Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits

Abstract

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.

Protective Effects of Omega-3 Fatty Acids in Cancer-Related Complications

“…As for the depression-like behavior related to cancer treatment, Orchard et al (2016) considered that omega-3 supplementation could be beneficial for chemotherapy-induced cognitive alterations, such as depression [132]. Regarding preclinical evidence, rats submitted to repeated LPS administration displayed depressive-like behaviors, associated with decreased levels of monoamines besides an increase of apoptotic markers in the hippocampus and prefrontal cortex.…”

Pathogenesis, Assessments, and Management of Chemotherapy-Related Cognitive Impairment (CRCI): An Updated Literature Review

“…This may be related to its role as a reactive oxygen species scavenger in the brain, reducing the oxidative stress and inflammation. Some researchers also recommend that a diet rich in long chain, omega-3 fatty acids and low sugar content could protect neurons from the toxic effects of chemotherapy through preventing or reducing neuroinflammation and oxidative stress [ 87 ]. Therefore, adjusting the diet structure and providing targeted nutrition can provide the basis for the treatment of CRCI.…”

Hippocampus—Related Cognitive and Affective Impairments in Patients With Breast Cancer—A Systematic Review

“…Secondly, it was based on the overall data retrieved from the literature, so the stated limitations of the studies must therefore also be regarded as limitations of the present work. It cannot be completely ruled out that errors have occurred or wrong conclusions have been drawn trying to link and compare studies using different experimental designs, chemotherapeutic agents, patient populations (12), and tests measuring hippocampus-related changes and resulting CRCI and CRAI differently. Thereby, as already emphasized, comparisons, and connections between studies conducted with animals and those with humans must also be drawn with caution.…”

“…Thereby, an increasing number of studies focused on measuring cancer-related cognitive impairments (CRCI) in those patients over the last ten years (12). They revealed attention, processing speed, executive function, and working memory as the most affected domains (9,13,14).…”