Benefits
Immune support in physically active adults
In a 150-day placebo-controlled trial in 465 healthy, physically active adults, 2 billion CFU of Bl-04 a day lowered the risk of an upper respiratory illness episode (hazard ratio 0.73) and delayed the first episode by about 0.7 months. The maker funded the trial, and later rhinovirus challenge trials did not show fewer infections or illnesses.
Nasal immune activity during a rhinovirus challenge
In 152 adults given Bl-04 or placebo for 28 days before a deliberate rhinovirus exposure, Bl-04 raised the nasal immune signal CXCL8 before exposure, blunted its rise afterward, and fewer people shed virus (76% versus 91%). Infection rate and symptom scores did not differ, and a larger repeat trial found no difference in virus shedding.
Illness after a rhinovirus challenge in healthy adults
In a larger maker-funded trial, 334 healthy adults took Bl-04 or placebo for 28 days and were then exposed to a rhinovirus. Illness developed in 56% on Bl-04 and 50% on placebo, a difference that was not significant, and illness length, infection rate, virus levels and symptom scores were similar in both groups.
Immune support with a Bl-04 fermented milk
In a 12-week trial in 136 adults in a haze-affected area of northern China, a daily 250 g yogurt with Bl-04 was followed by fewer colds (24% versus 46%) and shorter, milder respiratory symptoms than a control yogurt. The test yogurt also held fruit jams the control lacked, and dairy company staff co-authored the study.
Antibody response to an oral vaccine (immune marker)
In a 3-week trial in 83 healthy adults comparing seven single strains with placebo at 20 billion CFU a day, the Bl-04 group had a larger rise in vaccine-specific blood IgG after an oral cholera vaccine than controls. Saliva IgA did not differ and overall vaccination was not affected. Each group was small, and this is a lab marker.
Digestive comfort in healthy adults
In a 4-week placebo-controlled trial in 68 healthy adults, 1 billion CFU of Bl-04 alone did not improve digestive symptom scores more than placebo; its gastric function scores improved only within its own group, and the authors called its effects minimal. A five-strain blend that included Bl-04 did not ease bloating or speed transit more than placebo in adults with constipation.
Mechanism of action
Nasal innate immune signals (human marker)
In a rhinovirus challenge trial, people taking Bl-04 had higher nasal levels of the immune signal CXCL8 before virus exposure and a smaller CXCL8 rise after it. This suggests an effect on resting innate immunity in the nose, but the change did not alter symptoms and was not tested again as a main outcome.
Antiviral signaling in immune cells (lab and animal work)
In maker-run lab work, Bl-04 mildly stimulated antiviral responses in human macrophages and dendritic cells but had little effect on rhinovirus growth in cultured cells. In mice exposed to influenza virus, Bl-04 lowered lung virus levels by 48% on day 3. These are not human results.
Genome built for the gut
A genome comparison found genes linked to using dietary carbohydrates, tolerating bile and acid, and interacting with the gut lining. Bl-04 differs from another strain of its subspecies mainly by 47 single-letter DNA changes and part of one CRISPR region, so standard lab methods cannot tell such strains apart and strain names on labels matter.
Passage through the gut during antibiotic use (blend data)
In a trial of a four-strain blend taken during antibiotic treatment, Bl-04 was found in the stool of more people than on placebo at the end of the course and a week later, and dropped back to baseline once intake stopped. Bl-04 was one of four strains given in equal amounts.
Clinical trials
Randomized, double-blind, placebo-controlled three-arm trial at the Australian Institute of Sport and Griffith University; Bl-04 2 billion CFU a day versus L. acidophilus NCFM plus B. lactis Bi-07 versus a sucrose placebo, stirred into a drink, over about 5 winter months (ACTRN12611000130965). The trial registry lists 20 billion CFU for this arm, while the published paper reports 2 billion. Funded by Danisco; one author worked for DuPont/Danisco (West et al. 2014, Clin Nutr)
465 healthy, physically active adults (241 men, 224 women; mean age about 35).
Bl-04 lowered the risk of an upper respiratory illness episode compared with placebo (hazard ratio 0.73, 95% CI 0.55 to 0.95, p=0.022) and delayed the median time to a first episode from 2.5 to 3.2 months. The two-strain blend did not differ significantly from placebo (hazard ratio 0.81). There were too few digestive illness episodes to analyze. Illness was self-reported in daily online logs.
Randomized, placebo-controlled trial (NCT01669603); Bl-04 at a minimum of 2 billion CFU a day in a sucrose sachet for 28 days before nasal exposure to rhinovirus A39 and 5 days after. Funded by Danisco Sweeteners Oy; two authors were employees of the sponsor (Turner et al. 2017, Benef Microbes)
152 seronegative healthy adults challenged (73 Bl-04, 79 placebo); 58 and 57 met criteria for analysis.
Primary outcome: the nasal CXCL8 response to infection was smaller with Bl-04 (p=0.03), and baseline nasal CXCL8 was higher (90 versus 58 pg/mL). Fewer Bl-04 users shed virus (76% versus 91%, p=0.04) and nasal virus titers were lower. Symptom scores, infection rate and lower airway inflammation did not differ.
Randomized, double-blind, placebo-controlled, single-center phase II trial (NCT02679807); Bl-04 at a minimum of 2 billion CFU a day in a sucrose sachet for 28 days, then rhinovirus A39 challenge and 14 days of follow-up. Funded by Danisco Sweeteners Oy (now IFF); several authors worked for IFF (Turner et al. 2022, EClinicalMedicine)
334 healthy volunteers from a US university community randomized (165 Bl-04, 169 placebo); 232 in the per-protocol analysis.
Null primary result: rhinovirus-associated illness occurred in 56% on Bl-04 and 50% on placebo (p=0.34). Illness duration (median 11.0 versus 11.5 days), infection rate (86% versus 80%), the share shedding virus (78% versus 69%), nasal virus titers and daily symptom scores also did not differ. No adverse events were judged definitely or probably related to Bl-04.
Randomized trial (ChiCTR1900027437); 250 g a day of a yogurt with over 2 billion CFU Bl-04 per 100 g plus loquat and snow pear jams, versus a control yogurt without Bl-04 or the jams, for 12 weeks. Products were made by Bright Dairy, and three authors worked for Bright Dairy; no conflict of interest was declared (Zhang et al. 2021, Pharm Biol)
136 adults aged 25 to 55 with frequent past colds living in northern China randomized; 123 analyzed (62 test, 61 control).
The Bl-04 yogurt group had fewer common colds (24.2% versus 45.9%, OR 0.38) and influenza-like illness (OR 0.32), and shorter, milder respiratory symptoms. Blood interferon-gamma and secretory IgA were higher. Because the jams differed between yogurts, the effect cannot be credited to Bl-04 alone.
Double-blind, randomized, controlled trial; one of seven single probiotic strains, including Bl-04, at 20 billion CFU a day, or maltodextrin, for 3 weeks, with an oral cholera vaccine on days 7 and 14. Funding and most author affiliations were not stated in the abstract (Paineau et al. 2008, FEMS Immunol Med Microbiol)
83 healthy adults aged 18 to 62 split across eight groups.
Vaccine-specific serum IgG rose more from day 0 to day 21 with Bl-04 (and with L. acidophilus La-14) than with control (p=0.01). Salivary IgA did not differ, and overall vaccination was not influenced. These are immune markers in small groups, not infection outcomes.
Randomized, parallel-arm, double-blind, placebo-controlled trial (NCT04511221); Bl-04 1 billion CFU a day, Bl-04 plus a bacteriophage product, or maltodextrin placebo for 4 weeks. Funded by Deerland Enzymes, maker of the phage product, which also supplied the strains (Grubb et al. 2020, Nutrients)
68 healthy adults enrolled; 66 completed.
No digestive symptom score differed between groups. Within groups, gastric function scores improved with Bl-04 alone and GI inflammation scores improved with Bl-04 plus phages; the authors judged Bl-04 alone to have minimal effects. Gut microbial diversity did not differ between groups. Adverse events were mild or moderate, and the Bl-04 alone group reported the most.
Safety analysis of the randomized, placebo-controlled trial in active adults; Bl-04 alone, a two-strain blend, or placebo for 150 days. Two authors worked for DuPont/Danisco (Cox et al. 2014, Eur J Clin Nutr)
Healthy, physically active adults from the Australian Institute of Sport trial.
Routine blood counts and clinical chemistry differed from placebo in few measures, with exceptions including plasma calcium and urea, with changes that were small and stayed within laboratory reference ranges. No obvious safety or tolerability issues were seen.