Vitamin D und seine Bedeutung im Immunsystem und bei der Infektabwehr

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1 Vitamin D und seine Bedeutung im Immunsystem und bei der Infektabwehr Stefan Pilz Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Austria Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care, VU University of Amsterdam, The Netherlands

2 OUTLINE

3 Vitamin D Vitamin D metabolism Vitamin D sources UV-B induced Vitamin D production in the skin Nutrition 80-90% 10-20% Pilz S, et al. J Lab Med 2008, 32:

4 Vitamin D metabolism Pathophysiology ng/ml HL~1 month pg/ml HL<1 day Serum 1,25(OH)2D: Derived from the kidney Tissue 1,25(OH)2D: Produced from serum 25(OH)D Pilz S, et al. Nature Reviews Cardiology 2009, 6:

5 Vitamin D and skin The Survival advantage conferred by light skin as our ancestors migrated to higher latitudes is generally believed to have resulted from the importance of maintaining adequate vitamin D levels under conditions of reduced exposure to UV-B Giovannucci E, Therapy 2008; 5:

6 Intakes of at least 800 IU of vitamin D can be recommended in the general management of osteoporosis

7

8 OUTLINE

9 Vitamin D status Vitamin D SUFFICIENCY (>30 ng/ml, >75nmol/L) Vitamin D INSUFICIENCY (20 to 30 ng/ml,50 to 75nmol/L) Vitamin D DEFICIENCY (<20 ng/ml, <50 nmol/l ) 1) Intestinal calcium absorption decreases 2) Parathyroid horomone (PTH) increases 3) Osteomalacia/rickets

10 Unpublished data

11 Vitamin D and mortality in general populations Lowest mortality risk at 75 to 87.5 nmol/l

12

13 META-ANALYSIS

14 OUTLINE

15 Vitamin D and immune system

16 Vitamin D and immune system Prietl B & Pilz S, et al. IMAJ 2010, 12: Bouillon R et al. Endocrine Reviews 2008; 29:

17 Vitamin D and regulatory T cells Randomized controlled trial among 60 healthy subjects evaluating the effect of 3 monthly doses of IU vitamin D or placebo on peripheral blood regulatory T cells (Tregs, CD4 + CD25 high FoxP3 + ) 8 *** 80 25(OH)D [ng/ml serum] Tregs (% in CD4pos T cells) 6 4 *** < vitamin D group placebo group baseline 4 weeks 8 weeks 12 weeks 0 vitamin D group placebo group Bock G, et al. Diabetes Metab Res Rev 2011 Nov;27(8): baseline 4 weeks 8 weeks 12 weeks

18 Vitamin D and type 1 diabetes Common genetic determinants of vitamin D insufficiency: a genome wide association Study Wang TJ, et al. Lancet 2010;376:

19 Vitamin D and type 1 diabetes mellitus Mohr SB et al. Diabetologia 2008; 51:

20 Vitamin D and type 1 diabetes mellitus Hyppönen E et al. Lancet 2001; 358:

21 Vitamin D deficiency in children in Germany 20 ng/ml (50 nmol/l)

22 Vitamin D deficiency in children (rickets) Vitamin D deficiency causes rickets in children There exist general recommendations to supplement vitamin D in the first year of life

23 OUTLINE

24 Antimicrobial mechanisms of vitamin D

25 Vitamin D and mortality in chronic liver disease

26 Vitamin D and hepatitis C 25-hydroxyvitamin D(3) suppresses hepatitis C virus production Matsumura T, et al. Hepatology 2012 Apr 6. doi: /hep

27 Vitamin D and hepatitis C Vitamin D binding protein gene polymorphisms and baseline vitamin D levels as predictors of antiviral response in chronic hepatitis C Faletti E, et al. Hepatology 2012 May 18. doi: /hep

28 Vitamin D and influenza Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials. Jorde R, et al. Scand J Infect Dis 2012 Feb;44(2):

29

30 RCT in 173 hip fracture patients with 800 vs 2000 IU vitamin D

31 OUTLINE

32 Vitamin D supplementation Individuals (25(OH)D < 50nmol/L) were treated with cummulative vitamin D doses of 100,000 to 200,000 IU over 8 weeks (corresponding to daily doses of ~ 2000 to 4000 IU)

33 Natural Vitamin D treatment Natural vitamin D therapy is safe! No adverse events with doses up to 10,000 IU daily or below 150 ng/ml [25(OH)D] (Sun exposure: up to 20,000 IU daily); IOM report: 4,000 IU per day are safe Daily, weekly or monthly doses of natural vitamin D can be used (be careful with doses >100,000 IU) Re-Testing of 25(OH)D levels after at least three months of supplementation (DVO: > 20 ng/ml; optimal 25(OH)D for multiple health outcomes between 30 and 40 ng/ml; IOM: 20 is sufficient for 97.5% of the population; sufficiency ng/ml) Rule of thumb: 1,000 IU vitamin D increase 25(OH)D levels by 10 ng/ml (25 nmol/l) (6-10 ng/ml, nmol/l) Consider, beyond musculoskeletal effects the proposed multiple health benefits of vitamin D: survival, cardiovascular effects, anti-cancer and anti-autoimmunological actions, prevention of infectious diseases.

34 Large ongoing RCTs VITAL Study: 20,000 older study participants in the US Vida Study: 5,100 older study participants in New Zealand EVITA Study: 1,000 heart failure patients in Germany, etc. Results of these trials will be published ~2015 to 2017 Time window to get good funding and perform large RCTs on vitamin D will probably close after ~2015 to 2017 Therefore we have to critical discuss the design of these RCTs

35 Discussion of vitamin D RCTs Lets look at vitamin E as an example! What was the conclusion? Vitamin E exerts anti-oxidative actions but large RCTs including relatively unselected study participants with vitamin E levels mainly in the sufficiency range failed to prove significant benefits with suboptimal dosages of vitamin E Therefore, the open question still remains whether there are relevant effects in vitamin E sensitive individuals with e.g. low vitamin E levels and/or high oxidative stress Robinson I, et al. Vitamin E in humans: explanation of clinical trial failure. Endocr. Pract. 2006;12: What can we learn from this for vitamin D? My opinion is that before we aim to show that vitamin D is beneficial for everyone we should focus more on those populations that are likewise most sensitie to vitamin D supplementation.e.g. frail elderly, poststroke patients, only severe vitamin D deficient individuals.

36 Conclusion Vitamin D deficiency (reduced 25[OH]D) is prevalent, and this is mainly a consequence of current lifestyle with reduced sunlight exposure Accumulating evidence suggests that vitamin D may, beyond musculoskeletal diseases, also prevent various other chronic diseases, including autoimmune and infectious diseases While experimental and observational studies strongly support an important role of vitamin D in autoimmune and infectious diseases, the evidence from RCTs is still rare and partially inconclusive We still need more RCTs on vitamin D but vitamin D supplementation is relatively easy, safe and simple. The promising data on vitamin D regarding various health outcomes strongly argue that it is reasonable to prevent and treat vitamin D deficiency

37 Thank you for your attention!

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