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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.

Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1, 25-dihydroxycholecalciferol. Vieth R, Milojevic S, Peltekova V. J Nutr. 2000 Mar;130(3):578-84. PMID: 10702588 We conclude suppression of 1,25(OH)(2)D and PTH, and higher renal VDR mRNA and 24-hydroxylase did not involve higher free 1,25(OH)(2)D concentration or a first pass effect at the gut. Thus, 25(OH)D or a metabolite other than 1,25(OH)(2)D is a physiological, transcriptionally and biochemically active, noncalcemic vitamin D metabolite. When viewed from a perspective that starts with higher vitamin D nutrition, the results indicate that low vitamin D nutrition may bring about a form of resistance to 1,25(OH)2D. This situation would explain why, in humans, nutritional rickets and osteomalacia are commonly associated with normal or increased levels of 1,25(OH)2D (Chesney et al. 1981Citation , Eastwood et al. 1979Citation , Garabedian et al. 1983Citation ,Rasmussen et al. 1980Citation )-these are not like the low hormone levels associated with any other endocrine-deficiency disorder. A connection between lower vitamin D nutrition and vitamin D resistance helps to explain why the supposedly inactive compound 25(OH)D is more relevant in diagnosing nutritional rickets than is the active hormone 1,25(OH)2D. If the features of improved vitamin D nutrition shown here were demonstrated for any newly synthesized compound, the compound would be classified as a noncalcemic 1,25(OH)2D analogue (Brown et al. 1989Citation , Finch et al. 1999Citation , Goff et al. 1993Citation , Koshizuka et al. 1999Citation ). Thus, we contend that 25(OH)D or a metabolite of it other than 1,25(OH)2D exists as a physiological and biologically-active noncalcemic vitamin D metabolite whose effects require further examination, particularly in relationship to studies involving the synthetic analogs of 1,25(OH)2D.

P.T. Liu, S. Stenger, H. Li, L. Wenzel, B.H. Tan, S.R. Krutzik, M.T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al.\nVitamin D3-Triggered Antimicrobial Response--Another Pleiotropic Effect beyond Mineral and Bone Metabolism: Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science 311: 1770-1773, 2006\nJ. Am. Soc. Nephrol., November 1, 2006; 17(11): 2949 - 2953.

Bioactive vitamin D or calcitriol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism. The active form of vitamin D binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours. The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,25-dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol, which explains their relative biological potencies

Vitamin D and breast cancer. Bertone-Johnson ER. Ann Epidemiol. 2009 Jul;19(7):462-7. Epub 2009 Feb 20. Review. PMID: 19230714 Though the relationship between vitamin D and breast cancer remains unclear, a growing body of evidence suggests that vitamin D may modestly reduce risk. A large number of in vitro studies indicate that vitamin D can inhibit cell proliferation and promote apoptosis and cell differentiation in breast tumor tissue. Results from analytic studies of sunlight exposure and dietary intake have been inconsistent but together generally support a modestly protective role of vitamin D, at least in some population subgroups. Studies using blood vitamin D metabolites to assess vitamin D status may be less prone to misclassification than those of diet and sunlight exposure. Overall, the two prospective and four case-control studies of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D tend to support a protective effect in older women. The relationship between common vitamin D receptor polymorphisms and risk remains unclear. Many questions about this relationship clearly remain, including the utility of assessing vitamin D through diet and sunlight exposure, the relationship between plasma metabolites, and the potential modifying effects of age, menopausal status and tumor characteristics. Given that vitamin D status is modifiable, additional prospective studies are necessary to determine if vitamin D may have important potential for breast cancer prevention.

"Researchers at Johns Hopkins are reporting what is believed to be the first conclusive evidence in men that the long-term ill effects of vitamin D deficiency are amplified by lower levels of the key sex hormone estrogen, but not testosterone. In a national study in 1010 men, to be presented Nov. 15 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando, researchers say the new findings build on previous studies showing that deficiencies in vitamin D and low levels of estrogen, found naturally in differing amounts in men and women, were independent risk factors for hardened and narrowed arteries and weakened bones. Vitamin D is an essential part to keeping the body healthy, and can be obtained from fortified foods, such as milk and cereals, and by exposure to sunlight.

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

A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. Vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Bischoff HA, Stähelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M. J Bone Miner Res. 2003 Feb;18(2):343-51. PMID: 12568412 A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

Effect of Vitamin D on falls: a meta-analysis. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB. JAMA. 2004 Apr 28;291(16):1999-2006. Review. PMID: 15113819

The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Nursyam EW, Amin Z, Rumende CM. Acta Med Indones. 2006 Jan-Mar;38(1):3-5. PMID: 16479024

Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, Stehle P, Koertke H, Koerfer R. Am J Clin Nutr. 2009 May;89(5):1321-7. Epub 2009 Mar 25. PMID: 19321573

Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D ≤ 80 nmol or 32 µg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. Hollis BW. J Nutr. 2005 Feb;135(2):317-22. Review. PMID: 15671234 [

Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial. Cheng S, Lyytikäinen A, Kröger H, Lamberg-Allardt C, Alén M, Koistinen A, Wang QJ, Suuriniemi M, Suominen H, Mahonen A, Nicholson PH, Ivaska KK, Korpela R, Ohlsson C, Väänänen KH, Tylavsky F. Am J Clin Nutr. 2005 Nov;82(5):1115-26; quiz 1147-8. PMID: 16280447

Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Vieth R, Kimball S, Hu A, Walfish PG. Nutr J. 2004 Jul 19;3:8. PMID: 15260882 doi:10.1186/1475-2891-3-8 CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

The same annual dose of 292 000 IU of vitamin D(3) (cholecalciferol) on either daily or four monthly basis for elderly women: 1-year comparative study of the effects on serum 25(OH)D(3) concentrations and renal function. Pekkarinen T, Välimäki VV, Aarum S, Turpeinen U, Hämäläinen E, Löyttyniemi E, Välimäki MJ. Clin Endocrinol (Oxf). 2009 May 25. [Epub ahead of print] PMID: 19486025 DOI: 10.1111/j.1365-2265.2009.03637.x

Long-term effects of giving nursing home residents bread fortified with 125 {micro}g (5000 IU) vitamin D3 per daily serving. Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, Vieth R. Am J Clin Nutr. 2009 Feb 25. [Epub ahead of print] PMID: 19244376

Vitamin D2 is much less effective than vitamin D3 in humans. Armas LA, Hollis BW, Heaney RP. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. PMID: 15531486 Vitamin D2 potency is less than one third that of vitamin D3. Physicians resorting to use of vitamin D2 should be aware of its markedly lower potency and shorter duration of action relative to vitamin D3.

Long-term effects of giving nursing home residents bread fortified with 125 microg (5000 IU) vitamin D(3) per daily serving. Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, Vieth R. Am J Clin Nutr. 2009 Apr;89(4):1132-7. Epub 2009 Feb 25. PMID: 19244376 doi:10.3945/ajcn.2008.26890

Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption.J Clin Endocrinol Metab. 2002 Nov;87(11):4952-6.PMID: 12414856 [PubMed - indexed for MEDLINE]