For some breast cancer survivors, the effects of treatment may persist long after their cancer care ends. Memory loss, difficulty concentrating and persistent exhaustion can disrupt daily life, sometimes for years. Now, researchers at UCLA Health Jonsson Comprehensive Cancer Center have found promising early evidence that a supplement containing a natural molecule may help relieve these symptoms.
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 notable improvements in their thinking, memory, concentration, and fatigue.
The results, published in JCO advances in oncologyalso showed improvements on cognitive tests measuring how quickly participants processed information and completed tasks requiring planning, attention and mental flexibility. Although larger studies are needed to confirm these findings, they suggest a potential new way to address a problem that has long been difficult to treat.
“Cancer-related cognitive impairment can persist long after treatment ends and have a significant impact on a person’s daily life. Yet we still have very few effective treatments,” said Dr. Patricia Ganz, first author of the study and Distinguished Professor of Medicine at the David Geffen School of Medicine at UCLA and the UCLA Fielding School of Public Health.
Why brain fog may persist after cancer treatment
Cognitive difficulties are a lasting concern for many breast cancer survivors. Researchers estimate that about 15 to 25 percent of people have persistent problems with memory, concentration, or other thinking skills after their diagnosis and treatment. These symptoms are often described as “chemo brain” or “brain fog.”
Despite its name, chemotherapy is not necessarily the only cause. Scientists increasingly recognize that cancer-related cognitive impairment may develop through several overlapping processes. Cancer itself, chemotherapy, endocrine therapy, inflammation, hormonal changes, and other biological and behavioral influences can all contribute.
Because the causes are complex and effective treatments remain limited, researchers are studying ways to address the underlying changes that can disrupt normal brain function.
One area of interest concerns the relationship between inflammation, brain chemistry and energy production. Inflammation related to cancer and its treatments can interfere with glutamate signaling, an important part of communication between nerve cells. It can also disrupt the processes that allow brain cells to produce and use energy efficiently. Together, these disruptions could contribute to difficulty thinking and persistent mental exhaustion.
Oxaloacetate caught the attention of the UCLA team because it is involved in both cellular energy production and glutamate regulation. The researchers wanted to know if supplementing with oxaloacetate through a supplement could reduce the cognitive symptoms and fatigue experienced by cancer survivors.
Testing Oxaloacetate for Brain Fog and Fatigue
To investigate, researchers conducted 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 significant cognitive difficulties at the time of entry into the study.
The women were on average around 50 years old. Most had undergone chemotherapy and almost 90% were still receiving endocrine treatment during the trial.
Each participant was required to take 500 milligrams of oxaloacetate twice daily for eight weeks. Researchers tracked changes in cognitive symptoms using questionnaires completed by participants, as well as standardized tests designed to assess memory, attention, processing speed and executive function. Executive function includes the mental abilities needed to organize activities, maintain concentration, make plans, and manage tasks.
The study also looked at fatigue, sleep, anxiety, depression, physical health and mental well-being. Throughout the treatment period, the team monitored the 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 completed treatment reported significant improvement in their cognitive symptoms.
The changes were particularly striking on the study’s main measure of perceived cognitive impairment. Before treatment, participants had an average score of 29.1. After eight weeks, that average had increased to 55.5, putting 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 go beyond memory and concentration. Participants reported significantly less fatigue, including mental exhaustion that can make daily activities difficult. They also described significant improvements in their ability to function physically.
Standardized cognitive tests have provided additional encouraging evidence. The researchers observed improvements in processing speed and executive function, suggesting that some aspects of thinking performance may have improved alongside participants’ perception of their symptoms.
However, the scientists stressed that these results remained preliminary because the trial included very few participants.
Promising results, but more research needed
Oxaloacetate was generally well tolerated during the eight-week study. The most commonly reported side effects involved the digestive system, including indigestion, bloating, constipation, diarrhea, and nausea.
Two women stopped taking the supplement due to gastrointestinal symptoms. No serious adverse events were recorded.
Despite the encouraging improvements, researchers cautioned against drawing firm conclusions about the supplement’s effectiveness. The trial was small and did not include a placebo or other comparison group. Without this comparison, it is not possible to determine whether the oxaloacetate itself caused the improvements.
“These initial results give us good reason to continue investigating oxaloacetate as a potential approach to managing cognitive problems after breast cancer treatment,” Ganz said.
Larger clinical trial will test supplement’s benefits
To build on these initial results, the UCLA team prepared a randomized, placebo-controlled phase II clinical trial involving breast cancer survivors with cancer-related cognitive impairment. The study was expected to begin recruiting participants in late 2026.
By comparing oxaloacetate to a placebo, researchers hope to determine whether the supplement produces measurable benefits beyond those that might occur without active treatment.
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, study 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.
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