Vitamin D Supplements Very Safe: For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Total-body sun exposure easily provides the equivalent of 10,000 IU vitamin D/d, suggesting that this is a physiologic limit. Vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D response that is surprisingly flat up to 10,000 IU vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 4,000 IU/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 10,000 IU/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of at least 40,000 IU/d. Because vitamin D is potentially toxic, intake of >1000 IU/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 2000 IU/d is too low by at least 5-fold. The author notes that circulating 25-hydroxyvitamin D concentrations of early humans were surely far higher than what is now regarded as normal. Humans evolved as naked apes in tropical Africa. The full body surface of our ancestors was exposed to the sun almost daily. In contrast, modern humans usually cover all except about 5% of skin surface and it is rare for humans to spend time in unshielded sunlight. Sunshine alone can bring 25(OH)D concentrations to 210 nmol/L in normal people and vitamin D intakes of 1200 IU/d contribute only a negligible fraction of this. Although it can take 3–6 times longer for pigmented skin to reach the equilibrium concentration of dermal previtamin D, skin pigmentation does not affect the amount of vitamin D that can be obtained through sunshine exposure. However, aging does lower the amount of 7-dehydrocholesterol in the skin and lowers substantially the capacity for vitamin D production. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Vieth R. University of Toronto. Am J Clin Nutr. 1999 May;69(5):842-56. 

Hypercalcemia Cases From Vitamin D; Rare and All Due to Very High Doses: A case of hypercalcemia causing renal colic and neurologic disorders in a 62-year-old Italian man is reported. The hypercalcemia was caused by chronic treatment with injectible slow release vitamins D and A. J Nephrol. 2003 Nov-Dec;16(6):917-21. Hypercalcemia is usually caused by cancer or a parathyroid nodule excreting too much parathyroid hormone. Both processes break down bone tissue. Hyperthyroidism can also cause rare cases of hypercalcemia. A case of hypercalcemia due to vitamin D intoxication of a 3-month-old has been reported. The child recovered with bisphosphonate treatment without sequelae. Eur J Pediatr. 2004 Mar;163(3):163-5. A case of hypercalcemia due to an artificial vitamin D analogue tacalcitol cream being used in large amounts for psoriasis is report. It resolved in 7 days without treatment. The authors note that it was the first case ever reported due to the cream. J Dermatol. 2003 Nov;30(11):801-4. One Turkish study of infants with vitamin D deficiency rickets found that treatment with a single dose of vitamin D 150,000 or 300,000 IU worked fine, but that 600,000 IU caused hypercalcemia. J Pediatr Endocrinol Metab. 2003 Oct-Nov;16(8):1105-9.

Alfacalcidol Better than Vitamin D, but Vitamin K Not Used: In a DB study of D-hormone analog alfacalcidol vs. vitamin D in patients with established steroid-induced osteoporosis, 1 microg alfacalcidol plus 500 mg calcium per day (n=103) did better than 1000 IU vitamin D3 plus 500 mg calcium (n=101). During the 3-year study, the BMD at the lumbar spine increased 2.4% with alfacalcidol and decreased 0.8% with vitamin D ( P<0.0001). The 3-year rates of new vertebral fracture were 9.7% for alfacalcidol and 24.8% for vitamin D (risk reduction 0.61, P=0.005). The 3-year rates of nonvertebral fracture were 15% for alfacalcidol group and 25% for vitamin D (P=0.081). Alfacalcidol showed a substantially larger decrease in back pain than vitamin D ( P<0.0001). Three patients in the alfacalcidol group and two in the vitamin D group had moderate hypercalcemia. Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis. Ringe JD, Dorst A, Faber H, Schacht E, Rahlfs VW. Leverkusen, Germany.  Rheumatol Int. 2004 Mar;24(2):63-70.

Routine Testing for Vitamin D Hypercalcemia Not Cost-Effective: Clinically significant hypercalcemia appears rare with regular vitamin D, except in patients with severe kidney disease where vitamin D treatment is very helpful but occasional cases of hypercalcemia are reported. I have found hypercalcemia reports with long-acting injectibles in high doses, more potent vitamin D analogues, and very high doses of vitamin D given to infants. It does not appear cost-effective to routinely monitor for hypercalcemia in adults without kidney disease taking a moderate daily oral dose (1000 IU or less) of vitamin D chronically. 

No Harm From Vitamin D 15,000 IU/week: In a 2-month, 52-patient DB PC study of 15,000 IU/week of vitamin D for postmenopausal women with decrease bone mineral density with both groups receiving calcium 0.5 g/d, none of the vitamin D treated women suffered from hypercalcemia and mild hypercalciuria was observed in one patient. The study presented some evidence on the effectiveness and safety of 15,000 IU/week 25-hydroxycholecalciferol dosage schedule. Intensive vitamin D supplementation in the treatment of osteoporosis. Stefikova K, Chylova K, Krivosikova Z, Spustova V, Dzurik R. Bratislava, Slovenska republika. Vnitr Lek. 2004 Apr;50(4):286-90

Very High Levels of Tropical Sun Exposure May Increase Vitamin D to Harmful Levels: In a case-control study of  25-hydroxyvitamin D3 and IHD of 143 patients with either angiographic evidence of coronary artery disease or patients with acute myocardial infarction and 70 controls, all men ages 45-65, serum levels of 25-OH-D3 above 222.5 nmol/l (89 ng/ml) were observed in 59.4% of cases compared to 22.1% in controls (p < 0.001; unadjusted odds ratio (OR): 5.17). When controlled for age and selected variables using the multivariate logistic regression, the adjusted OR was 3.18. Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease. Rajasree S, Rajpal K, Kartha CC, Sarma PS, Kutty VR, Iyer CS, Girija G. Trivandrum, India. Eur J Epidemiol. 2001;17(6):567-71. Ed: Socioeconomic background may also be playing a role in this study since men spending so much time outdoors to get such high levels may be more economically disadvantaged, etc. These are very high vitamin D levels. I don't know how many Americans reach such levels, but in one study of adults, the upper quartile started at 81 nmol/l. This suggests few Americans reach the high levels in this study.  Of course, I am not familiar with studies showing high rates of heart disease in Americans who work a lot outdoors.  You would have to take an awful lot of supplements to reach such levels.

Hypervitaminosis D Damages Teeth: A case is reported of a 15 year old girl with hypercalcemia secondary to excess vitamin D derived from the consumption of milk that was incorrectly fortified. The changes in the permanent dentition to date are enamel hypoplasia and focal pulp calcification.  Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Apr;85(4):410-3

Vitamin D Recommendations Too Low: The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. Using parathyroid hormone, calcium absorption, and bone mineral density, vitamin D deficiency is 25(OH)D </= 80 nmol or 32 mug/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. Circulating 25-hydroxyvitamin d levels indicative of vitamin d sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin d. Hollis BW. Medical University of South Carolina. J Nutr. 2005 Feb;135(2):317-22

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