Secondary Zinc Deficiency and Its Association with Chronic Anemia in Patients with Malnutrition or Prior Bowel Resection
Authors: Hagele Adam , Hanson Zachary D , Fay Andrew , Borecky Michael , Mirshahidi Saied , Akhtari Mojtaba 
Published: December 2024

Background:

Zinc (Zn) is an essential micronutrient in erythropoiesis. Zn deficiency has been shown to be a reversible cause of anemia, but Zn is not stored in large quantities in the body, so it is critical to maintain adequate Zn intake through a healthy, balanced diet. Malnourished patients, and those with prior bariatric or bowel surgery may be at risk for Zn deficiency.

This descriptive retrospective study examined 23 Zn deficient patients who had undergone bowel surgery or bariatric surgery or were malnourished. Patients underwent daily, oral, Zn replacement and hemoglobin (HGB) and plasma Zn concentration (pZc) levels were followed for 1 year. This study was conducted on adult patients seen at an academic, outpatient, hematology center in Southern California.

Objectives:

Primary endpoint: determine if Zn replacement increased hemoglobin concentrations in chronically anemic patients who have had bariatric surgery, prior bowel resection, or are malnourished.

Secondary endpoints: determine the proportion of patients who had anemia resolution, determine the time to Zn deficiency resolution, and describe coexisting micronutrient deficiencies.

Methods:

Included patients had chronic anemia (HGB &lt;12 g/dL for women, HGB &lt;13 g/dL for men for &gt;3 months), age over 18 years, who had a history of bowel resection or bariatric surgery, or diagnosed with protein-calorie malnutrition, and were identified to have Zn deficiency (pZc &lt;65 ug/dL). Protein calorie malnutrition was defined by loss of more than 5% of body weight in 12 months, or decreased oral intake 50% of recommended intake. Zn sulfate 220 (50)mg was prescribed daily. Patients were documented to have coexisting iron deficiency (ferritin &lt;45 ng/mL and transferrin saturation &lt;20%, or &lt;25 in subjects with chronic kidney disease), copper deficiency (serum copper level &lt;85 mcg/dL), B12 deficiency (serum B12 &lt;400 pg/mL with methylmalonic acid &gt;0.4 umol/L), manganese deficiency (serum manganese &lt;0.5 ug/dL), selenium deficiency (serum selenium &lt;110 ug/dL), or folate deficiency (serum folate &lt;3.4ug/dL).

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 for response in all patients.

Results

Twenty-three patients met the inclusion criteria, 13 of which had a history of bowel resection or gastric bypass surgery, 12 patients had protein-calorie malnutrition and 3 patients were noted to have chronic alcohol use disorder.

Prior to replacement, mean HGB was 9.6 g/dL, WBC was 5.8 x103/uL, MCV was 89 fl, PLTS were 200 x103/uL, with pZc of 51.9 ug/dL. Following 1 month of replacement, the mean HGB was 10.19 g/dL (p = 0.26, n = 19) with pZc 64.8 ug/dL (p = 0.014). Mean HGB at 3 months was 11.05 g/dL (p = 0.0052, n = 24) with pZc 72.9 ug/dL (p = 0.0013). Mean HGB at 6 months was 12.0 g/dL (p= 3.8x10-5, n = 18), with pZc 74.5 ug/dL (p = 0.0007). Mean HGB at 12 months was 12.2 g/dL (p = 1.8x10-5 n= 16) with pZc of 70.4 ug/dL (p = 0.0015).

Anemia resolution was found in 11/22 patients (50%). Zn deficiency was resolved in 5/12 (42%) patients at 1 month, 6/11 (55%) patients at 3 months, 8/11 (72%) of patients at 6 months, 6/8 (75%) of patients at 12 months.

Other micronutrient deficiencies included iron deficiency in 5/20 patients, copper deficiency in 5/21 patients, B12 deficiency in 5/12 patients. Manganese deficiency in 1/4 tested patients, selenium deficiency in 2/6 patients. No folate deficiency was identified in 14 tested patients.

Conclusions:

Zn replacement significantly improved HGB levels in patients with Zn deficiency with a history of malnutrition or prior bariatric or bowel surgery. Many patients had coexisting micronutrient deficiencies. Anemia resolved in 50% of patients and Zn deficiency resolved in 75% of patients within 12 months. HGB showed a statistically significant increase in HGB levels at 3, 6, and 12 months, where pZc rose significantly at 1, 3, 6, and 12 months. Further prospective studies are warranted to determine the mechanism and risk factors for development of Zn deficiency, identify the specific relationship between Zn and erythropoiesis, as well as clinical studies determining Zn replacement dosing, monitoring, and toxicity.