Those Omega-3 fatty acids that are hopefully racing around in your bloodstream are on their way to becoming lots of other compounds.  These future structures are good for you in different ways that relate to cardiovascular health, brain health, and general health.  For a full list of healthful benefits click here, but for someone interested in or concerned by Alzheimer’s the benefits are these:

  • anti-inflammatory
  • neuroprotective
  • promotes neurite growth

Then we have omega-6 fatty acids.  The difference in name is because the double bond closest to the end of the fatty acid is 6 connections away from the end instead of 3.  If that doesn’t make sense, and I don’t know why it would, please look at  Just What Is Omega-3.  Omega-6 goes on to form beneficial compounds as well, but along the way it produces compounds that promote clotting and inflammation.

Simple Summary

Omega-3 fatty acids are the basis of compounds that regulate inflammation, protect neurons, and promote neurite growth.  Omega-6 fatty acids promote inflammation before they eventually get around to regulating inflammation.  If you are consuming way more omega-6 than omega-3 you are probably experiencing damage from inflammation and increasing your risk for Alzheimer’s.

More Detail

As discussed in the aforementioned article Just What Is Omega-3, ALA is an essential fatty acid and is converted to all the other forms of omega-3’s that we are interested in here.  This conversion is a multi-step process in the body that changes ALA to EPA.  EPA can then be converted to DPA, which is quickly converted to DHA.  This process can be reversed in what’s called  retroconversion where DHA can be converted back to DPA and then back to EPA.  That all sounds great, but it turns out we are not efficient at these conversions and the difference in conversion efficiency between individuals can be startling.

Men are not as efficient as women at converting ALA into other forms.  Those with the ApoE4 allele are even worse at this conversion process.  There are other genetic factors that may effect your production of some of the key ingredients necessary to convert one form of omega-3 to another.

On the omega-6 side we start with linoleic acid (LA), which like ALA can only be obtained through our diet and is therefore called an essential fatty acid.  LA, through another multi-step process is converted to gamma-linolenic acid (GLA) and then to dihomo-γ-linolenic acid (DGLA), and finally to arachidonic acid (AA).

After the omega-3 ALA and the omega-6 LA are metabolically converted to other forms (EPA, DPA, DHA, DGLA and AA), those other forms are converted to lipid mediators.  There are at least six lipid mediators.  The four we care about here are Prostaglandins, Leukotrienes, Specialized Pro-Resolving Mediators (SPMs), and EFOXs.  SPMs are then separated into another four sub-groups.

Prostaglandins –  derived from AA, DGLA, and/or EPA, these lipids elicit hormone-like effects.  Each compound can have different and sometimes opposite effects depending on what type of tissue it binds with.  Like Leukotriens they can either cause or mediate inflammation.

Leukotrienes – derived from AA or EPA they can either cause or mediate inflammation.

EFOX – derived from DHA or DPA.  These inhibit pro-inflammatory responses.

SPMs (Specialized Pro-Resolving Mediators):

  • Protectins – derived from DHA or DPA they are anti-inflammatory, anti-apoptotic (reduce cell death) and neuroprotective.
  • Resolvins – derived from EPA, DPR, or DHA they settle the inflammation process down after it has started.
  • Maresins – derived from DHA or DPA they also resolve inflammation.
  • Lipoxins – derived from AA they also (as the group name implies) resolve inflammation.

Again, omega-3s almost always end up in a form that reduces inflammation or performs some function that is good for the brain.  Omega-6 fatty acids are more of a mixed bag of good and bad effects.  The literature indicates that omega-6 results in inflammation more often than not.

Another example of this good effect versus bad effect is the formation of synaptamide from DHA, and anandamide from AA.  Both are endocannabinoids that bind to the cannabinoid receptors in the brain.  Synaptamide promotes the growth of neurites.  Anandamide has been shown to impair working memory in rats and enhances the pleasurable responses of rats to sucrose and food intake.  So while the omega-3 metabolite promotes growth in neurons, the omega-6 metabolite seems to promote a love of sugar and overeating, and impairs memory while it’s at it.

I don’t mean to be so down on Omega-6 PUFAs as they serve many beneficial roles in the body.  The point is that having a ratio of omega-3 to omega-6 that is somewhere around 1:2 means simply that the  anti-inflammatory derivatives are not being overwhelmed by their pro-inflammatory cousins.

How to make that ratio happen.  Importantly, some foods have both omega-3 and 6, but few are within the ratio we want to achieve.  In order to achieve the desired ratio one must either eat fish to the exclusion of some other food sources or use supplements.

Fish versus plant sources of omega-3 fatty acids.  There are some 20 different varieties of weeds that have very small amounts of EPA, DPA, and DHA and a large amount of ALA.  The berries and seeds that contain omega-3s only contain ALA.  Given that ALA is inefficiently converted in our bodies , I’m not sure how effective it is to try to get your omega-3s from plants.  If you are a male with the ApoE 4 allele, the EPA derived from ALA is probably trivial.  Fish do the hard work for you.  The fat and oil from fish and in supplements contain substantial quantities of EPA and DHA and obviate the need for your internal system to do anything other than reap the benefits (ok there’s always some work to be done, but you get the point).

Into The Weeds

LA and ALA are converted to longer-chain products by a series of desaturation plus elongation reactions in the liver and to a lesser extent in other tissues.  The very first step is to remove two hydrogen atoms from the fatty acid.  This is done with a enzyme called a desaturase.  

Genotype has been shown to influence the effectiveness of the FADS, which alone or combined with the ApoE 4 allele could seriously diminish one’s ability to convert any omega-3 form into another.

The next step is to add carbon atoms to the chain.  This is done with an enzyme cleverly called an elongase.  ALA and LA start with 18 carbon atoms, but after one round of desaturation and elongation, 2 more carbon atoms have been added to produce EPA, DGLA, and AA.  After another few rounds of desaturation and elongation the carbon atom count climbs to 22 with DPA and DHA.

Along the way AA, DGLA, EPA, DPA, and DHA are worked over by enzymes such as cyclooxygenase (COX 1 and 2) or lipoxygenases (ALOX3,5,12,15,12B, and 15B).  COX 1 and 2 produce the prostaglandins.  ALOX produces the Leukotrienes.  Most others are produced by a combination of COX and LOX including all of the SPMs.

COX is interesting for several reasons.  COX 1 is always active.  COX 2 is turned on and off except in some regions of the brain where it is always active.  Aspirin inhibits COX-1, but it switches COX-2 from producing prostaglandins (some of which are pro-inflammatory) to producing at least two types of SPMs (Protectins and Resolvins).  The metabolites of this altered process carry AT in their names for “aspirin triggered.”

Final Thoughts

Synaptamide, the endocannabinoid that binds to the cannabinoid receptors in the brain and promotes neurites may not be the only cannabinoid that promotes neurogenesis.

Those with ApoE 4 should not despair, studies show that omega-3 levels are lower in those with the allele, but the solution may simply be taking larger amounts of supplement to overcomes the deficiencies.

The larger the fish the greater the amount of mercury.  Tuna is a big fish, so either your pescetarian plans involve lots of sardines or you take supplements.

One more thing I just thought of.  In looking at foods that had a good balance between omega-3 and omega-6 it was noteworthy (hence this note) that whole milk was better than skim.  I have always been suspicious of the attempt to mess with mother nature in the area of milk.  Drinking more than one serving of low-fat or skim milk per day is associated with a greater risk of developing Parkinson’s disease – no such association was found with whole milk.  Probably more going on than just omega-3s, but….