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Vitamin D: Current Research and Recommendations Across the Life Span

Vitamin D: Current Research and Recommendations Across the Life Span. Seema Desai, MS, RD, LDN, CNSD Kerry Harwood, MSN, RN. Vitamin D Overview. It is a fat soluble vitamin. Not just a vitamin it is a prehormone Found in some food and made in the body after exposure to UV rays

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Vitamin D: Current Research and Recommendations Across the Life Span

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  1. Vitamin D: Current Research and Recommendations Across the Life Span Seema Desai, MS, RD, LDN, CNSD Kerry Harwood, MSN, RN

  2. Vitamin D Overview • It is a fat soluble vitamin. • Not just a vitamin it is a prehormone • Found in some food and made in the body after exposure to UV rays • Major biological function is to maintain normal blood levels of Ca and Po4 • Other tissues like macrophages, prostrate tissue also have vit D receptor

  3. History of Vitamin D • Existed over 500 million years • Industrial revolution : rickets • Cod liver oil: common folklore medicine • Discovery of Vit D as the antirachitic factor in cod liver oil(1920) • Discovery of conversion of 7-dehydrocholesterol in the skin to vit D (1937) • Antirachitic property in food • Fortification of food with vitamin D was patented • Complete eradication of rickets in US • US public service issuing warnings about sun-induced health risk • Over next 30 yrs skin cancer hazard of excessive sun exposure became well established

  4. Structure of Vitamin D

  5. Endocrine, paracrine and intracrine functions of Vitamin D

  6. Vitamin D Across the Lifespan • Factors influencing accumulation of bone minerals: • Heredity • Gender • Diet • Physical activity • Endocrine status • Maternal vitamin D status

  7. Maternal Vitamin D Status Association of low intake of milk and vit D during pregnancy with decreased birth weight. C.A. Mannion, Katherine Gray-Donald, kristine G. Koski. CMAJ April 25, 2006 -Women between ages 19-45yrs -In Calgary -</= 250 ml of milk = low birth weight -milk or vit D independent predictor of BW -1 cup milk = 41 gm increase in BW -1 Mcg increase in dietary vit D = 11 gm increase in BW

  8. Maternal vitamin D…. Maternal vitamin D status during pregnancy and childhood bone mass at age 9yrs. M.K. Javaid, SR Crozeir at al. Lancet Jan 7 2006 -198 children born in 1991-92 in South Hampton UK -children were followed up at age 9yrs -31% mother had insufficient and 18% had deficient serum vit D during late pregnancy -decrease vit D in mothers = decrease bone mineral content in children at age 9 yrs -mother’s exposure to UV rays and use of vit d predicted vit d and childhood bone mass

  9. Breastfed infants Vitamin D deficiency in breastfed infants in Iowa. Ekhard E. Ziegler, Bruce w. Hollis, Steven E Nelson and Janice M. Jeter. Pediatrics 2006 -84 breastfed infants -blood samples and dietary records were taken -35 infants were unsupplemented -49 infants were either supplemented with formula or vit D -10% were vit D deficient -Marked seasonal affect more so in the unsupplemented group -mainly but not exclusively during winter and occurred in light and dark skinned infants

  10. Healthy adolescents Prevalence of vitamin D deficiency among healthy adolescents. Catherine M Gordon, Kerrin C. DePeter, Henry A. Feldman, Estherann Grace, Jean Emans. Arch pediatr Adolesc med June 2004 -307 healthy adolescents 11-18 yrs, -annual physical between july 2001-june 2003 -Data collected on age, sex, ethnicity, Ht, wt, exercise, medical hx diet -Blood samples were drawn at the end of the visit -24.1% of the participants were vit D deficient -highest prevalence in African American -Most prevalent during winter -no difference in prevalence between girls and boys -+ correlation between soft drink consumption and vit D deficiency -inverse correlation between vit D deficiency and milk and cold cereal consumption

  11. Young girls in southern US Serum 25-hydroxy vitamin D concentration in girls aged 4-8 y living in the southeastern United States.Stein et al.. Am J clinical nutrition 2006 -168 prepubertal girls 4-8 yrs old -120 non-Hispanic white -48 non-Hispanic black -Oct 1997-Oct 2000 at U of GA -with in 1 wk of blood draw bone scan, anthropometric measure dietary intake, and physical activity were assessed https://docme.mc.duke.edu/ada/index.asp

  12. Mean vitaminD, Calcium and multivitamin use was higher in white girls than in black Both races had mean dietary vitamin D intake above adequate levels Race and season strongest predictor of vit D status Black girls had lower mean vit D value Vitamin D value were significantly higher in summer than in winter Living at low latitude does not entirely prevent poor vitamin D status

  13. Milk Allergies and vitamin D deficiency Milk allergy and vitamin D deficiency rickets: a common disorder associated with an uncommon disease. Case Report Joyce w. Yu at el… Annals of allergy, asthma and immunology…April 2006 -Case report of Vit D deficiency rickets in 2 yr old boy with milk allergy -BF for 6-7 months -failed trail of cows milk formula -drank 500-700ml of fruit juice with no vit D and Ca supplementation -18 months of age started to regress -Lab values: Vit D of 8 mmol/l, Ca: 1.98 mmol/l, alk phos: -2,822u/l

  14. Discharged taking 4000IU of vit D, 200mg calcitriol, and 300mg elemental Ca 2 weeks later was able to stand, and his lab values were improved.

  15. Adults

  16. Vitamin D Deficiency in Hospitalized Patients

  17. Vitamin D Deficiency in Renal Transplant Patients

  18. Vitamin D Inadequacy in Post-Menopausal Women

  19. Vitamin D and Cancer • May influence both incidence and mortality • Linked with GI cancer, prostate and breast cancers, lymphomas, endometrial and lung cancers

  20. Something New Under the Sun? Apperly FL. The relation of solar radiation to cancer mortality in North America. Cancer Research.1941(1):191-195

  21. 1979 - 1981 • Vitamin D receptors found in malignant melanoma cells and myeloid leukemia cells • 1,25(OH)2D inhibited melanoma cell proliferation and induced myeloid cell differentiation

  22. Northern vs. Southern U.S. 1 – 2 extra skin cancer deaths (per 100,000) 30 – 40 extra deaths for other major cancers (per 100,000)

  23. 1998 • Serum levels of 1,25(OH)2D are tightly controlled by the kidneys & don’t vary by sun exposure so how could vitamin D contribute to the north-south gradients and African-American excess in cancer rates? • Non-renal cells discovered to hydroxylate 25(OH)D and synthesize 1,25(OH)2D locally.

  24. Vitamin D & Cancer • Environmental: sunlight & diet • Calcitriol (hormonal form of vitamin D) controls the differentiation of many cells that possess vitamin D receptors (VDR) • Induce cell differentiation and apoptosis of cancer cells while inhibiting cell proliferation, angiogenesis, and metastasis • Genetic: VDR polymorphisms

  25. June, 2007 American Journal of Clinical Nutrition • Women who regularly took vitamin D3 and calcium had a 60% reduction in all-cancer incidence compared with a group taking placebo and a 77% reduction when the analysis was confined to cancers diagnosed after the first 12 months.

  26. Lung cancer 1,25(OH)2D: • inhibits proliferation and induces differentiation of lung cancer cell lines (Higashimoto, et al., 1996, Guzey, et al., 1998) • inhibits metastatic growth and locoregional recurrence of lung cancer cells in mice (Wiers, et al., 2000)

  27. Lung cancer • 456 patients with early stage NSCLC • Median age – 69 • 96% Caucasian • Data collection: • Season of surgery • Food frequency questionnaire • Recurrence free survival (RFS) • Overall survival (OS) Zhou, et al., 2005

  28. Lung cancer • Patients who had surgery during summer with the highest vitamin D intake had better RFS that patients who had surgery during winter with the lowest vitamin D intake. • Similar associations were seen for overall survival. Zhou, et al., 2005

  29. Lung cancer Insert survival graph from Zhou article here

  30. Breast cancer 1,25(OH)2D: • inhibits cell proliferation, induces differentiation & apoptosis, and inhibits angiogenesis in normal and breast cancer cells (Colston, et al, 1989, Saez, et al, 1993, Mantell, et al., 2000) • suppresses high-fat diet-induced mammary tumorigenesis in rats (Jacobson, et al., 1989, Xue, 1999)

  31. Breast cancer • Inverse association between vitamin D & calcium intake and breast density • Inconclusive results in studies looking at VDR genetic polymorphisms and breast cancer • Inverse association between high sunlight exposure and breast cancer risk • Association may be stronger for premenopausal than postmenopausal women due to interactions between vitamin D, the VDR, estrogen and insulin-like growth factor-I (IGF-I) Cui & Rohan, 2006

  32. Breast cancer • Case-control study – 972 women with newly-diagnosed breast cancer & 1,135 healthy controls • Interviews regarding vitamin D-related exposures, e.g. outdoor activities, use of sunscreen, dietary contributions Knight, 2007

  33. Breast cancer • More frequent sun exposure during adolescence was associated with a 35% reduction in breast cancer risk later in life • Lower risk also linked to cod liver oil and milk intake > 10 glasses / week • Milder protection seen for people age 20 – 29 • No protection for people over age 45

  34. Breast cancer • Epidemiologic study of different regions of Norway, each with a different annual UV exposure • Prognosis 15 – 25% better for women diagnosed / treated in the summer vs. winter <get this article: Breast Cancer Research and Treatment, May>Knight , 2007

  35. Endometrial cancer Is ultraviolet B irradiance inversely associated with incidence rates of endometrial cancer: an ecological study of 107 countries. Mohr, et al, 2007

  36. Endometrial cancer • Objective: perform an ecological analysis of the relationship between low levels of ultraviolet B irradiance and age-standardized incidence rates of endometrial cancer by country, controlling for known confounders

  37. Endometrial cancer • 107 countries: • UVB irradiance • cloud cover • intake of energy from animal sources • proportion overweight • skin pigmentation • cigarette consumption • health expenditure • total fertility rates • vs. age-standardized incidence of endometrial cancer

  38. Endometrial cancer • Association found between endometrial cancer incidence rates and: • Low UVB irradiance • High intake of energy from animal sources ( IGF-I?) • Per capital health expenditure • Proportion of population overweight

  39. Pancreatic cancer • Prospectively collected diet and lifestyle data • Nurses’ Health Study – 75,427 women • Health Professionals Follow-up Study – 46,771 men • Pancreatic cancer risk 41% lower among those who consumed > 600 IU of vitamin D / day vs. those who consumed < 150 IU / day Skinner, et al., 2006

  40. Cancer Survival • Summer / Fall (vs. Winter / Spring) diagnosis associated with improved survival in: • Colorectal cancer • Hodgkin’s lymphoma • NSCLC • Breast cancer

  41. Cancer Survival • Intermittent sun exposure associated with increased survival following a diagnosis of melanoma Berwick, et al., 2005

  42. Type 2 Diabetes • Altered vitamin D and calcium homeostasis may play a role in development of type 2 diabetes • Low serum levels of 25(OH)D are associated with impaired pancreatic β cell function and insulin resistance • High calcium intake is inversely associated with body weight

  43. Type 2 Diabetes • Nurses’ Health Study – 83,779 women (98% Caucasian) • Daily intake of >1,200 mg calcium & >800IU vitamin D was associated with a 33% lower risk of type 2 diabetes compared with an intake of <600 mg calcium & <400 IU vitamin D Pittas, et al., 2006

  44. Type 1 Diabetes • Birth-cohort study in Finland – all women due to give birth in 1966 enrolled • 10,366 children born alive and followed to one year; 81 diagnosed with Type 1 diabetes • Children who regularly took recommended dose of vitamin D (2000 IU) had a RR of 0.22 compared with those who did not. • Children suspected of having rickets had a RR of 3.0 compared with those not suspected. Hopponen, et al., 2001

  45. Metabolic Syndrome • Third National Health & Nutrition Examination Survey (NHANES III) • 8,421 men and non-pregnant women > 20 years of age and had fasted > 8 hrs • Unadjusted prevalence of metabolic syndrome - 21.9%

  46. Metabolic Syndrome • After adjustments for known risk factors, odd of metabolic syndrome decreased progressively across increasing concentrations of 25(OH)D • Relative risk compared with bottom quintile of vitamin D level: • 2nd quintile – 0.85 • 3rd quintile – 0.75 • 4th quintile – 0.62 • 5th quintile – 0.46 Ford, et al., 2005

  47. Pulmonary / COPD • Third National Health & Nutrition Examination Survey (NHANES III) • 14,000 subjects • Dose-response correlation between percent predicted FEV1 and FVC values and circulating 25(OH)D • Plausibility: vitamin D shown to prevent experimental inflammatory diseases in mice including allergic asthma Black, et al., Chest, 2005

  48. Congestive Heart Failure • RCT of vitamin D + calcium vs. placebo + calcium x 9 months in subjects with CHF • 93 subjects completed study • Anti-inflammatory cytokine interleukin 10 significantly higher • Suppressed release of TNF-α • No difference in survival but blood levels not optimized Schleithoff, et al., 2006

  49. Hypertension • Prospectively followed two cohorts: • Nurses’ Health Study – 1198 women • Health Professionals Follow-up Study – 613 men • Relative risk of hypertension: • < 15 ng/mL vs > 30 ng/mL 25(OH)D • Men: RR = 6.13 • Women: RR = 2.67

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