Vitamin D

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.

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

Long-latency deficiency disease: insights from calcium and vitamin D. Heaney RP. Am J Clin Nutr. 2003 Nov;78(5):912-9. Review. PMID: 14594776

Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. JAMA. 2005 May 11;293(18):2257-64. Review. PMID: 15886381 Conclusions Oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.

Vitamin D Deficiency - Treatment and Diagnosis

Hypovitaminosis D in medical inpatients. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. N Engl J Med. 1998 Mar 19;338(12):777-83. PMID: 9504937 Conclusions Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily amount and those without apparent risk factors for vitamin D deficiency.

Holick, M. F., MacLaughlin, J. A. & Doppelt, S. H. (1981) Factors that influence the cutaneous photosynthesis of previtamin D3. Science 211:590-593 When human skin was exposed to simulated solar ultraviolet radiation, epidermal 7-dehydrocholesterol was converted to previtamin D3. During prolonged exposure to simulated solar ultraviolet radiation, the synthesis of previtamin D3 reached a plateau at about 10 to 15 percent of the original 7-dehydrocholesterol content, and previtamin D3 was photoisomerized to two biologically inert isomers, lumisterol3 and tachysterol3. Increases either in skin melanin concentration or in latitude necessitated increases in the exposure time to simulated solar ultraviolet radiation required to maximize the formation, but not the total content, of previtamin D3. In order of importance, the significant determinants limiting the cutaneous production of previtamin D3 are (i) photochemical regulation, (ii) pigmentation, and (iii) latitude.

In vivo threshold for cutaneous synthesis of vitamin D3. Matsuoka LY, Wortsman J, Haddad JG, Hollis BW. J Lab Clin Med. 1989 Sep;114(3):301-5. PMID: 2549141

Matsuoka, L. Y., Wortsman, J., Hanifan, N. & Holick, M. F. (1988) Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D: a preliminary study. Arch. Dermatol. 124:1802-1804

Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. Vieth R, Ladak Y, Walfish PG. J Clin Endocrinol Metab. 2003 Jan;88(1):185-91. PMID: 12519850 This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function

Vitamin D3 and calcium to prevent hip fractures in the elderly women. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ. N Engl J Med. 1992 Dec 3;327(23):1637-42. PMID: 1331788 CONCLUSIONS. Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE. J Clin Endocrinol Metab. 2005 Jun;90(6):3215-24. Epub 2005 Mar 29. PMID: 15797954 doi:10.1210/jc.2004-2364 Conclusions: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.

Vitamin D status in apparently healthy adults in Kashmir Valley of Indian subcontinent. Zargar AH, Ahmad S, Masoodi SR, Wani AI, Bashir MI, Laway BA, Shah ZA. Postgrad Med J. 2007 Nov;83(985):713-6. PMID: 17989271 doi:10.1136/pgmj.2007.059113 Conclusions: In spite of abundant sunlight, healthy individuals in Kashmir valley are vitamin D deficient, particularly women. Serum 25 (OH) D concentrations are significantly related to sun exposure

Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. Ng K, Meyerhardt JA, Wu K, Feskanich D, Hollis BW, Giovannucci EL, Fuchs CS. J Clin Oncol. 2008 Jun 20;26(18):2984-91. PMID: 18565885 DOI: 10.1200/JCO.2007.15.1027 Conclusion Among patients with colorectal cancer, higher prediagnosis plasma 25(OH)D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted.

Epidemiology of vitamin D insufficiency and cancer mortality. Pilz S, Tomaschitz A, Obermayer-Pietsch B, Dobnig H, Pieber TR. Anticancer Res. 2009 Sep;29(9):3699-704. Review. PMID: 19667167 In conclusion, we still need further studies to evaluate the association of vitamin D insufficiency and cancer incidence and mortality, but the multiple health benefits of vitamin D and the easy, safe and inexpensive way by which vitamin D can be supplemented should already guide current public health strategies to achieve 25(OH)D levels of at least 75 nmol/l (30 ng/ml) in the general population.

Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Raimondi S, Johansson H, Maisonneuve P, Gandini S. Carcinogenesis. 2009 Jul;30(7):1170-80. Epub 2009 Apr 29. Review. PMID: 19403841

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.

Calcium plus vitamin D supplementation and the risk of colorectal cancer. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE; Women's Health Initiative Investigators. N Engl J Med. 2006 Feb 16;354(7):684-96. Erratum in: N Engl J Med. 2006 Mar 9;354(10):1102. PMID: 16481636 Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention.

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