The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials

Abstract

Context: Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.

Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.

Data sources: A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.

Data extraction: Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.

Data analysis: Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.

Conclusion: Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.

Prospero registration no: CRD42020196984.

Keywords: anemia; children; ferritin; ferrous bisglycinate; hemoglobin; iron; iron deficiency; pregnancy; systematic review.

Figure 1

PRISMA flow diagram of study selection.

Figure 2

Forest plot of trials (n = 8) comparing the effects of ferrous bisglycinate supplementation and other iron supplements on hemoglobin concentrations in pregnant women (>0 favors ferrous bisglycinate, <0 favors other iron supplements). CI, confidence interval; SD, standard deviation; SMD, standardized mean difference.

Figure 3

Forest plot of trials (n = 8) comparing the effects of ferrous bisglycinate supplementation and other iron supplements on ferritin concentrations in pregnant women (>0 favors ferrous bisglycinate, <0 favors other iron supplements). CI, confidence interval; SD, standard deviation; SMD, standardized mean difference.

Figure 4

Forest plot of trials (n = 7) comparing the effects of ferrous bisglycinate supplementation and other iron supplements on risk of adverse gastrointestinal side events in pregnant women (>1 favors other iron supplements, <1 favors ferrous bisglycinate). CI, confidence interval; IRR, incidence rate ratio.

Figure 5

Forest plot of trials (n = 4) comparing the effects of ferrous bisglycinate supplementation and other iron supplements on hemoglobin concentrations in children (>0 favors ferrous bisglycinate, <0 favors other iron supplements). CI, confidence interval; SD, standard deviation; SMD, standardized mean difference.

Figure 6

Forest plot of trials (n = 3) comparing the effects of ferrous bisglycinate supplementation and other iron supplements on ferritin concentrations in children (>0 favors ferrous bisglycinate, <0 favors other iron supplements). CI, confidence interval; SD, standard deviation; SMD, standardized mean difference.

Figure 7

Traffic-light plots presenting the risk of bias by 5 domains and overall for included studies.