Investigators found that iron protein succinylate may provide comparable or superior hematologic outcomes compared with conventional oral iron supplementation while causing fewer adverse gastrointestinal effects in patients with iron deficiency and iron deficiency anemia. Oral iron supplementation remains limited by poor tolerability and impaired absorption in patients with inflammatory conditions.
In a review, the investigators analyzed studies evaluating iron absorption physiology, conventional ferrous and ferric salt limitations, and iron protein succinylate (IPS) benefits. They described IPS as a ferric complex bound to succinylated casein. The investigators summarized pharmacokinetic studies and randomized controlled clinical trials involving approximately 6,450 patients, including those who were pregnant, blood donors, and had conditions such as gastrointestinal diseases, chronic inflammation, cancer, and chronic kidney disease. Outcomes included hemoglobin response, ferritin restoration, iron absorption, gastrointestinal tolerability, and treatment adherence.
In a double-blind, randomized controlled trial included in the review, the investigators found that IPS and controlled-release ferrous sulfate both normalized hemoglobin and ferritin levels within 60 days among patients with iron deficiency or iron deficiency anemia. IPS produced a higher clinical response rate of about 79% vs 68%, respectively, and fewer adverse events (12% vs 26%). Most of the adverse events were mild gastrointestinal symptoms such as heartburn and constipation.
Further, in a randomized controlled of blood donors with depleted iron stores, the investigators discovered that IPS achieved measured iron absorption of about 19% compared with 6% for ferrous sulfate and increased serum iron concentrations. In women with iron deficiency, IPS produced higher increases in hemoglobin and red blood cell indices as well as greater iron absorption compared with ferrous sulfate.
The investigators also summarized evidence suggesting that alternate-day oral iron dosing may improve net absorption and tolerability compared with consecutive-day dosing because of hepcidin-mediated absorption blockade. Studies cited in the review found greater cumulative iron absorption with alternate-day dosing in iron-depleted women receiving ferrous sulfate.
The investigators described several pharmacologic characteristics that may contribute to IPS tolerability. For instance, IPS precipitates in the acidic stomach and becomes soluble in the neutral or alkaline pH of the duodenum and proximal jejunum, potentially reducing gastric mucosal exposure to iron. The formulation also contains succinic acid, which may improve iron absorption up to 20% to 30%, according to the investigators.
The investigators noted that oral iron absorption remains limited in inflammatory conditions because elevated hepcidin levels reduce intestinal iron uptake. They stated that patients with inflammatory bowel disease, chronic kidney disease, heart failure, obesity, or cancer may still require intravenous iron therapy when oral treatment is ineffective or poorly tolerated. The findings in pregnant patients were mixed: one trial found greater hemoglobin improvement with ferri-mannitol-albumin compared with with IPS during early pregnancy, whereas another study reported similar prevention of gestational anemia with both therapies later in pregnancy.
The investigators acknowledged several limitations, including that many of the studies were older and several had relatively small sample sizes
“IPS offers an effective, better-tolerated alternative to conventional oral iron therapy,” wrote lead study author José Antonio García-Erce, of the Blood and Tissue Bank of Navarra in Spain, and colleagues.
The study was funded by ITF Research Pharma. García-Erce reported relationships with CSL-Vifor, Pierre-Fabre, Zambon, Italfarmaco, Sandoz, Terumo, Ferrer, and Inmucor. Co–study author Santiago García-López reported participation in advisory boards with Italfarmaco and Vifor. Senior study author Antonio Martínez-Francés reported no conflicts of interest.
Source: Journal of Clinical Medicine
