Effect of zinc supplementation on hemogram parameters and circulating concentrations of homocysteine, vitamin B12, and folate in zinc-deficient children and adolescents

J Trace Elem Med Biol. 2021 May:65:126724. doi: 10.1016/j.jtemb.2021.126724. Epub 2021 Jan 23.


Background: Zinc deficiency may exacerbate some pathologies and may also explain alterations in circulating concentrations of various molecules. Zinc has previously been reported to affect plasma concentrations of vitamin B12, homocysteine, and folate; however, the current evidence is inconclusive. We aimed to evaluate plasma zinc, hemoglobin, red blood cell count, mean corpuscular volume, ferritin, vitamin B12, folate, and homocysteine concentrations during and after zinc supplementation for treatment of zinc deficiency.

Methods: This prospective, open-label, single-arm study included children who presented to outpatient clinics with symptoms of growth retardation, anorexia or frequent infections, and who were considered deficient based on plasma zinc concentrations (<70 mcg/dl). Zinc supplementation of 15 mg per day was administered to all participants, and fasting blood samples collected 3 months later were analyzed for plasma zinc, vitamin B12, homocysteine, and folate concentrations.

Results: Eighty-three children (27 males and 26 females) admitted to the outpatient clinics with anorexia, growth retardation, and complaints of frequent infections. The mean age of the children was 9.64 ± 5.05 (min-max, 1-15) years, and the mean plasma zinc concentration before zinc supplementation was 61.7 ± 6.3 mcg/dl. Zinc concentrations were significantly elevated after zinc sulfate supplementation for 3 months, at 107.1 ± 18.8 mcg/dl (p < 0.01). Hemoglobin (p < 0.01), mean corpuscular volume (p < 0.01), and ferritin (p = 0.049) levels were significantly increased after zinc supplementation, but no significant difference was found in red blood cell count (p = 0.83). Vitamin B12 and homocysteine concentrations were significantly decreased after zinc treatment (743.5 ± 498.8 vs 373.3 ± 128 mcg/dl p < 0.01; and 11.2 ± 5.3 vs 6.7 ± 3.4 mcg/dl p < 0.01, respectively). However, the change in folate concentrations was not significant (p = 0.05).

Conclusions: Anemia was not detected in patients with zinc deficiency, but ferritin level significantly increased after zinc treatment. Therefore, it can be said that zinc therapy has a positive effect on iron absorption. Elevations in vitamin B12 and homocysteine may be associated with zinc deficiency, and these elevations may in turn influence the prognoses of liver, kidney, cardiorespiratory, and neoplastic conditions. This can be corrected through appropriate zinc supplementation.

Keywords: Children; Ferritin; Folate; Hemogram; Homocysteine; Vitamin B12; Zinc deficiency; Zinc treatment.

MeSH terms

  • Adolescent
  • Child
  • Dietary Supplements
  • Female
  • Folic Acid / blood*
  • Homocysteine / blood*
  • Humans
  • Male
  • Prospective Studies
  • Vitamin B 12 / blood*
  • Zinc / administration & dosage
  • Zinc / blood*
  • Zinc / deficiency


  • Homocysteine
  • Folic Acid
  • Zinc
  • Vitamin B 12