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Vitamin D Gajendra Singh PhD Student 1. CONTENTS 2  Introduction  Mechanism of action of Vitamin D(VD) in body  Vitamin D deficiency (VDD)  Causes.

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Presentation on theme: "Vitamin D Gajendra Singh PhD Student 1. CONTENTS 2  Introduction  Mechanism of action of Vitamin D(VD) in body  Vitamin D deficiency (VDD)  Causes."— Presentation transcript:

1 Vitamin D Gajendra Singh PhD Student 1

2 CONTENTS 2  Introduction  Mechanism of action of Vitamin D(VD) in body  Vitamin D deficiency (VDD)  Causes of VDD  Consequences of VDD  Prevention of VDD  Conclusion

3 Introduction 3  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.

4 .......Introduction 4  VD Synthesis Depends on:  Time of the day  Age  Skin pigmentation  Sunshine intensity/UV Index  Latitude  season

5 Synthesis of Vitamin D 5

6 Mechanism of action of Vitamin D 6  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 7  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.

8 …..Mechanism of action of Vitamin D 8  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 9  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

10 Mechanism of Action of Vitamin D 10

11 Functions of of Vitamin D 11

12 Metabolism Of Vitamin D 12

13 Vitamin D Deficiency (VDD) 13  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

14 Vitamin D StatusSerum 25(OH)D level (ng/ml) Sufficient 30 ng/ml and above Insufficient 20- <30 Deficiency<20ng/ml Mild 10- <20ng/ml Moderate 5- <10ng/ml Severe <5ng/ml Cut off values to define VDD as per Lips. P, (2001) 14

15 ….Vitamin D Deficiency (VDD ) 15  Silent epidemic and highly prevalent  Often unrecognized condition  VDD Global prevalence : 30-80%  Overall prevalence of VDD in India: 50-90%.

16 ….Vitamin D Deficiency (VDD) 16  More prevalent in - women of child bearing age - infants and growing children and - elderly.

17 Causes of VDD 17 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,

18 …..causes of VDD 18  Darker skin pigmentation,  Low physical activity  Malabsorption  Some diseases  Liver failure  Chronic renal disease

19 Associated Risk Factors 19  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

20 Consequences of VDD 20  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

21 Skeletal disorders 21 Calcium and Phosphorus imbalance leads to - Rickets - Osteomalacia - Osteoporosis - Frontal bossing - Proximal myopathy - Knock knee and bow leg etc.

22 Vitamin D & Cancer 22  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.

23 VDD and Type 2 Diabetes 23  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

24 VDD and Hypertension 24  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.

25 VDD and Immunity 25  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

26 VDD and Metabolic Syndrome 26  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

27 VDD and Psoriasis 27  Keratinocyte in skin---- -major source of 7DHC also have VDR  Calcitriol is a potent inhibitor of keratinocyte proliferation

28 VDD and Tuberculosis 28  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)

29 VDD and Multiple Sclerosis 29  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 Zittermann A. Br J of Nutr. 2003;89:552-572

30 VDD and Falls in the Elderly 30  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

31 VDD and Neurological disorder 31  Vit D modulates neurotransmitter and neurological function - Neuronal channels - Anticonvulsant and antidepressant effect

32 Prevention of VDD 32  Adequate Sun Exposure  Consumption of Vitamin D rich Food  Vitamin D fortification/supplementation  Proper Physical Activity

33 Conclusion 33  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.

34 34

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