The Science

Science Research

Why each ingredient was chosen for Relief Factor:


Omega-3 (EPA and DHA)

  • 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
  • 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

  • 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

  • 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

References

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  16. James M, Proudman S, Cleland L. Fish oil and rheumatoid arthritis: past, present and future. Proc Nutr Soc. 2010 Aug;69(3):316-23.
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  24. Thaloor D, Miller KJ, Gephart J, Mitchell PO, Pavlath GK. Systemic administration of the NF-kappaB inhibitor curcumin stimulates muscle regeneration after traumatic injury. Am J Physiol. 1999 Aug;277(2 Pt 1):C320-9.
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  32. 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.
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  46. Liu MH, Sun JS, Tsai SW, Sheu SY, Chen MH. Icariin protects murine chondrocytes from lipopolysaccharide-induced inflammatory responses and extracellular matrix degradation. Nutr Res. 2010 Jan;30(1):57-65.
  47. 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.
  48. 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.
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