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

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Presentation on theme: "Vitamin D: Current Research and Recommendations Across the Life Span Seema Desai, MS, RD, LDN, CNSD Kerry Harwood, MSN, RN."— Presentation transcript:

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

6 Endocrine, paracrine and intracrine functions of Vitamin D

7 Vitamin D Across the Lifespan  Factors influencing accumulation of bone minerals: –Heredity –Gender –Diet –Physical activity –Endocrine status –Maternal vitamin D status

8 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, Women between ages 19-45yrs -In Calgary -

9 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 children born in 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

10 Breastfed infants Vitamin D deficiency in breastfed infants in Iowa. Ekhard E. Ziegler, Bruce w. Hollis, Steven E Nelson and Janice M. Jeter. Pediatrics 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

11 Healthy adolescents 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 healthy adolescents yrs, -annual physical between july 2001-june 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

12 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 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

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

14 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 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 ml 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

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

16 Adults

17 Vitamin D Deficiency in Hospitalized Patients

18 Vitamin D Deficiency in Renal Transplant Patients

19 Vitamin D Inadequacy in Post-Menopausal Women

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

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

22  Vitamin D receptors found in malignant melanoma cells and myeloid leukemia cells  1,25(OH) 2 D inhibited melanoma cell proliferation and induced myeloid cell differentiation

23 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)

24 1998  Serum levels of 1,25(OH) 2 D 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) 2 D locally.

25 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

26 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.

27 Lung cancer 1,25(OH) 2 D:  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)

28 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

29 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

30 Lung cancer Insert survival graph from Zhou article here

31 Breast cancer 1,25(OH) 2 D:  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)

32 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

33 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

34 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

35 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 Knight, 2007 Knight, 2007

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

37 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

38 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

39 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

40 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 600 IU of vitamin D / day vs. those who consumed < 150 IU / day Skinner, et al., 2006

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

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

43 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

44 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 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

45 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

46 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 %

47 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: –2 nd quintile – 0.85 –3 rd quintile – 0.75 –4 th quintile – 0.62 –5 th quintile – 0.46 Ford, et al., 2005

48 Pulmonary / COPD Third National Health & Nutrition Examination Survey (NHANES III)Third National Health & Nutrition Examination Survey (NHANES III) 14,000 subjects14,000 subjects Dose-response correlation between percent predicted FEV 1 and FVC values and circulating 25(OH)DDose-response correlation between percent predicted FEV 1 and FVC values and circulating 25(OH)D Plausibility: vitamin D shown to prevent experimental inflammatory diseases in mice including allergic asthmaPlausibility: vitamin D shown to prevent experimental inflammatory diseases in mice including allergic asthma Black, et al., Chest, 2005

49 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

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

51 Stroke

52 Chronic Kidney Disease

53 Multiple Sclerosis

54 Osteo- & Rheumatoid Arthritis

55 Where do we go from here?  Routine screening  Rectify deficiency / insufficiency  Maintain levels through a patient- specific combination of diet, supplementation, and sun exposure

56 Recommendations  Annual testing of 25(OH)D  Consider time of year in testing –Lowest levels generally towards end of winter, early spring

57 Vitamin D Assessment  Lab assays are available to measure both 25(OH)D and 1,25-D.  25(OH)D closely reflects total amount of vit D produced in the skin and from diet  D2 and D3: have similar biological activity  Both D2 and D3 should be measured  DO NOT USE - 1,25-D. This can often be normal with vit D deficiency

58 Goals in Maintaining Vitamin D Levels 1. Prevent disease of deficiency – rickets, osteomalacia 2. Prevent complications of insufficiency – impaired calcium absorption and increased bone resorption 3. Minimize risks of future disease – cancer, cardiopulmonary diseases, diabetes, other immune-related diseases

59 25(OH)D concentration  To prevent deficiency disease – > 25 nmol / L  To prevent complications of insufficiency – > 50 nmol/L  For maximum bone health and prevention of chronic disease – 75 – 100 nmol/L

60 Who is at greatest risk?  Low dietary intake: BF infants, children who do not drink fortified milk  Malabsorption syndrome  Severe liver disease  Kidney disease  Drugs  Higher latitudes  People who spend little time outside  Older adults  Decreased sun exposure due to cultural reasons  Races with high skin melanin levels

61 Supplementation

62 Supplementation (adults) To correct deficiency: 50,000 IU vitamin D weekly x 8 weeks, reassess and repeat if necessary To correct deficiency: 50,000 IU vitamin D weekly x 8 weeks, reassess and repeat if necessary

63 Supplementation (peds)  To correct deficiency

64 IOM Recommendations (AI) AgeChildrenMenWomenPregnancylactation Birth- 13 yrs 5mcgs 5mcgs=200IU yrs 5200IU5 200 IU 5200IU5200IU 19-50Yrs5200IU Yrs IU IU 15

65 Do recommendations reflect the state of the science? ‘Our studies in children (3 – 16 years of age) in Edmonton, Alberta, show that 200 IU daily is not even adequate for maintaining levels now considered mildly to moderately deficient (40 nmol/L), let alone optimum (80 nmol/L).’ ‘Our studies in children (3 – 16 years of age) in Edmonton, Alberta, show that 200 IU daily is not even adequate for maintaining levels now considered mildly to moderately deficient (40 nmol/L), let alone optimum (80 nmol/L).’ A.B. Jones, Canadian Family Physician, 2006

66 Do recommendations reflect the state of the science? ‘Oral doses currently consumed in the US (an estimated mean of 320 IU / day) are far too low, and the designation of the 2000 IU/day dosage as safe by NAS provides latitude to the community to increase intakes to levels required to reduce risk of cancer, with essentially no likelihood of adverse effects.’ ‘Oral doses currently consumed in the US (an estimated mean of 320 IU / day) are far too low, and the designation of the 2000 IU/day dosage as safe by NAS provides latitude to the community to increase intakes to levels required to reduce risk of cancer, with essentially no likelihood of adverse effects.’ Grant and Gorham, International J of Epidemiology, 2006

67 Do recommendations reflect the state of the science? ‘…the present recommended allowance for vitamin D – 400 IU – for individuals aged 50 – 70 years is inadequate even to maintain skeletal health and is probably too low for meaningful anticancer effects.’ ‘…the present recommended allowance for vitamin D – 400 IU – for individuals aged 50 – 70 years is inadequate even to maintain skeletal health and is probably too low for meaningful anticancer effects.’ Schwartz & Blot, J National Cancer Institute, 2006

68 National Academy of Science Tolerable Upper Intake Levels Pediatrics 0 – 12 months – 1000 IU / Day All others – 2000 IU / Day

69 USDHHS Dietary Guidelines for America  Special groups – elderly and individuals with dark skin – 1,000 IU / day

70 Maintenance (adults)  To maintain recommended levels: IU / day if not getting enough sun exposure to maintain vitamin D levels or 50,000 IU 1-2 times monthly

71 North American Conference on Vitamin D “to minimize the health risks associated with UVB radiation exposure while maximizing the potential benefits of optimum vitamin D status, {dietary} supplementation and small amounts of sun exposure are the preferred methods of obtaining vitamin D.” “to minimize the health risks associated with UVB radiation exposure while maximizing the potential benefits of optimum vitamin D status, {dietary} supplementation and small amounts of sun exposure are the preferred methods of obtaining vitamin D.” Consensus statement, 2006

72 How much sun?  Depends on: –Age –Amount of vitamin D obtained from diet –Skin darkness –Sunshine intensity

73 How much sun?  Significant skin exposure –Face, neck, arms, hands –Arms, legs  Adequate sun strength  Time –25% of the time it would take to cause pinkness of the skin (Caucasians) –People with dark skin require significantly more sun exposure Holick, 2004

74 Food Sources of Vitamin D  Cod liver oil – 1 TBS  Salmon 3.5 oz.  Mackerel 3.5 oz.  Tuna, canned, in oil, 3 oz.  Sardines 3.5 oz.  Milk (fortified) 8 oz.  Ready to eat cereal (fortified) ¾ - 1 cup  Egg 1 whole  Liver, 3.5 oz.  Cheese, swiss 1 oz.  1,360 IU  360  345  200  250  98  40  20  15  12


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