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This new study [1] published today in JAMA (popular press account) seems to suggest Omega-6 PUFA is the type of fat associated with the lowest all-cause mortality. 


If followed the 80K women and 40K men in the Nurses/Health Professionals Studies checking their dietary intake of fats through food frequency questionnaires every couple years. During the followup period of 1980-2012, 33K of them died. 


Interestingly, being in the quintile that ate the most fat and the least carbs was associated with a 16% reduction in total mortality compared with the other extreme. Just goes to show how crappy the carbs are that the average American eats...


Regarding the association of specific fats and mortality, here was the ordering of most-healthy to least-healthy: Omega-6 PUFA > MUFA > Omega-3 PUFA > Saturated Fat > Trans-fat.


Here are the mortality hazard ratios (95% CI) associated with being in the top (vs. bottom) quintile for consumption of each fat type, after controlling for "known & suspected risk factors":


ω-6 PUFA     0.81 (0.78-0.84)

MUFA          0.89 (0.84-0.94)

ω-3 PUFA     0.96 (0.93-1.00)

Saturated     1.08 (1.03-1.14)

Trans-fat      1.13 (1.07-1.18)


I don't have the full text yet, so I haven't looked at the details, but it is interesting to see that omega-6 PUFA came out on top as the healthiest fat to consume. This seem to contradict the conventional (folk?) wisdom that Omega-6 PUFA is pro-inflammatory and so we shouldn't eat very much of it, at least without balancing it with sufficient Omega-3 fats (e.g. in a 3:1 ratio).


Some interesting quotes from the popular press interview with one of the authors:


f people replaced a mere 5% of their calorie intake from "bad" fats with polyunsaturated fats, they could reduce their risk of death by 27%. If those calories came from monounsaturated fats, the risk of mortality dropped by 13%.


One reason MUFA may not have done better is the fact that a large fraction of the MUFA in the average American diet comes from animal products, which contain saturated fat along with other unhealthy components, which the researchers couldn't entirely control for:


"A large proportion of food sources of monounsaturated fat in the typical American diet are animal-sourced, such as dairy and red meats," Hu said, pointing out that those are also major sources of saturated fats. "Therefore, current analysis may not be able to completely distinguish the benefits of monounsaturated fat from the effects of food source and saturated fats."


The Omega-6 PUFA that was protective was, not surprisingly linoleic acid:


One polyunsaturated fat, an omega-6 fatty acid called linoleic acid, was shown in the Harvard study to be especially protective against death by cancer and coronary artery disease, Hu said.
Prior studies showed linoleic acid to reduce total and bad cholesterol, and to be associated with better blood pressure and insulin sensitivity. Though some studies have connected too much omega-6 with inflammation in the body, others find no such link.
Linoleic acid is found in sunflower, soybean and safflower oils, as well as nuts and seeds. Walnuts, Brazil nuts and peanuts are excellent sources, as are safflower, pumpkin and squash seeds.


Omega-3 Alpha-linolenic acid (e.g. from flax seeds and walnuts) wasn't protective against all-cause mortality, but does appear to be healthy for the brain, as other studies have found:


Another key polyunsaturated fat, the omega-3 fatty acid called alpha-linolenic, was not associated with "all-cause mortality," Hu said, but "interestingly, we found that alpha-linolenic acid was protective against death due to neurodegenerative disease."


I'd be really interested to hear Michael's take on this one, particularly the Omega-6 vs. Omega-3 finding - even if it's just an off-the-cuff remark. As Sthira mentioned yesterday in the olive oil thread, a little of Michael's insight is better than an in-depth report from him that he never has time to finish to his own satisfaction...





[1] JAMA Intern Med. Published online July 05, 2016. doi:10.1001/jamainternmed.2016.2417


Association of Specific Dietary Fats With Total and Cause-Specific Mortality


Dong D. Wang, MD, MSc1,3; Yanping Li, PhD1; Stephanie E. Chiuve, ScD1,2; Meir J. Stampfer, MD, DrPH1,2,3,4; JoAnn E. Manson, MD, DrPH2,3,4; Eric B. Rimm, ScD1,3,4; Walter C. Willett, MD, DrPH1,3,4; Frank B. Hu, MD, PhD1,3,4




Importance  Previous studies have shown distinct associations between specific dietary fat and cardiovascular disease. However, evidence on specific dietary fat and mortality remains limited and inconsistent.
Objective  To examine the associations of specific dietary fats with total and cause-specific mortality in 2 large ongoing cohort studies.
Design, Setting, and Participants  This cohort study investigated 83 349 women from the Nurses’ Health Study (July 1, 1980, to June 30, 2012) and 42 884 men from the Health Professionals Follow-up Study (February 1, 1986, to January 31, 2012) who were free of cardiovascular disease, cancer, and types 1 and 2 diabetes at baseline. Dietary fat intake was assessed at baseline and updated every 2 to 4 years. Information on mortality was obtained from systematic searches of the vital records of states and the National Death Index, supplemented by reports from family members or postal authorities. Data were analyzed from September 18, 2014, to March 27, 2016.
Main Outcomes and Measures  Total and cause-specific mortality.
Results  During 3 439 954 person-years of follow-up, 33 304 deaths were documented. After adjustment for known and suspected risk factors, dietary total fat compared with total carbohydrates was inversely associated with total mortality (hazard ratio (HR) comparing extreme quintiles, 0.84; 95% CI, 0.81-0.88; P < .001 for trend). The HRs of total mortality comparing extreme quintiles of specific dietary fats were 1.08 (95% CI, 1.03-1.14) for saturated fat, 0.81 (95% CI, 0.78-0.84) for polyunsaturated fatty acid (PUFA), 0.89 (95% CI, 0.84-0.94) for monounsaturated fatty acid (MUFA), and 1.13 (95% CI, 1.07-1.18) for trans-fat (P < .001 for trend for all). Replacing 5% of energy from saturated fats with equivalent energy from PUFA and MUFA was associated with estimated reductions in total mortality of 27% (HR, 0.73; 95% CI, 0.70-0.77) and 13% (HR, 0.87; 95% CI, 0.82-0.93), respectively. The HR for total mortality comparing extreme quintiles of ω-6 PUFA intake was 0.85 (95% CI, 0.81-0.89; P < .001 for trend). Intake of ω-6 PUFA, especially linoleic acid, was inversely associated with mortality owing to most major causes, whereas marine ω-3 PUFA intake was associated with a modestly lower total mortality (HR comparing extreme quintiles, 0.96; 95% CI, 0.93-1.00; P = .002 for trend).
Conclusions and Relevance  Different types of dietary fats have divergent associations with total and cause-specific mortality. These findings support current dietary recommendations to replace saturated fat and trans-fat with unsaturated fats.
PMID: 27379574 
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What always troubles me about such studies is that we are not seeing the full context of how these nutrients are consumed. Like Dean points out, the "more fat, less carbs = healthier" may be due entirely to the poor quality of carbs, since there's also research showing high carbs diets doing very well. Without seeing the rest of the context, it's hard to draw conclusions. Maybe the omega 9 would come out better if the subjects got them from vegetable sources, with no admixture of animal sources. Who knows what the upshot is. There was a study not long ago that went back over decade long studies that purports to show vegetable n6 oils to be worse than saturated fat in health outcomes! If I currently consume mostly omega 9 from almonds and EVOO, n3 from flaxseed, omega 3 from fish, with a bit of n6 from almonds on a regular basis, with whatever smaller amounts of FA come with the various F&V I consume (while I do eat avocados occasionally, they are not a regular part of my diet). Does this mean I should cut back on my omega 9 in favor of omega 6, based on this study? I don't think that makes sense, given that my diet is very different from the diet most of the women in this study probably consumed. It's an interesting study, but of value, I suspect, mostly to policymakers who are in charge of making dietary and health recommendations for the population at large. But it's not a super useful study to CRONies and CRON-like folks reading these boards, seems to me - at least as far as actionable information in our own diet planning. Opinions may differ, of course.

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A few more tidbits from the full text of the study (sent to me by Al - thanks Al!) showing Omega-6 (and esp. linoleic acid) was the type of fat least associated with mortality. Interestingly and quite directly, the authors say:


The ω-6:ω-3 ratio was not significantly associated with total mortality (P = .29 for trend).


But from the discussion:


A higher ω-6:ω-3 PUFA ratio was not associated with increased mortality, but with a slightly lower

CVD and cancer mortality.


Suggesting there might be some modest benefit from keeping a reasonable ratio of Omega-6s to Omega-3s. So don't entirely throw out your flax seed.


Here is a good graph showing how modest replacement of (crappy) carbohydratesas with the different types of fat appeared to influence mortality risk in these two healthcare professional cohorts:




As you can see from the long caption, they corrected for a long list of potentially confounding factors, including dietary cholesterol in their analysis and the results remained robust.


Regarding the less-than-very-impressive MUFA results, here is what the authors said in the discussion:



We found a significant inverse association between MUFA

intake and total mortality. In contrast, previous studies [refs]

generally reported nonsignificant or even positive associations

with MUFA. This discordance might be owing to the

strong correlations between MUFA and SFA, because animal

fats are major sources of both types of fats in most Western

diets, and between MUFA and TFA, because partial hydrogenation

produces both. In our 2 cohorts, the correlation between MUFA and

SFA decreased during the follow-up, and the

major food sources of MUFA have shifted from animal sourced

to plant-sourced foods over time (eTable 20 in the

Supplement); thus we had greater power to differentiate the

association of MUFA with mortality. Consistent with our analysis,

the major source of MUFA in Mediterranean populations,

olive oil, has been associated with a substantially lower total

mortality.[ref] Important benefits of MUFA from plant sources

have also been supported by the Prevención con Diet a Mediterránea

(PREDIMED) trial,[refs] in which the addition of olive

oil and nuts, also high in MUFA levels, reduced the incidence

of CVD and diabetes.


In short, they confirm MUFA is often confounded with high SFA intake in studies of free living people like this, since for many people eating crappy diets, their primary MUFA sources are animal products. They speculate the reason they saw a modest benefit of MUFA in this study (in contrast with previous one, which found no benefit or even some harm from diets high in MUFA) was that over time the two health-conscious cohorts they were studying shifted from animal sources of MUFA to plant sources (e.g. nuts and olive oil).


Tom, regarding the relevance of this study for people like us, I'm not entirely sure. Certainly I would discount the only modest benefits of MUFA this paper observed - expecting a diet composed of good-quality, plant-derived MUFA would fare much better.


But as for Omega-6 vs. Omega-3 PUFAs, it suggests to me we may be worrying about minimizing Omega-6 and maximizing Omega-3 more than is warranted.


But again I'd be interested in hearing what Michael, our resident (or maybe migrant...) dietary fat expert, thinks on the topic.



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So, a few things ...
Total omega-6/linoleic acid: it should first be noted that the first 3 quintiles of either one were all either below or right on the border of 5% of energy, which is the minimum Dietary Reference Intake range for linoleic acid/omega-6 (5-10% of energy) set by the National Academy of Medicine (formerly Institute of Medicine), and the extreme-high quintile (≈6.6%) is still toward the lower end of the recommended range. In an ad lib sedentary male 2500 Cal/d diet, that's 18 g/d, and for a sedentary female 1800 Cal/d, that's 13.2 g/d, which are similar similar to the specified "Adequate Intakes" of 17 g/d for men  and 12 g/d for women for males (and an AI is not the same as an RDA: it's enough, but could be more than enough). So what they're really finding is largely attributable to the fact that it's bad to be frankly deficient in omega-6. I myself target 12 g/d, which is only a little shy of that based on my energy intake; Dean, your 36 g/d of omega-6 (linoleic acid, since you're vegan) is right up on the extreme of the acceptable intake range, and higher than the at-least-slightly-too-high AI — this being one criterion by which to judge it "stupid high."
Second, the numbers on omega-6 and omega-3 (and, specifically, linoleic (LA) and linolenic (ALA) acids) may also be mutually confounded in a way that exaggerates the benefits of "high-ish" omega-6 intake and underplays the benefits of "high-ish" LA. As discussed in sections of  PMID: 21865817,(6) it turns out that the FFQs used in the Nurses' Health Study (especially the first few rounds) and Physicians' Health Followup Survey have only rather limited ability to discriminate the two fatty acids, and the authors imputed intakes of each based on undisclosed criteria, so while we can be reasonably sure about total intake of the sum of the two (tho' they may both be distorted to the extent that there is unaccounted-for oleic acid in some vegetable oils), there is necessarily some doubt about possible misclassification of LA and ALA (and to an extent vice-versa).


Additional complications not mentioned in (6) occurred in teh food supply itself during the course of the run of these two studies. First, canola oil was first given GRAS status in 1985, and apparently first introduced to market in 1986: it seems to me that this would make it extremely unlikely that the investigators' imputations of nonspecific food categories on the 1986 and very possibly even the 1990 iterations of the FFQ would have accounted for the gradual penetrance of this mixed n3/n6/mostly MUFA oil into the market, displacing high-n6 corn, sunflower, and safflower oils. And while (as they document) the particular vegetable oils and other foods began to be specified more carefully in the FFQs used from the 1990s onward than they had been in earlier ones, at the same time the composition of many cooking oils was changing, as historically high-omega-6 sunflower, safflower, and to an extent canola oils were slowly replaced with high-oleic, lower-PUFA hybrid and GM varieties. This would tend to lead even more strongly and specifically to an exaggeration of LA (and to a smaller extent ALA) intake, and to imputation of the effects (benefits) of oleic acid to LA (and to a small extent possibly dilute, and certainly distort, the effects (benefits) of ALA).
Omega-6:Omega-3 Ratio: There is, first, the key issue that this is the general population, where nearly everyone is omnivorous and thus getting some highly-unsaturated fatty acids (HUFA): arachidonic acid (AA) and  EPA+DHA. The main harms from omega-6 intake come from their interactions with the metabolism of ALA into omega-3 , either by competing for desaturase enzymes (LA) or by later product inhibition (LA, AA), and thus the synthesis of eicosanoids, inflammatory tone, and maintenance of tissue EPA+DHA. Much of this is bypassed by consumption of preformed EPA+DHA, and the potential for direct harm from omega-6-derived eicosanoids from LA diluted by AA, so the real potential for high omega-6:omega-3 is necessarily masked and the potential for benefit from keeping it low denied.
There is, further, the same basic problem documented above with the FFQs misclassifying LA and ALA with each other and to an extent with oleic acid, probably tending to exaggerate LA intake in particular; hence, the range is likely tighter and shifted downward from what's reported.
Further, even taking the numbers at face value and ignoring the presence of HUFA, the range of ratios is biased too high for the benefit of a low ratio to manifest: while the evidence does not allow us tot identify an ideal LA:ALA, there's a fairly strong case that it should be <4:1, and possibly as low as 1:1, whereas the lowest omega-6:3 in the  study is 5.5.
We have, finally, the contrasting evidence from randomized controlled trials, starting with those involving substitution of PUFA for SaFA. Two meta-analyses of such trials(1,2) generically reported substitution of "PUFA" for SaFA to reduce adverse cardiovascular outcomes. The PUFA in these trials were of course largely LA, and imputed to be all LA in much commentary. But when actually broken down by the type of oil used in cooking oil and soft margarine used as the substitute fat in (3) (and subsequently updated with unpublished data semi-heroically recovered from additional trials (4),(5)), the authors find that those trials that used oils with mixed omega-6 and -3 (soybean oil ± cod liver oil, and in one case corn + soybean) did indeed reduce adverse cardiovascular outcomes, whereas there was a nominal increase in such outcomes in the omega-6 only trials (using corn and/or safflower). The increases in the LA-based trials did not quite reach statistical significance in any of the meta-analyses, and were highest in (4); the addition of the Minnesota Coronary Experiment in (5) brought the number down again, perhaps in part because of heterogeneity in the study centers' provision of LA which varied from a reasonably 8 g/d to a high 13 g/d, whereas most of the LA-only trials in the meta-analysis used ≈15 g/d.
Not included in these meta-analyses is the Lyon Diet Heart Study (7,8), which (let us remember, tho' it is riduculously undercited in the literature) achieved the most dramatic results of any primary or secondary prevention trial on cardiovascular outcomes ever achieved, with drug or diet: a reduction of 73% in the rate of cardiac deaths plus non-fatal heart attacks, and of 70% for death from all causes(7); in subsequent followup, there was a suggestion of a reduced cancer rate.(8) In this trial, involving primarily the substitution of canola and olive oils and a trans-fat free margarine for butter and other SaFA sources, even the control group had only 5.4% of energy from LA, and the experimental group's actually declined to 3.6% – but this was against an increase of ALA intake from 0.27% to 0.81% of energy, for a ratio of just 4.5:1. SaFA also declined (from 11.3% to 8.3%), and MUFA rose to a similar degree (from 10.3% to 12.9%).The Lyon trial was excluded because it is not a simple PUFA-for-SaFA substitution trial, but involved adoption of various aspects of a Mediterranean diet, tho' most of the changes were quite modest aside from the changes in fatty acid intake).
At the very least, all of this strongly suggests that truly high omega-6 intakes and/or a high n6:n3 ratio is not beneficial on cardiovascular outcomes, and may be actively deleterious, even in AL omnivorous subjects, whereas more favorable ratios are beneficial; in veg(etari)ans not taking the hard-to-find, little-known, and expensive vegan DHA±EPA supplements, the harm is likely to be greater, and I would posit the same is true for high overall PUFA in people on CR, tho' my greater concern is of course high HUFA and especially DHA may counteract some of the benefits of CR.

AHA Science Advisory on Omega-6
Much of this also explains the non-finding of inflammatory or other harm from high omega-6 intake, and the finding of benefits for CVD outcomes, in the AHA Science Advisory on "Omega-6 Fatty Acids and Risk for Cardiovascular Disease" referenced by Mechanism in his first post (welcome, Mechanism!). As Ramsden et al and other critics have noted, many of the studies on which the AHA panel relied suffer from the key problem of reporting studies on imperfectly-discriminated LA and ALA (including the NHS, PHFS) as studies on LA. Their studies on inflammation involve experimental groups whose intake of omega-6 (11-21% of energy) is higher than the National Academy of Medicine's range (5-10%), and substantially higher than the "high-n6/high-LA" consumers in the NHS and HPFS. And while noting that the use of mixed-omega-6/3 interventions in some of the individual clinical trials they review (the same ones included in the various meta-analyses), they none the less describe them collectively as providing "Intakes of PUFA (almost entirely omega-6 PUFA [my emphasis]) rang[ing] from 11% to 21%". They particularly downplay the role of n-3 in the Oslo Diet Heart Study, stating that intervention subjects were given "recommendations to increase fish and cod liver oil," when in fact they were given "substantial quantities of Norwegian sardines canned in cod liver oil" as part of the trial. They then summarize the collective (non-meta-analytic) outcome of the aggregated "PUFA studies" as showing a favorable effect, rather than segregating LA-only from mixed-PUFA studies as Ramsden et al have done(3-5)), and then take it one step further by treating it thenceforth as if it were support for higher LA consumption when it is no such thing.
1: Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010 Mar 23;7(3):e1000252. Review. PubMed PMID: 20351774; PubMed Central PMCID: PMC2843598.

2: Skeaff CM, Miller J. Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomised controlled trials. Ann Nutr Metab. 2009;55(1-3):173-201. Epub 2009 Sep 15. PubMed PMID: 19752542.
3: Ramsden CE, Hibbeln JR, Majchrzak SF, Davis JM. n-6 fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. Br J Nutr. 2010 Dec;104(11):1586-600. doi: 10.1017/S0007114510004010. PubMed PMID: 21118617.
4: Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707. Erratum in: BMJ. 2013;346:f903. PubMed PMID: 23386268; PubMed Central PMCID: PMC4688426.

5: Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, Davis JM, Ringel A, Suchindran CM, Hibbeln JR. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016 Apr 12;353:i1246. doi: 10.1136/bmj.i1246. PubMed PMID: 27071971; PubMed Central PMCID: PMC4836695.

6: Ramsden CE, Hibbeln JR, Majchrzak-Hong SF. All PUFAs are not created equal: absence of CHD benefit specific to linoleic acid in randomized controlled trials and prospective observational cohorts. World Rev Nutr Diet. 2011;102:30-43. doi: 10.1159/000327789. Epub 2011 Aug 5. PubMed PMID: 21865817; PubMed Central PMCID: PMC3195369.
7: de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994 Jun 11;343(8911):1454-9. Erratum in: Lancet 1995 Mar 18;345(8951):738. PubMed PMID: 7911176.

8: de Lorgeril M, Salen P, Martin JL, Monjaud I, Boucher P, Mamelle N. Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate. Arch Intern Med. 1998 Jun 8;158(11):1181-7. PubMed PMID: 9625397

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Holy Moses, MR, this is an epic takedown! What a tour de force - and how depressing re: the integrity of data and conclusions one can draw from the various studies given the shockingly sloppy methodology. I don't know if I should be more impressed by your thoroughness and diligence or the hopelessness of much of the realm of nutritional science studies.


For many years now I've been mulling over adjusting my C:P:F ratios to lower C and elevate F, because so far (going on close to 20 years), I've had high C, moderate P and low F, and I know you frown on such ratios; my escape route was to argue to myself that if you keep your calories low enough, and get enough fat and protein to cover your minimum needs, then you are OK with allowing the rest of your calories to go to C, since the overall calories are low enough that the C in absolute terms is not extravagant. But I do recognize that perhaps this is suboptimal, and I really should rebalance my C:F ratio. 

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... Dean, your 36 g/d of omega-6 (linoleic acid, since you're vegan) is right up on the extreme of the acceptable intake range, and higher than the at-least-slightly-too-high AI — this being one criterion by which to judge it "stupid high."

Responding in the spirit of actionability over theory, Dean's number is close to landing for my omega 6, too (I avg, according to six months of cronometer, 35.6g/d). That blooms out from eating a wide variety of nuts and seeds. I've increased ground flaxseed for more balance; but I eat a wide variety of nuts because they're allegedly "healthier" (than...) other sources of high calorie food. Gotta chew them calories in from some food, eh, especially if you're twiggy semi-CRish?


So I'm stupid high also in omg6, and would welcome ideas on how to aim for less while also eating sufficient (vegan) calories.


More fresh olive oil? More fruit? Legumes? More grains? Of options all have downsides so the very fact of eating -- anything -- what's less stupid than whole nuts?


The goal here (for me) is healthy life extension in the face of glacially moving longevity advances.

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Thanks much for your thoughtful analysis of the paper [1] we've been discussing, which now has been assigned a PMID (27379574 - I edited my original post to include it). Your analysis points out how shockingly little we know with any degree of certainty about the true effects of various dietary components on health and longevity, and how variable results of studies can be depending on the methodology employed. No wonder the general public is confused about what to eat - when some studies (like [1]) purport to show n6 is the healthiest type of fat, while others (like the Ramsey et al PMID 21118617 you point to) seem to show n6 may even be detrimental, especially if not balanced with n3 fatty acids.


One surprising thing I learned from your thoughtful analysis effectively busted a misconception I was harboring - namely that on average Americans eat too much n6. As you point out, the data is muddied by the imprecision of food frequency questionnaires and by the fact that dietary fatty acid intake is really hard to pin down since FAs are found in so many processed / prepared foods as well as in ill-characterized "vegetable oils and spreads" used in cooking in ill-quantified amounts.


But the evidence we do have seems to show the belief that Americans eat too much n6 is misconception on my part. As you point out, at least in the population of health professionals studied in [1], a substantial portion (approaching 50%) reported eating less than the minimum recommended daily intake, and even the highest quintile of n6 / LA intake was nowhere near the top of the recommended range (i.e. 6.6% of energy from LA for Q5 vs. 5-10% recommended as the RDI).


One thing I think this points out is that "nutritionism" (the idea that foods are simply the sum of their nutrients, and that it's appropriate to focus on the nutrients we consume, rather than the specific foods, to determine the healthiness of a diet) is fraught with peril. Trying to focus on a single nutrient (in this case, n6 fatty acids and particularly LA) leads to a lot of confusion and contradictory results. 


Along these lines, one thing that none of these studies comparing fatty acids against each other take into account is the sources of the FAs. For example, it seems almost certain that getting n6 LA from a highly processed, and likely highly oxidized source such as generic supermarket "vegetable oil" probably has dramatically different health implications than getting n6 LA from carefully sourced and cold-stored nuts. This seems equivalent in many respects to the difference between getting MUFA from highly processed, low-grade supermarket olive oil (which I presume Michael you wouldn't touch with a 10 foot pole) vs. cold-pressed, high-polyphenol EVOO (or nuts). They are two very different things, with (presumably) very different health implications.






[1] JAMA Intern Med. Published online July 05, 2016. doi:10.1001/jamainternmed.2016.2417


Association of Specific Dietary Fats With Total and Cause-Specific Mortality


Dong D. Wang, MD, MSc1,3; Yanping Li, PhD1; Stephanie E. Chiuve, ScD1,2; Meir J. Stampfer, MD, DrPH1,2,3,4; JoAnn E. Manson, MD, DrPH2,3,4; Eric B. Rimm, ScD1,3,4; Walter C. Willett, MD, DrPH1,3,4; Frank B. Hu, MD, PhD1,3,4

PMID: 27379574 
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Dean's number is close to landing for my omega 6, too (I avg, according to six months of cronometer, 35.6g/d). That blooms out from eating a wide variety of nuts and seeds. I've increased ground flaxseed for more balance; but I eat a wide variety of nuts because they're allegedly "healthier" (than...) other sources of high calorie food. Gotta chew them calories in from some food, eh, especially if you're twiggy semi-CRish?

So I'm stupid high also in omg6, and would welcome ideas on how to aim for less while also eating sufficient (vegan) calories.


I've seen no evidence that a diet replete in n6 linoleic acid (LA) from carefully sourced and stored nuts and seeds is likely to be harmful, particularly when balanced with n3 alpha linolenic acid (ALA) from those same sources. Despite all the big words and erudite prose, nothing in what Michael wrote above, or the studies he points to, seems to contradict this perspective, at least as far as I can decipher.


As far as I can tell, Michael's reference to my "stupid high" intake of n6 PUFA is pretty much groundless hyperbole. He may (rightly or wrongly) think I'm eating a "stupid high" number of total calories, but given that, my n6 PUFA intake is within the 5-10% recommended range of total calories, and my n6:n3 ratio is 2.5:1, which is also quite good. 


If Michael knows of credible evidence1 to the contrary, namely that extra n6 LA is likely to be harmful even if carefully sourced and balanced with n3 ALA, I'm anxious to hear about it. 




1And no, I don't consider Michael's speculative "DHA-accelerated aging hypothesis" to have sufficient support to be considered credible evidence in favor of keeping long-chain fatty acids low. For details see my criticism of Michael's theory starting with this post and subsequent ones in that thread.

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Dean wrote:


I've seen no evidence that a diet replete in n6 linoleic acid (LA) from carefully sourced and stored nuts and seeds is likely to be harmful, particularly when balanced with n3 alpha linolenic acid (ALA) from those same sources.


As you have pointed out, there is tremendous variety in the sources of FA in the average diet. Most CR and CR-like folks here take great care to source and store their nuts, seeds and EVOO so that valuable nutrients are not destroyed by heat, light, oxygen, time etc. But we don't seem to have paid enough attention to a phenomenon we're all well familiar with in other food contexts: food processing goes both ways. Many foods benefit from processing or intake with other food groups - this we all know about f.ex. vegetables, where boiling/steaming and combining with fat can free up more f.ex. lycopene and make nutrients more bioavailable, or transform them altogether, like raw garlic vs crushed garlic etc. There is a place for raw food, but also for processed food (fermenting is another way of processing). Yet, this discussion is strangely absent or at least infrequent when we speak of nuts, seeds and oils. Here is a couple of examples:


PMID: 17924703


Changes in the phytochemical composition and profile of raw, boiled, and roasted peanuts.



Peanuts are consumed mostly as processed products. Although the effect of processing on isoflavone composition of legumes has been extensively studied, there has been no such study on peanuts. The objective of this study was to evaluate the effect of processing (boiling, oil- and dry-roasting) on the phytochemical composition of peanuts. Boiling had a significant effect on the phytochemical composition of peanuts compared to oil- and dry-roasting. Boiled peanuts had the highest total flavonoid and polyphenol content. The biochanin A and genistein content of boiled peanut extracts were two- and fourfold higher, respectively. trans-Resveratrol was detected only in the boiled peanuts, with the commercial product having a significantly (p < or = 0.05) higher concentration. Ultraviolet and mass spectrometry chromatograms for the boiled peanut extracts show the presence of four additional peaks that were not observed in the raw peanut extracts. [my bold TomBA]


Or see:


PMID: 22470019  (full free text available)


"Ground roasted peanuts leads to a lower post-prandial glycemic response than raw peanuts."


The point being, that Dean's original instinct about eating a varied diet is quite correct, and can be extended to food processing - raw has its benefits, but it also pays to selectively incorporate certain kinds of processed foods to get greater variety of nutrients. This includes seeds and nuts - and who knows, now this is 100% speculative and probably quite wrong - what if some small amounts of processed OO might have actual benefits? I mean, nobody is going to claim that rancid olive oil is superior to properly sourced, handled and stored EVOO - but that's not the idea. The idea is that in addition to EVOO, perhaps very small amounts of OO might have benefits, if nothing else through hormesis. I base this at least partially on the idea that when you conduct these studies of the Med diet in the population, and show all those benefits of consuming OO, I just find it hard to believe that your average Greek/Italian/Spaniard goes to anywhere near the kinds of trouble we do to carefully source and store their EVOO. Now, I have zero doubt that EVOO handled the way we do it is vastly superior. I am not disputing that in the least. I am just saying, what if variety in processing might not have some benefits here too, just as it apparently has with nuts and seeds. It's a question more than an assertion. In any case, all this variety makes for more variables and makes it even more of a difficult task to properly study nutrition in the population.

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Correct me if I'm wrong but my unoriginal opinion about food is that it's sorta like breathing: necessary but not healthy. Food -- processed or not -- isnt very good for us. Sure, it's necessary to keep smiling in survival, but isnt food as on a spectrum of less bad? Collards are less bad than bok choi, eg.


The reductionist aspect of cronometer (and word tussles like this thread) make me take the dietary practice less than seriously. I did pay for the cronometer service, though, but it only serves as sketchy until clearer (individually based) dietary pix pop into life, then they'll pop out again and be replaced by more accurate dietary reflections. I mean, who can possibly take these nutrition studies very seriously? They're guideposts and sometimes whoopsie they're pointing in ulterior motive directions.

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Plasma n-6 PUFA Linoleic Acid Inversely Associated with Diabetes


Not that I think focusing on particular micronutrients is the way to go, but this new study [1] posted by Al (thanks Al!) showed that the level of the most common n-6 PUFA in plasma, linoleic acid in the blood (rather than as vaguely reported in the diet) is pretty strongly associated with a reduced risk of type 2 diabetes (HR 0.80; 95% CI 0.77-0.83). This again suggests Omega-6 fats might not be as bad as we've been led to believe.


No other fatty acid tested came close to LA in terms of reduced T2D risk, although the plant-based omega-3 alpha-linolenic acid (ALA) was modestly inversely associated with T2D (HR 0.93; 95% CI 0.88-0.98). They didn't test plasma MUFA levels unfortunately, and even if they had and found it positively correlated with T2D, it might be because the MUFA in most Westerner's diet comes more from animals flesh than from EVOO...





[1] PLoS Med. 2016 Jul 19;13(7):e1002094. doi: 10.1371/journal.pmed.1002094. eCollection 2016 Jul.


 Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

Forouhi NG, Imamura F, Sharp SJ, Koulman A, Schulze MB, Zheng J, Ye Z, Sluijs I, Guevara M, Huerta JM, Kr?ger J, Wang LY, Summerhill K, Griffin JL, Feskens EJ, Affret A, Amiano P, Boeing H, Dow C, Fagherazzi G, Franks PW, Gonzalez C, Kaaks R, Key TJ, Khaw KT, K?hn T, Mortensen LM, Nilsson PM, Overvad K, Pala V, Palli D, Panico S, Quir?s JR, Rodriguez-Barranco M, Rolandsson O, Sacerdote C, Scalbert A, Slimani N, Spijkerman AM, Tjonneland A, Tormo MJ, Tumino R, van der A DL, van der Schouw YT, Langenberg C, Riboli E, Wareham NJ.
Free full text:
Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.
Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, ?-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [sD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with ?-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.
These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.
PMID: 27434045
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Effects of Saturated Fat, Polyunsaturated Fat, Monounsaturated Fat, and Carbohydrate on Glucose-Insulin Homeostasis: A Systematic Review and Meta-analysis of Randomised Controlled Feeding Trials


Abstract Background


Effects of major dietary macronutrients on glucose-insulin homeostasis remain controversial and may vary by the clinical measures examined. We aimed to assess how saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), and carbohydrate affect key metrics of glucose-insulin homeostasis.

Methods and Findings


We systematically searched multiple databases (PubMed, EMBASE, OVID, BIOSIS, Web-of-Knowledge, CAB, CINAHL, Cochrane Library, SIGLE, Faculty1000) for randomised controlled feeding trials published by 26 Nov 2015 that tested effects of macronutrient intake on blood glucose, insulin, HbA1c, insulin sensitivity, and insulin secretion in adults aged ≥18 years. We excluded trials with non-isocaloric comparisons and trials providing dietary advice or supplements rather than meals. Studies were reviewed and data extracted independently in duplicate. Among 6,124 abstracts, 102 trials, including 239 diet arms and 4,220 adults, met eligibility requirements. Using multiple-treatment meta-regression, we estimated dose-response effects of isocaloric replacements between SFA, MUFA, PUFA, and carbohydrate, adjusted for protein, trans fat, and dietary fibre. Replacing 5% energy from carbohydrate with SFA had no significant effect on fasting glucose (+0.02 mmol/L, 95% CI = -0.01, +0.04; n trials = 99), but lowered fasting insulin (-1.1 pmol/L; -1.7, -0.5; n = 90). Replacing carbohydrate with MUFA lowered HbA1c (-0.09%; -0.12, -0.05; n = 23), 2 h post-challenge insulin (-20.3 pmol/L; -32.2, -8.4; n = 11), and homeostasis model assessment for insulin resistance (HOMA-IR) (-2.4%; -4.6, -0.3; n = 30). Replacing carbohydrate with PUFA significantly lowered HbA1c (-0.11%; -0.17, -0.05) and fasting insulin (-1.6 pmol/L; -2.8, -0.4). Replacing SFA with PUFA significantly lowered glucose, HbA1c, C-peptide, and HOMA. Based on gold-standard acute insulin response in ten trials, PUFA significantly improved insulin secretion capacity (+0.5 pmol/L/min; 0.2, 0.8) whether replacing carbohydrate, SFA, or even MUFA. No significant effects of any macronutrient replacements were observed for 2 h post-challenge glucose or insulin sensitivity (minimal-model index). Limitations included a small number of trials for some outcomes and potential issues of blinding, compliance, generalisability, heterogeneity due to unmeasured factors, and publication bias.



This meta-analysis of randomised controlled feeding trials provides evidence that dietary macronutrients have diverse effects on glucose-insulin homeostasis. In comparison to carbohydrate, SFA, or MUFA, most consistent favourable effects were seen with PUFA, which was linked to improved glycaemia, insulin resistance, and insulin secretion capacity.

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OMG here we r again on the merry go round of nutrition science. I so recall the decades of bastardizing omega 6 on these forums. It is really frustrating. I am just gonna stick with Michael Pollan: eat whole foods, mostly plants and not too much as well as use cron o meter to insure RDA OF all nutrients and TO HELL WITH ALL THE MICROMANAGING BEYOND THAT other than creating recipes I ENJOY within that framework

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Mike, you must keep up! If you miss that one vital paper, your whole life could be upended! What if you had changed that one thing, and gained another 40 years of healthy lifespan?? Shame on you for neglecting such opportunities. I urge you forthwith to start your day the way most of us here do - with one hour of PubMed searches. To do anything less is health management malpractice. You brush your teeth, daily, right? This is the same thing, only more important.

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  • 4 months later...

OMG here we r again on the merry go round of nutrition science. I so recall the decades of bastardizing omega 6 on these forums. It is really frustrating. I am just gonna stick with Michael Pollan: eat whole foods, mostly plants and not too much as well as use cron o meter to insure RDA OF all nutrients and TO HELL WITH ALL THE MICROMANAGING BEYOND THAT other than creating recipes I ENJOY within that framework


I remember those EFA debates from 14 years ago. Mike, you always had a lot of good common sense and still do.


I know Dr. Greger is into a lot of PR and can exaggerate interpretation of nutrition science studies, but I think these two videos are worthy of review. Links below.


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