A nicely controversial new paper from the American Heart Association, in which linoleic acid in plasma phospholipids is the only PUFA with negative correlation with total mortality. The more LA n-6 in the membranes of your red and white blood cells, together with your lipoproteins, the longer you live. So should we switch back from butter to margarine?
(tl;dr; if you really care eat some nuts, nuts are the only LA source convincingly associated with reduced mortality, although nuts also being associated with exercise, wealth, not smoking and other markers of virtue, it's hard to be sure, but this latest research does help the nut case).
Here's the abstract
Therefore it seems to me that the presence of higher levels of LA in plasma phospholipids, in an oxidising environment, is not a mere indication of its dietary ingestion, but rather a marker of the antioxidant status of the blood and of the lipoproteins, which carry carotenoids, coQ10, retinol, tocopherol and other lipid antioxidants to and from cells. This explains why nut consumption is inversely associated with mortality, but overall LA consumption is not (if it was, the authors of this study would have mentioned it - senior author Hu is the nut guy).
It would be pretty hard to have a less than adequate LA intake on a high-fat paleo diet, as I discussed here.
Another process destructive of plasma phospholipid LA is inflammation; the conversion of arachidonic acid to prostaglandins and eicosanoids. Because AA itself is essential and conserved in the cell membrane, there is a flux through AA, with a constant replacement from LA. And guess what? Plasma phospholipid PUFAs, including LA, are preserved on very low carb diets - one of the anti-inflammatory benefits.
In other words, the paper under discussion seems to support the good, old-fashioned, free radical theory of disease and ageing, as well as the inflammatory theory of CHD. It doesn't support the intake of high levels of high LA seed oils, because what is going to happen to that LA? Almost all of it is going to be oxidised in the liver, with 22% of the acetyl-CoA produced going to make cholesterol.
You heard me - linoleic acid has the opposite effect from statins, increasing hepatic cholesterol synthesis. It also increases hepatic LDL receptors and pulls cholesterol in from the blood stream. Sometimes too much cholesterol, because all this free cholesterol oxidises easily, and when it does, cardiolipin also oxidises and mitochondria die (all this is referenced in my NASH series, see the Labels sidebar). Statins, if you overlook the side effects, are probably anti-inflammatory; I don't think there's much chance that seed-oils are.
(tl;dr; if you really care eat some nuts, nuts are the only LA source convincingly associated with reduced mortality, although nuts also being associated with exercise, wealth, not smoking and other markers of virtue, it's hard to be sure, but this latest research does help the nut case).
Here's the abstract
Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study
Background—While omega-6 polyunsaturated fatty acids(n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including concerns over theorized pro-inflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid(LA, the major dietary PUFA), γ-linolenic acid(GLA), dihomo-γ-linolenic acid(DGLA), and arachidonic acid(AA),with total and cause-specific mortality in the Cardiovascular Health Study, a community-based US cohort.
Methods and Results—Among 2,792 participants(age≥65y) free of CVD at baseline, plasma phospholipid n-6 PUFAwere measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34,291 person-years of follow-up (1992-2010), 1,994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher LA was associated with lower total mortality, with extreme-quintile HR=0.87 (P-trend=0.005). Lower death was largely attributable to CVD causes, especially nonarrhythmic CHD mortality (HR=0.51, 95%CI=0.32-0.82, P-trend=0.001). Circulating GLA, DGLA, and AA were not significantly associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme-quintile HR was 0.97 (95%CI=0.70-1.34, P-trend=0.87). Evaluated semi-parametrically, LA showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.
Conclusions—High circulating LA, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.
You'll notice the name of Dariush Mozzafarian as senior author (he's from the U.S. but the research was done in Sydney, Australia, so it's unlikely he supervised it in person). Mozaffarian is open-minded about saturated fat and low-carb diets and has played a major role in rehabilitating dairy fat, which ought to lay to rest conspiracy theories about the study (publication bias might be another question). The result makes sense to me.
Remember that these are plasma phospholipids, that is, they exist in the oxidising environment of human blood. We make use of this dual state system of redox balance; antioxidant enzymes and glutathione keep the intracellular balance in favour of reduction, and the non-enzymatic reactions inevitable in the anarchic extracellular environment, and the relative lack of extracellular antioxidant enzymes, reverse that, so that insulin and amylin molecules and immunoglubulins adopt their active, oxidised structures only after exiting cells, and ascorbic acid is oxidised to dehydroascorbic acid before being taken up and regenerated - reduced - inside cells.
Everyone knows what happens if this balance is lost either way; reductive stress limits the cell's ability to perform metabolic functions, oxidative stress degrades cellular structures and closes them down.
Remember that these are plasma phospholipids, that is, they exist in the oxidising environment of human blood. We make use of this dual state system of redox balance; antioxidant enzymes and glutathione keep the intracellular balance in favour of reduction, and the non-enzymatic reactions inevitable in the anarchic extracellular environment, and the relative lack of extracellular antioxidant enzymes, reverse that, so that insulin and amylin molecules and immunoglubulins adopt their active, oxidised structures only after exiting cells, and ascorbic acid is oxidised to dehydroascorbic acid before being taken up and regenerated - reduced - inside cells.
Everyone knows what happens if this balance is lost either way; reductive stress limits the cell's ability to perform metabolic functions, oxidative stress degrades cellular structures and closes them down.
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| Cardiolipin - the 4 radicals are predominantly C18:2, linoleate. |
Linoelic acid is a major determinant of cellular health, because it's incorporated into a phospholipid called cardiolipin, which sits in mitochondrial membranes; the linoleate is essential precisely because it's the most easily oxidisable PUFA in living systems. When cardiolipin oxidises faster than glutathione and its enzymes can repair it, it's time to close that mitochondrion and start another - in this way, inefficient mitochondria that spew free radicals aren't kept alive forever. This isn't the only function of cardiolipin, but canary in the metabolic coalmine is a pretty useful job.
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| Cardiolipin radicals |
Therefore it seems to me that the presence of higher levels of LA in plasma phospholipids, in an oxidising environment, is not a mere indication of its dietary ingestion, but rather a marker of the antioxidant status of the blood and of the lipoproteins, which carry carotenoids, coQ10, retinol, tocopherol and other lipid antioxidants to and from cells. This explains why nut consumption is inversely associated with mortality, but overall LA consumption is not (if it was, the authors of this study would have mentioned it - senior author Hu is the nut guy).
It would be pretty hard to have a less than adequate LA intake on a high-fat paleo diet, as I discussed here.
Another process destructive of plasma phospholipid LA is inflammation; the conversion of arachidonic acid to prostaglandins and eicosanoids. Because AA itself is essential and conserved in the cell membrane, there is a flux through AA, with a constant replacement from LA. And guess what? Plasma phospholipid PUFAs, including LA, are preserved on very low carb diets - one of the anti-inflammatory benefits.
In other words, the paper under discussion seems to support the good, old-fashioned, free radical theory of disease and ageing, as well as the inflammatory theory of CHD. It doesn't support the intake of high levels of high LA seed oils, because what is going to happen to that LA? Almost all of it is going to be oxidised in the liver, with 22% of the acetyl-CoA produced going to make cholesterol.
You heard me - linoleic acid has the opposite effect from statins, increasing hepatic cholesterol synthesis. It also increases hepatic LDL receptors and pulls cholesterol in from the blood stream. Sometimes too much cholesterol, because all this free cholesterol oxidises easily, and when it does, cardiolipin also oxidises and mitochondria die (all this is referenced in my NASH series, see the Labels sidebar). Statins, if you overlook the side effects, are probably anti-inflammatory; I don't think there's much chance that seed-oils are.