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.
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 . 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 .
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.
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:
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) . 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.
Symptomatic patients with hypercalcemia should be treated. These are the following interventions:
Patients with vitamin D toxicity have excellent prognosis  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  .
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 .
Historically, vitamin D fortification of foods and beverages in the United States and Europe resulted in toxicity .
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 . The 2012 statistics for Vitamin D toxcity are:
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:
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.
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  depends on the age:
Following nutritional guidelines is recommended for all vitamin and nutrients.
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.
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: