'D' is for Dilemma: Two Vitamin Guidelines, Two Recommendations

Best Evidence Review

Charles P. Vega, MD


January 05, 2011

In This Article

Current Trial and Other Studies on Vitamin D

The review from Osteoporosis Canada reminds physicians that measuring serum 25-OH-D is the best way to evaluate a patient's level of vitamin D. However, this measurement may not be appropriate for patients with abnormalities of calcitriol synthesis, such as sarcoidosis. Moreover, the assays that measure 25-OH-D vary among laboratories, and physicians should keep this in mind when evaluating readings from different laboratories.

Who should be tested for vitamin D deficiency? The current recommendations do not advocate widespread screening among patients without osteoporosis or diseases that could interfere with vitamin D metabolism. The optimal serum level of 25-OH-D is debatable, but seems to be between 75 and 80 nmol/L. Vitamin D deficiency is usually defined by levels less than 25 nmol/L.

Among patients treated with oral vitamin D supplements, serum levels can be expected to plateau after 3-4 months. Therefore, among patients with osteoporosis, it is reasonable to check 25-OH-D levels at baseline and 3 months after initiation of vitamin D supplementation.

The record of clinical efficacy of vitamin D supplements in the prevention of disease is mixed. In the Women's Health Initiative (WHI), supplementation with calcium carbonate 1000 mg plus vitamin D3 400 IU daily improved bone mineral density at the hip but did not significantly affect the risk for fracture over a mean follow-up of 7 years.[3] However, women in the supplementation group had a 17% increase in the risk for renal calculi.

The WHI trial has been criticized for using a dose of vitamin D that was too low. Indeed, a meta-analysis demonstrated that doses of vitamin D at 700-800 IU daily reduced the risk for hip fracture by 26% and any nonvertebral fracture by 23% compared with either calcium supplements or placebo.[4] By contrast, the dose of 400 IU was not effective for fracture prevention.

Higher levels of vitamin D also seem to reduce the risk for falls, possibly by improving muscle strength. In a meta-analysis of 5 randomized trials involving a total of 1237 participants, vitamin D supplements reduced the risk for falling by 22% compared with calcium or placebo.[5] Although the dose of vitamin D did not seem to affect the main study result, the demographics of the included research meant that the conclusion was only significant for women.

Vitamin D has also received a significant amount of attention regarding its relationship to cancer. In the WHI cohort, the rate of colorectal cancer was the same whether the women were assigned to calcium and vitamin D supplements or to placebo.[6] Overall, although epidemiologic studies have suggested that lower serum markers of vitamin D are associated with a higher risk for colon cancer, intervention studies have mixed results regarding the ability of vitamin D supplements to reduce the risk for this disease.[7]

The authors from Osteoporosis Canada synthesize these themes into recommendations for vitamin D supplementation at significantly higher doses than those of previous guidelines. Overall, they believe that exposure to sunlight and dietary intake are insufficient to maintain 25-OH-D at recommended levels among most Canadians and offer the following recommendations for vitamin D supplementation:

  • Low-risk individuals are adults younger than 50 years without comorbid conditions. Supplementation should consist of 400-1000 IU daily. There is no need to monitor 25-OH-D levels during treatment of these individuals.

  • Moderate-risk individuals are adults older than 50 years with or without osteoporosis. These persons should take 800-2000 IU daily. Levels of 25-OH-D should be measured after 3-4 months of treatment, and the vitamin D dosage may be titrated upward if levels are insufficient.

  • High-risk individuals are those who have recurrent fractures or bone loss despite treatment for osteoporosis. Levels of 25-OH-D should guide treatment for these patients, who may require vitamin D supplements at dosages exceeding 2000 IU daily.

Vitamin D3 is the preferred supplement for adults. Calcitriol has a narrow safety index and should not be used for routine supplementation.


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