Chronic inflammation is recognised as a hallmark feature in the development of major disease (1).
There has been controversy over the effectiveness in omega-3 fatty acids, in particular fish oil and related supplements, in reducing inflammation. It seems that the issue is achieving the relevant dose.
There is robust evidence for a beneficial clinical effect of omega-3 fatty acids in rheumatoid arthritis, with suggestive but inconsistent evidence for effects in other inflammatory conditions like inflammatory bowel disease and asthma (2).
The mechanisms by which omega-3s may exert their effect appear to overlap (2).
The anti-inflammatory omega-3 eicosapentaenoic acid (EPA) competes directly with the pro-inflammatory omega-6 arachidonic acid (AA) for incorporation into cell membranes (3). The balance of these fatty acids in our cells is what dictates the expression of pro-inflammatory or anti-inflammatory mechanisms in the body.
Higher levels of EPA will increase the EPA content of cells in a linear manner (3), which occurs at the expense of AA (4). This increase in cellular EPA occurs acutely, within 1 week, and with a corresponding decrease in AA and in the omega-6:omega-3 ratio (4).
The ratio of omega-6:omega-3 may be a more important determinant of cellular EPA content, as a low levels of the omega-6 linoleic acid, the precursor to AA, correspond to increases in EPA (3).
A dose of 3.2g combined omega-3s EPA and DHA lead to a 20% decrease in AA content (5). AA promotes the expression of series-2-prostaglandins, or PGE2, which promotes inflammation (6). Omega-3s have a direct anti-inflammatory effect by suppressing PGE2 (6).
In particular, a dose of >1.35g EPA may be the minimum effective dose to change the fatty acid composition of phospholipids, and inhibit PGE2 (7). Thus, the inhibition of inflammatory eicosanoid expression is due to the fact that omega-3s outcompete AA (8).
It’s important to remember that inflammation is a normal process in the body, and is the first response to injury. In this context, what is important is a healthy and appropriate inflammatory response to bodily inflammation. High omega-3 levels help achieve that. In response to inflammatory stimuli, for example a twisted ankle, high levels of omega-3s results in a more moderate inflammatory response (9).
If you’ve ever taken aspirin for pain relief, you might be surprised to know that one of the mechanisms by which omega-3s act is the same. Aspirin inhibits the pro-inflammatory enzyme COX2, which converts AA to pro-inflammatory PGE2; omega-3s inhibit this enzymatic pathway (10).
Recall that inflammation is a normal bodily process, and while we don’t want an over expression of inflammation in response to injury, and equally important part of the process is resolving inflammation. In this respect, the omega-3s EPA and DHA also act as the precursor fatty acids to a family of molecules known as resolvins, which as their name implies, promote resolution of the inflammatory response (11). So the influence of omega-3s on inflammation goes beyond an inhibitory action alone.
1.65g combined EPA and DHA appears to be below the threshold for anti-inflammatory action (7). EPA in particular greater than 1.35g appears to be required to affect PGE2 production (7).
Alterations in the cellular fatty acid content have been observed at 2.25g omega-3 (of which 1.67 DHA), and 3.2g omega-3 (of which 1.1g DHA (5; 12).
Thus, the anti-inflammatory action of omega-3s appears to have a threshold minimum of 2g per day (1).
As you’ve gathered from above, the ratio of omega-3 fatty acids to omega-6 fatty acids is a vital determinant of whether we have a more pro-inflammatory or anti-inflammatory environment in the body.
The Standard Western Diet is characterised by an omega-6:omega-3 ratio of at least 17:1, while estimates of our evolutionary ratio of these fatty acids is around 2:1 (13).
This excessive intake of pro-inflammatory dietary fats, and lack of anti-inflammatory omega-3s, is associated with a state of low-grade systemic inflammation that is linked to cardiovascular disease, autoimmune disease, cancer and other diseases in which inflammation is present (13).
As far as a preventative health step goes, balancing intake of dietary fatty acids is an easy troubleshoot.
This largely depends on whether you have a specific condition, for which omega-3s can have a therapeutic effect.
Here is the general advice applicable to all of you, whether you have a condition or not:
1: Eliminate processed and packaged foods. The use of vegetable oils and shortenings in processed or packaged foods is the major source of of high pro-inflammatory omega-6 levels in the modern diet.
2: Stop cooking with vegetable oils. Sunflower, safflower, canola – any oils like this go rancid easily when exposed to heat. Use more stable oils and fats to cook; coconut oil, avocado oil, ghee.
3: Increase general omega-3 intake, both direct EPA and DHA from fish, and also alpha-linolenic acid (ALA) from plant sources. Eating oily fish like salmon, mackerel and sardines 3 times per week, while including omega-3 nuts and seeds like hemp, chia and walnuts will help bring your omega-6:omega-3 ratio into balance.
For specific conditions:
Rheumatoid Arthritis – strong evidence that 3.5g combined EPA and DHA per day reduces pain, stiffness and morning soreness (2).
Asthma – evidence is mixed, and no specific recommendation can be given beyond the general guidelines above, reducing omega-6 and increasing marine omega-3 intake (2).
Inflammatory Bowel Disease – evidence is weak and mixed, but potential therapeutic effect at an average dose of 4g per day combined EPA and DHA (2).
High triglycerides/lipid abnormalities (as risk factors for cardiovascular disease) – average intake of 3.5g combined EPA and DHA reliably reduces triglycerides (14).
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