2CONTENTS Introduction Mechanism of action of Vitamin D(VD) in body Vitamin D deficiency (VDD)Causes of VDDConsequences of VDDPrevention of VDDConclusion
3IntroductionVitamin D : Fat soluble vitamin that acts as a hormone in human body.Forms of vitamin D :Vitamin D3 (Cholecalciferol) andVitamin D2 (Ergocalciferol).The major source of vitamin D for humans is exposure to sunlight.
4Sunshine intensity/UV Index Latitude season IntroductionVD Synthesis Depends on:Time of the dayAgeSkin pigmentationSunshine intensity/UV IndexLatitudeseason
6Mechanism of action of Vitamin D Metabolism of vitamin D3 (produced in skin) by the liver to 25(OH)D3,Conversion of 25(OH)D3 by the kidney to the active hormone 1,25(OH)2D3.Systemic transport of the dihydroxylated metabolites to distal target organs
7…..Mechanism of action of Vitamin D Binding of 1,25(OH)2D3 to vitamin D receptpr (VDR), which is principally located in the nuclei of target cellsAct as a transcription factor that modulates the gene expression of transport proteins (such as TRV6 and calbindin), which are involved in calcium absorption in the intestine.
8…..Mechanism of action of Vitamin D VDRs expressed by cells in most organs, including the brain, heart, skin, gonads, prostate, breast.VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood and proper maintenance of bone architecture.
9…..Mechanism of action of Vitamin D The VDR is known to be involved in cell proliferation and differentiation.Vitamin D also affects the immune system, and VDRs are expressed in several WBC, including monocytes and activated T and B cells
13Vitamin D Deficiency (VDD) Debate in the literature regarding the cut off values and criteria that appropriately define sub optimal vitamin D levelsVDD deficiency differs and difficult to compare because-- season of sample collection,- lab. method used for estimation of VD, and- sensitivity of the test
14Cut off values to define VDD as per Lips . P, (2001) Vitamin D StatusSerum 25(OH)D level (ng/ml)Sufficient30 ng/ml and aboveInsufficient20- <30Deficiency<20ng/mlMild10- <20ng/mlModerate5- <10ng/mlSevere<5ng/ml
15….Vitamin D Deficiency (VDD) Silent epidemic and highly prevalentOften unrecognized conditionVDD Global prevalence : 30-80%Overall prevalence of VDD in India: 50-90%.
16….Vitamin D Deficiency (VDD) More prevalent in- women of child bearing age- infants and growing children and- elderly.
17Causes of VDD Inadequate exposure to sun The main risk factors for VDD in India areInadequate exposure to sunIndoor confinement during the day,Living in urban areas with tall buildings aroundClothing patternAtmospheric pollution,
19Associated Risk Factors Use of sunscreen creams/lotions,Low intake of Vitamin D rich foods,Low calcium intake,High fiber diet,Exclusive Breastfeeding,Some medications andSome genetic factors
20Consequences of VDDVDR is widely expressed in over 30 tissues and organs (like skin ,prostate, breast ,colon lung and placenta)Calcitriol maintains expression of more than 200 genesHypovitaminosis D has emerged as a potential risk factors for many disorders
21Skeletal disordersCalcium and Phosphorus imbalance leads to - Rickets - Osteomalacia - Osteoporosis - Frontal bossing - Proximal myopathy - Knock knee and bow leg etc.
22Vitamin D & CancerCalcitriol (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 metastasisLung cancer ,Breast cancer, prostate cancer etc.
23VDD and Type 2 DiabetesAltered vitamin D and calcium homeostasis type 2 diabetesLow serum levels of 25(OH)D are associated with impaired pancreatic β cell function and insulin resistanceCod liver studies also show significant reduction of incidence of Type I DMInsulin secretion-Ca dependent
24VDD and Hypertension BP higher in winter BP higher with increasing latitudeHTN pts given UV light treatments 3 times per week for 6 weeks had Vit D level increases of 162% and saw mild decreases in BP.-Krause et al. Lancet. 1998;352(9129):709.
25VDD and Immunity -peripheral blood monocyte -Macrophages VDR expressed in :-peripheral blood monocyte-Macrophages-dendritic cells-leukocytes & Th(CD4+) and Tc(CD8+) cellsAs a result VDD can have widespread effects on immune effector response
26VDD and Metabolic Syndrome After adjustments for known risk factors, odd of metabolic syndrome decreased progressively across increasing concentrations of 25(OH)DComponents of MS-Abdominal obesity,dyslipidemia,DM and HTN
27VDD and Psoriasis -major source of 7DHC also have VDR Keratinocyte in skin-----major source of 7DHC also have VDRCalcitriol is a potent inhibitor of keratinocyte proliferation
28VDD and TuberculosisActivated macrophages produce calcitriol(Liu et al)Activation of TLR with LPS results in upregulation of VDR and CYP27B1 gene.Mycobacterium tuberculosisLPS TLR Cathelicidin (antimicrobial peptide)
29VDD and Multiple Sclerosis 48% of MS pts are Vit D deficientMahon. J Neuroimmunol. 2003;134(1-2):128.MS rare near equatorZittermann A. Br J of Nutr. 2003;89:
30VDD and Falls in the Elderly VDR in skeletal muscleVDD reported to affect predominantly the weight- bearing antigravity muscles of the lower limb, which are necessary for postural balance and walking-Glerup H et al. Calcif Tissue Int 2000;66:419.Significant correlation between serum 25(OH)D3 concentration and the occurrence of falls in elderly reported in literature.-Mowé M et al. J Am Geriatr Soc 1999;47:220
31VDD and Neurological disorder Vit D modulates neurotransmitter and neurological function- Neuronal channels- Anticonvulsant and antidepressant effect
32Prevention of VDD Adequate Sun Exposure Consumption of Vitamin D rich FoodVitamin D fortification/supplementationProper Physical Activity
33ConclusionVDD is a common disorderVitamin D receptors found in gut, bone, brain, breast, prostate, lymphocytes, placenta, and other tissuesPotential health consequences are associated with the VDD.