Vitamin D

Vitamin D Deficiency - Treatment and Diagnosis

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.

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

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

Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Eur J Clin Nutr. 2001 Dec;55(12):1091-7. PMID: 11781676 INTERPRETATION: The self-reported vitamin D intake from milk and/or multivitamins does not relate to prevention of low vitamin D nutritional status of young women in winter. Recommended vitamin D intakes are too small to prevent insufficiency. Vitamin D nutrition can only be assessed by measuring serum 25(OH)D concentration.

Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls. Lehtonen-Veromaa M, Möttönen T, Irjala K, Kärkkäinen M, Lamberg-Allardt C, Hakola P, Viikari J. Eur J Clin Nutr. 1999 Sep;53(9):746-51. PMID: 10509773 CONCLUSION: Hypovitaminosis D is fairly common in growing Finnish girls in the wintertime, and three months of vitamin D supplementation with 10 microg/d was insufficient in preventing hypovitaminosis D. The daily dietary vitamin D intake was insufficient (< 5 microg/d) in the majority of participants, while the calcium intake was usually sufficient.

Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Autier P, Gandini S. Arch Intern Med. 2007 Sep 10;167(16):1730-7. Review. PMID: 17846391 Conclusions Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings.

Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Garland FC, Garland CF, Gorham ED, Young JF. Prev Med. 1990 Nov;19(6):614-22. PMID: 2263572 doi:10.1016/0091-7435(90)90058-R Vitamin D from sunlight exposure may be associated with low risk for fatal breast cancer, and differences in ultraviolet light reaching the United States population may account for the striking regional differences in breast cancer mortality. The ecological nature of this study is emphasized, and the possibility that an indirect association with dietary and socioeconomic factors could explain these findings is discussed.

An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Grant WB. Cancer. 2002 Jan 1;94(1):272-81. PMID: 11815987 CONCLUSIONS It is hypothesized that animal products are associated with risk for breast carcinoma because they are associated with greater amounts of insulin-like growth factor-1and lifetime doses of estrogen. Vegetable products contain several risk reduction components including antioxidants and phytoestrogens. The association with latitude is very likely because of solar UV-B radiation and vitamin D. Alcohol modulates estrogen's effects on breasts. Fish intake is associated with risk reduction through vitamin D and n-3 oils. These results are consistent with those of many case-control and cohort studies but should be assessed in well designed cohort studies.

Geographic variation of prostate cancer mortality rates in the United States: Implications for prostate cancer risk related to vitamin D. Grant WB. Int J Cancer. 2004 Sep 1;111(3):470-1; author reply 472. No abstract available. PMID: 15221981 10.1002/ijc.20220 The implications of our results and those of Tuohimaa et al.[1] include the following. Vitamin D supplementation should be undertaken in wintertime, a period when it is impossible to produce vitamin D by solar UVB exposure in northeastern states.[13] Given these new results, the optimal vitamin D intake and production and serum 25(OH)-vitamin D3 levels for prostate cancer appear to be lower than for other cancers. However, when developing guidelines for vitamin D fortification, many factors should be included in the analysis, including all of the potential health benefits and possible risks of vitamin D, as well as age, sex, residence, child-bearing status, etc.[14] Also, the suggestion that daily vitamin D3 supplement doses of 100 g (4,000 IU)/day are safe[15] should be reexamined. Finally, in terms of preventing prostate cancer, more attention should be given to diet, which has the greatest environmental impact on risk of prostate cancer, with animal products being important risk factors and vegetable products, especially onions and other allium family members, being important risk-reduction factors.[16]

van der Wielen RP, Lowik MR, van den BH, de Groot LC, Haller J, Moreiras O, van Staveren WA (1995) Serum vitamin D concentrations among elderly people in Europe. Lancet 346: 207-210 These findings show that free-living elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter and that dietary enrichment or supplementation with vitamin D should be seriously considered during this season.

An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Webb AR, Pilbeam C, Hanafin N, Holick MF. Am J Clin Nutr. 1990 Jun;51(6):1075-81. PMID: 2349922

Aging decreases the capacity of human skin to produce vitamin D3. MacLaughlin J, Holick MF. J Clin Invest. 1985 Oct;76(4):1536-8. PMID: 2997282 doi:10.1172/JCI112134 An evaluation of surgically obtained skin (age range, 8-92 yr) revealed that there is an age-dependent decrease in the epidermal concentrations of provitamin D3 (7-dehydrocholesterol). To ascertain that aging indeed decreased the capacity of human skin to produce vitamin D3, some of the skin samples were exposed to ultraviolet radiation and the content of previtamin D3 was determined in the epidermis and dermis. The epidermis in the young and older subjects was the major site for the formation of previtamin D3, accounting for greater than 80% of the total previtamin D3 that was produced in the skin. A comparison of the amount of previtamin D3 produced in the skin from the 8- and 18-yr-old subjects with the amount produced in the skin from the 77- and 82-yr-old subjects revealed that aging can decrease by greater than twofold the capacity of the skin to produce previtamin D3. Recognition of this difference may be extremely important for the elderly, who infrequently expose a small area of skin to sunlight and who depend on this exposure for their vitamin D nutritional needs.

SSeason of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Porojnicu AC, Robsahm TE, Ree AH, Moan J. Br J Cancer. 2005 Sep 5;93(5):571-4. PMID: 16136030 doi:10.1038/sj.bjc.6602722 Epidemiological data for this period indicate that season of diagnosis is a strong prognostic factor for Hodgkin's lymphoma, with approximately 20% lower case fatality for patients diagnosed during autumn vs winter diagnosis (RR = 0.783, 95% CI,-0.62 to 0.99; P = 0.041). Notably, the improved autumnal survival rate was higher than 60% (RR = 0.364, 95% CI, -0.15 to 0.87; P = 0.025) for patients younger than 30 years. This finding may be related to higher endogenous levels of vitamin D in autumn, with a favourable influence on the conventional therapy. In conclusion, we have found that the prognosis of Hodgkin's lymphoma is significantly correlated with the season of diagnosis, particularly for patients younger than 30 years. This seasonal effect is presumably due to the vitamin D3 synthesis in skin during sun exposure. The present findings should encourage further investigations of the possible adjuvant role of vitamin D derivatives in cancer therapy

Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Zhou W, Suk R, Liu G, Park S, Neuberg DS, Wain JC, Lynch TJ, Giovannucci E, Christiani DC. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303-9. PMID: 16214909 In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients. In summary, for early-stage NSCLC patients, patients who had surgery in summer with "high" recent vitamin D intake have a statistically significantly improved RFS and OS than patients who had surgery in winter with "low" vitamin D intake. These results should be confirmed in a prospective study to assess the serum vitamin D levels at time of surgery. If the results are confirmed, our results, combined with findings in other studies, suggest that dietary vitamin D supplementation may be advisable for early stages of lung cancer patients, particularly during the winter season and in groups that tend to be deficient in vitamin D.

The Toronto group gave a fixed low dose (2,000 units) of the prehormone, cholecalciferol, a very safe compound that never causes high calcium in the doses used. In fact, the lowest dose of cholecalciferol known to cause high blood calcium is more than 20,000 units. Therefore, the Toronto group got better results with one-tenth the comparable dose of deltanoids! Vieth wanted to use more cholecalciferol but widespread ignorance about the physiology and pharmacology of vitamin D remains and he could not get adequate dosing past the various review committees.

Rise in prostate-specific antigen in men with untreated low-grade prostate cancer is slower during spring-summer. Vieth R, Choo R, Deboer L, Danjoux C, Morton GC, Klotz L. Am J Ther. 2006 Sep-Oct;13(5):394-9. PMID: 16988533 doi: 10.1097/01.mjt.0000174346.36307.02

Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Int J Cancer. 2004 Jan 1;108(1):104-8. PMID: 14618623 DOI: 10.1002/ijc.11375

Enzyme kinetics hypothesis to explain the U-shaped risk curve for prostate cancer vs. 25-hydroxyvitamin D in nordic countries. Vieth R. Int J Cancer. 2004 Sep 1;111(3):468; author reply 469. PMID: 15221979 DOI: 10.1002/ijc.20218