1) The document discusses vitamin D deficiency and its link to various health issues. It reports that 61-82% of postmenopausal women and 98% of patients with osteoporotic fractures have inadequate vitamin D levels. 2) Several causes of vitamin D deficiency in the elderly are described, including lack of sun exposure and less effective vitamin D synthesis in the skin. 3) The text reviews results from studies that show vitamin D supplementation can reduce fracture risk by 33%, falling risk by 49%, and improve lower limb function. It is suggested that maintaining higher vitamin D levels may provide significant economic savings in healthcare costs.

1. Vitamin D deficiency and health - related issues Dr. Peter Lakatos Professor of Medicine 1st Department of Medicine Semmelweis University, Budapest

2. Inadequate serum vitamin D limits Defin ition Inadequate 25 - OH - D : <30 ng/ml ( < 75 nmol/ l ) Boonen S et al Osteoporos Int 2004;15:511–519; Lips P Endocr Rev 2001;22:477–501; Heaney RP Osteoporos Int 2000;11:553–555,

3. Frequency of inadequate vitamin D levels Prevalenc e (%) 0 Latin - Ameri c a Asia All region Austr a lia Europe Regions Middle-East 2589 postmenopausal osteoporotic women 10 30 40 60 80 90 N=2589 50 70 20 81.8% 63.9% 71.4% 53.4% 60.3% 57.7% Lips P et al. ASBMR, Nashville, TN, USA, 2005. sz eptember 23–27. ; Heaney RP Osteoporos Int 2000;11:553–555.

4. 2/3 of postmenopausal women have inadequate serum vitamin D levels Prevalence ( % ) 25-OH-D -concentration lower limits (ng/ml) Lips P et al. ASBMR, Nashville, TN, USA, 2005. sz eptember 23–27. ; Heaney RP Osteoporos Int 2000;11:553–555. 2589 postmenopausal osteoporotic women 0 10 30 40 60 80 90 30.8% 48.7% 2.8% 14.3% N=2589 63.9% 50 70 20 <20 <25 <9 <15 <30

5. All women with osteoporotic fractures have inadequate vitamin D levels Hospitalized patients with osteporotic fractures, age>60 yrs serum-25-OH-D < 3 2 ng/ml in 97,8%! Gallacher SJ et al Curr Med Res Opin 2005;21:1355–1361; Heaney RP Osteoporos Int 2000;11:553–555. Lower limits of 25-OH-D (ng/ml) Prevalenc e (%) 0 50 110 40 30 20 10 60 70 80 90 100 N=548 <32 98.9% <28 98.0% <24 95.6% <20 92.7% <16 81.0% <12 68.4%

6. Causes of inadequate vitamin D levels in the elderly Lack of staying open-air Inadequate food consumption Less effective vitamin D synthesis in the skin Less 7-deh y dro ch olester ol in the skin Allain TJ, Dhesi J Gerontology 2003;49:273–278; Holick MF Am J Clin Nutr 1994;60:619–630; Lips P. In: Advances in Nutritional Research , Vol 9, New York: Plenum Press, 1994:151–165 ; Webb AR et al Am J Clin Nutr 1990;51:1075–1081; Holick MF et al Lancet 1989;2:1104–1105; MacLaughlin J, Holick MF J Clin Invest 1985;76:1536–1538,

7. Recommended daily vitamin D intake (earlier) Eur o p e European Commission Food Council: daily 400 NE for the elderly USA Institute of Medicine : Adults < 50 yrs: 2 00 NE Adults 51–70 yrs: 400 NE Adults > 70 yrs: 600 NE European Commission. Report on Osteoporosis in the European Community: Action on Prevention . Luxembourg: Office for Official Publications of the European Communities, 1998; Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride . Washington, DC: Institute of Medicine, National Academy Press, 1997 . At present, the recommended daily dosage of vitamin D is 800 NE !

8. Results with vitamin D supplementation

9. Reduced fracture incidence 5-year, randomized, double blind, controled study N=2686 65 - 85 yrs Vitamin D = 100 000 NE in every 4 months ( equvivalent of daily 800 NE ) Trivedi D et al BMJ 2003;326:469, Fracture risk ( hip, wrist, forearm, spine ) – 33% Treated (n=1341) Untreated (n=1345) p= 0,0 2 0 , 2 0 , 4 0 , 6 0 , 8 1,0 1,2

10. Hip fx Bischoff-Ferrari HA et al, Arch Intern Med. 2009;169(6):551-561

11. Risk of falling 122 women 63 - 99 yrs Randomiz ed , double blind , controled study C alcium 1200 mg/ daily C alcium 1200 mg/ daily + vitamin D 800 NE / daily 12 weeks Initial s e rum - 25 - OH - D = 12 ng/ml Átvéve: Bischoff HA et al J Bone Miner Res 2003;18:343–351, Only calcium (n=44) C alcium + vitamin D (n=45) Risk of falling 0 , 2 0 ,4 0 , 6 0 , 8 1,0 1,2 – 49% Risk of falling decreased p= 0,0 1

12. 25 - OH - D and lower limb functions 4100 adults from NHANES III 60 yrs Time needed for 2,5 m walking LOWESS regress ion curve NHANES=National Health and Nutrition Examination Survey; LOWESS ( locally weighted regression ) = adatpontonként súlyozott regresszió Bischoff-Ferrari HA et al Am J Clin Nutr 2004;80:752–758, S e rum - 25 - OH - D (ng/ml) 0 8 16 32 48 64 Walking time ( sec ) 24 40 56 3,5 4,0 4,5 Referenc e- range Improvement of lower limb functions

13. T umorgene s is In vitamin D insufficiency, the prevalence of certain tumors is 35% higher.

14. DNA-weighted UVB

16. Tumors associated with UVB radiation Aerodigestive tract us – colon, esophagus, larynx, rectum, stomack, lung, pancreas Breast Reproductiv e organs – ovar y , prostat e , test is , uterus, vulva Others – bladder , gall-bladder , kidney , brain Blood – Hodgkin lymphoma, non-Hodgkin lymphoma

17. Lappe JM et al, Am J Clin Nutr 2007;85:1586–91. N=1179

18. Sunshine, vitamin D, SM Pierrot-Deseilligny, Souberbielle Brain 2010:133;1869–1888 10 n g/m l increase in 25-OH-D reduces the relapses by 34% (Mowry et al., 2010) .

19. Heart and vessels PTH ANF (pro-BNP) Vessel wall Blood pressure In vitamin D insufficiency, cardiovasc. events are 20-30% more frequent

20. Endocrinology Metabolic sy. Polycystic ovary sy. (PCOS) Glucose intolerance Diabetes mellitus

21. Immunity - infections Immunmodulatory effects Infections are more frequent in vitamin D insufficiency TBC of vegetarians Vírus infections

22. Dementia Nerve Growth Factor (NGF) Dementia – apoptosis Antiapoptotic effect

23. Economical aspects of vitamin D supplementation William B Grant et al Progress in Biophysics and Molecular Biology, March 4 (2009) 1–10. Hip fractures 26% ↓ T1DM 78% ↓ All tumors: 35% ↓ Flu: 90% ↓ Mortality: 7-10% ↓ Expected lifetime: 2–3 év ↑ Average 25OHD at present: 15-20 ng/ml. If it was increased to 30-40 ng/ml: Every 1 USD spent on vitamin D results in 20 USD savings in health care Vit. D suppl. 1346 USD/pers. health care savings Vit. D suppl. = 10 USD/year (USA-EU) Vit. D suppl. = 7.5 USD/year (HU) – 1.5 billion USD savings Gross Domestic Product, % GDP Healthcare, % Saved Achieving Vitamin D3 Adequacy Population GDP % GDP healthcare Cost of healthcare in US dollars 17.7% annual savings 40 ng/mL level vitamin D3 Northern Europe $16.4 trillion (€uros 12.05 trillion) 9.3% $1.568 trillion $261 billion (€uros 187 billion) USA $14.1 trillion 16.2% $2.284 trillion $404 billion Source: Extrapolated from data published in Progress in Biophysics and Molecular Biology, March 4, 2009. Chart by Knowledge of Health, Inc.

24. Suggested vitamin D statements Relatively high serum 25-OH-D levels are required for optimal health status. On Earth, sun UV ratiation is the primary source of vitamin D. Intake from food is not sufficient. In Europe, vitamin D supplementation is recommended for everyone from autumn to spring. Year-around supplementation is suggested for the elderly. Country-based surveys should be carried out for the establishment of vitamin D status.