Table 1.
Studies comparing “fermented milk based probiotic preparation” with placebo or “standard therapy + fermented milk based probiotic preparation” with “standard therapy”
| Ref. | Type of trial | Evidence grade1 | Quality rating2 | Subjects | Study design | Study groups/methods | Outcome variable/s | Results and conclusions |
| Positive | ||||||||
| Bekar et al[15], 2011, Turkey | Human | 1+ | + | 82 pts of dyspepsia and H. pylori infection | RCT | Two groups - Control group (n = 36; Triple therapy - lansoprazole, clarithromycin and amoxicillin + placebo) and Treatment group [n = 46; Triple therapy + kefir (fermented milk drink containing probiotics)]; given for 14 d | Eradication of H. pylori; adverse events of eradication therapy (Urease test after 45 d of treatment) | Significantly more patients (78.2% vs 50.0%) in the treatment group achieved eradication in comparison with control group. Side effects were less frequent and less severe in the treatment group |
| Sachdeva et al[14] 2009, India | Metaanalysis | 1+ | ++ | 10 eligible trials; data available for 963 patients | Metaanalysis of human RCTs/CCTs | Trials had to be randomized or quasi-randomized and controlled, using a FMPP in the intervention group treating Helicobacter-infected patients. The only difference between the two groups had to be FMPP | Eradication of H. pylori; adverse events of eradication therapy | The pooled odds ratio for eradication by ITT analysis in the treatment vs control group was 1.91 (1.38-2.67; P < 0.0001) using fixed effect model The pooled risk difference was 0.10 (95%CI: 0.05-0.15; P < 0.0001) by fixed effect model. Fermented milk based probiotic preparations improve H. pylori eradication rates by approximately 5%-15%, whereas the effect on adverse effects is heterogeneous |
| Sýkora et al[16], 2005, Czech Republic and United Kingdom | Human | 1+ | ++ | 86 symptomatic H. pylori positive children | RCT | Two groups - OAC-LC group - Omeprazole, amoxicillin and clarithromycin for 7 d with fermented milk containing L. casei DN-114001 for 14 d (n = 39) vs OAC group - Omeprazole, amoxicillin and clarithromycin for 7 d (n = 47) | Eradication of H. pylori, Endoscopic and Histologic comparison | ITT based eradication rates for the group A were 84.6% and 91.6% by PP analysis. Eradication in the group B was 57.5% in the ITT and 61.3% in the PP group. Eradication success was higher in the group A compared to group B in both ITT (P = 0.0045) and PP analysis (P = 0.0019) |
| Sheu et al[17], 2006, Taiwan | Human | 1+ | + | 138 patients in whom triple therapy failed | RCT | Two groups - yogurt (containing L. acidophilus La5, Lactobacillus bulgaricus, Bifidobacterium lactis Bb12 and Streptococcus thermophilus)-plus-quadruple therapy group for 7 d (n = 69) vs quadruple therapy only group (n = 69) for 7 d | Successful eradication of H. pylori, drug compliance, side effects | The yogurt-plus-quadruple therapy group had a higher H. pylori eradication rate than did the quadruple therapy only group (ITT analysis 85% vs 71.1%, P < 0.05; PP analysis- 90.8% vs 76.6%, P < 0.05). Side effects were more frequent in the quadruple therapy-only group than in the yogurt-plus-quadruple therapy group |
| Miki et al[20], 2007, Japan | Human | 1- | ++ | 69 subjects who were positive for H. pylori infection | RCT | Two groups - Fermented milk (Bifidobacterium bifidum YIT) (BF-1) (n = 34) vs placebo (untreated milk) (n = 35) for 12 wk | Suppressive effect of BF-1 fermented milk on H. pylori urease activity and gastric situation | H. pylori infection was judged by the C-UBT. H. pylori-negativity (below 5%: n = 6 and 4 in the BF-1 and placebo groups, respectively) subjects |
| Sheu et al[18], 2002, Taiwan | Human | 1- | + | 160 H. pylori infected patients | CCT | Two groups - triple plus yogurt (TYG) (containing L. acidophilus La5, Lactobacillus bulgaricus, Bifidobacterium lactis Bb12 and Streptococcus thermophilus) group (n = 80) vs triple only group (TG) (n = 80) for 7 d | Successful eradication of H. pylori, drug compliance, side effects | By ITT analysis, the triple-plus-yogurt group had a higher H. pylori eradication rate than the triple-only group (P < 0.05) and side effects were more commonly found in the TG than in the TYG. Also a significantly higher proportion of patients in the TYG completed the 7-d regimen than in the TG (67.5% vs 43.8%, P < 0.05) |
| Felley et al[21], 2001, Boston | Human | 1- | + | 53 volunteers infected with H. pylori | CCT | Two groups - Acidified milk containing L. johnsonii La1 (LC-1) (n = 25) vs Placebo (pasteurized milk) (n = 27) for 3 wk followed by 500 mg bid clarithromycin received by all subjects during the last 2 wk | Effect of the given treatment on H. pylori density, gastric inflammation and activity | In the LC-1 group, four had higher scores in the antrum, 14 were found to have a decreased H. pylori density reflected by lower scores (P = 0.02) and in the placebo group in antrum scores remain identical in 10 volunteers and decreased in 11 (0.08). The results suggest that H. pylori infection and gastritis can be down-regulated by LC-1 |
| Cats et al[22], 2003, Netherlands | Human | 1- | - | 14 H. pylori positive subjects | CCT | Two groups - Fermented milk (L.casei) for 3 wk (n = 14) vs control group (n = 6) | Effect of L.casei on urease activity in vivo (H. pylori positive subjects) | Urease activity decreased in nine of the 14 (64%) subjects with L. casei supplementation and in two of the six (33%) controls (P = 0.22). A slight, but non-significant, trend towards a suppressive effect of L. casei on H. pylori in vivo may exist |
| Wang et al[19], 2004, Taiwan | Human | 1- | - | 70 volunteers infected with H. pylori | CCT | Two groups - AB yogurt (containing L. acidophilus La5, Lactobacillus bulgaricus, Bifidobacterium lactis Bb12 and Streptococcus thermophilus) (n = 59) vs milk placebo (n = 11) for 6 wk | Effect of yogurt on H. pylori infection in humans | Administration of AB-yogurt decreased the urease activity of H. pylori after 6 wk of therapy (P < 0.0001). Regular intake of yogurt containing Bb12 and La5 effectively suppressed H. pylori infections in humans |
| Park et al[23], 2001, South Korea | Human | NR | - | 40 H. pylori infected volunteers | CCT | Two groups - Fermented milk (Lactobacillus acidophilus, Lactobacilus casei) (n = 21) vs Placebo (n = 19) for 4 wk | Eradication of H. pylori, Comparison of endoscopic findings, Compliance | All patients were compliant and the H. pylori density of antrum tended to decrease in treatment group compared with placebo group (P = 0.072). 3 cases in treatment group were noted for negative conversions of both rapid urease test and C-UBT |
| Kim et al[24], 2007, South Korea | Human | FTNA | FTNA | 262 H. pylori infected patients | CCT | Two groups - triple plus yogurt group for 3 wk (n = 147) vs triple only group (n = 115) for 1 wk | Eradication of H. pylori | In PP analysis, H. pylori eradication rate in the yogurt group, 87.7% was marginally higher than that in control group, 78.4% (P = 0.055). And according to ITT analysis, the eradication rate in the yogurt group, 78.2% was also marginally higher than that of control group, 69.5% (P = 0.062) |
| Negative | ||||||||
| Goldman et al[25], 2006, Argentina | Human | 1+ | ++ | 65 children who tested positive for H. pylori | RCT | Two groups - triple therapy with probiotic food (commercial yogurt containing Bifidobacterium animalis and Lactobacillus casei) (n = 33) vs triple therapy with placebo (milk fluid) (n = 32) | Eradication of H. pylori | We found no significant differences in H. pylori eradication rates at 1 and 3 mo between the treated group (ER 45.5% and 42.4%) and the control group (ER = 37.5% and 40.6%). Study could not demonstrate an adjuvant effect of the studied probiotic food to triple therapy in the eradication of H. pylori infection in children |
| Song et al[26], 2005, South Korea | Human | NA | - | 70 patients with duodenal ulcer | CCT | Two groups - triple-plus-fermented milk (Lactobacilli) (n = 35) vs triple plus placebo (n = 35) | H. pylori eradication rate, Fermented milk group reduces treatment-related adverse reactions | Eradication was successful in 88.6% in the Lactobacilli group and 85.7% in the placebo group (P = 1.00). Lactobacillus containing fermented milk couldn’t exert beneficial effects on H. pylori eradication or treatment-related adverse reactions |
1
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 studies with a low risk of confounding, bias, or chance and a significant risk that the relationship is not causal; 3 Non-analytic studies, e.g., case reports, case series; 4 Expert opinion.
2
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; FMPP: Fermented milk based probiotic preparation; NR: Not reported; FTNA: Full text not available; NS: Not significant; LC-1: L. johnsonii La1.