Identifying and Treating Zinc Deficiency Anemia in the Elderly

Background:

Zinc (Zn) is an essential micronutrient used as a catalyst, structural element, and regulatory ion in many metabolic processes including erythropoiesis. Zn is stored in limited quantities, so Zn deficiency is often due to decreased intake and absorption. NHANES found that only 42.5% of patients with advanced age (age >71) had adequate Zn intake, likely due to poor intake, intestinal absorption, poor mastication, and complex social situations.

Chronic anemia has an estimated prevalence of 5.6% within the US. In the elderly, anemia prevalence is 11% for men and 10.2% for women whose age is 65 and older according to NHANES. While iron deficiency is considered the most common nutritional deficiency leading to anemia, other nutritional deficiencies have been implicated in anemia including deficiencies of Vitamin A, B12, B6, C, D, and E, folate, Zn, riboflavin, and copper. While Zn fortification has been studied in developing countries and has been associated with a decrease in the overall prevalence of anemia within the pediatric and maternal populations, there have been no studies on Zn deficiency and its relationship to anemia in adults with advanced age in the USA. Given the clinical significance of anemia in the elderly, it is important to better understand the correlation of Zn deficiency and anemia in this elderly population.

This descriptive, retrospective study examined 59 patients, 70 years of age or older, with chronic anemia and Zn deficiency. All patients were prescribed oral Zn replacement and changes in hemoglobin (HGB) and plasma Zn concentration (pZc) were monitored over 12 months. This study was completed with a panel of patients from an academic outpatient hematology center in Southern California.

Objectives:

Primary endpoint: determine if Zn replacement significantly increases HGB in elderly patients (age over 70) who have Zn deficiency and anemia.

Secondary endpoints: determine the proportion of patients who will have anemia resolution and determine the time to Zn deficiency resolution.

Methods:

Fifty-nine patients over the age of 70, with chronic anemia (HGB <12 g/dL for women, HGB <13 g/dL for men for >3 months) were identified to have Zn deficiency (pZc, <65 ug/dL). The patients were started on Zn Sulfate 220 (50)mg and their blood counts and pZc were monitored over 12 months.

A retrospective analysis was completed for prior medical history, lab data, and HGB was tabulated at the time markers of 1, 3, 6, and 12 months following initiation of Zn replacement. Collected data was analyzed with T-Test, ANOVA, and CHI-squared analyses.

Results

Prior to replacement, average HGB was 10.1 g/dL, WBC was 7.1 x10³/uL, MCV was 91.9 fl, PLTS were 216 x10³/uL, with pZc 52.8 ug/dL. Following 1 month of replacement, the average HGB was 10.32 g/dL (p = 0.55, n = 46) with pZc of 65.3 ug/dL (p = 8.5x10^-6). The 3-month average HGB was 10.6 g/dL (p = 0.101, n = 67) with pZc 70.5 ug/dL (p = 3.6x10^-12). The 6-month average HGB was 11.06 g/dL (p= 0.0051, n = 44), with pZc of 80.3 ug/dL (p = 5.5x10^-8). The 12-month average HGB was 11.01 g/dL (p = 0.018, n= 35) with pZc of 70.8 ug/dL (p = 4.7x10^-12).

Anemia resolution was found in 23 of 59 patients (39%). Zn deficiency was resolved in 8/17 (47%) patients at 1 month, 16/22 (72%) patients at 3 months, 18/24 (75%) patients at 6 months, and 11/16 (69%) patients at 12 months.

Conclusions:

Zn replacement significantly improved HGB levels in elderly patients with Zn deficiency and chronic anemia, with resolution of anemia in 39% of patients. There was statistically significant improvement from baseline HGB at the 6, and 12-month time markers, and statistically significant improvement in pZc. Given the sample size, further study is warranted to determine the timing for follow-up serum Zn levels and when blood counts should be followed.

Given a statistically significant rise in plasma Zn level to normalization at the 1-month time point, it is possible that plasma Zn concentrations will rise prior to HGB rise. Further prospective studies are warranted to determine the specific mechanisms of Zn deficiency in anemia, the causes for decreased Zn intake and poor absorption in the elderly, and clinical studies determining Zn replacement dosing, monitoring, and toxicity.

Hanson:Bristol Myers Squibb: Consultancy. Akhtari:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Honoraria; CTI: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; JazzPharma: Speakers Bureau; Abbvie: Honoraria; Karyopharm: Speakers Bureau; PharmaEssentia: Speakers Bureau; SecuraBio: Speakers Bureau; J&J: Speakers Bureau; Genzyme: Speakers Bureau; Seagen: Speakers Bureau; Ispen: Speakers Bureau; Rigel: Consultancy; Takeda: Speakers Bureau.