DRUGS AND SUPPLEMENTS

Phosphates, phosphorus

March 22, 2017

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Phosphorus, Phosphate

Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • Aluminum phosphate, anhydrous sodium phosphate, bone ash, bone phosphate, calcium orthophosphate, calcium phosphate, calcium phosphate dibasic anhydrous, calcium phosphate dibasic dihydrate, calcium phosphate tribasic, colestilan, dibasic potassium phosphate, dibasic sodium phosphate, dicalcium phosphate, dicalcium phosphate, dipotassium hydrogen orthophosphate, dipotassium monophosphate, dipotassium phosphate, disodium hydrogen orthophosphate, disodium hydrogen orthophosphate dodecahydrate, disodium hydrogen phosphate, disodium phosphate, elemental phosphorus, MCI-196, monobasic potassium phosphate, monobasic sodium phosphate, neutral calcium phosphate, phosphate of soda, phosphatidylcholine, phosphatidylserine, potassium acid phosphate, potassium biphosphate, potassium dihydrogen orthophosphate, potassium phosphate, precipitated calcium phosphate, sevelamer (Renagel®), sodium orthophosphate, sodium phosphate, tertiary calcium phosphate, tribasic sodium phosphate, tricalcium phosphate, whitlockite.

  • Note: 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. Phosphate salts should not be confused with toxic substances such as organophosphates, or with tribasic sodium phosphates and tribasic potassium phosphates, which are strongly alkaline.

Background

  • Phosphorus is a mineral found in many foods, such as milk, cheese, grains, 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, the utilization of many B-complex vitamins, the buffering of body fluids, kidney excretion of hydrogen ions, proper muscle and nerve function, and 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 occurs 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 and 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 (a very serious complication in which the body only uses fatty acids as fuel and produces acidic ketone bodies).

  • Based on the potential for side effects associated with high blood levels of phosphorus, phosphorus supplementation should be done only under medical supervision.

Scientific Evidence

Uses

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.

Grade*

Constipation

Occasional constipation is a use of phosphates approved by the U.S. Food and Drug Administration (FDA) 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

Bone density (bone metabolism)

Early research shows that high amounts of phosphorus may have negative effects on bone density. This is because phosphorus decreases bone formation and increases bone resorption. In clinical research, there was a lack of an association between milk intake and hip fracture in women. Milk is a source of phosphorus, as are calcium, protein, and supplementary vitamin D in certain countries, such as the United States. Well-designed studies are needed to confirm these findings.

C

Burns

Patients with serious burns may lose phosphate, and replacement may be necessary. Well-designed clinical trials are necessary before conclusions may be drawn.

C

Diabetic ketoacidosis

The use of prophylactic phosphate therapy in diabetic ketoacidosis (a very serious complication in which the body only uses fatty acids as fuel and produces acidic ketone bodies) is controversial and may be considered, particularly in cases of low phosphate levels. In general, phosphate replacement is not routinely recommended, based on the lack of clinical benefit in some studies, as well as the potential for adverse effects, such as hypocalcemia and soft tissue calcification. In cases of low phosphate levels, some potassium replacement may be provided as potassium phosphate. Well-designed clinical trials are still necessary.

C

Exercise performance

Evidence is mixed with respect to the effect of oral phosphates on exercise performance. Further research is needed.

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 it appears to be well tolerated. This use of phosphates may be considered to prevent kidney stone formation. Further research is required.

C

Hyperparathyroidism

Hyperparathyroidism is the overactivity of the parathyroid glands. This results in excess production of parathyroid hormone (PTH), involved in the regulation of calcium and phosphate levels. At least in some patients with hyperparathyroidism, serum phosphate levels are low. However, well-designed clinical trials investigating the use of phosphates for this purpose are lacking, and further research is required.

C

Supplementation in preterm and very low birthweight infants

The effect of the addition of calcium and phosphorus to human milk on growth and bone metabolism in preterm infants is unclear. Further research is needed.

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. Inorganic phosphates avoid incompatibility with calcium in TPN solutions. The addition of phosphate to TPN solutions should be under the supervision of a licensed nutritionist.

C

Vitamin D resistant rickets

Vitamin D-resistant rickets is a fairly common type of rickets and is defined by its resistance to treatment with vitamin D. Low levels of phosphates are common in many of these patients. However, well-designed clinical trials investigating the use of phosphates for this purpose are lacking, and further research is required.

C

*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 (it may not work); F: Strong scientific evidence against this use (it likely does not work).

Tradition/Theory

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 health care professional.

  • Anxiety, appetite stimulant, bone diseases (pain), cancer, cancer (clear cell carcinoma), dental conditions, depression, encephalopathy (hypophosphatemic encephalopathy), fatigue, growth, irritability, joint problems, multiple sclerosis, muscle pain, osteoporosis, radioactive (thallium) parathyroid scanning enhancement, uterine cancer (uterine papillary serous carcinoma), weight gain, weight loss.

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 recommended daily intake has been suggested to be 700 milligrams of phosphorus daily for adults aged 18 years and older, including pregnant or breastfeeding women.

  • The tolerable upper intake level (UL) for adults 19-70 years old is four grams daily; for adults more than 70 years old, the UL is three grams daily. The recommended UL in pregnant women is 3.5 grams daily, and in breastfeeding women, it is four grams daily.

  • Phosphate salts should not be given to patients with hyperphosphatemia (high blood phosphorus levels) and should be used cautiously in those with impaired kidney function.

  • Doses typically range from one to three grams of phosphorus (as a phosphate salt (sodium phosphate or potassium phosphate) or elemental phosphate) daily 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 (it 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 refeeding 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 daily intake for infants and children is: infants 0-6 months old, 100 milligrams (additional phosphorus may be added to infant formulas); infants 7-12 months old, 275 milligrams; children ages 1-3 years old, 460 milligrams; children ages 4-8 years old, 500 milligrams; children ages 9-18 years old (including pregnant or breastfeeding females), 1,250 milligrams.

  • 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 daily; for children 9-18 years old the UL is 4 grams daily.

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

  • Children 5-10 years old may receive five milliliters of Fleet Phospho-soda® and should not exceed 10 milliliters in a 24-hour period. Children 10-12 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 Fleet Phospho-soda® to children under five 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.

Allergies

  • Avoid if allergic to any ingredients in phosphorus or phosphate preparations.

Side Effects and Warnings

  • 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. 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.

  • Nausea 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 may cause constipation. Oral sodium phosphate may cause bloating, cramps, abdominal pain, and nausea.

  • Phosphate salts should not be confused with toxic substances such as organophosphates, or with tribasic sodium phosphates and tribasic potassium phosphates, which are strongly alkaline.

  • Use cautiously in patients with gastrointestinal disorders, burns, pancreatitis, underactive parathyroid glands (with sodium phosphate or potassium phosphate), underactive adrenal glands, or liver disease, as excessive intake of phosphorus or phosphate may worsen these conditions.

  • Use cautiously in kidney stone formers.

  • Use phosphate enemas cautiously, following medical and label directions.

  • Use cautiously in patients with low blood pressure, or in those taking blood pressure-lowering agents.

  • Use cautiously when using agents that may affect electrolyte levels.

  • Use cautiously in patients at risk for osteoporosis, rickets, or osteomalacia (softening of bones), as early research shows that high amounts of phosphorus may have negative effects on bone density. Excessive phosphorus or phosphate supplementation may worsen these conditions.

  • Avoid in patients with kidney disease, and in those on dialysis, at risk for cardiovascular disease, or using prescribed phosphate binders, due to the increased risk of cardiovascular disease associated with increased phosphate levels, as well as due to the increased risk of parathyroidectomy. Excessive intake of phosphates may cause calcification of kidney tissue or acute kidney failure.

  • Avoid excessive amounts, and avoid use in patients with electrolyte imbalances, as excessive intake of phosphates may cause potentially serious or life-threatening toxicity or electrolyte disturbances, such as hypocalcemia (low calcium blood levels), hypomagnesemia (low magnesium blood levels), hyperphosphatemia (high phosphorus blood levels), or hypokalemia (low potassium levels). 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, and 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 or leg swelling, and weight gain have been reported.

  • Avoid with known allergy to any ingredients in phosphorus or phosphate preparations.

  • Avoid in pregnant women, especially those with toxemia of pregnancy, or lactating women, unless under the guidance of a health professional.

Pregnancy and Breastfeeding

  • The U.S. Food and Drug Administration (FDA) has categorized phosphorus as Pregnancy Category C. The tolerable upper intake level (UL) for phosphorus in pregnant women is 3.5 grams daily, and in breastfeeding women, it is four grams daily. The recommended daily intake in pregnant or breastfeeding females 18 years old and younger is 1,250 milligrams daily.

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).

  • Calcimimetics and insulin may decrease blood levels of phosphorus.

  • Estrogen may increase urinary phosphorus.

  • Phosphate binders decrease blood levels of phosphorus.

  • 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®).

  • Phosphates may cause low blood pressure. Caution is advised in patients taking agents that lower blood pressure.

  • Phosphates may also interact with ACE inhibitors, cardiovascular agents, gastrointestinal agents, hepatotoxic agents, osteoporosis drugs, and renal agents.

Interactions with Herbs and Dietary Supplements

  • Calcium may impair phosphates in the body and result in calcium deposits in tissues.

  • Pumpkin seed may increase urine phosphates.

  • Niacin might decrease blood levels of phosphorus.

  • Excessive doses of calcitriol, the active form of vitamin D (or its analogs), may result in hyperphosphatemia (high phosphate levels).

  • Phosphates may cause low blood pressure. Caution is advised in patients taking agents that lower blood pressure.

  • Phosphates may also interact with ACE inhibitors, antacids, anticonvulsants, anti-inflammatory agents, bile acid sequestrants, calcimimetics, cardiovascular agents, diuretics, electrolyte-modifying agents, fructose, gastrointestinal agents, hepatotoxins, high-phosphate beverages (such as cola drinks), hormonal agents, magnesium, osteoporosis agents, phosphate binders, potassium, renal agents, and salt substitutes.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Bredle DL, Stager JM, Brechue WF, et al. Phosphate supplementation, cardiovascular function, and exercise performance in humans. J Appl Physiol 1988;65(4):1821-1826.View Abstract

  2. Bugg NC, Jones JA. Hypophosphataemia. Pathophysiology, effects and management on the intensive care unit. Anaesthesia 1998;53(9):895-902. View Abstract

  3. Ehrenpreis ED, Nogueras JJ, Botoman VA, et al. Serum electrolyte abnormalities secondary to Fleet's Phospho-Soda colonoscopy prep. A review of three cases. Surg Endosc 1996;10(10):1022-1024. View Abstract

  4. Fakiris AJ, Moore DH, Reddy SR, et al. Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study. Gynecol Oncol 2005;96(3):818-823. View Abstract

  5. Fine A, Patterson J. Severe hyperphosphatemia following phosphate administration for bowel preparation in patients with renal failure: two cases and a review of the literature. Am J Kidney Dis. 1997;29(1):103-105. View Abstract

  6. Finn WF, Joy MS. A long-term, open-label extension study on the safety of treatment with lanthanum carbonate, a new phosphate binder, in patients receiving hemodialysis. Curr Med Res Opin. 2005;21(5):657-664. View Abstract

  7. Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J.Clin.Endocrinol.Metab 1983;57(1):177-180. View Abstract

  8. Garg JP, Chasan-Taber S, Blair A, et al. Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. Arthritis Rheum 2005;52(1):290-295. View Abstract

  9. Heaney RP, Nordin BE. Calcium effects on phosphorus absorption: implications for the prevention and co-therapy of osteoporosis. J Am Coll Nutr 2002;21(3):239-244. View Abstract

  10. Helikson MA, Parham WA, Tobias JD. Hypocalcemia and hyperphosphatemia after phosphate enema use in a child. J Pediatr Surg 1997;32(8):1244-1246. View Abstract

  11. Kastenberg D, Chasen R, Choudhary C, et al. Efficacy and safety of sodium phosphate tablets compared with PEG solution in colon cleansing: two identically designed, randomized, controlled, parallel group, multicenter phase III trials. Gastrointest Endosc 2001;54(6):705-713. View Abstract

  12. Kemi VE, Kärkkäinen MU, Lamberg-Allardt CJ. High phosphorus intakes acutely and negatively affect Ca and bone metabolism in a dose-dependent manner in healthy young females. Br J Nutr. 2006 Sep;96(3):545-52. View Abstract

  13. Kuschel CA, Harding JE. Calcium and phosphorus supplementation of human milk for preterm infants. Cochrane Database Syst Rev. 2001;(4):CD003310. View Abstract

  14. Kurihara S, Tsuruta Y, Akizawa T. Effect of MCI-196 (colestilan) as a phosphate binder on hyperphosphataemia in aemodialysis patients: a double-blind, placebo-controlled, short-term trial. Nephrol Dial Transplant 2005;20(2):424-430. View Abstract

  15. National Research Council, Food and Nutrition Board. Recommended Dietary Allowances. 10th ed. Washington, D.C.: National Academy Press; 1989:184-187.

Copyright © 2013 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Updated:  

March 22, 2017