Both ferrous gluconate and ferrous sulfate are commonly used preparations for iron supplementation in clinical practice and daily life. The differences in their iron supplementation efficiency and applicable scenarios stem primarily from variations in chemical structure, physicochemical properties, and human absorption and metabolism mechanisms. From the core evaluation dimensions of iron supplementation efficiency (bioavailability, onset speed, dose correlation), as well as comprehensive considerations of safety and applicability, the two exhibit distinct characteristics. A detailed comparison is conducted from the following aspects:
I. Core Determinant of Iron Supplementation Efficiency: Differences in Bioavailability
The essence of iron supplementation efficiency lies in the proportion of iron that is absorbed by the human body and converted into usable forms (e.g., for hemoglobin synthesis or storage in ferritin), i.e., bioavailability. This is also the most critical difference between the two preparations.
Ferrous Sulfate
As a traditional divalent iron (Fe²⁺) preparation, ferrous sulfate has the advantage of a high iron content (theoretical iron content of approximately 20%) and can be directly absorbed by the small intestinal mucosa without in vivo conversion. Under ideal conditions (e.g., on an empty stomach, without interfering substances), its initial absorption rate is relatively fast. However, it has prominent drawbacks:
Poor stability: It is easily oxidized by oxygen, gastric acid, etc., in the gastrointestinal tract into trivalent iron (Fe³⁺), which is difficult to absorb.
High susceptibility to interference: It readily binds to phytic acid, tannic acid, calcium, catechols, etc., in food to form insoluble precipitates.
As a result, its actual bioavailability is highly affected by external factors, typically only reaching around 10%–15%, with significant individual differences.
Ferrous Gluconate
Likewise a divalent iron preparation, ferrous gluconate features a more stable chelated structure, where iron ions are bound to gluconate groups via coordinate bonds. This structure significantly enhances its anti-interference ability in the gastrointestinal tract:
Resistance to oxidation: It is less likely to be oxidized to Fe³⁺, maintaining the absorbable divalent form for a longer period.
Low interference from food: It has weak binding ability to interfering substances in food, so it is less affected by dietary factors (e.g., tea drinking, consumption of high-calcium foods).
Although its theoretical iron content is lower (approximately 12%, lower than that of ferrous sulfate), its actual bioavailability is higher, usually reaching 15%–20%. Some studies have shown that when taken with a normal diet, its absorption efficiency can even be 1.5–2 times that of ferrous sulfate. Ultimately, it has an advantage in the total amount of "usable iron" converted.
II. Balance Between Onset Speed and Dose Requirement
The onset speed of iron supplementation is typically evaluated by "reticulocyte increase" (reflecting the initiation of bone marrow hematopoietic function) and "hemoglobin recovery." This is directly related to the absorption rate and dose design of the preparation.
Ferrous Sulfate
Due to its relatively fast initial absorption rate, when used in high doses (e.g., 100–150 mg of elemental iron per day), the increase in reticulocytes may be more significant in the short term (usually 1–2 weeks), and the time required for hemoglobin to return to normal levels (approximately 2–3 months) is slightly shorter under ideal conditions. However, this "rapid onset" relies on "high doses" and "administration on an empty stomach." Once taken with meals or at reduced doses, the onset speed slows significantly, and high doses amplify its gastrointestinal irritation.
Ferrous Gluconate
Its initial absorption rate is relatively moderate, but due to stable bioavailability, it can maintain continuous and stable iron absorption even at moderate doses (e.g., 60–100 mg of elemental iron per day) or when taken with meals. Although the increase in reticulocytes and hemoglobin may be 1–2 weeks slower than that of "high-dose ferrous sulfate taken on an empty stomach," the overall recovery cycle (approximately 2.5–3 months) is similar to that of ferrous sulfate, without relying on "high-dose shock therapy." More importantly, since its absorption is less interfered with, patients have higher compliance with regular administration as prescribed. This avoids missed doses caused by ferrous sulfate’s "requirement for empty-stomach administration and high side effects," ultimately achieving the goal of "stable onset."
III. Safety and Applicability: Hidden Factors Affecting Long-Term Iron Supplementation Efficiency
Iron supplementation efficiency depends not only on "absorption amount" but also on "whether patients can adhere to long-term administration." The gastrointestinal tolerability of the preparation is the core determinant of compliance.
Ferrous Sulfate
It has extremely strong gastrointestinal irritation, which is related to the direct stimulation of gastric mucosa by free divalent iron ions and the promotion of gastric acid secretion. Patients often experience adverse reactions such as nausea, vomiting, abdominal pain, diarrhea (or constipation), and a metallic taste in the mouth, with an incidence rate as high as 30%–50%. Many patients reduce the dose or discontinue medication on their own due to intolerance to side effects, resulting in "high nominal dose but insufficient actual intake," which ultimately reduces iron supplementation efficiency. It is particularly unsuitable for populations with gastrointestinal sensitivity (e.g., patients with gastritis, gastric ulcers), the elderly, and children.
Ferrous Gluconate
Its chelated structure reduces the release of free iron ions, significantly lowering gastrointestinal irritation. The incidence of adverse reactions is only about 1/3 that of ferrous sulfate, and the symptoms are mild (mostly mild bloating or constipation), so patients have much better tolerance. This expands its applicable population to include children, pregnant women, lactating women, the elderly, and individuals with weak gastrointestinal function. Patients can take the medication regularly for the full course (iron supplementation typically lasts until ferritin returns to normal, approximately 3–6 months), ensuring continuous iron supplementation. In the long run, the improvement in iron supplementation efficiency brought by this "high compliance" often outweighs the disadvantage of its "slightly lower iron content."
IV. Summary: Scenario-Based Selection Logic
In terms of "pure efficiency" (bioavailability and total usable iron), ferrous gluconate performs better overall due to more stable absorption and lower interference.
In terms of "short-term rapid onset" (at the cost of tolerability), ferrous sulfate has certain advantages under specific conditions (empty stomach, high dose, good gastrointestinal tolerance), but its applicable scenarios are narrow.
Recommendations for Specific Scenarios:
For "rapid correction of severe iron-deficiency anemia" (e.g., hemoglobin < 60 g/L), if the patient has good gastrointestinal function and can strictly adhere to empty-stomach administration, ferrous sulfate can be selected for short-term use to quickly supplement iron reserves with high doses.
For the vast majority of patients with iron-deficiency anemia (especially mild to moderate anemia), those requiring long-term iron supplementation (e.g., chronic blood loss, pregnancy, lactation), individuals with gastrointestinal sensitivity, children, or the elderly, ferrous gluconate is a better choice due to its "stable bioavailability, good tolerability, and high compliance." The long-term iron supplementation efficiency brought by its "stable absorption+low side effects" far surpasses the short-term advantages of ferrous sulfate’s "high dose+high irritation."
