The molecule, called oxaloacetate, is already present in the human body and plays an important role in how cells generate energy. In a small clinical trial, breast cancer survivors who took the supplement for eight weeks reported noticeable improvements in thinking, memory, concentration, and fatigue.

The results, published in JCO Oncology Advances, also showed improvements on cognitive tests measuring how quickly participants processed information and performed tasks requiring planning, attention, and mental flexibility. Although larger studies are needed to confirm the findings, the results suggest a potentially new way to address a problem that has long been difficult to treat.

"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, the study's first author and a distinguished professor of medicine at UCLA's David Geffen School of Medicine and UCLA Fielding School of Public Health.

Why Brain Fog Can Persist After Cancer Treatment

Cognitive difficulties are a lasting concern for many people who survive breast cancer. Researchers estimate that roughly 15% to 25% experience ongoing problems with memory, concentration, or other thinking abilities after their diagnosis and treatment. These symptoms are often described as "chemo brain" or "brain fog."

Despite the name, chemotherapy is not necessarily the only cause. Scientists increasingly recognize that cancer-related cognitive impairment can develop through several overlapping processes. The cancer itself, chemotherapy, endocrine therapy, inflammation, hormonal changes, and other biological and behavioral influences may all contribute.

Because the causes are complicated and effective treatments remain limited, researchers are investigating ways to address the underlying changes that may disrupt normal brain function.

One area of interest involves the relationship between inflammation, brain chemistry, and energy production. Inflammation linked to cancer and its treatments may interfere with glutamate signaling, an important part of communication between nerve cells. It may also disturb the processes that allow brain cells to produce and use energy efficiently. Together, these disruptions could contribute to difficulties with thinking and persistent mental exhaustion.

Oxaloacetate attracted the UCLA team's attention because it participates in both cellular energy production and the regulation of glutamate. The researchers wanted to learn whether providing additional oxaloacetate through a supplement might reduce the cognitive symptoms and fatigue experienced by cancer survivors.

Testing Oxaloacetate for Brain Fog and Fatigue

To investigate, the researchers carried out a phase II clinical trial involving 18 women who had been diagnosed with early-stage breast cancer between one and five years earlier. All participants were experiencing substantial cognitive difficulties when they entered the study.

The women were approximately 50 years old on average. Most had undergone chemotherapy, and nearly 90% were still receiving endocrine therapy during the trial.

Each participant was instructed to take 500 milligrams of oxaloacetate twice a day for eight weeks. The researchers tracked changes in cognitive symptoms using questionnaires completed by the participants, along with standardized tests designed to evaluate memory, attention, processing speed, and executive function. Executive function includes the mental abilities needed to organize activities, maintain focus, make plans, and manage tasks.

The study also examined fatigue, sleep, anxiety, depression, physical health, and mental well-being. Throughout the treatment period, the team monitored participants for possible side effects.

Brain Fog Scores Improved After Eight Weeks

Of the 18 women enrolled, 16 completed the full eight weeks of supplementation. Every participant who finished the treatment reported significant improvement in her cognitive symptoms.

The changes were particularly striking on the study's main measure of perceived cognitive impairment. Before treatment, the participants had an average score of 29.1. After eight weeks, that average had climbed to 55.5, placing the group in the range considered normal rather than impaired.

Signs of improvement were already apparent after four weeks, and the benefits reported by participants generally became more pronounced as treatment continued.

The results extended beyond memory and concentration. Participants reported significantly less fatigue, including the mental exhaustion that can make everyday activities difficult. They also described meaningful improvements in their ability to function physically.

Standardized cognitive testing provided additional encouraging evidence. Researchers observed improvements in processing speed and executive function, suggesting that some aspects of thinking performance may have improved alongside the participants' perceptions of their symptoms.

However, the scientists emphasized that these results remain preliminary because the trial included so few participants.

Promising Results, but More Research Is Needed

Oxaloacetate was generally well tolerated during the eight-week study. The most frequently reported side effects involved the digestive system, including indigestion, bloating, constipation, diarrhea, and nausea.

Two women stopped taking the supplement because of gastrointestinal symptoms. No serious adverse events were recorded.

Despite the encouraging improvements, the researchers cautioned against drawing firm conclusions about the supplement's effectiveness. The trial was small and did not include a placebo group or another comparison group. Without that comparison, it is not possible to determine whether oxaloacetate itself caused 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.

Larger Clinical Trial Will Test the Supplement's Benefits

To build on these initial findings, the UCLA team has been preparing a randomized, placebo-controlled phase II clinical trial involving breast cancer survivors with cancer-related cognitive impairment. The study was expected to begin enrolling participants in late 2026.

By comparing oxaloacetate with a placebo, the researchers hope to establish whether the supplement produces measurable benefits beyond those that might occur without active treatment.

The investigators are also conducting preclinical research in mice to better understand how oxaloacetate affects the body and brain. These experiments include a placebo-controlled study examining whether the molecule produces similar improvements (improved fatigue and physical function) in animals.

The research received partial financial support from the Breast Cancer Research Foundation and the National Cancer Institute.

In addition to Ganz, the study's authors were Kathleen Van Dyk, PhD, Catherine M. Crespi, PhD, Laura Petersen, MS, Mina Sedrak, MD, MS, and Julienne Bower, PhD, all affiliated with UCLA.