Ancestral Diet: Omega-3 and Omega-6 Fatty Acids

Butter will give you a heart attack! Only cook with Crisco  vegetable oil  canola oil   olive oil.  Wait — everyone is switching back to saturated fats.

Olive oil, grapeseed oil, avocado oil,  — cold expeller pressed, extra virgin hand squeezed oil from pine nuts grown in a pristine Siberian forest?  Am I the only one who is confused about which kind of fat is the best?

It turns out, like most things, that the answer to the ‘best type of fat’ question depends on your genes.

Most people carry genetic variants that are able to use the plant-based polyunsaturated fatty acids, but some of us still carry what is thought to be the ancestral genotype that makes relying on plant-based fats a poor choice.

Polyunsaturated Fats

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 their carbons bound to hydrogens, while unsaturated fats don’t have all of their carbon bonds filled with hydrogen, allowing for carbon-carbon bonds. Structurally, this makes saturated fats into a straight chain and allows them to be packed together as solids at room temperature (e.g. coconut oil).  Unsaturated fats have a bend at their carbon-carbon bond, so they are less tightly packed together and liquids at room temperature (e.g. olive oil).

Omega-6 fatty acids are named as such because they have a double carbon-carbon bond as the sixth bond, while omega-3 fatty acids have a double bond as the third bond. Omega-3 fatty acid can also be written as ω−3 or n−3. Same for omega-6.

Common sources of omega-6 (as linoleic acid) in the diet include corn, sunflower, cottonseed, soybean, walnut, and peanut oils. Notice that these are all plant-based oils. Small amounts of omega-6 (as arachidonic acid) are found in chicken, eggs, and beef.

Plant oils high in omega-3 include flaxseed and chia seed. The longer-chain omega-3 fatty acids, EPA and DHA, are found in abundantly fish oil.

We often think of fats as being used for energy or stored as unsightly fat around the belly. But fatty acids do more than just those two things. Fatty acids, including both saturated fats and polyunsaturated fats, make up the membrane surrounding each cell in the body. Omega-6 and omega-3 fatty acids can also be used by the body to make eicosanoids (pro- and anti-inflammatory molecules), endocannabinoids, and cellular signaling molecules.

Omega 6: Omega 3 ratio

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

Currently, 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 lead to a 136% increase in the amount of linoleic acid (an omega-6) in our adipose tissue. [ref]

Specific omega-6 fatty acids:

My simplified overview of the genes involved in PUFA conversion.

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 that you eat in foods are generally linoleic or gamma-linoleic acid. These are changed in your body into arachidonic acid, eicosatetraenoic acid, and docosapentaenoic acid. This conversion takes place using 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] One way in which arachidonic acid is thought to be pro-inflammatory is that it leads to higher eicosanoids, which are important in allergic inflammation.[ref]

Specific omega-3 fatty acids:

Similarly, omega-3 fatty acids are also transformed within your body. Most food sources of omega-3 from plants are in the form of alpha-linolenic acid. A small percentage of alpha-linolenic acid can be changed via the enzymes produced by FADS1 and FADS2 genes into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To get EPA and DHA without converting alpha-linolenic acid, you must consume animal products such as fish oil.

DHA and EPA are touted for their effects on lowering the risk of heart disease and for their brain health benefits.

Shared enzymes:

The same enzymes are involved in the metabolism of both the omega-6 and the omega-3 fatty acids. This is where the ratio of the 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 that more of the omega-6 will be metabolized into arachidonic acid and less EPA and DHA will be produced.

Genetics of Fatty Acid Metabolism

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

So what does a slowing of 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 of the linoleic acid (omega-6) turning into the sometimes inflammatory arachidonic acid due to having less of the enzyme can be good. But on the omega-3 side, this situation also produces less EPA and DHA if your diet is heavy on the 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]  The opposite has also been found in that those with variants slowing down the FADS enzymes can have a lower risk of heart disease.

FADS1 Variants:

There are multiple FADS1 variants that decrease enzyme activity. These variants are linked 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 alelle)– which is almost always inherited along 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, benefits more from EPA/DHA intake for lowering high triglycerides
  • C/C: normal FADS1 activity

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 is reduced[ref]
  • lower HDL, lower glucose, but higher triglycerides [ref]

FADS2 Variants:

This is also linked to the above genotypes as well as rs174575 (G) for most 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: normal FADS2



The same enzymes are used for converting both the 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 especially important 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.

Oils that are higher in omega 6 as linoleic acid include:

  • safflower
  • grapeseed
  • sunflower
  • corn
  • walnut
  • wheat germ
  • cottonseed
  • soybean
  • sesame
  • peanut

Foods high in these oils include most mayonnaises, salad dressings, margarine, walnuts, sunflower seeds, and peanut butter. And pretty much anything that is fried! Yes, this means most fast food choices are high in omega-6 fats. [ref]

Foods and oils that are high in omega-3 include:

  • fish oil (DHA, EPA)
  • seal oil
  • flax seed (alpha-linolenic acid)
  • chia seeds
  • caviar

Ancestral Diet:
Researchers believe that the FADS1/2 variants that are linked to lower enzyme activity were once the most common genotype.  They theorize that the shift to the higher enzyme variants being most common was selected for when humans shifted from hunter/gatherer diets to agriculture based diets. This shift to higher enzyme activity then allowed humans to benefit more from the seed-based oils, so genetically the higher enzyme variants have been selected for to best fit the shift to agriculture around 8,500 years ago. Read the whole article here.

An ancestral or paleo diet focuses more on fish, meat, and vegetables with little or no grains. This may be a great diet choice for anyone with two copies of the FADS1/2 low enzyme activity variants. It should shift the ratio of omega-6 to omega-3 fats to a good balance, and including fish will ensure enough DHA.  Of course, the ‘best diet’ for any one person can’t be based on just one gene, but this gene is a good starting point when trying to optimize your diet.

Decrease omega-6:
A recent study looked at the interaction between the FADS1 variant and dietary consumption of both linoleic acid (omega 6) and alpha-linolenic acid (omega-3).  The study found that people carrying the low enzyme variant had lower HDL levels with high omega-6 consumption. Conversely, study participants who carry the variant and who ate a diet low in omega-6 fatty acids had lower BMI and smaller waist circumference.[ref]

Let me make this simpler: if you carry the FADS variant, low omega-6 consumption = lower BMI. So cut out the fried foods, sunflower oil, and soybean oil.

Vegan diet:
If you are a carrier of the FADS1 variant and relying on flaxseed and chia for omega-3’s, you may be converting very little of that to DHA and EPA.There are vegan options for DHA supplements available now.

Pregnancy alert:
If you are pregnant or planning to get pregnant, carrying the FADS1/2 variants may influence your baby’s development. Babies need a lot of DHA for brain growth both in utero and through breast milk. Arachidonic acid is also essential in breast milk. [ref][ref][ref][ref]

A recent study of pregnant women found that those with the FADS1 variant had lower DHA status at baseline. The study then compared supplementing with 600 mg/day of algal DHA to placebo for the second and third trimesters of pregnancy. The DHA supplement increased everyone’s levels – with no differences seen due to genotype after supplementation. [ref]

Another study shows why DHA is so important in pregnancy. This study looked at maternal DHA status in pregnancy compared with infants’ problem-solving skills at 6 and 12 months. Higher maternal DHA status in pregnancy correlated to higher infant problem-solving skills at 12 months. So DHA makes for smarter babies? [ref]

Moderate fat intake:
A Korean study found that a moderate fat diet (compared to high or low fat) decreased the risk of metabolic syndrome in people carrying the FADS1 variant.[ref] The study didn’t break down the composition of the diet, so it may be that moderating omega-6 consumption was the key.

Fish Oil Supplements:
If you have read through all of this and realized that you need to increase your DHA/EPA levels, you may be tempted to reach for a fish oil supplement. Mercury and other contaminant are always a worry for fish oil (as well as when eating a lot of fish). A website called Labdoor does independent lab testing on supplements, including fish oil. If you register with them (free), you can see their in-depth report on different brands.

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8 Comments on “Ancestral Diet: Omega-3 and Omega-6 Fatty Acids

  1. Pingback: A little lithium and B-12 makes the world a happier place – for some. | Genetic Lifehacks

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  3. Wow, I’m homozygous for every single minor allele in this article! My parents and sister recently became vegan, maybe not such a great idea for them?

    Thank you for all of this Debbie, I’m learning so much!

    • Hi Lauren,
      I’m glad you are learning something from the Genetic Lifehacks website!
      When I found out that I was homozygous for the minor alleles, I tossed out the bottle of flaxseed oil that was in my fridge and then made a real effort to eat more fish.
      As far as your parents and sister go, without your parents both doing a DNA test, you can’t know if they are homozygous or just heterozygous (one copy of the variant). Either way, I would let them know that flaxseed and chia seeds are probably not working all that well for them for converting to EPA and DHA. I think there are some DHA supplements on the market that are made from algae that should be vegan.
      Thanks for reading and commenting,

  4. Turns out this vegan experiment is devolving (not surprised). My mom tells me that she and my dad are actually eating fish once or twice a week (I wish we were doing as much) and all 3 of them are taking fish oil. Apparently their version of vegan didn’t preclude a fish oil supplement. Yay!

  5. Great post, Debbie!

    Am I correct in my interpretation that having a minor allele for the FADS1 variants is positive, leading to lower production AA? The only downside seems to be associated with the minor allele at rs174550 and potentially lower HDL levels.

    You’re quite right in thinking vegan short chain omega 3 supplements are available, they’re derived from algae!

    Thanks :)

    • Hi Laura,
      Thanks for your comment on this. As far as the minor allele being positive, I would say that it is positive in some ways :-) Again, like most variants, there are both pros and cons, which in this case may depend on diet. Too much arachidonic acid is linked to higher rates of cardiovascular disease, but arachidonic acid is essential for the body to have for a number of other processes. My main takeaway from this is that carriers (including me!) of the minor allele shouldn’t rely on flax or chia seeds for the DHA and EPA. Instead, they need to eat fish or supplement with krill oil or, as you point out, algal forms of DHA supplements.

    • The article left out any mention of the anti-inflammatory GLA, which is an intermediate form in between LA and AA when you eat Omega-6 fatty acids. One study showed, for example, that people with the minor allele of the FADS1 SNP rs174546 have lower GLA levels. Beyond lowering inflammation, GLA helps to lower blood pressure, lessen menstrual cramps, prevent arthritis and common skin conditions, and lower risk of heart attack and stroke. If you have this minor allele you probably should also be supplementing with high GLA oils like borage and/or evening primrose oil.

      Beyond that, I wouldn’t say that having to rely on supplements is a good thing. What happens in a crisis where we can’t get those supplements for whatever reason? And after all, good quality, high dose EPA/DHA Omega-3 supplements are expensive! But if we don’t take them we run the risk of a whole host of bad diseases and health disfunctions. So no, I wouldn’t call having the rare genetic variant alleles a positive. Anyone can get lower AA levels just by eating less polyunsaturated oils.

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