A Randomized Double Blind Controlled Safety Trial Evaluating D-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri -containing Formula
Open accessAbstract
Background: D-Lactic acidosis in infants fed lactic acid bacteria-containing products is a concern. Methods: The primary objective of this non-inferiority trial was to compare urinary D-lactic acid concentrations during the first 28 days of life in infants fed formula containing Lactobacillus reuteri (1.2 x 10 6 colony forming units (CFU)/ml) with those fed a control formula. The non-inferiority margin was set at a two-fold increase in D-lactic acid (0.7 mmol/mol creatinine, log-transformed). Healthy term infants in Greece were enrolled between birth and 72 hours of age, and block randomized to a probiotic ( N = 44) or control ( N = 44) group. They were exclusively fed their formulae until 28 days of age and followed up at 7, 14, 28, 112, and 168 ± 3 days. Anthropometric measurements were taken at each visit and tolerance recorded until 112 days. Urine was collected before study formula intake and at all visits up to 112 days and blood at 14 days. Results: D-Lactic acid concentration in the probiotic group was below the non-inferiority margin at 28 days: treatment effect -0.03 (95% confidence interval [CI]: [-0.48 to 0.41]) mmol/mol creatinine but was above the non-inferiority margin at 7 and 14 days–-treatment effect 0.50 (95% CI: [0.05-0.96]) mmol/mol creatinine and 0.45 (95% CI: [0.00-0.90]) mmol/mol creatinine, respectively. Blood acid excess and pH, anthropometry, tolerance, and adverse events (AEs) were not significantly different between groups. Conclusion: Intake of L. reuteri-containing formula was safe and did not cause an increase in D-lactic acid beyond two weeks. Trial Registration: ClinicalTrials.gov NCT01119170.
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Lack of data in preterm infants led to a caution about using D-lactate-producing probiotics in this population, although a controlled trial in healthy full-term infants showed that D-lactate-producing L. reuteri DSM-17938 did not result in acidosis and probiotic-containing infant formulas were not associated with acidosis.
“Lack of data in preterm infants led to a caution about using D-lactate-producing probiotics in this population,125 although a controlled trial in healthy full-term infants showed that D-lactate-producing L. reuteri DSM-17938 did not result in acidosis126 and probiotic-containing infant formulas were not associated with acidosis.127”
From Emerging issues in probiotic safety: 2023 perspectives (2023) · cites this paper as [126]
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- Authors
- Papagaroufalis, K., Fotiou, A., Egli, D., Tran, L.-A., & Steenhout, P.
- Affiliations
- General-Maternity District Hospital Helena Venizelou (GR)
- Nestec (Switzerland) (CH)
- Corresponding author
- Steenhout, Philippe
- Venue
- Nutrition and Metabolic Insights
- Publisher
- SAGE Publications
- Published
- 2014-01
- Volume
- 7
- Pages
- 19-27
- ISSN
- 1178-6388 (ISSN-L)
- PMC
- PMC3999946
- OpenAlex
- W2002527867
- Cited by
- 47
- References
- 16
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 4
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nutrition and Metabolic Insights (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Health Sciences › Health Professions › Pharmacy › Infant Health and Development
- Keywords
- D-lactate, D-lactic acidosis, Lactobacillus reuteri, infant formula, non-inferiority, probiotic safety, term infants, blood pH
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