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Vitamin D Toxicity

Intoxication Vitamin D

Vitamin D, in moderate amounts, is necessary for bone formation and calcium absorption. However, excessive intake of this fat soluble vitamin can result in toxicity. Symptoms may be nonspecific but severe cases can develop renal dysfunction. 


Presentation

Vitamin D toxicity sequalae consists of nonspecific symptoms such as weakness, poor appetite, nausea, emesis, anorexia, weight loss, and polyuria. Due the vagueness of these symptoms, diagnosis is usually delayed until the picture is severe. In chronic toxicity, observed symptoms are abdominal cramps, constipation, polydipsia and backaches

Hypercalcemia can lead to serious manifestations such as calcification of cardiac, vascular, and renal tissues [5]. Elevated calcium levels can also cause cardiac arrhythmias. Furthermore, the Women’s Health Initiative demonstrated a 17% increased risk in developing nephrolithiasis in postmenopausal women who ingested of both calcium and vitamin D [6].

Nephrotoxicity

The increased calcium concentration overwhelms glomerular filtration and reduces the rate. Therefore, the excess calcium accumulates in the renal tubules. This phenomenon is observed in about 25% of individuals with vitamin D intoxication. In addition, 10% of nephrocalcinosis in children is due to vitamin D intoxication. The combination of dehydration, reduced filtration and calcium accumulation contributes to renal tubular acidosis

Correlation of vitamin D dose, calcium concentration and presentation

The Endocrine Society defines serum calcium concentrations above than 150 ng/mL as toxic. Also, it proposes that the safe levels are less than 100 ng/mL for children and adults. These numbers are supported by studies.

It is not clear what levels of vitamin D lead to toxicity and hypercalcemia. Documented vitamin D intoxication in the pediatric population involves severely elevated levels greater than 240,000 IU. The serum calcium levels in these patients are in the range of 14 to 18 mg/dL. These cases demonstrate that there is variability between the intake of vitamin D and corresponding serum calcium levels. In conclusion, it is difficult to establish what levels are associated with symptomatology.

Vomiting
  • Clinical manifestations included nausea, vomiting, altered sensorium, constipation, pancreatitis, acute kidney injury and weight loss. Median (range) age was 64·5 (42-86) years.[ncbi.nlm.nih.gov]
  • “This led to vitamin D toxicity and the boy was admitted in AIIMS with abdominal pain and vomiting.[timesofindia.indiatimes.com]
  • Signs of vitamin D toxicity can include nausea, vomiting, lack of appetite, constipation, weakness, weight loss or any combination of these. If vitamin D levels get extremely high, it can do your body serious harm.[sharecare.com]
  • The condition can cause weakness, vomiting and kidney problems, and is the main side effect of high vitamin D levels.[livescience.com]
Nausea
  • Clinical manifestations included nausea, vomiting, altered sensorium, constipation, pancreatitis, acute kidney injury and weight loss. Median (range) age was 64·5 (42-86) years.[ncbi.nlm.nih.gov]
  • Signs of vitamin D toxicity can include nausea, vomiting, lack of appetite, constipation, weakness, weight loss or any combination of these. If vitamin D levels get extremely high, it can do your body serious harm.[sharecare.com]
  • The first symptoms of vitamin D toxicity are loss of appetite, nausea and vomiting, followed by an incredible thirst, increased urination, weakness, anxiety and high blood pressure.[healthfame.com]
  • The main consequence of vitamin D toxicity is a buildup of calcium in your blood (hypercalcemia), which can cause nausea and vomiting, weakness, and frequent urination.[mayoclinic.org]
Constipation
  • Clinical manifestations included nausea, vomiting, altered sensorium, constipation, pancreatitis, acute kidney injury and weight loss. Median (range) age was 64·5 (42-86) years.[ncbi.nlm.nih.gov]
  • Constipation Constipation is a condition where bowel movement is painful and hard to pass.[searchhomeremedy.com]
  • Constipation Constipation is considered to be one of the major symptoms of vitamin d toxicity because the body is not able to get the desired amount of vitamin D that is considered to be essential for the body and at the same time it is also found that[findhomeremedy.com]
  • Signs of vitamin D toxicity can include nausea, vomiting, lack of appetite, constipation, weakness, weight loss or any combination of these. If vitamin D levels get extremely high, it can do your body serious harm.[sharecare.com]
  • It’s also associated with a wide range of symptoms, including vomiting, constipation, dehydration, fatigue, and muscle weakness.[bostonglobe.com]
Loss of Appetite
  • The first symptoms of vitamin D toxicity are loss of appetite, nausea and vomiting, followed by an incredible thirst, increased urination, weakness, anxiety and high blood pressure.[healthfame.com]
  • When symptoms do appear, they may include confusion, increased urination, increased thirst, loss of appetite, vomiting, and muscle weakness.[schmidtlaw.com]
  • A 67-year-old woman went to the hospital with a history of lethargy, memory impairment, confusion, loss of appetite, and loss of equilibrium for two-weeks duration. Her routine biochemistry showed elevated blood calcium at 14 mg/dl.[secondopinionnewsletter.com]
  • The symptoms to be aware of include: • Loss of appetite • Fatigue • Excessive thirst • Weight loss • Dehydration • Excessive urination • Nervousness and irritability • Constipation • Muscle weakness • Ringing in the ear, known as tinnitus • Vomiting and[vitamindsupplement.com]
  • Dr Sarah Brewer, GP and Medical Director at Healthspan said: “Excess vitamin D leads to raised levels of calcium which can cause headache, loss of appetite, nausea, vomiting, diarrhoea or constipation, palpitations and fatigue.”[express.co.uk]
Polydipsia
  • These are the conditions that are followed by polydipsia and polyuria which are conditions of excessive thirst and urine experienced by the body.[findhomeremedy.com]
  • Symptoms of vitamin D toxicity[ 2 ] Hypercalcemia Hypercalciuria Kidney stones Hyperphosphatemia Polyuria Polydipsia Ectopic calcification of soft tissues (kidney and lung) Nausea/vomiting Anorexia Constipation Headache Hypertension Diagnosis of vitamin[ncbi.nlm.nih.gov]
  • Vitamin D overdose causes elevated blood calcium level (hypercalcemia) and the main symptoms are: anorexia, nausea, and vomiting, frequently followed by excessive urination (polyuria), Â increase thirst (polydipsia), weakness, nervousness, itchiness,[drgeo.com]
  • Specifically, the tests will look for the presence of: • Hypercalcemia (excessive calcium levels in the blood) • Hypercalciuria (excessive calcium levels in the urine) • Polydipsia (excessive thirst) • Hypertension (high blood pressure) • Polyuria (excessive[vitamindsupplement.com]
  • There is high blood pressure, anorexia, polyuria, polydipsia, nervousness and itching. Excess vitamin D causes many kidney problems like high protein levels that are excreted in the urine .[searchhomeremedy.com]
Hypertension
  • It is suggested that normal renal function may be required for the hypertension of hyperparathyroidism to be reversible and that the hypertension may be directly related to the hypercalcemia in some patients.[ncbi.nlm.nih.gov]
  • She was hypertensive for last 20 years, which was well under control with Amlodipine (5 mg/day). Her part history revealed that she had undergone total right hip replacement 1 year back and had regular follow-up checkups with the orthopedic surgeon.[ncbi.nlm.nih.gov]
  • The patient's hypercalcemia persisted for 14 days and was complicated by persistent hypertension. No renal, cardiac, or neurologic complications were noted.[pediatrics.aappublications.org]
  • Low vitamin D levels are associated with all kinds of health problems, including cardiovascular disease, hypertension , type 2 diabetes, multiple sclerosis , cognitive impairment, and even cancer.[doctorshealthpress.com]
  • In addition, hypertension can result. The main consequence of vitamin D toxicity is a buildup of calcium in your blood (hypercalcemia), which can cause poor appetite, nausea and vomiting.[blogs.naturalnews.com]
Pruritus
  • Scaly seborrhoeic eczema Patchy hair loss Stomatitis Loss of appetite Nausea Vomiting Malaise Hepatosplenomegaly Liver failure Raised intracranial pressure Children can present with craniotabes, irritability, failure to thrive, decreased appetite and pruritus[patient.info]
Bone Pain
  • Bone Pain Excessive bone pain is one of the most important symptoms that can be associated with vitamin D toxicity.[findhomeremedy.com]
  • Symptoms might progress to bone pain and kidney problems, such as the formation of calcium stones. Treatment includes stopping vitamin D intake and restricting dietary calcium.[mayoclinic.org]
  • Bone Pain Excessive calcium as a consequence of higher levels of Vitamin D causes calcification of bones .[searchhomeremedy.com]
  • At this point, bone pain or bone loss can occur. Symptoms can also affect the urinary tract, ranging from excessive urine production by the kidney stones, and even kidney failure.[healthfame.com]
Muscle Weakness
  • It’s also associated with a wide range of symptoms, including vomiting, constipation, dehydration, fatigue, and muscle weakness.[bostonglobe.com]
  • When symptoms do appear, they may include confusion, increased urination, increased thirst, loss of appetite, vomiting, and muscle weakness.[schmidtlaw.com]
  • High levels of blood calcium (hypercalcemia) can cause a number of ailments. 3 Symptoms of hypercalcemia: Confusion Nausea Fatigue Dizziness Vomiting Weight loss Excessive urination Poor appetite High blood pressure Dehydration Muscle weakness Irregular[drclarkstore.com]
  • Central nervous system (CNS) examination showed that there was generalized muscle weakness without any focal deficit. Jerks were normal. Planters were down. MRI brain showed age-related diffuse cerebral cortical atrophy.[ncbi.nlm.nih.gov]
  • The symptoms to be aware of include: • Loss of appetite • Fatigue • Excessive thirst • Weight loss • Dehydration • Excessive urination • Nervousness and irritability • Constipation • Muscle weakness • Ringing in the ear, known as tinnitus • Vomiting and[vitamindsupplement.com]
Polyuria
  • These are the conditions that are followed by polydipsia and polyuria which are conditions of excessive thirst and urine experienced by the body.[findhomeremedy.com]
  • Ten cases of hypercalcemia due to vitamin D intoxication are presented with features of vomiting, polyuria, polydipsia, encephalopathy and renal dysfunction.[ncbi.nlm.nih.gov]
  • Symptoms of vitamin D toxicity[ 2 ] Hypercalcemia Hypercalciuria Kidney stones Hyperphosphatemia Polyuria Polydipsia Ectopic calcification of soft tissues (kidney and lung) Nausea/vomiting Anorexia Constipation Headache Hypertension Diagnosis of vitamin[ncbi.nlm.nih.gov]
  • Vitamin D overdose causes elevated blood calcium level (hypercalcemia) and the main symptoms are: anorexia, nausea, and vomiting, frequently followed by excessive urination (polyuria), Â increase thirst (polydipsia), weakness, nervousness, itchiness,[drgeo.com]
  • Specifically, the tests will look for the presence of: • Hypercalcemia (excessive calcium levels in the blood) • Hypercalciuria (excessive calcium levels in the urine) • Polydipsia (excessive thirst) • Hypertension (high blood pressure) • Polyuria (excessive[vitamindsupplement.com]
Headache
  • I've experienced dizziness, headaches, insomnia, heart disturbances (palpitations, sensation of hard beating, mild chest pain), irritated eyes, and generally feeling a bit weird and spaced out.[paleohacks.com]
  • There was no history of fever, headache, cough, urinary symptoms or any focal weakness. She was hypertensive for last 20 years, which was well under control with Amlodipine (5 mg/day).[ncbi.nlm.nih.gov]
  • In addition, increased thirst and dehydration, as well as severe headaches can occur. Along with the development of symptoms, nerves and muscles begin to be affected, which causes itching in the skin, fatigue, and weakness.[healthfame.com]
  • Megadoses of vitamin E may produce headaches, tiredness, double vision, and diarrhea in humans. Studies with animals fed large doses of vitamin E have revealed that this vitamin may interfere with the absorption of other fat-soluble vitamins.[medical-dictionary.thefreedictionary.com]
  • But in some cases there may be symptoms, eventually, and they can be any, or all of these- nausea vomiting dehydration (frequent thirst and urination) fatique muscle aches headaches weakness poor appetite confusion slurred speech.[vitamind3-cholecalciferol.com]
Lethargy
  • Although the toxicity of vitamin D has conventionally been attributed to its induction of hypercalcemia, animal studies show that the toxic endpoints observed in response to hypervitaminosis D such as anorexia, lethargy, growth retardation, bone resorption[ncbi.nlm.nih.gov]
  • Abstract A 67-year-old female was admitted to the hospital with a history of lethargy, memory impairment, confusion, anorexia and gait imbalance for 2 weeks duration. She did not have any history of fall or head injury.[ncbi.nlm.nih.gov]
  • A 67-year-old woman went to the hospital with a history of lethargy, memory impairment, confusion, loss of appetite, and loss of equilibrium for two-weeks duration. Her routine biochemistry showed elevated blood calcium at 14 mg/dl.[secondopinionnewsletter.com]
  • This class of drugs gradually reduces Coenzyme Q10 by at least 40% over a period of a year creating such unwanted symptoms such as: fatigue weak and tired muscles lethargy a general sense of low energy A deficiency of coenzyme Q10 can result in high blood[naturallysavvy.com]
  • During the previous 3 days, he had experienced vomiting, constipation, lethargy, and abdominal pain. With the exception of slightly elevated blood pressure, his physical examination results were benign.[pediatrics.aappublications.org]

Workup

When suspecting ingestion of unknown substance, a thorough history and physical are obtained from the patient or family (if patient is young or unable to speak).

Laboratory tests include electrolytes studies especially in patients with emesis or diarrhea. Calcium concentrations must be obtained (>11mg/dL is considered abnormal). A concomitant elevation in phosphate may occur. Renal functions tests are essential. Additional laboratory studies include urinalysis, which can provide insight regarding renal impairment. Of note, if the following laboratory studies are performed, the observed measurements are as follows:

  • Serum 25OHD increased 
  • Serum 1,25(OH)2D normal
  • PTH reduced

These trends differ in other pathologies with hypercalcemia

Imaging consists of a skeletal X-ray to survey all the bones for calcification (especially in vitamin D and A toxicity) [7]. Also important is a hand X-ray, which identifies periosteal calcification in toxicity. An electrocardiogram (EKG) is performed to discover any potential arrhythmias secondary to excess calcium.

Nephrolithiasis
  • Mutations in the CYP24A1 gene cause reduced serum 24,25(OH)2D3 to 25(OH)D3 ratio ( 0.02), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), hypercalcemia, hypercalciuria and nephrolithiasis.[ncbi.nlm.nih.gov]
  • Nephrolithiasis was not demonstrable upon ultrasonography in any of the patients and all had normal sized kidneys with maintained corticomedullary differentiation. Serum and urine electrophoresis were normal in all cases.[ncbi.nlm.nih.gov]
  • Complications Complications may include nephrolithiasis , nephrocalcinosis (calcium oxalate and calcium phosphate are radio-opaque stones), calcinosis of the joints and periarticular tissues, and chronic kidney disease .[patient.info]
Soft Tissue Calcification
  • tissue calcification, and death can be dissociated from the hypercalcemia that usually accompanies them, demanding that an alternative explanation for the mechanism of vitamin D toxicity be developed.[ncbi.nlm.nih.gov]
  • At best, they will not protect against soft tissue calcification, and at worst, they could perhaps actively faciliate soft tissue calcification.[blog.cholesterol-and-health.com]
  • tissue calcification, including nephrocalcinosis and kidney stones. 1, 5 The risk of vitamin D toxicity may be increased in individuals who have 5 : granulomatous disorders such as sarcoidosis and tuberculosis some lymphomas that produce 1,25-dihydroxyvitamin[questdiagnostics.com]

Treatment

Symptomatic patients with hypercalcemia should be treated. These are the following interventions:

  1. ABCs: In life threatening cases, secure airway and ensure all the necessary precautions. Monitor vitals and provide oxygen as needed. Also evaluate arrhythmias if present. Treatment may be indicated for certain types.
  2. Address the source: Expect the levels to reduce gradually over a few weeks. Even after discontinuing the source, 25(OH)D may still increase since due its long half life. Asymptomatic patients with high 25(OH)D concentration should be monitored for development of symptoms [8] [9].
  3. IV hydration: Administer normal saline at 1.5 to 2.5 maintenance rate. The goal of this therapy is to improve the glomerular filtration rate and the subsequent excretion of calcium. 
  4. Loop diuretics such as furosemide may be helpful. Avoid thiazide since can worsen calcium levels. 
  5. Diet: Order low calcium meals. Calcium disodium can use used facilitate fecal excretion. 
  6. Other drugs/therapy: Consider steroids, hydrocortisone, and/or mithramycin. In cases of with very high levels of serum calcium, dialysis may be beneficial.
  7. Calcitonin and its analogues can be considered as well. If hypercalcemia is secondary to diuretics, calcitonin should be considered. 
  8. In cases where patients consume other substances in toxic levels, gastric lavage may be indicated. If iron was ingested as well, this should be treated.

Of note, calcium itself is used therapeutically in conditions such as hyperparathyroidism, psoriasis and other disorders as well.

Prognosis

Patients with vitamin D toxicity have excellent prognosis [1] once they stop intake of the supplements. This also true for toxicity with other vitamins as well. Long term outcomes and fatalities are very rare. This is corroborated by the data published by The American Association of Poison Control Center. Approximately 59,000 single exposures to vitamins were reported in 2012, but there was one fatal case [3] [4].

Etiology

Vitamin D toxicity is secondary to ingestion of high amounts of dietary vitamin D supplements. Foods rich in calcium do not provide toxic levels of the vitamin. Excessive sun exposure is not a cause of toxicity either, since heat on the skin degrades vitamin D3 and previtamin D3 as they are produced [1]. 

Historically, vitamin D fortification of foods and beverages in the United States and Europe resulted in toxicity [2]. 

Epidemiology

The use of supplements is quite prevalent. In fact, a 2009 survey reported that approximately 56% American consumers take vitamin supplements, in which a majority admit to daily consumption. In addition, a study that took place from 2003 to 2006 demonstrated that a third of the United States population had taken a vitamin supplement in any given month.

The United States poison control receives greater than 60,000 reports yearly of vitamin overdoses. The American Association of Poison Control Center documents the relevant data for exposures, adverse outcomes, and mortality rates that stem from overdose [3]. The 2012 statistics for Vitamin D toxcity are:

  • Single exposures: 4494
  • Minor outcomes: 137
  • Moderate outcomes: 19
  • Major outcomes or fatal cases: none
Sex distribution
Age distribution

Pathophysiology

To understand the pathophysiology of vitamin D toxicity, it is important to demonstrate the normal physiology. Vitamin D (a prohormone) is metabolized by the liver to 25(OH)D which is then converted to 1,25(OH) 2D by the kidneys. Both metabolites may behave as hormones. The three factors that regulate this conversion are concentration of 1,25(OH) 2D, parathyroid hormone (PTH) and serum levels of calcium and phosphate.

There are three mechanisms responsible for vitamin D toxicity:

  1. Vitamin D intake raises serum 1α,25(OH)2D levels and this further elevates cellular levels of 1α,25(OH)2D. Investigations have not demonstrated this mechanism in human or animal studies.
  2. Vitamin D ingestion increases serum 25(OH)D which overwhelms the capacity of binding proteins and hence the unbound or "free" 25(OH)D enters the cells and stimulates gene expression. 
  3. Vitamin D consumption increases levels of its metabolites especially 25(OH)D. The elevated concentrations of vitamin D and its metabolites overwhelm the binding capacity of the binding proteins. This results in the subsequent release of 1α,25(OH)2D, which enters the cells and stimulates gene expression.

In all three theories, vitamin D metabolites reach the cell nuclei and alter gene expression. Normally, 1α,25(OH)2D3 has a low affinity for the binding protein but has high affinity for vitamin D receptor. In fact, 1α,25(OH)2D3, which is thought to mimic steroids, is the only ligand that can access transcription machinery. With severe levels of vitamin D (such as in intoxication), the other metabolites exceed the number of binding proteins and thus are free to subsequently access the nucleus. Hence, the second and third mechanisms above may be plausible. 

Prevention

Intoxication with vitamin D is not a frequent occurrence in individuals that use supplements. Those with underlying hepatic or renal disorders are more at risk and should discuss with their doctor before initiating supplement intake. The same recommendation applies to those taking thiazide diuretics. Furthermore, it is pertinent to exercise caution with excessive or chronic intake of vitamins in children. To avoid accidental overdose, parents and caretakers should place all medications and supplements out of the reach of children. In case of suspected ingestion, parents should seek immediate medical attention. 

The recommended daily intake for vitamin D [10] depends on the age:

  • 0 to 12 months: 10 mcg or 400 IU
  • 1 to 70 years of age: 15 mcg or 600 IU, This also applies to pregnant and lactating women.
  • Greater than 70 years of age: 20 mcg or 800 IU

Following nutritional guidelines is recommended for all vitamin and nutrients. 

Summary

Vitamin D plays an essential role in the body especially in bone development and mineralization. The fat soluble vitamin facilitates absorption of calcium and phosphate. Physiologically, humans are equipped to handle the synthesis and production of vitamin D (with sunlight exposure) but this does not cause toxicity. The latter occurs from excessive intake such as with supplements.

Toxicity is classified as either acute or chronic. The chronic form is associated with a dose greater than 50,000 IU daily in adults but the acute dose has yet to be clarified. In very young infants, 1000 IU daily is likely unsafe. There are recommendations for dietary intake of this and all vitamins. 

The nonspecific symptoms of toxicity are usually related to hypercalcemia. The vagueness of the clinical picture often delays the diagnosis. Furthermore, there are serious complications such as nephrotoxicity, which is a consequence of calcium accumulation in the renal tubules. 

The therapy consists discontinuation of the source. Treatment depends on the severity of the presentation. Overall, patients recover well. 

Patient Information

Vitamin D toxicity is not a common condition, but when it occurs, it is due to excessive intake of vitamin D such as with supplements. Large amounts of this vitamin cause an increase of calcium in the blood. Symptoms include nausea, vomiting, constipation, poor appetite, frequent urination, tiredness, weakness, and aches. Some patients will have an abnormal heart rhythm. The high calcium levels can cause kidney damage due to build up of calcium in the tubules. 

If your doctor suspects vitamin D toxicity, s/he will order important laboratory blood tests to assess the amount of calcium and phosphate. Also the doctor will order blood and urine tests to evaluate the kidney function. Also, X-rays of the bones may be necessary to detect any bone calcification. 

Treatments of toxicity include hydration with intravenous fluids to facilitate clearing of the excess calcium from the kidneys. Some patients may benefit from loop diuretics, steroids or bisphonates. 

There are recommendations for preventing vitamin D overdose. Patients with liver or kidney disease should ask their doctor before taking any supplement. Also, parents and caretakers should keep all medications and supplements away from children for safety. If there is suspected overdose, seek medical attention immediately.

The following are the recommended daily allowance of vitamin D for 3 main age groups:

  • 0 to 12 months: 10 mcg or 400 IU
  • 1 to 70 years of age: 15 mcg or 600 IU
  • Greater than 70 years of age: 20 mcg or 800 IU

References

Article

  1. Holick MF. Vitamin D deficiency.New England Journal of Medicine. 2007;357(3):266-81.
  2. Holick M.F. Vitamin D deficiency: What a pain it is. Mayo Clinic Proceedings. 2003;78(12):1457–1459. 
  3. Mowry JB, Spyker DA, Cantilena LR Jr, Bailey JE, Ford M. 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report. Clinical Toxicology (Phila). 2013; 51(10):949-1229.
  4. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database System Review. 2012;14:3.
  5. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
  6. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. New England Journal of Medicine. 2006;354(7): 669-83.
  7. Barker ME, Blumsohn A. Is vitamin A consumption a risk factor for osteoporotic fracture? Proceedings of the Nutrition Society. 2003; 62(4):845-50.
  8. Doneray H, Ozkan B, Caner I, Ozkan A, Karakelleoglu C. Intragastric alendronate therapy in two infants with vitamin D intoxication: a new method. Clinical Toxicology (Phila). 2008; 46(4):300–302.
  9. Orbak Z, Doneray H, Keskin F, Turgut A, Alp H, Karakelleoglu C. Vitamin D intoxication and therapy with alendronate (case report and review of literature). European Journal of Pediatrics. 2006; 165(8):583–584. 
  10. Office of Dietary Supplements. Dietary Supplement Fact Sheet: Vitamin D. National Institutes of Health. Available at http://ods.od.nih.gov/factsheets/vitamina.asp. Accessed: October 13, 2014.

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Last updated: 2018-06-22 05:23