# Improved Iron Uptake and Metabolism Through Combined Heme and Non-Heme Iron Supplementation: An In Vitro Study

## TL;DR

Combining heme and non-heme iron improves iron absorption and intestinal health more effectively than traditional supplements.

## Contribution

A novel combination of heme and non-heme iron formulations is shown to enhance iron absorption and preserve intestinal barrier integrity.

## Key findings

- All three iron formulations increased tight junction protein expression and TEER values, preserving intestinal barrier integrity.
- Nutraceutical product 1 showed the highest iron absorption, linked to increased DMT1 and HCP-1 transporter expression.
- The formulations increased ferritin and ferroportin levels, indicating improved iron storage and regulation.

## Abstract

Iron is essential for numerous physiological processes, including oxygen transport, energy metabolism, and immune function. This study evaluated the efficacy and safety of three iron formulations combining heme and non-heme iron, comparing them with existing market products and the original form of iron. The formulations tested were GlobiFer® Forte, a combination of heme and non-heme iron containing 18 mg of elemental iron (hereinafter referred to as nutraceutical product 1); GlobiFer®, a combination of heme and non-heme iron containing 14 mg of elemental iron (hereinafter referred to as nutraceutical product 2); and a double dose of nutraceutical product 2. Using an in vitro 3D intestinal barrier model, all three formulations significantly increased tight junction protein expression and TEER values, indicating preserved barrier integrity. Iron absorption analysis revealed that all three iron formulations had higher absorption rates than controls. Nutraceutical product 1 showed the highest absorption, associated with increased expression of the iron transporters such as the primary non-heme iron transporter, DMT1, and the leading apical heme transporter, HCP-1. All three new formulations increased ferritin and ferroportin levels, markers of systemic iron storage and regulation. Nutraceutical product 1 was found to be the most effective, based on percentage. Overall, combining heme and non-heme iron improved intestinal absorption and supported iron metabolism, with Nutraceutical Product 1 proving the most promising in terms of efficacy and safety. These results support the development of optimised dual-source iron supplements to improve bioavailability and maintain intestinal barrier integrity, prerequisites for better efficacy and tolerability in clinical use.