Nutritional Support in Management of Joint Discomfort and Chronic Inflammation The Chiropractic Perspective Mark Kaye, DC
Joint discomfort Joint pain and discomfort are the leading causes of disability among U.S. adults 1 Joint pain is the main complaint of the 2 most common types of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA) Data show 30% of U.S. adults report experiencing some type of joint pain every month 2 18.1% men and 23.5% women 60 y report knee pain 3 1. Murphy L and Helmick C. The impact of osteoarthritis in the United States: a population-health perspective. Am J Nurs 2012;112(3):S13-19. 2. National Health Interview Survey 2006. MMWR 2008;57(17):467. www.cdc.gov/nchs/nhis.htm 3. Andersen RE et al. Prevalence of significant knee pain among older Americans; results from NHANES III. J Am Geriatr Soc 1999;47(12):1435-8.
Common underlying causes of OA and RA Etiology of OA and RA involve Synovial inflammation Immune cell infiltration More immune cells with pro-inflammatory cytokines found in synovial tissues of RA patients as compared to OA patients Chrondrocyte pathology Leading to unresolved inflammation 1. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21:16-21. 2. Hoff P, et al. Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthop. 2013;37:145-51. 3. Otero M and Goldring MB. Cells of the synovium in rheumatoid arthritis. Chondrocytes. Arthritis Res Ther. 2007;9:220. 4. De Lange-Brokaar BJ, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage. 2012;20:1484-99.
Unresolved inflammation and chronic joint discomfort Recruitment of inflammatory cells & Primary lesion TNF-α, IL-6, IL-1 Activation of proteinases Cartilage extracellular matrix breakdown Aggrecanases, MMPs Chondrocyte death and cartilage loss Bone exposure Proteoglycan production Gupta PK et al. Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Research & Therapy 2012;3:25.
Normal vs. unresolved inflammation Normal inflammatory response Unresolved resolution of inflammation Ψ Max PMN T Max Apoptotic PMN M Ф Prolonged PMN Survival M Ф X Defective MФ Efferocytosis Magnitude T 50 MФ Efferocytosis Magnitude R i Time Time Spite et al. Cell Metab. 2014;19:21-36
Nutritional solutions to manage joint discomfort and inflammation Current options include: UC-11 and n THIAA, Xanthohumol and curcumin, omega-3 fatty acids
Undenatured collagen and kinase inhibitors: UC-II and nthiaa Undenatured type II collagen (UC-II) Reduces inflammatory response via oral tolerance 1-3 n-enriched tetrahydro iso-alpha acids (nthiaa) Reduces pro-inflammatory mediators and inhibits bone and cartilage degradation in experimental models 4,5 Data from the Functional Medicine Research Center s 12-week open-case series demonstrated that UC-II and nthiaa combination is safe and efficacious in subjects with OA and RA 6 Improvements were observed as early as 2 weeks Subjects were able to discontinue or reduce dosages of analgesic 1. Lugo JP et al. Journal of the International Society of Sports Nutrition 2013;10:48. 2. Crowley DC et al. International Journal of Medical Sciences 2009;6(6):312-321. 3. Lugo JP et al. Nutrition Journal 2016;15(1):14 4. Desai A et al. Inflammation Research 2009;58(5):229-34. 5. Konda VR et al. Arthritis & Rheumatism 2010;62(6):1683-92. 6. Lerman RH et al. Integrative Medicine: a Clinician s Journal 2015;14(5):52-61.
Anti-inflammatory supplements: Xanthohumol and curcumin Anti-oxidant and anti-inflammatory properties 1 Enhanced bioavailability through innovative technology Xanthohumol Curcumin XNT ProMatrix: a proprietary protein matrix using spent hop 2 CurQfen: a patented blend of a stable curcuminoid & galactomannan compound (from fenugreek) 3 1. Liu M, et al. Molecules. 2015;20:754-779. 2. Konda V, et al. Abstract presented at Scripps Natural Supplement Conference, January 2016. 3. Manuscript submitted for publication
Omega-3 fatty acids (EPA & DHA) EPA DHA Low pro-inflammatory potential Anti-inflammatory & pro-resolving properties
Novel nutritional supplement: specialized pro-resolving mediators Providing targeted and rapid anti-inflammatory results with endogenous molecules
Signaling Pathways of Resolution: Specialized Pro-Resolving Mediators (SPMs) EPA and DHA are Converted to SPMs that Resolve Inflammation But the conversion is inefficient in the face of inflammation SPMs EPA DHA 18-HEPE 17-HDHA Resolvins (E-series/D-series) Protectins HO HO OH Conversion from EPA and DHA is a multi-step process that may be affected by a person s health status CO OH O H COO H O H O H COO H Different SPMs work together to resolve the immune response and inflammation. Serhan CN. Nature. 2014;510:92-101
SPM (Specialized pro-resolving mediators) Tissue Impacted Progression Unresolved inflammation Resolution of inflammation SPMs Supporting the Resolution of inflammation: Curtail excessive neutrophil activity Trigger macrophages to remove dead neutrophils and debris Aid tissue remodeling Support return to homeostasis
Decision tree for clinical management of inflammation YES Does clinical evaluation suggest the presence of chronic inflammation requiring therapeutic management? Initiate condition-specific Medical Nutrition Therapy (MNT) Address dietary and life-style factors or other pro-inflammatory triggers and initiate MNT intervention to reduce magnitude of inflammation initiation as appropriate Nutrients to consider: curcumin, xanthohumol, polyphenol-rich extracts Co-initiate therapy with SPMs to actively facilitate inflammation resolution Oral intake of SPM supplements with maintenance dose of 2 SPMs softgels QD Higher intakes may be used for transitory periods for active management of inflammation load depending on clinical presentation Was positive change seen at 4-week evaluation of symptoms and biomarkers? YES NO Continue with therapeutic program MNT with SPM supplementation Evaluate recommended dose and increase for 4 weeks Ensure adherence to other diet and lifestyle recommendations Was positive change seen at 8 week evaluation of symptoms and biomarkers? YES NO Progress to maintenance dose of SPMs: 2 softgels QD Continue to monitor and avoid dietary and lifestyle triggers of inflammation and assess biomarkers of inflammation as routine GCPs Consider increasing SPM dose for additional 4 weeks Continue to monitor and avoid dietary and lifestyle triggers of inflammation, and biomarkers of inflammation as routine GCPs May consider additional treatments to manage disease
Summary of managing patients with chronic inflammation and joint pain Current supplements UC-II and n-enriched THIAA offer evidence based support in nutritional management of patients with joint discomfort Safe Effective Well tolerated Consider other bioavailable phytonutrients targeting inflammation Xanthohumol Curcumin Recommend using SPMs as a novel strategy to actively manage associated symptoms of chronic inflammation to provide resolution Balance inflammation initiation and resolution Manage trigger factors such as underlying diet and body weight
Relevance to the chiropractic clinician: Chiropractors are considered by patients to be pain specialists Relief of symptoms, and the underlying contributions to the pain, is a key focus of the chiropractic clinician and their patients Many patients are nutrient-deficient including omega-3 fats, phytonutrient protectant compounds (hops) Dietary and common lifestyle factors results in prolongation of inflammation (lack of resolution) Foods communicate with the immune system and some nutrients (UCII) may moderate immune response leading to clinical improvement
To learn more check out the following resources at www.mhicn.com Informational videos, podcasts, roundtable discussions and downloadable publications on nutritional solutions for chronic inflammation Posters from national and international congresses Nutritional Approach for Relief of Joint Discomfort: A 12-week, Open-case Series and Illustrative Case Report Total Antioxidant Capacity of Diet and Plasma Markers of Oxidant/antioxidant Status are Associated with Low-Grade Chronic Inflammation