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Vitamin D, the Right Stuff

 Vitamin D is a fat-soluble vitamin that your body makes after exposure to ultraviolet (UV) rays from the sun. Vitamin D functions as a hormone because it sends a message to the intestines to increase the absorption of calcium and phosphorus. By promoting calcium absorption, vitamin D helps to form and maintain strong bones.

Because vitamin D increases the absorption of calcium in the gastrointestinal tract and stimulates osteoblastic (bone-building cells) activity, vitamin D has  generated lots of interest  in the medical literature. Borderline low levels of vitamin D have been found to be very common in the United States and Canada.

It is estimated that over 50 million adults in the United States either have, or are at risk of developing, osteoporosis.1 Adequate storage levels of vitamin D help keep bones strong and help prevent osteoporosis in older adults. Vitamin D deficiency results in diminished calcium absorption, and has been linked to a higher incidence of osteoporosis-related bone fractures seen in postmenopausal women and older Americans.2,3

Because of limited access to sun exposure, supplementation is the only option for most Americans to assure Vitamin D adequacy. It is important to take into account the differences between D2 and D3 before choosing a supplement.  D3 is the natural form of the vitamin; the safer, higher-quality supplement; the form of vitamin D made by the body in response to sunlight.  D2 and D3 also have differences in biological activity that result  in more active vitamin D in the body in response to D3 supplements compared to D2. In a review of 56 trials of vitamin D supplementation in the elderly, vitamin D3 was found to decrease mortality risk, however D2 was not.4
Read more about D2 vs. D3

Some have claimed that a meta-analysis published in 2015 negates the need for vitamin D supplementation. The analysis pooled many studies and stated the conclusion that vitamin D supplementation does not reduce the risk of falls or other negative outcomes by 15% or more.5 However, there are details to be considered. This analysis did not take into account D2 vs. D3, and also did not group studies by the dose of vitamin D. A previous pooled analysis, which analyzed studies based on the dose of vitamin D, established that dose matters. This analysis took into account the actual intake of vitamin D, not just whether or not the person had been assigned to the supplement group. In this analysis, there was a 30 percent reduction in hip fracture rate at the highest level of vitamin D intake (792-2000 IU) in the supplement groups compared to the control groups. 6,7 An earlier meta-analysis supports this idea, recommending 800 IU as the minimum effective dose. 8

Not just bones
Vitamin D is known to have protective effects on bone health, via increasing calcium absorption. But it is now known that vitamin D has several other critical functions. Vitamin D insufficiency is thought to be a key contributor to many human diseases including several cancers, diabetes, cardiovascular disease, depression, and autoimmune diseases3,9 Scientists have found that Vitamin D has biological actions in almost every cell and tissue in the human body.

Vitamin D regulates several genes and cellular processes related to cancer progression. Some of the most groundbreaking findings in nutrition science in recent years have been evidence of the powerful protection provided by vitamin D against common cancers:

  • Breast cancer: About 75% of women with breast cancer are vitamin D deficient.4 A 2009 meta-analysis of 19 studies established a strong inverse relationship between circulating vitamin D levels and breast cancer – women in the highest vitamin D range reduced their risk of breast cancer by 45%.10 
  • Colorectal cancer: A 2009 review of 25 studies found that sufficient vitamin D levels were consistently associated with reduced risk of colorectal cancer.11 Even after diagnosis with colorectal cancer, higher vitamin D levels are associated with reduced mortality.12
  • Cancers of the prostate, pancreas, lung, and endometrium are also associated with vitamin D insufficiency9,13

Vitamin D has growth-inhibitory effects on cells derived from breast, colon, prostate, and skin cancers, and a 2014 meta-analysis concluded that supplementation with vitamin D3 was associated with a 12 percent lower risk of death from cancer.4
Read more about vitamin D and cancer prevention.

Too much vitamin D?
More of a vitamin is not necessarily better. Some concerns have been raised about vitamin D supplementation, arising from studies of excessively large doses given all at once. Annual injections of 300,000 IU of vitamin D2 (the synthetic form) for three years resulted in a 49% increase in hip fractures in one study of elderly participants.14 For comparison, the tolerable upper limit (the maximum recommended daily dose) is currently 4000 IU. Large doses of hundreds of thousands of IUs may be problematic even when using the natural form, vitamin D3. For example, a study testing a dose of 500,000 IU vitamin D3 in elderly women found an increased the rate of falls, and a trend toward an increase in fracture risk compared to placebo.15 One possible explanation of these negative effects is that the excessively large dose of vitamin D could have stimulated rapid bone turnover, resulting in the breakdown of existing bone. 16 Not all studies on high dose vitamin D showed negative effects.17 However, a recent meta-analysis pooled all the conflicting data, and concluded that high dose vitamin D supplementation had no effect on fracture risk but slightly increased the risk of falls.18

A moderate, consistent daily dose of D3 is a safe and conservative method to keep vitamin D levels in a healthy range, not too high and not too low. There is significant scientific agreement that a 25(OH)D of at least 30 ng/ml for several aspects of health. 19-21 It is reasonable therefore to supplement if one’s levels fall below this optimal range. Vitamin D insufficiency is now recognized as a pandemic, affecting 30-50% of the population.9,22 But again, more is not always better; the research suggests that increasing one’s 25(OH)D above approximately 45 ng/ml confers no further benefit and may even be detrimental.19,23-25

Getting the right amount of vitamin D
For most people, the principal source of vitamin D is production by the skin in response to sunlight. Very few foods naturally contain vitamin D, and achieving adequate vitamin D levels via sunlight can be difficult depending on your geographical location, skin color, and opportunities for sun exposure, especially in the winter months. Plus, sun exposure to assure optimal Vitamin D status may damage and age the skin increasing wrinkling, mottling and the risk of skin cancer. 

A smart option is a moderate daily dose of vitamin D3, not too much or too little. We should aim for the sweet spot of 30-45 ng/ml, as suggested by the scientific evidence. 19-21,23-25 Also, we should choose D3, the natural form of the vitamin, the form the body produces in response to sunlight. There is overwhelming evidence of benefit, and no risks to be cautious of. If you do not supplement, it makes sense to have your 25(OH)D levels tested and be proactive about your health because a long-standing deficiency can be harmful. 

To maintain adequate blood levels of vitamin D, it is sensible for individuals with limited sun exposure to either ingest a moderate daily dose of supplemental vitamin D3 (approximately 1000-2000 IU/day), or test their 25(OH)D to confirm sufficiency.


1. National Osteoporosis Foundation: What is Osteoporosis? [http://nof.org/articles/7]
2. Brincat M, Gambin J, Brincat M, Calleja-Agius J. The role of vitamin D in osteoporosis. Maturitas 2015, 80:329-332.
3. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 2004, 80:1678S-1688S.
4. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2014, 1:CD007470.
5. Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. Lancet Diabetes Endocrinol 2014, 2:573-580.
6. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005, 293:2257-2264.
7. Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 2012, 367:40-49.
8. Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007, 370:657-666.
9. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008, 87:1080S-1086S.
10. Chen P, Hu P, Xie D, et al. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat 2010, 121:469-477.
11. Zhou G, Stoitzfus J, Swan BA. Optimizing vitamin D status to reduce colorectal cancer risk: an evidentiary review. Clin J Oncol Nurs 2009, 13:E3-E17.
12. Ng K, Wolpin BM, Meyerhardt JA, et al. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. Br J Cancer 2009, 101:916-923.
13. Peterlik M, Grant WB, Cross HS. Calcium, vitamin D and cancer. Anticancer Res 2009, 29:3687-3698.
14. Smith H, Anderson F, Raphael H, et al. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford) 2007, 46:1852-1857.
15. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010, 303:1815-1822.
16. Rossini M, Gatti D, Viapiana O, et al. Short-term effects on bone turnover markers of a single high dose of oral vitamin D(3). J Clin Endocrinol Metab 2012, 97:E622-626.
17. Rossini M, Alberti V, Flor L, et al. Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study. Aging Clin Exp Res 2004, 16:432-436.
18. Zheng YT, Cui QQ, Hong YM, Yao WG. A meta-analysis of high dose, intermittent vitamin D supplementation among older adults. PLoS One 2015, 10:e0115850.
19. Zittermann A, Iodice S, Pilz S, et al. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012, 95:91-100.
20. Schottker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev 2013, 12:708-718.
21. Bischoff-Ferrari HA. Vitamin D and fracture prevention. Rheum Dis Clin North Am 2012, 38:107-113.
22. Lee JH, O'Keefe JH, Bell D, et al. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol 2008, 52:1949-1956.
23. Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population. Arch Intern Med 2008, 168:1629-1637.
24. Durup D, Jorgensen HL, Christensen J, et al. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab 2012, 97:2644-2652.
25. Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab 2013, 98:3001-3009.

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