D-Lactic acid-induced neurotoxicity in a calf model.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model (bovine study).
PubMed 17505055 · doi:10.1152/ajpendo.00063.2007
What was done
Eight Holstein calves (aged 32 ± 11 days, weighing 70 ± 10 kg) were surgically implanted with indwelling jugular intravenous and atlanto-occipital cerebrospinal fluid (CSF) catheters. In a randomized crossover design, each calf received 6-hour infusions of isomolar DL-lactic acid (dl-LA), L-lactic acid (l-LA), hydrochloric acid (HCl), or saline to test whether neurotoxicity is mediated by acidosis or D-lactic acid specifically.
What was found
Infusion of dl-LA caused ataxia after 4 hours and produced significant central nervous system depression (clinical score 8.0 ± 0.4 at 7 hours), whereas l-LA, HCl, and saline caused no ataxia and scores under 1.5 (P < 0.01 vs. dl-LA). dl-LA caused less severe acidemia at 6 hours than HCl (pH 7.13 ± 0.06 vs. 7.00 ± 0.04; base excess -16 ± 1 vs. -23 ± 3 mmol/L; bicarbonate 11 ± 1 vs. 8 ± 1 mmol/L; all P < 0.01), despite producing far greater neurological dysfunction. Similar patterns occurred in CSF acidosis.
Why it matters
These findings show that D-lactate-associated encephalopathy (seen in conditions like short-bowel syndrome) is driven by direct D-lactate neurotoxicity rather than secondary tissue acidification or general metabolic acidosis.
Limits
The study was conducted in a very small sample of calves (n = 8), using DL-lactic acid rather than pure D-lactic acid. Findings in ruminant calves may not fully translate to human gastrointestinal physiology or neural metabolism.
Cited by
- supports D-lactate is neurotoxic.