DESTIN, FLA. – More is not necessarily better when it comes to vitamin D.
“The optimal intake and blood levels are probably much more moderate than many have led us to believe,” Dr. JoAnn E. Manson said at the meeting.
As a member of the 14-person Institute of Medicine Committee charged with developing a recently published report on dietary reference intakes of vitamin D and calcium, Dr. Manson assisted in a “rigorous comprehensive review” of more than 1,000 studies, and while many researchers and clinicians have argued that people need much higher levels than the 400-800 IU/day intake (depending on age) recommended by the IOM to promote optimal health, the available evidence simply has not borne that out, said Dr. Manson, professor of epidemiology at Harvard University and chief of the division of preventive medicine at Brigham and Women's Hospital, Boston.
Although some IOM report naysayers advocate for levels up to 6,000 IU/day – and the lay press is replete with stories touting vitamin D as a panacea, it is actually very difficult to find any solid data showing increased benefit with higher doses, she said.
In fact, the committee's findings indicate that adequate intake for infants through age 12 months is 400 IU/day, and that the Recommended Dietary Allowance for individuals aged 1-70 years should be at least 600 IU/day, and those over age 70 years it should be 800 IU/day. The upper intake levels are 1,000 and 1,500 IU/day for those ages 0-6 months and 6-12 months, respectively, 2,500 IU/day for those ages 1-3 years, 3,000 IU/day for those ages 4-8 years, and 4,000 IU/day for those over age 8 years, according to the IOM report (J. Clin. Endocrinol. Metab. 2011;96:53-8).
These minimum levels represent the intake needed to meet the vitamin D requirements of 97.5% of the population, and correspond to a serum 25-hydroxyvitamin D (25-OHD) level of 20 ng/mL, which the data indicate is the optimal level. At levels above the upper intake level, which correspond to a serum 25-OHD level of about 50 ng/mL, adverse effects have been reported, Dr. Manson said.
Emerging evidence suggests excess intake may be associated with increased all-cause mortality, cancer, cardiovascular disease, falls, and fractures, she noted.
National Health and Nutrition Examination Survey (NHANES) data from 2008, for example, showed that age-adjusted mortality was highest among those with serum 25-OHD levels below 19 ng/mL in African Americans and below 27.5 ng/mL in the entire cohort, and that mortality decreased with increasing levels – but only to a certain point. At levels in the 50 ng/mL range for African Americans, and above 85 ng/mL in the entire cohort, mortality increased steadily.
Data on the effects of vitamin D on skeletal health, which provided the strongest basis for the IOM committee's report as they were most plentiful and convincing in terms of showing cause and effect (although evidence regarding numerous other diseases such as cancer, diabetes, and more were also considered), also suggest that too much vitamin D can lead to adverse effects. Women's Health Initiative findings, for example, show that adjusted hip fracture rates are highest among those with serum 25-OHD levels of 19.04 ng/mL and those greater than 28.3 ng/mL, and lowest among those between these levels (Ann. Intern. Med. 2008;149:242-50), Dr. Manson said.
In older men in the Osteoporotic Fractures in Men (MrOS) study, the adjusted risk of hip fractures was shown to be highest in those with serum 25-OHD levels less than 19 ng/mL (odds ratio 2.36, compared with those with levels greater than 28 ng/mL), with risk declining steadily in those with levels up to 28 ng/mL (J. Bone Miner. Res. 2010;25:545-53).
Other findings indicate the skeletal benefits of vitamin D are dependent on adequate calcium intake, which the committee determined is 200 and 260 mg/day for those aged 0-6 and 6-12 months, respectively; 700 mg/day for those aged 1-3 years; 1,000 mg/day for those aged 4-8 years, 19-70 years, and for women aged 19-50 years who are pregnant or lactating; 1,200 mg/day for those aged 51 years and older; and 1,300 mg/day for those aged 9-18 years, and for women aged 14-18 years who are pregnant or lactating.
An Agency for Healthcare Research and Quality report in 2009, for example, showed that three randomized controlled trials indicated no significant effect of vitamin D alone on fracture risk, but that one randomized controlled trial showed a benefit in those who received 800 IU of vitamin D3 plus 1,200 mg/day of calcium for 2 years (odds ratio of fractures 0.80), Dr. Manson said.