Toxicity
Vitamin D toxicity (hypervitaminosis D) has not been observed to result from sun exposure. The reason is that excessive sunlight exposure generates a number of biologically inert photoproducts from 7-dehydrocholesterol and cholecalciferol
(3). Vitamin D toxicity induces abnormally high
serum calcium concentration (hypercalcemia), which could result in bone loss,
kidney stones, and calcification of organs like the heart and kidneys if untreated over a long period of time. Hypercalcemia has been observed following daily doses of greater than 50,000 IU of vitamin D
(322). Overall, research suggests that vitamin D toxicity is very unlikely in healthy people at intake levels lower than 10,000 IU/day
(323-325). However, the Food and Nutrition Board of the IOM conservatively set the tolerable upper intake level (
UL) at 4,000 IU/day (100 μg/day) for all adults (
Table 3). Certain medical conditions can increase the
risk of hypercalcemia in response to vitamin D, including primary
hyperparathyroidism, sarcoidosis,
tuberculosis, and lymphoma
(323). People with these conditions may develop hypercalcemia in response to any increase in vitamin D nutrition and should consult a qualified health care provider regarding any increase in vitamin D intake.
T
able 3. Tolerable Upper Intake Level (UL) for Vitamin D
| Age Group | μg/day | IU/day |
|---|
| Infants 0-6 months | 25 | 1,000 |
| Infants 6-12 months | 37.5 | 1,500 |
| Children 1-3 years | 62.5 | 2,500 |
| Children 4-8 years | 75 | 3,000 |
| Children 9-13 years | 100 | 4,000 |
| Adolescents 14-18 years | 100 | 4,000 |
| Adults 19 years and older | 100 | 4,000 |
The following medications should not be taken at the same time as vitamin D because they can decrease the intestinal absorption of vitamin D: cholestyramine (Questran), colestipol (Colestid), orlistat (Xenical), and mineral oil
(326, 327). The following medications increase the
metabolism of vitamin D and may decrease
serum 25-hydroxyvitamin D concentrations: phenytoin (Dilantin), fosphenytoin (Cerebyx), phenobarbital (Luminal), carbamazepine (Tegretol), and rifampin (Rimactane)
(6). Cimetidine, a H2 blocker that suppresses stomach acid secretion, inhibits the
hydroxylation of vitamin D in the liver
(328). Treating acid reflux,
gastroesophageal reflux disease (GERD), or ulcers with proton-pump inhibitors (omeprazole, lansoprazole) might interfere with calcium absorption and increase the risk of
fracture such that patients are advised to take calcium and vitamin D supplements
(329). The oral antifungal medication, ketoconazole, inhibits the 25-hydroxyvitamin D3-1α-hydroxylase
enzyme and has been found to reduce serum 1α,25-hydroxyvitamin D concentrations in healthy men
(330). The Endocrine Society also recommends monitoring vitamin D status of patients on glucocorticoids and
HIV treatment drugs because these medications increase the
catabolism of 25-hydroxyvitamin D
(40). The use of some cytostatic agents (cell growth inhibitors) may also increase the degradation of 25-hydroxyvitamin D and 1α,25-hydroxyvitamin D in
cancer patients under
chemotherapy (6). The induction of hypercalcemia by toxic levels of vitamin D may precipitate cardiac arrhythmia in patients on digoxin (Lanoxin)
(328). Hypercalcemia may also reduce the effectiveness of verapamil (Calan) and diltiazem (Cardizem) in
atrial fibrillation (328).
The Linus Pauling Institute recommends that generally healthy adults take 2,000 IU (50 μg) of supplemental vitamin D daily. Most multivitamins contain 400 IU (10 μg) of vitamin D, and single-ingredient vitamin D supplements are available for additional supplementation. Sun exposure, diet, skin color, and
body mass index (BMI) have variable, substantial impact on body vitamin D levels. To adjust for individual differences and ensure adequate body vitamin D status, the Linus Pauling Institute recommends aiming for a serum 25-hydroxyvitamin D concentration of at least 30 ng/mL (75 nmol/L).
Observational studies suggest that serum 25-hydroxyvitamin D concentrations between 30 ng/mL and 60 ng/mL are associated with lower
risks of adverse health outcomes, including
cancers and
autoimmune diseases.
The American Academy of Pediatrics currently suggests that all infants, children, and adolescents receive 400 IU of supplemental vitamin D daily
(19). Consistent with the recommendations of the Endocrine Society
(40), the Linus Pauling Institute recommends daily intakes of 400 to 1,000 IU (10 to 25 μg) of vitamin D in infants and 600 to 1,000 IU (15 to 25 μg) of vitamin D in children and adolescents. Given the average vitamin D content of breast milk, infant formula, and the diets of children and adolescents, supplementation may be necessary to meet these recommendations.
Older adults (>50 years)
Daily supplementation with 2,000 IU (50 μg) of vitamin D is especially important for older adults because aging is associated with a reduced capacity to
synthesize vitamin D in the skin upon sun exposure.
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