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Omega-6s Surprisingly Outperform Omega-3s in Cancer-Related Fatigue

5/21/2019 5:16:19 PM
soy oilCancer-related fatigue (CRF) generally resolves within 6 months of completing cancer treatment, but as many as 1 in 3 cancer survivors continue to experience CRF for 5 to 10 years after diagnosis. One of the mechanisms thought to contribute to CRF is chronic Inflammation, with research showing a link between an increased inflammatory state and worse CRF. Given that omega-3 polyunsaturated fatty acids (PUFAs) are known to reduce inflammation, researchers conducted a clinical trial to evaluate the effects of omega-3 supplementation on CRF.

Study examines omega-3, omega-6 for CRF

The study was a phase II, randomized, double-blind controlled trial conducted at 5 sites across the United States. Subjects were randomized to one of 3 groups: high-dose omega-3 supplementation (3.3 grams per day of DHA + EPA from six 1000-mg capsules); low-dose omega-3 and omega-6 supplementation ( 1.65 grams per day of DHA + EPA from three 1000-mg omega-3 capsules and three 1000-mg omega-6 capsules); and high-dose omega-6 supplementation (six 1000-mg omega-6 capsules). The omega-3 capsules were purely fish oil, the omega-6 capsules were purely soybean oil, all capsules contained a blend of natural lemon and rosemary extract, and all capsules were provided by Nordic Naturals (Watsonville, CA).
Ninety-seven breast cancer survivors who had completed adjuvant treatment within the last 4-36 months and with a CRF score ≥ 4 out of 10 on the Symptom Inventory (SI) were randomized, and 80 completed the 6-week trial. The mean SI CRF score decreased significantly from baseline to week 6 by 2.51 points in the omega-6 group, 2.14 points in the omega-3/omega-6 group, and 0.93 points in the omega-3 group. Similar changes were seen for daytime drowsiness, brief fatigue inventory (BFI) total score, and multidimensional fatigue symptom inventory (MFSI).   
Between-group comparisons showed that the omega-6 group had a significant reduction in SI CRF score compared with the omega-3 group (p<.01) and the omega-3/omega-6 group (p=.048), with similar results for the BFI and MFSI scores. The greatest effects of the omega-6 supplementation were seen in subjects with severe baseline CRF.

Omega-6 shown more effective than omega-3 in CRF cases

The result that omega-6 supplementation was more effective than omega-3 supplementation for CRF was unexpected, but biological data from the study supported this result. The study found that omega-6 supplementation significantly reduced tumor necrosis factor-alpha (TNF-alpha) mRNA expression. Omega-6 supplementation also decreased pro-inflammatory serum markers TNF-alpha and C-reactive protein (CRP), although the results were not statistically significant.
Although surprised by the results, the study authors propose that it is possible that CRF may be most influenced by the TNF-alpha pathway, which is modulated by omega-6 supplementation. They also suggest that additional fats in soybean oil, such as omega-9 monounsaturated fatty acids, might contribute to the biological and clinical effects observed. Consumption of soy products is controversial in women because of the isoflavones that exert estrogen-like effects, and the authors of the current study conclude that additional trials are needed to replicate the findings presented here.    
Peppone LJ, Ingliss JE, Mustian KM, et al. 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. Oxford University Press. 2018.

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