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 address inflammatory processes as well as natural tissue repair processes. Studies provide some evidence that EPA and DHA help reduce minor pain associated with musculoskeletal exercise-induced inflammatory conditions.
1-3 Omega-3 fatty acids also have been shown to inhibit bone loss and cartilage degradation in in vitro and animal studies.4-7 A meta-analysis of 17 randomized, controlled trials assessing the pain relieving effects of omega-3 fatty acids supplements concluded that supplementation for 3–4 months significantly addresses joint health issues.1 C-reactive protein (CRP) is an inflammatory marker found in the blood, the levels of which rise in response to the inflammatory response process. 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 The US Food and Drug Administration has determined that “supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.”
Resveratrol has anti-inflammatory properties and has been shown to blood indices of oxidative and inflammatory stress.46 Like curcumin, resveratrol decreases inflammatory cytokines such as interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) by inhibiting NF-KappaB signaling.43 Results from human trials confirming resveratrol’s clinical benefits are beginning to emerge.44-45
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.46
Resveratrol, like curcumin, significantly decreases sensitivity to pain in animal studies.30-37 By decreasing pro-inflammatory cytokines, resveratrol significantly reduces pain behavior in rodents with disc-related pain.38 Signaling pathways in various types of joint cells can malfunction during aging, causing joint destruction and pain. When used together, resveratrol and curcumin have been shown to work synergistically to target multiple cellular signaling pathways in joint cells, effectively decreasing inflammation without adverse systemic effects.22 Resveratrol alone suppressed inflammation and destruction of inflamed joint cells in vitro.39
The principle component of the spice turmeric, has been used for its anti-inflammatory properties in India and China for centuries. 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 Different environmental stimuli activate nuclear factor KappaB (NF-KappaB): chemical, physical, mechanical, and psychological stress; environmental pollutants; high glucose; ultraviolet radiation; cigarette smoke; most inflammatory cytokines; and other disease-causing factors all activate NF-KappaB.17 Curcumin is a potent suppressor of NF-KappaB and has been shown to decrease NF-KappaB in humans when taken as a supplement. 20-21 Because of its effects on NF-KappaB, Curcumin is a powerful suppressor of COX-2, the key enzyme in the formation of mediators in the inflammatory response.23 Due to its anti-inflammatory activity, curcumin demonstrates beneficial effects on muscle regeneration after the effects of downhill running.24-25 Curcumin added to the diet hastens recovery of running performance in mice. Curcumin ameliorates pain sensitivity via mechanisms that are likely independent of its anti-inflammatory activity according to a number of animal studies.26-30
Icariin is the main active flavonoid from the herb known as Epimedium. Species of Epimedium have been widely used for a number of inflammatory response conditions in traditional Chinese medicine and other Asian systems of medicine. The anti-inflammatory and antioxidant properties of icariin have recently attracted a new wave of scientific interest.
48 Icariin has been shown to protect DNA, nerve cells, and stem cells against free radical-induced damage in vitro.48-49, 51 Like resveratrol and curcumin, icariin appears to exert its anti-inflammatory effects via inhibition of NF-KappaB.50 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.50,52 In another in vitro study icariin partially reversed markers of inflammation in cartilage cells from mice.47