EPA and DHA are essential omega-3 fatty acids from fish oil that are well known to promote healthy inflammatory balance. By acting as substrates for the body’s various anti-inflammatory mediators, EPA and DHA are essential to the promotion of a healthy inflammatory responses.
C-reactive protein (CRP) is an inflammatory marker found in the blood, the levels of which rise in response to inflammation.
Studies show that the higher the omega-3 levels in the blood of healthy individuals, the lower the CRP concentration.8
Supplementation with EPA and DHA has been shown in some, although not all, studies to decrease CRP levels as well as other biomarkers of inflammation in the blood.9-12
Published clinical trials and case studies also demonstrate the important role of EPA/DHA in supporting the health of the cardiovascular, immune, and nervous systems including mood.12-16
Curcumin exerts its anti-inflammatory effects via a number of diverse mechanisms involving cell signaling molecules known as transcription factors (such as nuclear factor KappaB (NF-KappaB)), inflammatory cytokines (such as tumor necrosis factor (TNF) and interleukin 6 (IL-6)) and enzymes (such as cyclooxygenase 2 (COX-2)).19
Curcumin is a potent suppressor of NF-KappaB and has been shown to decrease NF-KappaB in humans when taken as a supplement. 20
Because of its effects on NF-KappaB, Curcumin is a powerful suppressor of COX-2, the key enzyme in the formation of potent mediators in the inflammatory response.22
Due to its anti-inflammatory activity, curcumin demonstrates beneficial effects on muscle regeneration after trauma and the ability to offset muscle-damaging effects of downhill running.23-24
Curcumin speeds recovery of running performance in mice by reducing inflammation-induced deficits in regeneration of muscle fibers, soreness, and fatigue.23
Curcumin ameliorates pain sensitivity via mechanisms that are likely independent of its anti-inflammatory activity according to a number of animal studies.25-29 For example, in insulin-treated diabetic mice exhibiting increased sensitivity to pain either curcumin or resveratrol taken by mouth significantly reduced pain sensitivity.29
Resveratrol decreases blood indices of oxidative and inflammatory stress.45
Like curcumin, resveratrol decreases inflammatory cytokines such as interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) by inhibiting NF-KappaB signaling.42
Promising results from preclinicial and animal data are beginning to emerge.43-44
A double blind placebo controlled trial published in 2011 randomized two groups (10 each) of normal-weight healthy subjects to placebo or a standardized Polygonum cuspidatum extract containing 40 mg resveratrol daily for six weeks. Blood indices of oxidative and inflammatory stress were measured and resveratrol was found to induce significant reductions in reactive oxygen species generation, NF-kappaB binding, and numerous pro-inflammatory markers including TNF-alpha, IL-6, and C-reactive protein compared with the baseline and the placebo.45
Resveratrol, like curcumin, significantly decreases sensitivity to pain in animal studies.29-36
In rodents, pro-inflammatory molecules known as cytokines are key players in the development of back and leg pain resulting from unhealthy discs and spinal nerves. In rodents, by decreasing pro-inflammatory cytokines, resveratrol significantly reduces pain behavior with disc-related pain.37
Resveratrol alone suppressed inflammation and destruction of inflamed joint cells in vitro.38
Icariin has been shown to protect DNA, nerve cells, and stem cells against free radical-induced damage in vitro.47-48, 50
Like resveratrol and curcumin, icariin appears to exert its potent anti-inflammatory effects via inhibition of NF-KappaB.49
In recent studies, icariin significantly decreased lung inflammation in mice by inhibiting a number of inflammatory compounds in mice such as tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), cycloxygenase-2 (COX-2), prostaglandin E2 (PGE(2)), nitric oxide (NO) as well as NF-kappaB activation.49,51
In an in vitro study icariin partially reversed markers of inflammation and inflammation-induced joint degradation in cartilage cells from mice.46
Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23.
Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006 Apr;65(4):326-31.
Fontani G, Suman AL, Migliorini S, Corradeschi, Ceccarelli I, Aloisi A, Carli G. Administration of Omega-3 Fatty Acids Reduces Positive Tender Point Count in Chronic Musculoskeletal Pain Patients. Journal of Complementary and Integrative Medicine. 2010 Jan;7(1):Article 35.
Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009 Jan;41(1):40-59.
Sharma S, Chopra K, Kulkarni SK. Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain participation of nitric oxide and TNF-alpha. Phytother Res. 2007 Mar;21(3):278-83.
Sharma S, Kulkarni SK, Chopra K. Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain. Fundam Clin Pharmacol. 2007 Feb;21(1):89-94.
Sharma S, Chopra K, Kulkarni SK. Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF-alpha. Phytother Res. 2007 Mar;21(3):278-83.
Shakibaei M, Csaki C, Nebrich S, Mobasheri A. Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem Pharmacol. 2008 Dec 1;76(11):1426-39.
Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. Epub 2006 May 26.
Zhao F, Tang YZ, Liu ZQ. Protective effect of icariin on DNA against radical-induced oxidative damage. J Pharm Pharmacol. 2007 Dec;59(12):1729-32.
Wo YB, Zhu DY, Hu Y, Wang ZQ, Liu J, Lou YJ. Reactive oxygen species involved in prenylflavonoids, icariin and icaritin, initiating cardiac differentiation of mouse embryonic stem cells. J Cell Biochem. 2008 Apr 1;103(5):1536-50.