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Omega-3 Madness: Clarifying Recent Fish Oil “Research”

Written on September 17, 2012 at 5:12 am, by Eric Cressey

Today, I have a fantastic guest post from Dr. Hector Lopez, an expert in the world of nutritional supplements.  This post comes in response to a mainstream media report (you can read it here) that called into question the benefits of fish oil.  Hector and I had emailed privately about the concerns he had with this study, and I asked if he’d be willing to share his feelings with a larger audience.  Enjoy! -EC

I have been asked for my professional opinion on the recent attention drawn to the September 2012 systematic review and meta-analysis published in the prestigious Journal of the American Medical Association by Rizos EC et al [1].

As you can imagine, the few days have been very busy answering emails/calls from various stakeholders in the dietary supplement and omega-3 fish oil industries. The stakeholders range from friends and family to fellow scientists and colleagues, to high-level executives and principals of client companies. I have a few things to say about the manner (at times disingenuous) in which the meta-analysis has been misrepresented.

Multiple video segments from major media outlets have even quoted some of their experts as saying, “they would rather the public spend their money elsewhere as the proof is in with this study.” Perhaps they would feel more at ease suggesting the consumption of another box of “whole-grain” yet low fiber, highly processed cereal, “natural fruit juice,” or better yet, “linoleate-rich vegetable oils full of omega-6 fatty acids” (hey, they are polyunsaturated too, right)? ☺

I don’t mind the media sharing their opinion, but at the very least, they should attempt to educate the very audience that they are obviously trying to persuade. I find it hard to believe that the public would not be interested in some other material facts to allow consumers to make an informed decision:

1. Out of over 3600 clinical studies and citations retrieved, ONLY 20 were used in this “analysis.”

2. The absence of statistically significant association in these 20 studies between omega-3 and cardiovascular disease (CVD) endpoints does not prove that a significant reduction of CVD with omega-3 does not occur.

3. These 20 studies were on a diseased population that were already using multiple cardiovascular drugs such as beta-blockers, statins, niacin, fibrates, resins, and anti-thrombotics – all of which clearly confound outcomes/ endpoints of interest to dilute and wash-out effects of long-chain omega-3 polyunsaturated fatty acids (PUFA). Fish oil at this low dose was likely “too little, too late” to show any statistically significant benefit.

4. A similar meta-analysis on secondary prevention was published earlier this year [2].  And, clearly, the older studies showed benefit as these patients were likely not on as many cardio-protective medications. Hence, their was less of a “washout” in effect size.


5. A mean dose of less than 1.4g of EPA + DHA (the fish oils) was used in all 20 studies. This dose is typically far too low to compensate for the overabundance of omega-6 PUFA and imbalance in omega-6:omega-3 consumption in standard western diets. It’s no surprise that previous studies showing benefit of omega-3 fish oil in heart disease have utilized at least 2g of EPA + DHA. Future studies should also take this into consideration. In addition, future studies should attempt to carry out prospective data collection beyond two years.

6. There was no mention, consideration or control for background dietary intake of EPA/DHA or tissue fatty acids profiles. The researchers did not control for this important variable within each individual study included in this meta-analysis, and as a result, there is no way to determine if placebo groups already had sufficient levels of omega-3 in their diet or tissue, which would make it harder to demonstrate treatment effects of fish oil.

7. Clearly, these 20 studies were not adequately powered to detect changes in the CVD endpoints with omega-3 long-chain-PUFA, even if they were in fact present.

8. Interesting, despite all these flaws, based on the Confidence Interval data, there was still a “trend” toward cardioprotection! This was observed in terms of sudden death, myocardial infarction, cardiac and all-cause mortality. In other words, the data in this article still trended toward decreased risk of various cardiovascular disease outcomes. However, the headlines wouldn’t be juicy enough, though, so that was clearly glazed over. Hmm…

9. Sure, most Americans should eat more fish (in their whole food diet), but honestly, how many actually do? Where is the press coverage or meta-analyses looking at PCB/ Dioxin/ Persistent Organic Pollutants/Heavy Metal exposure? I suppose that when this omega-3 story dies down, the environmental toxin exposure story can quickly fill that void.

10. The findings of this selective meta-analysis are in direct conflict with the totality of the scientific evidence that demonstrates a cardiovascular benefit from fish oil in healthy populations, as well as in many of the populations with pre-existing CVD [3-10]. Consumers and health care providers alike continue to feel confident in the use of high-quality omega-3 fish oil for not only cardiovascular benefit, but also for supporting the health of just about every organ system in the body. The long chain omega-3 essential fatty acids found in fish oil are critical for everything from the cardiovascular system to the brain and nervous system, immune system, skin, joint and musculoskeletal tissues, to carbohydrate and lipid metabolism and beyond [11-19].

Finally, there is the issue of the potential mega-misrepresentation created by meta-analyses. It is evident that study selection criteria – as well as data extraction/synthesis – may allow researchers to make assumptions of consistency in the design individual studies included in the meta-analysis. As such, these assumptions may lead the authors – or worse, the less discerning media– to drawing erroneous conclusions. These erroneous conclusions then get virally disseminated throughout the general public. Doesn’t this string of events sound eerily familiar?

About the Author
 
Dr. Lopez is recognized for applying his uniquely diverse expertise in spine and sports medicine, endocrinology and metabolism, nutrition & exercise science, and clinical research to improving not only the health and quality of life in his patients, but also athletic performance in recreational and elite athletes. Dr. Lopez received his specialty training at the world-renowned Northwestern University Feinberg School of Medicine-Rehabilitation Institute of Chicago. He is currently a principal and the Chief Medical Officer of the Center for Applied Health Sciences, a multidisciplinary Clinical Research Organization in Ohio, and Supplement Safety Solutions, a Nutravigilance, Quality Assurance/Safety and Regulatory consulting company focused on dietary supplement/nutraceutical industry. An international speaker, author of popular press and peer-reviewed scientific journal articles, product developer, he consults for the nutritional supplement industry and professional athletes from the NFL, NBA, MLB, NHL, and Martial Arts. You can follow him on Twitter at @DrHectorLopez.

Note: You can find references for this entire article in the first post in the comments section below.

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33 Responses to “Omega-3 Madness: Clarifying Recent Fish Oil “Research””

  1. Eric Cressey Says:

    REFERENCES:

    1. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, and Elisaf MS. Association Between Omega-3 Fatty Acid Supplementation and Risk of Major Cardiovascular Disease Events. A systematic review and meta-analysis. JAMA. 2012; 308(10):1024-1033.

    2. Kwak SM, Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012 May 14;172(9):686-94.

    3. Yokoyama M, Origasa H, et al. JELIS Investigators. Effects of eicosapentaenoic acid on cardiovascular events in Japanese patients with hypercholesterolemia: rationale, design, and baseline characteristics of the Japan EPA Lipid Intervention Study (JELIS). Am Heart J. 2003;146:613-620.

    4. Kris-Etherton PM, Harris WS, Appel LJ. The Nutrition Committee. AHA Scientific Statement. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-2757

    5. von Schacky C. n-3 Fatty acids and the prevention of coronary atherosclerosis. Am J Clin Nutr. 2000;71:224S-227S.

    6. Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB. N Engl J Med. 1997;336:1046-1053.

    7. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trail (DART). Lancet. 1989;2:757-761.

    8. Albert CM, Hennekens CH, O’Donnell CJ, Ajani UA, Carey VJ, Willett WC, Ruskin JN, Manson JE. Fish consumption and risk of sudden cardiac death. JAMA. 1998;279(1):23-28.

    9. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011. 58(20):2047-67.

    10. Marchioli R, Levantesi G, Macchia A, et al. GISSI-Prevenzione Investigators. Antiarrhythmic mechanisms of n-3 PUFA and the results of the GISSI-Prevenzione trial. J Membr Biol. 2005 Jul;206(2):117-28.

    11. Simopoulos AP. Omega 3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991;54:438-463.

    12. Belluzzi A, Boschi S, Brignola C, Munarini A, Cariani G, Miglio F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr. 2000;71:339S-342S.

    13. Mills JD, Hadley K, Bailes JE. Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury. Neurosurgery. 2011. Feb;68(2):474-81.

    14. Black KL, Culp BR, Randall OS, Lands WEM. The protective effects of dietary fish oil and focal cerebral infarction. Prostaglandins. 1979;3:257-268.

    15. Milte CM, Sinn N, Street SJ, Buckley JD, Coates AM, Howe PR. Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls. Prostaglandins Leukot Essent Fatty Acids. 2011 May-Jun;84(5-6):153-61.

    16. Kremer JM. Effects of modulation of inflammatory and immune parameters in patients with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids. Lipids. 1996;31:243S-247S.

    17. Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. Am J Clin Nutr. 2011 Feb;93(2):402-12.

    18. Rodacki CL, Rodacki AL, Pereira G, et al. Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr. 2012 Feb;95(2):428-36.

    19. Sinn N, Milte CM, Street SJ, et al. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr. 2011 Sep 20:1-12.

  2. Jennifer Says:

    I’m not surprised that nobody asked for facts. Unfortunately many Americans will believe ANYTHING they see or hear from a “credible” source. It’s why politicians are so successful. I wish more people would ask questions and demand proof, but we have this self-proclaimed bright disease and we would never want to be proven incorrect! This is ‘merica!!

    Thank you for clarifying this research. I will continue eating my salmon. Yum yum!

  3. Jeff Says:

    Dr. Lopez, thanks for taking the time to set the record straight on this.

  4. Melissa Lehman Says:

    I conduct clinical researh for Ascenta Health,(who makes the #1 fish oil in Canada: NutraSea) and was also recently asked to comment on this study. Dr Lopez makes some excellent points. In addition to the flaws he has brought up; the studies reviewed also failed to assess serum levels of EPA and DHA before and after experimental intervention. Such a measure would be crucial to determine compliance and would help account for whether the dose given was substantial enough to impact membrane composition. Given that confounding variables were not properly controlled in the reviewed studies, information about physiological levels of EPA/DHA would have been necessary to ascertain cause and effect.

    I absolutely agree that dietary control during the study and qualitative information on diet prior to the start of the experiment were absolutely crucial! Without at least controlling for dietary intake of EFAs, the studies reviewed therein are frankly, quite useless.

    Thanks for opening up this topic for discussion!

  5. Sol Orwell Says:

    Great post. We did our own summary of this research too: http://examine.com/blog/fish-oil-and-major-cardiac-events—meta-analysis/

    I personally don’t fault the research, but the damn sensationalism that erupted out of it. Having my mom call me and say “hey you said fish oil is good for me, but the news is saying it’s just makes my urine expensive” is so damn frustrating.

    And great point on once this story is burned out, the toxin-in-fish story will be back in full force.

  6. Eric Cressey Says:

    Great post, Melissa; thank you!

  7. Bret Contreras Says:

    Good stuff guys!

  8. Greg Says:

    So let be be the first to ask..In Laymans terms what does this all mean?? Take or not?

  9. Brad Cole Says:

    Thanks for commenting. The media is terrible at accurately summarizing research. Based on your explanation, a proper summary would be that 1500mg of fish oil has little effect for a population that is diseased, medicated, and pursuing daily dietary trauma. One cannot out supplement an inflammatory diet and reverse a disease process with preventive interventions.

  10. Mike T Nelson Says:

    Good stuff from the doc as always. I totally agree with Melissa’s points above. You can run a simple at home blood test now that will tell you cell membrane levels (via red blood cell) of EPA and DHA, which is what you really want to compare.

    The media seems to have a fascination with any studies that are epi or meta-analysis based.

    Rock on
    Mike T Nelson PhD(c)

  11. Richard Todd Says:

    Dr. Lopez criticizes the other study for being “selective” in its choice of only 20 sources in its analysis. In the article above there are only 19 citations. Should we make anything of that? FYI: the Rizos EC et al study says the study selection was randomized.

    Also Dr Lopez, as noted in his bio above, is a “product developer” who “consults for the nutritional supplement industry”. His bio also includes two coined terms … “nutravigilance” and “nutraceuticals” which tells me he is on the side of encouraging/promoting supplement use and, no surprise, would be critical of any published article in JAMA or anywhere which concluded that a supplement was not associated with the benefits promoted by the industry he works for.

    Let’s keep it real, people.

  12. James Cipriani Says:

    This was simply a fantastic post. And a well needed one.

  13. Mike Canada Says:

    Good story. I submit though that we have to start looking to some other sources to get a good supply of Omega 3 because at this point in time, thanks to our greed and lack of proper oversight we have over fished our oceans and desecrated our rivers so that we no longer have a stable, healthy populated supply of fish.
    When I look at the state of our rivers and lakes it takes a mighty powerful hunger or a strong familiarity with the body of water that the fish is coming out of before I will eat fish anymore.

  14. Eric lagoy Says:

    Thanks for the guest post Dr. Lopez. Now that I’ve graduated from school and don’t have access to journal articles like I used to, its tough to critically review the new research out there. My questions would be what were the inclusion/exclusion criterias for selected studies if so few were selected out of so many initially sited, and yet even those selected still had inadequate effect sizes. It’s frustrating when meta analysis/systematic reviews, which we are suppose to hold at such a high standard, are still misrepresented to the general public, flawed, or lacking conclusive data.

  15. Ed Says:

    I think we need to be careful about how invested we are in a certain way of thinking, and accept the science for what it is. There is no use in stating that studies are invalid simply because we don’t like the results. That’s not a productive way to think about training or nutrition.

    There are a number of issues with Dr Lopez’ presentation of the evidence here.

    1. I don’t understand the “scare” quotes around “analysis”. I assume Dr Lopez is familiar with meta-analyses, and they are widely accepted. The study limited its scope to randomized clinical trials, which are widely considered the strongest, most useful evidence.

    2. This is true, but generally in science the burden of proof is on those claiming protective effects exist.

    3. I think this is the strongest part of Dr Lopez’ piece. This was a study of secondary prevention, rather than primary prevention of CVD. There may be benefits of n-3 in preventing CVD in the first place, however this is not as well studied.

    4. Agreed. This is a likely possibility.

    5. This is another very strong point.

    6. I’m sure Melissa and Dr Lopez are aware that in clinical trials, there is far less risk of confounding by any of the mentioned factors by virtue of the strength of the study design.

    7. On their own, some individual studies may not have been adequately powered for some endpoints, but that’s the point of the meta-analysis. To increase power to find an effect, which there was little of.

    8. These are not study “flaws,” as I’m sure you know, but limitations. There were not non-significant protective effects, but generally those are interpreted with great caution, particularly in the presence of multiple testing.

    9. Probably agree here.

    10. This current meta-analysis is a better representation of “the totality of scientific evidence” than the non-blinded trials and cohort studies which you cite. There is some heterogeneity in the studies, however, which is a valid concern about the validity of the analysis.

    Dr Lopez does make some valid points about the dose size being a possible reasons why we’re seeing this result, but I think this essay a disservice to the literature and scientific community by insinuating that a well-done study is somehow some conspiracy theory against fish oil.

  16. Ed Says:

    Also, and no disrespect to Dr Lopez, but I think his ties to the supplement industry don’t make him perhaps the most unbiased person to consult about the benefits of supplements.

  17. Ed Says:

    Also, please excuse many of the horrible typos!

    And! For the record, I still think fish oil is beneficial for a lot of other reasons. This meta-analysis is well-done, but of course limited in scope, as most studies are.

  18. Eric Cressey Says:

    Greg,

    I’m still taking it.

  19. Eric Cressey Says:

    Great post, Brad! Well said.

  20. Eric Cressey Says:

    Richard,

    I’d let Dr. Lopez speak to your specific concerns, but I can say without wavering that he’s among the most ethical and educated people I’ve encountered in the industry. He wouldn’t compromise his professional integrity just to defend a worthless supplement for the sake of someone’s bottom line.

  21. Time to see the light Says:

    Checking references is a good idea. Studies that apparently, for example, proved the “essentiality” of “EFA” done by the Burrs’ in 1929/1930 were done on rats.

    J. Biol. Chem. 1929 82: 345-367.
    A NEW DEFICIENCY DISEASE PRODUCED BY THE RIGID EXCLUSION OF FAT FROM THE DIET.
    BY GEORGE 0. BURR AND MILDRED M. BURR

    J. Biol. Chem. 86 (587)
    ON THE NATURE AND ROLE OF THE FATTY ACIDS ESSENTIAL IN NUTRITION.
    BY GEORGE 0. BURR AND MILDRED M. BURR

    The Burrs’ considered linoleic and linolenic acid as “essential” in the late 1920s, early 1930s, but at present EPA and DHA from fish oils are the “new” “EFA” despite no data backing up their essentiality either. I’ve never seen any research proving the essentiality of EPA, DHA, linoleic acid, or linolenic acid in humans (or rats) so this entire premise falls flat. “80 years of research” about “EFA” is not remotely true, especially as it pertains to DHA and EPA. Where is the 80-year-old research proving the essentiality of DHA and EPA?

    Here is what the “EFA” crowd has to do in order to remain relevant:
    1. Prove the essentiality of EPA, DHA, linoleic, and linolenic acid.
    2. Disprove the information that says these fats are harmful and find how “EFA” deficient rats were cured with nutritional interventions other than “EFA”.
    3. Provide explanation why humans and mammals that avoid such fats have a high respiratory quotient, resistance to stress and trauma, good health, and greater longevity than counterparts fed more “essential” unsaturates.

    The faulty premise of the existence of “EFA” only leads to more bad science. You can’t build a foundation of real science if the foundation itself is faulty. It’s bad science that’s product driven that the seed oil, pharma, and fish oil industries use to sell product. This false information trickles down into universities, and where it is stubbornly held onto as truth….BUT it’s nothing more than dogma.

    The skin problems that developed on the rats that were apparently from an “EFA deficiency” were later cured by nutritional interventions that were not “EFA” (like vitamin B6 – pyridoxine), disproving “EFA’s” apparent “essentiality.” Also, during this time researchers didn’t know what complete nutrition was nor had b-vitamins been discovered. Yet this is always THE research cited proving essentiality of fatty acids.

    Ray Peat, PhD says it quite well — “Several publications between 1936 and 1944 made it very clear that Burr’s basic animal diet was deficient in various nutrients, especially vitamin B6. The disease that appeared in Burr’s animals could be cured by fat free B-vitamin preparations, or by purified vitamin B6 when it became available. A zinc deficiency produces similar symptoms, and at the time Burr did his experiments, there was no information on the effects of fats on mineral absorption. If a diet is barely adequate in the essential minerals, increasing the metabolic rate, or decreasing intestinal absorption of minerals, will produce mineral deficiencies and metabolic problems.”

    Research Bulletin, University of Missouri, College of Agriculture,
    Agricultural Experiment Station, 333. September, pp. 1-12.
    Vitamin B6 pantothenic acid, and unsaturated fatty acids as they affect dermatitis in
    rats.

    J. Nutr. September 1, 1942 vol. 24 no. 3 225-234
    Linoleic acid, Pyroxidine, and Panthothenic Acid in Rat Dermatitis
    F. W. QUACKENBUSH, H. STEENBOCK, F. A. KUMMEROW
    AND B. E. PLATZ

    J. Biol. Chem. 1940 132: 539-551.
    ESSENTIAL FATTY ACIDS, VITAMIN B6, AND OTHER FACTORS IN THE CURE OF RAT ACRODYNIA
    H. Schneider, H. Steenbock, and Blanche R. Platz

    The skin problem was the consequence of a very high basal metabolic rate, and a greater need for nutrition that accompanies such a state. The rats weren’t “EFA deficient”; they were malnourished due to their high nutritional demands second to a high metabolic rate. By Burrs’ own admission, the “EFA deficient” rats had an exceedingly high respiratory quotient relative to the rats without the “deficiency.”

    The activity of cytochrome oxidase, a key respiratory enzyme, is very high in the absence of “EFA,” promoting a high metabolism. Supplementing with an “essential” fat predictably lowers the activity of the enzyme. Because metabolic intensity has a direct relationship to longevity in mammals, this simple suppression of metabolic activity is just one clue about the life shortening effects of the unsaturates. Anything that measurably shortens the lifespan shouldn’t be considered health promoting.

    Exp Biol Med May 1934 vol. 31 no. 8 911-912
    METABOLISM STUDIES WITH EATS SUFFERING FROM FAT DEFICIENCY
    GEORGE O. BURR AND A J. BEBER
    “The results show clearly that fat-deficient rats are very different from stock animals and that fat-deficient rats which have been cured with small doses of fats return to a much more nearly normal gas exchange. The most marked differences shown by the fat-deficient rats are higher basal rate, higher specific dynamic action of food, and higher respiratory quotients.”

    J. Biol. Chem., vol. 91, pp. 525-539.
    The metabolic rate and respiratory quotients of rats on a fat-deficient diet.
    WESSON, L. G., AND G. O. BURR 1931
    “Fat-deficient rats may synthesize much fat each day as indicated by high respiratory quotients. The fat synthesized from carbohydrate does not contain appreciable quantities of the essential fatty acids since these must be added to the diet to prevent decline and death. Although much smaller, the rats have a higher metabolic rate than their controls. Consequently, they have a much higher rate calculated as calories per square meter of surface.”

    (Note: “The fat synthesized from carbohydrate does not contain appreciable quantities of the essential fatty acids” — The fats the animals synthesized from sugar were not the “essential” variety. We don’t synthesize “EFA” from sugar because they’re harmful, NOT because they’re essential.)

    J Biol Chem. 1951 Apr;189(2):755-61.
    The effects of fat deficiency upon enzyme activity in the rat.
    KUNKEL HO, WILLIAMS JN Jr.
    The activity of the cytochrome oxidase, however, is markedly increased in fat deficiency…In each case the activity of livers from rats fed the basal diet was 38 per cent greater than from the linoleate-supplemented animals or from the animals receiving corn oil. This is particularly interesting in view of the observation of Burr and Beeber (8) and Wesson and Burr (9) that fat-deficient rats had a markedly increased metabolic rate. The latter authors reported that the basal and assimilatory metabolic rates of fat-deficient animals were 25 per cent greater than the rates of the control animals. Thus the liver cytochrome oxidase activity appears to parallel the metabolic rate in fat deficiency. This increased cytochrome oxidase activity in liver and perhaps other tissues may account in a large part for the increased metabolic rate.
    Summary
    “A fat deficiency in the rat causes a marked increase in liver cytochrome oxidase activity, a slight increase in choline oxidase activity, and a marked decrease in endogenous respiration. The activity of the succinic oxidase system is not altered by this deficiency condition. Supplementation with 100 mg. of methyl linoleate per rat per day reduced the cytochrome oxidase to the level of that produced by a 5 percent corn oil diet.”

    Experimental Gerontology Volume 2, Issue 3, August 1967, Pages 173–182
    Relation of lifespan to brainweight, bodyweight, and metabolic rate among inbred mouse strains
    John B. Storer

    J Gerontol A Biol Sci Med Sci. 2006 Oct;61(10):1009-18.
    Oxidation-resistant membrane phospholipids can explain longevity differences among the longest-living rodents and similarly-sized mice.
    Hulbert AJ, Faulks SC, Buffenstein R.

    Trends Neurosci. 2004 Oct;27(10):595-600.
    Free radicals and aging.
    Barja G.
    “The degree of unsaturation of tissue fatty acids also correlates inversely with maximum longevity.”

    Vopr Pitan. 1991 Mar-Apr;(2):36-40.
    [Characteristics of actual nutrition of the long-lived population of Azerbaijan].
    [Article in Russian]
    Grigorov IuG, Kozlovskaia SG, Semes’ko TM, Asadov ShA.

    The contrarian research that showed the non-essentiality of “EFA” was buried or just ignored because at that time seed oils companies were being ousted from the paint/varnish sector and needed to find a new market to sell their product. What better place than the supermarket. This also was teamed with the idea that saturated fats were causative in heart disease, and this created further momentum behind the marketing and refining/production of unsaturates as food. Bad research plus product marketing is a bad combo.

    A human study on the researcher William Brown done at the Burr’s laboratory (the same researcher who discovered “EFA”) produced some interesting results. I quote directly from my article “Errors in Nutrition: Essential Fatty Acids” below.

    “Attempts to intentionally induce an EFA deficiency in humans provided interesting results. (11) To test the effects of a very low fat diet on a human, biochemist William Brown volunteered to go six months in Burr’s laboratory eating such a diet. Chris Masterjohn discusses the results of this experiment in his article “Precious Yet Perilous: Understanding the Essential Fatty Acids.”

    “Inducing an essential fatty acid deficiency in an adult human proved much more difficult than curing one…Each day, he consumed three quarts of defatted milk, a quart of cottage cheese made from it, sucrose, potato starch, orange juice and some vitamin and mineral supplements. His blood lipids became more saturated and their concentrations of linoleic and arachidonic acids were cut in half. He experienced a marked absence of fatigue, his high blood pressure returned to normal, and the migraines he had suffered from since childhood completely disappeared.” (12)

    Brown experienced no skin abnormalities and “in spite of a supposedly adequate caloric intake” he lost weight as a result of improved metabolic function. The attempt to create an essential fatty acid deficiency improved the measured parameters in the experiment and Brown’s previous symptoms vanished. How could avoiding something dietarily essential create such marked improvements and produce NO skin abnormalities in six months?

    Animal studies where an EFA deficiency is induced by eating a no fat diet echo this same result as the animals in such experiments exhibit increased metabolic rate, low chance of cancer, and better withstood stress and trauma. Ray Peat further mentions the following in “Fats and degeneration”:

    “…a few experimenters were finding that animals which were fed a diet lacking the “essential” fatty acids had some remarkable properties: They consumed oxygen and calories at a very high rate, their mitochondria were unusually tough and stable, their tissues could be transplanted into other animals without provoking immunological rejection, and they were very hard to kill by trauma and a wide variety of toxins that easily provoke lethal shock in animals on the usual diet. As the Germans had seen in 1927, they had a low susceptibility to cancer, and new studies were showing that they weren’t susceptible to various fibrotic conditions, including alcoholic liver cirrhosis.”(10)”

    (10) Fats and degeneration by Ray Peat, PhD

    (11) THE JOURNAL OF NUTRITION, VOL. 16, NO. 6 DECEMBER, 1938
    Brown WR, Hansen AE, Burr GO, McQuarrie I.
    Effects of prolonged use of extremely low-fat diet on an adult human subject.

    (12) Precious Yet Perilous: Understanding the Essential Fatty Acids by Chris Masterjohn

    Since PUFA are found in small amounts even in all of the natural foods we’d (Ray Peat inspired folks) recommend, it’s difficult to be “deficient” in these “essential” fats. Coconut oil even contains 3% PUFA. We also have enzymes that can elongate and desaturate the ideally small amounts of linolenic acid we consume from plants into EPA and DHA; so why the need for supplementation?

    Why would I, as a 98+ degree human, supplement with oils that are the MOST unsaturated on earth (DHA having 6 double bonds and EPA having 5 double bond) and therefore the most unstable in the presence of heat and oxygen?! Why don’t cold water fish contain a predominant amount of saturated fat in their tissues yet coconut meat growing in temperatures analogous to the human body temperature is 97% saturated? Does body temperature play a role in the appropriate selection of fatty acid for humans? Does nature provide clues about appropriate food choices?

    Ray Peat, PhD (raypeat.com) has masterfully put together information about the toxicity of unsaturates since the 1970s. I suggest to anyone reading this to look into his material. His writings are of a completely different paradigm that is difficult to understand if you’ve been traditionally schooled or pumped full of dogmatic information for years.

    Additional sources in relation to the topic:
    Anti-Inflammatory Omega -9 Mead Acid (Eicosatrienoic acid)
    http://www.functionalps.com/blog/2012/04/10/anti-inflammatory-omega-9-mead-acid-eicosapentaenoic-acid/

    Errors in Nutrition: Essential Fatty Acids
    http://www.functionalps.com/blog/2010/12/19/errors-in-nutrition-essential-fatty-acids/

    Protective “Essential Fatty Acid Deficiency”
    http://www.functionalps.com/blog/2012/01/14/essential-fatty-acid-deficiency-resistance-to-traumastressshock/

    Metabolism, Brain Size, and Lifespan in Mammals
    http://www.functionalps.com/blog/2012/04/29/metabolism-brain-size-and-lifespan-in-mammals/

    Unsaturated Fats and Longevity
    http://www.functionalps.com/blog/2012/01/14/unsaturated-fats-and-longevity/

    PUFA, Development, and Allergy Incidence
    http://www.functionalps.com/blog/2011/12/01/pufa-and-development/

    PUFA, Fish Oil, and Alzheimers
    http://www.functionalps.com/blog/2011/02/12/pufa-and-brain-degeneration/

    PUFA Breakdown Products Depress Mitochondrial Respiration
    http://www.functionalps.com/blog/2012/03/22/pufa-breakdown-products-depress-mitochondrial-respiration/

    PUFA Accumulation & Aging
    http://www.functionalps.com/blog/2012/01/15/pufa-accumulation-aging/

    Fats and Oils: The significance of temperature
    http://www.functionalps.com/blog/2011/11/02/fats-and-oils-the-significance-of-temperature/

    Dietary Fats, Temperature, and Your Body
    http://www.functionalps.com/blog/2011/09/17/fats-temperature-and-your-body/

    “Curing” a High Metabolic Rate with Unsaturated Fats
    http://www.functionalps.com/blog/2012/04/03/curing-a-high-metabolic-rate-with-unsaturated-fats/

    Fat Deficient Animals – Activity of Cytochrome Oxidase
    http://www.functionalps.com/blog/2012/04/03/fat-deficient-animals-activity-of-cytochrome-oxidase/

    Fats and degeneration by Ray Peat, PhD
    http://raypeat.com/articles/articles/fats-degeneration3.shtml

    The Great Fish Oil Experiment by Ray Peat, PhD
    http://raypeat.com/articles/articles/fishoil.shtml

  22. Ed Says:

    Ray Peat writes in a completely different paradigm because his opinions seem to be unencumbered by any knowledge of the vast scientific literature that show benefits of fish oil.

    I would advise cracking open a basic nutrition textbook, rather than copying and pasting the titles of studies on rats from the 1930s.

  23. Time to see the light Says:

    Yes Ed and, clearly, you have looked at all the studies and links posted above AND corresponded (or at the very least read his books or newsletters) with Peat to support such a statement about his “paradigm and opinions being unencumbered”…

  24. Ed Says:

    Why would I need to correspond with the guy? All I have to do is read his writings. They don’t indicate any familiarity with modern nutritional research.

  25. Time to see the light Says:

    By his writings, you mean his website, I assume? And I susspect that you are assuming his research or the studies he explores and discusses have remained forever static? Have you even read one of his bimonthly newsletters? Like, ever? And, by your comment, I presume that you are proposing that good well-conducted studies, if they aren’t “modern”, are meaningless?

  26. Christian Says:

    I have to be honest as a student I find this all extremely disheartening, yet another frustrating finding to confuse health professionals. At uni you are shown how to effectively appraise and apply literature, mainly based on the quality of the methodology. Sytematic reviews of RCT’s are deemed most accurate, and when available their findings should drive best practice?
    In the absense of high quality research you work with what you have and combine with clinical experience and the specifics of the case at hand to determine the most appropriate diagnosis/screening/intervention e.t.c. To be honest it bothers me when such a paper is so heavily criticised when technically it is a reflection of the highest level of evidence available (considering methodology, statistical analysis e.t.c.).
    From my interpretation the findings of this article don’t dismiss the benefits of Omega-3, rather just conclude that based on the current availability of “best evidence”, we cannot say that it influences cardiovascular health” at this point in time. Sure as the author of this post mentions, the dosage, pharmaceutical interactions and the like may have influenced the outcome, but based on the highest quality of evidence that we currently have to date, we cannot make any conclusive statements. Hopefully this will inspire academics to conduct further high quality research that is mindful of the areas raised in this blog.

    Until then as a student and a consumer I wish the Ego’s of the world would stay out of the debate. This includes the educated and uneducated (media), who in many ways have conflicting intersts when associated with different supplement/media organisations.

  27. Ed Says:

    By his writings, you mean his website, I assume? And I susspect that you are assuming his research or the studies he explores and discusses have remained forever static? Have you even read one of his bimonthly newsletters? Like, ever? And, by your comment, I presume that you are proposing that good well-conducted studies, if they aren’t “modern”, are meaningless?

    Well, maybe he’s updated his website to include some stuff that makes sense. I don’t know. If he doesn’t believe the stuff that’s on his website anymore, then he should probably take it down.

    I don’t think that mouse studies from the 1930s are particularly useful when we have actual studies on humans using fancy modern assays. Things have changed a lot in the lab in the past 75 years, and we’ve learned how to measure stuff a lot more accurately. Think about how far we’ve come in training since then. Again, I strongly urge you to actually pick up a science textbook or take a class. It’s not easy, but you will learn good stuff!

  28. Time to see the light Says:

    “Again, I strongly urge you to actually pick up a science textbook or take a class. It’s not easy, but you will learn good stuff!”

    Aaahhhh, thank you for the kindly condescending remark Ed… If ONLY you knew…

    In case you hadn’t noticed these in my initial post, I’ll repost some worthwhile questions:

    “Here is what the “EFA essentiality” crowd has to do in order to remain relevant:
    1. Prove the essentiality of EPA, DHA, linoleic, and linolenic acid.
    2. Disprove the information that says these fats are harmful and find how “EFA-deficient” subjects were cured with nutritional interventions OTHER than “EFAs”.
    3. Provide explanation on why humans and other mammals that avoid such fats have a high respiratory quotient, resistance to stress and trauma, good health, and greater longevity than counterparts fed higher amounts of “essential” unsaturates.”

    And, I’ll reiterate: I am not suggesting we try to completely avoid unsaturated FAs. That would be unecessary, yet alone impossible, given that even the most saturated of fats contain at least some UFAs (coconut oil, for instance). But, to suggest that we should go out of our way to make sure we consume enough of these and worse, supplement them in isolated (i.e. fragile, oxidized states) form, that is the real issue here…

  29. Time to see the light Says:

    And, might I suggest you maybe read some unbiased science text and literature, on notions and paradigms that aren’t based on completely outdated and refutable basic physiology… Like, oh say, I don’t know, work by Albert Szent-Gyorgyi, Gilbert Ling, Broda Barnes, Hans Seyle, Constance Martin and the likes…

    As you suggested yourself: “It’s not easy, but you will learn good stuff…” :)

  30. Larry Says:

    So how is a consumer to know if the this Omega-3 supplement is better than that one ? Label clues, etc. Good vs. Bad or perhaps not so good. Obviously there are too many choices out there.

  31. Ed Says:

    Maybe those guys with all the conspiracy theories are right, and the overwhelming majority of other scientists are wrong, but I doubt it. I’ve already got way too much reading in peer-reviewed journals to do to finish grad school, though, so I guess I’ll just have to make do.

    Good luck with the theories, though!

  32. Dr. Lopez Says:

    Thanks for all the feedback and posts on this topic!

    First, my involvement as a consultant in the nutritional supplement industry is something that I fully and wholeheartedly disclose. However, it should not create an automatic dismissal of logic or rationale with respect to the topic. In one way or another we all have our biases. We should simply evaluate the position and points of contention with the understanding of any potential competing interests. It would be more problematic to read a position from someone who does not disclose it.

    Some great points above. Ultimately, in crowds we still make decisions as individuals. My criticism of this meta-analysis was based more so on how the media ran with a punchline of omega-3 fish oil supplementation being “useless.”

    The meta-analysis is pretty clear on the substantive limitations, yet those limitations in addition to the ones I mention in my post seem to have been overlooked by the media.

    Bottom Line: As both a health practitioner (and a clinical researcher who has followed this area for almost 2 decades), the totality of the available clinical evidence supports the use of methods to increase one’s tissue HUFA levels of omega-3 relative to omega-6 to at least approximately 50%. One of the most convenient, reliable and safe tools to reach this goal is via the use of a high-quality fish oil supplement. It is a matter of assessing risk vs. benefit. Therefore, it is in fact based on the preponderance of existing data on long-chain omega-3 intake for multiple organ systems (including the cardiovascular system) that should not dismiss this nutrient for OPTIMAL health.

    Unfortunately, the manner in which the media had interpreted this meta-analysis results in many individuals deciding to avoid fish oil supplementation that could otherwise have benefited substantially from it.

    Evidence-based medicine that relies strictly on the results of systematic reviews, Cochrane analyses and meta-analyses tend to oversimplify the interpretation of data with broad assumptions within the inclusion/exclusion criteria that the studies included in the analyses have a high degree of homogeneity. The sad truth is that many studies included in these analyses don NOT in fact have a high degree of homogeneity as I pointed out in the above reference.

    Finally, there are some fish oil manufacturers that pay very close attention to sustainability with respect to complying to fishery and marine stewardship guidelines for sustainability.

    My best to all, and it is very healthy to question and “trust, but verify” when someone takes a strong stance (for or against the conformist viewpoint).

    I will continue taking my fish oil and paying attention to my overall background diet.

    Cheers! :)

  33. Sifter Says:

    I believe there was study a couple of years ago, which surprised even the authors, showing that fish oil supplementation resulted in rats acquiring stage 4 stomach cancer. It was believed that while fish oil from sardines, etc is very beneficial, fish oil pills, per se, were not. Anyone care to comment on this?

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