Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada (summary)
David A. Hanley MD, Ann Cranney MB BCh, Glenville Jones PhD, Susan J. Whiting PhD, William D. Leslie MD;
- Vitamin D is essential for the prevention of osteoporosis.
- A serum level of 25-hydroxyvitamin D above 75 nmol/L reflects optimal vitamin D intake or synthesis to consistently improve clinical outcomes such as fracture risk; vitamin D supplementation is needed to achieve this target.
- Recommended intake for low-risk and younger adults should be increased to 10–25 ?g (400–1000 IU) daily and for high-risk and older adults, to 20–50 ?g (800–2000 IU) daily, with consideration of higher doses (key change from 2002 guideline).
- For individuals being treated with pharmacologic agents for osteoporosis, vitamin D status should be assessed by serum measurement of 25-hydroxyvitamin D after three months of vitamin D supplementation (key change from 2002 guideline).
- Measurement of 25-hydroxyvitamin D in the serum (with no restrictions on the timing of collection ) is the best indicator of vitamin D sufficiency2 (level 2 evidence).
- In the absence of external laboratory proficiency testing, serum 25-hydroxyvitamin D values from different clinical laboratories cannot be assumed to be comparable 8,10 (level 2 evidence).
- Monitoring of routine vitamin D supplementation by measurement of serum 25-hydroxyvitamin D is unnecessary (level 4 evidence). Monitoring of high-risk patients and those with osteoporosis should not be performed before three months of standard supplementation (20–50 ?g [800–2000 IU daily) 11 (level 2 evidence). Patients taking daily doses above Health Canada’s “tolerable upper intake level” (currently set at 50 ?g 2000 IU) should undergo monitoring of serum 25- hydroxyvitamin D (level 4 evidence).
- In Canada, some vitamin D is obtained with safe exposure to the sun during the summer months46–48 (level 1 evidence), but exposure to sunlight and dietary intake are insufficient to maintain average serum 25-hydroxyvitamin D concentration above 75 nmol/L throughout the year 11,18,19 (level 2 evidence).
- A daily intake of 25 ?g vitamin D3 (1000 IU) — a safe, commonly available dose — will raise the average serum level of 25-hydroxyvitamin D by 15–25 nmol/L 11,21 (level 2 evidence).
- The upper level for safe vitamin D3 intake has not been well defined but is probably as high as 250 ?g (10 000 IU) daily 11,22 (level 2 evidence). In clinical practice, supplementation with this dose of vitamin D is rarely required (level 4 evidence).
- Supplementation with vitamin D3 and calcium increases bone density in postmenopausal women and in men over age 50 years 24,27,28,49 (level 1 evidence).
- Vitamin D3 at daily doses of 20 ?g (800 IU), in combination with calcium (1000 mg), reduces the risk of hip and nonvertebral fractures in elderly people living in institutions (level 1 evidence). The evidence for community-dwelling individuals is less strong 50 (level 2 evidence).
- There is evidence that supplementation with 20 ?g (800 IU) vitamin D3 daily reduces the risk of falls, particularly from trials with adequate ascertainment of falls 38 (level 2 evidence).
- Vitamin D insufficiency has been associated with malignancies40 (especially colorectal cancer 41), diabetes mellitus,45 multiple sclerosis 51 and impaired immune response 44 (level 3 evidence).
- The benefits of vitamin D for these nontraditional roles are associated with 25-hydroxyvitamin D levels above 75 nmol/L (30 ng/ml) 21,40 (level 3 evidence).
- Levels of evidence are explained in detail in the full guideline. 4 In brief, levels of evidence range from very high quality (level 1+, systematic overview or meta-analysis of randomized controlled trials) to very low quality (level 6, case series without controls).
- Adequate vitamin D status, in addition to calcium from diet or supplements, is essential for the prevention of osteoporosis (level 1 evidence, grade A recommendation).
- Administration of vitamin D and calcium should not be used as the sole treatment for osteoporosis (level 1 evidence, grade A recommendation).
- The optimal level of serum 25-hydroxyvitamin D for musculoskeletal benefits is at least 75 nmol/L (30 ng/ml) (level 2 evidence, grade B recommendation).
- Laboratories performing 25-hydroxyvitamin D testing should take part in external proficiency surveys and should demonstrate that values reported for shared samples approximate the consensus values reported by others (level 4 evidence, grade D recommendation).
- In healthy adults at low risk for vitamin D deficiency (i.e., under age 50, without osteoporosis or conditions affecting vitamin D absorption or action), routine vitamin D supplementation (10–25 ?g 400–1000 IU daily) is recommended. Serum 25-hydroxyvitamin D should not be measured (level 5 evidence, grade D recommendation).
- Adults over 50 years of age are at moderate risk for vitamin D deficiency. Supplementation with at least 20–25 ?g (800–1000 IU) of vitamin D3 daily is recommended. To achieve optimal vitamin D status (> 75 nmol/L) (>30 ng/ml) , many individuals may require supplementation at greater than 25 ?g (1000 IU) daily. Doses up to 50 ?g (2000 IU) are safe and do not require monitoring (level 3 evidence, grade C recommendation).
- For individuals receiving pharmacologic therapy for osteoporosis, measurement of serum 25-hydroxyvitamin D should follow three to four months of adequate supplementation and should not be repeated if the optimal level is achieved (grade D recommendation).
- Measurement of serum 25-hydroxyvitamin D is recommended for individuals with recurrent fractures, bone loss despite osteoporosis treatment or comorbid conditions that affect vitamin D absorption or action (grade D recommendation). Dose requirements above Health Canada’s current tolerable upper intake level (50 ?g 2000 IU) may be needed, in which case monitoring of serum 25-hydroxyvitamin D levels is required (level 4 evidence, grade D recommendation).
- Exposure to natural sunlight , when used in moderation (avoiding sunburn) and individualized to the person’s skin type, can contribute to summertime vitamin D sufficiency (level 2 evidence, grade B recommendation).
- Research is needed to better define the minimum required daily dose and the optimal dose for musculoskeletal and other health benefits, and to better establish the tolerable upper level for vitamin D supplementation (grade D recommendation).
All authors were members of the Vitamin D Working Group of Osteoporosis Canada.
David A. Hanley has been an investigator in clinical trials, participated in advisory boards or received speaking honoraria from the following companies: Amgen, Merck Frosst Canada, Proctor and Gamble Canada (now Warner-Chilcott), sanofi-aventis, Novartis, NPS Phar- maceuticals, Eli Lilly Canada, Pfizer, Wyeth-Ayerst, Roche, Servier, Abbott Laboratories and Nycomed.
Glenville Jones serves on the scientific advisory board of the not-for-profit Vitamin D External Quality Assessment Scheme. He is also on the advisory board and has received a research grant from Cytochroma Inc. and is a member of the Genzyme speakers’ bureau.
Susan J. Whiting is a member of the International Institute for Nutrition and Bone Health, an educational initiative sponsored by Yoplait. She has received current or recent funding in the form of grants and contracts from the Canadian Institutes of Health Research and the Canadian Foundation for Dietetic Research. She is a nutrition consultant to Osteoporosis Canada. She has presented talks with sponsorship from the Dairy Farmers of Canada, the International Alliance of Dietary/Food Supplement Associations, the Vitamin D Society, GlaxoSmithKline and Amway/Nutrilite.
William D. Leslie has received speaker fees and unrestricted research grants from Merck Frosst Canada Ltd; unrestricted research grants from sanofi-aventis, Procter and Gamble Pharmaceuticals Canada, Novartis, Amgen Pharmaceuticals Canada and Genzyme Canada; and has served on advisory boards for Genzyme Canada, Novartis and Amgen Pharmaceuticals Canada.
Ann Cranney None declared
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Correspondence to: Dr. David A. Hanley, University of Calgary Health Sciences Centre, 3330 Hospital Drive NW, Calgary AB T2N 4N1; dahanley at ucalgary.ca