The Effects of Dietary Supplementation With Lipinova on Inflammatory and Proresolving Lipid Mediator Profiles in Patients Undergoing Total Knee Arthroplasty

The resolution of acute inflammation was once thought to be a passive process, meaning that inflammatory mediators from the acute response (e.g. chemoattractants, complement components, prostaglandins, chemokines and cytokines) would simply dilute and dissipate to stop the infiltration of leucocytes into the tissues. Conversely, more recently it was shown that tissue resolution of inflammation is actually an active programmed process, requiring a temporal lipid mediator class switch that leads to the production of specialized pro-resolving mediators (SPMs) derived from essential fatty acids.1-4

There are several distinct classes of SPMs: the lipoxins derived from the n-6 polyunsaturated fatty acid (n-6 PUFA), AA, and the resolvins, protectins and maresins derived from the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These SPMs counter regulate pro-inflammatory mediator production, including prostaglandins, leukotrienes, and select cytokines. They also stimulate leucocyte responses including bacterial phagocytosis and efferocytosis of apoptotic cells, key processes in the clearance of infections and return to homeostasis, without apparent immune suppression.5-7 In addition, Serhan and colleagues8 recently identified a new family of sulfido-conjugated mediators that promote wound repair and tissue regeneration. An increasing body of research has shown the beneficial actions of these mediators on improving the inflammatory process in several disease states, such as sepsis, peritonitis, colitis, Alzheimer's disease and peripheral vascular disease.9-13 In addition, it was demonstrated that RvE1 has direct bone-preserving and bone regeneration functions in a mouse model of periodontal disease.14

There is also increasing evidence suggesting that inflammation has a significant impact on postoperative clinical outcomes. Kimura et al.15 demonstrated that patients who developed postoperative infectious complications after liver resection had significantly higher levels of IL-6 on days 0 and 1 after surgery than did those without infections. In addition, elevated pre-operative CRP-levels in patients undergoing palliative surgery is associated with a higher complication rates and decreased overall survival.16 Pillai et al.17 demonstrated two groups among patients undergoing abdominal aorta aneurysm (AAA) surgery based on their temporal profile: one group displayed a pro-inflammatory profile throughout the intra-operative and postoperative time course, while the other group was characterized by a pro-resolving mediator profile. The authors suggested that these two broad categories may reflect an early resolver population and a delayed resolver population and that enhancing the patient profile of endogenous pro-resolving mediators may shorten recovery times, resolution and improve outcomes in these patients.

In this proposal the investigators aim to determine whether pre-operative dietary supplementation with a nutritional supplement containing omega-3 PUFA and its derivatives will improve the metabolo-lipidomic, inflammatory, and resolution profile of patients undergoing total knee arthroplasty. Lipinova® (Solutex) is an over the counter nutritional supplement that differs from other commercially available "Fish Oil" in that it contains standardized levels of the omega 3- PUFAs, Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) as well as the derived monohydroxylated precursors (17-HDHA, 18-HEPE and 14-HDHA). The standardized levels are obtained from anchovy and sardine oil through advanced fractionation technology and purification technology.

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