Saturday, September 6, 2008

Omega Fats and Cardiovascular Disease

I noticed something strange when I was poring over data about the Inuit last month. Modern Inuit who have adopted Western food habits get fat, they get diabetes... but they don't get heart attacks. This was a paradox to me at the time, because heart disease mortality typically comes along with the cluster of modern, non-communicable diseases I call the "diseases of civilization".

One of the interesting things about the modern Inuit diet is it's most often a combination of Western and traditional foods. For example, they typically use white flour and sugar, but continue to eat seal oil and fish. Both seal oil and fish are a concentrated source of long-chain omega-3 (n-3) fatty acids.The 'paradox' makes much more sense to me now that I've seen

It's from the same paper as the graphs in the last post. Note that it doesn't take much n-3 to get you to the asymptote. Here's another one that might interest you:

The finding in this graph is supported by the Lyon diet heart study, which I'll describe below. One more graph from a presentation by Dr. Lands, since I began by talking about the Inuit:

Cardiovascular disease mortality tracks well with the n-6 content of blood plasma, both across populations and within them. You can see modern Quebec Inuit have the same low rate of CVD mortality as the Japanese. The five red triangles are from
MRFIT, a large American intervention trial. They represent the study participants divided into five groups based on their plasma n-6. Note that the average percentage of n-6 fatty acids is very high, even though the trial occurred in the 1970s! Since n-3 and n-6 fats compete for space in human tissue, it makes sense that the Inuit are protected from CVD by their high n-3 intake.  [Update: I don't read too much into this graph because there are so may confounding variables.  It's an interesting observation, but take it with a grain of salt.. SJG 2011].

Now for a little mechanism. Dr. Lands' hypothesis is that a high n-6 intake promotes a general state of inflammation in the body. The term 'inflammation' refers to the chronic activation of the innate immune system. The reason is that n-3 and n-6 fats are precursors to longer-chain signaling molecules called eicosanoids. In a nutshell, eicosanoids produced from n-6 fatty acids are more inflammatory and promote thrombosis (clotting) more than those produced from n-3 fatty acids. Dr. Lands is in a position to know this, since he was one of the main researchers involved in discovering these mechanisms. He points out that taking aspirin to 'thin' the blood and reduce inflammation (by inhibiting inflammatory eicosanoids) basically puts a band-aid over the problem caused by excess n-6 fats to begin with.
  [Update- this mechanism turns out not to be so straightforward. SJG 2011]

Lyon Diet Heart Study assessed the effect of n-3 fat supplementation on CVD risk. The four-year intervention involved a number of diet changes designed to mimic the American Heart Association's concept of a "Mediterranean diet". The participants were counseled to eat a special margarine that was high in n-3 from alpha-linolenic acid. Overall PUFA intake decreased, mostly due to n-6 reduction, and n-3 intake increased relative to controls. The intervention caused a 70% reduction in cardiac mortality and a large reduction in all-cause mortality, a smashing success by any measure.

In a large five-year intervention trial in Japan,
JELIS, patients who took EPA (a long-chain n-3 fatty acid) plus statins had 19% fewer cardiac events than patients taking statins alone. I don't know why you would give EPA by itself when it occurs with DHA and alpha-linolenic acid in nature, but it did nevertheless have a significant effect. Keep in mind that this trial was in Japan, where they already have a much better n-6/n-3 ratio than in Western nations.

In my opinion, what all the data
(including a lot that I haven't included) point to is that a good n-6 to n-3 ratio may be important for vibrant health and proper development. In the next post, I'll talk about practical considerations for achieving a good ratio.


Charles R. said...

My understanding from a lot that I've read is that the desirable ratio of n-6 to n-3 is 1:1 or 2:1, and that in the standard American diet it's upwards of 15:1 to 20:1.

How could it be more obvious what the major problem is in terms of heart disease? And for my dollar, it also explains the increasing incidence of ADD and ADHD, which years ago was shown to be connected to an imbalance of n3 to n6 fatty acids.

It ain't rocket science! But the idea that fat--any kind of fat--can be good for you, has been made impossible for people to entertain.

Jeff said...


Great post. I look forward to your advice on how to get in the right ratio in your next posts.



Dr. B G said...


You're a ROCKSTAR! This is awesome!!


Robert Andrew Brown said...


Not just heart disease or ADD and ADHD but all western conditions including neurological degeneration.

The Omega 3:6 balance, intake, conversion and oxidation to the downstream chemicals will be the nub of future medicine once people begin to accept this is the simple explanation for the dreadful rise in western conditions.

The probelms are;

There is no money to be made from the message by the drugs companies and the related "medical" industries.

It will require an enormous shift in medical priorities from treatment to prevention.

A significant number of medical truths will require rethinking. The whole of medicine will need to shift priorities to degenerations in ageing and condition's other than western ones.

National health will improve greatly. Many common profitable drugs will have reduce markets which means lower health bills but lower research funding.

Savings in treatment will have to be diverted into research on a model of social benefit rather than market driven product profit.

All of which suggests that this message will have to come from the top or the grass roots.

Nations are in competition and the health of the nation and associated costs are factors. Get those who wield power to personally change their Omega 3:6 profiles and see the results, and we may just be able to speed up what otherwise may be a very long process of change.

All of the human pressures are against this message getting the audience it deserves.

When the wider behavioural effect of pushing us to be more aggressive more selfish and dumber are taken into account the consequences of inaction could be the early demise of the species.

Robert Brown


Omega Six The Devils Fat

Pasi said...

Excellent post! Thanks!

I think that omega-3's prevents heart disease but you get diabetes instead. The answer is in that Krauss's picture Peter linked in his blog. Ox-omega-3 keeps lipids made from fructose or alcohol in hepatocyte saving vascular system from triglyserides but same time increases hepatic insulin resistance which leads to type 2 diabetes.

Does this make any sense?

Here's what happens if you don't have enough omega-3 to deal with omega-6:

"Predominance of esterified hydroperoxy-linoleic acid in human monocyte-oxidized LDL"

Stephan Guyenet said...

Hi Westie,

Peter also posted a link showing n-3 supplementation improves insulin sensitivity in the long term.

Pasi said...

Sorry to bother you but do you mean this from "On the plus side for fish (oils?)":

"Specific insulin sensitivity and leptin responses to a nutritional treatment of obesity via a combination of energy restriction and fatty fish intake."

There are billion links in Peter's blog; which is it??


- westie -

Stephan Guyenet said...


That's the one.

Pasi said...

I have to put few more words here about fish oil and IR. :)

That research was done with energy restriction and it shows that when you are living with negative caloric balance greasy fish will improve your HOMA-IR (which by the way isn't best predictor of hepatic insulin resistance).

I don't think this shows that fish oil supplement is good for IR if you are eating lot of carbs (wheat,fructose) or with more than moderate alcohol consumption.

In that case omega-3s will "fight" against reactive aldehydes from fructose or ethanol and lower inflammation but it will also lead to build up of fat in the liver and liver will be also more IR. In my opinion this is how Inuits get diabetes with high omega-3's.


Stephan Guyenet said...


Fair enough. There may be something to that idea.

The Pima get rampant diabetes without all the n-3 though. The major common thread seems to be the flour and sugar in my opinion.

Pasi said...

Flour and sugar will contribute to the issue of course but if you eat them only moderate amounts you will not get IR.

I think that it's the de novo lipogenesis in the liver(with the help of omega3s and 6s) that causes pathogenic insulin resistance.

By the way if Inuits lower their omega-3 intake in favor for omega-6 plant oils they might develope also CHD. Is there research to test this hypothesis?

Stephan Guyenet said...


I don't know of any study where n-3 was replaced by n-6 in the Inuit diet.

Anonymous said...

"Specific insulin sensitivity and leptin responses to a nutritional treatment of obesity via a combination of energy restriction and fatty fish intake."

The problem is that there are two variables in that study - energy restriction and fatty fish intake. You can't prove that omega-3 gave the benefits, unless the diet was iso-caloric. Also, they should try other interventions, like getting people to eat less PUFAs and more SFAs and MUFAs.

Herman Taller claims to have lost weight by eating 5,000 Calories a day with a very-low-carb and high PUFA diet. He told people eat eat safflower oil and corn oil as the main fat. Like 5 oz a day of those oils (1260 kcal). Did they worsen their cardiovascular health? Maybe and maybe not. The elimination of carbs probably gave some protection against the high-PUFA diet. Those PUFAs would probably have all been burned off in ketosis. The rest of his diet was meat, butter, cheese, eggs, fish, and nuts.

Stephan Guyenet said...


I do believe you can lose weight on a low-carb, high PUFA diet, but I don't think either of us would recommend it! Your point is well taken though that you may need more than one 'hit' to cause problems (e.g. PUFA plus glucose or fructose).

Anonymous said...
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Anonymous said...

Right. I think the combination of a high-PUFA and high-carb diet is the worst possible way to eat. High-fat and high-carb can be bad, unless it is combined with very high activity level: Michael Phelps, for example. The worst offenders are things like french fries, potato chips, pastry, cookies, pies, cakes, etc. PUFA may speed up metabolism, in the absence of carbs, but they're not palatable and probably not healthy long-term.

Jeremyinc said...

This is a great post, you obviously know a lot about the subject. I try to get my omega's but a lot of people do not know the food that they naturally occur in! I am working on a fitness site and I thought you might find this article informative benefits of cardio

P1 said...

You indicated that "Cardiovascular disease mortality tracks well with the n-6 content of blood plasma, both across populations and within them." Just a point of order: doesn't William Lands' research actually say that the risk tracks to concentration in *BODY TISSUE* and doesn't he go out of his way that the correlation is NOT to the concentration *IN PLASMA*?

For Westie: where are the studies that say Omega-3 promotes insulin resistance. Aren't essential fatty acids like Omega-3 only required in trace amounts by the body? How would dietary traces of Omega-3 cause any kind of substantial insulin resistance? I have seen studies that show saturated fats cause insulin resistance, and there you have a very very big problem, because saturated fats make up a huge part of the caloric intake for so many people. But Omega-3? I mean does anyone get even 3% of daily calories from Omega-3? It seems like a very odd idea to tie something like this to insulin resistance.

There is a SUPERB article in the American Society for Biochemistry's magazine here that summarizes the position of biochemists like Lands versus the AHA studies that say Omega-6 is good for you:

The point of the biochemists is that we should eat less Omega-6, not just eat more Omega-3, and there is an excellent point made in the linked article about why the definitive study testing this will not be done in our lifetimes.

It is extremely frustrating to me that the work of Lands and other biochemists has been completely drowned out by the American Heart Association.