In 2011, the Vitamin D and Calcium Dietary Guidelines Committee of the Institute of Medicine (IOM) of the National Academies published revised guidelines on vitamin D and calcium requirements9. The evidence used in preparing the guidelines was largely from randomized controlled trials (RCT’s) vetted by the Tufts Evidence-based Practice Center2. Observational studies were included only to the extent that they provided evidence of possible increased risk of adverse health outcomes at higher serum 25-hydroxyvitamin D [25(OH)D] concentrations. Benefits were identified only for bones. For people between the ages of 1 and 70 years, oral intakes of 600 IU/d vitamin D and serum 25(OH)D concentrations of 20 ng/ml (50 nmol/l) were recommended.
The Endocrine Society reviewed the data and found reasonable evidence for cancer, cardiovascular disease, and pregnancy, and subsequently recommended the following11:
“We suggest that all adults aged 50–70 and 70_ yr require at least 600 and 800 IU/d, respectively, of vitamin D to maximize bone health and muscle function. Whether 600 and 800 IU/d of vitamin D are enough to provide all of the potential nonskeletal health benefits associated with vitamin D is not known at this time. However, to raise the blood level of 25(OH)D above 30 ng/ml may require at least 1500–2000 IU/d of supplemental vitamin D.”
This month, the IOM committee members responded to the Endocrine Society’s rebuttal. They dug in their heels and did not accept any evidence for non-skeletal benefits8. The Endocrine Society committee responded by providing evidence that even for skeletal effects, the evidence supports values higher than 20 ng/ml and 600 IU/d vitamin D, and also provided more evidence for non-skeletal benefits4.
The position of the IOM committee is very difficult to understand. For one thing, the evidence of non-skeletal benefits has increased since the reviews by Chung et al.2 and Ross et al.9 were published.
For another, the concern about adverse effects of higher 25(OH)D concentrations is based solely on prospective observational studies in which a single serum 25(OH)D concentration at time of enrollment is used, with a follow-up period lasting anywhere from three to 28 years. As follow-up time increases, the usefulness of that single value decreases3,10. Case-control studies, in which serum 25(OH)D concentration is measured at the time of diagnosis, do not show any U-shaped response for cancer1.
Based on the rapidly rising journal literature on the benefits of vitamin D and the absence of adverse effects, it appears that the IOM report is best ignored and that those interested in determining optimal serum 25(OH)D concentrations and oral intake amounts consider 40 ng/ml (100 nmol/l) and 1000-5000 IU/d vitamin D3 as the values that correspond more closely with what nature suggests7. However, there is considerable individual variability in serum 25(OH)D concentration vs. oral intake6, so testing of serum 25(OH)D concentration may be advisable.
As for pregnancy and lactation, Bruce Hollis and colleagues showed that it takes about 4000 IU/d vitamin D3 to increase serum 1,25-dihydroxyvitamin D concentrations to optimal concentrations and to provide sufficient native vitamin D (cholecalciferol) in breast milk for the nursing infant5.
For those wishing more information on the health benefits of vitamin D, there are a number of documents at http://www.vitamindcouncil.org/health-conditions/, and those wishing to see the original journal articles may find links to them at www.pubmed.gov.
- Abbas S, Chang-Claude J, Linseisen J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009 Jan 1;124(1):250-5.
- Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, et al. (2009). Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess (Full Rep)(183), 1-420. (Prepared by Tufts Evidence-based Practice Center under Contract No. 290-2007-10055-I). AHRQ Publication No. 09-E015, Rockville, MD: Agency for Healthcare Research and Quality. August 2009. (http://www.ahrq.gov/downloads/pub/evidence/pdf/vitadcal/vitadcal.pdf)
- Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011:31: 617-22.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012;97(4):1153-8.
- Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26(10):2341-57.
- Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol. 2010 Apr 15;171(8):903-8.
- Luxwolda MF, Kuipers RS, Kema IP, Janneke Dijck-Brouwer DA, Muskiet FA. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr. 2012 Jan 23:1-5. [Epub ahead of print]
- Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Manson JE, Mayne ST, Ross AC, Shapses SA, Taylor CL. IOM Committee members respond to Endocrine Society Vitamin D Guideline. J Clin Endocrinol Metab. 2012;97(4):1146-52.
- Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8.
- Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines. Dermato-Endocrinology. 2011;3(3):199-204.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2011 Jul;96(7):1911-30.