As a commonly used iron fortifier, the biological utilization rate (i.e., the efficiency of iron absorption and utilization by the body) of ferric pyrophosphate is affected by multiple factors, involving the structure of the compound itself, the physiological state of the body, and the dietary environment. The following analysis covers the definition, evaluation methods, key influencing factors, and optimization strategies of biological utilization:
I. Biological Utilization: Definition and Evaluation System
1. Essence of Utilization
Iron in ferric pyrophosphate exists in the trivalent state (Fe³⁺), and its biological utilization rate refers to the proportion of iron released from the compound, absorbed by the intestine, and involved in body iron metabolism (such as hemoglobin and myoglobin synthesis). Compared with ferrous sulfate (divalent iron, Fe²⁺), ferric pyrophosphate has lower water solubility (solubility < 0.1 g/L at 25°C), but its high stability makes it less likely to cause color or flavor changes during food processing, which also gives its utilization rate unique characteristics.
2. Evaluation Methods
Animal Experiments: Determine iron accumulation in blood and liver using models such as rats and mice. For example, iron-deficient rats fed with ferric pyrophosphate-containing feed were tested for hemoglobin elevation after 28 days. Compared with ferrous sulfate, its relative biological availability (RBA) is usually 20%-50% (ferrous sulfate RBA is set as 100%).
Human Studies: Isotope labeling methods (such as ⁵⁷Fe, ⁵⁸Fe) are used. Subjects ingest labeled ferric pyrophosphate, and the absorption rate is calculated by detecting isotope excretion in urine and feces. Clinical data show that the iron absorption rate of ferric pyrophosphate in healthy adults is about 3%-8%, lower than 10%-20% of ferrous sulfate but higher than some insoluble iron salts (such as iron oxide).
II. Core Factors Influencing Biological Utilization
1. Compound Structure and Physicochemical Properties
Chelation of Pyrophosphate: Pyrophosphate (P₂O₇⁴⁻) forms a stable complex with iron ions, which can delay iron release in the stomach and reduce irritation to the gastric mucosa (one of the advantages as a food additive), but it may also reduce the dissolution rate of iron. Studies have shown that when the molar ratio of Fe³⁺ to pyrophosphate in ferric pyrophosphate is 4:3, its dissolution rate in simulated gastric juice (pH 1.2) is only 5%-10%, while that in simulated intestinal juice (pH 7.4) can increase to 30%-40%, indicating that its absorption mainly occurs in the intestine.
Particle Size and Surface Area: The dissolution rate of micron-scale ferric pyrophosphate (particle size 1-10 μm) is higher than that of nanoscale (particle size < 100 nm), because small-size particles are prone to agglomeration, reducing the contact area with digestive juice. For example, after refining ferric pyrophosphate particles from 5 μm to 100 nm, the intestinal iron absorption rate of rats decreased from 4.2% to 2.8%.
2. Physiological State and Iron Demand of the Body
Iron Reserve Level: The utilization rate of iron-deficiency anemia patients is significantly higher than that of individuals with sufficient iron. When the body's ferritin level is < 12 μg/L, the absorption rate of ferric pyrophosphate can increase to 10%-15%, because iron deficiency induces intestinal mucosal cells to express more transferrin receptors, promoting iron uptake.
Age and Gender Differences: The utilization rate of ferric pyrophosphate in infants (especially 6 months to 2 years old) is about 1.5-2 times that in adults, because the intestinal mucosa of infants is underdeveloped and the expression of iron transporter proteins (such as DMT1) is higher. In the second and third trimesters of pregnancy, due to increased fetal iron demand, the utilization rate can also increase by 30%-50%.
3. Synergistic and Antagonistic Factors in Diet
Absorption-Promoting Components:
Vitamin C: It can reduce Fe³⁺ to Fe²⁺ and enhance its water solubility. When ferric pyrophosphate is taken with vitamin C at a mass ratio of 1:5 (iron: vitamin C), the human iron absorption rate can increase by 2-3 times. For example, adding 50 mg of vitamin C per 100 g of iron-fortified rice flour can increase its utilization rate from 5% to 12%.
Heme Iron in Meat and Fish: Although it does not directly affect the absorption of ferric pyrophosphate, it can indirectly promote the dissolution of non-heme iron (such as ferric pyrophosphate) by stimulating gastric acid secretion. Studies have shown that matching 100 g of lean beef in meals can increase its absorption rate by 40%.
Absorption-Inhibiting Components:
Phytic Acid (Present in Grains and Legumes): It can form insoluble complexes with Fe³⁺, reducing utilization. When the molar ratio of phytic acid to iron in the diet is > 10:1, the absorption rate of ferric pyrophosphate can drop to below 2%. For example, when ferric pyrophosphate is added to whole wheat bread as a carrier, if no phytase treatment is performed, the biological utilization rate of iron is 50% lower than that in white bread.
Polyphenols (Such as Tea Polyphenols and Tannins): Common in tea, coffee, and spinach, they can complex with Fe³⁺ and inhibit its absorption. In vitro experiments show that 50 mg of tea polyphenols can reduce the dissolution rate of ferric pyrophosphate in simulated intestinal juice by 35%.
III. Strategies to Improve Biological Utilization
1. Structural Modification and Formulation Optimization
Compound with Organic Acids: Compound ferric pyrophosphate with organic acids such as citric acid and succinic acid to form Fe³⁺-organic acid complexes, which can improve water solubility. For example, the dissolution rate of ferric pyrophosphate-citric acid complex (Fe:P:citric acid = 1:1.5:0.8) under pH 7.4 conditions reaches 60%, which is 50% higher than that of pure ferric pyrophosphate.
Microencapsulation Technology: Use gelatin-gum arabic as wall material to wrap ferric pyrophosphate, which slowly releases iron ions in the intestine and reduces inactivation in the stomach. Animal experiments show that the hemoglobin elevation value of rats after microencapsulation is 30% higher than that of the unencapsulated group.
2. Dietary Collocation and Processing Technology Adjustment
Simultaneous Addition of Vitamin C: Add vitamin C (such as orange juice, kiwi juice) to iron-fortified foods, or use fermentation technology to degrade phytic acid (such as the utilization rate of ferric pyrophosphate in fermented noodles is 40% higher than that in unfermented noodles).
Avoid Concurrent Intake with High Polyphenol Beverages: Avoid taking with high polyphenol beverages (such as strong tea and coffee), and it is recommended to eat at an interval of 2-3 hours to reduce absorption inhibition.
IV. Utilization Performance and Challenges in Practical Applications
1. Food Fortification Scenarios
When adding ferric pyrophosphate to low-moisture foods such as salt and flour, its stability advantage is significant, but due to the lack of digestive juice dissolution, the utilization rate may be further reduced. For example, the human absorption rate of ferric pyrophosphate in salt is only 2%-4%, which needs to be compensated by "high addition + vitamin C synergism" (such as adding 30 mg of iron + 150 mg of vitamin C per 100 g of salt).
2. Limitations of Clinical Iron Supplementation
Due to its lower utilization rate than ferrous sulfate, ferric pyrophosphate is less used in the treatment of severe iron-deficiency anemia and is more suitable as a preventive iron fortifier (such as the addition amount in infant formula milk powder is usually 10-20 mg/100 kcal). However, for people with sensitive gastrointestinal tracts, its low irritation is still an important advantage—ferrous sulfate may cause nausea and constipation in 10%-20% of subjects, while the adverse reaction rate of ferric pyrophosphate is < 5%.
The biological utilization rate of ferric pyrophosphate is jointly regulated by three factors: "compound-body-diet", and its essence is the balance between stability and absorption efficiency. Although its low water solubility makes its utilization rate lower than that of divalent iron salts, its high stability and low irritation make it irreplaceable in food fortification. Through structural modification (such as organic acid compound), dietary collocation (such as vitamin C synergism), and precise application for specific populations (such as iron-deficient people and infants), its biological value can be effectively improved, making it play a greater role in public nutrition intervention.
