Gajendra Singh PhD Student 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.

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

Synthesis of Vitamin D

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

Mechanism of Action of Vitamin D

Functions of of Vitamin D

Metabolism Of Vitamin D

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

Cut off values to define VDD as per Lips . P, (2001) 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

….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 Inadequate exposure to sun 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 -peripheral blood monocyte -Macrophages 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 -major source of 7DHC also have VDR 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.

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