Iron Supplementation: When

Transcription

1 Iron Supplementation: When & When Not? Nancy F. Krebs, MD, MS Division of Nutrition Department t of Pediatrics i University of Colorado School of Medicine Clinical Nutrition Update 2012 Experimental Biology Sponsored by the Medical Nutrition Council

2 Disclosures Nothing to disclose

3 Objectives Clinical scenarios of iron deficiency (ID) Acute inflammation & deficiency Chronic deficiency Review iron homeostasis, how current understanding informs clinical management

4 Case AC Chief Complaint: Progressive weakness & unable to walk

5 Case AC: 16 yr old male w/ Down Syndrome, T1DM & Celiac Disease Past year, progressively worsening gait, initially starting with difficulty walking & choosing to scoot or sit instead of walk; then unable to stand w/o support; lost 15 lb/past 6 mo Continuing to eat well, varied diet Diet not gluten free; stools daily soft w/o diarrhea; no MVI

6 Case 1-AC: PMHx & Exam Diabetes & celiac x years BMI: 15.3 (< 5 th %) Exam: Thin, non-ambulatory, alert/cooperative Skin: + Pallor, hyperpigmentation ti +fine macpap rash over upper extremities & trunk DTR s ~ absent; bradykinesia; (+Trousseau & Chvostek)

7 Labs Calcium 5.7 (Mg & P also low) F.S. Vitamins: A, D, E, PT Zinc 36 CBC: Hb/Hct 7.7/24.9; MCV 72.3, RDW 23.7 Fe studies: Ferritin: 3.9 ( ) TIBC: 266 (wnl) % sat n: 6 ( ) ESR: 87 (CRP wnl)

8 Iron Deficiency + Inflammation: Pros Treat? When? Severely iron deficient absorption IDA contributing ti to functional impairment i (lethargy, weakness) Cons Very high inflammatory marker (ESR) absorption Iron supplements + Vit E deficiency oxidant stress, low antioxidant capacity

9 AC: Hospital course (~ 7 days) IV calcium (slow repletion) High dose f.s. vitamins After initially starting, held iron supplements Rationale: IDA chronic High inflammatory state poor absorption Low Vit E, low anti-oxidant status

10 Iron Homeostasis

11 Fe Homeostasis: 4 major cell types: Enterocytes (absorption) Erythroid precursors (utilization) Reticulo-endothelial macrophages (storage & recycling) Hepatocytes (storage & endocrine regulation)

12 Regulation of Iron Homestasis Hepcidin Small peptide hormone, secreted primarily by hepatocytes Central regulator of iron absorption, plasma iron levels, iron distribution Inhibits flows into plasma from macrophages, enterocytes, hepatocytes Production regulated by iron & erythropoietic activity, inflammation

13 Overview of Iron Homeostasis Fleming, NEJM, 2005

14 Conditions w/ Fe-restricted erythropoiesis Absolute Fe deficiency: Dietary Chronic blood loss Decreased absorption Fe sequestration Anemia of chronic disease Inflammation Infections Autoimmune Iron refractory IDA Patients don t restrict themselves to one category!

15 Inflammation + Iron Deficiency: Competing Signals Iron absorption in children postmalarial or non-malarial anemia Iron supplementation x 30 d Iron rbc incorporation (absorption) at day 1 ( 57 Fe) & day 15 ( 58 Fe) How do inflammatory markers & Fe status markers correlate w/ Fe rbc incorporation? Prentice et al, Blood, 2012

16 Results: Iron Absorption Isotope rbc Inco orporation (%) Iron Fe Absorption-Day 1 ( 57 Fe) Postmalarial Anemia Non-malarial Anemia 20 * * Univariate analysis: *(P<.01) Fe Absorption-Day 15 ( 58 Fe) Combined data (day 1 & 15): Inflammatory markers strongest predictors cf iron status CRP & hepcidin: R 2 39 & 35 (p < 0.001) Ferritin, stfr, Zn-PP: R 2 26, 18, 12 (p < 0.01) Multivariate i t analysis: Hepcidin most consistent predictor of Fe incorporation, both periods Conclusion: with competing signals hepcidin idi powerfully controls use of dietary iron Prentice et al, Blood, 2012

17 Case AC: Response to Fe Supplementation (~ 2-3 mg/kg) 6 wk later: ESR: Hb & MCV: no Ferritin: ~ 2 mo later: Hb: MCV: Conclusion: Fe suppl slow repletion, still ID overall much improved

18 Obesity Pre- & post- bariatric surgery (Absolute deficiency + Sequestration)

19 Obesity Moderate risk for ID & IDA: Low dietary Fe intake Chronic inflammation Rates prior to bariatric surgery: 12-47% (Xanthalos) IDA: < 5-8 % (Ruz, 2009 & 2012) ID & IDA post surgery: 20-49% (A J Med Sci 2006; JAMA 2002)

20 Iron Status: pre/post RYGBP Suppl A Suppl B Supp C P (RM (n=20) (n=20) (n=23) ANOVA) Iron, mg (3.7) Vit C, mg Vit E, mg hscrp(mg/l) 6/2 10/4 6/1 <0.001 Ferritin,(ug/L) 29/29 39/28 35/16 <0.001 Hb 13.7/ / /13 <0.001 Dietary iron: 11 6 mg/day ( meat) Type of supplement: no effect on changes in Fe status Individuals w/ low ferritin: 5 14 Rojas P et al, Obes Surg 2011

21 Iron Absorption 18 mo s/p RYGBP N= 36, 27, 25, 22 Fe intake: mg/d Avg supp: 20 mg/d (0-200mg) Fe absorption w/ test meal(a) & ferrous ascorbate (B) Ferritin: * Ferritin<12: 7.5% 25%* IDA: 1.5% 23.9%* Ruz et al, AJCN, 2009

22 Heme & Non-Heme Fe Absorption: 12 mo s/p Bariatric Surgery Preliminary i data indicates: Impaired heme and non-heme Fe absorption in both gastric sleeve & RYGBP at 12 mo post surgery Despite routine Fe supplementation, % of subjects with low ferritin s in both groups, RYGBP > SG [Ruz et al, 2012, under review]

23 Management of ID & IDA Oral Fe therapy: Tolerance & non-compliance High doses inflammatory markers Hepcidin level to predict response? Limitations of diagnostic markers trial warranted Intravenous Fe therapy Co-existence of absolute deficiency, inflammation, blood loss, etc hepcidin options: (Fe-dextran), Fe sucrose, ferric gluconate

24 Iron Supplementation When & When Not? Iron restricted erythropoiesis - challenge due to potentially competing signals & complexity Hepcidin = principal regulator; if elevated (or likely to be), hold oral Rx If oral supplement w/o effect or contraindicated, consider intravenous Rx [Goodnough,Nemeth, Ganz, Blood 2010]