Small Uncontrolled Trial Links Oxaloacetate to Improved Cognition After Breast Cancer

In a small, uncontrolled phase II clinical trial led by researchers at the UCLA Health Jonsson Comprehensive Cancer Center, 18 women with early-stage breast cancer who reported significant cognitive difficulties were given the nutritional supplement oxaloacetate for eight weeks. Sixteen participants completed treatment, and all 16 reported significant improvements in cognitive symptoms. The group also showed improvements in fatigue and physical functioning, while objective testing detected gains in processing speed and executive function. Because the study included no placebo or comparison group, the findings do not establish that oxaloacetate caused the improvements, the researchers cautioned.

Participants were between one and five years from their breast cancer diagnosis and had an average age of about 50. Most had previously received chemotherapy, and nearly 90% were receiving endocrine therapy at the time of the study. Researchers designed the trial around the possibility that inflammation associated with cancer and its treatments may disrupt glutamate signaling and cellular energy production in the brain, processes that could contribute to cognitive problems and mental fatigue. Oxaloacetate is naturally present in the body and participates in both glutamate regulation and cellular energy production, giving the researchers a biological rationale for testing it as a supplement.

Each participant took 500 milligrams of oxaloacetate twice daily for eight weeks. The researchers measured cognitive symptoms before and during treatment using patient-reported questionnaires and standardized neuropsychological tests assessing attention, memory, processing speed and executive function. They also evaluated fatigue, sleep, anxiety, depression, physical health and mental health, and monitored participants for side effects. On the study’s primary measure of perceived cognitive impairment, the average score increased from 29.1 before treatment to 55.5 after eight weeks, moving the group average from a range considered impaired to a range considered normal. Improvements were observed after four weeks and generally became greater by the end of treatment.

Participants also reported significant reductions in fatigue, including mental fatigue, and significant improvements in physical functioning. Neuropsychological testing showed improvements in executive function, which includes skills such as planning, focusing and managing tasks, as well as processing speed. The investigators described the cognitive-testing findings as preliminary because of the small sample. Oxaloacetate was generally well tolerated, although gastrointestinal symptoms—including indigestion, bloating, constipation, diarrhea and nausea—were the most common adverse effects. Two participants discontinued treatment because of gastrointestinal symptoms, and no serious adverse events were reported.

Cancer-related cognitive impairment can persist after breast cancer treatment and affect daily life, but effective treatments remain limited. An estimated 15% to 25% of breast cancer survivors may experience persistent cognitive difficulties. Although the condition has historically been associated with chemotherapy, its causes may include cancer itself, chemotherapy, endocrine therapy, inflammation, hormonal changes and other biological and behavioral factors. The UCLA team is preparing a randomized, placebo-controlled phase II trial in breast cancer survivors with cancer-related cognitive impairment, expected to open in late 2026. Preclinical studies in mice are also under way to investigate how oxaloacetate works and whether related outcomes for fatigue and physical function are observed with a placebo comparison. Further research is needed to determine whether oxaloacetate was responsible for the improvements reported in this initial trial.

Subject of Research: Preliminary evaluation of oxaloacetate for cancer-related cognitive impairment in breast cancer survivors

Article Title: Nutritional supplement may help ease ‘brain fog’ after breast cancer treatment

Article References: Nutritional supplement may help ease ‘brain fog’ after breast cancer treatment. Original publication (Bibliographic details unavailable.)

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Keywords: oxaloacetate, breast cancer, cancer-related cognitive impairment, chemo brain, fatigue, cognition, phase II trial, nutritional supplements, UCLA, neuropsychological testing, Nutritional, supplement