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Table 1 Characteristics of included trials

From: 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

RT

Country

Sample

LF intervention group

Comparison group

Main findings

Darwish et al. (2018) [23

Egypt

93 pregnant women, with IDA, > 18 years, gestational age between 14–28 weeks

60 participants LF oral sachets 200 mg per day

33 participants Τotal dose infusion of low molecular weight iron dextran (Iron (III)-hydroxide dextran complex)

The dose for each participant was calculated according to the Ganzoni formula according to weight and iron stores

Both the iron and the LF therapy showed a rise in Hb concentration levels in participants. LF oral sachets can be used as an alternative to total dose infusion iron dextran supplementation

El-Asheer et al. (2021) [24]

Egypt

96 children, with IDA between 2–15 years old

32 participants 100 mg per day

32 participants Ferrous sulfate 6 mg/kg/day elemental iron administered orally once daily

There was a statistically significant difference in the increase of Hb concentration levels favouring LF treatment. Oral bovine LF was a more effective and safer alternative to oral ferrous sulfate. It has a better patient compliance and fewer side effects

El-Hawy, Abd Al-Salam and Bahbah. (2021) [30]

Egypt

120 children, with IDA, between 1–18 years old

30 participants

100 mg per day for children < 3 years old

200 mg per day for children > 3 years old

30 participants Iron bisglycinate chelate (FeBC) taken at a dose of 0.75 mg/kg/d

30 participants Iron polymaltose complex (IPC) (50mg/5 ml) at a dose of 6 mg/kg/d

The administration of LF with iron was more effective for increasing Hb concentration levels than the administration of iron alone

El-Nasr et al. (2021) [34]

Egypt

300 pregnant women, with IDA, second trimester (12 weeks of gestation onwards), with single fetus

150 participants combined intake of 200 mg of LF and 30 mg of iron per day

150 participants Dried ferrous sulfate 150 mg per day

Combined LF with ferrous sulfate was a more effective treatment, with a statistically significant difference, in increasing Hb concentration levels in pregnant women, than iron alone

Kamal, Rezk and Hafez. (2021) [31]

Egypt

150 children, with IDA, > 2 years of age

50 participants 200 mg per day

50 participants

Ferric hydroxide polymaltose 6mg/kg/day 3X per day

There was a significant increase in Hb concentration levels in all three intervention groups. However, there was a significant difference favouring the LF and ferrous gluconate compound group. Therefore, LF with iron may be a more effective, alternative, treatment for increasing Hb concentration levels than the traditionally used iron alone

Macciò et al. (2010) [20]

Italy

148 cancer patients undergoing chemotherapy, ≥ 18 years old, histological diagnosis of a solid tumor at an advanced disease stage (stage III–IV)

75 participants s.c. rHuEPO-β, 30,000 UI once weekly and LF 200 mg/day

73 participants s.c. rHuEPO-β, 30,000 UI once weekly and ferric gluconate (125 mg i.v. weekly)

There was no significant difference in the mean Hb increase between the LF arm and the intravenous iron group. LF and i.v iron exhibited similar efficacy for increasing Hb concentration levels, in cancer patients undergoing chemotherapy

Nappi et al. (2009) [21]

Italy

97 pregnant women, with IDA, gestational age > 12 weeks and < 36 weeks, singleton pregnancy

49 participants 200 mg per day

48 participants Ferrous sulfate 100 mg of iron at the daily oral dose of one tablet of 520 m

Both the LF and the iron groups showed a significant increase in Hb concentration levels. However, there were no statistically significant differences between both treatments. Bovine LF had the same efficacy as ferrous sulfate

Omar et al. (2021) [32]

Egypt

66 children, with Cerebral Palsy and who met the WHO diagnostic criteria of IDA, aged between 1–10 years

34 participants oral bLF (30% iron-saturated) 200 mg per day

32 participants Iron Polymaltose complex at a dose of 6 mg/kg/day of elemental iron in 2 divided doses

Both the LF and the iron groups showed a statistically significant increase in Hb concentration levels. Bovine LF was effective and superior to the effect of iron hydroxide polymaltose complex, with fewer side effects, for children with cerebral palsy, suffering with IDA

Paesano et al. (2006) [22]

Italy

205 pregnant women, suffering from ID and IDA, in different stages of pregnancy

107 participants 200 mg per day

98 participants

Ferrous sulfate 520 mg tablet dose containing 156 mg of elemental iron per day

Hb concentration levels showed a significant increase in all groups of women. However, in women receiving bovine LF treatment the mean values of Hb were higher than those in the ferrous sulfate group

Paesano et al. (2010) [19]

Italy

60 pregnant women, with mild IDA, third trimester of gestation

30 participants oral bLF (30% iron saturated)

200 mg per day

30 participants

Ferrous sulfate 520 mg tablet dose containing 156 mg of elemental iron per day

Women treated with bovine LF showed a statistically significant increase in Hb concentration levels. Women treated with ferrous sulfate showed an increase in Hb concentration levels, but values did not reach statistical significance

Paesano et al. (2010) [19]

Italy

166 non-pregnant women of childbearing age, aged between 19–45 years old, with mild IDA

90 participants oral bLF (30% iron saturated)

200 mg per day

76 participants Ferrous sulfate 520 mg tablet dose containing 156 mg of elemental iron per day

Women treated with bovine LF showed a statistically significant increase in Hb concentration levels, in contrast to women treated with ferrous sulfate

Rezk et al. (2016) [33]

Egypt

200 pregnant women, with IDA, second trimester of gestation, single fetus

100 participants

250 mg per day

100 participants Dried ferrous sulfate capsules

150 mg per day

The total increase in Hb concentration levels in the LF group was higher than that compared to the ferrous sulfate group. Bovine LF was more effective than ferrous sulfate, with fewer gastrointestinal side effects and better patient compliance to treatment

Hemeda et al. (2018) [35]

Egypt

146 pregnant women, with IDA, gestational age > 14 weeks

73 participants

200 mg per day

73 participants

Ferrous fumarate

350 mg iron (115 mg elemental iron) per day

The increase in Hb concentration levels was statistically significantly higher in the LF group in comparison to the iron fumarate group. Bovine LF was more efficacious than ferrous fumarate in the treatment of patients with a low Hb concentration profile. It is safer and has a better patient compliance to treatment

El-Khawaga and Abdelmaksoud (2019) [36]

Egypt

85 primary school children, with IDA, primary school age, between 6–12 years

43 participants

200 mg per day

42 participants

Elemental iron

6 mg/kg/day

There was a statistically significant increase in Hb concentration levels in the LF group of patients compared to the elemental iron group. LF was a more effective and a safer alternative for treating patients with a low Hb concentration profile than elemental iron

Atia et al. (2021) [37]

Egypt

40 obese children and adolescents, with IDA, aged between 6–18 years

20 participants

100 mg per day

20 participants

Ferric hydroxide polymaltose

6 mg/kg/day

There was significant elevation in the mean value of Hb concentration after therapy with bovine LF compared to the mean value after oral iron therapy. Bovine LF was superior to ferric hydroxide polymaltose for the treatment of Hb concentration levels, in obese children, with less gastrointestinal side effects

Fawzy Mohamed, Soliman Taha and Farrag Ismaeil Farag. (2020) [25]

Egypt

200 pregnant women, with IDA, gestational age 24–32 weeks, singleton pregnancy

100 participants

LF plus folic acid

100 mg per day

100 participants

Dried ferrous sulfate

150 mg per day

Hb concentration levels significantly increased in both the LF and iron groups, but the increase was statistically significantly higher in the LF group. Bovine LF was more efficacious in improving Hb concentration levels and better tolerated, with better patient compliance to treatment

Bayoumy, Ragab and Elghareeb. (2021) [26]

Egypt

140 pregnant women, with IDA, gestational age < 28 weeks, singleton pregnancy

70 participants

200 mg per day

70 participants

Ferrous sulfate

200 mg per day

The increase of Hb concentration levels was significantly higher in the LF group compared to the ferrous sulfate group. Bovine LF was more effective than ferrous sulfate in improving Hb concentration levels and more tolerable

Ali et al. (2015) [29]

Egypt

600 pregnant women, Hb concentration level ≥ 10.5, gestational age 20–32 weeks, singleton pregnancy

200 participants

250 mg per day

200 participants

Ferrous sulfate

150 mg per day

200 participants

Amino acid chelated iron

15 mg per day

Hb concentration levels showed an increase in all groups after treatment. 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. LF was an effective alternative to iron treatment with fewer side effects, in children with inflammatory bowel disease

  1. RT Randomized trial, LF Lactoferrin, bLF Bovine lactoferrin, IDA Iron deficiency anemia, Hb Hemoglobin