Table 5.
Studies comparing bovine lactoferrin with placebo or “standard therapy + bovine lactoferrin” with “standard therapy”
| Ref. | Type of trial | Evidence grade1 | Quality rating2 | Subjects | Study design | Study groups | Outcome variable | Results and conclusion |
| Sachdeva et al[58], 2009, India | Metaanalysis | 1+ | ++ | 5 trials; 682 subjects [bLF group (n = 316); control group (n = 366)] | Metaanalysis of human RCTs/CCTs | Trials had to be randomized or quasi-randomized and controlled, using bLF in the intervention group treating Helicobacter-infected patients. The only difference between the two groups had to be bLF | Eradication of H. pylori; adverse events of eradication therapy | The pooled odds ratio (5-studies) for eradication by intention to treat analysis was 2.22 (95%CI: 1.44-3.44; P = 0.0003) using the fixed effects model (FEM) and 2.24 (95%CI: 1.15-4.35; P = 0.0003) using the random effects model (REM) (Cochran’s Q = 6.83; P = 0.145). The pooled risk difference was 0.11 (95%CI: 0.05 -0.16; P = 0.0001) by FEM (Cochran’s Q = 6.67; P = 0.154) and 0.10 (95%CI: 0.04-0.17; P = 0.0023) by REM. There was no significant difference in incidence of adverse effects |
| Di Mario et al[51], 2003, Italy | Human | 1+ | + | 150 consecutiveH. pylori-positive patients suffering from dyspeptic symptoms, gastritis and peptic ulcer disease | RCT | Three groups – A-triple therapy (rabeprazole,clarithromycin,tinidazole) with lactoferrin for 7 d (n = 51), B-triple therapy for 7 d (n = 52), C- triple therapy for 10 d (n = 47) | Efficacy of standard triple therapy plus bovine lactoferrin in the eradication of H. pylori | Eradication rates (ITT) were A- 92.2%, B-71.2%, C-70.2 %. Results suggest that lactoferrin tested in the present study was effective in curing H. pylori and could be a new agent to assist the antimicrobials in the eradication of the bacterium |
| Di Mario et al[52], 2006, Italy | Human | 1+ | + | 402 consecutiveH. pylori-positive patients suffering from dyspeptic symptoms, gastritis and peptic ulcer disease | RCT | Three groups – A- triple therapy (esomeprazole,clarithromycin,tinidazole) for 7 d (n = 136), B-lactoferrin followed by triple therapy for 7 d (n = 132), C- triple therapy with lactoferrin (n = 134) | Efficacy of bovine lactoferrin in the treatment of H. pylori infection | Eradication rate (ITT)- A- 77%, B- 73%, C = 90%. Incidence of side effects was A- 9.5%, B- 9%, C- 8.2%Results demonstrate that bovine lactoferrin is an effective adjuvant to triple therapy for eradication of H. pylori Infection |
| Okuda et al[53], 2005, Japan | Human | 1- | + | 59 H. pylori infected healthy volunteers or children who were enrolled in a previous epidemiological study | CCT | Two groups- bLF (n = 31), placebo (n = 28) | Efficacy of a single administration of bLF. Improvement of H. pylori infection, adverse effects | Positive response (> 50% decrease in C-UBT values) was observed in 10 of 31 bLF-treated subjects and 1 of 28 control subjects, indicating that the rate of positive response in the bLF group was significantly higher than that in the control group |
| Tursi et al[54], 2007, Italy | Human | 1- | + | 70 consecutive patients with persistent H. pylori infection after failure of a first standard treatment | CCT | Two groups- A-quadruple therapy (ranitidine bismuth citrate plus triple therapy- esomeprazole ,amoxicillin, tinidazole) (n = 35), B- quadruple therapy plus lactoferrin (n = 35) | Efficacy and tolerability of bLF supplementation to this quadruple therapy in re-treating H. pylori infection | Eradication rate- A-88.57%, B-94.28%. Side effects- A-29.41%, B-17.64%. bLF supplementation was found effective in reducing side-effect incidence. It seems capable of achieving a slight (NS statistically) improvement in eradicating H. pylori |
| Zullo et al[55], 2005, Italy | Human | 1+ | ++ | 133 consecutive patients with non-ulcer dyspepsia and H. pylori infection | RCT | Two groups- A- triple therapy for 7 d (n = 68), B- quadruple therapy (triple therapy plus lactoferrin) (n = 65) | Eradication rate of H. pylori infection, side effects and compliance | Eradication rate (ITT) A- 77.9%, B- 76.9%. Side effects- A –10.3%, B- 9.2%. Quadruple therapy with bLF did not significantly increase the H. pylori cure rate of standard 7-d clarithromycin-amoxycillin based triple therapy in non-ulcer dyspepsia patients |
| Zullo et al[56], 2007, Italy | Human | 1+ | + | 144 consecutive dyspeptic patients | RCT | Two groups – A- triple therapy (rabeprazole, levofoxacin, amoxycillin) (n = 72), B- quadruple therapy (rabeprazole, clarithromycin, tinidazole plus bovine lactoferrin) (n = 72) | Eradication rate of H. pylori infection, side effects and compliance | Eradication rate (ITT) A- 68.1%, B-72.2%. H. pylori eradication rate following both quadruple therapy with lactoferrin and a low-dose PPI, triple therapy with levofloxacin is disappointingly low |
| Imoto et al[57], 2004 | Human | FTNA | FTNA | 25 H. pylori positive healthy volunteers | CCT | Two groups- A- bLf mixed with a commercial yogurt (n = 16) B- yogurt (n = 9) | Effect of bLf against H. pylori | The C-UBT values at week 8 were significantly lower than those at week 0 in the bLf group (P < 0.01), whereas no difference was observed in the control group |
Levels of evidence: 1++ High quality meta-analysis, systematic reviews of RCTs, or RCTs with a very low risk of bias; 1+ Well conducted meta-analysis, systematic reviews of RCTs or RCTs with a low risk of bias; 1- Meta-analysis, systematic reviews or RCTs or RCTs with a high risk of bias; 2++ High quality systematic reviews of case-control or cohort studies or High quality case-control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal; 2+ well conducted case control or cohort studoes with a low risk of confounding, bias, or chance and a significant risk that the relationship is not causal; 3 Non-analytic studies, eg case reports, case series; 4 Expert opinion.
Quality rating for individual studies: ++ Applies if all or most criteria from the checklist are fulfilled; where criteria are not fulfilled the conclusions of the study or review are thought very unlikely to alter; + Applies if some of the criteria from the checklist are fulfilled; where criteria are not fulfilled or are not adequately described, the conclusions of the study or review are thought unlikely to alter; - Applies if few or no criteria from the checklist are fulfilled; where criteria are not fulfilled or are not adequately described, the conclusions of the study or review are thought likely or very likely to alter. H. pylori: Helicobacter pylori; RCT: Randomised controlled trial; CCT: Controlled clinical trial; CT: Clinical trial; C-UBT: 13C-urea breath test; FTNA: Full text not available; NS: Not significant.