Omega-3 and Omega-6 Fatty Acids

Key takeaways:
~ Polyunsaturated fats are transformed using a couple of enzymes.
~ Genetic variants impact how well you convert fatty acids, such as from plants, into DHA and EPA.
~ Understanding your genetic variants can help you understand the best form of omega-3s for you.

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Table of Contents

Polyunsaturated Fats:

Most people carry genetic variants enabling them to use plant-based polyunsaturated fatty acids. What is thought to be the ancestral genotype shows up now in a minority of people. This genotype makes the reliance on plant-based fats a poor choice for brain-healthy DHA and EPA.

Background science:

Fats are made up mainly of hydrogen and carbon molecules. They are categorized as saturated or unsaturated based on their carbon bonds.

Saturated fats have all of their carbons bound to hydrogens, while unsaturated fats don’t have all of their carbon bonds filled with hydrogen, allowing for carbon-carbon bonds.

Saturated fats form straight chains that are tightly packed together, resulting in solids at room temperature (e.g., coconut oil, butter).
Unsaturated fats, with a bend at their carbon-carbon bond, pack less tightly together and become liquids at room temperature (e.g., olive oil).

Omega-6 fatty acids are named because the double carbon-carbon bond is the sixth bond, while omega-3 fatty acids have a double bond as the third bond. You will also find the omega-3 fatty acid written as ω−3 or n−3. Same for omega-6 (ω−6 or n−6).

Omega-6 fats include:

corn
sunflower
cottonseed
soybean
walnut
peanut

Plant oils high in omega-3 include flaxseed and chia seed. Fish oil contains abundant longer-chain omega-3 fatty acids, EPA, and DHA.

Why do we need fats? Fatty acids, including both saturated and polyunsaturated fats, make up the membrane surrounding each cell in the body. The body also uses omega-6 and omega-3 fatty acids to make eicosanoids (pro- and anti-inflammatory molecules), pro-resolving lipid mediators, endocannabinoids, and cellular signaling molecules.

Omega 6: Omega 3 ratio in Modern Diets

Most nutritionists agree that the ratio of omega-6 to omega-3 fatty acids is important to our health. Current thought suggests our ancestors ate a diet with a ratio of omega-6 to omega-3 of less than 4:1 and maybe even as low as 1:1.[ref]

Presently, an average Western diet has a ratio of 16:1 or higher of omega-6 to omega-3 consumption. Omega-6 fats can have both inflammatory and anti-inflammatory properties, and it is thought that the modern imbalance of omega-6 to 3 may be causing an increase in inflammatory diseases such as heart disease and diabetes.[ref]

You are what you eat. And a recent study makes it clear that most of us have a lot more omega-6 in our fat cells than people did fifty years ago. Our modern diet has led to a 136% increase in the amount of linoleic acid (an omega-6) in our adipose tissue.[ref]

Going in-depth on Omega 6s

There isn’t just one “Omega-6” fat. The term applies to a series of different chains of fatty acids, defined by the length of the carbon-hydrogen chain.

The omega-6 fatty acids you eat in foods are generally linoleic or gamma-linolenic acid and our bodies change them into arachidonic acid, eicosatetraenoic acid, and docosapentaenoic acid. This conversion uses enzymes called fatty acid desaturase (coded for by the FADS1 and FADS2 genes).

For example, if you eat a plant-based oil high in omega-6 fats (sunflower, cottonseed, corn, etc.), you are consuming it in the form of linoleic acid. Linoleic acid can then be converted by FADS1 and FADS2 (in a couple of steps) to arachidonic acid.

Arachidonic acid can be pro-inflammatory under some conditions, but it can also be beneficial in building muscle mass for weight lifters.[ref] Arachidonic acid also leads to higher eicosanoids, which are important in allergic inflammation.[ref]

My simplified overview of the genes involved in PUFA conversion.

Omega 3 transformations

Your body also transforms omega-3 fatty acids.

Most plant sources of omega-3 are in the form of alpha-linolenic acid. A small percentage of alpha-linolenic acid changes via the enzymes produced by FADS1 and FADS2 genes into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). More on this is in the genetics section.

To get EPA and DHA without converting alpha-linolenic acid, you must consume animal products such as fish oil. DHA and EPA are hailed for their effects on lowering the risk of heart disease and for their brain health benefits.

Why are DHA and EPA so essential? These marine oil-derived omega-3s are the foundational molecules forming pro-resolving lipid mediators. Recently, researchers have figured out that the resolution of inflammation is actually an active process that relies on specific pro-resolving lipid mediators derived from DHA and EPA.

Related article: Specialized Pro-resolving lipid mediators

Shared enzymes: FADS1 and 2

The metabolism of both the omega-6 and omega-3 fatty acids involves the same enzymes.

This is where the ratio of fats in your diet comes into play. With only a limited amount of the desaturase enzymes available, a high ratio of omega-6 to omega-3 means more of the omega-6 will be metabolized into arachidonic acid, and less EPA and DHA will be produced.

FADS1 and FADS2 Genotype Report:

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The FADS1 (encodes delta-5 desaturase) and FADS2 (encodes delta-6 desaturase) genes have several different variants that slow down the production of the enzymes.

So what does slowing the production of these enzymes mean for your body? It depends on how much omega-6 and omega-3 you consume.

If you eat a diet high in omega-6, having less linoleic acid (omega-6) turning into the sometimes inflammatory arachidonic acid due to having less of an enzyme can be good. But on the omega-3 side, this situation also produces less EPA and DHA if your diet is heavy on omega-6 fatty acids. One way around this is to eat very little omega-6 fat; another way is to directly get EPA and DHA from fish or fish oil.

Quite a few studies have found that those with variants that slow down the conversion of linoleic acid to arachidonic acid affect disease risks. A 2008 study found that those with higher arachidonic acid to linoleic acid ratios had a higher risk of coronary artery disease.[ref] Conversely, those with variants slowing down the FADS enzymes can have a lower risk of heart disease.

FADS1 Variants:

There are multiple FADS1 variants that are inherited together such that if you inherit one, you should inherit all the variants.

Below, I’ve only included one variant, rs174546 (T is the risk allele)– which is almost always inherited together with rs174547 (C allele), 174537 (T allele), rs174550 (C allele), and rs174548 (G allele).[ref] I’ve included studies on all of these variants below.

Check your genetic data for rs174546 (23andMe v4, v5; AncestryDNA):

T/T: low FADS1 enzyme activity; decreased risk of coronary artery disease due to lower arachidonic acid; benefits more from EPA/DHA intake for lower triglycerides[ref][ref][ref][ref]
C/T: lower FADS1 enzyme activity, decreased risk of coronary artery disease, benefit more from EPA/DHA intake for lowering high triglycerides
C/C: typical FADS1 activity

Members: Your genotype for rs174546 is —.

Studies on the linked FADS1 variants that decrease enzyme activity – rs174546 (T ), rs174547 (C), 174537 (T), and rs174548 (G) show:

People carrying the low activity variant had decreased LDL levels when they had low consumption of omega-3 fatty acids.[ref]
Lower arachidonic acid and EPA levels[ref]
Lower risk of type 2 diabetes[ref]
Arachidonic acid and phosphatidylcholine are reduced[ref]
lower HDL, lower glucose, but higher triglycerides[ref]

FADS2 Variants:

This FADS2 variant is inherited together with the FAD1 variant for many people.

Check your genetic data for rs1535 (23andMe v4, v5; AncestryDNA):

G/G: low FADS2 enzyme activity, decreased ALA to EPA conversion[ref], benefits the most from fish oil supplement post-heart attack[ref]
A/G: somewhat decreased FADS2 enzyme activity
A/A: typical FADS2

Members: Your genotype for rs1535 is —.

Lifehacks:

The body uses the same enzymes to convert both omega-6 and 3 to the longer chain forms needed in the body. The ratio between omega-6 and omega-3 intake is important for everyone, but it may be significant for people carrying the FADS variant. In general, most people with the FADS1/2 variants probably need to shift their diets away from too much omega-6 and increase DHA/EPA (omega-3) from fish oil.

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