Twice-Daily Oxaloacetate Activates Brain Bioenergetic Metabolism in Alzheimer Disease

PET scan of brain with Alzheimers
PET scan of brain with Alzheimers
The study assessed the pharmacokinetics and pharmacodynamics of 2 doses of oxaloacetate in patients with Alzheimer disease.
The following article is part of conference coverage from the 2018 Alzheimer’s Association International Conference in Chicago, Illinois. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAIC 2018.

CHICAGO – Interim study results presented at the 2018 Alzheimer’s Association International Conference, held July 22-26, 2018 in Chicago, Illinois suggest that twice-daily 1000 mg oxaloacetate (OAA) activates brain bioenergetic metabolism, which is defective in Alzheimer disease (AD).

“Brain bioenergetic function is defective in AD, and may contribute to reduced glucose utilization on fluorodeoxyglucose positron emission tomography (FDG PET) scans,” the investigators reported. “Preclinical studies found oxaloacetate (OAA) enhanced brain bioenergetics and glucose flux, but human pharmacokinetic and pharmacodynamic data are lacking.”

The study assessed the pharmacokinetics and pharmacodynamics of 2 doses of OAA in patients with AD. Participants were allocated to either twice-daily 500 mg OAA (n=14) or twice-daily 1000 mg OAA (n=7). The trial included a treatment duration of 1 month.

FDG PET scans of participants were obtained prior to treatment initiation. Baseline FDG PET scans were compared with scans taken following the 1-month intervention. A total of 7 different regions of interest were used to measure the FDG PET signal, with regional pre- and post-intervention values compared at final assessment.

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Treatment with twice-daily OAA 1000 mg resulted in a greater favorable response than the 500 mg dose in 6 of the FDG PET regions of interest, either in regard to an increase or less decline in FDG PET signal at 1 month.

Participants receiving twice-daily OAA 1000 mg also demonstrated a significantly greater mean change in hippocampal signal compared with the twice-daily 500 mg OAA arm (2.5% mean increase, 0.9% standard error vs 0.3% mean decline, 0.7% standard error, respectively; P <.05, unpaired T-test).

Since these data are considered preliminary, the researchers warrant caution in interpreting the results and/or extrapolating the findings to clinical practice. “Whether or not positive findings persist at the conclusion of this study remains to be seen,” the researchers concluded.

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Vidoni ED, Clutton J, Becker AM, et al. Trial of oxaloacetate in Alzheimer’s disease (TOAD): interim FDG PET analysis. Presented at: 2018 Alzheimer’s Association International Conference. July 22-26, 2018; Chicago, IL. Abstract 23999.