Vnitr Lek 2026, 72(4):256-260 | DOI: 10.36290/vnl.2026.050
Combined heme and nonheme iron: a detailed perspective on their synergy, biology, and significance based on new in vitro evidence
- Ústav farmakologie, 3. LF UK, Praha
Combining heme and nonheme iron represents a promising strategy capable of overcoming the limitations of conventional nonheme iron supplements. New in vitro evidence demonstrates that such formulations not only enhance iron absorption but also preserve and stabilise intestinal barrier integrity, supporting improved safety and tolerability. They concomitantly activate both major iron transport pathways, DMT1 and HCP1, while promoting intracellular metabolic handling through ferritin and ferroportin. These synergistic mechanisms explain the significantly higher bioavailability observed with combined formulations compared with traditional soluble iron salts. The recent findings suggest that combined heme and nonheme iron may provide an optimal supplementation approach, particularly for individuals with increased iron demands or impaired iron absorption.
Keywords: heme iron, nonheme iron, intestinal absorption, intestinal barrier integrity, metabolism.
Accepted: June 11, 2026; Published: June 24, 2026 Show citation
References
- Kumar A, Sharma E, Marley A, et al. Iron deficiency anaemia: pathophysiology, assessment, practical management. BMJ Open Gastroenterol. 2022 Jan;9(1):e000759. doi: 10.1136/bmjgast-2021-000759.
Go to original source... - Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet. 2021 Jan 16;397(10270):233-248. doi: 10.1016/S0140-6736(20)32594-0.
Go to original source...
Go to PubMed... - Gedfie S, Getawa S, Melku M. Prevalence and Associated Factors of Iron Deficiency and Iron Deficiency Anemia Among Under-5 Children: A Systematic Review and Meta-Analysis. Glob Pediatr Health. 2022 Jul 6;9:2333794X221110860. doi: 10.1177/2333794X221110860.
Go to original source... - Tayal A, Kaur J, Sadeghi P, Maitta RW. Molecular Mechanisms of Iron Metabolism and Overload. Biomedicines. 2025 Aug 25;13(9):2067. doi: 10.3390/biomedicines13092067.
Go to original source... - Laftah AH, Latunde-Dada GO, Fakih S, et al. Haem and folate transport by proton-coupled folate transporter/haem carrier protein 1 (SLC46A1). Br J Nutr. 2009 Apr;101(8):1150-6. doi: 10.1017/S0007114508066762.
Go to original source... - Wallace DF. The Regulation of Iron Absorption and Homeostasis. Clin Biochem Rev. 2016 May;37(2):51-62.
- Dev S, Babitt JL. Overview of iron metabolism in health and disease. Hemodial Int. 2017 Jun;21 Suppl 1(Suppl 1):S6-S20. doi: 10.1111/hdi.12542.
Go to original source...
Go to PubMed... - Ginzburg YZ. Hepcidin-ferroportin axis in health and disease. Vitam Horm. 2019;110:17-45. doi: 10.1016/bs.vh.2019. 01. 002.
Go to original source... - Kalman D, Hewlings S, Madelyn-Adjei A, Ebersole B. Dietary Heme Iron: A Review of Efficacy, Safety and Tolerability. Nutrients. 2025 Jun 27;17(13):2132. doi: 10.3390/nu17132132.
Go to original source... - Parini F, Galla R, Mulè S, et al. Improved Iron Uptake and Metabolism Through Combined Heme and Non-Heme Iron Supplementation: An In Vitro Study. Biomedicines. 2025 Dec 24;14(1):43. doi: 10.3390/biomedicines14010043.
Go to original source...
Go to PubMed... - Krug SM, Schulzke JD, Fromm M. Tight junction, selective permeability, and related diseases. Semin Cell Dev Biol. 2014 Dec;36:166-76. doi: 10.1016/j.semcdb.2014. 09. 002.
Go to original source... - Garcia-Casal MN, Pasricha SR, Martinez RX, et al. Serum or plasma ferritin concentration as an index of iron deficiency and overload. Cochrane Database Syst Rev. 2021 May 24;5(5):CD011817. doi: 10.1002/14651858.CD011817.pub2.
Go to original source...
Go to PubMed...




