New thoughts concerning optimal vitamin D levels in the US population December, 2008

A quick review of vitamin D metabolism Vitamin D3 (cholecalciferol) is made in sun-exposed skin, or can be absorbed in the diet or as a supplement. Vitamin D3 (cholecalciferol) is made in sun-exposed skin, or can be absorbed in the diet or as a supplement. liver Vitamin D3 is converted into 25-OH vitamin D (calcidiol) in the liver. I It can also be taken as an oral supplement. This is the form of the hormone we test for in the blood. kidney25-OH-vitamin D is converted to 1,25-OH vitamin D (calcitriol) in the kidney. This is the active form of the hormone.

Action of vitamin D Vitamin D is a steroid hormone that primarily acts to increase transcription of vitamin D responsive genes primarily in the small intestine – These genes mediate increased absorption of calcium and phosphorous in the gut However, there is evidence that other cell types express the vitamin D receptor – Vitamin D plays a role in maintaining normal neuromuscular function and immunity – There is some evidence that vitamin D regulates apoptosis, cell proliferation and inflammation as well

Vitamin D deficiency Vitamin D deficiency causes osteomalacia in which bone mineralization is defective – In children this causes rickets. A common presenting syndrome is bowing of the legs – In adults this causes fragility of the bones which can lead to fractures Other symptoms of vitamin D deficiency include diffuse body aches and muscle weakness

Risk factors for vitamin D deficiency Female gender Age > 50 Minimal sun exposure Dark skin Fat malabsorption Obesity

Prevalence of vitamin D deficiency Numerous studies of both young and older people both in the United States, Europe, and parts of Asia demonstrate that vitamin D deficiency, even as defined by the lower goal levels, is extremely common. – Deficiency is likely to be present in the majority of people during the winter

Standards in healthy vitamin D levels Previously, optimal vitamin D levels have been defined by the blood levels needed to maximally suppress PTH levels – This makes sense in that it reduces bone resorption – However, PTH levels fluctuate dependent on diet, exercise, time of day and renal function making these studies difficult Studies have suggested optimal vitamin D levels ranging from 9 to 38 ng/ml

Current recommended vitamin D levels Vitamin D levelHealth Status >10-15 ng/mlCurrently considered to be sufficient in otherwise healthy people >30 ng/mlNew recommendations of some researchers based on new studies suggesting improved health outcomes at higher levels

Current vitamin D intake recommendations AgeCurrent Recommended Daily Intake Under IU IU Over IU

New studies of the health effects of vitamin D The authors of recent meta analyses that use health outcomes rather than PTH suppression to determine optimal vitamin D levels.

Study Design The authors pooled numerous RCT and epidemiological studies and performed regression analysis in order to create a plot relating health outcomes as a function of vitamin D level.

Copyright ©2006 The American Society for Nutrition Bischoff-Ferrari, H. A et al. Am J Clin Nutr 2006;84:18-28 FIGURE 1. Regression plot of difference in bone mineral density by 25-hydroxyvitamin D [25(OH)D] concentrations in younger ( y; A) and older (>=50 y; B) adults after adjustment for sex, age, BMI, smoking, calcium intake, estrogen use, month of vitamin D measurement, and poverty income ratio FIGURE 2. Relative risks (RRs; {square}) of hip fracture (A) and nonvertebral fracture (B) between subjects who took vitamin D and control subjects Regression analysis of BMD and fracture risk versus vitamin D levels

Other benefits of vitamin D This meta analysis suggests improvement of the following outcomes with increasing vitamin D levels – Bone mineral density – Fracture risk – Lower extremity function – Fall risk – Oral health – Colorectal cancer risk

Major results The analysis performed suggests that many of the proposed health benefits of vitamin D supplementation are not realized at current intake and goal levels. – Vitamin D levels in excess of 30 ng/ml are suggested and maximum benefits come at levels closer to 40 ng/ml – An increase in recommended daily intake is required to attain these vitamin D levels.

What would new vitamin D goals mean? Based on evidence of improved health outcomes, some have proposed making ng/ml the goal vitamin D level. – By this standard, less than 30% of Americans aged years, and less than 10% of those over 50 would meet their goal. – It is estimated that dietary intake in excess of 1000 IU/day would bring 50% of our population to this new goal

Considerations Do all age, racial, geographic groups require the same vitamin D levels for general health? Is widespread supplementation of vitamin D safe in all populations? Would supplementation benefit younger people? Is it possible that some people have low calcidiol levels, but adequate calcitriol levels and thus no adverse consequence to “low” vitamin D?

Controversy over vitamin D goals In 2007, the Scientific Advisory Commission on Nutrition recently found insufficient evidence to support increasing vitamin D goals However the American Association of Pediatrics has recently recommended vitamin D intake of 400 IU/day rather than the current standard of 200 IU/day

Take home message There is considerable evidence to support vitamin D deficiency screening and supplementation in elderly individuals at risk for osteoporosis, falls and fractures. Controversy remains as to whether new vitamin D goals which would require population-wide supplementation are safe and beneficial. New recommendations regarding vitamin D testing and supplementation are likely in the coming years.

References Scientific Advisory Committee on Nutrition. Update on Vitamin D. Position Statement by the Scientific Advisory Committee on Nutrition. London: The Stationery Office, Limited, Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr 2007;85: Yetley EA. Assessing vitamin D status of the U.S. population. Am J Clin Nutr. 2008;88: 558S-564S Wagner CL, Greer FR, and the Section on Breastfeeding and Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008;122: Bischoff-Ferrari H, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84: Dietary Supplement Fact Sheet: Vitamin D. Office of Dietary Supplements National Institutes of Health. Accessed at: