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Vitamin D Fat-soluble vitamin Sources –Foods Naturally found in very few foods Added to many foods on the market –Supplements –Sunlight.

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Presentation on theme: "Vitamin D Fat-soluble vitamin Sources –Foods Naturally found in very few foods Added to many foods on the market –Supplements –Sunlight."— Presentation transcript:

1 Vitamin D Fat-soluble vitamin Sources –Foods Naturally found in very few foods Added to many foods on the market –Supplements –Sunlight

2 Vitamin D Daily Recommended Intake –Current minimum intake recommendations Birth-50 years = 200 IU 51-70 years = 400 IU 71+ years = 600 IU –Currently being debated

3 Food Sources of Vitamin D 3 oz smoked salmon = 583 IU 3 oz light tuna, canned in oil = 229 IU 1 large, whole egg = 29 IU

4 Foods Fortified with Vitamin D 8 oz skim milk = 115 IU 8 oz orange juice = 100 IU 1 cup Cheerios = 40 IU ½ cup yogurt = 40 IU

5 Definitions 7-dehydrocholesterol: provitamin D 3 Previtamin D 3 : cholecalciferol Vitamin D 3 : produced in the skin from irradiated 7-DHC, isomerized previtamin D 3 Vitamin D 2 : from plants, from irradiated ergosterol

6 Vitamin D synthesis

7 Vitamin D 3 is hydroxylated in the liver: 25 OH vitamin D: inactive, measured in serum as the biomarker of vitamin D status from all sources Second hydroxylation: 1,25 (OH) 2 vitamin D in the kidney *** These hydroxylation steps can also occur in keratinocytes, prostate cells and others

8 Vitamin D3 can be obtained in diet, or derived from cholesterol in a reaction that requires UV light. UV light spontaneous liver enzyme 25-hydroxylase Vitamin D3 calcitriol

9 Vitamin D binds to a “vitamin D binding protein” (VDP) for transport to target organs. Vitamin D is not active itself (it’s a prohormone); it is modified to yield biologically active forms, such as calcitriol. Calcitriol (derived from vitamin D) is a transcription factor, influencing expression of proteins involved in calcium absorption and transport. Vitamin D is also important for immune system function. Deficiency causes rickets, bone loss. Calcitriol, from vitamin D.

10 Vitamin D production requires UV light (sunlight). Sometime after humans migrated north out of Africa about 50,000 years ago, mutations appeared that reduced melanin (pigment) production in the skin, permitting vitamin D production with less sunlight. Disadvantages of less melanin production are skin that is easily damaged by the sun, skin cancer risk, and loss of folic acid due to UV damage. The melanin-reducing mutations helped early humans make vitamin D in northern europe in winter.

11 Vitamin D 25(OH)D 1,25(OH)D 26 + cells throughout the body 7-dehydrocholesterol UVB photons

12 Vitamin D Functions Many uses in the body –Promotes absorption of calcium from the small intestine –Maintain blood levels of calcium and phosphate for bone formation, mineralization, growth, and repair –Improves muscle strength and immune function –Reduces inflammation

13 Noncalcemic Functions of 1,25-dihydroxyvitamin D Cytokines Adaptive Innate Immune modulation

14 Vitamin D Deficiency At risk populations –Breastfed infants –Older adults –People with limited sun exposure –Darker skin pigments –Certain religious groups

15 Vitamin D Related Diseases –Rickets –Osteomalacia –Osteoporosis

16 Vitamin D Deficiency Rickets, Osteomalacia Influenza, Tuberculosis MS, RA, SLE, Type I diabetes Hypertension, CAD, PVD, CHF Syndrome X, Type 2 Diabetes Chronic Fatigue, SAD, Depression Cataracts, Infertility Osteoporosis Cancer

17 System and Tissue Distribution of Nuclear Vitamin D Receptors (VDR) System Tissue Immune Thymus, bone marrow, macrophages, B cells, T cells Gastrointestinal Esophagus, stomach, small intestine, colon, rectum Cardiovascular Endothelial cells, smooth muscle cells, myocytes Respiratory Lung alveolar cells Hepatic Liver parenchyma cells Renal Proximal and distal tubules, collecting duct Endocrine Parathyroid, thyroid, pancreatic beta cells Exocrine Parotid gland, sebaceous gland CNS Brain neurons, astrocytes, microglia Epidermis/appendage Skin, breast, hair follicles Musculoskeletal Osteoblasts, osteocytes, chondrocytes, striated muscle Connective Tissue Fibroblasts, stroma Reproductive Testis, ovary, placenta, uterus, endometrium, yolk sac

18 Diverse Structure of Ligands for Nuclear Receptors


20 Nutrigenomics Vitamin D Wood RJ, Tchack L, Angelo G, etal. DNA Microarray Analysis of Vitamin D- induced Gene Expression in a Human Colon Carcinoma Cell Line. Physiological Genomics 2004;17:122-129. Confirmatory PCR for 1,25-dihydroxyvitamin D-regulated genes found by Affymetrix GeneChip transcriptional profiling

21 Vitamin D and Cancer Roles in prevention of –Colon cancer –Breast cancer

22 Human Migration Out of Africa 35° N 35° S Lamson Rl, etal. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 2005;310:1782-1786.




26 Vitamin D and Cancer How it prevents –Promotes cellular differentiation –Decreases cancer cell growth –Stimulates cell deaths

27 Vitamin D Cancer Research Mostly observational studies, only show correlation –Food frequency questionnaires –Interviews –Diet records

28 Vitamin D & Colon Cancer Research Third National Health and Nutrition Examination Survey –Epidemiologic study –16,818 participants –Examined blood levels of vitamin D –Results Blood levels 80nmol/L or higher reduced risk by 72%

29 Vitamin D Cancer Research American Cancer Society’s Cancer Prevention Study II Nutrition Cohort –Studied 120,000 men and women –Analyzed diet, medical history, and lifestyle –Results Men with intakes of 520 IU or higher from both diet and supplementation slightly lowered risk No effect in women

30 Vitamin D & Breast Cancer Research Cancer Prevention Study II Nutrition Cohort –Participants 68,567 postmenopausal women –Completed questionnaire on dietary intake, family history, and supplement use –Results Women who consumed higher amounts of vitamin D and calcium from dairy products reduced their risk of breast cancer

31 Multiple Sclerosis in World War II Veterans by Latitude and State of Residence Wallin MT, etal. Multiple sclerosis in US veterans… Ann Neurol 2004;55:65-71

32 Tuberculosis Treated with Sunshine

33 Preop Vitamin D3 levels in 73 Veterans Undergoing Heart Surgery at the Seattle VA Hospital No. of Patients History of Cancer 25-hydroxyvitamin D 3 Level (ng/ml) 7 (9.6 %) 1 (colon) < 8 (severely deficient) 41 (56.2%) 6* 8-19.9 (deficient) 9 (12.3%) 0 20-29.9 (insufficient) 13 (17.8%) 0 30-49.9 (sufficient) 3 (4.1%) 0 50-100 (optimal) * Prostrate cancer – 3; Colon cancer – 1; Tonsillar cancer – 1; Melanoma -- 1 Surgery performed December 2006 – July 2007

34 Benefits of Vitamin D Skeletal-muscularSkeletal-muscular –Strong muscles and bones InfectionsInfections –Prevent influenza, treat tuberculosis CancerCancer –Prevent breast, colon, and prostate cancer –? Suppress metastasizes Autoimmune DiseasesAutoimmune Diseases –Prevent multiple sclerosis and type 1 diabetes Cardiovascular DiseaseCardiovascular Disease –Slow progression of atherosclerosis –Treat hypertension and congestive heart failure Neuropsychiatric DisordersNeuropsychiatric Disorders –Prevent schizophrenia and relieve depression

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