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Efficiency of iron absorption along with separate and simultaneous intake of calcium

Authors:Drjzdov VN, Noskova KK, Petrakov AV
Location:The Central Research Institute of gastroenterology, Moscow

Iron is a essential microelement, which actively participates in biochemical processes of metabolism, growth and proliferation of cells (1). Besides iron-containing proteins – hemoglobin and myoglobin, iron can be found in cytochromes – enzymes which maintain the process of energy production. Iron-containing enzymes participate in biosynthesis of deoxyribonucleic acid (DNA), cell division, in the functioning of antioxidant system (peroxidases, cytochrome oxidases, catalases). Iron-containing proteins (ferretin – FR, transferring – TF and others), besides their main function - synthesis of hemoglobin, are also involved in the development of cellular immunity, control of brain activity and other functions of the body. It is often noted that latent iron deficiency, does not lead to anemia, but causes weakness, fatigue, anxiety, lack of concentration, morning headaches, depression, dystrophy, emotional lability, decreased performance, loss of appetite, susceptibility to infection, communication difficulties (decreased fluency), forgetfulness (2).

Elevated physiological requirements for iron, changes of feeding behavior, special characteristics of food and unhealthy habits could lead to deficiency of iron, which could not be corrected by diet. Absorption of iron from food is determined by activity of absorption inhibitors and promoters (3). In the gastrointestinal tract, various dietary components exert a stimulating or inhibitory effects on iron absorption (4). For example: ascorbic acid is a strong stimulator of iron absorption. Foods obtained by natural fermentation (eg, sauerkraut) also accelerate the absorption of iron. Acids present in such products, form complexes with iron, and prevent the formation of iron phytates, which are absorbed poorly. Heat treatment and grinding of vegetable products also reduces formation of iron phytates.

Besides phytates, which are rich in minerals and phosphates, calcium salts also inhibit absorption of iron. Phytates could be found in cereals, vegetables, seeds and nuts. Calcium is found in dairy products. The absorption of calcium could be inhibit by phenol-like substances, which are present in plant foods, tea, coffee, cocoa. Phenolic compounds like tannins in tea could reduce the absorption of iron by 62% compared with water.
Thereby, one way to correct physiological iron deficiency are vitamin-mineral complexes. Such preparations sometimes combine vitamins and various minerals. Most of such compositions include calcium, magnesium, phosphorus, iron, iodine, selenium, zinc, copper and manganese (5). The relationship between this elements during absorption are formed in different ways, some of them are antagonistic for each other (Table 1).

Table 1

Competition of some minerals for absorption in the gut

Mineral substance

Mineral substances "competitors" for the absorption


Iron, copper, magnesium, lead,


Iron, zinc, lead


zinc, calcium, cadmium


Calcium magnesium, lead, phosphates, zinc, cadmium


Zinc, copper, selenium, calcium, iron


Calcium, magnesium, copper, iron, lead

The aim of our study was to determine the absorption of iron in the vitamin-mineral complex ALFAVIT, with separated and simultaneous intake of pills containing iron and calcium.

Materials and methods

The study was conducted on 15 patients with chronic gastritis in the period of remission, with preserved function of the stomach, and no symptoms of malabsorption. The study included 10 men and 5 women, average age of patients was 41,3 ± 6,1 year, all women were in menopause. Key variables of the clinical blood analysis and biochemical investigations are given in Table 2.

Table 2

Main laboratory parameters in patients with chronic gastritis



Average values in the studiedgroup


12,0–14,0 g/l



3,9–4,7 106/mm3



10,7–32,2 umol/l


Latent iron-binding capacity of serum

27,8–53,7 umol/l



35–52 g/l



4,2–6,4 mmol/l



2,7–5,2 mmol/l


As can be seen from Table 2, patients had normal levels f hemoglobin and red blood cells, and the levels of iron and latent iron binding capacity of serum and other biochemical parameters were also in the normal range.

The study of iron absorption was carried out by the following method:
Phase 1 study. In the morning, on an empty stomach, patients received two "white" tablets of vitamin-mineral complex ALFAVIT, containing 36 mg of iron in total. Blood sampling was performed through an intravenous catheter to the vacutainer tubes, in an amount of 5 ml, before the treatment (sample 0) and 1, 2, 3, 4, 6 and 8 hours after the treatment (samples 1-8). Four hours after intake of the pills patients received a standard breakfast (2 pieces of white bread with butter, scrambled eggs (1 egg), non-carbonated drink without caffeine), containing about 2.4 mg of iron.

Phase 2 studies. After 4 days the same patients took two "white" tablets of vitamin-mineral complex ALFAVIT, containing 36 mg of iron in total, and at the same time two "pink" tablets containing 200 mg of calcium, in total. Blood sampling was performed through an intravenous catheter to the vacutainer tubes, in an amount of 5 ml, before the treatment (sample 0) and 1, 2, 3, 4, 6 and 8 hours after the treatment (samples 1-8). Four hours after intake of the pills patients received a standard breakfast (2 pieces of white bread with butter, scrambled eggs (1 egg), non-carbonated drink without caffeine), containing about 2.4 mg of iron.

All blood samples were, after the clot formation, centrifuged at 3000 rpm, serum was evaluated visually for the presence of hemolysis, and in its absence, the tubes containing samples of serum were marked (with name of the patient, number of samples) and frozen at - 400 C for determination of iron in the samples.

After collection of material from all patients in the first and second phases of the study, the levels of serum iron were determined on an automatic biochemical analyzer "Olympus" with the help of commercial kits for the iron determination «Iron», (lot - OSR6186 company "Olympus"), the instrument was calibrated with Care multikalibratora «Serum-protein multicalibrator», Lot - ODR3021 firm Olympus; one set of reagents and one calibration was used for all samples. Statistical analysis of results of the study was performed with the program "Biostatistics".

Measurement error of the method did not exceed 2%. The level of serum iron in 15 patients prior to the first study was 17.4 mmol / l (mean), the level of iron in the zero point in the second phase of the study did not differ significantly from previous measurements and was 16,8 ± 4,2 mmol/l.
After intake of 2 tablets of vitamin-mineral complex ALFAVIT, containing 36 mg of iron, there was an increase in serum iron concentration at 1 hour, reaching a maximum at the second hour, and by the 6 hour the iron content in the blood serum did not significantly differ from its value at the zero point. The mean value of incoming iron was assessed by calculating the value of the area under the curve (AUC), the standard value of ion absorption of iron, per mg was determined as the ratio of AUC to the dose of iron that was given to the patients; half-life and rate of elimination were also calculated. For patients who took two tablets with a total iron content of 36 mg, AUC was 157 ± 32 (mmol / l / h), ionic iron absorption was 4,36 ± 0,8 (mmol / l / h / mg), with half-life period of 6 hours and the constant elimination of 0,12.
For patients with chronic gastritis who took 36 mg of iron together with two tablets containing a total 200 mg of calcium, AUC was 86 ± 11 (mmol / l / h), the ion absorption of iron - 2,39 ± 0,4 (mmol / l / h / mg) and the half-life period and elimination constant was the same (Figure 1). Intake of calcium simultaneously with iron leads to a decrease in iron absorption, which was shown by decrease in AUC (p = 0,045) and ion absorption of iron by 45.2% (p = 0.036), with the same half-life and the elimination constant of iron from serum in first and second stages of the study.

Figure 1. Pharmacokinetics of iron

Thus, the simultaneous intake of iron and calcium in the vitamin-mineral complex leads to a decrease in iron absorption in the gastrointestinal tract, and does not affect its elimination from the blood plasma. Calcium and zinc also have a significant effect on the absorption of iron. If calcium and iron are taken together, the absorption of iron is reduced by 50% (6). This effect was also observed, when iron supplements were taken with foods rich in calcium. Iron absorption is reduced if iron is a part of the vitamin-mineral preparations and also if iron is contained in food. Addition of calcium reduces the absorption of heme iron by 20%, the total absorption of iron from food further decreases by 25% (7). About 12% of iron is absorbed from monopreparations containing 65 mg of iron, and only 3-5% of iron is absorbed from complex preparations containing iron and other macro-and micronutrients (8). It was also noted that iron absorption from cow milk, which is rich in calcium, absorption is only 19,5 ± 17,3%, while absorption from human milk, which is less rich in calcium, is 48 ± 25,5% of contained iron, and addition of calcium salts reduces absorption of iron (9).

To prevent the mutual antagonism of calcium and iron, food and medicines containing them, shall be separated in time. Such interactions could be avoided by sustaining of 4 hour intervals between intake of this minerals. Such interval shall divide also consumption of calcium from dairy products and vegetables, and iron from meat and liver. Drinking milk and cheese for breakfast does not affect the absorption of iron from meat products, taken after 4 hours. Many authors recommend to separate reception of calcium and iron products. This is also true for vitamin-mineral complexes. It is not rational to put in one tablet calcium, iron, zinc and other vitamins and elements (10). The need for separation of vitamins and minerals has led to the creation of vitamin and mineral supplements that contain the standard daily dose of vitamins and minerals in three separate tablets, which must be taken at breakfast and dinner, or at breakfast-lunch-dinner. The most acceptable option is reception of various elements of vitamin-mineral complexes with a gap greater than 4 hours. It is also necessary to consider the influence of drugs on iron absorption, so iron should not be take simultaneously with antacids, calcium and magnesium preparations.


  1. Simultaneous reception of preparations containing iron and calcium, significantly reduces the absorption of iron.
  2. Separate intake of iron and calcium in the vitamin-mineral complex ALFAVIT gives the opportunity to avoid the adverse effects of calcium on iron absorption.
  3. The minimum gap between the intake of iron and calcium, contained in different tablets of vitamin-mineral complex ALFAVIT should be 4 hours. Is also reasanoble to avoid eating within 4 hours after taking iron preparations.


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