Effect of Lactoferrin Supplementation on Serum Iron level and ‎Haematological Parameters after Sleeve Gastrectomy

INTRODUCTION

Due to its necessity for healthy erythropoiesis, oxidative metabolism, and cellular immunological responses, iron is a crucial micronutrient [1]. The erythrocytes in the human body contain roughly 2.0–2.5 g of haemoglobin and 3–4 g of iron, which is also present in iron-containing enzymes, ferritin in hepatocytes, and macrophages (about 0.5 g). Only 10%, or around 1-2 mg, of the iron in an equilibrated diet, which is a modest source of iron, is absorbed each day, making up a little portion of the iron's daily intake of roughly 15 mg. An important supply of iron comes from the lysis of senescent erythrocytes by macrophages, which recycles iron at a rate of around 20 mg per day [2].

Iron deficiency (ID) is the most serious nutritional disorder on the planet. Early detection and prompt treatment of iron deficiency and iron deficiency anaemia (IDA) are strongly encouraged. Low levels of total serum iron (TSI), serum ferritin (sFtn), the creation of hypochromic and microcytic RBCs, as well as low levels of RBC production in general, are all described by low haemoglobin readings [3].

Some of the causes that lead to IDA include decreased iron intake or absorption, increased iron requirements during puberty and pregnancy, bariatric surgery, excessive menstrual blood loss, chronic gastrointestinal (GI) blood loss, polyps, or cancer. People who are affected by this condition often report fatigue, dyspnea, pale conjunctiva, headaches, and pica. Children who have low brain iron levels may experience cognitive issues or adults who have restless legs syndrome. Although oral supplementation has been the mainstay of IDA treatment for many years, defining a treatment plan has proven challenging due to a lack of information on the quantity and timing of the most effective dosages. Studies have demonstrated that the treatment of anaemia with newer, safer intravenous (IV) iron formulations is more effective and has a quicker recovery time [4].

Iron deficiency (ID) is a condition that affects people with obesity particularly frequently due to elevated levels of the acute-phase reactant hepcidin and inflammation caused by obesity. In patients who are obese, ID and inflammation are closely related. Hepcidin levels are increased, which leads to decreased iron absorption and is associated with the suppression of duodenal ferroprotein expression. Obese patients who have undergone bariatric surgery frequently experience decreased inflammatory response, lower serum hepcidin levels, and therefore improved iron absorption [5].

Oral ferrous sulphate therapy for hemodialysis patients and pregnant women resulted in substantial increases in serum IL-6 and decreases in total serum iron and ferritin. These results provide compelling evidence that ferrous sulphate-supplemented iron accumulates inside host cells rather than being transferred from cells to the circulation and causing inflammatory disorders. This research has raised significant questions concerning the efficacy and safety of oral ferrous sulphate, prompting the development of novel techniques for the treatment of ID and IDA as well as the prevention of toxicities brought on by an excess of iron [6].

Lactoferrin (formerly known as lactotransferrin) is one of the proteins that may bind and transfer iron since it is a non-haem glycoprotein and a member of the transferrin family [7]. Serum transferrin, which transports iron in the blood, and lactoferrin are structurally and chemically related. Large amounts of it are released in milk, saliva, tears, nasal secretions, and bronchial secretions after being produced by mucosal epithelial cells [8].

Milk from cows and humans both contains lactoferrin. Colostrum, the first milk produced after birth, has a sizable amount of lactoferrin—roughly seven times more than subsequent milk. It does all of these tasks by a variety of mechanisms, some of which include specific receptors, direct contact with the cellular membrane wall, competition for iron ions, and enzymatic activity. Its properties are made possible by its capacity to bind to other molecules, such as DNA, oxalates, carboxylates, lipopolysaccharides, heparin, glycosaminoglycans, and other metallic ions (Al3+, Ga3+, Mn3+, Co3+, Cu2+, and Zn2+), as well as by its ability to retain iron attached in low pH conditions [9].

Supplementing with lactoferrin improves haematological values by lowering blood IL-6 and raising serum hepcidin, which is detectable as prohepcidin, whereas ferrous sulphate elevates IL-6 and fails to enhance haematological parameters or prohepcidin. Lactoferrin is a more effective and secure alternative to ferrous sulphate when treating IDA [10].

Bariatric surgery is the greatest option for weight loss and long-term weight maintenance. It improves quality of life by reducing obesity-related comorbid issues such cardiovascular and cerebrovascular disorders, respiratory illnesses, degenerative joint disease, and even cancer [11]. The bariatric procedures include gastric banding, sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion (BPD), with or without duodenal switch (DS). SG is the most often used surgical weight-loss method among them. A sleeve gastrectomy is a weight-loss procedure that decreases the stomach to around 15% of its original size by surgically removing a sizeable portion of the stomach along the greater curve. The result is a tube- or sleeve-like structure [12]. Following SG, iron shortage is caused by two factors: reduced iron intake, and decreased generation of hydrochloric acid [13].

Preventive iron supplements are routinely advised after bariatric surgery, however the quantity and kind of iron that would most effectively postpone the onset of iron deficiency are not generally agreed upon [14].

This study aimed to evaluate the effect of lactoferrin supplementation for three months on serum iron level and haematological parameters after sleeve gastrectomy operation.

PATIENTS AND METHODS

Study design: It is a prospective interventional study.

Study settings: This study was carried out in bariatric surgery unit and main laboratories in Ain Shams university hospital. This study was done in the period between January-June 2021.

Study patients: Forty patients after sleeve gastrectomy were included in this study; they were divided into two groups as follows: Group 1: 20 cases received ferrous sulphate capsule once daily for 3 consecutive months. Group 2: 20 cases received lactoferrin sachet twice daily for 3 consecutive months with ferrous sulfate capsule once daily.

Inclusion criteria: Patient after Sleeve gastrectomy, both sexes are involved. Hemoglobin level > or equal 10gm/dl and  BMI > or equal 35.

Exclusion criteria: Patients who received iron therapy for conditions not related to sleeve gastrectomy.

Patient assessment: All patients were subjected to the following; thorough history taking, Complete physical examination, Anthropometric measures (weight in kilograms [15] and height in centimeters[16] ),  laboratory investigations and body mass index [17].

-Laboratory investigations including:

-    Complete blood count (CBC): hemoglobin concentration (Hb %), red blood cells (RBCs), white blood cells (WBCs), platelet count.

-    Serum iron.

-    Serum ferritin.

All clinical and laboratory evaluations reported above were done post-operative and were repeated three months after surgery including investigations CBC, serum iron and serum ferritin.

Outcome: to detect changes in haematological parameters (hemoglobin concentration (Hb %), red blood cells (RBCs), white blood cells (WBCs), platelet count), total serum iron and serum ferritin after three months of supplementations.

Statistical Analysis:

The data collected were tabulated and analyzed by SPSS (statistical package for social science) version 20.

RESULTS

In the current study, there is no statistical significance in demographic data (age, sex) and anthropometric measures between two studied groups at the start of the study (table 1). There is no statistical significance inhaematological parameters between studied groups at the start of the study (table 2). There is no statistical significance inserum iron and serum ferritin between studied groups at the start of the study (P= 0.883, 0.787 respectively) (table 3).

The current study showed that after 3 months post-operative supplement there was a significant difference between the two studied groups regarding hemoglobin as hemoglobin increased more in lactoferrin supplement group (P=0.009). There was no significant difference between the two studied groups regarding other heamatological parameters (HCT, RBCs, MCHC, lymphocytes, and platelets). As theses parameters increased by the same magnitude in both studied groups (table 4).

There is no statistical significance inserum iron and serum ferritin between studied groups 3-months postoperative (table 5).

Comparing the baseline results of the same group and the results after 3 months of supplementation, it was found that after three months post-operative supplementation; there is a significant increase in hemoglobin, HCT, RBCs, MCHC, lymphocytes, and platelets. As in each group all these parameters increased during supplementation for 3 months. However, the improvement in hematological parameters was more significant in Lactoferrin group. Meanwhile, there is a significant decrease in serum ferritin after 3-months supplementation in both groups that was more significant on Lactoferrin supplementation group (table 6, 7).

The present study showed that as regard side effects; there was a significant difference between the two studied groups regarding diarrhea only as diarrhea occurred more in ferrous sulfate supplement group (P=0.35) (table 8).

Table (2): Postoperative heamatological parameters between the two studied groups.

Table (3): Postoperative iron panel between the two studied groups

Table (4): 3-months postoperative heamatological parameters between the two studied groups.

Table (5): 3-months postoperative iron panel between the two studied groups.

Table (6): Postoperative and 3-months follow up change in laboratory parameters among Lactoferrin with ferrous sulfate group (n=20).

Table (7): Postoperative and 3-months follow up change in laboratory parameters among ferrous sulfate group (n=20).

Table (8): Side effects distribution between the two studied groups

DISCUSSION