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Omega-6: Omega-3 PUFA Ratio, Pain, Functioning, and Distress in Adults with Knee Pain

Sibille, Kimberly T. MA, PhD; King, Christopher; Garrett, Timothy J.; Glover, Toni L.; Zhang, Hang; Chen, Huaihou; Reddy, Divya; Goodin, Burel R.; Sotolongo, Adriana; Petrov, Megan E.; Cruz-Almeida, Yenisel; Herbert, Matthew; Bartley, Emily J.; Edberg, Jeffrey C.; Staud, Roland; Redden, David T.; Bradley, Laurence A.; Fillingim, Roger B.
The Clinical Journal of Pain: Post Acceptance: May 24, 2017
doi: 10.1097/AJP.0000000000000517
Original Article: PDF Only


Osteoarthritis (OA) is associated with inflammation, chronic pain, functional limitations, and psychosocial distress. High Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with lower levels of inflammatory mediators, anti-nociception, and adaptive cognitive/emotional functioning. High Omega-6 (n-6) PUFAs are associated with inflammation, nociception, and psychological distress. While findings related to n-3 supplementation in knee OA are mixed, consideration of the n-6:n-3 ratio and additional outcome measures may provide improved understanding of the potential relevance of these fatty acids in OA. Based on recommended and typical ranges of the n-6:n-3 ratio, we hypothesized that in adults with knee pain, those with a high n-6:n-3 ratio would have greater pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared to those with a low n-6:n-3 ratio.


A cross-sectional investigation of clinical and experimental pain and physical and psychosocial functioning was completed in 167 adults ages 45-85 meeting knee OA screening criteria. Blood samples were collected and the plasma n-6:n-3 PUFA ratio determined. Quartile splits were computed and low (n=42) and high (n=41) ratio groups were compared.


The high ratio group reported greater pain and functional limitations, (all P’s<0.04), mechanical temporal summation (hand and knee, P<0.05), and perceived stress (P=0.008) but not depressive symptoms.


In adults with knee pain, a high n-6:n-3 ratio is associated with greater clinical pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared to a low ratio group. Findings support consideration of the n-6:n-3 PUFA ratio and additional clinical endpoints in future research efforts.

Sources of Funding: The current study was supported by the National Institutes of Health/National Institute on Aging (R37AG033906), the University of Florida Clinical and Translational Science Institute (UL1TR000064 and KL2TR000065), and the University of Alabama at Birmingham Center for Clinical and Translational Science Institute (UL1TR000165). KTS is funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, K23AR062099; CK by the National Institute on Dental and Craniofacial Research, K99DE022368; YCA by the National Institute on Aging, K01 AG048259; and EJB by the NIA K99AG052642. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflicts of Interest: Dr. Fillingim reports grants from Pfizer, personal fees from Algynomics, outside the submitted work. All other authors report no competing interests.

Reprints: Kimberly T. Sibille, MA, PhD, Department of Aging and Geriatric Research, University of Florida, P.O. Box 112610, Gainesville, FL 32610-3628 (e-mail:

Received April 29, 2016

Accepted May 15, 2017

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