Butter is evil. Butter is the best! Only cook with Canola oil. Wait — everyone switch back to saturated fats. Olive oil, grapeseed oil, avocado oil, cold pressed, expeller pressed….  is palm oil now good?

Am I the only one who is confused by 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.

My simplified overview of the genes involved in PUFA conversion.

Polyunsaturated Fats:
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. Each one is metabolized in the body into other essential fatty acids. Common sources of omega-6 (as linoleic acid) in the diet include corn, sunflower, cottonseed, and peanut oils. Fats high in omega-3 as ALA include flaxseed and chia seed, while EPA and DHA can be found in fish oil.

Most nutritionists seem to agree that the ratio of omega-6 to omega-3 fatty acids is important to our health. It is thought that our ancestors in the past ate a diet with a ratio of omega-6 to omega-3 was less than 4:1. Currently, an average Western diet has a ratio of 16:1 or higher. Omega-6 fats can have both inflammatory and anti-inflammatory properties, and it is thought that the higher ratio of omega-6 to 3 is causing an increase in inflammatory diseases such as heart disease and diabetes.[ref]

There isn’t just one “Omega-6” fat. The term applies to a series of different chains of fatty acids that are changed in your body by 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, which can be pro-inflammatory.

Similarly, omega-3 fatty acids from plant sources usually 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). DHA and EPA are touted for their effects on lowering the risk of heart disease and for their brain health benefits.

So notice that 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.

Genetics of Fatty Acid Metabolism:
Genes definitely come into play here.  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? On the one hand, 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:
Note that some of these variants are considered linked, meaning that if you have the minor allele for one of them it is highly likely to have the minor allele for all of them.  

rs174546  (v.4 and v.5) – Risk allele is T.
Those with a T allele have lower enzyme activity[ref];  lower risk of coronary artery disease [ref]; lower conversion of LA to AA; minor allele benefits more from high intake of EPA and DHA to lower high triglycerides [ref]

rs174547 (v.4 and v.5 ) Risk allele is C
Lower gene expression for those with a C. [ref]

rs174537   (v.4 and v.5) Risk allele is T
Lower arachidonic acid and EPA levels [ref]; lower total cholesterol levels for the minor allele [ref] lower risk of type 2 diabetes [ref]

rs174548 (v.4 and v.5) Risk allele is G
Arachidonic acid and phosphatidylcholine is reduced in those with the minor allele[ref]

rs174550 (v.4 and v.5) Risk allele is C
Risk allele is associated with lower HDL and higher triglycerides [ref]

FADS2 Variants:

rs1535  (v.4 and v.5) Risk allele is G
A lower rate of ALA to EPA conversion in adults with the minor allele [ref]; increased DHA levels in breastfed babies with the minor allele [ref];

rs174575  (v.4 and v.5) Risk allele is G
Found to be part of a haplotype corresponding to higher linoleic acid and lower levels of arachidonic acid[ref]; several other studies on DHA in breastmilk that seem to possibly contradict each other.


Things to think about doing if you have FADS2 and FADS1 variants listed above: 

  • Reducing your omega-6 to omega-3 ratio is a good idea (cut out the fried fast food!)
  • If you have a clean source of fish, increase your fish consumption.
  • If you are supplementing with flaxseed oil or chia seeds, you may be converting very little into DHA and EPA.  A fish oil supplement may be a better way to go.

More to read:


Lauren · February 23, 2018 at 12:29 am

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!

    Debbie Moon · February 23, 2018 at 11:50 am

    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,

Lauren · February 24, 2018 at 12:16 am

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!

Laura · January 5, 2019 at 12:01 am

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 :)

    Debbie Moon · January 6, 2019 at 1:30 pm

    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.

A little lithium and B-12 makes the world a happier place – for some. | Genetic Lifehacks · May 22, 2016 at 12:17 pm

[…] Several studies have found that lithium reduces arachidonic acid (inflammatory polyunsaturated fatty acid) production in the brain.  It is theorized that this reduction of neuroinflammation is the reason that prescription strength lithium chloride works for bipolar disorder.  For more information about genetics and polymorphisms that affect fatty acid composition, check out the article on Omega-3 vs. Omega-6 fats and your genes. […]

Weight Loss Genetics – Leptin Receptor Polymorphisms | Genetic Lifehacks · July 15, 2016 at 2:16 pm

[…] Omega-3 fats can be found in fish and in flax seed.  You can find out which one is better for you by looking at your FADS1 polymorphisms. […]

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