The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review. PMID: 17389701 .CONCLUSIONS: Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. Epub 2007 Dec 18. PMID: 18089691 Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Am J Clin Nutr. 1998 Oct;68(4):854-8. PMID: 9771862 Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

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.

Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Schwalfenberg G. Can Fam Physician. 2008 Jun;54(6):864-6. PMID: 18556494 Conclusion These cases support information that is already known about VTD and its effect on the islet cell. As discussed above, this might be true only for vitamin D3 and not vitamin D2, although vitamin D2 has been shown to improve bone health. Vitamin D insufficiency or deficiency is common, and repletion might improve glycemic control early in type 2 diabetes. Diabetes is one of the fastest growing chronic diseases worldwide. Vitamin D3 is inexpensive and readily available. Well-designed clinical studies are required to ascertain if improving 25(OH)D levels from an insufficiency or deficiency to sufficiency improves glycemic control in diabetes. These studies need to be properly designed: a randomized controlled trial with VTD deficiency or insufficiency identified in diabetic patients of various ethnic

Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Diabetes. 2008 Oct;57(10):2619-25. Epub 2008 Jun 30. PMID: 18591391 doi: 10.2337/db08-0593 CONCLUSIONS: This prospective study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance. These associations are potentially important in understanding the etiology of abnormal glucose metabolism and warrant investigation in larger, specifically designed prospective studies and randomized controlled trials of supplementation.

Vitamin D and type 2 diabetes: are we ready for a prevention trial? Scragg R. Diabetes. 2008 Oct;57(10):2565-6. PMID: 18820212 doi: 10.2337/db08-0879 Despite evidence from the current article (3) and the Finnish study (17), doubts still remain about whether low vitamin status is a cause of type 2 diabetes. Further cohort studies are required, assessing baseline vitamin D status using blood 25(OH)D to be sure that the Ely and Finnish studies are not false-positive results. Glucose clamp studies are also required because we are still not sure of the mechanism influenced by vitamin D-whether it is insulin resistance, secretion, or both. But most importantly, given that nearly three decades have passed since the first studies linking vitamin D with insulin metabolism (6,7), well-designed clinical trials of the effect of vitamin D supplementation on glycemia status and diabetes risk are urgently required to settle this question. And they need to prevent past mistakes. In particular, the vitamin D dose given in such trials needs to be high enough-above 2,000 IU per day (19)-to raise blood 25(OH)D levels above 80 nmol/l because diabetes risk is lowest at this level (9,20). If well-designed trials are carried out and confirm a protective effect from vitamin D, it could be used by the general population as a simple and cheap solution to help prevent the diabetes epidemic.

Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. J Nutr. 2009 Feb;139(2):329-34. Epub 2008 Dec 23. PMID: 19106328 doi:10.3945/jn.108.093831 After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI(0,120), plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Cardiovasc Diabetol. 2009 Feb 3;8:7. PMID: 19187564 doi:10.1186/1475-2840-8-7 CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Jorde R, Figenschau Y. Eur J Nutr. 2009 Apr 16. [Epub ahead of print] PMID: 19370371 10.1007/s00394-009-0020-3 Conclusions We were not able to demonstrate that vitamin D supplementation had a significant effect on glucose metabolism in subjects with type 2 diabetes but without vitamin D deficiency. Further studies are needed in larger groups of subjects with type 2 diabetes or impaired glucose tolerance, who also exhibit low serum 25-hydroxyvitamin D levels.

Serum vitamin D and subsequent occurrence of type 2 diabetes. Knekt P, Laaksonen M, Mattila C, Härkänen T, Marniemi J, Heliövaara M, Rissanen H, Montonen J, Reunanen A. Epidemiology. 2008 Sep;19(5):666-71. PMID: 18496468 doi: 10.1097/EDE.0b013e318176b8ad Conclusions: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.

Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Diabetes Care. 2007 Oct;30(10):2569-70. Epub 2007 Jul 12. PMID: 17626891 doi: 10.2337/dc07-0292 We found a significant inverse association between serum 25OHD and risk of type 2 diabetes in the simple model. However, the association was attenuated in the multivariate analysis, adjusting for potential risk factors of type 2 diabetes. To our knowledge, this is the first cohort study investigating the association between serum 25OHD and incidence of type 2 diabetes. Our results are in line with those from the Nurses' Health Study (5), where an inverse association was observed for the intake of vitamin D supplements. We could not differentiate whether the results depended on the effect of vitamin D deficiency on β-cell function or on insulin resistance. In summary, the results are in line with the hypothesis that a high serum 25OHD concentration may reduce the risk of type 2 diabetes. Further research is needed to confirm the association and to distinguish between the independent role of vitamin D and the role of healthy dietary and lifestyle patterns in reducing the risk of type 2 diabetes.

Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Hyppönen E, Power C. Diabetes Care. 2006 Oct;29(10):2244-6. PMID: 17003300 doi: 10.2337/dc06-0946 CONCLUSIONS-Body size was a strong determinant for 25(OH)D, with concentrations being suboptimal in most obese participants. Randomized controlled trials [using dosages sufficient to improve 25(OH)D also for the obese] are required to determine whether clinically relevant improvements in glucose metabolism can be obtained by vitamin D supplementation.

Suomalaisten ravitsemussuositusten mukaan päivittäisen D-vitamiinisaannin tulisi olla ennen 70 ikävuotta 7,5 µg/VRK ja 10 µg/VRK sen jälkeen. Tällaisella saannilla elimistön D-vitamiinin tarve ei tule koskaan turvattua ilman riittäviä erillisiä D-vitamiinilisiä tai "etelän aurinkolomia". Valtion Ravitsemusneuvottelukunnan vuonna 2004 laatimat suositukset ovatkin aikansa eläneitä eivätkä nykytiedon mukaan turvaa väestön D-vitamiinin tarvetta. D-vitamiinireseptoreita, jotka yhdessä D-vitamiinin kanssa toimivat solun sisäisinä säätelijöinä, on mm aivoissa, eturauhasessa, rintarauhasessa, paksussa suolessa ja vasta-aineita tuottavissa soluissa. D-vitamiini säätelee yli 200 geeniä, joista osa säätelee solujen lisääntymistä, erilaistumista, kuolemaa ja verisuonten syntyä. Riittävän D-vitamiinin saanti vähentää tutkimustiedon mukaan selvästi riskiä sairastua eturauhasen, rintarauhasen ja imukudoksen syöpiin, diabetekseen ja sydän- ja verisuonisairauksiin - siis sairauksiin, jotka ovat suomalaisten suuria terveysongelmia. Lisätietoja: Olli Simonen, Suomen Osteoporoosiliiton pj puh 044-3080306 ( D-vitamiinin puute kansanterveyshaasteena) Christel Lamberg-Allardt, professori, puh 09-19158266 tai 040-5769500 (väestön D-vitamiinin tarve ja saanti) Hannu Aro, professori puh 040-353 7644 (osteoporoosin, -malasian ja murtumien diagnostiikka ja hoito)

Vitamin D deficiency is the cause of common obesity. Foss YJ. Med Hypotheses. 2009 Mar;72(3):314-21. Epub 2008 Dec 2. PMID: 19054627 doi:10.1016/j.mehy.2008.10.005

Frank Garland

Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003 May;89(5):552-72. Review. PMID: 12720576 Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Thomsen J, Charles P, Eriksen EF. J Intern Med. 2000 Feb;247(2):260-8. PMID: 10692090 Conclusions. Severe vitamin D deficiency is prevalent amongst sunlight-deprived individuals living in Denmark. In veiled Arab women, vitamin D deficiency is the result of a combination of limitations in sunlight exposure and a low oral intake of vitamin D. The oral intake of vitamin D amongst veiled ethnic Danish Moslems was, however, very high, at 13.53 µg (approximately 600 IU), but they were still vitamin D-deficient. Our results suggest that the daily oral intake of vitamin D in sunlight-deprived individuals should exceed 600 IU; most probably it should be 1000 IU day-1 to secure a normal level of 25-hydroxyvitamin D. This finding is in contrast with the commonly used RDA (recommended daily allowance) for adults in Europe: 200 IU day-1.

Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation. Webb AR, DeCosta BR, Holick MF. J Clin Endocrinol Metab. 1989 May;68(5):882-7. PMID: 2541158 doi:10.1210/jcem-68-5-882 Vitamin D3 proved to be exquisitely sensitive to sunlight, and once formed in the skin, exposure to sunlight resulted in its rapid photodegradation to a variety of photoproducts, including 5,6-transvitamin D3, suprasterol I, and suprasterol II.suprasterol I, and suprasterol II.

nfluence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. Webb AR, Kline L, Holick MF. J Clin Endocrinol Metab. 1988 Aug;67(2):373-8. PMID: 2839537 doi:10.1210/jcem-67-2-373 These results quantify the dramatic influence of changes in solar UVB radiation on cutaneous vitamin D3 synthesis and indicate the latitudinal increase in the length of the "vitamin D winter" during which dietary supplementation of the vitamin may be advisable.