Omega-3 (ω3) supplementation versus omega-6 (ω6) supplementation for fatigue among breast cancer survivors: A URCC NCORP RCT.

Cancer-related fatigue (CRF) is one of the most frequently reported and disabling symptoms in cancer survivors. With its negative impact on the activities of daily living, work, social activities, and mood, CRF causes severe impairment of quality of life. A previous study showed that omega-6 polyunsaturated fatty acid (PUFA) supplementation unexpectedly reduced CRF compared with omega-3 PUFA supplementation and that omega-6 PUFA supplementation reduced pro-inflammatory serum markers in fatigued American breast cancer survivors. Meanwhile, a recent meta-analysis of individual patient data revealed significant benefits of exercise interventions on CRF. Recently, we completed our randomized controlled trial among early-stage Japanese breast cancer survivors, in which we examined the effect of baseline blood PUFA characteristics on change in CRF during the 12-week trial by exercise group and confirmed that increased Cancer Fatigue Scale (CFS) was associated with both docosahexaenoic acid (DHA) (p = 0.06) and omega-3 index (p = 0.08) at baseline in all participants (n = 46, omega-6/omega-3 ratio = 6.79, SD = 1.90). On the contrary, DHA at baseline was positively correlated with change in CRF (r = 0.40, p = 0.06) in the control group (n = 24, omega-6/omega-3 ratio = 7.0). Moreover, eicosapentaenoic acid (EPA) at baseline was positively correlated with leg strength (r = 0.39, p = 0.10) in the exercise group. In conclusion, blood PUFA balance might be associated with the effect of exercise on CRF. In addition, higher EPA in individuals who conducted exercise likely has a beneficial effect on muscle strength. Further investigation is needed to clarify the interaction between PUFAs and exercise for alleviating CRF.

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Multicenter Randomized Controlled Trial of Omega-3 Fatty Acids Versus Omega-6 Fatty Acids for the Control of Cancer-Related Fatigue Among Breast Cancer Survivors

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz005 ◽

2019 ◽

Vol 3 (2) ◽

Cited By ~ 5

Author(s):

Luke J Peppone ◽

Julia E Inglis ◽

Karen M Mustian ◽

Charles E Heckler ◽

Gilbert D A Padula ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Mrna Levels ◽

Omega 3 ◽

Symptom Index ◽

Cancer Related Fatigue ◽

Brief Fatigue Inventory ◽

Omega 6

Abstract Background Cancer-related fatigue (CRF) is a common side effect of adjuvant therapy and becomes a chronic problem for approximately one-third of survivors. Omega-3 polyunsaturated fatty acids (O3-PUFA) demonstrated preliminary antifatigue effects in previous research, but have not been investigated in fatigued cancer survivors. Methods Breast cancer survivors 4–36 months posttreatment with a CRF score of 4 or more of 10 using the symptom inventory (SI) were randomly assigned to O3-PUFA (fish oil, 6 g/d), omega-6 PUFA (O6-PUFA; soybean oil, 6 g/d), or a low-dose combination of O3-/O6-PUFA (3 g/d O3-PUFA and O6-PUFA) for 6 weeks. CRF was assessed by the SI (screening question), the Brief Fatigue Inventory, and the Multidimensional Fatigue Symptom Index. Protein and mRNA levels of inflammatory and antioxidant biomarkers, along with fatty acid and lipid levels, were assessed at baseline and week 6. Statistical tests were two-sided. Results A total of 108 breast cancer survivors consented; 97 subjects were randomly assigned and 81 completed the trial. The SI CRF score decreased by 2.51 points at week 6 with O6-PUFA and by 0.93 points with O3-PUFA, with statistically significant between-group difference (effect size = −0.86, P < .01). Similar changes were observed for the Brief Fatigue Inventory and Multidimensional Fatigue Symptom Index but were not statistically significant. Stratified analyses showed the largest benefit was observed in those with severe baseline CRF (≥7). Compared with O3-PUFA, O6-PUFA supplementation statistically significantly decreased proinflammatory markers in the TNF-α signaling pathway. Conclusion Contrary to our original hypothesis, O6-PUFA statistically significantly reduced CRF compared with O3-PUFA. Further research is needed to confirm these findings and to elucidate mechanisms of action.

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Efficacy of omega-3 (ω3) supplementation versus omega-6 (ω6) supplementation for reducing pain among breast cancer survivors: A URCC NCORP RCT.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.10118 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 10118-10118

Author(s):

Luke Joseph Peppone ◽

Julia Ellen Inglis ◽

Karen Michelle Mustian ◽

Kah Poh Loh ◽

Eva Culakova ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Omega 3 ◽

Omega 6

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Association between blood omega-3 polyunsaturated fatty acids and the gut microbiota among breast cancer survivors

Beneficial Microbes ◽

10.3920/bm2019.0034 ◽

2019 ◽

Vol 10 (7) ◽

pp. 751-758 ◽

Cited By ~ 6

Author(s):

A. Horigome ◽

R. Okubo ◽

K. Hamazaki ◽

T. Kinoshita ◽

N. Katsumata ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Gut Microbiota ◽

Polyunsaturated Fatty Acids ◽

Cancer Survivors ◽

Breast Cancer Survivors ◽

Cross Sectional Study ◽

Omega 3 ◽

Cross Sectional ◽

History Of

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.

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