Ancestral Diet: Omega-3 and Omega-6 Fatty Acids Impact the FADS1 gene

At one point, researchers thought that butter would give you a heart attack. Therefore, we should only cook with Crisco, vegetable oil, canola oil, flaxseed, olive oil. Wait! Everyone is switching back to butter now…

Am I the only one who is confused about which kind of fat or oil 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 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 when it comes to brain-healthy DHA and EPA. You can check your data below to see which group you fall into.

Polyunsaturated Fats

Fats, made up mainly of hydrogen and carbon molecules, 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 allows saturated fats to form straight-chains packed together, resulting in solids at room temperature (e.g. coconut oil). 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 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. You will also find the omega-3 fatty acid 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. There are small amounts of omega-6 (as arachidonic acid) found in chicken, eggs, and beef.

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

Often, we think of fats as 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. The body also uses omega-6 and omega-3 fatty acids 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. 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]

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-linolenic acid and our bodies change them 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 train of thought for why it might be pro-inflammatory, arachidonic acid leads to higher eicosanoids, which are important in allergic inflammation.[ref]

Specific omega-3 fatty acids:

Similarly, your body also transforms omega-3 fatty acids. Most food sources of omega-3 from plants 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).

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 from which pro-resolving lipid mediators are formed. Recently, researchers have figured out that the resolution of inflammation is actually an active process that relies on specific pro-resolving lipid mediators that are derived from DHA and EPA.

Related article: Specialized Pro-resolving lipid mediators

Shared enzymes:

The metabolism of both the omega-6 and the omega-3 fatty acids involves the same enzymes. 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 more of the omega-6 will be metabolized into arachidonic acid and less EPA and DHA will be produced.

Genetics of Fatty Acid Metabolism

Members: Log in to see your data below
Not a member? Join now to see your data below.

The FADS1 (codes for delta-5 desaturase) and FADS2 (codes for delta-6 desaturase) genes have several different variants that 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]  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 is 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 .


The body uses the same enzymes 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.

Diet: Limiting omega-6s and increasing omega-3s

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 is high in omega-6 oils. [ref]

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

  • fish oil (DHA, EPA)
  • seal oil
  • flax seed (alpha-linolenic acid) (must be converted with FADS enzyme)
  • chia seeds (must be converted with FADS enzyme)
  • caviar

Ancestral Diet:

Researchers believe the FADS1/2 variants 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 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 carried the variant and who ate a diet low in omega-6 fatty acids had a lower BMI and a 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 cautions:
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 it to DHA and EPA. There are vegan options for DHA supplements available now.

Moderate fat intake to lose weight:
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.

Pregnancy alert:

Pregnant or TTC? 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]


Fish Oil Supplements:
After reading through this information and realizing you might need to increase your DHA/EPA levels, reaching for a fish oil supplement could be on your list. Mercury and other contaminants 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.

Recap of your genes:

Gene RS ID Risk Allele YOU Notes about the Risk Allele:
FADS1 rs174546 T These variants decrease conversion of linoleic acid to arachidonic acid, and alpha-linolenic acid to EPA and DHA.
FADS2 rs1535 G

Related Genes and Topics:

Do you carry the Hunter-Gatherer or the Farmer Genetic Variant?
Our ancient ancestors lived much differently than we do today. They were hunter-gatherers, living off of fish, meat, and plant foods that they gathered. A huge shift took place when those hunter-gatherers began farming, growing grains, and storing them so that there would be food available all year.

LDL Cholesterol
Heart disease is the leading cause of death in the US and around the world, and high LDL-cholesterol levels have been linked in many studies to increased heart disease. Standard medical advice on ideal cholesterol levels and cardiovascular disease is often confusing, ever-changing, and sometimes downright contradictory.

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.