So I’m opening a HUGE CAN OF WORMS here, but hopefully in doing so I’ll “bait” you into reading subsequent posts…breaching the topic of Fish Oil is a Deep Dive into some confusingly murky waters! But for a little bit of background, Fish Oil is usually taken because of its omega-3 fatty acid content. Omega-3 fatty acids are polyunsaturated fatty acids (meaning they have some double bonds…saturated fats, in contrast, have all single bonds). Since omega is the last letter of the Greek alphabet, the omega carbon is the final carbon in the fatty acid chain. So if you count backwards from the last carbon, the first double bond in an omega-3 fatty acid is 3 carbons away from the omega carbon. Additionally, “omega” sounds cool, and any time you can use Greek it enhances your academic street cred.
The 3 primary omega-3 fatty acids we will discuss are alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Buckle up and put on your lifejacket…let’s dive in!
Alpha linolenic acid is first on our list (not to be confused with alpha linoleic acid, an omega-6 fatty acid, or alpha lipoic acid, an important cofactor in aerobic metabolism). In this omega-3 context, it is often abbreviated as ALA, but the nomenclature is often confusing…if you lose an “N” you’ve got a completely different class of fat, and if you’re not specific, your Biochem nerd friend might start talking about the pyruvate dehydrogenase complex. ALA is an 18-carbon fatty acid with 3 double bonds, so it is abbreviated as 18:3(n-3). When the “shorthand” is still long and full of colons, hyphens, and parentheses, you know you’re in the Deep End of the Community Pool!
ALA is an essential fatty acid, meaning you must obtain it from dietary sources; your body can’t synthesize it from scratch. And via complicated interactions with delta 5 and delta 6 desaturases and various elongases (encoded by the FADS1/2 and ELOVL genes), ALA can be converted to EPA and then EPA can be converted to DHA.
So what foods contain ALA? Well, FLAXSEEDS are notoriously rich in ALA. However, the FACTS are that FLAX cannot be converted in adequate amounts to get sufficient EPA and DHA from ALA…the enzymatic machinery is neither robust nor efficient enough to facilitate that process.
BONUS ROUND: Some of you baseball fans may also remember that Barry Bonds claimed he began taking “flaxseed oil” during the height of his career, and this magically led to him gaining 35 pounds of muscle, growing 3 hat sizes, and turning into the most legendary superhuman homerun-hitting machine that has ever walked the planet. The likelihood of this story being true is about as likely as ALA being converted to adequate amounts of EPA and DHA.
Up next, eicosapentaenoic acid, or EPA, has 20 carbons and 5 double bonds, so this would be 20:5(n-3). EPA is a precursor of various specialized pro-resolving anti-inflammatory mediators which are thought to have contributed to the 25% fewer cardiovascular events observed in the REDUCE-IT trial. This trial used a high-dose (4g/day) ethyl ester formulation of just EPA. Curiously, cardiovascular trials of combination EPA/DHA products (such as the STRENGTH trial) did not demonstrate the same benefit.
Finally, docosahexaenoic acid, or DHA, has 22 carbons and 6 double bonds, so this would be 22:6(n-3). DHA is the predominant omega-3 fatty acid in the brain and is thought to enhance amyloid clearance, improve synaptic transmission, and assist in the maintenance of proper neuronal health. Carriers of APOE4, a well-known genetic risk factor for Alzheimer’s Disease, tend to have lower DHA levels and tend to need greater quantities of DHA to increase cellular levels compared to APOE3 and APOE2 carriers. This article suggests that high-dose DHA supplementation may be a reasonable preventative measure for APOE4 carriers, although once folks show signs of cognitive decline it doesn’t seem very effective. From a dietary standpoint, salmon, herring, fatty fish, and certain algae are good sources of both EPA and DHA.
Measuring Omega-3 Levels
The preferred measurement of EPA and DHA levels is with the red blood cell omega-3 index, as plasma measurements merely reflect short-term intake. It’s sort of like HbA1c vs a fasting glucose measurement; even a person with type 2 diabetes could have a normal random glucose measurement, and even a fish hater could game the system and have a reasonable plasma omega-3 measurement if he or she went on a salmon bender the night before. But HbA1c and omega-3 indices better reflect the past ~3 months of glucose homeostasis and omega-3 levels, respectively.
So which supplement is best?
Whichever one your local chiropractor, Costco sample lady, or supplement shop owner promises is THE MOST BIOAVAILABLE and doesn’t give you fishy burps, of course! Well, there are free fatty acid formulations…and triglyceride formulations…and ethyl ester formulations…and phospholipid krill oil formulations…and great-tasting gummies that probably have more sugar than omega-3 in them! And all of these supplements have different amounts of EPA and DHA…and there are always concerns about bioavailability and propensity for oxidation…Holy Mackerel! (On a side note, if I made a phospholipid-based omega-3 supplement line, I’d call it All Kriller, No Filler…you know you’d buy it)!
We’ll discuss this more in the future, but for now I’ll leave you with this meta-analysis, which estimated the risk of fatal coronary disease would be reduced by about 30% if someone went from an omega-3 index of <4% (pretty low) to >8% (pretty high). Since this is readily measurable and actionable, it seems reasonable to get a baseline measurement. Then, if you’re low, you may want to start eating more salmon! And if you can’t stomach the thought of increasing your intake of fatty fish, it may be worth doing a Deep Dive to find a quality, safe product that can boost your levels if your omega-3 index is closer to a Nomega-3 one!
I’m not fishing for compliments, but hopefully this is a helpful start that will provide a foundation for future fatty acid festivities!
