74 replies to this topic

[Michael]

The DHA-Accelerated Aging Hypothesis has just, finally, been tested — and validated — experimentally:

DHA-Accelerated Aging Hypothesis Validated

I'd prefer it if folks would carry on the discussion in the CR Society Forum, where it's most relevant, to avoid having a dozen different discussions going on all over the place. If you prefer to discuss it here, please at least avoid copy-pasting the whole damned thing here (though selected quotes for contextualizing your questions or comments are fine and even desirable).

[timar]

I don't think that rodents are a particular relevant model for human aging when it comes to the impact of fatty acid metabolism. In contrast to mice, we are evolutionary adapted to consume significant amounts of HUFAs - and we have a much larger brain to supply with them in proportion to our body weight. Moreover, the literature is full of examples where rodent studies have shown toxicity from fatty acids completely benign to humans - a notorious example is erucic acid, which has long been considered toxic (and was therefore bred out of rape cultivars used for the production of canola oil) based on rodent studies, but has in fact traditionally been consumed in significant amounts in parts of Europe and India and never shown any toxicity. Studies with pigs have shown no toxicity as well.

 

Anyway, the basic hypothesis "highly unsaturated = highly unstable = increased oxidation = accelerated aging" seems too simplistic to me to really take it seriously.

[Dolph]

Anyway, the basic hypothesis "highly unsaturated = highly unstable = increased oxidation = accelerated aging" seems too simplistic to me to really take it seriously.

 

And this is still very polite! (As you always are, other than me...) All the evidence we have shows the exact opposite. 

[Michael]

I don't think that rodents are a particular relevant model for human aging when it comes to the impact of fatty acid metabolism. In contrast to mice, we are evolutionary adapted to consume significant amounts of HUFAs

Whether or not we're evolutionarily adapted to consume significant amounts of HUFAs (and I'm inclined to accept that we are), you have to remember that we're evolutionarily adapted to "nasty, short, brutish" lives, where the threats to survival are tigers, freezing, tuberculosis, and war, and in which intense daylong physical activity mitigates a range of harmful effects. The fact that we evolved under certain circumstances and may have been selected against or even coevolved with them doesn't mean they help us as regards longevity.
 
In any case, there is significant data that the relationships involved also apply in humans. Despite what you would assume from our regular evolutionary consumption of HUFA, we actually have exceptionally low levels of DHA and other HUFA in our tissue membranes. Indeed, our skeletal and liver membrane peroxidizability indexes are far lower than other mammals of the same size, or that would be predicted from the general relationship between body mass and PI:
 

 

The relationship between the peroxidation index of liver mitochondrial phospholipids and body mass (A)  of mammals.(2)
 

... and the membrane peroxidizability index of humans and other organisms that are exceptionally long-lived for our body size have maximum lifespans in the same relationship as all other mammalian species:
 

 

 

 Skeletal muscle data combined from Valencak and Ruf (2007) and those cited in Hulbert (2005); liver mitochondrial data combined from Pamplona et al. (1998) and those cited in Hulbert (2005). Data for naked mole-rat from Hulbert et al. (2006b); echidna from A. Hulbert (1) Whole figure from (2).

... and there is some preliminary evidence that low PIs are linked to exceptional longevity in individual humans and genetically long-lived families:
 

Measurement of the fatty acid composition of human erythrocyte membrane lipids, as well as in vitro measurements on erythrocytes, has shown that centenarians have a reduced susceptibility to peroxidative membrane damage (Rabini et al. 2002). Part of longevity variation is genetic in origin. Studies of Danish twins suggests the heritability of longevity is 0.23 for females and 0.26 for males (Herskind et al. 1996); hence children of centenarians have been used as a model system for the study of the genetic basis of human aging (e.g. Atzmon et al. 2006). The fatty acid profile of erythrocyte membranes has been proposed as a potential biomarker of human longevity. A recent Italian study reported that the children of nonagenarians had erythrocyte membrane lipids with a PI of 64 (Fig. 6), which was significantly lower both than the value of 85 measured for a group of matched controls and the value of 83 for unmatched controls (Puca et al. 2008).[2]

 

 (And note that erythrocytes are actually the weakest case to look at, based on the animal evidence: you would expect a stronger link in postmitotic tissues like skeletal muscle).
 

- and we have a much larger brain to supply with them in proportion to our body weight.

 
Yes, but we also eat a lot more food . In the animal feeding studies, distribution of HUFA is differential in different tissues, based on their metabolic requirements, and DHA and EPA in brain are as a result far less susceptible to dietary manipulation than other tissues (see studies in original post). And there is no evidence of neurological disorders or increased risk of age-related cognitive declines in veg(etari)ans generally: indeed, there is (very limited) evidence of protection against cognitive decline and dementia in veg(etari)ans,(3-5) even though most veg(etari)ans really should be getting more omega-3 than they do (and of course get little to no HUFA, except for the extremely rare and recent fraction of them taking high-DHA algae supplements or DHA-fortified eggs, which are trends to recent to be impacting the epidemiological evidence) and also despite the confounding fact that B12 deficiency is shockingly common in vegetarians and especially vegans.
 

Moreover, the literature is full of examples where rodent studies have shown toxicity from fatty acids completely benign to humans - a notorious example is erucic acid, which has long been considered toxic (and was therefore bred out of rape cultivars used for the production of canola oil) based on rodent studies, but has in fact traditionally been consumed in significant amounts in parts of Europe and India and never shown any toxicity. Studies with pigs have shown no toxicity as well.

 
 Well, there is toxicity in nursling pigs, at least.(6) But IAC, (a) we're not talking about toxicity per se, and (b) part of the background driving the Hypothesis is the strong relationship between membrane HUFA and lifespan across multiple species and across multiple taxa.
 

Anyway, the basic hypothesis "highly unsaturated = highly unstable = increased oxidation = accelerated aging" seems too simplistic to me to really take it seriously.

 
I'm not at all clear what makes you think this is simplistic. IAC, there's no sense having an allergy to simplicity .
 

 

Anyway, the basic hypothesis "highly unsaturated = highly unstable = increased oxidation = accelerated aging" seems too simplistic to me to really take it seriously.

 
And this is still very polite! (As you always are, other than me...) All the evidence we have shows the exact opposite.

 

 
Er, to what evidence would you point as showing the exact opposite?
 
I will also remind all that the dietary implications here are primarily and perhaps exclusively for people on CR: the rest of the population has the species-specific resistance to membrane HUFA incorporation, but doesn't have the additional HUFA-suppressing background metabolism observed in CR animals that would be expected to be disrupted by HUFA in the diet.

References
1: Hulbert AJ. Explaining longevity of different animals: is membrane fatty acid composition the missing link? Age (Dordr). 2008 Sep;30(2-3):89-97. doi: 10.1007/s11357-008-9055-2. Epub 2008 May 31. PubMed PMID: 19424859; PubMed Central PMCID: PMC2527634. 
 
2: Hulbert AJ, Beard LA, Grigg GC. The exceptional longevity of an egg-laying mammal, the short-beaked echidna (Tachyglossus aculeatus) is associated with peroxidation-resistant membrane composition. Exp Gerontol. 2008 Aug;43(8):729-33. doi: 10.1016/j.exger.2008.05.015. Epub 2008 Jun 11. PubMed PMID: 18586080.

3: Sanders TA. Plant compared with marine n-3 fatty acid effects on cardiovascular risk factors and outcomes: what is the verdict? Am J Clin Nutr. 2014 Jun 4;100(Supplement 1):453S-458S. [Epub ahead of print] PubMed PMID: 24898234. 
 
4: Sanders TA. DHA status of vegetarians. Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):137-41. doi: 10.1016/j.plefa.2009.05.013. Epub 2009 Jun 4. Review. PubMed PMID: 19500961. 
 
5: Giem P, Beeson WL, Fraser GE. The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology. 1993;12(1):28-36. PubMed PMID: 8327020.
 
6: Food Standards Australia New Zealand (June 2003) Erucic acid in food: A Toxicological Review and Risk Assessment Technical report series No. 21; Page 4 paragraph 1; ISBN 0-642-34526-0, ISSN 1448-3017

[noots6494]

I'm confused by this thread. If I were a vegan, should I just treat the shitload of claims about DHA deficiency as marketing hype, or are you saying a small amount of algal oil supplementation would still be a good idea?

[Chupo]

I'm confused by this thread. If I were a vegan, should I just treat the shitload of claims about DHA deficiency as marketing hype, or are you saying a small amount of algal oil supplementation would still be a good idea?

 

This isn't a vegan study but may be of interest. Those on low fat (20% fat) had the same increase in plasma phospholipid DHA that would be expected with supplementation even though dietary DHA and total O3 consumption fell.  http://jn.nutrition..../131/2/231.full

[JohnD60]

I don't think that rodents are a particular relevant model for human aging when it comes to the impact of fatty acid metabolism. In contrast to mice, we are evolutionary adapted to consume significant amounts of HUFAs - and we have a much larger brain to supply with them in proportion to our body weight. Moreover, the literature is full of examples where rodent studies have shown toxicity from fatty acids completely benign to humans - a notorious example is erucic acid, which has long been considered toxic (and was therefore bred out of rape cultivars used for the production of canola oil) based on rodent studies, but has in fact traditionally been consumed in significant amounts in parts of Europe and India and never shown any toxicity. Studies with pigs have shown no toxicity as well.

 

People a lot more knowledgeable than I have posted in this thread, but I will throw out my two cents.... I agree with Timar's point about rodent studies not being a good model for humans, since humans have adapted to consume significant amounts of HUFAs. But I would turn it around and say that the test results show that rodents fed significant amounts HUFAs live shorter lives, because rodents are not adapted to consume significant amounts of HUFAs. Rodents are not truely omnivores, and would not be expected to consume significant DHA in the wild.

Edited by JohnD60, 07 November 2014 - 06:28 PM.

[drew_ab]

I'm really confused.  Could someone translate Michael's update to those of us who aren't so adept at reading the hardcore science?

[Michael]

I'm really confused.  Could someone translate Michael's update to those of us who aren't so adept at reading the hardcore science?

 

Gosh, I really thought the outlines were pretty clear:

 

There is a ton of correlative and now experimental evidence that having high levels of HUFA, and DHA in particular, in tissue and especially mitochondrial membranes, imposes limits on maximum longevity.

 

CR is an intervention that extends max LS in rodents (etc), and consistent with this, it reduces the amount of HUFA, and DHA in particular, in tissue and especially mitochondrial membranes.

 

There is even some very preliminary evidence (which I haven't (re)posted yet) that this happens in humans on CR.

 

When you feed animals more HUFA, and DHA in particular, more of them get into tissue and mitochondrial membranes.

 

This suggests that eating HUFA, and DHA in particular, may block the anti-aging effects of CR.

 

This suggests that people on CR should avoid eating HUFA, and DHA in particular, in favor of the actual essential fatty acids (alpha-linoleic (omega-3) and linoleic (omega-6)), and let their bodies' CR-altered metabolic systems sort it out.

 

Is that clear enough?

 

I'm confused by this thread. If I were a vegan, should I just treat the shitload of claims about DHA deficiency as marketing hype, or are you saying a small amount of algal oil supplementation would still be a good idea?

 

The shitload of claims about DHA deficiency in vegans are indeed marketing hype if you are getting enough omega-3, which most vegans (like most omnivores in past decades) are not. If you're not getting enough omega-3, you should get more omega-3 -- but it's hype to claim that you have to get preformed EPA or DHA.

 

On the other hand, if you're not on CR, I think it's harmless to get your omega-3 from such supplements.

 

 

I'm confused by this thread. If I were a vegan, should I just treat the shitload of claims about DHA deficiency as marketing hype, or are you saying a small amount of algal oil supplementation would still be a good idea?

 

This isn't a vegan study but may be of interest. Those on low fat (20% fat) had the same increase in plasma phospholipid DHA that would be expected with supplementation even though dietary DHA and total O3 consumption fell.  http://jn.nutrition..../131/2/231.full

 

 

That's very interesting ... it's not totally clear that that would automatically translate into tissue levels, though you would certainly expect it to.

 

I agree with Timar's point about rodent studies not being a good model for humans, since humans have adapted to consume significant amounts of HUFAs. But I would turn it around and say that the test results show that rodents fed significant amounts HUFAs live shorter lives, because rodents are not adapted to consume significant amounts of HUFAs. Rodents are not truely omnivores, and would not be expected to consume significant DHA in the wild.

 

 

Hm. I would say that I've refuted that argument in my reply to Timar. Why do you still think it cogent?

[drew_ab]

 

I'm really confused.  Could someone translate Michael's update to those of us who aren't so adept at reading the hardcore science?

 

Gosh, I really thought the outlines were pretty clear [SNIP]

Thanks for the clearer explanation.  I'm very tired today so it was likely just that.  It pretty much just solidifies what i've already been doing for the past 3.5 years on my own mild CR regime (with the exception of a brief couple on months on a raw food diet where I gobbled tonnes of flax/chia/hemp/walnuts).

 

[Edit: nixed unnecessary quotation -MR].

Edited by Michael, 06 January 2015 - 10:50 PM.

[JohnD60]

Hm. I would say that I've refuted that argument in my reply to Timar. Why do you still think it cogent?

 

The charts you provided regarding membrane peroxidation indexes are not adequately detailed and referenced for me to be convinced that you have refuted Timar's argument. Only a few data points are referenced, I don't have access to the complete Pubmed links (and I suspect the sources you cited end up having cited even more sources which I would have to read).  More than likely after tracking down all the links, I will find that the peroxidation index data on humans was accumulated from a cross section of 21st century humans eating typical 21st century diets with n6/n3 ratio  >10/1, which is not representative of the n6/n3 ratio diet that humans ate for hundreds of thousands of years prior 1800. I would assert that  a more balanced n6/n3 diet representative of the diet humans evolved eating would result in a much higher membrane peroxidation index for human muscle and mitochondria, and that such a peroxidation index would no longer be supportive of your graphical argument. 

[Logic]

Am I right in thinking that a good balance of all 8 forms of Vit E decrease peroxidation?

What about decreasing it further with BHT which has a proved to increase lifespan? (I cant remember if it was mean or maximum lifespan?)
http://jn.nutrition....132/6/1289.long
http://www.longecity...opic/42592-bht/

[tfor]

So what's the consequence of this? Does this mean that we should only eat saturated fats?

Does this mean that everything which contains PUFAS such as nuts,fish oil etc is bad?

 

[ikon2]

Forgive my idiocy, but what is the net/net here (assuming one subscribes to this theory,which I for one am becoming increasingly convinced of given the continued studies supporting it)?

 

Would a good approach be to make 30% of one's diet fats and within that percentage make:

 

33% LA (coconut oil, macadamia nuts)

 

33% ALA (Flax)

 

33% MUFA (olive oil, avocado)

 

Would this approach satisfy realizing the benefits of MUFA's, realize the benefits of keeping n-3 to n-6 at approx 1:1 and also keep the DHA intake to a minimum and let the body convert what it needs?  And am I correct to assume that Flax, although a PUFA is the type one would want?

 

Am I missing anything here or are any of my foods/fat sources or ratios off?  Is Olive oil considered a HUFA?

 

Also, how does one know if a PUFA (when reading a nutrition label) know if it is a short chain or long chain?

 

And not too much talk about MUFA's in this thread.  Are these good or bad in terms of this theory?

 

Edited by ikon2, 20 November 2014 - 12:50 PM.

[ikon2]

Forgive my idiocy, but what is the net/net here (assuming one subscribes to this theory,which I for one am becoming increasingly convinced of given the continued studies supporting it)?

 

Would a good approach be to make 30% of one's diet fats and within that percentage make:

 

33% LA (coconut oil, macadamia nuts)

 

33% ALA (Flax)

 

33% MUFA (olive oil, avocado)

 

Would this approach satisfy realizing the benefits of MUFA's, realize the benefits of keeping n-3 to n-6 at approx 1:1 and also keep the DHA intake to a minimum and let the body convert what it needs?  And am I correct to assume that Flax, although a PUFA is the type one would want?

 

Am I missing anything here or are any of my foods/fat sources or ratios off?  Is Olive oil considered a HUFA?

 

Also, how does one know if a PUFA (when reading a nutrition label) know if it is a short chain or long chain?

 

And not too much talk about MUFA's in this thread.  Are these good or bad in terms of this theory?

 

Bump (for answer)

[Logic]

Am I right in thinking that a good balance of all 8 forms of Vit E decrease peroxidation?

What about decreasing it further with BHT which has a proved to increase lifespan? (I cant remember if it was mean or maximum lifespan?)
http://jn.nutrition....132/6/1289.long
http://www.longecity...opic/42592-bht/

For that don't believe that miserable depravation makes a long life worth it, and would like a simple solution to this problem:

"...showed the greater loss,
with higher total loss in the open environment. Overall, antioxidants were found to be effectively
reduced the loss of ω-3 FAs, and the 100ppm astaxanthin model system was the most effective at
preventing the loss of the ω-3 FAs in the closed environment..."
www.mdpi.com/2072-6643/4/5/372/pdf

"...For example vitamine C and vitamine E have been found to interact as antioxidants, tocopheroxy
radicals are reduced back to tocopherols by ascorbic acid [32]. As in meat and fish products
this mechanisms takes place at the border between lipid and water phase, the radical is
removed from the lipid phase and the lipid oxidation process due to that radical is terminated..."
http://cdn.intechope...fs-wm/41625.pdf

"...The antioxidant synergism of vitamin E and Astaxanthin was supported by their ability to reduce malondialdehyde formation in an in vitro stimulation of microsomal lipid peroxidation and to reduce plasma levels of 8-isoprostane. The results of this study suggest that both vitamin E and the carotenoid Ax have antioxidant functions in Atlantic salmon..."
http://jn.nutrition....130/7/1800.long

[Michael]

Am I right in thinking that a good balance of all 8 forms of Vit E decrease peroxidation?

It's not really clear that any form of vitamin E (with or without vitamin C) reduces peroxidation in vivo in normal, healthy people (nonsmoking, nondiabetic, not otherwise diseased), or that it does so in tissues other than the blood, or that it does so long-term.
 
And certainly, no dietary antioxidant has been shown to reduce peroxidation in mitochondrial structures, which is what's at issue here.
 

What about decreasing it further with BHT which has a proved to increase lifespan? (I cant remember if it was mean or maximum lifespan?)
http://jn.nutrition....132/6/1289.long
http://www.longecity...opic/42592-bht/

 

It's "the usual nonsense."

 

Harman (who has, sadly, recently had life ripped from him by the aging process) took a small groups (10 mice each -- you need ≈50 mice in each group to get a statistically-significant readout of mean and max LS in mice) of abnormally short-lived, sickly LAF mice (mean lifespan: 14.5± 4.6 months), and threw a bunch of different single and/or combination antioxidants and vitamins at them. This is typical of the vast majority of claims of "extended lifespan" from supplement use.A normal, healthy, well-husbanded, non-genetically-fucked-up mouse given no special treatment will on av'g live twice as long as these mice: ~900 days (≈30 months), with a maximum (tenth-decile survivorship) LS of 1100 d, as is routine in the standard control groups in studies run by people who know what they're doing (Spindler, Weindruch, Miller, etc). But in report after report of 'life extension' in mice, NONE of the animals even live THIS long (or at best, the INTERVENTION group does).

 

Some of the antioxidants and supplements nothing; two synthetic antioxidants (2-MEA and huge doses of BHT) allowed mice to live longer than their miserably short-lived cousins. BHT partially normalized this miserably-short life mean LS (at 0.25% of diet, 17.0± 5.0 mo; at 0.50% of diet, 20.9± 4.7 mo).(1) Note the huge variability, and the short lives in all the animals in the study, whether treated with BHT or not. This is where you get the ridiculous claim of a 45% increase in lifespan from BHT. There was no ostensible effect on maximum LS: it did look on the survival curve as if the max LS might have been increased, but it's impossible to say when you have so few mice -- but (again) even if it ostensibly did, it's not real maximum lifespan, but a partial normalization of a miserably-short life.

 

 

Reference

1: Harman D. Free radical theory of aging: effect of free radical reaction inhibitors on the mortality rate of male LAF mice. J Gerontol. 1968 Oct;23(4):476-82. PubMed PMID: 5723482.

[pone11]

I don't think that rodents are a particular relevant model for human aging when it comes to the impact of fatty acid metabolism. In contrast to mice, we are evolutionary adapted to consume significant amounts of HUFAs - and we have a much larger brain to supply with them in proportion to our body weight. Moreover, the literature is full of examples where rodent studies have shown toxicity from fatty acids completely benign to humans - a notorious example is erucic acid, which has long been considered toxic (and was therefore bred out of rape cultivars used for the production of canola oil) based on rodent studies, but has in fact traditionally been consumed in significant amounts in parts of Europe and India and never shown any toxicity. Studies with pigs have shown no toxicity as well.

 

 

How do you figure than mankind is adapted to large amounts of HUFA and rats and mice are not?   The average rodent has 27% to 50%+ PUFA in their tissues and their diets are very high in nuts, seeds, and other foods that are loaded in Omega-6 polyfats.   What did rodents "evolve" to eat if it is not those types of foods?  See for example:

http://www.ncbi.nlm....pubmed/18029129

 

You see this same relationship across all species.  The subset of the species that has high polyfats in their body tissues do not live as long as the ones that have lower polyfats in their body tissues.

 

It is completely specious to talk about fatty acids that are poisonous to a species.   He's talking about a fatty acid that is at a 35% saturation level in brain tissues across many species, and which binds to phospholipids like phosphatidylcholine in the same way across many species.   It's basic biochemistry that is shared by many different types of animals. Polyfat composition is different across different species but the way cell membranes are built is not.

 

 

Anyway, the basic hypothesis "highly unsaturated = highly unstable = increased oxidation = accelerated aging" seems too simplistic to me to really take it seriously.

 

2+2 = 4 is also pretty simplistic.   The fact that you have simple and true premises, and the application of some basic logic, is NOT an argument for something being incorrect!

 

Simplicity here is a virtue.   Polyunsaturated Omega-3 and Omega-6 fats with double bonds are unstable.   That's not species specific!!  That's biochemistry.

 

When animals get old, they get more oxidative stress and they lose their antioxidant systems to combat that.    The details are species specific, but the basic concept is the same across all mammals.   Don't create differentiation where do you do not need it to understand a simple idea.

 

When oxidative stress hits unstable cell membranes made up of largely unstable fats, you get peroxidation.   That's just biochemistry, and the basic concept plays out across all mammals.

 

When humans get old, we produce more superoxide radicals.  We lose our superoxide dismutase (SOD) that converts those radicals to hydrogen peroxide.  We lose our catalase that converts the hydrogen peroxide to water and O2.   Now those superoxide radicals hit the cell membranes, and how much damage they are able to do is a function of how biochemically stable those cell membrane fats are.  All he is telling you is that when your membranes are loaded with O3 and O6 polyfats, those superoxide radicals will do much more damage than they would if the membranes were instead loaded with monounsaturated and saturated fats.  It's not something anyone should argue.

 

Any biochemist would look at this and say "It's simple.  It's obvious.   It's true."       Yet clinicians continue to fight this tooth and nail, because they have studies showing when you give lots of Omega-6 to heart patients they do better in the short term.   It's true you increase fluidity of the membrane with more polyfat, but at what cost?  You lowered a short term risk of heart disease, and you exposed the patient to horrible oxidative stress as he ages and these other factors kick in.  You are robbing Peter to pay Paul.  It's obscene that science looks at 2+2 = 4 and says "Well, I'm just not convinced."

 

 

Edited by pone11, 27 December 2014 - 02:56 PM.

[pone11]

 

Hm. I would say that I've refuted that argument in my reply to Timar. Why do you still think it cogent?

 

The charts you provided regarding membrane peroxidation indexes are not adequately detailed and referenced for me to be convinced that you have refuted Timar's argument. Only a few data points are referenced, I don't have access to the complete Pubmed links (and I suspect the sources you cited end up having cited even more sources which I would have to read).  More than likely after tracking down all the links, I will find that the peroxidation index data on humans was accumulated from a cross section of 21st century humans eating typical 21st century diets with n6/n3 ratio  >10/1, which is not representative of the n6/n3 ratio diet that humans ate for hundreds of thousands of years prior 1800. I would assert that  a more balanced n6/n3 diet representative of the diet humans evolved eating would result in a much higher membrane peroxidation index for human muscle and mitochondria, and that such a peroxidation index would no longer be supportive of your graphical argument. 

 

 

Prior to the agricultural revolution 10K years ago, we had O6 to O3 ratios under 2:1.   Modern ratios are > 15:1.  

 

Prior to the agricultural revolution, total calories consumed as polyfats were under 6% of total calories consumed.   Modern diets make polyfats (O3 + O6) as much as 25%.   

 

For the last two see for example government guidelines:

http://www.health.go...ml/chapter6.htm

 

How does either of those things get us to a higher peroxidation index value for historical diets?

Edited by pone11, 27 December 2014 - 02:58 PM.

[pone11]

 

Am I right in thinking that a good balance of all 8 forms of Vit E decrease peroxidation?

It's not really clear that any form of vitamin E (with or without vitamin C) reduces peroxidation in vivo in normal, healthy people (nonsmoking, nondiabetic, not otherwise diseased), or that it does so in tissues other than the blood, or that it does so long-term.
 
And certainly, no dietary antioxidant has been shown to reduce peroxidation in mitochondrial structures, which is what's at issue here.
 

 

I tried to respond to you on that CR Society site with more detailed questions.   It's kind of cumbersome to divide the conversation....

 

So we know the sequence here is not very complicated:   Oxidative stress means lots of superoxide radicals in the mitochondria, as the side effect of aerobic metabolism or mitochondrial failure.   Superoxide dismutase (SOD) converts the radical to hydrogen peroxide.  Catalase converts the hydrogen peroxide to water and O2.   It's not like we need to discover very much science to understand how to quench those radicals and prevent superoxide radical from destroying the mitochondrial membrane.

 

The question is how to do you permanently elevate those two antioxidants inside mitochondria without the system downregulating its endogenous production.

 

I have read studies showing that supplemental catalase improves recovery from exercise.   Do you think some of that supplement is getting into mitochondria?  That's worth some research probably given your interests.   If supplemental catalase only gets into the cytoplasm, it might improve our overall performance, but unfortunately it does nothing to stop destruction of mitochondrial membranes.

 

Maybe it might make sense to create a liposomal catalase?  That should improve how much you can get into mitochondria?  I think people here could make this supplement.

 

SOD normally does not survive digestion, but what about delivering that in a liposomal supplement?   It should work.   The problem in SOD is that I have a feeling the system would downregulate its own SOD production.   So the trick here would be to learn how to cycle the supplement so you fake out the system and constantly keep things at a higher than normal level.

 

The only major point you make that I would not agree with is that consuming ALA is a good way to guarantee DHA sufficiency.   ALA conversion to DHA in humans is very poor, about 10% conversion.   I think you have to overeat ALA to get enough DHA that way.   Just bite the bullet and you can buy salmon eggs and get the DHA and some very good phospholipids in a single package.   You don't have to eat a lot.   I am guessing a tablespoon a day is plenty.   If you eat 10 times as much polyfat in the form of ALA, now you have 10 times as much unstable polyfats in your tissues and you still ended up with the amount of DHA your body wants.   You didn't avoid the DHA and you did create additional targets for oxidation.

Edited by pone11, 27 December 2014 - 03:01 PM.

[drew_ab]

"The only major point you make that I would not agree with is that consuming ALA is a good way to guarantee DHA sufficiency.   ALA conversion to DHA in humans is very poor, about 10% conversion.   I think you have to overeat ALA to get enough DHA that way.   Just bite the bullet and you can buy salmon eggs and get the DHA and some very good phospholipids in a single package.   You don't have to eat a lot.   I am guessing a tablespoon a day is plenty.   If you eat 10 times as much polyfat in the form of ALA, now you have 10 times as much unstable polyfats in your tissues and you still ended up with the amount of DHA your body wants.   You didn't avoid the DHA and you did create additional targets for oxidation."

 

This is a very interesting point and one I had never thought of.  I'd be curious to hear Michael's response to this, as well as anyone else who feels up to answering it.

 

 

 

[pone11]

 

Maybe it might make sense to create a liposomal catalase?  That should improve how much you can get into mitochondria?  I think people here could make this supplement.

 

SOD normally does not survive digestion, but what about delivering that in a liposomal supplement?   It should work.   The problem in SOD is that I have a feeling the system would downregulate its own SOD production.   So the trick here would be to learn how to cycle the supplement so you fake out the system and constantly keep things at a higher than normal level.

 

 

This got me thinking, and I started a new thread here to discuss SOD supplementation:

 

http://www.longecity...ation/?p=704673

[ta5]

If someone took high-dose fish oil for years, how long after stopping would it take for the HUFAs to leave the ​tissues and mitochondrial membranes?

[drew_ab]

If someone took high-dose fish oil for years, how long after stopping would it take for the HUFAs to leave the ​tissues and mitochondrial membranes?

I asked a similar question to Mistere about omega-6, and I believe the half-life was around 600 days. Which is very, very long. But I'm not sure if that means it wouldn't be utilized via some other mechanism before then. It also doesn't answer about omega 3.

[pone11]

If someone took high-dose fish oil for years, how long after stopping would it take for the HUFAs to leave the ​tissues and mitochondrial membranes?

 

I read online (in a source I won't quote because it does not appear to be authoritative) that the half life for polyfats in tissue is about 600 days.   *IF* that value is correct, then 98% removal from tissue would take a little under 10 years.

 

I think someone who has read the literature on this can give much better numbers, as well as maybe suggest ways to speed that up.   Just pure thinking out loud:  maybe if you were supplementing phospholipids in pure form (with the fat removed) while using a low polyfat diet that would improve the rate of turnover of your own cell membranes, incorporating in better fats to the newer membranes.

 

A good place to start would be to get a fatty acid analysis done that uses RBC membranes instead of plasma to make the measurements.   BodyBio has one such test but it is hard to order.   This is another good one by OmegaQuant, but you have to contact them by phone and make special arrangements to have them process a tube of blood instead of using a drop of blood on paper (which is their default).   You can instruct them to spin down the blood to RBC membranes and report against that:

 

http://www.omegaquan...-omega-3-index/

 

OmegaQuant told me that they would gladly do the measurement against mitochondrial membrane, but that begs the question who is equipped to isolate mitochondria from any of your tissue?   I have no idea who could do that outside of a research environment.

 

But the point is you need that test to even decide if you have a problem.  Don't self diagnose your tissue composition.    When I got tested I was amazed to find out that I had the lowest 5% in Omega-6, and my EPA Omega-3 was about 250% off the high end of the scale.   That suggested that I was possibly under consuming Omega-6 (don't know how that is even possible in the USA) and way overconsuming Omega-3.   The other point is what do the scales that they provide on these tests really mean?    I'm not sure I trust OmegaQuant to correctly determine what is the healthiest concentration of Omega fats in tissues.   This is an area where you might be in the bottom 10% and still have too much....

 

My Omega-6 to Omega-3 ratio was around 1.6 to 1, which my osteopath told me is one of the lowest 5 ratios he has seen in over 2000 patients.   He wants me at 4:1, and I just can't say if he is right on that.  There are no good human experiments at those levels (and there probably never will be because US diets are too loaded with omega-6).   It's just as important to consider what is the total percentage of calories being consumed as polyfats, independent of the ratios in tissue.   And that is just HARD to calculate.

Edited by pone11, 28 December 2014 - 03:55 AM.

[misterE]

The lower the total fat in the diet, the easier it is to control the omega-3 to omega-6 ratio, plus you have less overall polyunsaturated-fat accumulation. In regards to the omega-6 overload and how to fight it, I think that complete avoidance of overt sources of omega-6 is needed, but using fish-oil to counteract the omega-6 is probably not good either, due to free-radical formation. Low-dose aspirin works like fish-oil to a degree and is a better strategy against omega-6 overload than fish-oil.

 

Many people are afraid of refined-foods like white-rice, white-flour or white-sugar. But these foods are virtually void of omega-6 and if you eat too much, your body will make saturated and monounsaturated-fats; the kind that protect from oxidative-stress. Eating food sources of "saturated-fat" like meat, eggs and cheese also gives you arachidonic-acid with it; premade fats always come in mixtures!

 

Queen-bees live on average four years while worker-bees live 70 to 90 days or something like that. Queen-bees are mostly saturated and monounsaturated while the worker-bee has a much higher degree of unsaturation, due to eating polyunsaturated-fat rich pollen. The queen-bee is mostly saturated but it does not eat any saturated-fat directly, but rather it synthesizes its own fat from the royal-jelly which is fed to the queen.

 

I think that humans should do this also. Load up on starch and sugar and keep premade-fats low. This allows for you to better manage your omega-3 to omega-6 ratio, decreases your intake of dioxins, pesticides and heavy-metals, it would enable you to make the right type and amount of fat you need, it would keep your free-fatty-acids low (like free arachidonic-acid, which when "free" is able to stimulate inflammatory eicosanoid synthesis), lower blood-pressure, reduce lipid-peroxidation, improve the immune-system and it will also profoundly increase insulin-sensitivity.

Edited by misterE, 28 December 2014 - 10:04 PM.

[misterE]

Also polyunsaturated-fat affects metabolism. Plants produce polyunsaturated-fat to protect their seeds from freezing temperatures; the seed cannot survive the winter without a portion being polyunsaturated (which is unable to freeze).

 

Artic animals like seals, polar-bears and salmon also contain lots of polyunsaturated-fat, to protect them from the cold and to prevent them from freezing. Come winter, when the plants start producing seeds and nuts, animals come and eat these nuts and soon after they enter hibernation. Even bears go into hibernation after eating polyunsaturated-fat rich salmons. Birds don't have much ability to gather many nuts and seeds and are forced to migrate south.

 

Plants in the tropics never experience winter and therefor don't produce much polyunsaturated-fat, so the animals down in the tropics don't enter hibernation, while the ruminant animals like cows, deer, goats, sheep, buffalo, camels and lamas don't experience hibernation either because their digestive-system removes most of the polyunsaturated-fat they eat.

 

Perhaps the massive consumption of polyunsaturated-fat present today is forcing our metabolism to work at a reduced and slower rate of efficiency.

 

 

Edited by misterE, 28 December 2014 - 10:28 PM.

[pone11]

The lower the total fat in the diet, the easier it is to control the omega-3 to omega-6 ratio, plus you have less overall polyunsaturated-fat accumulation. In regards to the omega-6 overload and how to fight it, I think that complete avoidance of overt sources of omega-6 is needed, but using fish-oil to counteract the omega-6 is probably not good either, due to free-radical formation. Low-dose aspirin works like fish-oil to a degree and is a better strategy against omega-6 overload than fish-oil.

 

 

I get more than 50% of my calories from fats, mainly saturated fats from coconut milk and meat, but lots of monounsaturated from macadamia oil as well.   I don't believe that either claim you are making is true.   In fact having alternate fats makes it easier for phospholipids to form that do not use polyunsaturated fats in the tails of the phospholipid.     And I have O6:03 under 2:1 and I don't believe that this reflects anything other than deliberate dietary intake of O3 and O6.

 

 

I think that humans should do this also. Load up on starch and sugar and keep premade-fats low. This allows for you to better manage your omega-3 to omega-6 ratio, decreases your intake of dioxins, pesticides and heavy-metals, it would enable you to make the right type and amount of fat you need, it would keep your free-fatty-acids low (like free arachidonic-acid, which when "free" is able to stimulate inflammatory eicosanoid synthesis), lower blood-pressure, reduce lipid-peroxidation, improve the immune-system and it will also profoundly increase insulin-sensitivity.

 

Obviously you are a disciple of Ray Peat.   If you have fully functioning glucose metabolism (i.e., you are 25 years old) this is an intriguing theory and worth discussing.

 

If you have defective glucose metabolism (e.g., pre-diabetic, type 2 diabetes, or the average person over 40), then this is some of the worst advice you could give a person.   A prediabetic with fasting sugar at 120 who "loads up on starch" will get post-meal glucose over 200 and insulin levels will skyrocket.   Neither of those things is desirable in any way, and in particular sending someone's blood sugar over 140 will create all kinds of glycation products in the blood.    It's just bad advice.

 

What would be good advice would be go buy a blood glucose meter and start using it frequently during the day.  Learn your own personal biology and how you react to foods.   Take immediate action to always keep your blood sugars post-meal under 140, and try to find a diet that will get your fasting number under 100.   There is too much individual variation in this to make generalizations about diet.

Edited by pone11, 28 December 2014 - 10:58 PM.

[misterE]

I asked a similar question to Mistere about omega-6, and I believe the half-life was around 600 days. Which is very, very long. But I'm not sure if that means it wouldn't be utilized via some other mechanism before then. It also doesn't answer about omega 3.

Am J Clin Nutr. 1980 Jan;33(1):81-5.
A mathematical relationship between the fatty acid composition of the diet and that of the adipose tissue in man.

Beynen AC, Hermus RJ, Hautvast JG.

Abstract

Based on literature data, the hypothesis is advanced that in human subjects a direct mathematical relationship exists between the average fatty acid composition of the habitual diet and that of the lipid stores of subcutaneous adipose tissue. Since the half-life of adipose tissue fatty acids in man is in the order of 600 days, the fatty acid pattern of depot fat provides a qualitative measure of the fat intake over a period of 2 to 3 years. It is concluded that in long-term experimental and epidemiological nutritional surveys the adipose tissue fatty acid pattern of the subjects is a useful index of the average composition of their habitual dietary fat.

The way I see it: During lipolysis free-fatty-acids (FFAs) are being released as energy. Once energy demands are met, any excess FFA is repackaged inside VLDL and sent back to storage inside the adipocyte. Eating carbohydrates and stimulating insulin lowers lipolysis and FFAs and stimulates lipoprotein-lipase, which removes the fatty-acids from VLDL back into the adipocyte for safe-keeping.

If you are insulin-resistant, you either lack insulin production or your insulin is insufficient enough to stimulate lipoprotein-lipase and are unable to store fat inside the adipocyte, thus you accumulate it outside of  the adipocytes, which is unhealthy, it that case your adipose-tissue turnover rate is accelerated, like what is seen in diabetes.

Also since fatty-acids are mobilized and released from the adipocytes by their degree of unsaturation, too much lipolysis would release a huge outpour of free-AA into the circulation, which would be harmful.

[EDIT: Blocking off abstract quotation, and trimming extra hard returns -MR]

Edited by Michael, 06 January 2015 - 11:00 PM.

[misterE]

•{1} I get more than 50% of my calories from fats, mainly saturated fats from coconut milk and meat, but lots of monounsaturated from macadamia oil as well.   I don't believe that either claim you are making is true.   In fact having alternate fats makes it easier for phospholipids to form that do not use polyunsaturated fats in the tails of the phospholipid.     And I have O6:03 under 2:1 and I don't believe that this reflects anything other than deliberate dietary intake of O3 and O6.

{2} Obviously you are a disciple of Ray Peat.  
 
{3} If you have defective glucose metabolism (e.g., pre-diabetic, type 2 diabetes, or the average person over 40), then this is some of the worst advice you could give a person.   A prediabetic with fasting sugar at 120 who "loads up on starch" will get post-meal glucose over 200 and insulin levels will skyrocket.   Neither of those things is desirable in any way, and in particular sending someone's blood sugar over 140 will create all kinds of glycation products in the blood.    It's just bad advice.

 
•{1} Well OK... eating coconuts and macadamia is virtually deficient in polyunsaturated-fats. So of course it will be easy to manage your ratios properly if that is your only fat source. Try doing that with peanuts or almonds.
 
•{2} I've read his work and I'm no disciple, I think he makes some good points about lipids though.
 
•{3} Most people would agree with you here, until they realize that the cause of diabetes is an elevation of glucocorticoids and the elevated blood-sugar in diabetics is caused by excessive gluconeogenesis; brought about by an elevation in glucagon, cortisol and GH. Eating carbohydrates stimulates insulin and incretin secretion, which lowers glucocorticoids, inhibits gluconeogenesis and LOWERS blood-sugar.
 
more info here:    http://www.longecity...ate-deficiency/

Edited by Michael, 06 January 2015 - 11:05 PM.