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Omega 3 vs Omega 6 intake: what your ratio may mean for you

In some of the recent podcasts with John you’ll have heard us discussing omega-3 and omega-6 fats and how it may be the ratio of each of these fats, rather than the total amount of either, which play an important role in health and immune signaling.

But before we get into that aspect, a quick refresher of what these fats are, where they come from and what they’re used for in the body will likely be helpful.

Extending a bit on this post, omega-3 and -6 fats are both polyunsaturated fatty acids (PUFAs). So, as you may already know, this means some of the bonds between the carbon atoms are “unsaturated” with hydrogen atoms, this causes a double bond to form between the two carbon atoms which can introduce a kink into the structure of the fatty acid, meaning the molecules form a more disordered structure. This is why animal fats, which are typically saturated, are more likely to be solid at room temperature. This double bond also makes PUFA molecules more reactive than their saturated counterparts. 1

In sum, PUFA are more likely to be damaged and oxidized than are saturated fats.

So, both are PUFAs, where does the omega and the 3 or 6 come from? Below is the chemical structure of a PUFA molecule (in this case  alpha-linolenic acid (ALA)). To the left is what is known as the carboxyl group, and the carbon here (marked 1 in blue the diagram) is named the alpha carbon. If you go all the way to the right of the structure you have carbon number 18 (blue), as this is the last carbon it’s called omega.

To get the omega number you simply count backwards from the omega carbon, and note where the double bonds are. Here the first one is found at carbon 3 (red) from the omega end, hence ALA is an omega-3 fatty acid 2.

Common PUFAs, their sources and functions in the body

There are three main omega-3 fatty acids of interest α-linolenic acid (ALA), which is typically found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which can be made in the body from ALA but are also commonly found in marine oils and the fatty fish that eat them. On the omega-6 side there are two particular fatty acids we’re interested in, linoleic acid (LA) commonly found in plant oils (think sunflower oil) and arachidonic acid (AA) which is a product of the metabolism of LA, but can also be sourced from lean meats, eggs and particular oily fish 3.

Two important things to note here are that both ALA and LA are considered essential fats, in that the body cannot synthesize them and so they must be obtained through the diet, and that humans lack the ability to convert ALA to LA or vice-a-versa 3.

Our body needs both types of fats to control key processes, omega-6 fats for example are produced during and after strenuous activity for the purpose of promoting growth and during the inflammatory response to halt cell damage and promote cell repair by their conversion to omega-6 eicosanoids, lipoxins and endocannabinoids 4. However, alongside this anti-inflammatory aspect they also have a pro-inflammatory character which can occur when intake is too high (or omega-3 intake is too low).

Omega-3 is generally thought to be more benign or desirable with important roles in the resolution of inflammation, maintenance of brain health and even overall mood which John covers in this post.

So the simplistic approach is to just maximize your omega-3 intake, avoid omega-6 and enjoy good health right? Well sadly it’s not that clear cut for a few of reasons:

  • Avoiding omega-6 is actually really hard, many plant sources of omega-3 ALA are also rich in omega-6 LA;
  • Very high doses of omega-3 may actually be harmful to health, and may also contain omega-6;
  • Omega-3 and omega-6 share common enzymes, so too much of one can prevent the processing of the other, with omega-6 typically being vastly in excess (a typical western diet has a 6:3 ratio of 15:1 and upwards 4
  • It may be that omega-3:-6 ratio is not the best metric and EPA and DHA deficiency are instead 5

In both cases it’s hard to separate one from the other, and difficult to control the ratio. So the first step is to be aware of this ratio in your diet. John talks about an excellent tool Cronometer which you can use to do this. Assessing your omega-3 and -6 load in the body is more difficult, there are some labs, like Boston Heart Diagnostics, which will provide a readout of the ratio, but I’m not aware of any consumer available kit that can break it down further into specific types. This is important as knowing where you have an excess or lack of a particular fatty acid can alter how you choose to address this.

Therefore, the second step is understanding the pathway and how omega-3 and -6 can interact with each other.

The PUFA pathway

The omega-3 and omega-6 metabolism pathways. 

Image taken from: https://www.researchgate.net/figure/The-omega-3-and-omega-6-metabolism-pathways_fig3_317868706

Scary diagram time! So what we have here is a pathway diagram showing how the omega-6 LA and the omega-3 ALA are metabolized in the body. There are more steps than I’ve previously discussed, but on the omega-6 side you can see AA, as well as EPA and DHA on the omega-3 side.

Down the middle of the graph are the enzymes responsible for this processing, and as you can see they’re shared between omega-3 and 6 fats. The exact same enzymes are involved in converting LA into GLA as are in converting ALA into stearidonic acid 6.

This shared pathway is key to understanding health, if you overload one aspect of the pathway, and it is almost certainly going to be the omega-6 side, then those enzymes are going to be monopolized. The much smaller amount of ALA isn’t going to be converted to the same extent, and so there can be many more omega-6 downstream products than omega-3 downstream products.

There are several ways to target this, the first is to improve that ratio. A ratio of ~1:1 is thought to be optimal, but nigh on impossible to hit with current lifestyles and diets. But 10:1 is better than 20:1 etc… so making some dietary adjustments here can have a large effect. The 2nd option is to bypass the pathway and supplement directly with EPA and DHA, the things our body often really needs, and again this is something John covers in his post.

The final thing to take note of are your genetics, in particular one gene known as FADS1.

Fatty acid desaturase 1 (FADS1)

In the above diagram Δ-5 desaturase represents FADS1 and is important in the conversion of LA into AA and ALA into EPA and DHA 7. Located near the FADS1 gene the SNP rs174537 is particularly interesting 8. The ‘G’ allele is thought to be more active than the ‘T’ allele, with an almost 20% difference in processing efficiency between GG and TT homozygotes, the interesting thing here is it’s hard to assign a risk without an understanding of someones diet.

So for someone with a high omega-6:3 ratio then the slower ‘A’ allele may actually be more beneficial as it limits the conversion of LA into AA, potentially mitigating against the potentially harmful effects of AA. But such a person may benefit from adding EPA and DHA directly into their diet.

Conversely someone with a low omega-6:3 ratio may prefer to have the ‘G’ allele, in this case sufficient EPA and DHA should be being produced, and as overall omega-6 intake is low the potentially harmful effects of AA may be lessened.

This all leads into the final question. You know your ratio, understand the pathway and genetics, but what is a good level of AA?

Arachidonic acid and health

There is an emerging view that AA and omega-6 is that they’re purely bad for our health, promoting inflammation and disorders such as CVD and diabetes by driving things such as oxidative stress and lipid peroxidation 9-12. While there is a lot of evidence for this, the idea that they are purely bad is incorrect as there is also significant work showing AA having a beneficial effect 13. So how do we square this circle?

Well firstly we should remember that AA has important physiologic (used to maintain everyday health) roles, it forms part of the membranes that surrounds all our cells and the organelles within them, acts as a precursor for eicosanoid signalling molecules and can regulate gene expression directly through the PPAR-gamma receptor. It is likely only when this is dysregulated or overloaded that issues will arise.

A major part of this is the conversion of AA into a phospholipid (PL), rather than the triglycerides (TG) which you usually hear people talk about when discussing fatty acids. While not as simple as this you can broadly think of PLs as the bioactive form of lipids and TGs as the storage form. Now the conversion of AA into PLs is very efficient, but also quite low throughput, meaning it can get saturated very quickly. When this happens AA are instead converted into TGs and stored or circulated around the body in VLDL particles for storage in fat tissue. The important point here is that AA is required by the body and widely dispersed throughout all our cells and tissues, but when in excess tends to be stored as TGs in fatty tissue.

When required, these AA derived PLs can be converted into free AA and then converted into the various signaling molecules to kick-start an immune response right where it’s needed, and then also resolve when the issue is cleared. Problems arise however when this immune response becomes chronic and leads to systemic inflammation throughout the body. The question is whether increased omega-6 fats and AA can lead to this effect directly in someone with otherwise good health, or if an underlying health disorder is required for the and here there isn’t really a firm answer yet, with several very large studies showing conflicting effects, and there are several strands here which require further research.

Image take from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274989

In the diagram above you can see some of the key pathways that AA feeds into, and the huge array of effects they can have. It also demonstrates the many often competing effects AA can have. The cyxlooxegenase (COX) pathway is important in modulating the immune response. But what you can see is that both the cytochrome P450 and non-enzymatic pathways can inhibit this effect. So we have one molecule which can be converted to push multiple ways 14.

Free or stored

Is it free AA or AA stored as PLs and TGs that is the issue? Free AA is that which is circulating in the body and provides an immediate effect, the local stores of PL then come into play with all then being replenished by TG stores. One hypothesis is that having large amounts of omega-6 TGs stored in fat tissue prolongs and strengthens the immune response, increasing the risk of systemic inflammation developing and the associated health issues 15. Conversely, excess free AA has been shown to have potent cytotoxic abilities leading to cell death in numerous studies, which can be directly attributed to AA and not any of its metabolites in a cell model 16, how this fairs in vivo however is unknown as a wide range has been reported in health (0.1 µM to 50 µM in plasma) and disease (100 µM to 500 µM) 17.

Mediator, resolver or marker

The final question is perhaps the most fundamental. Is the elevated AA described in several disorders a mediator, i.e. are elevated levels of AA driving an increased CVD risk on their own (or in conjunction with an already poor environment)? Or are elevated levels a sign of the body trying to resolve the systemic inflammation? Or as a third option are elevated AA levels just a marker for poor health outcomes, and just a bystander 20?

Of the three the latter is the least likely option, but elevated serum AA will act as a good biomarker for poor health outcomes. For the other two questions the answer is likely to vary and we may need to identify which particular AA metabolites are elevated along with AA. For example if high AA levels correlate with pro-inflammatory AA metabolites in an individual we can say this will be harmful. If the reverse is true the effects are likely beneficial. This variation in response by different people likely accounts for the differing responses but we currently don’t have a good handle on what drives this difference, or how to reliably and cheaply test it in individuals.

What to do about arachidonic acid PUFAs

There are some things we can pull out and state with relative confidence though. In health plasma concentrations of AA can range from 0.1 µM to 50 µM, so quite a large range. In diseased individuals however levels of of to 500 µM have been found. So regardless of whether AA is causative of poor health, or a marker for it, those with an increased plasma concentration have a clear bio-marker of poor health. Getting a handle on your AA levels however can be tricky, as I’m not aware of any tests that available to consumers currently.

In those with pre-existing inflammatory conditions, or those that may be driven by inflammation, a high omega-6 intake is associated with worse outcomes. Reducing overall intake of omega-6 and increasing omega-3 is key here. How AA ties in here is clear, but a high level of AA with an underlying health issue is associated with worse outcomes, regardless of whether AA is just a marker or an actual mediator.

A high omega-6 to omega-3 ratio is associated with poorer outcomes, ideally we should all attempt to shift this ratio to include more omega-3, or bypass the pathway and supplement with EPA and DHA directly. The latter option may be better for individuals who may struggle to adjust their dietary intake, and with evolving research may actually be the best approach for all.

Finally, the SNP can be rs174537 useful to determine the best mechanism to modulate your omega-3 intake relative to omega-6. Homozygotes for ‘G’ may wish to alter dietary ratios, whereas homozygotes for ‘T’ may wish to try direct supplementation of downstream products.

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.

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