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Caution regarding 25-hydroxyvitamin D monitoring in women with breast cancer. Chlebowski RT. J Clin Oncol. 2009 Aug 20;27(24):e72-3; author reply e74. Epub 2009 Jul 20. PMID: 1962047

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Cranney A, Weiler HA, O'Donnell S, Puil L. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. Review. PMID: 18689393 We found inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.

Effectiveness and safety of vitamin D in relation to bone health. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235. Review. PMID: 18088161 CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

Why would vitamin D be prescribed when vitamin D3 is available over-the-counter? Let's review the known differences between vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol): --D3 is the human form; D2 is the non-human form found in plants. --Dose for dose, D3 is more effective at raising blood levels of 25-hydroxy vitamin D than D2. It requires roughly twice to 250% of the dose of D2 to match that of D3 (Trang H et al 1998). --D2 blood levels don't yield long-term sustained levels of 25-hydroxy vitamin D as does D3. When examined as a 28-day area under the curve (AUC--a superior measure of biologic exposure), D3 yields better than a 300% increased potency compared to D2. This means that it requires around 50,000 units D2 to match the effects of 15,000 units D3 (Armas LA et al 2004). --D2 has lower binding affinity for vitamin D-binding protein, compared to D3 --Mitochondrial vitamin D 25-hydroxylase converts D3 to the 25-hydroxylated form five times more rapidly than D2. --As we age, the ability to metabolize D2 is dramatically reduced, while D3 is not subject to this phenomenon

Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility.\nSimmons JD, Mullighan C, Welsh KI, Jewell DP.\nGut. 2000 Aug;47(2):211-4.\nPMID: 10896912 \ndoi:10.1136/gut.47.2.211

This article discusses our experience at the one-day Institute of Medicine workshop on vitamin D and calcium. Both of us had an opportunity to make comments before the committee. Here are Paul's comments and slides and here are Amy's comments and slides. Note that our 2009 paper in Autoimmunity Reviews[1] discusses some of the science we allude to in further detail.

ScienceDaily (Aug. 3, 2009) - Seven out of ten U.S. children have low levels of vitamin D, raising their risk of bone and heart disease, according to a study of over 6,000 children by researchers at Albert Einstein College of Medicine of Yeshiva University. The striking findings suggest that vitamin D deficiency could place millions of children at risk for high blood pressure and other risk factors for heart disease.

White Europeans could have evolved as recently as 5,500 years ago, according to research which suggests that the early humans who populated Britain and Scandinavia had dark skins for millenniums. It was only when early humans gave up hunter-gathering and switched to farming about 5,500 years ago that white skin began to be favoured, say the researchers. This is because farmed food was deficient in vitamin D, a vital nutrient. Humans can make this in their skin when exposed to sunlight, but dark skin is much less efficient at it.

High-dose oral vitamin D3 supplementation in the elderly. Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. Osteoporos Int. 2009 Aug;20(8):1407-15. Epub 2008 Dec 20. PMID: 19101755 Sixty-three elderly participants were randomized to three regimens of vitamin D supplementation: a 500,000-IU loading dose; the loading dose plus 50,000 IU/month; or 50,000 IU/month. CONCLUSIONS: Large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels in the frail elderly. Monthly dosing is similarly effective and safe, but takes 3-5 months for plateau 25OHD levels to be reached.

Vitamin D deficiency and mortality. Zittermann A, Gummert JF, Börgermann J. Curr Opin Clin Nutr Metab Care. 2009 Aug 25. [Epub ahead of print] PMID: 19710612

A new study has concluded that one key part of the immune system, the ability of vitamin D to regulate anti-bactericidal proteins, is so important that is has been conserved through almost 60 million years of evolution and is shared only by primates, including humans - but no other known animal species.

Sunlight, vitamin D and the prevention of cancer: a systematic review of epidemiological studies. Rhee HV, Coebergh JW, Vries ED. Eur J Cancer Prev. 2009 Aug 26. [Epub ahead of print] PMID: 19730382 We, therefore, conclude that there is accumulating evidence for sunlight as a protective factor for several types of cancer. The same conclusion can be made concerning high vitamin D levels and the risk of colorectal cancer. This evidence, however, is not conclusive, because the number of (good quality) studies is still limited and publication biases cannot be excluded. The discrepancies between the epidemiological evidence for a possible preventive effect of sunlight and vitamin D and the question of how to apply the findings on the beneficial effects of sunlight to (public) health recommendations are discussed.

Evidence-based decision making on micronutrients and chronic disease: long-term randomized controlled trials are not enough. Ames BN, McCann JC, Stampfer MJ, Willett WC. Am J Clin Nutr. 2007 Aug;86(2):522-3; author reply 523-4. PMID: 17684228

Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. J Clin Oncol. 2009 Aug 10;27(23):3757-63. Epub 2009 May 18. PMID: 19451439 DOI: 10.1200/JCO.2008.20.0725 Conclusion Vitamin D deficiency may be associated with poor outcomes in breast cancer.

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density. Outila TA, Kärkkäinen MU, Lamberg-Allardt CJ. Am J Clin Nutr. 2001 Aug;74(2):206-10. PMID: 11470722 Conclusion: A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.

Vitamin D fortification as public health policy: significant improvement in vitamin D status in young Finnish men. Laaksi IT, Ruohola JP, Ylikomi TJ, Auvinen A, Haataja RI, Pihlajamäki HK, Tuohimaa PJ. Eur J Clin Nutr. 2006 Aug;60(8):1035-8. Epub 2006 Feb 15. PMID: 16482069

Development of a model for optimal food fortification: vitamin D among adults in Finland. Hirvonen T, Sinkko H, Valsta L, Hannila ML, Pietinen P. Eur J Nutr. 2007 Aug;46(5):264-70. Epub 2007 May 18. PMID: 17514377

Depression may be triggered by low vitamin D levels in the blood, according to a new study published in the Aug 19, 2009 issue of European Journal of Clinical Nutrition. The study led by Nanri A and colleagues from International Medical center of Japan in Shinjuku-ku, Tokyo, Japan found that in November, people with their serum levels of vitamin D falling in the highest quartile were 49 percent less likely to feel depressed. The study involved 527 municipal employees aged 21 to 67 who worked in two municipal offices in Japan. It was meant to examine the association between vitamin D deficiency and depression

Pharmacokinetics of vitamin D toxicity. Jones G. Am J Clin Nutr. 2008 Aug;88(2):582S-586S. Review. PMID: 18689406