Benefits
Illness episodes and sick days in young school-age children
In a 3-month placebo-controlled pilot trial in 135 children aged 3 to 7 who had at least three ear, nose and throat, respiratory or digestive illnesses the winter before, a daily sachet of the three strains with fructooligosaccharides lowered the share with any illness episode, the main outcome (51.6% vs 68.5%, a borderline result), and with a sick day off school (25.8% vs 42.5%). It is one small trial.
Gut secretory IgA levels in formula-fed infants
In 132 healthy formula-fed infants aged 3.5 to 6 months, a daily sachet of the three strains in formula for 4 weeks kept stool secretory IgA steady while it fell on placebo. Saliva IgA did not differ, and gut bacteria composition, part of the registered main outcome, did not differ either. Secretory IgA is a marker, not a measure of fewer illnesses.
Growth and digestive tolerance in healthy infants
In the 4-week trial in 132 formula-fed infants, growth did not differ from placebo and all adverse events were mild and judged unrelated to the product; infants on the strains had more stools a day in the last week. In a separate 221-infant trial, each strain given alone for 8 weeks matched placebo for growth and adverse events.
Stool outcomes in open-label add-on studies of Chinese children
A review written by the maker's employees pooled 12 Chinese studies in which children with diarrhea got the formula alongside standard care and reported fewer unresolved cases (risk ratio 0.31). None used a placebo, blinding was unclear in all of them, and the review found signs of publication bias, so these results are weak support.
Healthy days in stressed students: B. bifidum R0071 alone
This was a single-strain trial, not the three-strain formula. In 581 students during exam stress, B. bifidum R0071 for 6 weeks gave a larger share of days free of cold or flu symptoms than placebo, while B. infantis R0033 alone and L. helveticus R0052 alone did not differ from placebo. A maker employee was a coauthor.
Mechanism of action
Cytokine signals in rats (animal work)
In two rat infection models, the three strains with short-chain fructooligosaccharides lowered blood levels of the inflammatory cytokines IL-1α, IL-1β, IL-6 and TNF-α. For most cytokines the blend averaged the effects of the single strains. These are animal results and do not show a benefit in children.
Infant gut bacteria and stool immune markers (single strains)
In healthy infants given one strain each for 8 weeks, gut bacteria stayed closer to their starting profile than on placebo, the IL-10 to IL-12 ratio rose with R0033, and the TNF-α to IL-10 ratio rose with R0052. These stool markers came from single strains, not the three-strain blend, and were not tied to a health outcome.
A blend dominated by R0052 by count
In the infant trial sachet, L. helveticus R0052 supplied 9.6 billion CFU and each bifidobacterium about 0.14 billion CFU, and the commercial formula adds a prebiotic fiber. Trials tested the blend, so results cannot be credited to one strain, and results for Lacidofil or Cerebiome, which share R0052, do not carry over.
Clinical trials
Randomized, double-blind, placebo-controlled multicenter pilot trial; daily synbiotic of L. helveticus R0052, B. infantis R0033 and B. bifidum R0071 with fructooligosaccharides (one sachet a day per the maker's review) during a winter; the abstract does not name the funder or maker, though PubMed indexes it as having non-government research support (Cazzola et al. 2010, Ther Adv Respir Dis)
135 otherwise healthy children aged 3 to 7 (mean age 4.1) in France who had at least three ear, nose and throat, respiratory or digestive illness episodes the previous winter; 62 synbiotic, 73 placebo.
The main outcome favored the synbiotic: 51.6% had at least one illness episode versus 68.5% on placebo (relative risk reduction 25%, 95% CI 0.6% to 44.3%, p = 0.045). At least one sick day off school, a parent-diary outcome that was not the main outcome, was recorded in 25.8% versus 42.5% (p = 0.043). No treatment-related side effects were found. The probiotic was not tested without the prebiotic.
Randomized, double-blind, placebo-controlled trial (NCT02317406, sponsored by Biostime); one sachet a day in formula holding 9.6 billion CFU of R0052 and about 0.14 billion CFU each of R0033 and R0071 per the protocol, products supplied by Lallemand; one author works for Lallemand and three for Biostime (Xiao et al. 2019, Benef Microbes)
132 healthy formula-fed infants aged 3.5 to 6 months in China (66 probiotic, 66 placebo).
Gut microbiota composition, part of the registered main outcome, did not differ between groups; the registered stool L. helveticus count is not reported in the abstract. Stool secretory IgA held steady on the probiotic and fell on placebo (p = 0.0044); saliva IgA did not differ (p = 0.28). Stools per day were higher on the probiotic in the last week in the per-protocol group. Growth did not differ, and no serious adverse event was reported.
Open-label before-and-after study without a control group, indexed as observational; a synbiotic of 5 billion CFU of Rosell-52 (named L. acidophilus), Rosell-33 and Rosell-71 for up to 9 months (Stojković et al. 2016, Srp Arh Celok Lek)
Children younger than five who had been hospitalized, grouped by recurrent respiratory illness, wheezing or both (78 children per the maker's review).
Respiratory illness became less frequent than before supplementation and serum total IgA rose over the first 3 months, with total IgE lower after 9 months. Without a placebo or control group, these changes cannot be separated from children growing older or from the season.