Ferrous Gluconate, an organic ferrous compound in oral iron supplements, has an absorption mechanism involving multiple steps such as dissociation in the gastrointestinal tract, transport, and intracellular metabolism, which is closely related to the intestinal environment, chemical form of iron, and body regulation. The key steps of the absorption process and regulatory mechanisms are explained as follows:
I. Dissociation and Maintenance of Solubility in the Gastrointestinal Tract
After entering the gastrointestinal tract, ferrous gluconate exists as a complex where gluconate anions are weakly coordinated with ferrous ions (Fe²⁺). This structure gradually dissociates under physiological pH conditions (e.g., the acidic environment of the stomach, pH 1.5-3.0), releasing free Fe²⁺. Compared with inorganic iron supplements (such as ferrous sulfate), the dissociation of ferrous gluconate is more gradual. Additionally, the presence of gluconate anions reduces direct binding between Fe²⁺ and other components in the gastrointestinal tract (e.g., phytic acid, tannic acid), lowering the risk of forming insoluble precipitates and thus maintaining high solubility—this is a key basis for its higher absorption efficiency than some inorganic iron supplements. In the neutral or weakly alkaline environment of the small intestine, incompletely dissociated ferrous gluconate complexes can be captured by intestinal mucosal cells through passive diffusion or carrier-mediated mechanisms, further reducing the oxidation or precipitation of Fe²⁺.
II. Active Transport and Absorption by Intestinal Mucosal Cells
The absorption of Fe²⁺ mainly occurs in the duodenum and upper jejunum, relying on a specific transporter—divalent metal transporter 1 (DMT1)—located on the apical membrane of intestinal mucosal cells (facing the intestinal lumen). This protein has high selectivity for Fe²⁺ and transports it from the intestinal lumen into the cells. The transport process depends on the proton gradient across the cell membrane (maintained by the Na⁺/H⁺ exchanger) and belongs to an active transport mechanism, enabling efficient absorption even at low Fe²⁺ concentrations in the intestinal lumen.
For incompletely dissociated ferrous gluconate complexes, some can be taken up by intestinal mucosal cells through pinocytosis (especially at high doses), but this contributes far less than DMT1-mediated active transport. Once inside the cells, Fe²⁺ is oxidized to Fe³⁺, which either binds to intracellular ferritin for storage or is transported out of the cells through ferroportin 1 (FPN1) on the basolateral membrane, entering the bloodstream and binding to transferrin for utilization by body tissues.
III. Regulatory Role of Body Iron Homeostasis
The absorption efficiency of ferrous gluconate is not fixed but dynamically regulated by the body's iron storage status, primarily through the "hepcidin-FPN1" axis. When iron reserves are sufficient, the liver secretes more hepcidin, which binds to FPN1 on the basolateral membrane of intestinal mucosal cells, leading to its internalization and degradation, thus blocking Fe²⁺ transport from the cells into the blood. Meanwhile, intracellular stored iron is excreted through the "mucosal block" mechanism as intestinal epithelial cells shed, reducing absorption. Conversely, during iron deficiency (e.g., iron deficiency anemia), hepcidin secretion decreases, FPN1 activity increases, promoting Fe²⁺ entry into the blood, and the absorption efficiency of ferrous gluconate can be significantly enhanced.
IV. Mechanisms of Absorption Differences from Other Iron Supplements
Compared with inorganic iron supplements such as ferrous sulfate, the absorption of ferrous gluconate is less interfered by diet. For example, Fe²⁺ in inorganic iron easily forms insoluble salts with phytic acid, oxalic acid, etc., in food, while the complex structure of ferrous gluconate reduces such interactions, allowing more Fe²⁺ to remain in a soluble state for DMT1 transport. In addition, the gluconate anions produced by its dissociation are less irritating to the gastrointestinal mucosa, reducing absorption disorders caused by mucosal damage—this is one reason why it is better tolerated and absorbed more stably in people with sensitive gastrointestinal tracts.
The absorption of ferrous gluconate is a continuous process of "dissociation-transport-regulation": its chemical structure ensures the solubility of Fe²⁺ in the gastrointestinal tract; active transport mediated by DMT1 and FPN1 is the core pathway of absorption; and body iron homeostasis precisely regulates absorption efficiency through hepcidin. These mechanisms collectively determine its advantages in bioavailability and clinical applicability as an oral iron supplement.
