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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
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
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
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
Definitions • 7-dehydrocholesterol: provitamin D3 • Previtamin D3: cholecalciferol • Vitamin D3: produced in the skin from irradiated 7-DHC, isomerized previtamin D3 • Vitamin D2: from plants, from irradiated ergosterol
Vitamin D3 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
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 calcitriol Vitamin D3
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.
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.
Vitamin D 25(OH)D 1,25(OH)D 26 + cells throughout the body UVB photons 7-dehydrocholesterol
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
Noncalcemic Functions of 1,25-dihydroxyvitamin D Cytokines Adaptive Innate Immune modulation
Vitamin D Deficiency • At risk populations • Breastfed infants • Older adults • People with limited sun exposure • Darker skin pigments • Certain religious groups
Vitamin D Related Diseases • Rickets • Osteomalacia • Osteoporosis
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
System and Tissue Distribution of Nuclear Vitamin D Receptors (VDR) SystemTissue 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
Nutrigenomics Vitamin D Confirmatory PCR for 1,25-dihydroxyvitamin D-regulated genes found by Affymetrix GeneChip transcriptional profiling 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.
Vitamin D and Cancer • Roles in prevention of • Colon cancer • Breast cancer
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.
Vitamin D and Cancer • How it prevents • Promotes cellular differentiation • Decreases cancer cell growth • Stimulates cell deaths
Vitamin D Cancer Research • Mostly observational studies, only show correlation • Food frequency questionnaires • Interviews • Diet records
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%
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
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
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
Preop Vitamin D3 levels in 73 Veterans Undergoing Heart Surgery at the Seattle VA Hospital * Prostrate cancer – 3; Colon cancer – 1; Tonsillar cancer – 1; Melanoma -- 1 Surgery performed December 2006 – July 2007
Benefits of Vitamin D • Skeletal-muscular • Strong muscles and bones • Infections • Prevent influenza, treat tuberculosis • Cancer • Prevent breast, colon, and prostate cancer • ? Suppress metastasizes • Autoimmune Diseases • Prevent multiple sclerosis and type 1 diabetes • Cardiovascular Disease • Slow progression of atherosclerosis • Treat hypertension and congestive heart failure • Neuropsychiatric Disorders • Prevent schizophrenia and relieve depression