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Heart disease begins with the oxidation of lipoproteins that are then taken up by macrophages, which may become foam cells, fatty streaks, necrotic lesions and then cause a heart attack or stroke if ruptured. Anything that increases the rate at which lipoproteins become oxidized will probably increase the potential for heart disease. In this study they fed 5g/day (which isn't even a megadose these days) to people with elevated triglycerides and gauged the resulting effects on the resistance that their VLDL and LDL had to oxidation. The result was a reduction in the time it took for oxidation to occur.

If it is generally accepted that PUFAs are unstable and prone to oxidation, and that you don't want your cellular membranes constructed of omega-6 fats, it stands to reason that you don't want them constructed of omega-3 fats either. Sure, triglycerides dropped, but you could do that with fasted exercise without the increased risk of lipoproteins becoming pathogenic due to oxidation and without the concomitant rise in LDL. Copper doesn't oxidize LDL or VLDL in vivo but the relative rates of oxidation should still be relevant for ROS in our blood. If 5 grams per day for 6 weeks caused that big of a change in oxidation rates, what about if you consumed that much for a year? Or if you consumed double or triple that much for a year?

It seems like the safe range for fish oil is not much more than 1 gram per day so that you're meeting the EFA requirement without flooding the system with so much of it that membranes construction is noticeably affected. I can't remember who it is in the community who recommends massive fish oil doses, but I sure as hell wouldn't do that. The best answer to past omega-6 intake isn't current omega-3 intake to "balance it out," it's current saturated fat intake to balance out PUFAs in general. Worrying about whether the oil itself is oxidized before you eat it is irrelevant if your lipoproteins are becoming oxidized as a result of PUFA-constructed membranes and PUFA transported in the VLDL as triglycerides.

Before and at the end of supplementation with 5 g/d fish oil the lag times and propagation rates of VLDL oxidation also correlated with the total number of double bonds in all PUFAs of VLDL

I pondered in another thread about whether omega 6 fats are really dangerous if you get enough omega 3s. Seeing this leads me to believe that overall PUFA intake needs to be only so large as to hit the EFA targets and not a bit more. Even better would be to take Chris Masterjohn's advice and to consume DHA and AA (instead of EPA) from normal food sources like pastured egg yolks, have them constitute a very small percentage of your diet, and avoid fish oil supplements altogether.

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Insightful, and I agree with your reasoning. I take a teaspoon of Carlson's each morning, which is around a 1 gram, but I'm starting to wonder if I really need it. I eat grassfed meats, dairy, and eggs every day, and I don't have any significant source of n-6 other than bacon. – Sean Drew Sep 21 2011 at 19:44
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 The fish oil used was only contained about 56% omega-3 fats. So the 5 g/d fish oil group were only getting ~2.8 g/d of omega-3. – Matt Sep 21 2011 at 19:48
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 If Travis keeps this up I'm going to be paranoid about everything......which likely does cause heart disease. – Don Sep 21 2011 at 20:43
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 What about the second and third study, the first study is hardly conclusive only testing for 3-7 weeks. "in HTG patients fish oil supplementation increased the serum LDL cholesterol concentration and the susceptibility of VLDL and LDL to oxidation." "These findings suggest that intake of fish oil increases oxidative stress, decreases cellular function, and causes organ dysfunction in SAMP8 mice, thereby promoting aging and shortening the lifespan of the mice." " – cliff Jan 13 2012 at 14:13
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 Our body tissue changes with diet, citing that the brain is 25% dha means absolutely nothing in terms of our actual need for DHA. – cliff Jan 13 2012 at 14:14
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6 Answers

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Ha you inspired me onto pubmed.

In the study that you linked the patients consumed 2.8 grams per day of omega-3 fat.

This more recent study looked at whether fruit and veg prevented fish oil induced LDL oxidation in smokers taking 4 g/d of fish oil.

"To determine whether consumption of five portions of fruit and vegetables per day reduces the enhancement of oxidative stress induced by consumption of fish oil."

Their assumption seems to be that oxidative stress is increased at least in smokers.

"Fish oil reduced the oxidative stability of plasma and LDL, but the effects were partially offset by the increased consumption of fruit and vegetables."

So maybe a good plant intake can mitigate the harm. This interesting quote is from the full text:

"The study lasted a total of 9 weeks, with three treatment periods. Plans to use a fish oil only supplemented group for 9 weeks as control were considered, but abandoned on ethical grounds because of the risk to health of an extended period of oxidative stress."

Curious about the difference between fish and fish oil I found this study. They fed 150 grams of baked herring 5 days a week for 6 weeks with an average of about 1.2 g/d of omega-3.

"No adverse effects on in vivo oxidation or serum antioxidants were found after herring intake."

A quote from the full text:

"Studies on n-3 PUFA intake have reported varied results on LDL susceptibility to oxidation (oxidation of isolated LDL); some observed no changes, some decreases, and some increases(56). It has also been shown that HDL can protect LDL against oxidation(57). Seierstad et al.(46) observed (1) no effect on circulating oxidised LDL after a salmon diet with 2·9 g EPA and DHA per d and (2) a small increase in circulating oxidised LDL after a salmon diet with only 1·5 g/d. These and our own results indicate that fish muscle antioxidants may play an important role in preventing in vivo oxidation."

I don't know if fish oil could cause heart disease. Maybe other beneficial effects outway the damage of oxidation. Still probably better not to increase your oxidation. Personally I am biased towards thinking that foods such as fish are better than fish oil supplements. I would not worry about a regular moderate intake of oily fish.

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I'm going to have a post in the next day or so about how to attack the risks of atherosclerosis from a bunch of angles. You're right in that oxidative stress is a major factor and by no means a constant. It's higher if you're a smoker, if you breathe air polluted with ozone, if you are deficient in vitamin E and vitamin C etc. Some of it like pollution is unavoidable so long as you live in a city, so it may be wise to be a little cautious with things like this. I'm also not going to avoid my weekly meal of sushi as a result of this however. – Travis Culp♦ Sep 21 2011 at 22:00
Very interesting - I wonder what the results would have been if they had tested cod liver oil, as it contains its own antioxidants eg retinol, vitamin e e.t.c. Equally, I wonder if there are any studies on say fish oil taken in conjunction with an antioxidant supplement instead of whole foods. – Simibee Sep 22 2011 at 0:56
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My main concern with large doses of fish oil are that there is a distinct anticoagulant effect (you get prone to bleeding) and the negative effect that large doses of EPA would have on your immune system. So I would say that yes, 1 gram per day looks like the upper bound, and even so, only when you are not having much fish during that particular days, or perhaps if you have in your diet a significant source of omega 6 as in poultry. Otherwise, I am convinced that oily fish is safer than fish oil!

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I take a much larger dose that you're describing, and have no issues with bleeding or bruising. In fact, the higher dose (resulting in a better ratio) results in (what I suspect to be) lower systematic inflammation and better cellular integrity, less bleeding in my case. – Matt Jan 13 2012 at 12:32
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I've tried 4 times to stop taking fish oil for anxiety and it doesn't work. I keep thinking that eating fish once a week, grass fed beef and eggs should eliminated my need for fish oil, but it doesn't work and I'm to the point that I don't want to the point I don't want to try, again. I can't get any work done, if I don't have a teaspoon of fish oil a day. It may be a placebo effect, but it's a damn good placebo effect.

But, this experiment was done on people that have elevated triglycerides. Is the experiment repeatable in people that have low triglycerides :under 50? People with low TRI's may not oxidize the fat. Under the new ratio guidelines, that aren't all that accurate they predict my VLDL at 9 because my TRI's are at 45. The funny thing is that my TRI's have gone down from 50 to 45 since increasing my carb in-take. I used to be ultra low carber at 10% and go a high as 20%. Now, when I calculate the percentages most days I'm not lower than 20% and no higher than 50%. I've eaten a lot of rice to get to the 50%. I wonder how fructose consumption plays into the oxidation of fat. Dropping fructose/fructan has been the biggest change in my my diet. And I haven't lost any weight.

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I postulated in another thread that the way in which we cook meat may cause the unsaturated fats to run off, so whether you catch and consume that runoff could indicate how much n-3 and n-6 fats you actually get from beef. Egg yolks are something else entirely, though the oxidation of those fats in cooking may render them less useful. Cooking eggs by boiling or by lightly cooking the yolk may be ideal. Eggs from conventional battery hens may not yield much DHA/AA. – Travis Culp♦ Sep 21 2011 at 21:18
Anyway, if there is a tangible benefit that you are experiencing, then obviously you should continue that practice. I wouldn't increase the dose however. Your points regarding the fact that their triglycerides are elevated (and thus turning over slowly) is absolutely valid. The difference in oxidation of the lipoproteins themselves may not be all that important in someone with low trigs like you or I, but if you're recommending fish oil to a non-paleo relative, that may actually not be good advice. – Travis Culp♦ Sep 21 2011 at 21:20
Another thing to consider is that these are but two types of molecules in the body that are affected by this tendency toward oxidation. What about endothelial cells in general? What about brain cells? What effect does this have on adipocytes? This could be a systemic problem that could affect the structure and function of all newly manufactured cells in the body, or at least anything originating from the liver. Seems risky to go down that road. – Travis Culp♦ Sep 21 2011 at 21:22
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 @Amy - Eating fish once a week will provide very much less omega-3 fat than a teaspoon of fish oil a day will. Beef and eggs contain very little. – Matt Sep 21 2011 at 21:53
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Are studies that mega-dose fish oil to more or less standard diets relevant to somebody eating a nutrient-dense paleo diet? I'm inclined to think that humans are perfectly capable of thriving at various ratios and amounts of PUFA in our diet. It's what we consume and do besides the PUFA that makes the difference. I don't have Pubmeds to reference and would guess there's no studies on the fact anyway, more of a logic-based sort of gut feeling.

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 PUFAs are implicated in cancer, heart disease, estrogen dominance etc. etc. Humans evolved in a tropical climate most likely on a low PUFA diet and when they did eat PUFA the foods were probably extremely rich in vit E. When you replace PUFA with saturated fat in alcoholics with fatty liver the fatty liver heals itself. – cliff Jan 13 2012 at 14:18
Nice answer, because it addresses the same issue that I have trumpeted for so long... that we can only extrapolate so much from these studies because they are not done on a massive group of people who eat Paleo (or at least a truly healthy diet). But even still, I don't think eating massive doses of fish oil is now or ever has been necessary. In fact, doing that doesn't even make sense logically. I think there is definitely some middle ground between the extremes. – Jack Kronk Jan 13 2012 at 16:13
For me, the burden of proof is on those espousing a particular practice that is inconsistent with the general understanding of evolution and evolutionarily-appropriate eating. It's true that if you're eating tons of saturated fat, you will dilute the fish oil in a way, but that still doesn't justify it. – Travis Culp♦ Jan 13 2012 at 18:25
@cliff, you're already looking a deranged system when considering liver-diseased alcoholics to begin with. It sort of makes my point, we don't really know the effects of high PUFA intake (via fish oil or otherwise) in paleo dieting folks. – Matt Jan 13 2012 at 23:11
I agree with you, Jack. Massive doses (how much do we mean by this) of fish oil probably aren't necessary. Heck, they probably aren't a good idea for folks who aren't eating a nutrient-rich diet and may have higher oxidation levels in their bodies. – Matt Jan 14 2012 at 3:58
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I have always used 2 grams per day as the upper limit and have always taken 1 gram per day.

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It depends on the quality of the fish oil and how it is handled and packaged to prevent oxidation.

http://paleodietnews.com/4136/paleo-diet-is-fish-oil-really-any-better-than-vegetable-oil/

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