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VITAMIN D DEFICIENCY

VITAMIN D DEFICIENCY. Evolving Concepts And Importance In Overall Health Status. Silent epidemic. Vitamin D deficiency is a highly prevalent condition, present in approximately 30% to 50% of the general population. More prevalent in elderly, women of child bearing age and infants.

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VITAMIN D DEFICIENCY

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  1. VITAMIN D DEFICIENCY Evolving Concepts And Importance In Overall Health Status

  2. Silent epidemic. • Vitamin D deficiency is a highly prevalent condition, presentin approximately 30% to 50% of the general population. • More prevalent in elderly, women of child bearing age and infants. • Often unrecognized by clinicians.

  3. Case 1 • An elderly AA obese woman was readmitted to the hospital from a nursing home because of progressive weakness. She had been discharged two weeks earlier following a four-month hospitalization for severe chronic obstructive pulmonary disease. During her previous hospital stay, she required prolonged mechanical ventilation through a tracheostomy tube and total, or central, parenteral nutrition (CPN). She was discharged to the nursing home on low-flow oxygen therapy. On readmission, she had a weak cough and required vigorous tracheal suctioning through her tracheostomy tube. PMH is significant for seizure disorder, HTN, CRF. Depressed levels of serum calcium and phosphate resistant to vigorous oral and intravenous replacement were noted on both hospital admissions.

  4. Question • Can you identify risk factors for Vitamin D deficiency in this patient?

  5. Elderly • Dark skin • No sun exposure • Diet • Obesity • CPN-provides 200 IU/d. • Dilantin • CRF

  6. For our patient, before she was to return to the nursing home, her 25-hydroxyvitamin D level was 7 ng per mL (17 nmol per L; normal: 8 to 38 ng per mL [20 to 95 nmol per L]), and her PTH level was 161 pg per mL (17 pmol per L; normal: 9.5 to 49.4 pg per mL [1.0 to 5.2 pmol per L]). Vitamin D and calcium supplementation was to begin in the nursing home.

  7. Risk Factors • Individuals older than 65 years • Nursing home residents • Individuals with nonvertebral or hip fractures • Individuals with kidney disease • Individuals with low bone mass or osteoporosis • Individuals with a history of falls

  8. Causes • Inadequate sun exposure • Sunscreen use SPF>=8 • Pigmented skin • Aging (older than 65 years) • Winter season • Northern latitudes above 40° • Decreased absorption • Bowel bypass surgery • Crohn’s disease • Celiac disease • Fat and cholesterol absorption inhibitors

  9. Other Causes • Breastfeeding • Liver failure • Chronic renal disease • Medications; Steroids decrease half life of vitamin D. Dilantin, Phenobarbital, and Rifampin can induce hepatic p450 enzymes to accelerate the catabolism of vitamin D.

  10. Metabolism Of Vitamin D

  11. Metabolism • Source: Skin and diet • Stores: 25 OH Vitamin D3 (calcidiol) • Active form: 1,25(OH)2 Vitamin D (calcitriol) • MOA: Steroid hormone. Binds to VDR in nucleus to upregulate gene expression in target cells. • Functions: • Calcium absorption in the intestines and is required for the efficient utilization of dietary calcium.

  12. Metabolism • Involved in cellular growth, differentiation and apoptosis • Simulates insulin secretion • Modulates the immune system. • Reduces inflammation • Muscle development • Telomere protective

  13. Associated Clinical Conditions • Muscle Weakness and Falls • Proximal muscle weakness • Chronic muscle aches • Myopathy • Increase in falls • Recent studies suggest that vitamin D supplementation at doses between 700 and 800 IU/d in a vitamin D-deficient elderly population can significantly reduce the incidence of falls.

  14. Bone Density and Fractures • Risk of osteoporosis may be reduced with adequate intake of vitamin D and calcium. • Studies support the concept that vitamin D at doses between 700 and 800 IU/d with calcium supplementation effectively increase hip bone density and reduced fracture risk, whereas lower vitamin D doses may have less effect.

  15. Role in Cancer Prevention • Low intake of vitamin D and calcium has been associated with an increased risk of non-Hodgkin lymphomas, colon, ovarian, breast, prostate, and other cancers. • The anti-cancer activity of vitamin D is thought to result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. These effects may be mediated through vitamin D receptors expressed in cancer cells. • Vitamin D is not currently recommended for reducing cancer risk

  16. Autoimmune Disease • Vitamin D supplementation is associated with a lower risk of autoimmune diseases. • In a Finnish birth cohort study of 10,821 children, supplementation with vitamin D at 2000 IU/d reduced the risk of type 1 diabetes by approximately 78%, whereas children who were at risk for rickets had a 3-fold higher risk for type 1 diabetes. • In a case-control study of 7 million US military personnel, high circulating levels of vitamin D were associated with a lower risk of multiple sclerosis. • Similar associations have also been described for vitamin D levels and rheumatoid arthritis.

  17. Role in Cardiovascular Diseases • Vitamin D deficiencyactivates the renin-angiotensin-aldosterone system and can predisposeto hypertension and left ventricular hypertrophy. • Additionally,vitamin D deficiency causes an increase in parathyroid hormone,which increases insulin resistance secondary to down regulation of insulin receptors and is associated with diabetes,hypertension, inflammation, and increased cardiovascular risk.

  18. Role in Reproductive Health • Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia. • Role in All Cause Mortality • Researchers concluded that having low levels of vitamin D (<17.8 ng/mL) was independently associated with an increase in all-cause mortality in the general population.

  19. Diagnostic Tests • Measurement of 25(OH) vitamin D serum levels best reflects the vitamin D status of an individual. • Normal levels 25 (OH) vitamin D are in the range of 30 to 80 ng/mL (75 to 200 nmol/L). • Concentrations < 12 to 20 ng/mL (30 to 50 nmol/L) are considered deficient. • Levels > 150 ng/mL (374 nmol/L) are considered toxic.

  20. Dietary Reference Intakes: Vitamin DEstablished in 1997

  21. Dietary Sources • Natural sources of vitamin D include: • Fish liver oils, such as cod liver oil, 1 Tbs (15 mL) provides 1,360 IU • Fatty fish species, such as: • Herring, 85 g (3 ounces) provides 1383 IU • Catfish, 85 g (3 oz) provides 425 IU • Salmon, cooked, 100 g (3.5 oz]) provides 360 IU • Mackerel, cooked, 100 g (3.5 oz]), 345 IU • Sardines, canned in oil, drained, 50 g (1.75 oz), 250 IU • Tuna, canned in oil, 85 g (3 oz), 200 IU • Eel, cooked, 100 g (3.5 oz), 200 IU • A whole egg, provides 20 IU • Beef liver, cooked, 100 g (3.5 oz), provides 15 IU

  22. Fortified Sources • Some of the dietary sources: • Fortified milk (100 IU/8 oz) • Cheeses and yogurt • Fortified cereals

  23. Updated Recommendations In Process • Studies suggest that the daily vitamin D intakes should be much higher than 400 IU/d. • Daily intakes in the range of 800 to 1000 IU/d should be strongly considered. • Although there are concerns regarding vitamin D toxicity, side effects at intakes exceeding the current upper limit of 2000 IU/d have not been reported to date. • Assessment of vitamin D status with serum measurements of 25(OH) vitamin D levels for a broader range of patients should be encouraged.

  24. Causes and Management of Vitamin D Deficiency • Lack of adequate sunlight or chronic sunscreen use; Ultraviolet lamp or increased sun exposure. In a Boston study, exposure of hands, face, and arms to sunlight for five to 15 minutes daily between 11 a.m. to 2 p.m. provided adequate vitamin D. • Total (central) parenteral nutrition; 400 to 800 IU of vitamin D orally per day, or 20 to 25 IU of vitamin D per kg intravenously per day.

  25. Causes and Management of Vitamin D Deficiency • Vitamin D-deficient diet; Usually 1,500 to 5,000 IU of vitamin D2 orally per day, or 50,000 IU of vitamin D2 orally per week or 10,000 to 50,000 IU of vitamin D2 intramuscularly per month • Fat malabsorption; 25-hydroxyvitamin D, 20 to 30 mcg per day • Cirrhosis, nephrotic syndrome, renal failure, gastric or small bowel resection, rifampin, chronic corticosteroids, anticonvulsants; 1,25-dihydroxyvitamin D, 0.15 to 0.5 mcg daily.

  26. Key clinical recommendation • Daily vitamin D supplementation of 800 to 1,000 IU is a reasonable dose for adults. Levels of 25-OH vitamin D should be maintained > 32 ng per mL (80 nmol per L) to maximize bone health. • The (AAP) has doubled the recommended intake of vitamin D to 400 IU per day for infants, children, and adolescents. • In patients with severe vitamin D deficiency, 50,000 IU of vitamin D should be given daily for one to three weeks, followed by weekly doses of 50,000 IU.

  27. After repletion of body stores, 800 IU of vitamin D daily or 50,000 IU of vitamin D once or twice monthly is adequate maintenance therapy. • Patients with no sun exposure, malabsorption, or those taking antiepileptic drugs may require larger maintenance doses of vitamin D (i.e., up to 50,000 IU one to three times week. • In critically ill patients, albumin-adjusted calcium levels underestimate true or ionized hypocalcemia. Therefore, measured ionized calcium levels are recommended, particularly in patients who are being treated in an intensive care unit. • If calcium supplementation alone fails to maintain normal serum levels, the patient is vitamin D deficient or resistant and may benefit from a trial of calcitriol (Rocatrol). • Vitamin D toxicity is very uncommon, and there is a wide safety margin at these higher supplement doses.

  28. References • Grant WB. An estimate of premature cancer mortality in the US due to inadequate doses of solar ultraviolet-B radiation. Cancer.2002;94:1867-1875. • 2. Holick MF. Calcium plus vitamin D and the risk of colorectal cancer. N Engl J Med. 2006;354:2287-2288. • 3. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451-459. • 4. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252-261. • 5. Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr. 2007;137:447-452. • 6. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D

  29. prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76:187-192. • 7. Lips P, Chapuy MC, Dawson-Hughes B, Pols HA, Holick MF. An international comparison of serum 25-hydroxyvitamin D measurements.Osteoporos Int. 1999;9:394-397. • 8. Chen TC, Shao A, Heath H III, Holick MF. An update on the vitamin Dcontent of fortified milk from the United States and Canada. N EnglJ Med. 1993;329:1507. • 9. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281

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