WASHINGTON—Consumers looking to consume more vitamin D to achieve numerous health benefits demonstrated by many recent studies can do so without concern of health risks, according to Andrew Shao, Ph.D., senior vice president of scientific and regulatory affairs, Council for Responsible Nutrition (CRN). Shao and CRN’s senior vice president of scientific and international affairs, John Hathcock, Ph.D., co-authored a risk-benefit analysis on vitamin D intake, with colleagues from Harvard University, Tufts University and the University of Zurich (Osteoporos Int. 2010 Jul; 21(7):1121-32. DOI: 10.1007/s00198-009-1119-3).
The analysis compared the benefits of supplemental vitamin D as measured by the incidence of falls, fractures, cardiovascular outcomes and colon cancer with the potential risk of adverse effects as measured by elevated blood calcium. The authors concluded vitamin D intake needed for optimal benefit is far from that which poses a risk.
To assess benefit, the authors based their analysis on published double blind, randomized controlled trials (RCTs) examining the effect of supplemental vitamin D on fall and fracture risk. They found optimal benefits were observed at a mean serum 25(OH)D level—the body’s marker of vitamin D nutritional status—between 75 and 110 nmol/l (30-44 ng/ml), resulting from a vitamin D dose of about 1,000 IU/d. The authors also assessed published cohort data on cardiovascular outcomes and colorectal cancer risk, and found optimal benefit at similar serum 25(OH)D levels. To assess risk, the authors examined data from these same studies as well as additional trials involving supplementation with high doses of vitamin D. At these optimal and even much higher levels, the authors observed no increase in risk for elevated blood calcium, consistent with findings from a previous analysis by Shao and Hathcock, which concluded up to 10,000 IU/d can be consumed without risk for adverse effects (Am J Clin Nutr. 2007;85:6-18)
“Over the years, a large body of research has accrued on both the benefits and potential risks of vitamin D, but these analyses on efficacy and safety have been conducted separately," Shao said. “This combined benefit-risk analysis allows for the comparison of the efficacy and safety of vitamin D in a side-by-side manner. It is clear from our present and past analyses that optimal blood levels of vitamin D achieved with oral doses of up to 4,000 IU/d are associated with little, if any, risk."
With the Institute of Medicine (IOM) currently reviewing the scientific literature to revise the Dietary Reference Intakes (DRIs) for vitamin D to more closely match the updated science, Shao expects this type of published analysis will be useful. “The IOM recommendations will be released soon and we trust they will take this latest analysis into consideration," he said. “We’re so much farther along scientifically than where we were when the current DRIs were published more than 13 years ago. We now know much more about the benefits of vitamin D, and we know there is a wide safety margin between the dose that is beneficial and where risk for adverse effects begins in normal healthy adults. The next step is to get more useful recommendations to the general public.”
Osteoporos Int. 2010 Jul;21(7):1121-32. Epub 2009 Dec 3.
Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC.
Centre on Aging and Mobility, Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Gloriastrasse 25, 8091, Zurich, Switzerland. Heike.Bischoff at usz.ch
Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D.
INTRODUCTION: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk.
METHODS AND RESULTS: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk.
CONCLUSION: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population. PMID: 19957164
Dose of vitamin D and achieved 25(OH)D levels based on RCTs with a duration of at least 4 weeks. a Lower-dose trials (double- blind fall and fracture RCTs).
This graph summarizes data from identified RCTs (as illustrated in Fig. 1) with oral doses of vitamin D of less than 10,000 IU vitamin D per day and a treatment duration of at least 4 weeks.
Dots either represent the mean 25(OH)D level from a single trial or the mean and the range of several trials.
There were three RCTs with 400 IU vitamin D per day with a mean increase in 25 (OH)D levels to 56.7 nmol/l (range, 44 to 64 nmol/l) after a mean treatment duration of 653 days (range, 140 to 1148 days).
The trial with 700 IU vitamin D and achieved mean serum levels close to 100 nmol/l may be an outlier due to the high starting levels documented in the trial (84 nmol/l in men and 72 nmol/l in women age 65 years and older ).
There were nine RCTs for 800 IU per day with a mean increase in 25(OH)D levels to 75 nmol/l (range, 60 to 105 nmol/l) after a mean treatment duration of 697 days (range, 56 to 1,680 days).
There were seven RCTs with 2,000 IU vitamin D per day with a mean increase in 25(OH)D levels to 87 nmol/l (range, 71 to 103 nmol/l) after a mean treatment duration of 146 days (range, 42 to 365 days).
There were three RCTs for 4,000 IU per day with a mean increase in 25(OH)D levels to 120 nmol/l (range, 85.5 to 160 nmol/l) after a mean treatment duration of 168 days (range, 56 to 365 days), and there were four trials with a treatment dose between 5,720 and 7,600 IU vitamin D per day with a mean increase in 25(OH)D levels to 128 nmol/l (range, 120–147 nmol/l).
From this summary of available dose–response data from RCTs, most trials among healthy younger and older adults reached a mean value in the target range of 75 to 110 nmol/l with 1,800 IU to 4,000 IU vitamin D3 per day treated for at least 42 days
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