Benefits
Oral and upper respiratory immune defenses in children
In a randomized study of 222 children starting kindergarten, those given K12 daily for 6 months had streptococcal throat infections in about 16% vs 48% of untreated children, and ear infections in 44% vs 80%. Smaller studies in children with repeated strep throat reported similar drops versus the year before. None used a placebo, and most were led by the product's formulator.
Upper respiratory symptom days in active young adults
In a 4-month double-blind trial in 112 people aged 19 to 25, the overall severity of upper respiratory symptoms did not differ between K12 and placebo. Participants who took more than 90% of their doses reported more symptom-free days, but that comparison was not randomized, so the finding is uncertain.
Salivary IgA, an antibody of the mouth and airway lining
Results disagree. In 20 active young adults on a hard training program, those taking K12 for 30 days had higher salivary IgA after exercise than those on placebo, with no difference in respiratory episodes. In a 4-week trial in 31 adults at rest, K12 did not raise salivary IgA or saliva flow, though dental plaque decreased.
Fresher breath
In 23 adults with bad breath who first used a chlorhexidine rinse, 85% on K12 lozenges vs 30% on placebo had large drops (over 100 ppb) in breath sulfur compounds after one week; that study was run by the strain's developer. In 208 children, the group given chlorhexidine plus K12 was the only one with a stable improvement in breath odor scores over 3 months.
Tolerability in children and adults
In a double-blind safety trial, 53 volunteers took 10 billion CFU of K12 or placebo daily for 28 days; blood chemistry, blood counts and the frequency of side effects did not differ between groups. The pediatric studies reported no side effects, though they were too small to detect rare ones.
Mechanism of action
Salivaricin A2 and salivaricin B
K12 carries a 190 kb megaplasmid with nearly adjacent gene clusters for two lantibiotic bacteriocins, salivaricin A2 and salivaricin B, which inhibit Streptococcus pyogenes in lab tests. Only some S. salivarius strains carry both: in one survey, 19 of 61 strongly inhibitory strains had the salivaricin B gene.
Settling in the mouth and throat
S. salivarius is a natural resident of the mouth, so K12 is given as a lozenge or slow-release tablet to colonize the oral cavity. In the adult breath study, K12 changed the bacterial profile of saliva in most subjects after a chlorhexidine rinse had cleared space for it.
Odor-producing bacteria
In lab tests from the adult breath study, K12 suppressed black-pigmented bacteria in saliva samples and reference strains of bacteria linked to bad breath, which produce volatile sulfur compounds.
Salivary antibody signals
Salivary IgA is the main antibody in saliva. One small trial found higher salivary IgA after hard exercise with K12, while another found no change at rest, so whether K12 works through this pathway is unsettled.
Clinical trials
Children were randomized to K12 (Bactoblis) daily for 6 months or to an untreated control group, then followed for 3 months without treatment. There was no placebo. (Di Pierro et al. 2016, Eur Rev Med Pharmacol Sci)
222 children aged 3 in their first year of kindergarten, 111 per group; 29 per group in the follow-up.
During treatment, streptococcal throat infection affected about 16% vs 48%, scarlet fever 9% vs 4% (not lower with K12), and ear infection 44% vs 80%. During follow-up the rates were 15% vs 26%, 0% vs 6% and 12% vs 36%. No side effects were seen and all children completed the study.
Open-label study. 45 children took one slow-release tablet (5 billion CFU K12, Bactoblis) daily for 90 days, then were followed for 6 months off the product; 20 untreated children with the same history and 17 without it served as controls. Results were compared with each child's previous year. (Di Pierro et al. 2012, Int J Gen Med)
82 children: 65 with recent recurrent streptococcal throat infections (45 treated, 20 untreated) and 17 without that history.
The 41 children who finished treatment had about 90% fewer streptococcal throat infections and about 40% fewer ear infections than in the previous year, and about 65% fewer throat and ear infections during the 6 months off the product. No side effects or dropouts were reported. The main comparison was with the prior year, not with placebo.
Children took a slow-release tablet with at least 1 billion CFU K12 (Bactoblis) daily for 90 days or received nothing; 10 children per group were also tracked for viral throat infections. No placebo. (Di Pierro et al. 2014, Drug Healthc Patient Saf)
61 children with recurrent streptococcal throat infections: 31 treated, 30 untreated.
The 30 children who completed treatment had over 90% fewer streptococcal throat infections than in the previous year, with no change in the untreated group, and about 80% fewer viral throat infections. Days on antibiotics were 30 vs 900 and school absence days 16 vs 228. One child dropped out over the taste.
Pilot study. Treated children took BLIS K12 daily for 90 days and were followed for 9 months; the control group was children with very few recent strep infections, so the groups were not alike at the start. The lead author disclosed that he formulated the tested product. (Di Pierro et al. 2016, Drug Healthc Patient Saf)
124 children: 48 with recent recurrent streptococcal throat infections (treated) and 76 controls.
Streptococcal throat infections fell about 90% compared with the year before treatment. Compared with untreated children, treated children had significantly fewer episodes of tracheitis, viral pharyngitis, rhinitis, flu, laryngitis, ear infection and enteritis, but not stomatitis.
Retrospective analysis comparing a year without K12 (2014 to 2015) with a year in which K12 was given for two 3-month periods (2015 to 2016). (Di Pierro et al. 2018, Minerva Pediatr)
133 children without a history of recurrent streptococcal infection.
Throat infections were about 90% lower and ear infections about 70% lower in the K12 year (both P<0.001). With no concurrent control group, other differences between the two years cannot be ruled out.
Pilot uncontrolled study: K12 (Bactoblis) daily for 90 days, followed by hearing tests, tympanometry, endoscopy, otoscopy and tonsil examination. (Di Pierro et al. 2015, Int J Gen Med)
22 children with secretory otitis media (persistent fluid in the middle ear).
The authors reported fewer acute ear infections and positive results on all clinical measures, with good tolerability. With no control group, natural recovery cannot be ruled out; the authors called for a placebo-controlled study.
Randomized double-blind placebo-controlled trial of daily K12 (Bactoblis) for 4 months, with symptoms tracked on the Jackson scale and WURSS-11. The first author advises a company that markets K12 in Italy. (Bertuccioli et al. 2024, Microorganisms)
112 healthy adults aged 19 to 25.
Overall upper respiratory symptom severity did not differ between K12 and placebo. Participants with more than 90% adherence reported more days without symptoms; this adherence comparison was not randomized.
Randomized double-blind placebo-controlled study: K12 or placebo daily for 30 days, followed by an exercise test and five high-intensity sessions in 3 days, with saliva sampled before and after. (Bertuccioli et al. 2023, Front Immunol)
20 active young adults (14 men, 6 women), average age 23.5.
Salivary IgA was higher in the K12 group 72 hours after the last session, and its secretion rate was higher at 0 and 72 hours. The number of upper respiratory episodes did not differ between groups.
Pilot double-blind placebo-controlled trial: K12 for 4 weeks, then 2 weeks without it. No outside funding. (Babina et al. 2022, Nutrients)
31 adults (15 on K12, 16 on placebo); 30 completed.
K12 did not increase salivary IgA or saliva flow compared with placebo. Dental plaque decreased significantly in the K12 group at 4 and 6 weeks.
Preliminary study: 3 days of chlorhexidine rinse, then K12 or placebo lozenges. Run by researchers at BLIS Technologies. (Burton et al. 2006, J Appl Microbiol)
23 adults with halitosis.
One week after starting, 85% of the K12 group and 30% of the placebo group had large (over 100 ppb) reductions in volatile sulfur compounds. The saliva bacterial profile changed in most subjects after K12.
Randomized controlled trial comparing brushing and flossing alone, plus tongue scraping, plus chlorhexidine, or plus chlorhexidine and K12, with breath odor scored at 1 week and 3 months. (Jamali et al. 2016, Oral Health Prev Dent)
208 children with breath odor scores of 2 or more.
The chlorhexidine plus K12 group showed a significant and stable improvement in odor scores. Chlorhexidine without K12 improved scores, but the effect was not stable; brushing alone and tongue scraping did not improve them.
Randomized double-blind placebo-controlled safety study of 10 billion CFU K12 daily for 28 days, then a 28-day washout. Run by researchers at BLIS Technologies. (Burton et al. 2011, Food Chem Toxicol)
53 volunteers (25 on K12, 28 on placebo).
Blood chemistry and blood counts did not differ between groups, both treatments were well tolerated, and the frequency and intensity of side effects were similar.