Oxaloacetate Supplement Improves Cognitive Function in Early-Stage Breast Cancer Survivors

A small UCLA-led trial reported that oral oxaloacetate supplementation reduced chemotherapy-related “brain fog” and fatigue in women who had completed treatment for early-stage breast cancer. Eighteen participants, average age 49.6 years, received 500 mg anhydrous enol-oxaloacetate capsules twice daily for eight weeks. Cognitive ability was measured with the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Perceived Cognitive Impairment (PCI) subscale, where scores < 54 indicate impairment. Baseline mean score was 29; after eight weeks the mean rose to 55.5, moving the group from the impaired to the non-impaired range. Sixteen women who completed the regimen also reported significant reductions in fatigue and marked improvements in physical functioning. Two participants withdrew because of gastrointestinal side effects (severe diarrhea and other GI symptoms). The study was published in *JCO Oncology Advances* on October 20.

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Cognitive impairment and persistent fatigue are frequently reported by breast-cancer survivors and may last for years after surgery, chemotherapy, and radiotherapy. These “chemo-brain” symptoms negatively affect quality of life and have been identified as a major post-treatment complication. Oxaloacetate, a naturally occurring metabolic intermediate, has been hypothesized to act as a glutamate “sponge,” potentially mitigating neuroinflammation triggered by certain chemotherapeutic agents.

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• Participants: 18 women, all >=12 months post-primary treatment; 89 % were on endocrine therapy.

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• Dosage: 500 mg oxaloacetate capsule, taken twice daily.

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• Cognitive Scores: Mean FACT-Cog PCI score improved from 29 to 55.5 (scores < 54 denote impairment).

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• Fatigue & Physical Function: Participants reported “significant improvement” in fatigue and “dramatic improvement” in physical functioning; minor, non-significant changes were noted for insomnia, anxiety, and depression.

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• Adverse Events: Two discontinuations due to severe diarrhea; other participants experienced mild GI symptoms (bloating, constipation, nausea).

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Mauricio Reginato, a professor of biochemistry and molecular biology at Drexel University, explained that chemotherapy-induced inflammation and excess glutamate may underlie cognitive deficits, and that oxaloacetate could reduce glutamate-mediated damage. He emphasized that the findings are preliminary and that larger, placebo-controlled trials are required to confirm efficacy and clarify mechanisms.

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• “More studies are needed to fully understand specific mechanisms of oxaloacetate in cancer-related cognitive impairment,” — Mauricio Reginato, a professor of biochemistry and molecular biology at Drexel University

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The trial’s small sample size and lack of a control group limit the strength of conclusions. Researchers acknowledge the need for a larger phase-two placebo-controlled study and an accompanying animal investigation to elucidate oxaloacetate’s mechanistic role.

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The study team plans to initiate a phase-two randomized, placebo-controlled trial to validate the cognitive and fatigue benefits observed, alongside preclinical work to explore oxaloacetate’s impact on glutamate regulation and neuroinflammation.

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