Complementary actions of curcumin and fish oil with SPMs to combat inflammation

Pain and inflammation are widely encountered in clinical practice. In arthritis and,other chronic pain conditions, practitioners may include strategies to reduce pain and inflammation, improve range of motion, maintain functional ability, reduce further tissue damage or destruction and improve quality of life.1,2  Management often includes a combination of herbal and nutritional therapies, pharmacological treatments and lifestyle modifications.

Curcumin

Curcumin has significant potential in the management of pain, arthritis and joint pain due to its anti-inflammatory and antioxidant activity.3-5

  • Curcumin inhibits synthesis of multiple pro-inflammatory mediators including NF-kβ, which has been identified as a key mediator of inflammation and inflammatory processes.6 Inhibition of NF-kβ activity interrupts the NF-kβ signalling pathway and modulates the subsequent expression and activity of various factors involved in inflammation, joint destruction and immune response, including pro-inflammatory genes, chemokines, cytokines, cell-cycle regulators and adhesion molecules.4,5,7
  • Curcumin also inhibits cyclooxygensase-2 (COX-2), lipoxygenase, prostaglandins, leukotrienes, thromboxane, nitric oxide, tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) interleukin-6 (IL-6), interleukin-12 (IL-12), monocyte chemoattractant protein-1 (MCP-1) and interferon-inducible protein.3,8-10
  • Curcumin has been found to significantly reduce circulating C-reactive protein levels.11
  • Curcumin has been shown to reduce pain and may inhibit TRPV1-mediated pain hypersensitivity. TRPV1 is involved in the transmission and modulation of pain (nociception).3,12
  • Curcumin also appears to inhibit inflammatory enzymes such as collagenase, elastase and hyaluronidase.3,8
  • In addition, curcumin suppresses production of matrix metalloproteinases, which are proteolytic enzymes involved in cartilage and tissue destruction.13,14
  • Curcumin exerts direct free radical scavenging effects and to decrease levels of reactive oxygen species.5,6 Curcumin also has an indirect antioxidant effects.4,15

 *Figure 1: The role of NF-kB in regulation of inflammatory processes.16

Although curcumin displays multiple mechanism by which it may aid in the relief of inflammation, symptoms of mild arthritis and mild joint aches and pain, curcumin is poorly bioavailable. This is due to a combination of poor solubility, low gut absorption, rapid metabolism and rapid systematic elimination.17  Complexing curcumin with dimethyl sulfone (MSM) to form a solubilization matrix has been shown to significantly enhance curcumin bioavailability by increasing its water-solubility.18 In addition, MSM may independently aid in the management of osteoarthritis by inhibiting degenerative joint changes and by stabilizing cell membranes and scavenging hydroxyl free radicals which trigger inflammation.3,19

Omega-3 fatty acids (Fish oils)

Omega-3 fatty acids reduce inflammation via multiple pathways, including inhibiting production of potent pro-inflammatory mediators (PGE2, and LTB4) derived from omega-6 fatty acids. LTB4 is a pro-inflammatory mediator involved in modulating the intensity and duration of inflammatory response and enhancing macrophage chemotaxis.20

Omega-3 fatty acids also promote the formation of low inflammatory mediators PGE3 and LTB5.20,21 Omega-3 fatty acid intake indirectly leads to decreased production of inflammatory COX-2, as well as TNF-α, a cell signalling protein involved is systemic inflammation. They also inhibit macrophage production of IL-1β, which is involved inflammation

Research supports use of omega-3 fatty acids (EPA and DHA) for the relief of inflammation.22-27

Specialised pro-resolving mediators (SPMs) for inflammation

Omega-3 fatty acids are also precursor compounds for a family of naturally occurring lipid mediators known as specialised pro-resolving mediators (SPMs), including resolvins, protectins, and maresins.28 SPMs play a crucial role in actively switching off the inflammatory response once it has served its purpose, allowing for resolution or ‘ending’ of inflammation and accelerating a return to homeostasis. SPMs actively help the body to shut down the immune response, inhibit additional inflammation, clear away the damaging by-products of inflammation and aid tissue repair.28-31

Although omega-3 fatty acids form the foundation compounds for biosynthesis of SPMs, conversion is a complex, multi-step process and is affected by a person’s health status. Optimal production of SPMs is highly dependent on both genetic predispositions as well as healthy lifestyle and nutrition. The rate and extent of conversion may be variable and unpredictable for each individual. In addition, an individual may have elevated SPM requirements due to injury, trauma or chronic inflammation.29  SPMs are thus gaining recognition as an innovative therapeutic strategy in their own right for the management of conditions associated with chronic inflammation.29-31 

* Figure 2. Summary of the pro-resolving properties of SPMs, with a focus on tissue repair and regeneration.31 

In conclusion, curcumin, omega-3 fatty acids and specialized pro-resolving mediators (SPMs) all have uniquely different, yet complementary mechanisms by which they may assist in relieving inflammation. They can be used in combination to support the management of conditions relating to chronic inflammation.

*References available on request.