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Safety


Safety in Adults

Reference

Sendelius M, 2023
]Sweden

Study Objectives

To evaluate safety and coloniza tion of L. reuteri ATCC PTA 4659 in humans, as well as in vitro characterization of the strain.

Study Design*

R, DB, PC

28 days + follow up at 42 days

No. of Subjects (dose)

L. reuteri low dose: 12 (1×109 CFU) L. reuteri high dose: 12 (1×1011 CFU) Placebo: 6

Results

L. reuteri ATCC PTA 4659 was shown to be safe for hu man consumption. There were no differences in adverse advents reported between the groups and colonization was described. Basic characteristics of the strain were reported, including antibiotic resistance traits and genomic safety.

Reference

Böttcher MF, 2008
(Substudy of Abrahamsson 2007) Sweden

Study Objectives

To evaluate effect on the immu nological composition of breast milk (as part of a study on allergy prevention in the offspring). Preg nant women ingested L. reuteri ATCC 55730 before giving birth.

Study Design*

R, DB, PC 4 weeks before delivery, follow up after 1 month

No. of Subjects (dose)

L. reuteri: 54 (1×108 CFU) Placebo: 55

Results

• Colostrum content of the cytokine TGF-beta2 was signifi cantly reduced while its content of the anti-inflammatory cytokine IL-10 increased
• The effect was not retained at follow-up
• Development of eczema during the first 24 months of life was not associated with any of the analysed breast milk parameters

Reference

Egervärn M, 2010
Sweden

Study Objectives

To evaluate the risk of transfer of plasmid borne antibiotic resist ance in L. reuteri ATCC 55730 to other gut microbes.

Study Design*

R, DB 14 days + 14d follow-up

No. of Subjects (dose)

L. reuteri ATCC 55730: 7 (5×108 CFU) L. reuteri DSM 17938: 7 (5×108 CFU)

Results

• No clinical safety or tolerance problems
• There was no transfer of antibiotic resistance to other gut bacteria species

Reference

Mangalat N, 2012
USA

Study Objectives

To investigate the safety of drops with L. reuteri DSM 17938, according to FDA’s policies of Investigational New Drug, administered to healthy adults for 2 months. Changes in some immune factors were also monitored.

Study Design*

R, DB, PC 2 months with follow-up after 1 and 4 months

No. of Subjects (dose)

L. reuteri: 30 (5 drops/d = 5×108 CFU) Placebo: 10

Results

L. reuteri drops were safe to consume and well tolerated. There was no increased risk of adverse events or differences in adverse events reported in the probiotic vs. the placebo group. None of the adverse events were related to the pro biotic. No severe adverse events were reported.

Reference

Oberhelman RA, 2014
Peru

Study Objectives

A phase I study to assess the safety and tolerability of L. reu teri DSM 17938 in oil suspension in healthy adult volunteers.

Study Design*

R, DB, PC 5 days + follow-up until day 36 and at 6 months after start of study

No. of Subjects (dose)

L. reuteri: 30 (1×108 CFU) Placebo: 15

Results

• There was no evidence of invasive infection due to L. reuteri administration and no differences between groups for laboratory parameters, vital signs, clinical tolerance, or symptoms reported.
• The frequency of subject-reported symptoms on the daily log sheets was similar between study groups.
• The frequency of adverse events was similar between study groups, and no serious adverse events were reported.

Reference

Rosander A, 2008
Sweden

Study Objectives

To verify the safety and colonisa tion of L. reuteri (Lr) DSM 17938 in healthy adults, and also in high dose.

Study Design*

R, DB, PC 28 days + 28d follow-up

No. of Subjects (dose)

Lr DSM 17938: 4 (8×108 CFU) Lr DSM 17938: 5 (6.5×1010 CFU) Lr ATCC 55730: 3 (8×108 CFU) Placebo: 4

Results

No clinical safety or tolerance problems with any of the dos ages or L. reuteri strains

Reference

Wolf BW, 1998
USA

Study Objectives

Safety and tolerance in immu nocompromised, i.e. HIV-positive adults. The subjects were 23 50yr, the majority men, and not using antiretroviral therapy. They consumed high dose of freeze dried L. reuteri SD2112 (=ATCC 55730) powder in sachets.

Study Design*

R, DB, PC 21 days + 14d follow-up Physical exami nation, serum chemistries, hematology, urinalysis, and faecal fat: at ba seline, day 21 and 35. Faecal total Lactobacillus and L. reuteri were analysed every week, including baseline. Any GI symptoms were reported in a daily diary.

No. of Subjects (dose)

L. reuteri: 15 (1×1010 CFU) Placebo: 20

Results

There were no clinical safety or tolerance problems compared to placebo.
• Blood analyses showed no growth of bacteria.
• Faecal numbers of L. reuteri and total Lactobacillus were unusually low in the active group, though L. reuteri tended to increase in the active group. The lifestyle of most sub jects, being homosexual men, might explain this deviation from the results of the safety trial in healthy men (Wolf 1995).

Reference

Wolf BW, 1995
USA

Study Objectives

Safety and tolerance in healthy adult males consuming a capsule with powder of freeze dried L. reuteri SD2112 (=ATCC 55730) in high dose.

Study Design*

R, DB, PC 21 days + 7d follow-up Serum chemistries, hema tology, urinalysis, urinary indican excretion, faecal fat and faecal total Lactobacillus and L. reuteri, were analysed every week, including baseline. Physical examination: day 0, 21 and 28. Any GI symptoms were reported in a daily diary. Faecal level of L. reuteri was checked also at day 77 after f irst day of probiotic consump tion.

No. of Subjects (dose)

L. reuteri: 15 (1×1011 CFU) Placebo: 15

Results

The incidence of subjective tolerance factors was infre quent and similar for both treatments. Serum chemistry associated with heart, liver, and kidney function, protein balance, and bone maintenance was analysed: although significant differences were observed for a few of the serum chemistry and hematology variables, all of the values remained within the normal range for healthy adult males.
Subjects consuming
L. reuteri had increased (p<0.01) levels of L. reuteri in their feces on day 7, 14, 21, and 28. Colonisation was lost within 2 months. Total Lactobacillus numbers did not differ bet ween groups during the study. Conclusion: L. reuteri at this high dosage was safe to use and with good tolerance.