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

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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.

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Abbreviations

MRI:

Magnetic resonance imaging

fMRI:

Functional magnetic resonance imaging

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor alpha

AHN:

Adult hippocampal neurogenesis

EPA:

Eicosapentaenoic acid

DHA:

Docosahexaenoic acid

n-3 FA:

Omega-3 fatty acid

DOX:

Doxorubicin

RCT:

Randomized controlled trial

IL-1β:

Interleukin one beta

CES-D:

Center for Epidemiologic Studies Depression

NF-KB:

Nuclear factor kappa beta

CRP:

C-reactive protein

PPAR-α:

Peroxisome proliferator-activated receptor alpha

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Acknowledgements

Maryam Lustberg, MD, MPH for her expertise in clinical implications of chemotherapy and her contributions to preliminary data. TO and ACD received funding on this topic from NCI (R01CA18997); the funding source provides salary support for TO, ACD, and MMGD but was not directly involved in any aspect of the preparation of this review paper.

Author contributions

TSO & ACD were involved in conceptualization of the manuscript; TSO, ACD, MMGD, and KRW were involved in writing the manuscript; all authors were involved in revision of the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Human Sciences, The Ohio State University, 325 Campbell Hall, 1787 Neil Avenue, Columbus, OH, 43210, USA

    Tonya S. Orchard & Kellie R. Weinhold

  2. Department of Neuroscience, The Ohio State University Wexner Medical Center, 614 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH, 43210, USA

    Monica M. Gaudier-Diaz & A. Courtney DeVries

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  1. Tonya S. Orchard
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  2. Monica M. Gaudier-Diaz
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Correspondence to Tonya S. Orchard.

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Orchard, T.S., Gaudier-Diaz, M.M., Weinhold, K.R. et al. Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits. Breast Cancer Res Treat 161, 391–398 (2017). https://doi.org/10.1007/s10549-016-4073-8

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  • DOI: https://doi.org/10.1007/s10549-016-4073-8

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