Single-Arm Trial Evaluating the Safety and Efficacy of Anhydrous Enol-Oxaloacetate on Improving Cognitive Complaints in Breast Cancer, 2026, Ganz

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https://ascopubs.org/doi/10.1200/OA-26-00063

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ORIGINAL REPORTS

October 20, 2026
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

Spoiler: Authors

Authors: Patricia A. Ganz, MD https://orcid.org/0000-0002-1841-4143 pganz@mednet.ucla.edu, Kathleen Van Dyk, PhDhttps://orcid.org/0000-0003-1500-930X, Catherine M. Crespi, PhD https://orcid.org/0000-0002-6150-2181, Laura Petersen, MS https://orcid.org/0000-0002-4843-2692, Mina S. Sedrak, MD, MS https://orcid.org/0000-0002-8379-391X, and Julienne E. Bower, PhD https://orcid.org/0000-0003-0813-4444AUTHORS INFO & AFFILIATIONS

JCO Oncol Adv 3, e2600063(2026)
Volume 3, Number 4
DOI: 10.1200/OA-26-00063

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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 bioenergetic 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 randomized, placebo-controlled trial to confirm efficacy.

Context​

Key Objective
Is the nutritional supplement anhydrous enol-oxaloacetate effective in reducing symptoms of cognitive impairment in breast cancer survivors?

Knowledge Generated
Among 16 of 18 study participants with severe cognitive impairment, the nutritional supplement was well-tolerated and there were statistically significant improvements in self-reported cognition, fatigue, and physical functioning, including significant improvements in neurocognitive test performance over an 8-week period. These findings support further testing of oxaloacetate in a randomized placebo-controlled trial.

Relevance (M. Lustberg)
Cancer-related cognitive impairment (CRCI) is common among cancer survivors and currently there are no effective pharmacologic interventions. Oxaloacetate, a naturally occurring metabolic intermediate with glutamate-scavenging, anti-inflammatory, and mitochondrial bioenergetic properties, was evaluated in breast cancer survivors with CRCI and was shown to have evidence of preliminary safety and efficacy. These findings will need to be further evaluated in a randomized, placebo-controlled trial.*
*Relevance section written by JCO Oncology Advances Associate Editor Maryam B. Lustberg, MD, MPH.

 

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

A new study led by researchers at the UCLA Health Jonsson Comprehensive Cancer Center found that a nutritional supplement containing oxaloacetate, a molecule naturally found in the body that helps cells produce energy, may help improve cognitive function and reduce the fatigue experienced by...

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NEWS RELEASE 20-OCT-2026

Nutritional supplement may help ease ‘brain fog’ after breast cancer treatment​

Small UCLA-led study found improvements in cognition, fatigue and physical functioning after eight weeks of oxaloacetate treatment

Peer-Reviewed Publication
UNIVERSITY OF CALIFORNIA - LOS ANGELES HEALTH SCIENCES


A new study led by researchers at the UCLA Health Jonsson Comprehensive Cancer Center found that a nutritional supplement containing oxaloacetate, a molecule naturally found in the body that helps cells produce energy, may help improve cognitive function and reduce the fatigue experienced by some breast cancer survivors following treatment.

The findings, published in JCO Oncology Advances, show that breast cancer survivors with significant cancer-related cognitive impairment, sometimes referred to as “chemo brain” or “brain fog,” experienced improvements in memory, concentration and other cognitive symptoms after taking oxaloacetate for eight weeks. Participants also reported less fatigue and better physical functioning, while cognitive testing showed improvements in processing speed and executive function, which includes skills such as planning, focusing and managing tasks.

“Cancer-related cognitive impairment can persist long after treatment ends and can have a significant impact on a person’s daily life, yet we still have very few effective treatments for it,” said Dr. Patricia Ganz, a distinguished professor of medicine at the David Geffen School of Medicine at UCLA and the UCLA Fielding School of Public Health, and first author of the study.

An estimated 15% to 25% of breast cancer survivors may experience persistent cognitive difficulties following breast cancer and its treatment. While cancer-related cognitive impairment has historically been associated with chemotherapy, researchers now recognize that its causes are complex and may involve cancer itself, chemotherapy, endocrine therapy, inflammation, hormonal changes and other biological and behavioral factors. With few treatment options available, researchers have been exploring new approaches that target the biological processes that may contribute to these symptoms.

Researchers have been interested in oxaloacetate because inflammation associated with cancer and its treatments may disrupt normal glutamate signaling and cellular energy production in the brain, processes that could contribute to cognitive problems and mental fatigue. Because oxaloacetate plays a role in both glutamate regulation and cellular energy production, the researchers wanted to determine whether taking it as a supplement could help alleviate these symptoms.

To evaluate the supplement’s potential effects, the researchers conducted a phase II clinical trial involving 18 women with early-stage breast cancer who were between one and five years from diagnosis and reported significant cognitive difficulties. The participants 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.

Participants took 500 milligrams of oxaloacetate twice daily for eight weeks. Researchers assessed cognitive symptoms before and during treatment using patient-reported questionnaires and standardized neuropsychological tests measuring attention, memory, processing speed and executive function. They also evaluated fatigue, sleep, anxiety, depression and physical and mental health, and monitored participants for side effects throughout the study.

Sixteen of the 18 participants completed the eight-week treatment, and all 16 reported significant improvements in their cognitive symptoms. On average, scores on the study’s primary measure of perceived cognitive impairment increased from 29.1 before treatment to 55.5 after eight weeks, moving the group from a range considered impaired to a range considered normal. Improvements were seen after four weeks and generally became greater by the end of treatment.

The researchers also found significant reductions in fatigue, including mental fatigue, and significant improvements in physical functioning. Neuropsychological testing showed improvements in executive function and processing speed, although the researchers noted that these findings are preliminary given the small size of the study.

Oxaloacetate was generally well tolerated. Gastrointestinal symptoms, including indigestion, bloating, constipation, diarrhea and nausea, were the most common side effects. Two participants discontinued treatment because of gastrointestinal symptoms, and no serious adverse events were reported.

The researchers caution that the study was small and did not include a placebo or comparison group, so further research is needed to determine whether oxaloacetate was responsible for the improvements.

“These early findings give us a strong reason to continue studying oxaloacetate as a potential approach for managing cognitive problems after breast cancer treatment,” Ganz said.

The team is now preparing for a randomized, placebo-controlled phase II trial in breast cancer survivors with cancer-related cognitive impairment that is expected to open in late 2026. Preclinical studies in mice are also underway to better understand how oxaloacetate works and whether there are similar outcomes (improved fatigue and physical function) in a placebo-controlled study in mice.

The study was funded in part by the Breast Cancer Research Foundation and the National Cancer Institute.

Other authors, all from UCLA, are Kathleen Van Dyk, PhD, Catherine M. Crespi, PhD, Laura Petersen, MS, Mina Sedrak, MD, MS, and Julienne Bower, PhD.

JOURNAL​

JCO Oncology Advances

DOI​

10.1200/OA-26-00063