Vitamin D Gajendra Singh PhD Student
CONTENTS • Introduction • Mechanism of action of Vitamin D(VD) in body • Vitamin D deficiency (VDD) • Causes of VDD • Consequences of VDD • Prevention of VDD • Conclusion
Introduction • Vitamin D : Fat soluble vitamin that acts as a hormone in human body. • Forms of vitamin D : • Vitamin D3 (Cholecalciferol) and • Vitamin D2 (Ergocalciferol). • The major source of vitamin D for humans is exposure to sunlight.
.......Introduction • VD Synthesis Depends on: • Time of the day • Age • Skin pigmentation • Sunshine intensity/UV Index • Latitude • season
Mechanism 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
…..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 cells • Act 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.
…..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.
…..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
Vitamin D Deficiency (VDD) • Debate in the literature regarding the cut off values and criteria that appropriately define sub optimal vitamin D levels • VDD deficiency differs and difficult to compare because- - season of sample collection, - lab. method used for estimation of VD, and - sensitivity of the test
….Vitamin D Deficiency (VDD) • Silent epidemic and highly prevalent • Often unrecognized condition • VDD Global prevalence : 30-80% • Overall prevalence of VDD in India: 50-90%.
….Vitamin D Deficiency (VDD) • More prevalent in - women of child bearing age - infants and growing children and - elderly.
Causes of VDD The main risk factors for VDD in India are • Inadequate exposure to sun • Indoor confinement during the day, • Living in urban areas with tall buildings around • Clothing pattern • Atmospheric pollution,
…..causes of VDD • Darker skin pigmentation, • Low physical activity • Malabsorption • Some diseases • Liver failure • Chronic renal disease
Associated Risk Factors • Use of sunscreen creams/lotions, • Low intake of Vitamin D rich foods, • Low calcium intake, • High fiber diet, • Exclusive Breastfeeding, • Some medications and • Some genetic factors
Consequences of VDD • VDR is widely expressed in over 30 tissues and organs (like skin ,prostate, breast ,colon lung and placenta) • Calcitriol maintains expression of more than 200 genes • Hypovitaminosis D has emerged as a potential risk factors for many disorders
Skeletal disorders Calcium and Phosphorus imbalance leads to - Rickets - Osteomalacia - Osteoporosis - Frontal bossing - Proximal myopathy - Knock knee and bow leg etc.
Vitamin D & Cancer • 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 • Lung cancer ,Breast cancer, prostate cancer etc.
VDD and Type 2 Diabetes • Altered vitamin D and calcium homeostasis - type 2 diabetes • Low serum levels of 25(OH)D are associated with impaired pancreatic β cell function and insulin resistance • Cod liver studies also show significant reduction of incidence of Type I DM • Insulin secretion-Ca dependent
VDD and Hypertension • BP higher in winter • BP higher with increasing latitude • HTN 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.
VDD and Immunity • VDR expressed in : -peripheral blood monocyte -Macrophages -dendritic cells -leukocytes & Th(CD4+) and Tc(CD8+) cells • As a result VDD can have widespread effects on immune effector response
VDD and Metabolic Syndrome • After adjustments for known risk factors, odd of metabolic syndrome decreased progressively across increasing concentrations of 25(OH)D • Components of MS- Abdominal obesity, dyslipidemia, DM and HTN
VDD and Psoriasis • Keratinocyte in skin---- -major source of 7DHC also have VDR • Calcitriol is a potent inhibitor of keratinocyte proliferation
VDD and Tuberculosis • Activated macrophages produce calcitriol(Liu et al) • Activation of TLR with LPS results in upregulation of VDR and CYP27B1 gene. • Mycobacterium tuberculosis LPS TLR Cathelicidin (antimicrobial peptide)
VDD and Multiple Sclerosis • 48% of MS pts are Vit D deficient • Mahon. J Neuroimmunol. 2003;134(1-2):128. • MS rare near equator • Zittermann A. Br J of Nutr. 2003;89:552-572
VDD and Falls in the Elderly • VDR in skeletal muscle • VDD 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
VDD and Neurological disorder • Vit D modulates neurotransmitter and neurological function - Neuronal channels - Anticonvulsant and antidepressant effect
Prevention of VDD • Adequate Sun Exposure • Consumption of Vitamin D rich Food • Vitamin D fortification/supplementation • Proper Physical Activity
Conclusion • VDD is a common disorder • Vitamin D receptors found in gut, bone, brain, breast, prostate, lymphocytes, placenta, and other tissues • Potential health consequences are associated with the VDD.