Bring back clarity: what scientists have learned about "head fog" after cancer treatment

Cancer treatment can be left behind, and difficulties with memory and concentration can persist for years. Scientists at the University of California at Los Angeles have tested whether a dietary supplement with oxaloacetate can alleviate these symptoms after breast cancer. After eight weeks, participants in the small study reported clearer thinking and less fatigue, and some test results also improved. What is called "fog in the head", why researchers are interested in cellular metabolism and how convincing the first results are — in the Izvestia material.

Why it can be difficult to concentrate after treatment

Problems with memory and attention after cancer are sometimes referred to as "head fog." It may become more difficult for a person to hold information, focus, and organize routine activities. The severity of these changes varies.

According to UCLA estimates, 15 to 25% of women with breast cancer may experience persistent cognitive difficulties. Such symptoms can persist even after the completion of basic treatment, affecting the return to work and daily activities.

Historically, these complaints were often associated with chemotherapy, hence the English expression chemo brain. However, the causes are more complicated: the disease itself, various types of therapy, inflammation, hormonal changes, and other biological and behavioral factors may be important.

Therefore, researchers are looking for ways to influence the processes that can support the symptoms, rather than considering them solely as a consequence of one type of treatment.

Why did scientists turn to cellular metabolism?

Oxaloacetate is a compound that is naturally present in the body and is involved in the processes of energy production by cells. Researchers are also interested in its role in the regulation of glutamate, a substance involved in the transmission of signals between nerve cells.

According to the team's hypothesis, inflammatory processes associated with cancer and its treatment can disrupt glutamate signaling and energy metabolism in the brain. These changes have the potential to contribute to cognitive difficulties and mental fatigue.

The participation of oxaloacetate in both processes became the basis for testing the additive. However, a biologically plausible mechanism by itself does not prove that taking a substance will improve the condition of patients.

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The interest in inflammation is based on previous observations. In the Thinking and Living with Cancer study, which UCLA reported in 2022, scientists observed women aged 60 and over after breast cancer and participants without cancer. The data has been collected for five years.

Higher levels of C-reactive protein, a marker of inflammation, were associated with more pronounced complaints of cognitive difficulties in cancer survivors. At the same time, no similar relationship was found with the results of standard neuropsychological tests. This work supported interest in a possible mechanism, but did not test the effectiveness of oxaloacetate.

Who participated in the new study

The second phase clinical trial included 18 women who reported significant cognitive difficulties. It has been from one to five years since they were diagnosed with breast cancer. The average age of the participants was about 50 years old.

Most had previously received chemotherapy, and almost 90% were continuing endocrine therapy at the time of the study. Therefore, the expression "after treatment" in this case does not mean that all types of antitumor therapy have already been completed.

According to the registration card of the study at the US National Cancer Institute (NCI), women without signs of active or recurrent breast cancer were allowed to participate. At least 12 months should have passed after surgery, chemotherapy, or radiation therapy. For eight weeks, participants took 500 mg of oxaloacetate twice a day. This is a scheme of a research course, the effectiveness of which has yet to be confirmed.

Before and during the appointment, the researchers assessed complaints using questionnaires and conducted standardized tests. They tested attention, memory, information processing speed, and executive functions—the ability to plan actions, hold goals, and manage tasks. Additionally, fatigue, sleep, anxiety, depressive symptoms, and tolerance to the supplement were monitored.

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What has changed in eight weeks

16 of the 18 participants completed the course. All 16 reported improvements in cognitive symptoms. The changes were noticeable after four weeks and generally became more pronounced by the end of the study.

The average score of the main indicator reflecting the subjective assessment of cognitive impairment increased from 29.1 to 55.5. According to the authors' interpretation, the average result of the group moved from the range of violations to the range considered normal on this scale.

When reading these figures, it is important to consider the direction of the assessment: a higher score here corresponds to a more favorable condition. This is not an indicator of intelligence or a percentage of stored memory. An almost twofold increase in the value cannot be interpreted as a "twofold" improvement in brain function.

Participants also reported less fatigue, including mental fatigue, and improved physical functioning. Neuropsychological tests showed positive dynamics in the speed of information processing and executive functions. The results were not limited to answering questions about well-being. But the researchers emphasize that the changes in the test indicators should still be considered preliminary due to the small number of participants.

Why can't the effect of the supplement be confirmed yet?

The main limitation of the work is the lack of a placebo and another comparison group. The researchers saw improvements during the course, but were unable to determine which part of them was related to oxaloacetate. Without a control group, it is difficult to separate the expected effect of the substance from the participants' expectations, natural fluctuations in symptoms, and other changes in condition. Repeated cognitive tests should also take into account the possible impact of familiarity with the tasks.

A small sample limits the transfer of results to other patients. The study involved only women with a history of breast cancer. It does not show whether the result will be the same for other tumors, at other stages of treatment, or in people with other causes of memory impairment.

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Portability also requires further study. The most common adverse events were gastrointestinal symptoms: indigestion, bloating, constipation, diarrhea, and nausea. Two participants stopped receiving because of such complaints.

No serious adverse events were reported. However, eight weeks of follow-up for a small group is insufficient to draw conclusions about rare complications and long-term safety.

What kind of help is available for memory problems

While the new approach is being tested, complaints about memory and concentration should be discussed with the treating team. The NCI notes that the assessment should take into account concomitant conditions: sleep disorders, fatigue, anxiety, depression, and malnutrition. Working with them can also alleviate cognitive difficulties.

For everyday tasks, the institute recommends maintaining a daily routine, planning tasks that require concentration, while feeling well, and using notes or electronic reminders. Appropriate physical activity can be discussed with your doctor.

The first study of oxaloacetate gives reason to continue the search, but so far it does not offer a confirmed treatment. Its practical value is in trying to find help for people whose underlying illness is a thing of the past, and difficulties with memory, attention, and fatigue continue to affect their lives.