Efficacy of fermented milk and whey proteins in Helicobacter pylori eradication: A review

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

¹Levels 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.

²Quality 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.