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The Importance of Zinc for Patients with Thalassemia

The Importance of Zinc for Patients with Thalassemia. Ellen B Fung, PhD RD. Cooley’s Anemia Patient & Family Conference June 21, 2014. 1958 Case Series (Iran & Egypt): 40 young adult males Severe anemia, hypogonadism, enlarged livers, severe growth retardation. NOT THALASSEMIA!. Zinc

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The Importance of Zinc for Patients with Thalassemia

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  1. The Importance of Zincfor Patients withThalassemia Ellen B Fung, PhD RD Cooley’s Anemia Patient & Family Conference June 21, 2014

  2. 1958 Case Series (Iran & Egypt):40 young adult malesSevere anemia, hypogonadism, enlarged livers,severe growth retardation NOT THALASSEMIA! Zinc Deficiency 90 mg Zinc/d Improved growth & pubertal development Staff MD 6 ft 21 yo 4’ 11.5” 18 yo 4’ 9” 18 yo 4’ 6” 21 yo 4’ 7” H Sanstead et al Am J Clin Nutr 1967:422-442. A Prasad et al. Am J Medicine 1961;31:532-546.

  3. Zinc Deficiency is Common • Most common childhood nutritional deficiency world wide • Diarrhea & pneumoniarelated deaths <5 years • Zinc supplementation: adjunctive therapy (infectious diseases) & preventative supplement in Developing Countries • Clinical appreciation of zinc deficiency in individual patients is hindered: • non-specific signs of zinc deficiency Poor growth, delayed puberty, night blindness, anorexia, hypogonadism, hair loss,

  4. Zinc Deficiency is Common • Most common childhood nutritional deficiency world wide • Diarrhea & pneumoniarelated deaths <5 years • Zinc supplementation: adjunctive therapy (infectious diseases) & preventative supplement in Developing Countries • Clinical appreciation of zinc deficiency in individual patients is hindered: • non-specific signs of zinc deficiency • lack of sensitive biomarkers Plasma Zinc- effected by hemolysis, inflammation, infection, food intake, time of day, hormones.

  5. Are Patients with Thalassemia Zinc Deficient? • Plasma zinc depressed (<70 ug/dL) in 10-80% of contemporary samples of patients with Thalassemia • Transfused and non-transfused patients • Children & Adults

  6. How else can we tell?If we give ZINC…

  7. Zinc Improves Growth p<0.01 N=32 patients B-Thal Major Turkey 22 – 90 mg/d 1-7 years n=21 n=11 Arcasoy et al Amer J Heme 1987;24:127-136

  8. Zinc Improves Bone Health in Thalassemia25 mg/d for 18 months Longitudinal Change in Spine BMD Z-score WB BMC % Change from Baseline p=0.041 AbsoluteDifference 4.1% 0.3 SD *Data controlled for pubertal development and baseline BMC value Fung EB et al AJCN 2013;98:960-71.

  9. How hungry are you when it’s time to eat? Change in Appetite with Time of Study by Group p=NS p=0.02 Not Hungry   Very Hungry 3mo 6mo 12mo 18mo 3mo 6mo 12mo 18mo Appetite improved more in the Zn Group Fung EB et al AJCN 2013;98:960-71.

  10. Altered Glucose Response Curve in Patients with Thalassemia with Low Zn (n=13) vs. Normal Zn (n=23) Abnormal 2 hr: >200 mg/dL Abnormal Fasting: >100 mg/dL Diabetic Fasting: >126 mg/dL Models controlling for baseline p=0.048 Fung EB et al, unpublished data

  11. Zinc Supplementation & Glucose Response 120 min Glucose Fasting Glucose 98.3 126.9 94.4 135.5 Reduction in 120 minute Glucose after 25 mg Zinc Supplementation (p=0.02) Reduction in Fasting Glucose after 25 mg Zinc Supplementation (p=0.03) Fung EB et al, unpublished data

  12. Why Are Patients with Thalassemia Zinc Deficient? • Poor Dietary Intake

  13. Best Sources of Zinc in Food

  14. Dietary Zinc vs. Circulatory Zinc in Patients with Thalassemia Low PZn 10 of 11 With low PZn Consuming low Dietary Zn Fung EB et al, unpublished data

  15. Why Are Patients with Thalassemia Zinc Deficient? • Poor Dietary Intake • Inadequate Absorption • Inadequate Intestinal reabsorption Intestinal Lumen Inside body Inside body Fe Fe DFP Fe Fe Fe Zn Fe Fe Fe Exjade Fe Fe Fe Fe Zn

  16. Why Are Patients with Thalassemia Zinc Deficient? • Poor Dietary Intake • Inadequate Absorption • Inadequate Intestinal reabsorption Intestinal Lumen Inside body Inside body Fe Fe Fe Fe Fe Zn Fe Fe Zn Fe Fe Fe Fe Fe

  17. Why Are Patients with Thalassemia Zinc Deficient? • Poor Dietary Intake • Inadequate Absorption • Inadequate Intestinal reabsorption • Increased urinary excretion

  18. Diabetics have Elevated Zn Excretion with Chelation Therapy Al-Rafaie et al J Clin Pathol 1994

  19. Elevated Zn Excretion withDeferiprone & Deferoxamine Therapy DeVirgiliis S et al 1988 Children w/ Tx-Thal n=28 no chelation n=30 LI n=29 controls Mumbai, India Before & After 1 month DFO Ferritin <1000 >2500 >2500 Bartakke S et al 2005

  20. Summary Take Home Message Many patients with thalassemia may be at risk for marginal zinc status- - Diabetics - Poor Growth - Chelation Toxicity - Low dietary intake - High LIC Zinc deficiency not always apparent from plasma/serum Zn analysis Traditional theory that Iron Overload Co-morbidities is limiting—broaden our view Daily supplementation with zinc has the potential to improve growth, bone health, and glucose homeostasis

  21. For other nutrition questions… Ellen Fung, PhD RD Email: efung@mail.cho.org

  22. Special Thanks To… Elliott Vichinsky, MD Janet King, PhD Annie Lui Lisa Calvelli Nancy Sweeters, PNP Lisa Lavrisha, PNP Betty Flores, PNP Laurie Schumacher, PhD Dru Haines, PNP Ash Lal, MD Janice Hamer Leah Hagar James Huang, MD Laura Quill, PNP Jonah Todd-Geddes David Kilillea, PhD Janet Kwiatkowski, MD Babette Zemel, PhD Ginny Gildengorin. PHD CTSI Grants UL1 RR024131 (CHRCO) & UL1 RR024134 (CHOP)

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