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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.

A vitamin D nutritional cornucopia: new insights concerning the serum 25-hydroxyvitamin D status of the US population. Norman AW. Am J Clin Nutr. 2008 Dec;88(6):1455-6. PMID: 19064502 doi:10.3945/ajcn.2008.27049 In summary, the report of Looker et al should be required reading for all nutritionists, clinicians, and vitamin D aficionados who are decision makers with regard to 25(OH)D assays, vitamin D nutritional policy, and the care of patients with vitamin D-related diseases.

Vieth R, Fraser D. Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. CMAJ. 2002 Jun 11;166(12):1541-2. PMID: 12074121 In fact, current recommendations for vitamin D are not designed to ensure anything. They are simply based on the old, default strategy for setting a nutritional guideline, which is to recommend an amount of nutrient similar to what healthy people are eating. This approach underlies the circular logic behind a familiar refrain about nutrition: "If you eat a good diet, you won't need supplements." By this logic, the answer to the question, "How much nutrient do you need?" is, "Whatever healthy people happen to be eating." The essential point, lost in the confusing terminology of modern nutrient recommendations, is that a recommended daily allowance (RDA) does not yet exist for vitamin D. Instead, the recommendations for it are referred to as "adequate intake" (AI).12,13 The AI for young adults (5 µg or 200 IU) was chosen to approximate twice the average vitamin D intake reported by 52 young women in a questionnaire-based study reported from Omaha, Neb., in 1997.13,14 Because the available evidence was acknowledged as weak, the Food and Nutrition Board of the US Institute of Medicine called its recommendation an AI.

Nutrients, endpoints, and the problem of proof. Heaney RP. 2008 W. O. Atwater Memorial Lecture J Nutr. 2008 Sep;138(9):1591-5. PMID: 18716155 To sum up, I think that there would be general agreement to the effect that nutrition is important, despite the fact that the still growing number of failed trials of individual nutrients might suggest that no nutrient actually made much of a difference, a conclusion that is absurd on its face and ought to have alerted us to the possibility that there was something wrong with how we were investigating the matter. To provide the proof needed to sustain revised intake recommendations, we shall have to find a design better suited to nutrients than the randomized controlled trial as currently implemented, and we need to develop a series of global indices, nutrient by nutrient, which better capture the polyvalent nature of most nutrients. Perhaps it would be useful for the ASN, in collaboration with concerned governmental entities such as the USDA, to convene a workshop to address these structural issues. Such deliberation may well be arduous and frustrating, but it is terribly important and, in my view, well worth the effort.

Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. Judd SE, Nanes MS, Ziegler TR, Wilson PW, Tangpricha V. Am J Clin Nutr. 2008 Jan;87(1):136-41. PMID: 18175747 Conclusions: SBP is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. This observation provides a rationale for studies on the potential effects of vitamin D supplementation as a method to reduce SBP in persons at risk of hypertension.

Nutrition, chronic disease, and the problem of proof. Heaney RP. Am J Clin Nutr. 2006 Sep;84(3):471-2. No abstract available. PMID: 16960157

Vitamin D, nutritional deficiency, and the medical paradigm. Heaney RP. J Clin Endocrinol Metab. 2003 Nov;88(11):5107-8. Review. No abstract available. PMID: 14602734

Bread fortified with cholecalciferol increases the serum 25-hydroxyvitamin D concentration in women as effectively as a cholecalciferol supplement. Natri AM, Salo P, Vikstedt T, Palssa A, Huttunen M, Kärkkäinen MU, Salovaara H, Piironen V, Jakobsen J, Lamberg-Allardt CJ. J Nutr. 2006 Jan;136(1):123-7. PMID: 16365070 Both fortified breads increased serum 25-hydroxyvitamin D concentration as effectively as the cholecalciferol supplement. Supplementation or fortification did not affect serum intact parathyroid hormone concentration or urinary calcium excretion. In conclusion, fortified bread is a safe and feasible way to improve vitamin D nutrition.

Nutritional vitamin D status during pregnancy: reasons for concern. Hollis BW, Wagner CL. CMAJ. 2006 Apr 25;174(9):1287-90. PMID: 16636329 doi:10.1503/cmaj.060149.

Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Am J Clin Nutr. 2008 Jun;87(6):1952-8. PMID: 18541590 The mean daily dose was 86 microg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75-220 nmol/L predicted an optimal daily dose of 115 microg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. CONCLUSIONS: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 microg/d (5000 IU) for those below that threshold.

Serum Vitamin D and Risk of Prostate Cancer in a Case-Control Analysis Nested Within the European Prospective Investigation into Cancer and Nutrition (EPIC). Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Argüelles MV, Sánchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Am J Epidemiol. 2009 Apr 9. [Epub ahead of print] PMID: 19359375 doi:10.1093/aje/kwp022

Assessment of dietary vitamin D requirements during pregnancy and lactation. Hollis BW, Wagner CL. Am J Clin Nutr. 2004 May;79(5):717-26. Review. PMID: 15113709 We found that high-dose maternal vitamin D supplementation not only improves the nutritional vitamin D status of breastfeeding infants but also elevates the maternal concentrations into the mid-normal range. Thus, a dual benefit is achieved from high-dose maternal supplementation. It is noteworthy that in the Finnish study, the authors added a disclaimer, "A sufficient supply of vitamin D to the breastfed infant is achieved only by increasing the maternal supplementation up to 2000 IU/d. Such a dose is far higher than the RDA [DRI] for lactating mothers [and therefore] its safety over prolonged periods is not known and should be examined by further study." This point of concern was valid when this study was conducted in 1986 (92); however, on the basis of the current findings of Vieth et al (2) and of Heaney et al (3)-which showed that vitamin D intakes <= 10 000 IU/d (250 µg) are safe for prolonged periods (up to 5 mo)-we believe that it is time to reexamine the understated DRI of vitamin D for lactating mothers. This work is now being conducted in our clinics and laboratory.

Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Am J Clin Nutr. 2007 Jun;85(6):1586-91. Erratum in: Am J Clin Nutr. 2008 Mar;87(3):794. PMID: 17556697 Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.

Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Arch Ophthalmol. 2007 May;125(5):661-9. PMID: 17502506

Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, van Duijnhoven FJ, Chirlaque MD, Barricarte A, Larrañaga N, González CA, Argüelles MV, Sánchez MJ, Stattin P, Hallmans G, Khaw KT, Bingham S, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ. Am J Epidemiol. 2009 May 15;169(10):1223-32. Epub 2009 Apr 9. PMID: 19359375 In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.

Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. Whiting SJ, Calvo MS. J Nutr. 2005 Feb;135(2):304-9. Review. PMID: 15671232 In summary, vitamin D has emerged as a critical nutrient for which there is a compelling health need to establish adequate dietary guidelines in North America and worldwide given the increasing evidence of vitamin D deficiency and insufficient links to risk of chronic disease. We strongly argue that now there are enough data to consider setting an estimated average requirement for vitamin D and to recognize the crucial need for more research to determine the role of vitamin D in noncalciotropic functions and prevention of chronic diseases

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 [

Strategies to improve vitamin D status in northern European children: exploring the merits of vitamin D fortification and supplementation. Tylavsky FA, Cheng S, Lyytikäinen A, Viljakainen H, Lamberg-Allardt C. J Nutr. 2006 Apr;136(4):1130-4. PMID: 16549494

Prevention of rickets and vitamin D deficiency in infants, children, and adolescents.\nWagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition.\nPediatrics. 2008 Nov;122(5):1142-52. Erratum in: Pediatrics. 2009 Jan;123(1):197.\nPMID: 18977996

Holick MF. The vitamin D epidemic and its health consequences. J Nutr. 2005 Nov;135(11):2739S-48S. PMID: 16251641 [PubMed - indexed for MEDLINE]