Nutritional supplement shows promise for cancer-related brain fog

Clinical takeaway: Anhydrous enol-oxaloacetate showed promising signals for improving persistent cancer-related cognitive impairment in breast cancer survivors, but the findings come from a small, single-arm study and require confirmation in a randomized placebo-controlled trial.

Persistent cognitive difficulties affect an estimated 15% to 25% of breast cancer survivors, and effective drug treatments remain elusive. Oxaloacetate, a naturally occurring metabolite involved in cellular energy production and glutamate regulation, may target biological processes implicated in these symptoms.

In a UCLA-led, single-arm phase II trial published in JCO Oncology Advances, 18 women with early-stage breast cancer and substantial cognitive complaints received anhydrous enol-oxaloacetate 500 mg twice daily for eight weeks. Participants averaged about 50 years of age; most had received chemotherapy, and 89% were taking endocrine therapy.

All 16 participants who completed treatment achieved clinically meaningful improvements in self-reported cognition. Mean scores on the FACT-Cog perceived cognitive impairment scale rose from 29.1 to 55.5—a 26.4-point gain that moved the group average above the impairment cutoff.

Improvements appeared by four weeks and generally increased through week eight. Participants also reported less fatigue and better physical functioning, while testing suggested gains in executive function and processing speed; these test findings were exploratory.

GI symptoms predominated, including indigestion in 39%, constipation in 28%, and bloating in 22%. Two participants discontinued treatment because of GI symptoms; no serious adverse events occurred.

The small sample and absence of a placebo group prevent attributing improvements to oxaloacetate. A randomized, placebo-controlled trial is planned.

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

Source: Ganz PA, et al. (2026 Oct 20) JCO Oncol Adv. 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