Phosphates, phosphorus

Phosphorus is a mineral found in many foods, such as milk, cheese, dried beans, peas, colas, nuts, and peanut butter. Phosphate is the most common form of phosphorus. In the body, phosphate is the most abundant intracellular anion. It is critical for energy storage and metabolism, for the utilization of many B-complex vitamins, to buffer body fluids, for kidney excretion of hydrogen ions, for proper muscle and nerve function, and for maintaining calcium balance. Phosphorus is vital to the formation of bones and teeth, and healthy bones and soft tissues require calcium and phosphorus to grow and develop throughout life. Inadequate intake of dietary phosphate can lead to hypophosphatemia (low levels of phosphate in the blood), which can lead to long-term potentially serious complications. Conversely, excess phosphate intake can lead to hyperphosphatemia (high blood phosphorus levels), which can occur particularly in people with impaired kidney function, and can lead to potentially serious electrolyte imbalances, adverse effects, or death.

In adults, phosphorus makes up approximately 1% of total body weight It is present in every cell of the body, although 85% of the body's phosphorus is found in the bones and teeth.

Phosphates are used clinically to treat hypophosphatemia, hypercalcemia (high blood calcium levels), as saline laxatives, and in the management of calcium-based kidney stones. They may also be of some benefit to patients with vitamin D resistant rickets, multiple sclerosis, and diabetic ketoacidosis.

Synonyms

Aluminum phosphate, calcium phosphate (bone ash, bone phosphate, calcium orthophosphate, calcium phosphate dibasic anhydrous, calcium phosphate dibasic dihydrate, calcium phosphate tribasic, di-calcium phosphate, dicalcium phosphate, dicalcium phosphates, neutral calcium phosphate, precipitated calcium phosphate, tertiary calcium phosphate, tricalcium phosphate, whitlockite), potassium phosphate (dibasic potassium phosphate, dipotassium hydrogen orthophosphate, dipotassium monophosphate, dipotassium phosphate, monobasic potassium phosphate, potassium acid phosphate, potassium biphosphate, potassium dihydrogen orthophosphate), MCI-196 (colestilan), sevelamar (Renagel), sodium phosphate (anhydrous sodium phosphate, dibasic sodium phosphate, disodium hydrogen orthophosphate, disodium hydrogen orthophosphate dodecahydrate, disodium hydrogen phosphate, disodium phosphate, phosphate of soda, sodium orthophosphate).

Brand Names: Fleet Enema, Fleet Phospho-soda, K-Phos MF, K-Phos Neutral, K-Phos No. 2, K-Phos Original, Neutra-Phos, Neutra-Phos-K, Uro-KP-Neutral.

Note on terminology: The term "phosphates" in this monograph refers to anhydrous sodium acid phosphate, dibasic sodium phosphate, dipotassium phosphate anhydrous, monobasic potassium acid phosphate, monobasic sodium phosphate, phosphorus, potassium phosphate, sodium biphosphate, and sodium phosphate.

Caution: Do not confuse phosphate salts with toxic substances such as organophosphates, or with tribasic sodium phosphates and tribasic potassium phosphates, which are strongly alkaline.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidence	Grade^*
Constipation Occasional constipation is an FDA-approved use of phosphates in adults and children, both in oral form and as an enema (for example, Fleet Enema). Phosphates are also used to restore bowel activity after surgery.	A
Hypercalcemia (high blood calcium levels) Phosphate salts (except for calcium phosphate) are effective in the treatment of hypercalcemia. However, intravenous phosphate for treating hypercalcemia may not be recommended, due to concerns about lowering blood pressure, excessively lowering calcium levels, heart attack, tetany, or kidney failure. Sudden hypotension (low blood pressure), kidney failure, and death have been reported after phosphate infusion.	A
Hypophosphatemia (low blood phosphorus level) Hypophosphatemia is an FDA-labeled use of phosphates in adults. Taking sodium phosphate or potassium phosphate is effective for preventing and treating most causes of hypophosphatemia, and should be directed under medical supervision. The underlying cause of the hypophosphatemia should be identified and corrected whenever possible.	A
Kidney stones (calcium oxalate stones) Kidney stones (nephrolithiasis) are an FDA-labeled use of phosphates in adults. Taking potassium and sodium phosphate salts orally may help prevent kidney stones in patients with hypercalciuria (high urine calcium levels), and in patients with kidney stones made of calcium oxalate. However, phosphate administration when stones are composed of magnesium-ammonium-phosphate or calcium phosphate may increase the rate of stone formation.	A
Laxative/bowel preparation for procedures This is an FDA-labeled use of phosphates in adults and children. Sodium phosphate taken orally or as an enema may be used for bowel cleansing in preparation for surgery, imaging studies, or endoscopy (for example, Fleet Phospho-soda, Fleet Enema). Phosphates appear to increase peristalsis and cause an influx of fluids into the intestine via osmotic action. Aluminum phosphate is used orally to neutralize gastric acid.	A
Refeeding syndrome prevention After periods of severe malnutrition or starvation (for example, anorexia nervosa), intravenous phosphate may be necessary in order to prevent a refeeding syndrome. Phosphate levels should be closely monitored in such patients.	B
Burns Patients with serious burns may lose phosphate, and replacement may be necessary.	C
Diabetic ketoacidosis The use of prophylactic phosphate therapy in diabetic ketoacidosis is controversial and may be considered, particularly in cases of low phosphate levels.	C
Hypercalciuria (high urine calcium levels) Long term, slow release neutral potassium phosphate has been shown to reduce calcium excretion in subjects with absorptive hypercalciuria, and appears to be well tolerated. This use of phosphates may be considered to prevent kidney stone formation.	C
Hyperparathyroidism This use of phosphates has not been clearly demonstrated as being beneficial in scientific studies.	C
Total parenteral nutrition (TPN) Critically ill patients receiving intravenous feedings often have low phosphate levels. Phosphate levels should be closely monitored in such patients, particularly if kidney function is impaired. Addition of phosphate to TPN solutions should be under the supervision of a licensed nutritionist.	C
Vitamin D resistant rickets This use of phosphates has not been clearly demonstrated as being beneficial in scientific studies.	C
Exercise performance Several studies report that taking phosphates orally does not improve exercise performance.	D

*Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use;
F: Strong scientific evidence against this use.

Grading rationale

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Cancer, clear cell carcinoma, depression, hypophosphatemic encephalopathy, multiple sclerosis, radioactive (thallium) parathyroid scanning enhancement, uterine papillary serous carcinoma.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

The National Academy of Sciences has recommended 700 milligrams of phosphorus per day in adults ages 18 years and older, including pregnant or breastfeeding women.

The Tolerable Upper Intake Level (UL) for adults ages 19-70 years-old is 4 grams per day; for adults 70 years and older the UL is 3 grams per day. The recommended UL in pregnant women is 3.5 grams per day, and in breastfeeding women is 4 grams per day. Phosphate salts should not be administered to patients with hyperphosphatemia, and should be used cautiously in those with impaired kidney function.

Doses typically range from 1-3 grams of phosphorous (as a phosphate salt (sodium phosphate or potassium phosphate) or elemental phosphate) per day by mouth for the treatment of calcium oxalate kidney stones, hypercalcemia, or hypophosphatemia. Doses are usually divided and taken throughout the day.

Fleet Enema (118 milliliters) can be used as a laxative when administered rectally. It should be administered as a single daily dose. Laxatives should not generally be used for more than one week. 4-8 grams of sodium phosphate dissolved in water has also been used as a saline laxative (should be taken with plenty of water).

Intravenous phosphate 50 millimoles (sodium 81 millimoles, potassium 9.5 millimoles) over 24 hours has been used during refeedng syndrome when serum phosphate falls below 0.5 millimoles per liter. Phosphate blood levels should be closely followed.

Children (younger than 18 years)

The recommended adequate intake in infants 0-6 months-old is 100 milligrams per day (additional phosphorus may be added to infant formulas); the recommended adequate intake in infants 7-12 months old is 275 milligrams per day; the recommended daily intake in children ages 1-3 years-old is 460 milligrams per day; the recommended daily intake in children ages 4-8 years-old is 500 milligrams per day; the recommended daily intake in children ages 9-18 years-old is 1,250 milligrams per day (including pregnant or breastfeeding females).

The Tolerable Upper Intake Level (UL) for infants aged 0-12 months-old is not clearly established and the source of intake should be from food and formula only; for children 1-8 years-old the UL is 3 grams per day; for children 9-18 years-old the UL is 4 grams per day.

Children under 12 years of age should not receive an adult size Fleet enema. Children 2 to 12 years of age may receive a Fleet Ready-To-Use Enema for children in a single daily dose (2 fluid ounces). Laxatives should not generally be used for more than one week.

Children 5 to 10 years-old may receive 5 milliliters Fleet Phospho-soda and should not exceed 10 milliliters in a 24-hour period. Children between 10 to 12 years-old may receive 10 milliliters and should not exceed 20 milliliters in a 24-hour period. Children over 12 years-old may receive a dose of 20 milliliters and should not exceed 45 milliliters in a 24-hour period. Do not administer to children under 5 years of age.

Children may also receive intravenous preparations, which should be given under the supervision of a licensed healthcare professional.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Avoid if allergic to any ingredients in phosphorus/phosphate preparations.

Brief Safety Summary

In general, sodium, potassium, aluminum, and calcium phosphates are likely safe when used orally in recommended doses for short-term periods by people without hyperphosphatemia, impaired kidney function, or other health conditions known to increase the risk of hyperphosphatemia (see below). Sodium phosphate is likely safe when used rectally for short-term periods in otherwise healthy individuals with normal kidney function. Long-term use or high doses used orally or rectally require monitoring of serum electrolytes. Intravenous phosphate is likely safe when used as an FDA-approved prescription drug under medical supervision in people without hyperphosphatemia, impaired kidney function, or other health conditions known to increase the risk of hyperphosphatemia. Phosphate (expressed as phosphorus) intake taken via any route that exceeds the tolerable upper intake level (UL) is possibly unsafe, and may cause hyperphosphatemia (low phosphate levels), hypocalcemia (low calcium blood levels), calcification of nonskeletal tissues, and other electrolyte disturbances. Baseline electrolyte levels should be measured prior to starting phosphate therapy, including sodium, potassium, chloride, bicarbonate, calcium, phosphate, blood urea nitrogen (BUN), and creatinine. Sodium phosphate and potassium phosphate are cathartic agents, which can cause diarrhea.

Excessive intake of phosphates can cause potentially serious or life-threatening toxicity. Intravenous, oral, or rectal/enema phosphates may cause electrolyte disturbances including hypocalcemia (low calcium blood levels), hypomagnesemia (low magnesium blood levels), hyperphosphatemia (high phosphorus blood levels), or hypokalemia (low potassium levels). Calcification of non-skeletal tissues (particularly in the kidneys), severe hypotension (low blood pressure), dehydration, metabolic acidosis, acute kidney failure, or tetany can occur. Death has been reported in infants or adults with oral, rectal, or intravenous phosphates, particularly in those at increased risk for electrolyte disturbances. Late symptoms may include abdominal pain, vomiting of phosphorescent materials, bloody vomiting and diarrhea, headache, limb aches, tongue coating, foul breath, weakness, yellow conjunctivae (whites of the eyes). Rare complications may include confusion, convulsions (seizures), headache, dizziness, numbness, tingling, pain, weakness, anxiety, increased thirst, muscle cramps, or fatigue. Abnormal heart rhythms, shortness of breath, foot/leg swelling, and weight gain have been reported. Management of toxicity may include sulfate of copper emetic, or lavage with Epsom salts in water (repeated every hour); repeated small doses of sulfate of copper and large doses of bicarbonate of soda. Oxygen inhalation, external heat, camphor, old oil of turpentine, and permanganate of potassium have been recommended.

Sodium phosphate and potassium phosphate are cathartic agents, and may cause diarrhea. Nausea, vomiting, or gastrointestinal irritation can occur. A reduction in dosage may be necessary to minimize diarrhea. Potassium acid phosphate may cause dyspepsia in patients with a history of peptic ulcer disease. Aluminum phosphate can cause constipation.

Conditions which may be worsened with excessive phosphorus/phosphate supplementation include burns, heart disease, pancreatitis, rickets, osteomalacia (softening of bones), underactive parathyroid glands (with sodium phosphate or potassium phosphate), dehydration, underactive adrenal glands (potassium phosphate may increase the risk of hyperkalemia), edema, high blood pressure, liver disease, toxemia of pregnancy, hyperphosphatemia, kidney disease.

Pregnancy and Breastfeeding

U.S. Food and Drug Administration Pregnancy Category: C.

The Tolerable Upper Intake Level (UL) for phosphorus in pregnant women is 3.5 grams per day, and in breastfeeding women is 4 grams per day.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

Antacids containing aluminum, calcium, or magnesium can bind phosphate in the gut and prevent its absorption, potentially leading to hypophosphatemia (low phosphate levels) when used chronically.

Some anticonvulsants (including phenobarbital and carbamazepine) may lower phosphorus levels and increase levels of alkaline phosphatase.

Bile acid sequestrants such as cholestyramine (Questran®) and colestipol (Colestid®) can decrease oral absorption of phosphate. Therefore, oral phosphate supplements should be administered at least one hour before or four hours after these agents.

Corticosteroids may increase urinary phosphorus levels.

Potassium supplements or potassium-sparing diuretics taken together with a phosphate may result in high blood levels of potassium (hyperkalemia).

Alcohol (ethanol) may increase urinary phosphorus. Wine may enhance absorption of phosphorus (as well as calcium and magnesium).

Medications that may affect electrolyte levels should be used cautiously with phosphates. Examples include: amiloride (Midamor®); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten®), enalapril (Vasotec®), fosinopril (Monopril®), lisinopril (Zestril®, Prinivil®), quinapril (Accupril®), or ramipril (Altace®); cyclosporine; cardiac glycosides (Digoxin®); heparins; anti-inflammatory drugs; potassium-containing agents; salt substitutes; spironolactone (Aldactone®); and triamterene (Dyrenium®).