A small, preliminary single-arm clinical study found that after eight weeks of treatment, cognitive function score almost doubled in breast cancer survivors who were treated with the supplement oxaloacetate, reports MedPage Today.
Fatigue and physical function also improved, the researchers wrote in JOC Oncology Advances. On the basis of these results, a phase 2 placebo-controlled study of oxaloacetate for cancer-related cognitive impairment is expected to begin enrolment before year-end.
Aside from gastrointestinal symptoms, the treatment was generally well tolerated, reported Patricia Ganz, MD, of UCLA Health in Los Angeles, and colleagues.
“These early findings give us a strong reason to continue studying oxaloacetate as a potential approach for managing cognitive problems after breast cancer treatment,” she said.
Despite the small number of patients and lack of control group, the results are impressive, said Halle Moore, MD, of the Cleveland Clinic, who was not involved in the study.
“They had impressive improvement in patient-perceived cognitive function measures and improvement in fatigue and physical functioning,” Moore said. “It would be great to have a relatively easy option for patients to use for this troublesome symptom. I think the main point is that it supports proceeding to a longer randomised trial where we would compare to a control group.”
The intervention stands out from most previous studies that have focused on cognitive-behavioural interventions, such as exercise and managing anxiety, depression, and associated symptoms or issues, she added.
“I will be interested to see where this research goes, and I would love to have more options for our patients,” said Moore.
A substantial fraction of patients with cancer exhibit post-treatment cognitive impairment – commonly called chemo brain or brain fog.
The condition is especially prevalent in breast cancer survivors, among whom it has been studied most extensively, but it is not limited to those patients.
“It’s an issue for all types of cancer,” said Moore. “Breast cancer is just such a common cancer and there are so many breast cancer survivors, but we are seeing [cognitive impairment] more often in other cancers.”
Although the precise cause of and mechanisms underlying CRCI remain unclear, the condition became more prevalent in breast cancer after widespread adoption of adjuvant chemotherapy for early disease. Some of the agents used in adjuvant regimens cross the blood-brain barrier and have recognised neurotoxic effects. Early reports suggested a direct relationship between the intensity of chemotherapy treatment and cognitive dysfunction.
Oxaloacetate is a natural human metabolite involved in intracellular energy production. Additionally, it has a key role in regulation of the neurotransmitter glutamate, which has been studied extensively for its contributions to cognitive function.
Several clinical studies evaluated oxaloacetate’s ability to improve cognition and reduce fatigue. A small randomised study of patients with symptoms of long Covid showed significant improvement in cognitive performance with oxaloacetate and correlations between symptom response and cognitive gains.
Evidence linking oxaloacetate to cognitive function, as well as the paucity of pharmacologic interventions for CRCI, provided the rationale for a prospective clinical study in breast cancer survivors with diagnosed CRCI. Eligible patients were one to five years removed from cancer treatment and had a score of <12 on the PROMIS questionnaire, indicating moderately severe impairment.
Given the lack of a control group, the investigators approached the study with some scepticism, and sought to minimise the trial’s limitations with an initial two-step design, which defined a positive outcome as a 4-point improvement in the FACT-Cog PCI in the first nine patients. The preliminary data analysis showed a 27-point improvement.
“The impressive and universal improvements in perceived cognitive impairment in the first nine study participants encouraged us to redesign the study to be able to complete it with a smaller total sample size and to hasten the development of a randomised, placebo-controlled trial,” the authors wrote.
The investigators enrolled 18 patients, who received oxaloacetate 500 mg twice daily for eight weeks. All but two patients completed the study. The primary endpoint was perceived change in cognitive impairment at eight weeks.
Every patient who completed the study had significant improvement from baseline, and the mean score on the FACT-Cog PCI increased from 29.1 at baseline to 55.5 at eight weeks, moving the cohort from impaired to within the normal range. Improvement was observed after four weeks and generally increased during the remaining four weeks of the study. Neuropsychological testing showed improvement in executive function and processing speed.
The most commonly reported adverse effects (AEs) were indigestion, bloating, constipation, diarrhoea, and nausea. Two study participants discontinued because of gastrointestinal symptoms. No serious AEs occurred during the study.
Study details
Results From a Phase II Single-Arm Trial Evaluating the Safety and Efficacy of Anhydrous Enol-Oxaloacetate on Improving Cognitive Complaints in Breast Cancer Survivors
Patricia Ganz, Kathleen Van Dyk, Catherine Crespi et al.
Published in JSO Oncology Advances on 20 October 2026
Abstract
Purpose
Cancer-related cognitive impairment (CRCI) affects a substantial proportion of breast cancer survivors (BCSs), yet effective pharmacologic interventions are lacking. Oxaloacetate, a naturally occurring metabolic intermediate with glutamate-scavenging, anti-inflammatory, and mitochondrial bio-energetic properties, was evaluated for its safety and preliminary efficacy in improving cognitive complaints in BCS with moderate to severe CRCI.
Methods
We conducted a single-arm, phase II trial enrolling early-stage BCSs who were 12 months to 5 years’ post–primary treatment and reported significant cognitive complaints on the PROMIS Cognitive Function questionnaire. Participants received oxaloacetate 500 mg orally twice daily for 8 weeks. The primary end point was improvement in perceived cognitive impairment, measured by the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) score. Secondary outcomes included fatigue, insomnia, psychological symptoms, physical and mental health–related quality of life, neuropsychological test performance, and safety. Simon's two-stage design with subsequent sequential monitoring was used.
Results
Eighteen participants were enrolled; 16 completed the intervention. All evaluable participants demonstrated clinically and statistically significant improvement in perceived cognitive impairment (mean FACT-Cog PCI change +26.4 points; P < .0001), with improvement from the impaired to the normative range. Statistically significant improvements were also observed in total fatigue (P < .0001), mental fatigue (P < .0001), and physical function (P = .0003), with a trend toward improvement in insomnia (P = .09). Neuropsychological testing showed improvements in executive function and processing speed. Oxaloacetate was generally well-tolerated; GI symptoms were the most common adverse events, leading to treatment discontinuation in two participants. There were no serious adverse events.
Conclusion
Oxaloacetate treatment led to significant improvements in perceived cognitive impairment, fatigue, and physical functioning among BCSs with CRCI, with acceptable tolerability. These findings support further investigation in a randomised, placebo-controlled trial to confirm efficacy.
See more from MedicalBrief archives:
Dealing with the real issue of ‘chemo brain’
Exercise may alleviate ‘chemo brain’ in breast cancer — Washington University study