PUFAs Role On Skin

[What-a-Riot]

He's anti-PUFA for sure, but he may also feel a responsibility to push an extreme viewpoint because of the mass acceptance of the "facts" of "healthy fats." I mean one day he's calling out avocados for being potentially carcinogenic and liver toxic, another he's actively condoning a meal of salmon avocado and rice as a healthy macronutrient balance with nary a mention of PUFA.
Peat thinks everyone should think. Of course we're here in part because of a respect for his research and philosophy, so we care what he thinks, but I think he'd cringe to see his name invoked under the assumption that it should be considered as evidence

EDIT

I think "peat thinks" should be taken as evidence that there is most likely evidence to be found. I'm not trying to cause a fuss or make any accusation with all this, this is just something I think about and I think should be said from time to time

 

[schultz]

he doesnt say that clearly!

for example i asked him a question,have you seen his reply?! Ray Peat Email Advice Depository

He seems to be saying that the symptoms of EFAD are more apparent with cats because they already have higher metabolic rates than rats. I was under the impression that he believes the problems associated with EFAD are not because we need EFA's but because the higher metabolic rate requires a higher intake of micronutrients.

The need for higher micronutrients at least in hyperthyroidism has been known for a long time. The Thomas McGavack book called "The Thyroid" states that people with hyperthyroidism should be given 3-4 times the RDA of vitamins A, B and C, though I imagine "hyperthyroidism" and a "high metabolic rate" aren't necessarily the same thing.

EFAD does increase oxygen consumption, cytochrome oxidase content and gives an increase in maximal ATP synthesis rate. I wonder if it comes with a linear increased need for vitamins or an exponential one.

 

[Drareg]

First off, looking at infant PUFA requirements has not been something that I have done. This post is an attempt to make sense of more information .

I will address both posts simultaneously.




I just this study, done on actual pre-term infants at very young ages (<1 month) -- Pediatric Research - The Very Low Birth Weight Premature Infant Is Capable of Synthesizing Arachidonic and Docosahexaenoic Acids from Linoleic and Linolenic Acids

It shows that there is some level of delta-6 desaturase activity going on in these infants, and that even this limited amount does actually produce significant absolute values of Arachidonic Acid (AA) and Docosahexaenoic Acid (DHA).

The researcher's conclude:

This observation suggests that the δ6 desaturation may not be a rate-limiting step in our patients.
​

But only after acknowledging that:

Several studies measuring plasma polyunsaturated FA levels indicate that the infants fed formulas devoid of LCP exhibit lower plasma levels than their human milk-fed counterparts (8).

Decreasing plasma LCP concentrations are also described in preterm infants fed their own mother's milk (28).

Whether this results from a complete inability by the small preterm infant to synthesize LCP (circulating LCP would then result from the recirculation of LCP acquired during fetal life) or whether the requirements are so high that the levels decrease despite active LCP synthesis was not known.​

Another interesting note:

Our data allow us to only estimate the amount of dietary LA and LNA converted into plasma phospholipid AA and DHA. We found that 6.05 ± 2.26% and 14.07 ± 4.20% of the total dose of[13C]LA and LNA were converted into plasma phospholipid AA and DHA, respectively.​

Which in my mind, is a very efficient conversion ratio .... Note that "LNA" is used here to refer to alpha-linolenic acid, and "LA" to refer to linoleic acid. In adults, usually we see low single digits conversion efficiencies (eg: 3.8% LNA to DHA in this study -- Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? - PubMed - NCBI)

----

If delta-6 desaturases are not the rate limiting step in infant PUFA elongation, then we need to look for other pathways. This paper suggests some potential alternative pathways -- Pediatric Research - Intermediates in Endogenous Synthesis of C22:6[omega]3 and C20:4[omega]6 by Term and Preterm Infants

----

This will change my opinion on the mechanics of PUFA metabolism, and bring more uncertainty into play. We are seeing less reliance on the direct consumption of highly unsaturated fats like AA and DHA.

I think it is fair to say that it is part of healthy function to be able to regulate PUFA levels, and apparently even human infants can do this well.

NOTE: this doesn't change the fact that older infants can elongate PUFAs better than younger infants, nor that young infants excrete more PUFA. But the idea that young infants must rely on direct highly-unsaturated PUFA intake may not be true. ie: direct AA and DHA supplementation may not be absolutely essential.​

----

While the inability to regulate PUFA is rare, it does exist

Here is a paper showing a 9-year-old patient who had a couple of skin disease conditions, and also had skin fibroblasts that did not exhibit delta-6 desaturase activity -- Identification of a fatty acid Δ6-desaturase deficiency in human skin fibroblasts

She improved upon direct supplementation of a combined AA and DHA supplement. It is cases like these where dietary consumption of PUFA is probably needed. I expect such cases to be rare.

If you want mice studies, full deletion of the FADS2 gene responsible for delta 5 and 6 desaturase activity resulted in no metabolic nor longevity consequences, but rendered the mice sterile -- Δ6-Desaturase (FADS2) deficiency unveils the role of ω3- and ω6-polyunsaturated fatty acids

The mice could not make leukotrienes in white blood cells. I'd expect immune response to be impaired.

The mice could not heal induced thrombotic injury as quickly (twice as long bleeding times).

Dietary supplementation of AA, EPA, and DHA reversed some of the conditions (see section 'The fads2-null mutant is an auxotrophic mutant')

-----

Personally, I would expect similar effects in humans that completely lack this gene. More likely, we'll not see loss of gene activity, but will see some variation in the ability to synthesise PUFA -- Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phosph... - PubMed - NCBI

What this means for actual real-life humans I do not know, since there is no way to measure the degree of a lack of PUFA in a particular tissue. I want to say, "if you have a serious PUFA regulatory issue, you'd already be dead or seriously impaired", since this touches so many important functions, but do not know if that is true.

On a practical note, I do not see much harm with low dose PUFA consumption (like 3 eggs a day), and really don't think people should try and "optimise PUFA intake" unless there is a good reason to.

----

Finally, I do not have much to say regarding the hibernation or coma state.

Clearly there are massive reductions in metabolic rate during hibernation -- https://www.une.edu.au/__data/assets/pdf_file/0013/32701/AnnuRevPhysiol04.pdf

See Table 1, we're talking at least 50% reduction, and in some cases up to 90+% reduction. This reduction is proportionate to the observed decrease in body temperature (with some of the listed animals dropping their body temp all the way down to the low single digits Celsius).

Induced coma definitely also reduces metabolic rate even further than a regular resting individual (maybe about -5% in this study) -- Energy expenditure during barbiturate coma. - PubMed - NCBI


I do not think it is accurate to describe babies as being comatose by the actual medical definition . The discussion of coma state metabolism does not apply to a healthy infant.

.....

It's about building for the infant,sleep assists this quicker than being awake.
I was guessing something is enducing sleep possibly pufa.

What signals the infant to sleep so much? A particular hormone?

 

[tyw]

Brief Commentary on Peat

I like Peat for not giving a flying **** about what anyone else thinks , and just saying whatever he wants to say. He is basically capable of "living in his own head" and coming up with ideas that are not tainted by mainstream views.

But as @What-a-Riot said, sometimes this leads to seemingly contradictory statements (which may or may not be contradictory).

Any interface with Dr Peat shall be taken to be an honest reflection of what he thinks at the time -- ie: he does not demonstrate any incentive to sell anyone on his position.

It is then the responsibility of the individual looking at information to decide what it means to them on a practical level. To put it bluntly, Peat doesn't care about what you think . I like that sort of attitude.

----
Assert. De-complect. Falsify

This phrase is in my forum signature for a very good reason

"Complect" means to entwine two or more objects together. In the case of the "Is PUFA essential?" question, the concepts of "PUFAs present in the organism" is complected with "Dietary PUFA Intake"

NOTE: one piece of Programmers' Propaganda today .... everyone should watch 'Simple made Easy' by Rich Hickey, whom I credit all use of the words "Complect" and "Simple" to -- Simple Made Easy

(political sidenote comes next)

This whole notion of complecting concepts which can be treated separately, is IMO, the biggest political obstacle in public discourse right now. Just one example: people complect "vaccines", "virus", "autism", "heavy metals", and a bunch of separate concepts all into an irresponsible moral judgment of either "vaccines are evil", or "vaccines are necessary".

Even someone smart (in areas of knowledge other than health and medicne) like Ben Shapiro will say something along the lines of we need vaccines, and maybe even mandatory vaccine laws, without trying to break apart all these concepts and address them individually.

Separating these concepts allows for an answer to the goal that the 'Vaxxed' documentary folks want -- Safer Vaccines, that actually provide the benefits of better immunity, whilst minimizing the negative side effects.

Apply the same logic to other political topics please (I won't name them, but anyone can look up all the recent issues and find this problem)​

Regarding PUFAs, I have provided evidence that the amount of PUFAs present in an organism, is not necessarily linked to the amount of dietary PUFA consumption.

I have then stated that I think that dietary PUFA minimisation is the ideal in most cases (with some discussion in my previous post about a specific context where extra supplementation may be needed).

This doesn't change the fact that almost every eukaryotic organism requires some degree of PUFAs to be alive.

....

 

[Drareg]

Brief Commentary on Peat

I like Peat for not giving a flying **** about what anyone else thinks , and just saying whatever he wants to say. He is basically capable of "living in his own head" and coming up with ideas that are not tainted by mainstream views.

But as @What-a-Riot said, sometimes this leads to seemingly contradictory statements (which may or may not be contradictory).

Any interface with Dr Peat shall be taken to be an honest reflection of what he thinks at the time -- ie: he does not demonstrate any incentive to sell anyone on his position.

It is then the responsibility of the individual looking at information to decide what it means to them on a practical level. To put it bluntly, Peat doesn't care about what you think . I like that sort of attitude.

----
Assert. De-complect. Falsify

This phrase is in my forum signature for a very good reason

"Complect" means to entwine two or more objects together. In the case of the "Is PUFA essential?" question, the concepts of "PUFAs present in the organism" is complected with "Dietary PUFA Intake"

NOTE: one piece of Programmers' Propaganda today .... everyone should watch 'Simple made Easy' by Rich Hickey, whom I credit all use of the words "Complect" and "Simple" to -- Simple Made Easy

(political sidenote comes next)

This whole notion of complecting concepts which can be treated separately, is IMO, the biggest political obstacle in public discourse right now. Just one example: people complect "vaccines", "virus", "autism", "heavy metals", and a bunch of separate concepts all into an irresponsible moral judgment of either "vaccines are evil", or "vaccines are necessary".

Even someone smart (in areas of knowledge other than health and medicne) like Ben Shapiro will say something along the lines of we need vaccines, and maybe even mandatory vaccine laws, without trying to break apart all these concepts and address them individually.

Separating these concepts allows for an answer to the goal that the 'Vaxxed' documentary folks want -- Safer Vaccines, that actually provide the benefits of better immunity, whilst minimizing the negative side effects.

Apply the same logic to other political topics please (I won't name them, but anyone can look up all the recent issues and find this problem)​

Regarding PUFAs, I have provided evidence that the amount of PUFAs present in an organism, is not necessarily linked to the amount of dietary PUFA consumption.

I have then stated that I think that dietary PUFA minimisation is the ideal in most cases (with some discussion in my previous post about a specific context where extra supplementation may be needed).

This doesn't change the fact that almost every eukaryotic organism requires some degree of PUFAs to be alive.

....

He does care about what people think,he wouldn't answer dozens of emails if he didn't. He takes on board what people say.

I'm not sure about him having a profound amount of contradictions, when being interviewed he is on the spot,he does well enough with poor callers and interviewers without having to have every piece of advice spot on.
I'm not sure where he recommended salmon and avocado?

Have you had dialogue with Peat with your evidence?

 

[Luna]

Interesting to note that the Phillipines is also where Linoleic acid is the lowest (8%), and the medium chain fats are the highest.

They probably had more coconut food items in the content of their foods.
This may mean that coconut may affect lipid profiles, making it deviate from the norm.

 

[James IV]

"I think people have extrapolated ideas from EFAD rats to cats, without recognizing that carnivores have higher metabolic rates and nutritional needs, so that the mistakes of the Burrs are even easier to make."

I'm surprised no one questioned this line.

 

[schultz]

"I think people have extrapolated ideas from EFAD rats to cats, without recognizing that carnivores have higher metabolic rates and nutritional needs, so that the mistakes of the Burrs are even easier to make."

I'm surprised no one questioned this line.

Once you posted this, I questioned it, but it seems to be true.

"We have confirmed an idea, originally espoused by McNab (1989), that species of carnivores that consume vertebrate prey tend to have higher BMR than species that include vegetable material in their diet"

"We propose that changes in the proportion of muscle fiber types can provide a mechanism to account for the differences in BMR observed between meat eaters and vegetarian species."

http://www.journals.uchicago.edu/doi/full/10.1086/432852

 

[James IV]

Once you posted this, I questioned it, but it seems to be true.

"We have confirmed an idea, originally espoused by McNab (1989), that species of carnivores that consume vertebrate prey tend to have higher BMR than species that include vegetable material in their diet"

"We propose that changes in the proportion of muscle fiber types can provide a mechanism to account for the differences in BMR observed between meat eaters and vegetarian species."

http://www.journals.uchicago.edu/doi/full/10.1086/432852

Yes. I do believe it is true. I just find it is interesting that many looking to increase metabolic rate seem to be most focused on carbohydrate.

 

[tyw]

@James IV and @schultz

I personally do not find it that useful to compare differences in metabolic between species, for the reasons that I've discussed here -- Some Thoughts On Avocadoes

You'll find parrots, which have extremely high metabolic rates and long longevity, fare better off (live longer) by eating MORE seeds and grains, aka: more PUFA, but also more Vitamins found in the seeds. The net effect is actually less PUFA on mitochondrial membranes; these animals can use the compounds in seeds and grains specifically to exclude PUFAs from their mitochondria membranes, despite a high PUFA diet.

Ref: 'Metabolic rate and membrane fatty acid composition in birds: a comparison between long-living parrots and short-living fowl', (Montgomery et. al, 2011)

And then you'll find rats who deplete their PUFA get much larger mitochondria, with more cristae, and higher rates of substrate flux:

- Effect of polyunsaturated fatty acids deficiency on oxidative phosphorylation in rat liver mitochondria
- MITOCHONDRIAL CHANGES IN THE LIVER OF ESSENTIAL FATTY ACID-DEFICIENT MICE


The differences worth comparing are from dietary manipulation within the same type of organism, and watching for effects. So far, the only effect that seems to universally increase metabolic rate in the same organism, is reduction of overall mitochondrial membrane PUFA levels.

----

Also, let's not ignore the higher level effects, like Thyroid hormones and Gluthathione, all of which are boosted by carbohydrates.

Also, let's not make the mistake of saying that just because some carbs are needed for a well-functioning thyroid, that more is better

....

 

[James IV]

@James IV and @schultz

I personally do not find it that useful to compare differences in metabolic between species, for the reasons that I've discussed here -- Some Thoughts On Avocadoes

You'll find parrots, which have extremely high metabolic rates and long longevity, fare better off (live longer) by eating MORE seeds and grains, aka: more PUFA, but also more Vitamins found in the seeds. The net effect is actually less PUFA on mitochondrial membranes; these animals can use the compounds in seeds and grains specifically to exclude PUFAs from their mitochondria membranes, despite a high PUFA diet.

Ref: 'Metabolic rate and membrane fatty acid composition in birds: a comparison between long-living parrots and short-living fowl', (Montgomery et. al, 2011)

And then you'll find rats who deplete their PUFA get much larger mitochondria, with more cristae, and higher rates of substrate flux:

- Effect of polyunsaturated fatty acids deficiency on oxidative phosphorylation in rat liver mitochondria
- MITOCHONDRIAL CHANGES IN THE LIVER OF ESSENTIAL FATTY ACID-DEFICIENT MICE


The differences worth comparing are from dietary manipulation within the same type of organism, and watching for effects. So far, the only effect that seems to universally increase metabolic rate in the same organism, is reduction of overall mitochondrial membrane PUFA levels.

----

Also, let's not ignore the higher level effects, like Thyroid hormones and Gluthathione, all of which are boosted by carbohydrates.

Also, let's not make the mistake of saying that just because some carbs are needed for a well-functioning thyroid, that more is better

....

Excellent points. I specifically like your final statement.

 

[paymanz]

doesnt unsaturated fatty acids ,PUFA or MUFA improve nutrient entrance into the cells by increasing membrane fluidity?

 

[schultz]

Yes. I do believe it is true. I just find it is interesting that many looking to increase metabolic rate seem to be most focused on carbohydrate.

Oh okay I wondered if that's what you meant (the carbohydrate thing).

That paper I linked is actually pretty interesting. I didn't think it would be at first, I was just trying to confirm if carnivores actually had higher BMR. I'm not sure they actually know why they have a high BMR but they proposed a new theory near the end of the paper called the "Muscle Performane Hypothesis".

"Neither hypothesis that we have explored, the “activity hypothesis” or the “food quality hypothesis,” provides much insight into mechanisms responsible for elevation in metabolism of those species that eat entirely meat. Identification of a correlation among metabolism, diet, and home range size is necessary but not complete if one wants to understand how natural selection has brought about elevated oxygen consumption in meat eaters. So where do we go from here? We develop a new hypothesis, the “muscle performance hypothesis,” that states that BMR is elevated in vertebrate eating carnivores because natural selection has designed their muscle structure for endurance rather than power, and the resulting increase in mitochondria density in particular muscle fiber types requires elevated oxygen consumption."

"Foraging for vertebrate prey typically requires movement over large distances; one can imagine that selection has maximized efficiency of muscle movement in these species. When species include vegetable material in their diet, home range size can be decreased; therefore, endurance requirements of their muscle tissue may be reduced, or power requirements of muscles may be increased as a result of species becoming more arboreal. We know that muscle tissue is the primary determinant of total oxygen consumption, accounting for 35% of BMR (Martin and Fuhrman 1955)."

@tyw very interesting points, especially the parrot thing!

 

[MB50]

@James IV and @schultz

I personally do not find it that useful to compare differences in metabolic between species, for the reasons that I've discussed here -- Some Thoughts On Avocadoes

You'll find parrots, which have extremely high metabolic rates and long longevity, fare better off (live longer) by eating MORE seeds and grains, aka: more PUFA, but also more Vitamins found in the seeds. The net effect is actually less PUFA on mitochondrial membranes; these animals can use the compounds in seeds and grains specifically to exclude PUFAs from their mitochondria membranes, despite a high PUFA diet.

Ref: 'Metabolic rate and membrane fatty acid composition in birds: a comparison between long-living parrots and short-living fowl', (Montgomery et. al, 2011)

And then you'll find rats who deplete their PUFA get much larger mitochondria, with more cristae, and higher rates of substrate flux:

- Effect of polyunsaturated fatty acids deficiency on oxidative phosphorylation in rat liver mitochondria
- MITOCHONDRIAL CHANGES IN THE LIVER OF ESSENTIAL FATTY ACID-DEFICIENT MICE


The differences worth comparing are from dietary manipulation within the same type of organism, and watching for effects. So far, the only effect that seems to universally increase metabolic rate in the same organism, is reduction of overall mitochondrial membrane PUFA levels.

----

Also, let's not ignore the higher level effects, like Thyroid hormones and Gluthathione, all of which are boosted by carbohydrates.

Also, let's not make the mistake of saying that just because some carbs are needed for a well-functioning thyroid, that more is better

....

Very briefly could you explain the significance of the ATP/O ratio and exactly why decreasing the Proton motive force is good in the rat study? Just trying to get a better grasp on this (I thought the protons moving across the IMM were good for producing ATP?) Any insight from those more knowledgeable would be appreciated. Thanks.

 

[tyw]

Very briefly could you explain the significance of the ATP/O ratio and exactly why decreasing the Proton motive force is good in the rat study? Just trying to get a better grasp on this (I thought the protons moving across the IMM were good for producing ATP?) Any insight from those more knowledgeable would be appreciated. Thanks.

Whether or not these observations are good or not depends on the context

Firstly, these were liver mitochondria -- I like this, since it is actually a tissue that has major control over metabolic rate.

Important Note: Look at the "PUFA Deficient" fatty acid concentrations in Table 1. We are basically talking about a reduction across almost all PUFAs, and most critically 22:6 (DHA), which is the most peroxidisable PUFA. Also note that 20:3 n-9 (Mead acid) drastically increased.

PUFAs are still there, just different kinds, with less double bonds on the whole.

Cardiolipin also increased drastically. @haidut has talked about this before.​

Then what we find is:

(1) ATP/O ratio Decreased with PUFA deficiency

In other words, for PUFA deficiency reduces the amount of ATP produced per unit Oxygen.
In other words, metabolic uncoupling -- more heat, less ATP

This is a survival disadvantage when you want to preserve resources. Animals probably accumulate PUFA in winter for this reason.

This is an advantage when substrate flux is high -- which is the behaviour you see in Bird mitochondria, and to a lesser extent, in those of human centenarians.

Key Assumption: there is lots of food around for substrate flux to be high. PUFA deficiency will kill you in times of scarcity.​

Having more ATP is also not necessarily a survival advantage when there is so much substrate to begin with.

More Electron Flux is not always a good thing when substrate is very high. eg: There are risks of electron leak and formation of Reactive Oxygen Species, which is something that definitely sends a feedback to the rest of the cell.

(2) State 3 and State 4 Respiration is elevated

See -- OXPHOS - What is "State 1-5"

State 3 basically refers to "how much electrons are able to flow through Complex 1/2, 3, and 4"
State 4 then refers to "how many of those electrons are accepted at Complex 4" (by oxygen or other terminal electon acceptor)

Both increased by about 10-13%, which actually means that more ATP is likely to be produced, despite that lower ATP/O ratio.

Note that this doesn't account for uncoupling. In reality, "amount of energy consumed" will be much greater. Hence the extreme increases in observed metabolic rate in animals which are either made PUFA deficient, or are PUFA deficient by design. Rats probably see 30-40% increases in metabolism, whereas birds are known to have ridiculous metabolic rates.

For example a "low metabolic rate bird" like a swan goes through 47 kcal/kg/day as a Basal metabolic rate, whereas most humans will barely get to 30 kcal/kg/day (that's 2100kcal for a 70kg human in full bed rest). Many many birds churn through upwards of 100 kcal/kg/day -- Bird Energy Balance and Thermoregulation
​

-----

IMO the right way to think about this, is that PUFA deficiency allows for a "Wider Mitochondrial Pipe". This is based on the fact that mitochondria increase in size, and have more sites for Electron transport to occur.

A wider pipe allows for a "more relaxed flow", as seen by reductions in delta-psi during State 3 and State 4 metabolism.

Proton Leak is then a natural consequence of having a wider pipe.

In a way, this provides a larger error margin in terms of tolerable flow rates. There is a larger queue buffer, and both very high and very low rates of flow are is "business as usual".

Contrast that with a smaller pipe -- when flow rate gets high, you need to be very eager about sending signals to stop entry into the queue. This is the case we see with mitochondria getting backed up at Complex 1, and additional inputs causing Complex 1 electron backflow and the production of a lot of Reactive Oxygen Species. The observation is then that the cell shut downs insulin signalling, and prevents extra substrate from entering the queue. Looks like an elegant regulatory mechanism to me

PUFA deficiency thus is a signal to "accept everything". On the whole, with more substrate availability, this will most likely lead to more ATP, with less Reactive Oxygen Species. And observationally, this is exactly what we see with birds.

.....

 

[MB50]

Whether or not these observations are good or not depends on the context

Firstly, these were liver mitochondria -- I like this, since it is actually a tissue that has major control over metabolic rate.

Important Note: Look at the "PUFA Deficient" fatty acid concentrations in Table 1. We are basically talking about a reduction across almost all PUFAs, and most critically 22:6 (DHA), which is the most peroxidisable PUFA. Also note that 20:3 n-9 (Mead acid) drastically increased.

PUFAs are still there, just different kinds, with less double bonds on the whole.

Cardiolipin also increased drastically. @haidut has talked about this before.​

Then what we find is:

(1) ATP/O ratio Decreased with PUFA deficiency

In other words, for PUFA deficiency reduces the amount of ATP produced per unit Oxygen.
In other words, metabolic uncoupling -- more heat, less ATP

This is a survival disadvantage when you want to preserve resources. Animals probably accumulate PUFA in winter for this reason.

This is an advantage when substrate flux is high -- which is the behaviour you see in Bird mitochondria, and to a lesser extent, in those of human centenarians.

Key Assumption: there is lots of food around for substrate flux to be high. PUFA deficiency will kill you in times of scarcity.​

Having more ATP is also not necessarily a survival advantage when there is so much substrate to begin with.

More Electron Flux is not always a good thing when substrate is very high. eg: There are risks of electron leak and formation of Reactive Oxygen Species, which is something that definitely sends a feedback to the rest of the cell.

(2) State 3 and State 4 Respiration is elevated

See -- OXPHOS - What is "State 1-5"

State 3 basically refers to "how much electrons are able to flow through Complex 1/2, 3, and 4"
State 4 then refers to "how many of those electrons are accepted at Complex 4" (by oxygen or other terminal electon acceptor)

Both increased by about 10-13%, which actually means that more ATP is likely to be produced, despite that lower ATP/O ratio.

Note that this doesn't account for uncoupling. In reality, "amount of energy consumed" will be much greater. Hence the extreme increases in observed metabolic rate in animals which are either made PUFA deficient, or are PUFA deficient by design. Rats probably see 30-40% increases in metabolism, whereas birds are known to have ridiculous metabolic rates.

For example a "low metabolic rate bird" like a swan goes through 47 kcal/kg/day as a Basal metabolic rate, whereas most humans will barely get to 30 kcal/kg/day (that's 2100kcal for a 70kg human in full bed rest). Many many birds churn through upwards of 100 kcal/kg/day -- Bird Energy Balance and Thermoregulation
​

-----

IMO the right way to think about this, is that PUFA deficiency allows for a "Wider Mitochondrial Pipe". This is based on the fact that mitochondria increase in size, and have more sites for Electron transport to occur.

A wider pipe allows for a "more relaxed flow", as seen by reductions in delta-psi during State 3 and State 4 metabolism.

Proton Leak is then a natural consequence of having a wider pipe.

In a way, this provides a larger error margin in terms of tolerable flow rates. There is a larger queue buffer, and both very high and very low rates of flow are is "business as usual".

Contrast that with a smaller pipe -- when flow rate gets high, you need to be very eager about sending signals to stop entry into the queue. This is the case we see with mitochondria getting backed up at Complex 1, and additional inputs causing Complex 1 electron backflow and the production of a lot of Reactive Oxygen Species. The observation is then that the cell shut downs insulin signalling, and prevents extra substrate from entering the queue. Looks like an elegant regulatory mechanism to me

PUFA deficiency thus is a signal to "accept everything". On the whole, with more substrate availability, this will most likely lead to more ATP, with less Reactive Oxygen Species. And observationally, this is exactly what we see with birds.

.....

Thanks for the great response. Kind of getting off track, but what determines whether or not mitochondria grow in size or number? And is one or the other necessarily better in certain circumstances?

 

[tyw]

Thanks for the great response. Kind of getting off track, but what determines whether or not mitochondria grow in size or number? And is one or the other necessarily better in certain circumstances?

Factors for amount and morphology of mitochondrial growth are unknown. The observed pattern is clearly that less PUFAs always precede mitochondrial changes to increase substrate flux and reaction site count, but there are no known mechanics as to why and how this happens.

Because of the clear differences between the species, we know that the mitochondrial DNA (mtDNA) of that specific organism, and the interaction of the mtDNA and the nuclear DNA of the cell nucleus is going to determine the fate of the mitochondria. We still do not know what these interactions are, how they occur, and what determines the outcome.

Again, still doesn't change the fact that these observations are robustly replicated across every single eukaryotic organism.

-----

Which is better:

(a) high PUFA mitochondria

- low total flux potential
- highly coupled to ATP production, not much excess heat production
- normal levels of ROS wrt energetic flux
- lower total energetic demands​

(b) low PUFA mitochondria

- high total flux potential
- not highly coupled to ATP production when flux is high (and only when flux is high)
- excess heat production in the face of energetic flux, with lower levels of ROS during high flux
- higher total energetic demands​

IMO, low PUFA mitochondria is "better" from the human perspective so long as there is an excess food in the environment.

Mechanically speaking, (b) gives you the best of everything really .... it is a highly adaptive state that can deal with both very high and very low levels of energetic flux through the mitochondria without any issues at all.

At a high level, all the longest lived, most adaptable organisms, have mitochondria with low PUFA. Hence you manage to have birds which can perform insane metabolic tasks (like migratory flight), be fine in both extreme cold and extreme heat, and yet live for decades and decades ....

The caveat is of course -- take away their food supply, and these organisms die off pretty quick.

.....

 

[schultz]

The caveat is of course -- take away their food supply, and these organisms die off pretty quick.
.....

PUFA serves a purpose here. Living tends to be a positive, and in times of scarcity or seasonal change, a lower metabolism would be a welcome thing . There was once a time when supermarkets didn't exist. Imagine that!

 

[tyw]

PUFA serves a purpose here. Living tends to be a positive, and in times of scarcity or seasonal change, a lower metabolism would be a welcome thing . There was once a time when supermarkets didn't exist. Imagine that!

The accumulation of PUFA is required for hibernation. Many animals do this of course.

On the flip side, there are almost zero birds that hibernate, including the non-migratory ones. These birds basically ramp up their metabolic rate during winter time to survive. Food supply is not as big an issue when you are a relatively smaller organism.

There is really no uniform strategy across organisms, and much less humans, who have basically spread to many different environments. eg: Where I am, large quantities of food can and is grown year-round. Then you have the more extreme latitudes, where seasonal variation in food supply is a very real thing.

Whether or not PUFA accumulation is useful will then be dependent on prevailing factors. In times of true famine, they may help one survive a little longer. Personally, in today's world, I see innovation, and the high metabolism required to support it, as the key survival trait, even in these seasonally varying locales.

IMO, this is no longer the world where the prior evolutionary role of PUFAs will prove to be useful.

.....

 

[skycop00]

Was over on Science Driven Nutrition website and found this criticizing RP:

Seneca Rapson says:
May 17, 2016 at 6:30 pm


I’d say Ray Peat would be entirely wrong as there are studies showing that PUFA’s aid insulin sensitivity. In particular, one study showed that replacing saturated fats in the diet with PUFA improved insulin sensitivity for muscle uptake of glucose for people with insulin resistance of the form of muscle glucose uptake (though not for those with livers that have developed insulin resistance).

Do Carbohydrates Control Body Fat? - Science Driven Nutrition


Brad Dieter PhD replies:

Brad Dieter, PhD says:
May 17, 2016 at 11:46 pm


The literature regarding PUFA vs SFA and insulin resistance is pretty all over the map. It depends on the cell type, assays used, populations used (when looking at humans), diet history, etc. There aren’t any good data I am aware of that convince me about the superiority of SFA over PUFAs. I’d be happy to read anything you send my way on the topic