Vitamin d

lecture of 75 slides

1. Vitamin D Deficiency Myths & Facts and Guidelines Mangement DR. Magdy Shafik Senior Pediatric Consultant Diploma, M.S , Ph.D of Pediatric

2. INTRODUCTION  Vitamin D is an Fat-soluble vitamin .It is present in animals, plants and yeast & has several important functions in the body. Technically it should be considerd as Hormone ( Secosteroid ) because – -It is synthesized by the body(skin ) from sunlight ( UV-B ray, wave band-290-315 nm), -It is transported by blood , activated & then acts on specific receptors in the target tissue.

3. - Feedback regulation of Vit D activation occure by plasma Ca level & by active form of Vit D.

4. D2 = ergocalciferol . Plant based from irradiated fungi ergosterol . Brand names: Drisdol , Calcidol , Deltalin . D3 = cholecalciferol . Animal based , most supplements from irradiated lanolin . Not FDA approved . Most resources suggest equivalent activity .  Most insurance plans cover

5. D2 vs D3 - Summary . D2, if given in high enough doses, prevents infantile rickets and is capable of healing osteomalacia . D2 has 1/3 to 1/9 the potency of D3 . 25-OH-D2 has shorter duration of action, less binding to VDR . D2 has shorter shelf life . “D2 should no longer be regarded as a nutrient appropriate for supplementation or fortification of foods.

6. 1,25(OH)2D = Calcitriol 1 - Most biologically active form of Vitamin D 2 - Increases GI calcium and phosphorus absorption 3 - Increases renal tubular reabsorption of calcium thus reducing the loss of calcium in the urine 4- Induces osteoclast maturation for bone remodeling 5- Promotes calcium in bone and reduction of parathyroid hormon e

7. 1,25(OH)2D – Not Just Kidneys . Circulating 25(OH)D levels are directly related to dietary vitamin D intake plus skin exposure to ultraviolet light. . Circulating 1,25(OH)2D is controlled largely by calcium homeostasis and is not directly related to one's nutritional vitamin D status. . Although the kidney supplies 1,25(OH)2D to the circulation, we are just beginning to understand the importance of the supply of 25(OH)D to various tissues that use 25(OH)D to produce, in a paracrine–intracrine fashion, 1,25(OH)2D for tissue-specific use. . The conversion of 25(OH)D to 1,25(OH)2D in these tissues appears not to be controlled by calcium , but rather to be directly linked to the substrate availability of 25(OH)D

8. Sources of Vitamin D

9. DAILY REQUIRMENT  Children & adults –400IU(10 μ g/day)  Pregnancy and lactation – 400IU(10 μ g/day)  Over 70years- 800IU (20 μ g/day) 1microgram of vitamin D = 40 International Units

10. The metabolic pathway for vitamin D

11. Risk factors for Vitamin D deficiency

12. Sun Exposure Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7- dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3. Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis.

13. • Approximately 5–30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen lead to sufficient vitamin D synthesis. • Minimal Erythrismal Dose. • White skin synthesis more vit D than Black/Brown during short time exposure.

14. Prolonged exposure of the skin to sunlight does not produce toxic amounts of vitamin D3 because of photoconversion of previtamin D3 and vitamin D3 to inactive metabolites. • In addition, sunlight-induces production of melanin, which reduces production of vitamin D3 in the skin.

15. People with dark skin Greater amounts of the pigment melanin in the epidermal layer result in darker skin and reduce the skin's ability to produce vitamin D from sunlight It is not clear that lower levels of 25(OH)D for persons with dark skin have significant health consequences.

16. Risks vs Benefits of Sun Exposure Review article assessing relative risk for cutaneous malignant melanoma (CMM) and UV exposure. Increased sun exposure to the Norwegian population raising 25-OH-D by 25nmol/L (10ng/ml).

17. Clinical features of Vitamin D deficiency

18. Diseases associated with Vitamin D

19. There is a cause of Fear! • VDR is present in the nucleus of many tissues. • In epidermal keratinocytes , activated T cells of the immune system, antigen-presenting cells, macrophages and monocytes , and cytotoxic T cells. • Calcitriol regulates several hundred genes throughout the body or as much as 5 percent of the human genome. The 1α-hydroxylase (CYP27B1) gene h as been reported to be expressed in many extra-renal tissues. How it works – not known

20. The cause of Fear – Extra Renal • Extra-renal 1a-hydroxylation sites that can act as intracrine systems primarily involved in regulation of cell or tissue growth: skin, gastrointestinal tract, or glandular tissue, such as prostate and breast. • Extra-renal CYP27B1 may be up-regulated during inflammation, or down-regulated in cancerous tissue proliferation.

21. • Extra-renal production of calcitriol is found in certain pathological diseases , including granulomatous conditions such as sarcoidosis , lymphoma, and tuberculosis, which can be associated with hypercalcemia .

22. Subjects and methods The studied cases were classified into 2 groups, patients group and control group: A-Patients group : it comprised 100 critically ill neonates who had RDS or neonatal sepsis or pneumonia or bronchopulmonary dysplasia. Both term (≥ 37 weeks gestation) and preterm (<37 weeks gestation) neonates B- Control group : it included 100 healthy neonates of matched age and sex.

23. Conclusion serum 25- OHvitamin D concentrations in the critically ill neonates was significantly lower than those of healthy newborn . there was no correlation between vitamin D status and disease severity except in pneumonia. There was positive correlation between serum 25-OH vitamin D and gestational age, birth weight, length, head circumference in critically ill neonates

24. Recommendation Measuring serum 25-OH vitamin D level in critically ill neonates is advised . Adequate vitamin D intake for mother should be emphasized during pregnancy and lactation . All breastfed infants should receive vitamin D supplementation during the period of breastfeeding

25. Investigations 25-OH Vitamin D levels, U+Es, calcium, phosphate, LFTs (FBC and Ferritin if concomitant deficiencies are suspected)

26. As vitamin D has a much shorter half-lif e than 25(OH)D3 (1–2 days versus 2–3 weeks ), 25(OH)D3 was favoured as the best indicator of vitamin D status. it enters the host, either by cutaneous synthesis or by ingestion in the diet and it is the most abundant and stable vitamin D metabolite in human serum , as determined by its high affinity to vitamin D binding protein and by other members of the albumin superfamily of circulating proteins. Why 25(OH)D3 becoming the parameter of choice for estimating the vitamin D status

27. Conversely, 1,25(OH)2D3 circulates in the serum at concentrations that are about 0.1% of those of the prohormone 25(OH)D3 and its synthesis is tightly regulated by the endocrine system. For these reasons 1,25(OH)2D3 l evels in the serum are not used to evaluate the vitamin D status in humans

28. VITAMIN D STATUS- 25(OH)D LEVEL ( ng / ml)  Normal level of vitamin D - > 30( ng /ml) ( ng /ml)  Vitamin D insufficiency -- 10-20 ng /ml)  Vitamin D deficiency -- < (10 N.B 25-OH-D: 1 ng /ml ≈ 2.5 nmol /L

29. Why 30ng/ml optimal Relationship between serum PTH and 25(OH)D levels demonstrate a plateau in suppression of PTH when the 25(OH)D level reaches approximately 30 ng / mL. This is the rationale for selecting 30 ng / mL as the cut-off value. Vitamin D level < 10 ng /ml will lead to rickets & osteomalasia . This is another cut-off point. Anything below is severe deficiency.

30. Prevalence of Vitamin D Deficiency 1 -The overall prevalence rate of deficiency was 41.6% . 2 - Highest rate seen in blacks (82.1%), followed by Hispanics (69.2%). . 3 - Vitamin D deficiency was significantly more common among those who had no college education, were obese , with a poor health status , hypertension, low high-density lipoprotein cholesterol level, or not consuming milk daily (all P < .001).

31. Indian scene • A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India. We observed a high prevalence of physiologically significant hypovitaminosis D among pregnant women and their newborns

32. Millions Of U.S. Children Low In Vitamin D • • The researchers found that 7.6 million children across the U.S., were vitamin D deficient, while another 50.8 million, were vitamin D insufficient . Low vitamin D levels were especially common in children who were older, female, African- American, Mexican-American, obese, drank milk less than once a week , or spent more than four hours a day watching TV, playing videogames , or using computers .

33. Vitamin D - One outfit for All • Anti aging, • Anti cancer, • Anti diabetes, • Anti infective, • Anti depressant, • Anti hypertensive, • Cardiac protective

34. Guidelines for the Treatment of Vitamin D Deficiency and Insufficiency in childern

35. Management of Insufficiency in childern Vitamin D levels 10-20 ng /L Provide lifestyle advice and prescribe: Invita D3 25,000IU Oral Solution •Dose 0-1 years- 1 ampoule (25,000IU) every 8 weeks • Dose 1-18 years- 1 ampoule (25,000IU) every 6 weeks

36. Treatment of Deficiency in childern Vitamin D levels <10 ng /L .

37. Treatment of deficiency with symptoms Children with rickets, hypocalcaemia or other significant symptoms due to Vitamin D deficiency, and children with blood levels below 25 nmol /L should be prescribed treatment doses of Vitamin D before starting long-term supplements.

38. Treatment Dose Duration Vitamin D dose and frequency Category 4 – 8 weeks 1,000 units - 3,000 units Daily Up to 1 year 4 – 8 weeks 3,000 units - 6,000 units Daily 1 year - 12 years 4 – 8 weeks 6,000 units - 10,000 units Daily 12 - 18 years The same effect may be achieved by multiplying the dose by 7 and giving it weekly . In older children, especially if compliance is a concern, a single dose can be used ( multiply daily dose by 30 ). It is essential to check the child has a sufficient dietary calcium intake, and that a maintenance Vitamin D dose follows the treatment dose

39. Follow-Up : Some recommend a clinical review a month after treatment starts , asking to see all vitamin and drug bottles . A blood test can be repeated then if it is not clear that sufficient vitamin has been taken.

40. Combined “Calcium and Vitamin D” tablets are available but unless the patient has insufficient calcium intake it is often better, and cheaper, to prescribe a pure Vitamin D product

41. After treatment , children who were deficient or insufficient should continue long-term supplements at least until completion of growth, unless lifestyle changes to provide a reliable intake from diet and sun exposure

42. Vitamin D dosing regimens in pregnancy current DH guidance recommends 10mcg ( 400 units ) daily in all pregnant women; supplementation will provide the daily recommended vitamin D Vitamin D use in pregnancy is not associated with an increased risk of congenital malformation bolus injections or oral doses of more than 10,000units per day should be avoided and very high single bolus doses (i.e. 300,000-500,000units) should not be used in pregnancy.

43. Dose for correction of vitamin D deficiency an oral dose of 2000-4000units per day for up to 11 weeks in the 2nd or 3rd trimester because the majority of skeletal growth and development is thought to occur in the 2nd or 3rd trimester.

44. Dose for rapid correction 7,000unit s/day for 6-7 weeks or 10,000units/day for 4-5 weeks The higher doses should only be used with the input of an obstetrician and with monitoring of calcium levels

45. Which Vitamin D preparation should be used? Vitamin D deficiency in pregnancy should be managed with colecalciferol Preparations licensed for use in pregnancy  Thorens 10 000 I.U. /ml oral drops, solution  InVita D3 2,400 IU/ml oral drops, solution Fultium-D3 Preparations : Fultium-D3 Drops Fultium-D3 800 IU Capsules • Fultium-D3 3,200 IU Capsules

46. Products containing vitamin A (such as Cod Liver Oil) should be avoided because this is a known teratogen . Combined calcium and vitamin D products should not routinely be used to correct vitamin D deficiency in pregnancy.

47. Treatment Monitoring serum calcium levels checked a month after starting treatment and then three months later , when steady state vitamin D levels have been achieved Routine monitoring of vitamin D levels is not necessary If calcium levels are raised , then the prescriber should review the prescription for vitamin D or reduce the dose.

48. Guidelines for the Treatment of Vitamin D Deficiency and Insufficiency in adlut

49. Management of Insufficiency in adult Vitamin D levels 2 5-50nmol/L (10-20 ng ) Lifestyle advice and recommend that the patient purchases colecalciferol 1000-2000 iu (25-50mcg) daily or 10,000iu weekly.

50. Treatment of Deficiency in adult Vitamin D levels <25nmol/L (10 ng ) Lifestyle advice and prescribe: ( Invita D3 25,000IU oral solution )- 2 ampoules (50,000IU) every week for 6-8 weeks , then switch t o 1 ampoule every month for 3 months or Fultium D3 800iu for 3 months.

51. After 3 months stop prescribing medication and recommend that the patient purchases a product that will allow them to continue taking a dose of 800iu daily

52. Indication of use of active form of Vit . D 1-Treatment of  hypocalcaemia  –  hypoparathyroidism   2-osteomalacia  (adults),  rickets  (infants, children)   3-renal osteodystrophy ,  4-chronic kidney disease 5-Treatment of  osteoporosis 6-Prevention of  corticosteroid-induced osteoporosis

53. Overdose of Vitamin D Vitamin D toxicity is exceedingly rare below serum concentrations of 375nmol/L . ( 150 ng ) Massive overdose causes hypercalcaemia but there is no agreement on the threshold concentration or amount of Vitamin D that results in toxicity . In adults , prolonged daily intake of Vitamin D up to 10,000 IU or serum concentrations of 25(OH)D of up to 240 nmol /L (96ng) appear to be safe. The European Food Safety Authority recommendations of a safe upper limit of 1,000 units/day for infants up to 1 year of age, 2,000 units/day for children aged 1-10 years and 4,000 units/day for those older than 10

54. Both Vit . D2 and D3 are lipophilic and rapidly removed from circulation by various tissues such as adipose tissue and muscle where they may remain stored for almost 2 month . Their metabolite, 25OH Vit . D as high affinity for its transport protein, vit . D binding protein , which result in long half life of 2-3 weeks . Vit.D intoxication may take weeks to resolve and require a prolonged course of treatment

55. Toxicity . Toxicity appear with level >150ng/ml . Anorexia, nausea, vomiting, weakness , nervousness, pruritis , polyuria , polydipsia , renal impairment, soft tissue calcifications

56. Diagnosis of Vit . D Intoxication

57. Treatment of Vit . D Intoxication 1 -Stop vit . D . T he levels are allowed to decrease with time, an event hat typically occurs over several weeks. 2 -IV hydration with normal saline at 1.5 – 2.5 mainteince to increase GFR& calcium excretion. May add specific diuretics that increase calcium execration such as loop diurtics ( furosimide ). Thaizides , should be avoided because they increase calicum resorption at the distal tubule, there fore can exacerbate hypercalcimia

58. 3-Glucocorticoids and calcitonin can be used if symptomatic hypercalcaemia persist despite hydration and diurtics . Glucocorticoids prevent renal calcium reabsorption and inhibit the production and activity of 1,25(OH)2 Vit . D thus decrease intestinal calcium absorption. 4 - Prednisone of 1-2 mg/kg/ day , given as divided doses every 4 hours up to 2 weeks Steriods can be combined with sc calcitonin , given at a dose of 2-4 I.U/kg every 6-12 hours, because of its a rapid effect on serum calcium

59. Vitamin D PREPERATIONS

60. Vitamin D PREPERATIONS

61. Vitamin D PREPERATIONS devit-3-vitamin-d3-injection-oral -

62. Vitamin D PREPERATIONS

63. Vitamin D PREPERATIONS 1 I.U Vit.D = 0.025 mcg or 1 mcg = 40 i.u

64. Vitamin D PREPERATIONS

65. Vitamin D PREPERATIONS

66. Take Home Massage 1 - Vitamin D is an Fat-soluble vitamin .It is present in animals, plants. And has several important functions in the body. 2- Circulating 25(OH)D levels are directly related to dietary vitamin D intake plus skin exposure to ultraviolet light . 3 - Circulating 1,25(OH)2D is controlled largely by calcium homeostasis and is not directly related to one's nutritional vitamin D status.

67. 4- Approximately 5–30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen lead to sufficient vitamin D synthesis. 5 - 25(OH)D3 is the parameter of choice for estimating the vitamin D status. 6 -Normal level of vitamin D - > 30( ng /ml ), insufficiency -- 10-20, deficiency -- < ( 10 7 - All breastfed infants should receive 400 iu vitamin D up to 1 year

68. 8 -All pregnant and breastfeeding women should take a daily supplement containing 400iu. 9- Indication of use of active form of Vit . D: hypocalcaemia  –  hypoparathyroidism - 2-osteomalacia ,   rickets   - renal osteodystrophy ,  chronic kidney disease