Omega-3 Fats, Angiogenesis, and Cancer: Part I

In the book we discuss the issue of omega-3 toxicity (pp 56-58, 71-72), why it is most dangerous when omega-3 fats are combined with alcohol or fructose, and why fish oil capsules are particularly dangerous (see Fish, Not Fish Oil Capsules, June 16, 2010).

We recommend eating about 1 pound per week of omega-3 rich marine fish, like salmon, sardines, or herring, but taking no omega-3 supplements. This amount is sufficient to optimize the tissue omega-6 to omega-3 ratio for cardiovascular health, and is not so great as to raise great risks of toxicity. We also recommend avoiding mixing omega-3 fats with sugar or alcohol – a point I reiterated in last week’s post (How to Raise HDL, April 20, 2011):

Drink alcoholic beverages – but only when consuming meals low in polyunsaturated fats. Drink up when you eat beef, but be cautious when the entrée is salmon.

Some new papers have recently come out on the subject of omega-3 toxicity, and may lead some in the Paleo community, possibly including us, to reconsider our advice about omega-3 fats.

High Omega-3 Intakes in the Paleo Community

Our 1 pound fish per week recommendation works out to about 1.5 g omega-3 fats per day. But some Paleo authorities recommend much higher intakes.

Various emailers and commenters have mentioned Robb Wolf’s recommendations. Beth summarized Robb’s advice:

Robb Wolf promotes a short period of hefty omega 3 supplementation for unhealthy folks — on the order of 1g/10lbs of body weight per day.

Which would work out to 18 g/day for me, about 12-fold more than we recommend. Of course, if this is only for a short period, it may not be a big deal. However, I know from emails that some people take large doses continuously. Here’s one of my emailers:

Supplements are 10g of fishoil – 3.5g of epa/dha …

Bit surprised about [recommendation to reduce] the Fish oil, since i’m on the very low end of what other people are recommending, for fat loss as well, ie. robb wolf, poliquin etc.

The Whole9 folks host a Robb Wolf fish oil calculator which recommends that a 180-pound man take 4.5 g EPA+DHA per day. Depending on whether it is accompanied by other omega-3 fats in fish oil, this could be anywhere from 3 to 10 times our recommended intake, and is in line with what my emailer was taking.

Some Known Consequences of Omega-3 Excess

What are the likely consequences of omega-3 toxicity?

The obvious dangers are those related to oxidative stress from lipid peroxidation. The concern with omega-3 fats is not direct toxicity, but toxicity from their oxidation products. Omega-3 fats have a lot of fragile carbon double bonds which are easily oxidized: EPA has 5 double bonds and DHA 6. These are therefore among the most fragile lipids in the human body.

We would expect such problems to show up primarily in the liver and in the nervous system, where EPA and DHA levels are highest.

Indeed, they do. In mice, high dietary omega-3, in conjunction with alcohol or sugar, induces fatty liver disease. [1] In pregnant rats, excessive doses of omega-3 fats cause offspring to have shortened life span and neural degeneration. The authors concluded, “both over- and under-supplementation with omega-3 FA can harm offspring development.” [2]

However, there are associations of high omega-3 intake with disease in other tissues. In particular, emerging work is linking high omega-3 intake to diseases of pathological angiogenesis.

Angiogenesis is the creation of new blood vessels in mature tissue. (Vasculogenesis is the creation of vessels in a developing embryo.) It is a normal part of wound healing, but over a dozen diseases feature inappropriate angiogenesis.

Omega-3 Intake Is Usually Anti-Angiogenic

Before I go further, let me emphasize that nothing I am saying here repudiates the idea that it is desirable to bring tissue omega-6 and omega-3 fats into proper balance.

There are many studies showing that when tissue omega-6 to omega-3 ratios are too high, as on the standard American diet (SAD), additional omega-3 DHA and EPA can improve the omega-6 to omega-3 balance, reduce inflammatory signaling, and through reduced inflammation exercise an anti-angiogenic effect.

The mechanisms linking the anti-angiogenic effects of omega-3 to a condition of omega-6 excess are fairly well understood. Here is one description of the mechanism:

Here, we demonstrate that omega-6 PUFAs stimulate and omega-3 PUFAs inhibit major proangiogenic processes in human endothelial cells, including the induction of angiopoietin-2 (Ang2) and matrix metalloprotease-9, endothelial invasion, and tube formation, that are usually activated by the major omega-6 PUFA arachidonic acid. The cyclooxygenase (COX)-mediated conversion of PUFAs to prostanoid derivatives participated in modulation of the expression of Ang2. Thus, the omega-6 PUFA-derived prostaglandin E2 augmented, whereas the omega-3 PUFA-derived prostaglandin E3 suppressed the induction of Ang2 by growth factors. Our findings are consistent with the suggestion that PUFAs undergo biotransformation by COX-2 to lipid mediators that modulate tumor angiogenesis, which provides new insight into the beneficial effects of omega-3 PUFAs. [3]

So the question at issue is not whether omega-6 and omega-3 balance needs to be achieved. Rather, two points are at issue:

(a)  At what level of polyunsaturated (and omega-3) fat intake should balance be achieved – high or low?

(b)  Does overshooting toward an omega-3 excess generate significant or insignificant dangers?

If omega-3 toxicity is significant, then it will be important to achieve balance at low intakes of both omega-6 and omega-3, and to be careful to avoid overshooting to an omega-3 excess.

New Paper: DHA Linked to Cancer Progression

A new paper, just published yesterday, from “the largest study ever to examine the association of dietary fats and prostate cancer risk” has linked blood DHA levels to cancer risk. Specifically:

Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65) … [4]

This is a large effect: the highest quartile had 2.5-fold higher risk than the lowest-quartile.

That it was the omega-3 DHA specifically, and not polyunsaturated fats generally, that caused the problem, is supported by the fact that (note: edited to correct error in original post – PJ) omega-6 linoleic acid had no effect, and 18:1 and 18:2 trans-fats which are mostly obtained from partially hydrogenated vegetable oils were associated with protection against cancer:

TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). [4]

People in the top trans-fat quartile had only half the risk of people in the lowest omega-6 quartile. This makes it looks like omega-6-derived trans-fats were protective.

This result conflicts with the idea that the only influence of omega-3 fats is through regulation of inflammation; if so the anti-inflammatory omega-3 would have suppressed cancer. As lead study author Theodore Brasky said in the press release:

“We were stunned to see these results and we spent a lot of time making sure the analyses were correct,” said Brasky, a postdoctoral research fellow in the Hutchinson Center’s Cancer Prevention Program. “Our findings turn what we know — or rather what we think we know — about diet, inflammation and the development of prostate cancer on its head and shine a light on the complexity of studying the association between nutrition and the risk of various chronic diseases.”

Angiogenesis A Possible Pathway

Angiogenesis is very important for cancer progression. Cancers need to form angiogenic vessels if the tumor is to be able to grow beyond about 0.5 mm (0.02 inch) in diameter.

Indeed, angiogenesis seems to be a controlling factor for cancer mortality risk. It is believed that 50% of adults over age 40, and 100% of adults over age 70, have microscopic cancers. However, most tumors never develop an ability to induce angiogenesis and thus the tumors never grow beyond 0.5 mm and cause no observable disease.

Dietary factors that promote angiogenesis favor cancer progression, and anti-angiogenic factors tend to prevent cancer progression. Diet seems to be crucial for cancer prevention. Here is a TED video by Dr. William Li discussing the link between angiogenesis, dietary influences upon angiogenesis, and cancer.

Conclusion

So far, we’ve set the stage. On Thursday I’ll discuss a mechanism by which excessive DHA intake may promote angiogenesis. If this mechanism is important, then excessive fish oil or DHA supplementation may act as a major cancer-promoting food.

UPDATE: The next post in this series: Omega-3s, Angiogenesis and Cancer: Part II

References

[1] Nanji AA et al. Dietary saturated fatty acids: a novel treatment for alcoholic liver disease. Gastroenterology. 1995 Aug;109(2):547-54. http://pmid.us/7615205.

[2] Church MW et al. Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring. Neurotoxicol Teratol. 2010 March – April;32(2):171-181. http://pmid.us/19818397.

[3] Szymczak M et al. Modulation of angiogenesis by omega-3 polyunsaturated fatty acids is mediated by cyclooxygenases. Blood. 2008 Apr 1;111(7):3514-21. http://pmid.us/18216296.

[4] Brasky TM et al. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial. Am. J. Epidemiol. April 24, 2011 DOI: 10.1093/aje/kwr027 (Will be at http://pmid.us/21518693.)

Leave a comment ?

69 Comments.

  1. One of my favorite ways of eating herring is to eat it marinated in wine sauce, although finding this commercially made without HFCS is difficult. Fortunately, our local food coop does carry it. But this preparation tends to be fairly sweet. I have taken to rinsing the fish chunks before I eat them, but now I wonder if eating them at all is a good idea? It is hard to find herring in any other form readily available. In Europe, herring comes bottled with all kinds of flavors, even curry. Too bad we can’t get that in the U.S.!

  2. I’m not buying a blanket statement that linoleic acid prevents cancer. If that were true, then Americans, who consume large amounts of linoleic acid, should have very little cancer.

    I also find it tough to believe that DHA is causing prostate cancer, as again, most Americans are on the low side of DHA consumption, and yet prostate cancer is common.

    And as you’re well aware, there’s a fair bit of evidence tying linoleic acid to cancer in animals, at least.

    That said, it sounds like an interesting series.

    I’ve stopped supplementing fish oil, but tend more toward the view that n-6 consumption should be around 1% of calories daily, with n-3 at a similar or somewhat higher level, say up to 2%.

  3. Hi Paul,

    It seems that minimizing PUFA consumption and getting a low ratio between omega3 and 6 are important.

    I have been tracking my PUFA consumption using nutritiondata.com. I have found that a low ratio can be challenging at times if nuts, oilve oil, certain meats or avocado are in the diet. If I do consume a lot of omega 6 fats, I balance it with a tablespoon of cod liver oil. My PUFA consumption generally tends to be low since I try to avoid industrial seed oils.

    What are your thoughts on consuming cod liver oil? Should this be something I stop taking? I use Nordic Naturals that contains Vitamins D, A and E. I try to get about 1 gram of DHA and EPA a day from either cod liver oil or fatty fish.

    Thank you for your time.

    Erik

  4. And I thought I was supposed to drink wine with fatty meals, as wine protects from lipid peroxidation (PMID: 18540628 , 17712060)

  5. It’s all rather confusing, and sometimes it’s difficult to sort it all out.

    The only Omega 3 fish oil I will take is called Wholemega, from New Chapter. And I don’t take it every day, about 3X a week, because I have never been able to digest fish oil very well. I’ve never been much of a fish eater, unfortunately. The excellent quality wild-caught fish that I like – salmon, halibut, is very expensive here.

    I know you don’t recommend fish oil capsules, but what do you think of Wholemega? Hype? http://www.newchapter.com/fish-oil

  6. Hi Ann,

    It sounds tasty – as long as the sugar is removed!

    I do think moderate consumption is still advisable, but it’s best not to mix fish oil with fructose.

    Hi Tuck,

    Well, I wouldn’t buy such a statement either. Omega-6 fats can promote metastasis. They are also immunosuppressive, and immune activity against cancer is crucial. If omega-6 have benefits are due to DHA suppression, then eating less fish oil would be a better solution.

    Note also that I mis-stated the fat in question in the first post – it’s a trans-fat derived from omega-6. This complicates the interpretation.

    Cancer has many causes, and obviously DHA isn’t a common one. But fish oil has been a much-lauded nutrient for some time, and some people have started taking high doses. It may be that the dangers of high-dose DHA are starting to show up in studies.

    This study ran 1994-2003. I wonder when high-dose fish oil or cod liver oil supplementation became common?

    Hi Erik,

    Well, you seem to be following our book recommendations fairly precisely.

    The difficulty of getting omega-6 down is why we recommend red meats and seafood, butter coconut oil and beef tallow as fats, and suggest moderate intake of olive oil, avocados, chicken, pork, and nuts. It sounds like you’re doing well. It’s not necessary to take omega-6 to zero. Getting rid of vegetable seed oils is a huge step forward.

    I’m not sure whether there’s reason yet to adjust our omega-3 recommendations. Let me get through some more blog posts – Thursday’s and then some later posts on oxidation mechanisms – then I’ll be in a better position to make a judgment.

    Hi eric,

    There’s a substantial body of evidence linking omega-6 to cancer, and omega-3 to cancer suppression. You could have added a hundred more links!

    Obviously the mechanisms are complex. There are some pathways by which DHA retards cancer and some by which it promotes it. How this plays out in any given person is complex. But at very high DHA intakes, it appears the balance may shift toward cancer promotion in most people.

    This is not the only cancer study finding dangers from high DHA, as they note in their discussion.

    This is an emerging research area, so we’re going on little information.

    Hi Ben,

    Thanks much, hadn’t seen those and will have to read them! I’m more familiar with animal studies where they give high doses of alcohol and induce fatty liver.

    It would be great if low doses of alcohol are protective.

    It sounds like alcohol is protective against absorption of MDA generated in the stomach or in food, but is pro-oxidative in the liver.

    Hi Suzan,

    It is confusing and I’m afraid we won’t have solid answers for some time.

    Wholemega sounds like it’s very good when it starts … the issue is what is it by the time you swallow the capsule? Is the cost of eating wild-caught salmon once in a while really higher than the cost of the Wholemega pills for a similar dose of fish oil?

  7. I’ve been giving my (possibly autistic)toddler the Blue Ice fermented Cod liver oil every day for the past three weeks now…assuming it’s good for him. He hates it though and maybe I should lay off a few days each week? We don’t eat fish and the fish oil was the one aberration to our vegetarian diet. Any advice?

    thanks,

    Jay

  8. Hi Jay,

    It’s tough for me to advise you because I’m not familiar with the autism-fish oil literature, I’m not a fan of vegetarianism, and I don’t have much idea of how autism, vegetarianism, and fish oil interact.

    But personally I would probably follow his taste and back off. For a little person a teaspoon of cod liver oil is a huge dose.

  9. Thank you for the post.

    The best source of omega 3 from fish are fish eggs.

    http://nutritiondata.self.com/facts/finfish-and-shellfish-products/4098/2

    http://www.eurekalert.org/pub_releases/2009-12/f-sf-rom121109.php

    Yet, I have one concern about fish eggs. I am concerned that the eggs may contain anti-nutrients which we don’t know much about. For example, chicken eggs contain trypsin inhibitors and avidin (blocks biotin). Because fish eggs are defenseless against predation, I would expect that fish eggs would contain some form of anti-nutrients to discourage predation. Do you have an opinion of this?

  10. I have to wonder if a lot of the problem is the preparation.

    Most of this post is way above my pay grade, but if I understand it, the danger from omega3/6 and PUFA is when the oxidate. And cooking them, well, leads to oxidation.

    Perhaps sushi really is PHD?

    Bocherones, herring, other non-cooked fish (ceviche?) might be even better.

    My olive crusted salmon roasted under a broiler for 20 minutes — probably not.

  11. Hi JRM,

    That’s an interesting idea that I’ve never heard before.

    I’m not aware of any antinutrients in fish eggs, and a Pubmed search doesn’t turn anything up. But I suppose it’s possible.

  12. Hi eric,

    I’m looking at the first link you gave, a review of 1210 full-text articles: http://www.ahrq.gov/clinic/epcsums/o3cansum.htm

    They say:

    Significant associations between omega-3 consumption and cancer risk were reported for lung cancer in two studies; for breast cancer in one; for prostate cancer in one; and for skin cancer in one. However, for lung cancer, one of the significant associations was for increased cancer risk and the other was for decreased risk (four other risk ratios were not significant for lung cancer). For breast cancer, five other estimates did not show a significant association. Only one study assessed skin cancer risk. No effects were reported for cancers of the aerodigestive tract, bladder cancer, colorectal cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer. Thus, omega-3 fatty acids do not appear to decrease overall cancer risk.

    Data were insufficient to permit assessment of a temporal or dose-response relationship.

    This surprised me because I thought there was more evidence of omega-3 helping against cancer, at least at low doses and for standard dieters. It may be that we’re just starting to get real evidence.

  13. Hi robert,

    I suspect what’s most interesting is what other things are going on in the body to make DHA dangerous.

    But that’s a topic for another time.

  14. Seems like an opportune time to ask something I’ve wondered since I read your book, Paul. You recommend fish but not fish oil because of oxidation. But wouldn’t cooking fish at high temperature cause far more oxidation than what’s present in fish oil?

  15. Hi eric,

    I’m looking at the paper from your second link. It is interesting but hard to interpret. I am not sure why they did one set of measurements in female Swiss albino mice, and a totally different set of measurements in male Sprague-Dawley rats. You’d think they’d have measured serum markers at least in both, since it’s so easy. Yet they don’t report whether the effects are consistent in the different species. It’s suspicious when you have to exclude genders and use specific non-wild-type breeds to see an effect. Makes you wonder if they did more experiments than are reported and selected the data sets that produced results.

    However, it does count as evidence against the ideas I’m exploring this week.

    Nobody ever said biology was easy!

  16. Hi Dennis,

    Yes, cooking fish at high temperatures is unsafe.

    I prefer baking salmon, but sometimes we pan-fry at relatively low heat.

  17. Then there’s …

    Science Daily, 3/25/2009
    “Omega-3 Fatty Acids Reduce Risk Of Advanced Prostate Cancer”
    http://www.sciencedaily.com/releases/2009/03/090324131444.htm

  18. Thanks for the response, Paul.

    So we should start taking synthetic trans fats to protect our prostates? LOL. Pity about the other effects of trans fats…

    I don’t think I’m going to change my behavior based on this study, interesting as it is; but happily my behavior is well in line with your work already.

    Finally got the book and read it, and my wife is now trying to treat what looks like a mild hypothyroid condition using your supplements as plan A.

    Thanks for the great work, I left you a five-star review on Amazon. That seems to be about your average.

  19. Hi Gary,

    Thanks for that one. Seems in direct contradiction to the study in this post. I’ll look that one up.

    I would prefer that one to be true, since the 0.5 g/day they found beneficial is in the neighborhood of our recommendations.

    Hi Tuck,

    The trans-fat association is a mystery!

    Thanks for the review! I liked the “business-like … no time wasted” line.

  20. Paul,

    In regards to Iodine… so lets say 1 drop of Iosol gives me some bromide acne after a week. Will this taper off at this dosgae at some point? For instance, perhaps maybe in 2-3 months time, will I maybe not get the bromide acne at this single drop dose? Or will I have to keep going higher?

    Cheers.

  21. Hi Bill,

    If you’re getting acne I would be inclined to stay at that dose. It will taper off eventually, but I don’t know how long. It depends how much bromine you have in your body. Months is a reasonable estimate, but it could take longer.

    Higher iodine doses might chase the bromine out faster, but would give you more symptoms. I would wait for symptoms to lessen before increasing. With iodine, patience pays.

    Drink lots of water and take salt to speed up the excretion.

  22. Oy. I had held off on getting off fish oil supplements, because my husband has been so patient with all the changes I’ve fobbed on him, and I know he won’t want to give them up…

    Any thoughts on Dr. Mercola’s krill oil? He says they pass muster in terms of not being rancid, etc.

    Also, we talked a while back about my kids, who are on Carlson’s bottled fish oil, which is kept in the fridge, and Paul, you said that perhaps that’s OK because you can smell for rancidity…but I’ve been giving it to them in their juice! I’m guessing that’s a big fat no no?

    Sigh. Might be time to just toss the supplements, but the problem is, only one son and I will eat fish that is not fried.

  23. Hi Steph,

    Well, I’m not ready yet to change our advice for omega-3 consumption … this new study, combined with the mechanisms study, are just new information and it’s not looking as good for high-dose omega-3 as it was last year.

    I can believe that krill oil is very high quality when it goes into Dr Mercola’s pills. But in the end, DHA is DHA whether it comes from krill or salmon. And if the pills end up sitting on shelves or shipping crates, or even in refrigerators, for a long time, I’d rather eat salmon that I know was recently killed and kept on ice ever since.

    I do think it’s better not to mix the fish oil with fructose. Maybe put it in mashed potatoes?

  24. Fresh salmon is a bit expensive for a grad student like me.

    What do you think about canned salmon and sardines as a primary source of omega 3?

  25. Hi Eric,

    Since there’s not much oxygen they should stay in reasonably good shape, but you have concerns about BPA and such. You might look for BPA-free cans. Also frozen salmon may not be that expensive.

  26. The more we learn, the more it seems there is a j-curve for everything.

    Looking forward to the next post.

  27. Paul,

    As you know, I am also not generally a fan of fish oil supplementation. At the same time, I question whether DHA supplementation would truly play a causative role in the absence of a *pro-oxidative environment*.

    In other words, perhaps in someone eating a SAD, not exercising, under a lot of stress, etc. DHA is more easily oxidized and thus potentially carcinogenic.

    But in someone that is keeping all other oxidative risk factors low (i.e. they’re avoiding n-6, exercising, managing stress, reducing exposure to chemical toxins, etc.) I tend to doubt that supplementing with DHA could cause significant harm.

    Studies like this can be helpful in generating ideas, but my mantra lately has been “it’s the environment, stupid”. Meaning that it’s very difficult to parse out the effect of a single nutrient even in a well conducted study because 99% of them don’t control for very important variables (like those I mentioned above) that would affect the results.

    Of course there’s the question of therapeutic supplementation to correct an imbalance vs. long-term supplementation, too. For example, I could see a role for short-term, high-dose DHA supplementation for a senior with signs of dementia or early-onset Alzheimer’s, and there are quite a few studies demonstrating benefit. But I imagine that benefit would decrease over time as the n-6 ratio normalizes and the risk of oxidative damage from excess PUFA increases.

    Tricky, tricky.

    Thanks for another great article.

  28. Hi Chris,

    Yes, it’s true … DHA is not the problem, oxidized DHA is. So the question is what leads to high levels of oxidized DHA. High levels of DHA could be one ingredient in that, but at most is only part of the story.

    That said, everybody generates ROS. It’s central to a lot of biological processes, from metabolism to immune function.

    I suspect a lot of low-carb Paleo dieters may be deficient in some antioxidant minerals. As such, they may be vulnerable to lipid peroxidation. The sources of oxidative stress would be very different from that of SAD dieters, but could be significant.

    Well, the risk is not a matter that we’ll resolve quickly. Perhaps in 10 years! But we can build a better understanding of the issues.

    Best, Paul

  29. I’m confused now.

    Based on the current evidence what gives the best odds of preventing prostate cancer? (it runs in my family)

    Am I best to keep following the diet as laid out in the book?

    Also on a non-confused note before starting the diet I used to have extreme lethargy after getting home from work. When I’d come home from work, or if I went to the gym I’d feel like my blood sugar was negative 10,000. If I laid down I’d instantly fall into the deepest sleep imaginable. If I managed to go to the gym I’d feel like I could almost black out in between sets. I kept telling my boss I had “sick building syndrome” which I found on the internet, but he still made me work. 🙁

    I’m not sure what was wrong or what part of the diet fixed that, but I don’t experience that anymore. It was that way for a few years too, so that’s a good thing. So thanks.

  30. Hi MacAttack,

    I’d stick with the diet as laid out in the book. Intermittent fasting may also be helpful.

    Great news about your “sick building syndrome”!

    Best, Paul

  31. I don’t know, all this PUFA-oxidation is still a riddle to me. If they’re really that fragile how do they survive any processing at all? I mean even slow cooking fish is at least 70-80 C. And what about the n-3 in beef where the temperature is usually higher? Cooking (at least 100 C) of soups?
    And in this setting I don’t want even to think what happens to the n-3 in my kerrygold when preparing ghee!
    What about salting, smoking or marinating?
    Is there any hard data on oxidation-rate and end products?

  32. I have wondered myself whether cooking fish degrades the omega-3 content. From a quick pubmed search I have come across these 3 abstracts that seem to indicate that the PUFA content of fish does NOT degrade. However, I dont have the full text so I cant make any firm conclusions.

    Here are the links:
    Stability of Polyunsaturated Fatty Acids after Microwave Cooking of Fish
    http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2621.1987.tb14100.x/abstract

    Effects of cooking on the fatty acids of three freshwater fish species
    http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6R-49NPVTN-3F&_user=10&_coverDate=12%2F31%2F1993&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1733538298&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=1c4a3fb7f3d9493c0dfdba068332bd60&searchtype=a

    Stability of polyunsaturated omega-3 fatty acids during deep fat frying of Atlantic mackerel (Scomber scombrus L.)
    http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6V-49KK574-5F&_user=10&_coverDate=12%2F31%2F1993&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_searchStrId=1733536413&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9d07ada5f0912cd29b23ed3fc39308f3&searchtype=a

  33. Paul, Ray Peat has been talking about the dangers of pufa’s, both 3 and 6,for years. Chris Masterjohn also has a article EFA’S. Both have changed my opinion on taking fish oil.

  34. Hi Franco, molecular oxygen in air is much less dangerous than reactive oxygen species, or oxidative reactions involving eg sugars. Cook your salmon in sugar and you’ll get a lot more DHA oxidation.

    Woly, thanks much for those links. I always appreciate reader research!

    Kevin, thanks. Those are both very smart guys.

    I think as Abby says there is a J-curve, but it’s tricky to tell where the optimum is. I don’t think it’s above 1 g/day DHA however.

  35. I guess creme bruelle are not PHD compliant…..

  36. No DHA in creme brulee, robert! Eat away!

  37. Maybe if someone knew of the average amounts of DHA and omega-3s that the Kitava ingest we could get some clue as to what a safe amount is?

  38. Speaking of Ray Peat, I just came across this article in which he claims that steaming salmon at lower heat for longer duration produces more oxidized cholesterol than a quick pan fry at higher heat. What do you make of it? I can’t figure out which of his references relates to the statement.

    http://raypeat.com/articles/articles/cholesterol-longevity.shtml

  39. Hi Nelson,

    I don’t think the Kitavans ate much DHA – they are in warm waters and DHA is found in cold-water fish.

    But I don’t think we can assume that the Kitavan diet was perfect in all ways. Excellent, yes. Perfect, no.

    Hi Matt,

    That’s my trouble with Ray – he makes so many interesting assertions, but doesn’t link them to his references and it can take hours to investigate them to see how well supported they are.

    I am not sure what to make of that claim, as generally lower heats and longer cooking times lead to fewer chemical modifications. It could be that steam/water cooking is more dangerous than oil frying, since hot water can promote oxidation (as in iron rust). Or it could be the meat temperature that matters, and frying produces more oxidation near the surface but steaming more in the interior, since the internal temperature is high for a longer period. Or it could be a weakly supported assertion.

    We do baking and pan frying mostly, so I guess we’re in luck.

    His next line – “The toxic cholesterol content of the steamed salmon was much higher than that of beef cooked at a high temperature” – is no surprise: beef has little polyunsaturated fat and less cholesterol, so there’s going to be much less lipid peroxidation than in salmon even if the beef is cooked in a more dangerous way.

    I guess I’m doubtful as to the validity of that claim, but would be interested in seeing a reference.

  40. I’d like to see a comparison between fish oil and the comparable amount of oily fish, and then the outcome from that. I have to wonder if the fish oil is the problem – that it is not being detected appropriately and thus broken down, causing all sorts of problems in the meantime.

  41. Thanks, woly!

    I feel better now. 🙂

    Hi Paul,

    couldn’t it be that the pan frying (high heat) does exactly prevent oxidation because the surface is sealed quickly? So, no oxygen – no oxydation?
    Makes sense to me and seems congruent with the findings in the links woly posted.

  42. Hi Franco,

    It’s possible … maybe we should follow the chefs and sear at high heat for a few seconds and then lower the heat.

    I thought they did that for taste but maybe it’s healthy too.

  43. Ok, this is what infuriates me. :)) I am on a 2 week loading phase of fish oil per Poliquin’s advice then I read this about not taking fish oil supps. Its frustrating BUT EDUCATIONAl. Should I stop taking the fish oil and send it back?

    Because of a high LDL level recently(190) I switched from cooking with coc. oil to grapeseed oil to lower my ldl levels. Now, I don’t think that was the best idea. My sat. fat intake is probably helping me with all the beer I drink, no?

    mark

  44. Hi Mark,

    I think coconut oil is beneficial, especially for beer lovers.

    I don’t know what Poliquin’s advice is but it might be better to give the fish oil to one of your enemies!

    Best, Paul

  45. Health Links of the Week - 05/01/11 | StickItMedia - pingback on May 1, 2011 at 1:17 pm
  46. Ann-
    Costco in my area carries herring in wine sauce. It’s sweeter than I’d like but at least it’s sweetened with sugar and not HFCS. It’s in a glass jar (no BPA) and contains no preservatives.
    I agree with you – I wish Americans were as interested in herring as Europeans are.

    Peter

  47. I love the PHD book and diet. I’ve been following it several months. I am an ovarian cancer survivor and have been learning about nutrition since I was diagnosed in 2006. I am interested in the omega 3 controversy about quantity. I’m sure we haven’t heard the last word–science never provides that. But here is another study. How do you explain this one compared to the studies finding omega 3 promotes angiogenesis?
    Eur J Cancer. 2009 Aug;45(12):2077-86. Epub 2009 Jun 1.
    The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential.
    http://www.ncbi.nlm.nih.gov/pubmed/19493674

  48. Hi Sandra,

    In general dietary omega-3s are anti-inflammatory and anti-angiogenic. My conclusion after doing this series was that the drug, not dietary omega-3s, was responsible for high blood DHA levels and the elevated cancer mortality risk.

    Still, there is a risk of omega-3 toxicity under conditions of oxidative stress. So as you say, the issue is quantity. We’re sticking with our 1 lb salmon per week recommendation.

    Best, Paul

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