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BlogEFAs, EICOSANOIDS AND INFLAMMATION

January 30, 2023

Inflammation is characterized by swelling, redness, pain and heat, and underlies many diseases such as arthritis, asthma, certain cancers, atherosclerosis, Alzheimer’s disease, as well as skin conditions such as atopic dermatitis, eczema and pyotraumatic dermatitis (hot spots). Key inflammatory mediators responsible the level of inflammatory response are called eicosanoids, and are derived from Omega-3 or Omega-6 EFAs.

When consumed, dietary Omega-3s and Omega-6s are broken down into various subgroup forms that the cells can utilize. The phospholipids in the cell membranes then store (esterify) these subgroup forms within the cell. The EFA subgroups involved in inflammatory response are those with 20 carbons, which are arachidonic acid (AA) and docosahexaenoic acid (DGLA), derived from Omega-6, and eicosapentaenoic acid (EPA), from Omega-3.

Detailed analysis of the inflammatory pathways indicate that, in response to a variety of inflammatory signals, the AA, EPA or DGLA is released from the cell as free fatty acid and enters a multi-stepped cascade of biochemical events. This includes oxygenation by one of two enzymatic pathways, cyclooxygenase (COX) or lipoxygenase (LOX).

AA, EPA and DGLA each sits at the head of its own ‘cascade’ and competes for access to COX and LOX enzymes. Each cascade yields particular subclasses and series of eicosanoids (leukotrienes, prostaglandins, prostacyclins or thromboxanes), some more benign than others (see table 1).

Eicosanoids exert complex control over many bodily systems via numerous signalling pathways (mainly in inflammation and immunity) and as messengers in the central nervous system (eg. prostaglandins play a role in immune function by regulating inflammation and encouraging the body to fight infection.¹)

The eicosanoid signalling pathways are incredibly complex, but as an overview, although AA is vital for certain processes in the body, the eicosanoids derived from AA generally promote inflammation and are critical to the occurrence of various disease-causing biochemical and physiological events.² Those from EPA and from DGLA are generally less inflammatory, inactive or, in some cases, anti-inflammatory.

Low or insufficient dietary intake of the less inflammatory EFAs (especially Omega-3s) generally means a higher concentration of the more inflammatory Omega-6s and its derivative, AA, in the cells. Conversely, higher concentrations of EPA and DGLA in the cells have the potential to ‘soften’ or counter the inflammatory effects of the AA eicosanoids in three ways: through displacement (less AA in the cells to form inflammatory eicosanoids), by competitive inhibition / substrate substitution (less AA to access the COX and LOX enzymes to form AA’s eicosanoids) and through counteraction (some DGLA and EPA derived eicosanoids counteract their AA derived counterparts).

The most common medical treatments for inflammation are NSAIDs and corticosteroids, which block the production of the body’s inflammatory mediators. Although these can often provide immediate symptomatic relief and can break the inflammation cycle, they do not address the underlying cause of the issue and can have serious side-effects (e.g. gastrointestinal upset/bleeding, immuno-suppression, liver strain, decreased wound healing and increased risk of cardiovascular events³).

As the body of scientific literature grows regarding the role dietary EFAs play in modifying inflammation and disease, medical professionals are increasingly turning to beneficial EFAs, especially long chain Omega-3s like those found in C. Frondosa, to delay, reduce or as an alternative to, ant inflammatory medication (and their associated potential risks).

References

  1. Rotella, P, Healthy Fats – Essential Fatty Acids, GoodFats.PamRotella.com, 2004
  2. Review by Dharmananda, Subhuti, PhD, Reducing Inflammation with Diet and Supplements: The Story of Eicosanoid Inhibition, Institute for Traditional Medicine, Portland Oregon, 2003
  3. Rudic RD, COX-2 derived prostacyclin modulates vascular remodelling,Circ Res 2005;96(12):1240-7.
  4. Pace-Asciak CR, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995;235(2):207-19.
  5. Hughes DA. Effects of dietary antioxidants on the immune function of middle-aged adults. Proceedings of the Nutrition Society 1999; 58:79-84.