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Omega-3 PUFA Ratio, Pain, Functioning, and Distress in Adults With Knee Pain

Sibille, Kimberly T. MA, PhD*,†; King, Christopher PhD; Garrett, Timothy J. PhD§; Glover, Toni L. ARNP, PhD†,∥; Zhang, Hang MS; Chen, Huaihou Phd; Reddy, Divya BS; Goodin, Burel R. Phd#; Sotolongo, Adriana MPH**; Petrov, Megan E. PhD††; Cruz-Almeida, Yenisel MSPH, PhD*,†; Herbert, Matthew PhD‡‡; Bartley, Emily J. PhD; Edberg, Jeffrey C. PhD**; Staud, Roland MD§§; Redden, David T. PhD∥∥; Bradley, Laurence A. PhD**; Fillingim, Roger B. PhD

doi: 10.1097/AJP.0000000000000517
Original Articles

Objectives: 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. On the basis of 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 with those with a low n-6:n-3 ratio.

Materials and Methods: A cross-sectional investigation of clinical and experimental pain and physical and psychosocial functioning was completed in 167 adults ages 45 to 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.

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

Discussion: 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 with a low ratio group. Findings support consideration of the n-6:n-3 PUFA ratio and additional clinical endpoints in future research efforts.

Departments of *Aging & Geriatric Research

§Pathology, Immunology, and Laboratory Medicine

Biobehavioral Nursing Science, College of Nursing



Pain Research & Intervention Center of Excellence, University of Florida, Gainesville, FL

Department of Anesthesia, Cincinnati Children’s Hospital, Cincinnati, OH

Department of #Psychology

**Medicine/Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham

∥∥Biostatistics Department, School of Public Health University of Alabama at Birmingham, Birmingham, AL

††College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ

‡‡Center of Excellence for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, and University of California, San Diego, CA

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).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

K.T.S. is funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, K23AR062099; C.K. by the National Institute on Dental and Craniofacial Research, K99DE022368; Y.C.-A. by the National Institute on Aging, K01 AG048259; and E.J.B. by the NIA K99AG052642. R.B.F. reports grants from Pfizer, personal fees from Algynomics, outside the submitted work. The remaining authors declare no conflict of interest.

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

Received in revised form April 21, 2017

Accepted May 15, 2017

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