Polyunsaturated Fatty Acids, Exercise, and Fatigue in Breast Cancer

2021 Year in Review - HER2-Negative Breast Cancer

According to several studies, humans developed on a diet with a ratio of omega-6 to omega-3 essential fatty acids of 1, whereas the ratio in Western diets is approximately 15:1. When compared with the diet on which human beings developed and their genetic patterns were established, Western diets are low in omega-3 fatty acids and excessive in omega-6 fatty acids. A ratio of 4:1 was linked to a 70% reduction in total mortality in secondary prevention of cardiovascular disease. In women with breast cancer, a lower omega-6/omega-3 ratio was linked to a lower risk. According to these studies, the ideal ratio varies depending on the condition being studied. Chronic diseases are multigenic and multifactorial, which supports this theory. As a result, it is probable that the therapeutic amount of omega-3 fatty acids will be determined by the severity of sickness caused by a hereditary predisposition. A lower omega-6/omega-3 fatty acid ratio is preferable for reducing the risk for many chronic diseases that are prevalent in Western societies as well as developing countries that export to the rest of the globe.1

Cancer-related fatigue is one of the most common and debilitating symptoms experienced by cancer survivors. It causes substantial degradation in quality of life because of its negative effect on everyday activities, job, social activities, and mood. A recent study surprisingly found that omega-6 polyunsaturated fatty acid (PUFA) supplementation reduced cancer-related fatigue in exhausted American breast cancer survivors when compared with omega-3 PUFA supplementation, and that omega-6 PUFA supplementation lowered proinflammatory blood markers.2

Meanwhile, a recent meta-analysis of individual patient data demonstrated that exercise therapies have a considerable impact on cancer-related fatigue. In a randomized controlled trial among early-stage Japanese breast cancer survivors in which the effect of baseline blood PUFA characteristics on change in cancer-related fatigue during the 12-week trial by exercise group was studied and confirmed that increased Cancer Fatigue Scale was associated with docosahexaenoic acid and omega-3 index, and that docosahexaenoic acid was positively correlated with change in cancer-related fatigue in the control group.2

Furthermore, in the exercise group, baseline eicosapentaenoic acid was favorably connected with leg strength. The effect of exercise on cancer-related fatigue may be related to blood PUFA balance.2 If there is indeed a link between omega-6 and cancer-related fatigue, then finding the right balance between an increased omega-6 to omega-3 ratio to combat fatigue while not going too high to protect against mortality and cardiovascular disease will be the challenge. Higher essential fatty acid levels in people who exercised are likely to help them build muscle strength. To better understand the interplay between PUFAs and exercise in the treatment of cancer-related fatigue, more research is needed.2


  1. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56:365-379.
  2. Matsuoka Y, Tsuji K, Ochi E. Polyunsaturated fatty acids, exercise, and cancer-related fatigue in breast cancer survivors. Front Physiol. 2021;12:759280.

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