Omega-3 and omega-6 fatty acids have been front and center in nutrition news for many years now because of their relationship to cardiovascular health.  But their role in modulating all types of inflammation in the body makes these fats of even more important to healthy diets and lifestyles. 

Essential Fatty Acids: What are they?

Both omega-3 and omega-6 fatty acids are long-chain polyunsaturated fatty acids, both 18 carbons long with two double bonds. They are considered “essential” because they are necessary for health and cannot be synthesized by humans (or in any mammals for that matter) from other fatty acids. Therefore, they must be consumed in the diet.1

Omega-3 fatty acids include alpha-linolenic acid and its metabolites, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-6 fatty acids include linoleic acid and its most notable metabolites, gamma-linolenic acid (GLA) and arachidonic acid (AA). 
 

Where They Are Found?

The most bioavailable source of omega-3 fatty acids are oils from fatty fish. Nut and seed oils are also rich in omega-3 fatty acids, though their conversion to DHA and EPA may not be as efficient as those from fish. Omega-6 fatty acids tend to be more plentiful in many people’s diet, which can affect how well omega-3 fatty acids convert to EPA and DHA.

Omega-3 fatty acid foods:

  • Fish and seafood, especially fatty fish like sardines, anchovies, tuna, mackerel, and salmon
  • Flaxseed oil and flax seeds
  • Walnuts
  • Chia seeds
  • Hemp seed oil and seeds

Omega-6 fatty acids foods:

  • Liver and organ meats
  • Poultry and red meat
  • Fish and seafood
  • Egg yolk
  • Butter
  • Avocado
  • Flax seed oil and flax seeds
  • Hemp seed oil and hemp seeds
  • Pumpkin and sunflower seeds
  • Nuts
  • Borage oil
  • Black currant seed oil
  • Evening primrose oils
  • Other oils, such as corn, safflower, and soybean oils


Essential Fatty Acids At Work

Both omega-3 and omega-6 fatty acids are components of cell membranes, built into the phospholipid bilayers of cells. In response to inflammation or injury, fatty acids including AA and EPA are released, triggering the formation of eicosanoids like prostaglandins, leukotrienes and lipoxins, which modulate the inflammatory process. 

There are two phases to inflammation: initiation and resolution. The idea of using an “anti-inflammatory” medication, such as non-steroidal anti-inflammatory medication (NSAID) to address inflammation has begun to lose favor, because if inflammation is artificially interrupted or blocked, healing is also blocked. By contrast, nutrients like essential fatty acids are not anti- or pro-inflammatory per say. Rather, they either up- or down-regulate the production of pro-inflammatory mediators, thereby balancing inflammatory processes so that healing can occur without undue damage to surrounding tissues. Once adequate healing has occurred, essential fatty acid metabolites down-regulate the inflammatory process, and pro-resolvin mediators can bring the inflammatory process to an end.

Omega-3 fatty acids are important inflammation-balancing nutrients due to their critical role in blunting and resolving the inflammatory process via molecules called resolvins that are synthesized from EPA and DHA. While GLA is known to reduce inflammation, omega-6 fatty acids in general and AA in particular, have been mislabeled as “pro-inflammatory.” Yet their role in contributing to the inflammatory response has been overly simplified and represents only half of the story. 

While AA metabolites do contribute to the inflammatory cascade, they do not actually initiate inflammation, and their downstream effects also lead to the generation of specialized pro-resolving mediators, as do omega-3 metabolites.2 AA is converted to pro-inflammatory prostaglandins during the inflammatory process by enzymes such as cyclooxygenase 2 (COX-2). But during the resolution phase of inflammation, different enzymes act on AA yielding pro-resolving mediators that support healing, such as lipoxin A4. Together with specialized pro-resolving mediators synthesized from omega-3 fatty acids, lipoxins help to dampen and resolve the inflammatory cascade like a biological shut-down mechanism.3

These long chain fatty acids work together to modulate inflammation with checks and balances built into place. When the diet provides a good balance of high quality omega-3 and omega-6 fatty acids, this system works well to perpetuate inflammation when necessary and to quell and resolve the inflammatory cascade when the threat is over. However, most Western diets have an overabundance of omega-6 fatty acids and include insufficient amounts of omega-3s. High omega-6 and low omega-3 intake can tip this system out of balance, resulting in the inhibition of the inflammation-resolving effects of omega-3s, and allowing for low levels of chronic inflammation to continue.

Linolenic acid + delta-6-desaturase ->Series 1 prostaglandin (yields metabolites  that continue or dampen the inflammatory response) 
Arachadonic acid + delta-6-desaturase -> Series 2 prostaglandin (yields pro-inflammatory and pro-resolvin mediators)
Eicosapentaenoic acid + delta-6-desaturase ->Series 3 prostaglandin ->pro-resolvin mediators (dampen and resolve inflammation)

Delta-6-desaturase is an enzyme that starts the production of prostaglandins from essential fatty acids. If there is an over-abundance of omega-6 fatty acids, there may not be enough of the enzyme to go around, resulting in an inhibited Series 3 pathway and insufficient synthesis of pro-resolvin mediators. 

The miRNA Connection

MicroRNA or miRNA is a type of non-coding RNA molecule found in plants and animals that up- or down-regulate gene expression by binding to target messenger RNAs (mRNAs). miRNA appear to be involved in an important way that cells to communicate between one another and share biological information and may also be related to specialized pro-resolving mediators. Recently, it has been proposed that plasma membrane lipid concentration, including the concentration of EPA, DHA and AA, may directly influence the miRNA-mediated regulation of inflammation. Both the abundance and ratio of omega-3 to omega-6 fatty acids housed within cell membranes appears to affect the actions of miRNA expression. If levels of these omegas are insufficient or the ratio suboptimal, it can result in altered miRNA signaling, resulting in a diminished ability to trigger the formation of specialized pro-resolving mediators to promote inflammation resolution.   Therefore, clinicians may opt to recommend omega-3 fatty acids to enrich tissues and membranes with EPA and DHA to support the resolution of inflammation. This may be particularly important for those who may not have sufficient amounts of essential fatty acids to produce adequate amounts of specialized pro-resolving mediators and therefore would require nutritional support to achieve inflammatory balance. Learn more about miRNA's role in the resolution phase of inflammation.

Potential health benefits to essential fatty acids span different systems and conditions, as chronic inflammation is the core etiology to most illnesses and chronic conditions. People with these conditions may not have the essential fatty acid substrate to form sufficient amounts of endogenous specialized pro-resolving mediators and may benefit from supplementation. Essential fatty acids may be beneficial to the prevention and treatment of:

  • Age-related macular degeneration
  • Arthritis and rheumatoid arthritis 
  • Asthma and allergies
  • Autoimmune conditions
  • Cancer 
  • Cardiovascular disease
  • Cell membrane structure, cellular aging and optimizing telomere health
  • Diabetes and diabetic complications
  • Inflammatory bowel disease
  • Irritable bowel disease
  • Neurological and cognitive health
  • Obesity and metabolic syndrome

Inflammation is a normal and healthy part of a functioning immune system. However, illnesses and complications arise from the body’s inability to efficiently dampen and ultimately resolve the inflammatory cascade once the initial threat is over. Essential fatty acids are crucial nutrients to the product of specialized pro-resolving mediators, underscoring a vast body of previous research illustrating the importance of omega-3 and omega-6 fatty acids.

1 Bazinet RP, Chu MWA. Omega-6 polyunsaturated fatty acids: Is a broad cholesterol-lowering health claim appropriate? CMAJ. 2014 Apr 1; 186(6): 434–439.
Tallima H, El Ridi R. Arachidonic acid: Physiological roles and potential health benefits – A review. J Adv Res (2017), https://doi.org/10.1016/j.jare.2017.11.004
3 Tallima H, El Ridi R. Arachidonic acid: Physiological roles and potential health benefits – A review. J Adv Res (2017), http://linkinghub.elsevier.com/retrieve/pii/S2090123217301273
Shumann 2016