Benefits
Parent-reported illness rates in children at daycare and school
In 638 children aged 3 to 6 drinking one bottle a day for 90 days, common infections were 19% less frequent than on a placebo drink, one of two main outcomes, at a margin (P = 0.046) that a correction for two main outcomes would not pass, mainly from stomach and bowel infections; illness-related behavior change did not differ. In 599 children in Russia, two bottles a day did not lower the main infection count.
Length of illness episodes in older adults
In 1,072 older adults drinking 200 g a day for 3 months, the main outcome, the number of common infections, did not differ from a non-fermented control, but episodes were shorter on average (6.5 vs 8 days). A 360-person, 3-week pilot also found no change in how often infections occurred, with shorter illnesses (7.0 vs 8.7 days).
Illness counts in shift workers
In 1,000 healthy shift workers drinking 200 g a day for 3 months, the main outcome, the total number of common infections, did not differ from control. Fewer people on the drink had at least one infection (43% vs 51%), and a later added analysis found fewer infections overall. These secondary findings were not the trial's main test.
Vaccine antibody response in adults over 70
In two controlled trials in 86 and 222 healthy adults over 70, drinking Actimel twice a day for 7 or 13 weeks, with flu vaccination after 4 weeks, raised antibody titers to the vaccine strains more than a non-fermented control drink. Antibody titers are markers; the trials did not test whether fewer people became ill.
Bowel regularity in hospital patients taking antibiotics
In 135 older hospital patients taking antibiotics, a 100 g drink twice a day during the course and for a week after fewer had antibiotic-associated loose stools (12% vs 34% on a sterile milkshake placebo). A later hip fracture study against past patients found no reduction, and EFSA judged the evidence insufficient for a related claim.
Stool health in toddlers compared with plain yogurt
In 928 healthy children aged 6 to 24 months given 100 g a day of milk fermented with the strain and yogurt cultures, fewer had episodes of acute loose stools than children given standard yogurt (15.9% vs 22%). The trial was run from Danone's research center, and the abstract does not name a primary outcome.
Mechanism of action
Survival through the human gut
In a human sampling study, up to 51.2% of the strain swallowed in fermented milk survived to the ileum and up to 28.4% to the feces, and in older adults L. casei counts in stool rose during intake. Survival shows the strain reaches the gut alive; it is not itself a health benefit.
Immune cell and antibody markers
In shift workers, natural killer cell counts and activity rose during infections on the drink, and in students under exam stress, lymphocyte and CD56 cell counts held steadier than on plain milk while anxiety and cortisol did not differ. Vaccine antibody titers rose more in adults over 70. These are markers, not illness outcomes.
Close genetic match to the Yakult strain (lab work)
Genome sequencing of strains taken from Actimel and Yakult bottles found them nearly identical, differing by 29 single-letter changes and one small insertion, which the authors read as a recent common ancestor. Each strain's trials were still run on its own product, so results are reported separately.
Clinical trials
Double-blind, cluster-randomized, placebo-controlled trial; one strawberry DanActive drink a day (L. casei DN-114 001 at 1 x 10^8 CFU/g plus S. thermophilus and L. bulgaricus) or a sweetened, flavored non-fermented acidified dairy drink with no live cultures for 90 days (Merenstein et al. 2010, Eur J Clin Nutr).
638 children aged 3 to 6 attending daycare or school in the Washington, DC area (314 active, 324 placebo).
Of two parent-reported primary outcomes, common infection incidence was 19% lower on the drink (incidence rate ratio 0.81, 95% CI 0.65 to 0.99, P = 0.046), mainly from gastrointestinal infections, while change of behavior because of illness did not differ. With two primary outcomes, P = 0.046 would not pass a Bonferroni cutoff of 0.025, the threshold the authors used for subgroup comparisons. Randomization was by household. Lower respiratory infections did not differ. Both drinks had 19 g of added sugars per 200 mL. Funded by The Dannon Company, and three authors were Dannon employees.
Multicenter, double-blind, randomized, placebo-controlled trial; two 100 g bottles a day of Actimel (at least 10^10 CFU CNCM I-1518 per 100 g plus yogurt cultures) or a matched non-fermented acidified dairy drink for 3 months plus 1 month of follow-up (Prodeus et al. 2016, J Pediatr Gastroenterol Nutr).
599 children aged 3 to 6 at 12 day-care centers in Russia (300 active, 299 control).
The primary outcome, common infection incidence during intake, did not differ (98 vs 93), and the authors note overall incidence was unexpectedly low. Duration, severity, sick leave and quality of life did not differ. Rhinopharyngitis, a secondary count over the whole study, was lower (81 vs 100, P = 0.017). Danone Research sponsored and funded the trial (NCT01200173), and one author was a Danone Research employee.
Multicenter, double-blind, controlled trial; 200 g a day of the fermented dairy product with L. casei DN-114 001 or a non-fermented control dairy product for 3 months plus 1 month of follow-up (Guillemard et al. 2010, Br J Nutr).
1,072 free-living older adults, median age 76 (537 active, 535 control).
The primary outcome, the cumulative number of common infections, did not differ, nor did severity, fever, medication use, immune blood measures or quality of life. Average episode duration was shorter (6.5 vs 8 days, P = 0.008), as was cumulative duration (7 vs 8 days, P = 0.009). The first author is from Danone Research.
Single-center, randomized, double-blind, controlled trial; 200 g a day of the fermented dairy product with L. casei DN-114 001 or a control product for 3 months plus 1 month of follow-up (Guillemard et al. 2010, J Am Coll Nutr).
1,000 healthy shift workers (500 per group).
The primary outcome, the cumulative number of common infections, did not differ. A post hoc categorical analysis found fewer (OR 0.75, P = 0.017), and fewer people had at least one infection (43% vs 51%, P = 0.005). Natural killer cell counts and activity rose during infections, a marker. The first author is from Danone Research.
Randomized, controlled pilot study; milk fermented with yogurt cultures and L. casei DN-114 001 for 3 weeks, or control; a Danone-funded review describes it as open-label at 200 mL a day with a no-product control group (Turchet et al. 2003, J Nutr Health Aging).
360 free-living older adults (180 per group).
The incidence of winter infections did not differ. Illnesses were shorter on the fermented milk (7.0 vs 8.7 days, P = 0.024), and maximal temperature was slightly lower (38.3 vs 38.5 C). The abstract does not state funding.
Two randomized, multicenter, double-blind, controlled trials; Actimel (L. casei DN-114 001 plus yogurt cultures) or a non-fermented control dairy product twice daily for 7 weeks (pilot) or 13 weeks (confirmatory), with flu vaccination after 4 weeks (Boge et al. 2009, Vaccine).
86 (pilot) and 222 (confirmatory) healthy adults over 70 in France.
Antibody titers to the vaccine strains rose more on Actimel; in the confirmatory study, the B strain titer rise was larger at 3, 6 and 9 weeks (p = 0.020), with similar results for H3N2 and H1N1. These are antibody markers; illness was not the outcome. The abstract does not state funding.
Randomized, double-blind, placebo-controlled trial; a 100 g Actimel drink (L. casei DN-114 001 at 1 x 10^8 CFU/mL, S. thermophilus, L. bulgaricus) or a sterile long-life milkshake twice a day during an antibiotic course and for one week after (Hickson et al. 2007, BMJ).
135 hospital patients in London, mean age 74, taking antibiotics; 113 were analyzed for the primary outcome.
Antibiotic-associated diarrhea, the primary outcome, occurred in 7 of 57 (12%) vs 19 of 56 (34%) on placebo (P = 0.007), and C. difficile diarrhea in 0 vs 9 of 53. Funding included Danone Vitapole, and three authors had Danone-funded convention travel. A later non-randomized hospital study found no reduction, and EFSA did not accept a related claim.
Randomized trial; a yogurt containing L. casei or a non-probiotic yogurt; a Danone-funded review identifies the product as the CNCM I-1518 drink at 100 mL a day for 8 weeks and describes the trial as single-blind (Pereg et al. 2005, Am J Infect Control).
541 young male military recruits in Israel (502 analyzed).
Diarrhea incidence was 12.2% on the probiotic vs 16.1% on control (P = 0.207), and duration did not differ (3.0 vs 2.6 days). The authors called this a nonsignificant trend. The abstract does not state funding.