Glycoprotein Matrix-Bound Iron Improves Absorption Compared to Ferrous Bisglycinate Chelate and Ferrous Fumarate: A Randomized Crossover Trial

Introduction The biotransformation of minerals through glycosylation by microorganisms, such as yeast or probiotics, can produce nutrients bound to a food matrix, potentially enhancing their bioavailability. This study aimed to compare the absorption kinetics of iron bound to a glycoprotein matrix (GPM) with those of ferrous bisglycinate chelate (FBC) and ferrous fumarate (FF). Methods In a double-blind, crossover design, 17 participants ingested 11 mg of iron in one of three forms: GPM (Pharmachem Innovation, Kearny, NJ, USA), FBC (Ferrochel^®, Balchem Corp., Montvale, NJ, USA), or FF (FerroPharma Chemicals Ltd, Hungary). Blood samples were collected at baseline and 30-, 60-, 90-, 120-, 180-, 240-, 300-, 360-, 420-, and 480-minutes post-ingestion. Water intake was standardized throughout the protocol, and an iron-free snack was provided at four hours post-ingestion. Pharmacokinetic analysis was performed, with key outcome variables including the incremental area under the concentration vs. time curve (iAUC), maximum concentration (Cmax), and time to maximum concentration (Tmax). The a priori significance level was set at p < 0.05. Results Linear mixed-effects models indicated statistically significant effects of the GPM condition for both raw iron concentrations and changes from baseline (p = 0.03). On average, participants had iron concentrations that were 27.1 mcg/dL (95% CI: 2.8 to 51.4) higher after consuming GPM iron compared to the FF reference condition. Changes in iron concentrations from the baseline were 16.6 mcg/dL (95% CI: 1.5 to 31.7) higher after GPM consumption compared to FF. In contrast, iron concentrations and changes in iron levels after FBC consumption did not significantly differ from those observed with FF. Significant effects of time were also observed in both linear mixed-effects models. When expressed as percentage changes from baseline, iron concentrations in the GPM condition were 9.4% to 35.0% higher than FF and 5.9% to 32.6% higher than FBC. Pharmacokinetic analysis revealed a significant effect of condition on the iAUC (p = 0.047), but no significant effects for Cmax (p = 0.15) or Tmax (p = 0.81). Post hoc tests for the iAUC indicated a trend (p = 0.07) for a difference between the GPM and FBC conditions, but no significant differences between GPM and FF (p = 0.17) or FBC and FF (p = 0.75). Conclusion These findings suggest that iron bound to a glycoprotein matrix can improve absorption kinetics without any associated side effects. This data could have important implications for addressing iron deficiency or absorption disorders in a variety of populations.