Excretion
The kidneys are the primary regulators of phosphate balance, determining how much of the filtered mineral is reabsorbed back into the blood versus how much is excreted in the urine. Hypophosphatemia occurs when the kidneys inappropriately excrete too much phosphate, a process known as renal phosphate wasting.
A significant cause of increased urinary loss is hyperparathyroidism, where the parathyroid glands secrete excessive parathyroid hormone (PTH). PTH acts on the kidney tubules, signaling them to reduce the reabsorption of phosphate. This mechanism, which involves downregulating sodium-phosphate cotransporters, ultimately causes phosphate to be flushed out in the urine.
A second category involves specific defects in the kidney tubules themselves, such as Fanconi syndrome, which can be acquired or inherited. This disorder results from a generalized dysfunction of the proximal tubule, impairing its ability to reclaim phosphate, glucose, amino acids, and other substances from the filtrate. Furthermore, certain intravenous iron formulations can lead to renal phosphate wasting by increasing the levels of fibroblast growth factor 23 (FGF23), a hormone that signals the kidneys to excrete phosphate.
Low Phosphorus Due to Internal Cellular Shifts
In some cases, the total amount of phosphate in the body may be normal, but the serum level drops because the mineral rapidly shifts from the bloodstream (extracellular space) into the cells (intracellular space). This internal redistribution often occurs during periods of sudden, high metabolic demand.
A prime example is refeeding syndrome, which can occur when severely malnourished individuals begin receiving nutrition again. The sudden influx of glucose stimulates a massive release of insulin, which is an anabolic hormone. Insulin drives glucose and phosphate into the cells to support glycolysis and the synthesis of new tissues, consuming large amounts of phosphate to produce ATP. This rapid movement depletes the serum phosphate concentration, leading to acute hypophosphatemia.
A similar physiological shift happens during the treatment of diabetic ketoacidosis (DKA). When insulin is administered to treat DKA, it quickly reverses this process, pushing phosphate back into the cells and causing a precipitous drop in the serum level. Another mechanism is respiratory alkalosis, caused by hyperventilation, which increases the blood’s pH. The resulting alkaline environment stimulates glycolysis, driving the mineral into the intracellular compartment.
Common Medications and Substances That Affect Phosphorus Levels
Several pharmaceutical agents can directly interfere with phosphate homeostasis, acting as a contributing cause of low serum levels.
Medications Causing Reduced Absorption
Phosphate binders, such as aluminum- or calcium-containing antacids, are commonly used to reduce high phosphate levels in patients with kidney disease. These agents prevent the absorption of dietary phosphate in the digestive tract. While effective, excessive or unmonitored doses can inadvertently lead to hypophosphatemia.
Medications Causing Increased Excretion
Certain diuretics, including loop diuretics like furosemide and carbonic anhydrase inhibitors like acetazolamide, increase the excretion of various electrolytes by the kidneys. These medications increase the amount of phosphate lost in the urine, contributing to renal phosphate wasting. Chemotherapeutic agents, such as ifosfamide and cisplatin, are known to be nephrotoxic and can cause damage to the kidney tubules. This damage can result in an acquired Fanconi syndrome, leading to excessive urinary phosphate loss.
Medications Causing Cellular Shifts
Finally, the administration of bicarbonate infusions can quickly correct metabolic acidosis, which then allows phosphate to shift rapidly back into the cells, similar to the mechanism seen in DKA treatment.