1. Gajendra Singh PhD Student
Vitamin D
Gajendra Singh
PhD Student

2. 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

3. 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.

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

5. Synthesis of Vitamin D

6. 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

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 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
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

10. Mechanism of Action of Vitamin D

11. Functions of of Vitamin D

12. Metabolism Of Vitamin D

13. 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

14. 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

15. ….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%.

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

17. 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,

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

19. 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

20. 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

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

22. 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.

23. 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

24. 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.

25. 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

26. 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

27. 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

28. 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)

29. 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:

30. 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

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

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

33. 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.

34. Thank You