Vitamin D: Is it a superhero?? Dr. Ashraf Abdel Basset Bakr Prof. of Pediatrics
1 2 History of vitamin D discovery Sources of vitamin D and its metabolism 13 Actions of vitamin D 4 Vitamin D deficiency 15 Vitamin D supplementation
Introduction Vitamin D is a fat-soluble vitamin. It has a role in bone metabolism and other extra-mineral metabolism functions
History of vitamin D In 17 th century, the first extensive description of the clinical picture of rickets, carried out by Daniel Whistler and Francis Glisson. At the beginning of the 20th century, the discovery of the dual origin of vitamin D; dietary vitamin D and the curative effects of UV light.
History of vitamin D In 1938, Adolf Windaus earned the Nobel prize due to the chemical identification and chemical synthesis of vitamin D. In 1964 1984, acceptance that Vitamin D was a precursor of a steroid hormone (1,25(OH)2 D3) and the first isolation and characterization of a specific binding protein (receptor) for 1,25(OH)2 D3; vitamin D receptor (VDR).
History of vitamin D In 1987 2012, expansion of the vitamin D endocrine system after discovery of VDR in many tissues.
Sources and Metabolism of vitamin D 25-OHase 1 α-ohase
Sources and Metabolism of vitamin D 1,25(OH)2 D3 Major biologically active metabolite The hormonal form of vitamin D A steroid hormone Binds to hormone receptor (VDR) VDR Widely distributed VDR in over 40 tissues applying the endocrine paradigm beyond intestinal calcium absorption and the prevention of rickets and osteomalacia
Sources and Metabolism of vitamin D Pancreas Immune system Cardiovascular system Add Title Bone Kidney Muscle Nervous system
Sources of Vitamin D and its mineral role were discovered since 20 th century Vitamin D Active metabolite of vitamin D is 1,25 (OH)2 D3 VDRs are widely distributed in many tissues
Actions of vitamin D Pancreas Immune system Cardiovascular system Add Title Bone Kidney Muscle Nervous system
Action of vitamin D on calcium homeostasis These actions of 1,25 (OH)2 D3 Maintain an adequate calcium and phosphorus product which results in the mineralization of osteoid laid down by osteoblasts.
Deficiency of vitamin D and bone disease Decrease in the efficiency of intestinal calcium absorption and results in a decrease in ionized calcium itamin D deficiency Hypocalcemia stimulates calcium sensor in the parathyroid glands and increases the production and the secretion of PTH Increasing tubular reabsorption of calcium Stimulation of 1 α (OH) Act on their receptors in bone which stimulates the formation of osteoclasts, which in turn dissolves the bone matrix to release the calcium into the extracellular space
Deficiency of vitamin D and bone The net result is an inadequate calcium phosphate product necessary for the mineralization of the collagen matrix Rickets osteomalacia osteopenia osteoporosis
Sources and Metabolism of vitamin D Pancreas Immune system Cardiovascular system Add Title Calcium homeostasis Kidney Muscle Nervous system
Action of vitamin D and immune system
Action of vitamin D and immune system VDR is widely expressed in the immune system leads to the recognition of a central immunomodulatory role for 1,25(OH)2D Vit D effect on innate immunity Enhancing the antimicrobial properties of immune cells such as monocytes and macrophages. Vit D effect on adaptive immunity Exerts an inhibitory action on the adaptive immune system
Action of vitamin D and immune system Role in autoimmunity Role in infection Role in allergy
Action of vitamin D and immune system Role in autoimmunity Role in infection Role in allergy
Deficiency of vitamin D and infection Respiratory tract infection TB Vitamin D Neonatal infection www.themegallery.com
Deficiency of vitamin D and infection Sun light and cod liver oil had been used in TB treatment 1840 Vit D and TB Vit D isolated from cod liver oil 1930 Using chemotherapy decreased the interest in using sun light, cod liver oil in TB treatment Discovery chemotherapy Vit D deficiency is a risk factor for active TB and impaired antimicrobial activity Last two decades
Deficiency of vitamin D and infection Vit D and TB These initial clinical associations and early trials suggest that vitamin D may be beneficial as an adjunctive treatment to the traditional therapy for TB; however, additional randomized trials need to be conducted to clarify the role of vitamin D.
Deficiency of vitamin D and infection Vit D and RTI Early epidemiological studies found a strong association between rickets and RTI as influnza and RSV.
RTI Deficiency of vitamin D and infection More studies are needed to examine the direct effect of vitamin D supplementation and to establish the optimal serum levels of 25(OH)D to aid prevention of RTI
Deficiency of vitamin D and infection Neonatal infections Many studies performed in neonates and infants supported the preventive role of vitamin D against respiratory tract infections. Low cord blood levels of 25-OHD were found to be associated with a higher risk of RTI by the age of 3 months and a higher cumulative risk of wheezing in early childhood.
Deficiency of vitamin D and infection Neonatal sepsis
Deficiency of vitamin D and infection Respiratory tract infection TB Vitamin D Neonatal infection www.themegallery.com
Action of vitamin D and immune system Role in autoimmunity Role in infection Role in allergy
Action of vitamin D and autoimmunity 1,25(OH)2 D3 Immunomodulatory effects T cells *Decreases Th1/Th17 CD4+ T cells *Increases regulatory T cells B cells Inhibits Igs production Dentritic cells Maturation and the differentiation
Deficiency of vitamin D and autoimmune diseases
Deficiency of vitamin D and autoimmune diseases There have been several animal models of autoimmunity in which disease could either be prevented or ameliorated with the administration of either 1,25(OH)2D3. Type-1 diabetes mellitus Inflammatory bowel disease Autoimmune uveitis Systemic lupus Autoimmune encephalomyelitis Collageninduced arthritis
Deficiency of vitamin D and autoimmune DM diseases
Deficiency of vitamin D and autoimmune diseases SLE
Action of vitamin D and immune system Role in autoimmunity Role in infection Role in allergy
Deficiency of vitamin D and autoimmune diseases BA Experimental studies and genetic association studies of the VDR have motivated observational studies of vitamin D and asthma in humans.
Deficiency of vitamin D and autoimmune diseases BA Increased serum vitamin D Decreases atopy Increases steriod responsiveness Decreases viral infection Increases lung maturity and development Differentiation of naive T cells into IL-10 secreting Tregs * Vitamin D can increases glucocorticoidinduced secretion of IL-10 bytregs *Enhanced corticosteroid receptor signalling Down-regulates dendritic cell required for Th2 priming Up-regulates TGF-b Increase TGF-b positive Tregs and lower Th2 cytokine levels Modulates fetal lung maturation and airway smooth muscle cell proliferation and differentiation, although the mechanisms are unclear Decreases Asthma morbidity
Deficiency of vitamin D and autoimmune diseases Can vitamin D protect against or reduce asthma morbidity?
BA Deficiency of vitamin D and autoimmune diseases Observational studies Many observational studies of vitamin D and asthma were carried out with many limitations and controversy results.
Deficiency of vitamin D and autoimmune diseases BA
Sources and Metabolism of vitamin D Pancreas Immune system Cardiovascular system Add Title Calcium homeostasis Kidney Muscle Nervous system
Action of vitamin D and glucose metabolism Increases insulin sensitivity Expression of insulin receptors Increases insulin secretion Increases glucose uptake
Deficiency of vitamin D and glucose metabolism DM type 2
Deficiency of vitamin D and glucose metabolism Pre-diabetes
Sources and Metabolism of vitamin D Pancreas Immune system Cardiovascular system Add Title Calcium homeostasis Kidney Muscle Nervous system
Action of vitamin D and renoprotection
Action of vitamin D and renoprotection Increases nephrin expression Decreases inflammation Concept of renoprotection Antiproteinuric effect Supression of renin, AT II, AT1R and vascular endothelial growth factor
Deficiency of Vitamin D and kidney diseases CKD
Action of vitamin D and renoprotection DN - - - - -
Action of vitamin D and renoprotection
Action of vitamin D and renoprotection
Vitamin D: Is it a superhero??
Definition of vitamin D deficiency What do we measure to define vit D deficiency?
Definition of vitamin D deficiency
Definition of vitamin D deficiency Why do we use vit D3 to define vit D deficiency?
Definition of vitamin D deficiency It has long half-life of 2 to 3 weeks Robust circulating concentration Resilience to fluctuations in PTH concentrations
Definition of vitamin D deficiency How can we define vit D deficiency?
Definition of vitamin D deficiency Actual values of 25- OH-D that determine vitamin D insufficiency in children have not been defined. Low levels of vitamin D refers to hormone deficiency which is defined by a serum level <20ng/mL. Vitamin D insufficiency, typically defined by levels ranging from 20-29ng/ ml, has also been regarded as clinically important particularly in children.
Definition of vitamin D deficiency Vitamin D Status Based on Calcidiol Concentrations
Requirement for prevention of vit D deficiency
Requirement for prevention of vit D deficiency Full-body exposure during summer months for 10 to 15 minutes in an adult with lighter pigmentation will can generate 10,000 to 20,000 IU of vitamin D. The amount of sunshine exposure necessary to maintain an adequate 25-OH-D concentration in any given infant at any point in time is not easy to determine. Skin pigmentation, latitude, and amount of skin exposed can influence vitamin D synthesis.
Requirement for prevention of vit D deficiency According to the American Academy of Pediatrics, 2008
Requirement for prevention of vit D deficiency AAP 2008 Infants who are formula-fed exclusively will most likely have an adequate level of vitamin D. AAP recommend 200 to 400 units per day of vitamin D supplementation in very low birth weight infants (<1500 g) and 400 units per day of vitamin D supplementation in infants weighing > 1500 g. Vitamin D should begin within the first few days of life and continue throughout childhood
Requirement for prevention of vit D deficiency The Endocrine Society recommendation for vit D deficiency
Requirement for prevention of vit D deficiency The Endocrine Society recommendation for vit D deficiency 0-1 y 1-18 y M\F The U.S. Endocrine Society recommendation for vit D supplementation is higher than AAP Pregnancy Lactation
Requirement for prevention of vit D deficiency Obese children Anticonvulsant medications Antifungals medications Given at least two to three times more vitamin D for their age group to satisfy their body s vitamin D requirement Children with malabsorption Medications for AIDS Glucocorticoids medication
Requirement for treatment of vit D deficiency
Requirement for treatment of vit D deficiency The Endocrine Society recommendation for vit D deficiency For infants and children aged 0 18 yr who are vitamin D deficient, the Endocrine Society suggests treatment with 2000 IU/d of vitamind2 or vitamind3, or with 50,000 IU of vitamind2 or vitamind3 once weekly for 6wk to achieve a blood level of 25(OH)D above 30 ng/ml followed by maintenance therapy.
Widespread expression of VDR in many organ systems constitutes the biological basis for the pleiotropic and non-skeletal actions of vitamin D. Current clinical and experimental evidences suggest that vitamin D deficiency is a new risk factor for progression of many diseases.
Further clinical trials should more accurately define the precise therapeutic agent, dose, timing, monitoring parameters and indications of vitamin D therapy.
Although 1,25 (OH)2D is the active form of vitamin D, 25(OH)D level is recommended in evaluation of vitamin D state. Parents should be adherent to the recommended dose of vitamin D supplementation.