Lactoferrin for iron-deficiency anemia in children with inflammatory bowel disease: a clinical trial

Abstract

Background Iron-deficiency anemia (IDA) is common in children with inflammatory bowel disease (IBD); however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. We compared the effect of lactoferrin versus oral ferrous sulfate for the treatment of IDA in children with IBD. Methods Ninety-two IBD children with IDA were included but only 80 children completed the study and they were randomized into two groups: ferrous sulfate group (n = 40) who received ferrous sulfate 6 mg/kg/day for 3 months and lactoferrin group (n = 40) who received lactoferrin 100 mg/day for 3 months. Complete blood count, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TS), serum ferritin, interleukin-6 (IL-6), and hepcidin 25 were measured before and after the treatment. Results Hemoglobin (Hb), mean corpuscular volume, serum iron, TS, and serum ferritin significantly increased, while TIBC decreased significantly after the administration of either ferrous sulfate or lactoferrin compared to their baseline data. In addition, lactoferrin significantly increased Hb, serum iron, TS, and serum ferritin compared to ferrous sulfate. Moreover, lactoferrin significantly decreased IL-6 and hepcidin levels. Conclusion Lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA. Clinical trial registration The study was registered at www.pactr.org (PACTR202002763901803). Impact Iron-deficiency anemia (IDA) in children with inflammatory bowel disease (IBD) is treated with oral iron therapy; however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. To the best of our knowledge, our study was the first in pediatrics that compared the effect of lactoferrin versus oral ferrous sulfate as an iron supplement for the treatment of IDA in children with IBD. We found that lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.

The effectiveness of oral bovine lactoferrin compared to iron supplementation in patients with a low hemoglobin profile: A systematic review and meta-analysis of randomized clinical trials

“…This represented 68% of all participants involved in the trials [ 19 , 21 – 23 , 25 , 26 , 28 , 29 , 33 – 35 ]. Seven trials (37%) involved children aged over 2 [ 24 , 27 , 30 – 32 , 36 , 37 ], and one trial targeted cancer patients undergoing chemotherapy [ 20 ]. Additionally, four trials included 334 individuals with chronic health conditions (cancer, cerebral palsy, inflammatory bowel disease, obesity), all of whom had anemia (Hb < 11.5 g/dL) [ 20 , 27 , 32 , 37 ].…”

“…The difference in the mean Hb values among groups were statistically insignificant. LF was equally effective in improving Hb concentration levels as the other two trialled oral iron preparations El Amrousy et al (2022) [ 27 ] Egypt 80 children with inflammatory bowel disease, suffering with IDA, aged between 5–18 years 40 participants 100 mg per day 40 participants Ferrous sulfate 6mg/kg/day Hb concentration levels were significantly increased in both groups. However, the LF group had a significantly higher mean Hb value than the ferrous sulfate group.…”

“…Our meta-analysis demonstrated a statistically significant increase in Hb concentration favoring the oral bLF group over the ferrous sulfate group, with an overall pooled SMD of 0.81 (95% CI: 0.42, 1.21, p < 0.0001, I 2 = 95.8%, P heterogeneity < 0.001). While several studies conducted, mainly on pregnant women [ 19 , 22 , 25 , 26 , 33 , 35 ] and children [ 24 , 27 , 32 , 36 , 37 ], support this result, stating that LF showed a statistically significant increase in Hb concentration levels, compared to those in the iron group, some state that there were no statistically significant differences in the mean Hb increase between both treatments and that both treatments can be considered equally effective in improving Hb concentration levels [ 21 , 29 , 20 ].…”

Adjunctive therapeutic effects of micronutrient supplementation in inflammatory bowel disease

“…Considering that oral iron is poorly tolerated and may increase mucosal inflammation, it is only applicable to IBD patients in the quiescent phase ( 58 ). However, some new oral iron agents, such as lactoferrin and ferric maltol, have also shown good safety and tolerance, and are promising forms of iron supplements that are expected to replace standard oral iron agents ( 47 , 59 ). Concerning intravenous iron, many clinicians worry about its allergic reactions ( 60 ), but more and more studies have confirmed the safety of intravenous iron supplementation (mainly ferric carboxymaltose) ( 61 , 62 ), and the reaction rate of intravenous iron is higher than that of oral iron ( 63 ).…”

Current Knowledge on the Preparation and Benefits of Cruciferous Vegetables as Relates to In Vitro, In Vivo, and Clinical Models of Inflammatory Bowel Disease

“…Inflammatory bowel disease (IBD) is a chronic condition that can last a lifetime and reoccur, causing inflammation, diarrhea, rectal bleeding, and abdominal pain due to severe anatomical damage, immune overactivation, oxidative stress, and microbiome disruption [ 1 , 2 ]. Ulcerative colitis (UC) primarily affects the rectum and colon, leading to inflammation, pain, and diarrhea, including mucous and bloody stool, resulting in anemia and iron deficiency [ 1 , 3 ] as well as a greater risk factor for colon cancer, the second leading cause of cancer death globally [ 4 , 5 ]. Crohn’s disease (CD) involves chronic inflammation of the distal gut, leading to lesions along the entire intestine, immune intolerance of commensals, fever, tiredness, and complications such as stenosis, fistulas, and strictures [ 6 ].…”