A Randomized Double Blind Controlled Safety Trial Evaluating D-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri-containing Formula

Abstract

BACKGROUNDd-Lactic acidosis in infants fed lactic acid bacteria-containing products is a concern.METHODSThe 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 × 106 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.RESULTSd-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.CONCLUSIONIntake of L. reuteri-containing formula was safe and did not cause an increase in d-lactic acid beyond two weeks.

Probiotics, D–Lactic acidosis, oxidative stress and strain specificity

“…The bacterial species from the LAB genera can produce L(C)-Lactic acid, D(¡)-Lactic acid, the racemate DL-Lactate, or a combination of these ( Table 1). [30][31][32][33][34] Recently there has been a deliberate misperception directed at an excess of D(¡)-Lactic acid production by certain probiotic bacteria as being responsible for the symptomology associated with chronic conditions such as Chronic Fatigue Syndrome (CFS); conclusions that are made upon the selective interpretation of research results while intentionally overlooking conclusive evidence that supports quite the opposite. Sheedy et al 35 proposed that an elevated fecal count of the lactic acid producing bacteria Enterococcus sp.…”

“…Supporting such a conclusion is scientifically flawed especially when clinical studies conducted with children demonstrate that administering probiotic bacteria that produce D(¡)-Lactic acid are safe and do not cause any long-term increases in blood D (¡)-Lactic acid. 30 Furthermore, D(¡)-Lactic acid producing bacteria have been consumed by humans for centuries from fermented foods such as yoghurt, sauerkraut and pickles and more recently from probiotic supplementation with no associated negative symptomatology.…”

Rapid review shows that probiotics and fermented infant formulas do not cause d‐lactic acidosis in healthy children

“…At days seven and 14, the urinary d ‐lactic acid levels were significantly higher in the probiotic group, but they were still within the normal range throughout the study. On day 14, neither the blood acid excess nor pH significantly differed between the groups .…”

“…We identified five randomised controlled trials from 2005 to 2017 covering 544 healthy infants from one day to 12 months of age. These all included d ‐lactate concentration measurements and lactic acid‐related outcome assessment in infants receiving d ‐lactate producing probiotic strains . Table summarises the characteristics of all the RCTs we included.…”

The status of probiotics supplementation during pregnancy

“…In other study 38 on healthy term infants, use of Lactobacillus paracasei was not associated with increase of lactic acid in blood. There were 88 infants, aged up to 72 hours, involved in this study.…”