Description

Phosphorus is an essential macromineral in human nutrition and plays pivotal roles in the structure and function of the body. Phosphorus, in its pentavalent phosphate form, is essential for the process of bone mineralization and makes up the structure of bone. Approximately 85% of phosphorus in the adult body is in bone. Phosphorus in the form of phospholipids makes up the structure of cellular membranes. Phosphorus also makes up the structure of nucleic acids and nucleotides, including adenosine triphosphate, among other things. Life has been said to be built around phosphorus.

The ability of cells to actively transport phosphate is recognized as a requirement for mineralization in bone. There is some recent evidence that phosphate may regulate the expression of a gene that might be involved in bone mineralization. Phosphate has been found to regulate the expression of the phosphorylated glycoprotein osteopontin. Osteopontin is thought to modulate hydroxyapatite crystal elongation, among other things.

Phosphorus is a non-metallic element with atomic number 15 and an average atomic weight of 30.97 daltons. Its symbol is P. Phosphorus occurs in nature as phosphates in the soil and, in particular, the mineral apatite. The total adult body content of phosphorus is about 700 grams. It accounts for about 2%-4% of the dry weight of most cells.

Phosphorus, mainly in the form of phosphates, is widely distributed in the food supply, and phosphorus intake from the normal diet is usually sufficient to meet the body's phosphorus needs. Milk and milk products are particularly rich sources of phosphorus. One liter of milk contains about 1,000 milligrams of phosphorus. Phosphorus deficiency states, however, do occur but usually they are caused by some disease process. For example, those with malabsorption syndromes and those with diseases causing renal tubular losses of phosphorus can become phosphorus depleted. In addition, those with malnutrition, alcoholics and critically ill patients, such as those being treated for diabetic ketoacidosis, are at risk for phosphorus deficiency, as well as phosphorus imbalance. The so-called refeeding syndrome can cause hypophosphotemia which may be life-threatening.

Phosphorus deficiency can result in anorexia, impaired growth, osteomalacia, skeletal demineralization, proximal muscle atrophy and weakness, cardiac arrhythmias, respiratory insufficiency, increased erythrocyte and lymphocyte dysfunction, susceptibility to infectious rickets, nervous system disorders and even death. Phosphate salts are used in the treatment of phosphorus deficiency. Besides their use for the treatment of phosphorus deficiency, phosphorus supplements are not widely used in the United States. The one exception is calcium phosphate, which is mainly used as a delivery form of calcium.

Actions & Pharmacology

Actions

Supplemental phosphorus is used to treat phosphorus deficiency. Calcium phosphate is mainly used as a delivery form of calcium. Phosphorus has putative ergogenic (exercise performance-enhancement) activity.

Mechanism of Action

Phosphate salts are delivery forms of phosphorus and are used parenterally and orally under conditions of phosphate deficiency.

See Calcium for actions and mechanism of actions of that nutrient.

Short term phosphate-loading, using phosphate salts such as dibasic calcium phosphate (CaHPO₄), tribasic sodium phosphate (Na₃PO₄) or dibasic sodium and dibasic potassium phosphates, are used by some athletes who are not phosphorus deficient for performance enhancement.

The effectiveness of phosphate-loading is questionable. The mechanism proposed for this putative effect is attributed to the possible increase of 2, 3-diphosphoglycerate (2,3-DPG) with increased intake of phosphate. 2,3-DPG shifts the oxyhemoglobin dissociation curve to the right, thus allowing a greater unloading of oxygen at the tissue level. Although a few studies suggest that phosphate supplementation in phosphorus-sufficient subjects may increase 2,3-DPG levels in erythrocytes, most studies have reported that it does not have this effect.

Pharmacokinetics

Phosphorus supplements are inorganic phosphate salts of sodium, potassium or calcium. Calcium phosphate is a supplement used to supply both calcium and phosphorus. The efficiency of absorption of inorganic forms of phosphorus from the gastrointestinal tract ranges from 55% to 70% in adults. The efficiency of absorption of food phosphorus, which is a mixture of inorganic and organic forms of phosphorus, is similar. Organic forms of phosphorus are hydrolyzed by phosphatases, and therefore most phosphorus absorption occurs as absorption of inorganic phosphate. Absorption of phosphate occurs by both a saturable, active transport process and by passive diffusion. The saturable, active transport process is stimulated by the active form of vitamin D, 1, 25 dihydroxycholecalciferol (1, 25 (OH₂) D₃). The absorption of phosphorus is mainly via the passive, concentration-dependent process.

Phosphorus is transported via the portal circulation to the liver where the hepatocytes extract a fraction of it for their metabolic requirements. Phosphorus is transported via the systemic circulation to the various tissues of the body, where it is used for the metabolic requirements of these tissues. Excretion of phosphorus is mainly via the kidneys. Phosphorus is freely filtered in the glomerulus. Greater than 80% of the filtered phosphorus is reabsorbed in the proximal tubule and a small amount in the distal tubule. Parathyroid hormone adjusts the renal clearance of phosphorus. In the healthy adult, urine phosphorus is essentially equal to absorbed phosphorus.

Indications & Usage

Apart from its use in conditions of phosphorus deficiency, supplemental phosphorus has produced mixed results in tests of its putative ability to enhance exercise performance.

Overdosage

There are no reports of overdosage with oral phosphorus supplements in healthy individuals.

Dosage

Sodium phosphate is available as monobasic sodium phosphate (NaH₂PO₄), dibasic sodium phosphate (Na₂HPO₄) and tribasic sodium phosphate (Na₃PO₄). Potassium phosphate is available as monobasic potassium phosphate (KH₂PO₄), dibasic potassium phosphate (K₂HPO₄) and tribasic potassium phosphate (K₃PO₄). There are also preparations which are mixtures of the different forms. Monobasic sodium and potassium phosphates are the least basic, and tribasic sodium and potassium phosphate are the most basic of these salts. Use of these salts for the treatment of phosphorus deficiency requires medical supervision.

Calcium phosphate salts used for nutritional supplementation are tribasic calcium phosphate (Ca₃(PO₄)₂) and dibasic calcium phosphate (CaHPO₄). These are used mainly as calcium supplements (see Calcium for dosage).

Some athletes use calcium phosphate for phosphate-loading.

Several homeopathic remedies are phosphate salts. They include kali phosphoricum (potassium phosphate), ferrum phosphoricum (iron phosphate), magnesia phosphorica (magnesium phosphate), natrum phosphoricum (sodium phosphate) and mixtures of phosphates called biochemic phosphates.

Milk is frequently recommended for phosphorus supplementation in phosphorus-deficient individuuals. One milliliter of milk contains approximately one milligram of phosphorus.

The Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences has recommended the following adequate intakes (AI) and Recommended Dietary Allowance (RDA) for phosphorus:

A NOAEL (No-Observed-Adverse-Effect Level) for phosphorus for adults is 10.2 grams/day.

Tolerable upper Intake Levels (UL) for phosphorus for adults is calculated by the Food and Nutrition Board by dividing the NOAEL for phosphorus by an uncertainty factor (UF) of 2.5.

Literature

Research & Summary

Oral, enteral and parenteral phosphorus are used as replacement therapy in hypophosphatemia, a condition seen in some with chronic alcoholism or diabetic ketoacidosis, among others.

Claims that supplemental phosphorus enhances athletic performance are supported by some studies and are refuted by others. The majority of studies provide some support. In an early study, phosphate loading in ten trained distance runners attenuated increases in blood lactate after exercise. In another study, 1,000 milligrams of tribasic sodium phosphate four times a day for six days significantly increased maximal oxygen uptake and ventilatory anaerobic threshold. Phosphate loading did not, however, significantly improve five-mile run times compared with placebo, in these subjects.

Tribasic sodium phosphate loading enhanced endurance performance in competitive cyclists and triathletes in a placebo-controlled study. Dosage was 1 gram of phosphate four times a day for three days prior to exercise testing. Another study has suggested that athletes on caloric-restricted diets may benefit from increased dietary phosphorus intake. Researchers have cited limited data indicating that low-phosphorus status may increase incidence of muscle cramps. Again, increased dietary intake of, rather than supplementation with, phosphorus has been suggested. Long-term phosphate supplementation may pose serious health risks.

Not all studies have found benefit from phosphate loading. In a double-blind trial, 1.24 grams of sodium acid phosphate and potassium phosphate, administered one hour before exercise, produced results no better than placebo in male subjects, in terms of leg power and performance on a high-intensity treadmill exercise. Calcium phosphate loading similarly failed to improve work tolerance or aerobic capacity among male runners, compared with placebo, and, in yet another trial, dibasic calcium phosphate loading was found to be ineffective as an ergogenic aid in subjects of different aerobic fitness levels.

More study will be needed to determine whether phosphate loading has significant benefits in exercise performance.

Contraindications, Precautions & Adverse Reactions

Contraindications

Phosphorus supplements are contraindicated in those with hyperphosphatemia and in those with severely impaired renal function (less than 30% of normal). In addition, potassium phosphate is contraindicated in those with hyperkalemia, and calcium phosphate is contraindicated in those with hypercalcemia.

Inorganic phosphates are contraindicated in those with hypersensitivity to any component of an inorganic phosphate-containing supplement.

Precautions

The use of supplementary phosphorus in those with phosphorus deficiency requires medical supervision.

Pregnant women and nursing mothers should avoid phosphorus intakes greater than RDA amounts.

Athletes who use supplementary phosphorus should avoid using such supplements for more than four to six days since they may cause hypocalcemia.

Adverse Reactions

The most common adverse reaction with use of sodium or potassium phosphate is diarrhea. The salts are less likely to cause diarrhea when they are used by phosphorus-deficient individuals than when used by those with normal phosphorus status. Other gastrointestinal symptoms that may occur include nausea, vomiting and stomach pain. Those with renal failure may develop hyperphosphatemia and hypocalcemia with potassium or sodium phosphate supplementation. Hyperphosphatemia can result in ectopic calcification. Prolonged use of high doses of inorganic phosphate salts may result in hypocalcemia even in healthy individuals with normal renal function.

Interactions

Drugs

Aluminum-containing antacids: Aluminum-containing antacids are used in the treatment of hyperphosphatemia. Concomitant intake of aluminum-containing antacids and phosphorus will decrease absorption of phosphorus (in the phosphate form).

Nutritional Supplements

Zinc: Concomitant intake of zinc and phosphate salts (sodium phosphate, potassium phosphate, calcium phosphate) may decrease the absorption of zinc.