Mitochondria, the engine of life
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| Your body's motor: ATP Synthase. |
(If you want more detail, see Nick Lane's website, or read his excellent book, Power, Sex, Suicide: Mitochondria and the Meaning of Life
.)One of the hallmarks of the metabolic syndrome is mitochondrial dysfunction, where the mitochondria fail to generate power correctly. This review focuses on the heart, but does a good job of explaining some of the many symptoms, while not addressing the cause:
"The metabolic syndrome represents a cluster of abnormalities, including obesity, insulin resistance, dyslipidaemia and Type 2 diabetes, that increases the risk of developing cardiovascular diseases, such as coronary artery disease and heart failure. ... Recent findings suggest that myocardial mitochondrial dysfunction may play an important role in the pathogenesis of cardiac contractile dysfunction in obesity, insulin resistance and Type 2 diabetes."They forgot cancer, but that's fine, we'll get to it.
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One of your excerpts from Power et alter (my bolds): "Feeding the HCO [hydrogenated coconut oil] and OO [olive oil] diets increased the proportions of stearic and oleic acids, respectively, while decreasing the proportion of linoeic acid." But afterwards you say (my bolds) "And don't makes nuts, avocados, or olive oil a staple part of your diet." Non sequitur. Moreover, virgin olive oil is labeled as 8-10% polyunsaturated around here in Spain.
ReplyDeleteThat's a fair point, Serdna. Thanks for taking the time to read this post so carefully.
ReplyDeleteI wrote that having in mind two things (which weren't included in this post).
First, this isn't the only line of evidence that excess linoleic acid consumption is a bad idea.
See this post: "Linoleic Acid and Blindness" for instance, which details how excess LA consumption interferes with the body's ability to incorporate n-3 into tissues.
Stephan Guyenet has posted evidence that in animals cancer risk increases up to 4% E consumption of LA, but then doesn't increase further, and it's been reported that it's not possible to induce cancer in lab animals if LA is left out of the diet.
Given that we don't really know what the "harmless" level of LA is, I think it's reasonable to minimize LA as much as possible.
Second, Along the Paleo Diet line of reasoning, is that both olive oil and avocados are relatively new additions to the human diet in large amounts, within the last 150 years. Even the !Kung don't eat mongongo nuts year-round, the way many Paleo enthusiasts can with avocados and olive oil.
I personally eat nuts, olive oil, and avocados, but as advised in my post, they're not a staple part of my diet.
Not that I completely disagree about the LA issue and the advice to ditch seed oils. I was convinced too by the total parenteral nutrition effect commented by Wolverine. But. 1) Perhaps we should focus on whole food effects and not on its parts since nuts seem to have overall positive effects. 2) Lard seems to be as high in polyunsaturated fat as olive oil or even worse (I don't know if it is consequence of either whole corn feed or direct vegetable oil feed... I hope it is the second option).
ReplyDeleteNot that it is clear how much time have we been consuming olive oil (I know Nina Teicholz is highly critical about it) but it is explicitly named by Orthodox Christians to be excluded during lent. It seems to me we have been taking it for one thousand years at least.
I personally eat a lot of cheese and butter but a generous amount of virgin olive oil too. We all must take our decisions under incomplete information.
Pork fat solidify at room temperature around here.
DeleteI will have to do the fridge experiment with a little bit of virgin olive oil. Nevertheless it will not be a completely reliable measure of LA content since I suppose those LAs still within triacylglycerols (oleic-oleic-linoleic, palmitic-oleic-linoleic) are going to solidify anyway (there is a method to estimate their melting points —via cyberlipid— but I have been unable to use and verify it though).
Thank you for mentioning Wolverine. I ran across his website years ago and it made a huge impression on me.
DeleteHave you seen this paper, i think it's consistent with your hypothesis
ReplyDeleteSoybean Oil Is More Obesogenic and
Diabetogenic than Coconut Oil and Fructose
in Mouse: Potential Role for the Liver
PLOS ONE | DOI:10.1371/journal.pone.0132672 July 22, 2015
@Steven Weil: Yes, I have. I think it is too. Don't know why I didn't include it, except that I think it's more in the line of evidence that follows from the TPN feeding experience.
DeleteTucker, what do you think of this study?
ReplyDeletehttps://www.researchgate.net/publication/233829427_Dietary_Docosahexaenoic_Acid_226_Incorporates_into_Cardiolipin_at_the_Expense_of_Linoleic_Acid_182_Analysis_and_Potential_Implications
It's interesting, but it's essentially a meta-analysis of other studies—many of which I've not seen yet, so thank you very much. I'll have to take a look at them.
DeleteProblems are, I think, that a lot of the studies they're looking at use supra-physiological levels of n-3 and n-6: knowing that DHA will outcompete LA if they're 20% and 56% of a diet is interesting, but not really helpful in the real world. I want to see what happens at levels people might actually eat. So I'd want to go through and look at some of the actual studies and see what they say.
They look at the liver and the heart, but not the brain. DHA is a major component of CL in the brain, so when they say n-3s are "proposed to be more reactive, and potentially disruptive," they don't discuss the brain, where such evidence would be expected, but is lacking. The harmful metabolites there, from what I've seen, are also from n-6. That said, I think it's likely that high levels of n-3 are also bad, they clearly are in conjunction with high levels of alcohol, and epidemiological evidence from Japan and the Eskimos suggest that's the case. So don't OD on fish oil...
Plus I'd like to find out where I can get some crocodile oil!
Oh, and the other thing is that I found it disappointing that they excluded studies where LA < 2%, as I think that's likely the place where most of us should be. Observing that LA "18:2 is the most readily consumed PUFA in the human diet" is true today, but not in the past. I'm more worried about what the right level is.
DeleteI suspect that I've been consuming a level of LA that's at or below 2% for 6 years now, and I've not seen any of the effects of LA deficiency, for instance, only benefits.
I'm wondering if the brain is different here? for a good reason - we don't want to tell brain cells to self destruct unless there is a good reason - we would lose information.
ReplyDeleteI think the mechanism is a bit more complicated, but the net effect is the same:
Delete"A Direct Line From Dietary Linoleic Acid To Alzheimer's Disease?"
Appreciate your responses.
ReplyDeleteWell, it seems Linoleic acid is one of the prime health concerns of our day.
So strategies for approaching this:
1. Reduce dietary LA acid intake to <2%
2. Consume plenty of good fats ( butter, chocolate, tallow, quality olive oil etc )
3. Use fish, krill, cod liver oil temporarily to restore some sort of balance, probably not needed in large amounts for the rest of one's life.
Am I interpreting the issue correctly? I ask this a lot but I enjoy a variety of opinions.
The worst thing is it doesn't just go away when you reduce dietary intake <2% because most of us are carrying around plenty of it, as you well know.
In addition to the strategies I mentioned above, I wonder if maximizing the detox pathways for LA metabolites is something to focus on?
http://www.jlr.org/content/44/6/1182.long
They don't mention 4-HNE here but I couldn't find info on how your body deals with that specific metabolite. Glucuronidation appears to be dependent on glucose. In my personal experience I do feel ok on very low carb but feel better with a generous amount of non-starchy vegetables and significantly better with fermented dairy products ( less so unfermented milk ). Just trying to make sense of what I've experienced working for me. Obviously there's more going on there than just the glucose intake but it must be a factor.
@Jimmy: You're welcome.
ReplyDelete"Well, it seems Linoleic acid is one of the prime health concerns of our day."
That's my conclusion.
For point 3., when I started this I got some cod liver oil, and for six month or so, couldn't get to sleep without eating it. Then I just forgot about it, and haven't touched it since. That's consistent with behavior of deficient people, who tend to eat a lot of something until they're replete.
I don't take any fish oil, just avoid LA and eat fish occasionally (I love sardines, happily), but it's not that often.
"The worst thing is it doesn't just go away when you reduce dietary intake <2% because most of us are carrying around plenty of it, as you well know."
Yes, the half-life in adipose tissue is 600 days, but I think if you reduce the excess, to your next question:
"...I wonder if maximizing the detox pathways for LA metabolites is something to focus on?"
That you don't need to worry about that part. Vitamin E, for instance, apparently doesn't make it into the mitochondria. Vitamin C, another antioxidant, reacts badly with 4-HNE. Glutathione is the primary antioxidant involved in this process, from what I've read, and seems to work very well if there's not too much LA.
Since every antioxidant-supplementation trial out there has been found to reduce health, I've not looked into supplementation, therefore. But just found this:
"...exogenous GSH per se was an ineffective delivery agent of GSH to tissues."
http://jap.physiology.org/content/77/5/2177.short
My general approach is to try to get the system back to it's base state, so I'm not a big fan of supplementation, in general, except to address short-term deficiency, as above.
I started to see benefits in fairly short order, and within six weeks, I guess, it was pretty revolutionary.
http://yelling-stop.blogspot.com/2010/12/my-vitamin-d-experiment.html
If you're low-carb, you shouldn't count non-starchy vegetables as carbohydrates. They're digested to short-chain fatty acids, so they count towards fats. Eat as much as you want, in other words.
"...exogenous GSH per se was an ineffective delivery agent of GSH to tissues."
ReplyDeleteI believe that's the case for plain reduced GSH but liposomal glutathione ( fairly recent thing ) is different.
http://www.ncbi.nlm.nih.gov/pubmed/20535554
http://www.liposomalglutathione.com/studies/
I've taken liposomal GSH before and it did have a very noticeable effect, brain fog and fatigue decreased highly significantly. Unfortunately the effects only last around 4-6 hours and it's too expensive to use for many people ( around $1 per dose ).
Curcumin may help? I'm not sure if you would consider it a supplement since it's a cooking spice but you could certainly use it as a supplement...
ReplyDeleteDo you think these studies translate to practical use in LA-overloaded humans?
https://sci-hub.io/10.1002/ptr.2517
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637698/
Interesting, thanks for sharing. I don't know that I've ever eaten curcumin.
Delete"Do you think these studies translate to practical use in LA-overloaded humans?"
It's certainly possible, but again, I'd rather remove the cause than treat the symptoms. LA has many other negative effects beyond what happens in the liver, so even if we assume that this works as well in humans, it doesn't necessarily mean it will address the rest of the issues.
But I'm going to go check the spice cabinet! :)
Thanks so much for your article! I have been looking into the problem of too much LA in our diet while, at the same time, we eat little arachidonic acid. Here's a study about ARA and mitochondria: Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids. And in: Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy?, PGE2 from ARA prevents mitochondrial damage. I've been suggesting that people eat more eggs and chicken to get more arachidonic acid-of course, best if pastured.
Delete@Tucker—" I don't know that I've ever eaten curcumin."
DeleteYou have if you've ever had curry.
'"Do you think these studies translate to practical use in LA-overloaded humans?"
'It's certainly possible, but again, I'd rather remove the cause than treat the symptoms.'
I think Unknown was referring to the effect of stored LA being released from fat cells. Especially if one starts fasting, that could be a significant impact. Seems reducing your stores of LA gradually would be a better idea.
I don't think getting rid of it gradually would be superior. It does little of any damage when it's oxidized as fuel, especially on a keto diet it seems. It does damage if it's in storage.
DeleteI haven't seen any reason to think there's a benefit to keeping it!
..."the brain seems to limit the rate of LA uptake (the only place I've seen a rate-limiter on the incorporation of LA into tissues outside of cattle)."
ReplyDeleteand
"The only way to get excess amounts [of LA] in the diet are: eat oils made from seeds, eat animals that are fed on excessive amounts of grain that concentrate LA, or eat far too much grain yourself."
I'm curious about the cattle remark. We keep being told to avoid grain-fed beef, so does the rate-limiting incorporation of LA in cattle come into play here?
Can you tell us what to eat, exactly, to reduce LA? I don’t think I’m understanding the exact things that really will help. And do we eat the solid part of the olive oil or the liquid part? I’m sorry to ask such dumb questions but I got confused about the best approach. Thank you so much for any advice.
ReplyDeleteI deleted this response above (since Blogger won't let me edit it!) because the fridge test I recommended does not actually work. Here's the old comment, below, and here's the link to the failed attempt to validate the fridge test:
ReplyDelete"Olive oil ‘fridge test’ doesn’t reliably detect fraud".
Science marches on!
"All fair points, again.
"One of the age-related macular degeneration studies I read observed that eating a nuts a few times a week seemed to have a protective effect. That seems like a fine level of consumption, to me. I personally find nothing more fattening than salted pistachio nuts, although I love them, as the salt promotes over-consumption. I can't eat a bag of unsalted pistachios, but can easily do that with the salted ones.
"Pigs, and every other animal I'm aware of except cattle, concentrate LA based on the diet. Geese are fed grain to create fois gras, aka fatty liver. So I think it's pretty clear that veggie oil feed is not necessary to get the "benefits" of excess LA consumption. I tend to avoid unpastured chicken and pork for that reason, and don't use pig fat in large quantities when cooking.
"It's a pretty easy test to find out how much LA is in fat, however (important given wide-spread adulteration in the olive oil market).
"If you're eating, say, bacon grease, and it doesn't solidify at room temperature, throw it out. If you like olive oil, put it in the fridge. The non-solid part is the LA. I pour that off, then keep the rest. I have bought cheap olive oil in the past that didn't solidify at all after a few days in the fridge.
"But as you said, it's imperfect information."
Just a quick question from a newbie working at improving my health. When you mention reduce dietary intake to 2%, is that 2% of total calories, total fat or exactly what do you mean? Thanks in advance
ReplyDeleteTotal calories.
DeleteThis comment has been removed by the author.
ReplyDeleteOne thing you said caught my eye. "Pigs, and every other animal I'm aware of except cattle, concentrate LA based on the diet." Peter has said something similar. Does that mean it's not so important to eat grassfed beef? I would still tend toward organic, but at least here in the US it's harder to find grassfed. Also, is that just cows, or all ruminants? Lamb, for instance?
ReplyDeleteIt's all ruminants. The bacteria in the rumen convert LA to other fats, notably conjugated linoleic acid (CLA) which seems quite beneficial, apparently by blocking LA.
DeleteI think grassfed is better, but it seems to be a small difference, and it's probably worth the price difference, if that's an issue. Eat some fish along with your grain-finished beef, and you'll get the n-3 you need.