vitamin d gajendra singh phd student 1. contents 2 introduction mechanism of action of vitamin...

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Vitamin D

Gajendra Singh

PhD Student

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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

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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.

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.......Introduction VD Synthesis Depends on:

Time of the day Age Skin pigmentation Sunshine intensity/UV Index Latitude season

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Synthesis of Vitamin D

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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

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…..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.

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…..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.

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…..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

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Mechanism of Action of Vitamin D

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Functions of of Vitamin D

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Metabolism Of Vitamin D

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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

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Vitamin D Status Serum 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)

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….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%.

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….Vitamin D Deficiency (VDD)

More prevalent in

- women of child bearing age

- infants and growing children and

- elderly.

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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,

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…..causes of VDD

Darker skin pigmentation,

Low physical activity

Malabsorption

Some diseases

Liver failure

Chronic renal disease

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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

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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

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Skeletal disorders

Calcium and Phosphorus imbalance leads to

- Rickets

- Osteomalacia

- Osteoporosis

- Frontal bossing

- Proximal myopathy

- Knock knee and bow leg etc.

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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.

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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

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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.

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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

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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

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VDD and Psoriasis Keratinocyte in skin----

-major source of 7DHC also have VDR

Calcitriol is a potent inhibitor of keratinocyte proliferation

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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)

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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

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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

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VDD and Neurological disorder

Vit D modulates neurotransmitter and neurological function

- Neuronal channels

- Anticonvulsant and antidepressant effect

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Prevention of VDD

Adequate Sun Exposure

Consumption of Vitamin D rich Food

Vitamin D fortification/supplementation

Proper Physical Activity

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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.

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Thank You