Why PUFA is bad: how high membrane polyunsaturation decreases longevity

[Aimer]

His blog is recovered PUFA, Birds, and Genetics

 

[Mauritio]

His blog is recovered PUFA, Birds, and Genetics

Yes finally! Thanks . I'll check it out . I like the way he writes

 

[Mauritio]

I'll post it here ,just in case ...


"PUFA, Birds, and Genetics
Front Matter
I wanted to write this article at least 3 months before the publish date, but never got around to forming a coherent message. The reader should treat this article as such -- incoherent ramblings which may or may not be useful.

In any case, the motivation of this article was to push back against particular notions of "PUFA Depletion" that I see in various Ray Peat articles and related communities, and try to take an objective view on what exactly is practically achievable.

Initially, the idea was to take a view of PUFAs from an evolutionary perspective with regards to metabolic function and longevity, but in truth, all I found was genetic control, with not much conclusions to be drawn that is practical to humans .... I still included some of this discussion anyway, and reserved the section regarding Practical Considerations for last.

Intro
Readers of Ray Peat's works will know that he is no fan of Polyunsaturated Fatty Acids (PUFA). It is fair to say that he would advise one to eat as little PUFA as is humanly possible.

In terms of broad generalisations, I agree, and it is fair to say that the longevity of an animal, is in general inversely related to the amount of PUFA that it keeps on the membranes of its cells (especially pertinent to mitochondrial membranes).

More accurately, researchers measure the "Peroxidation Index", which is a function of the number of double bonds present in a particular structure. A membrane with 10 moles of Arachidonic Acid (AA), which has 4 double bonds per molecule, is less peroxidisable then a membrane with 10 moles of Docosahexanoic Acid (DHA), which has 6 double bonds per molecule.

Sidenote: I have written a never-will-be-complete, but comprehensive enough article about DHA. Clearly, I am not a fan of large scale DHA consumption.

Sidenote: the authors of 'Human Longevity' are also not fans of excess DHA consumption. This is by far one of the best treatments of the role of Polyunsaturated Fats in biology, and is recommended reading.

In any case, we have quite a fair bit of data to support the idea that "Efficient Mitochondria" are often associated with longevity.

This refers to mitochondria that have the ability to:

Precisely match inputs to the of output of either ATP or Heat, with little Reactive Oxygen Species (ROS) production.

Doing this in the face of highly variable energetic demands, ranging from being asleep to sprinting.

Cleanup whatever inevitable damage that occurs.

Birds are the best examples of organisms with mitochondria which can exactly perform this task, modulating themselves as a coherent unit to power everything from intense flight, and then to collectively slow down to near hibernation levels during sleep.

Birds then have some of the longest lifespans of any animal (except bats) as measured by their body mass, and usually have very little PUFA on their mitochondrial membranes as compared to other species (humans included).

In general, this is the origin of the idea that "the longest-lived animals have little PUFA, and hence more PUFA on membranes is bad", and thus the recommendation for humans to avoid eating PUFA at all costs.

However, that is not accurate, and many other factors play into how a particular Human Individual handles their own mitochondrial energetics (and it is important to remember that we are looking to obtain "Efficient Mitochondria", regardless of whether that means high PUFA or not)

TL;DR
The TL;DR for this post is is:

In Birds, Bats, Rats, and likely all organisms, Mitochondrial Peroxidation Index seem to be the main determinate of longevity and health. In general, higher PUFA concentration => high Peroxidation Index, though there are cases where specific PUFA composition is significant.

Mitochondrial PUFA concentration doesn't necessarily depend on dietary PUFA consumption; particular Species have adapted to use and converse PUFA in their own unique ways

The lower level we go in biological hierarchies, the more that genetics plays a role; Once we get down to the mitochondrial level, we find a remarkable genetic determinism for a lower bound to PUFA incorporation.

It is likely that the more PUFA a human eats, the more gets accumulated in their mitochondrial membranes, and the more potential for damage occurs. I am generally in the "less PUFA is better" camp, with the appropriate note in the pen-ultimate section regarding energy balance.

There is no Conclusion ~(^ ▽ ^ ~) ~(^ ▽ ^ ~) ~(^ ▽ ^ ~)

Don't expect anything said here to be practically useful to determining how much PUFA you in particular should be eating.

I willl look at four studies this time, and make some commentary on each.

While I will make extracts, it is recommended that you read each study in full to appreciate the nuances.

A Philosophical Note before we Begin
Some people hate the term "Genetics".

However, from my perspective, whether it is because they find the obsession with the genetic theory of disease distasteful, or if it because the term implies a degree of choicelessly, I do not bother with any subjective treatment of the term.

Regardless, it is clear, that some humans are "blessed" with mutations in mitochondrial DNA which make them better at preventing damage to mitochondrial membranes, and that these mutations have very significant effects.

For those who really want details about said genes. Pick up 'Human Longevity' by David Valentine, and read the whole thing, especially chapter 18.

Everything from FOXO3A variants, to Uncoupling Protein related SNPs that allow certain people to produce more heat (and hence less Reactive Oxygen Species) in mitochondria, will make one person more or less susceptible to chronic mitchondria damage during the process of aging.

The only useful distinction to me is that between:

(a) Things which are definitely beyond one's control to influence ("Genetics")
(b) Things which there is some small possibility of influencing
Focus on (b), and be entertained by (a).

Now we move on to the studies .....

(~ ^ ▽ ^)~ ☼ ~(^ ▽ ^ ~)

See Figure 1 -- Metabolic rate for Parrots are about 50% higher than Quails. Parrots live a lot longer on averge (27 years vs 5.5 years) ....

The researchers fed different birds the same diet for 2 months, and observed changes in their fatty acid status in mitochondria. The diet was listed in Table 1.

My rough estimate of the diet was, assuming standard calories amounts for the wheat, sorghum, and then these values for soybean and canola meal (3% fat by weight), would have placed the diet at around 30% fat, with 15% of that being Saturated, 35% being MUFA, and the remaining 50% being PUFA. This is definitely a high PUFA diet.

What they found was basically no significant difference in Tissue PUFA concentrations between the long-lived and short-lived birds. In fact, the long lived birds in general had more potential oxidisable PUFA in their tissues. See Figure 2

There is some difference in the mitochondria. See Figure 3. But the difference in Peroxidation Index is so small ... I can hardly make it out to be anything more than 10-20%. True to the predictions though, n-6 PUFAs is less harmful to longevity than n-3 PUFAs.

I quote the researchers:

Although little is known about the mechanisms by which membrane fatty acid composition is regulated, research in mammals strongly suggests that membrane fatty acid composition is genetically determined and not strongly influenced by diet (as long as the diet is not deficient in essential fatty acids)

I agree -- what each organism decides to do with PUFA is going to be different. This assumes what I would call a "high PUFA diet", which also happens to be a diet with natural precedence; PUFAs existed in nature.

Membrane Composition under high PUFA Diets likely constrained by Genetic Control
Back to the article proper, here is another quote from the previous study, mentioning naked mole rats (despite the paper being about birds):

the evidence to date suggest membrane fatty acid composition is relatively constant throughout a species lifespan. For example, in naked mole rats membrane composition is essentially the same in individuals that are below 1%, 7%, and ~80% of their MLSP (Hulbert et al. 2006b).

I agree, and would raise the same caveat that this usually refers to a high PUFA dietary context.

What this statement implies is that a Naked Mole Rat is "advantaged", in that it does not store as much Peroxidisable Fatty acids in Mitochondria, despite eating PUFA.

I believe that regular rats, and humans as well, will be able to get the same benefits by reducing PUFA intake, and will opine that this is an advantaged position to deal with the modern world.

That is the case of organisms with "normal speed" mitochondria. However, we shall now look at the objective data of Birds and Bats, which have mitochondria in HYPERDRIVE, and see that dietary PUFAs really don't make as much of a difference between these blessed organisms.

Some Parrots eat a lot of PUFA. They still live long.
I'll just make some quotes from these studies:

(2) 'Diet Influences Life Span in Parrots (Psittaciformes)' (Jason Munshi-South and Gerald S. Wilkinson, 2006)

Quote:

Although larger parrots live longer than smaller parrots (Fig. 1), change in dietary specialization was the primary factor associated with the evolution of life span after controlling for both body size and phylogenetic ancestry.

Specifically, evolution of granivory was associated with the evolution of longer life span.

"Granivorous" means "eats grains and seeds". ie: lots of PUFA.

But it seems this is concurrent with another significant effect:

Seed-eating parrots often inhabit relatively arid environments with unpredictable resources and form large flocks during periods of patchily distributed food or water (Cannon 1984).

Communal roosting and flocking may increase survival rates by improving detection of scarce resources (Jullien and Clobert 2000, Peach et al. 2001), facilitating social transfer of information about foraging sites (Chapman et al. 1989), or reducing predation through increased vigilance (Westcott and Cockburn 1988, South and Pruett-Jones 2000).

...

After controlling for body size, only diet type and restriction to islands explained a significant proportion of variation in life span (Table 1 and Fig. 2). Parrots that form communal roosts tended to exhibit higher residual longevity, a difference that approached significance (P = 0.065).

However, contingency-table analyses confirmed that diet was significantly associated with both island restriction (χ2 = 24.45, df = 2, P < 0.0001) and communal roosting (χ2 = 8.06, df = 2, P < 0.05). Multiway ANOVA revealed that the island effect was attributable to an interaction between diet type and island restriction rather than island restriction by itself (diet * island interaction: F = 3.19, df = 2 and 136, P < 0.05; Fig. 2).

One way to see this: These other things are beneficial to observed longevity, and just happen to co-incide with a high PUFA diet.

Another way to see this: a high PUFA diet did not affect the parrots' longevity at all.

This next claim, however, I am dubious of, but can see plausible mechanism, and will include for completeness, and because the theme of calorie restriction is re-visited in the next study:

Alternatively, periodic resource shortages faced by granivorous parrots may extend longevity through caloric restriction.

All in all, I will agree with the researchers' conclusion:

The evolution of dietary specialization on fruit or nectar appears to be related to reduced longevity in parrots, whereas the evolution of communal roosting and granivory are associated with extended life span.

These results support evolutionary hypotheses of longevity, because extrinsic mortality rates are likely to vary depending on the characteristics of a species’ behavior, habitat, and diet.

ie: No conclusions to see here ()

Bats are similarly priveliged
On to bats:

(3) 'Life history, ecology and longevity in bats' (Gerald S. Wilkinson and Jason M. South, 2002)

This was a statistical analysis, which I guess is useful in discussing a variety of factors to explain the differences between longevity amongst bats.

Note that this is NOT a comparison between Bats and other Mammals:

Rather than attempt to determine how bats differ from other mammals, in this study we aim to explain variation in the longevity of bats using differences in their ecology and life history.

Thus, we assume that mortality risk by predation or accidents is influenced by body size, the presence of conspecifics, use of protected sites and the amount of time spent flying.

Metabolic Rate / Rate of Living Theory
As a quick reminder, the metabolic rate of an organism is not a good predictor of longevity.

Previous studies indicated that the longevity of non-hibernating tropical bat species was no shorter than hibernating temperate bat species (Herreid, 1964) and all bats, including those that do not undergo hibernation, live longer than other mammals of comparable body size (Jurgens & Prothero, 1987; Austad & Fischer, 1991).

Furthermore, marsupials, which have lower average metabolic rates than placental mammals, have much shorter life spans than bats and other placental mammals (Austad & Fischer, 1991)

Inter-Bat Comparison
Some quotes from the study:

"The longevity of every species of bat in our data set exceeds that predicted for their body size from non-flying placental mammals (Fig. 1a)."

"body mass did not explain a significant amount of variation in bat longevity; however, evolutionary change in body mass positively covaried with evolutionary change in longevity"

Also note that among the 6 species to have been recorded living over 30 years of age, we have body masses ranging from 7 grams to 1,000 grams.

"average longevity did not differ between animals kept in captivity and those observed in the wild"

"The source of the longevity record had no effect on this relationship. The number of progeny produced per year was a significant predictor of longevity for both captive records and field records ... The number of progeny produced per year was a significant predictor of longevity for both captive records and field records."

"Hibernating species live, on average, 6 years longer than species that do not hibernate (Fig. 3). The only other variable to explain significant variation in longevity was cave roosting, which was also significant in both species and contrast analyses "

"Bats that sometimes roost in caves live more than 5 years longer than bats that either never or always roost in caves "

"Hibernating species have lower reproductive rates, on average (1.22 ± 0.06 progeny per year), than non-hibernating species (1.48 ± 0.13 progeny per year)."

Diet has Little Influence
As far as I'm concerned, these variables are all over the place ..... with no particular pattern at all.

Then the researchers claim:

The absence of any effect of diet on longevity appears to contradict our predictions. These predictions were, however, relatively weak as the connection between diet and mortality risk is unlikely to be simple.

To facilitate analysis, we used a binary code for diet, i.e. species either fed predominantly on animal or plant material. An alternative approach using, for example, mode of prey capture, such as aerial hunting vs. gleaning, might prove more informative.

Also, hibernation is a robust survival strategy:

we found that hibernation prolongs longevity independent of reproductive rate, body size and phylogeny.

This result suggests that hibernation influences extrinsic sources of mortality risk, which could occur in more than one way. For example, hibernation may reduce the risk of mortality by predation. Bats typically hibernate in locations within caves that are inaccessible to predators and thermally stable

Alternatively, if hibernation is an adaptation to periods of unpredictable food availability, as many believe, then hibernation may also reduce the risk of starvation.

This is where I have to disagree with the stance taken by Pranarupa in his article on Bats, and say that we just have no idea whether or not it is the diet that makes Bats live long, or their environment, or their reproductive strategies, or just some lucky evolutionary mutation that came with the ability to fly.

And as much as Ray Peat fans would like to push the "faster metabolism is better" idea:

Hibernating bats typically reduce their body temperature from about 40 °C to 6 °C, and then maintain that temperature for several weeks at a time.

As a consequence, the metabolic rate of a hibernating bat is about 5% of its resting metabolic rate at room temperature and a fraction of a percent of its metabolic rate when endothermic at cold temperatures

Note that this is very similar to the case of Hummingbirds, which go into deep torpor in sleep, during which body temperature often drops dramatically from 40.6°C to as low as 15.6°C.

Clearly, what we have in both these cases (Bats and Birds) is:

(a) A high maximum potential for energetic bursts

(b) An ability to modulate energy levels to exactly meet demands.

Again, we are back to my original discussion of "Efficient Mitochondria".

From a practical standing, there are no conclusions that can be made, and we cannot say anything certain about human longevity with the existing knowledge we have about bats.

ie: Bats live long because they are Bats .... (-_-)

Naked Mole Rats. Or why PUFA in Mammalian Mitochondria makes them very Eager.
OK, so mitochondrially-blessed animals aside, let's look another mammal that maintains good longeviy and sexual function despite not having crazy efficient mitochondria.

While the link between membrane lipids and longevity is not as strong between the animals with the highest maxmimum metabolic rates (Birds and Bats) and most efficient mitochondrial, in animals with lower metabolic rates (including us humans), membrane PUFAs likely select for a shorter lifespan.

More PUFA on mitochondrial => shorter life, but a "more eager" metabolism during that life.

First, to elaborate on the point regarding "more eager" metabolism, I quote David Valentine again (from the book 'Human Longevity'):

Note that DHA is used in the quote, but the mechanism is applicable to all fatty acids with double bonds, and the effect is more pronounced the more double bonds a fatty acid has.
We predict that DHA/EPA contributes at least three fundamental biochemical properties essential for membrane function, all being a reflection of the extraordinary physical/chemical/biochemical properties of these chains, as follows:

Extreme lateral and rotational motion, which maximizes collisions of membrane components and maintains a functional physical state of the bilayer even under deep-sea conditions

A mediocre permeability barrier for bioenergetically important cations (i.e., H+, Na+, and K+) with a bias toward Na+ bioenergetics

Extreme susceptibility to membrane peroxidation avoided by growth of bacteria in the cold and under anaerobic conditions, otherwise requiring novel protection mechanisms against peroxidation in the presence of air

ie: PUFAs cause stuff to bump into each other more often; metabolic substrate has a much higher chance of banging into its acceptor.

Conversely, rates of oxidative damage also go up.

To test if this is the case, Hagopian and colleagues (2010) used isolated mitochondria from transgenic mice overexpressing EPA (2.55 percent total fatty acids) and DHA (1.74 percent total fatty acids) to test effects of omega-3 on electron transport activity and reactive oxygen species (ROS) production.

And I quote:

The most striking change was seen with complex 3, where activities more than doubled from about 600 units in controls to about 1300 units in mitochondria from transgenic mice

Note: see Chapter 10.2 in 'Human Longevity' for references and further elaboration
So we definitely see increased mitochondrial activity, which apparently, mice evolutionary decided was a worthy tradeoff despite the cut to longevity.

Again, mice do this because they are mice -- "mice Genetics" determine that more PUFA on their membranes is a "worthy evolutionary tradeoff".

With the above in mind, we step back to the Naked Mole Rat study mentioned at the beginning of this section.

To be specific, this study looked at the Peroxidation index of Liver mitochondria and Skeletal Muscle mitochondria.

I quote:

Phospholipids from all tissues have approximately the predicted content of total unsaturated fatty acids (% UFA), but a much lower than predicted % n-3 PUFA content which is compensated for by either a higher than predicted % MUFA or higher than predicted % n-6 PUFA depending on the tissue.

Indeed, comparative differences in DHA content between mice and naked mole-rats (that mice have 9 times more DHA) correspond well, albeit inversely, with the 8- to 9-fold observed difference in longevity

This is perfectly in line with the idea that:

DHA (22:6 n-3) is the fatty acid most susceptible to peroxidation, being 320 times more prone to peroxidation than is the monounsaturated oleic acid (18:1 n-9) and 8 times more susceptible than is the n-6 linoleic acid (18:2 n-6)

And again, the authors rightly say that these differences can only be explained by species-level differences:

We currently do not know the exact contribution of these differences in PUFA composition. Naked mole-rats consume a variety of mixed fruits and vegetables supple-mented with a high protein cereal that is rich in both linolenic and linoleic acids; rodent chow also has similar proportions of these two important fatty acids.

Although diet may contribute slightly to the observed differences, we believe that the very pronounced tissue differences reflect species-specific traits.

And again another reminder that Omega-3 fats aren't that good for you:

The n-3/n-6 ratio for skeletal muscle phospholipids from rats is 0.36, whereas from pigeons it is 0.18 and from naked mole-rats it is 0.15.

Similarly, the value of the ratio for liver mitochondrial membranes is 0.46 for rats, compared to 0.22 for pigeons and 0.18 for naked mole-rats.

Pigeons have the same body mass as rats, but live 35 years on average compared to the 3-4 years for rats. PUFAs in your mitochondria is not good.

Sidenote: "Eager Metabolism" vs "Metabolic Capacity"
PUFAs on Mitochondrial membranes clearly make the mitochondrial Electron Chain Transport (ECT) more eager to do work.

However, they do not increase the maximum capacity of that ECT.

What we find, at least in mice, is that if you don't feed them enough PUFA, there will be less PUFA on their mitochondria, and there will be more metabolic capacity.

References:

The abstract from study (2) basically sums up the observations:

Besides the changes in lipid composition, mitochondrial volume was enlarged (+45% in state 4 and two-fold in state 3).

State 4 respiration was increased together with a decrease in protonmotive force

State 3 oxygen consumption as well as the rate of ATP synthesis showed no difference between the two groups, whereas the protonmotive force decreased substantially in mitochondria from PUFA-deficient animals.

In contrast, ATP/O ratios were decreased in the PUFA-deficient group when determined at subsaturating ADP concentration.

And study (1) provides the explanation:

In light microscopy the mitochondria appear very much enlarged in the periportal region of the lobule. In electron micrographs they have additional cristae, sometimes very abundant. ranged in stacks in the central cavity.

It is known that there is an uncoupling of oxidative phosphorylation in EFA-deficient mitochondria.

It is important to note that State 3 and State 4 mitochondrial respiration is probably not very relevant to living cells, since the conditions these states assume are not realistic.

State 3 respiration demands "ADP saturation relative to ATP", whereas in normal cells, ATP is often in much greater quantities relative to ADP.

State 4 respiration is when all ATPases are maximally saturated, with saturation levels of substrate, and metabolic flow through ECT is at its maximum. This is by definition, and uncoupled state (some degree of inputs "uncoupled from ATP production"). Again, not usually the case in living cells for any significant period of time.
Despite these limitations, what is significant are the morphological changes on the mitochondria, which then drive the observations we see in study (2) using isolated mitochondria.

Essentially, what we find with "PUFA-deficient mitochondria" is a wider pipe, with more sites for respiration to take place.

This means more potential for electron flow along ECT, and also less potential for leakage along the chain; Maximum leakage occurs with high pressure / wider pipes can accomodate more stuff before building up to the same level of pressure.

Personally, I speculate that this is an adaptation to the decrease in eagerness of the ECT when PUFAs are deficient -- there are no "excited troublemakers" (PUFAs) to push things in random directions, so mitochondria need to maximise respiration rates through addition of reaction sites and more folds (cristae) for stuff to bump into.

It is tempting to say immediately that "PUFA depletion in Humans hence leads to more uncoupled mitochondria and more metabolic capacity", but we must remember that this is a mice study, and mice have evolved to put much more PUFAs on their mitochondrial membranes, and hence a PUFA deficient diet has a much more pronounced effect.

That's why you see large magnitudes of metabolic increase in mice (up to 50%. Refer to the Burr mice studies in Ray Peat's article here).

This effect is definitely not going to be as pronounced in humans, though some of the protocols using near-fat-free diets hint that there is some degree of metabolism raising effect (amongst other things).

From a practical standpoint, we will not know how a particular individual will react to such a protocol, and we will not be able to measure any of the mitochondrial adaptations other than studying higher level factors like overall metabolic rates (which have so many other confounders, especially since such PUFA-less diets also cut out a lot of potentially harmful foods).

All commentary regarding the benefits of uncoupled mitochondria and reduced ROS formation, then hinges upon how significant a very-low-PUFA diet is capable of actually producing very-low-PUFA mitochondria. And as we've seen above with Birds and Bats, low level PUFA mechanics in organisms designed to not have a lot of them (like humans) are highly regulated.

No recommendations are made. The reader can experiment at their own risk if they so wish.

Human Dietary Implications
It is clear that Humans are not designed to function with a lot of PUFA on cell and mitochondrial membranes.

Also, all indicators are that in humans, the more PUFA you eat, the more gets stored in your tissues, and the more potential for these to be mobilised at any time to participate in disruptive effects.

Note that I said "tissues", and not necessarily "mitochondria". Adipose tissue PUFA composition obviously rises in response to PUFA overfeeding, and the rise in serum Free FFAs containing PUFAs as a result would hint at these PUFAs potentially affecting the function of other organs.

However, whether or not human cells decide to place PUFA on energy production sites in mitochondria, is not yet confirmed, and I will guarantee that it will exhibit a large degree of individual and tissue variance.

"Disruptive Effects" can then only refer to higher level effects, like systemic insulin resistance.
Also, it is likely that we can make all the "essential fatty acids" (EFAs) we need in adipose tissue (see my DHA article), and I tend to agree with the sentiment that EFAs do not really need to be consumed in levels that most mainstream sources recommend.

NOTE: but just because you can make EFAs yourself, doesn't mean that you should. This depends on particular desaturase enzymes, and other systems in the body to be working properly.

Whether or not a particular individual is going to be able to make enough of these compounds if they don't eat them, is dependent on so many factors, that the only way to find out is to experiment with a truly EFA-deficient diet.

Remember that "EFA Deficiency" should be thought of in a system localised manner, whereby your Heart and Brain may get enough EFAs from Endogenous production (yay no brain disease), but then your Hair follicles may not ...

I personally find it ideal to try and limit PUFA intake, because:

(a) they are so ubiquitous
(b) I'd rather endogenously produce whatever PUFAs my body decides it needs, to settle at an individualised minimum.
This is purely a matter of personal experimentation and taste though; no generalised recommendations are made.

I won't be bothered by the idea of consuming some degree of inevitable PUFAs in the diet, just because that makes diets palatable and enjoyable for the individual, and then keeping body composition good and other systems functioning, so that systemic energetic overload does not hinder the use and deposition of said PUFA.

Philosophical Sidenote: DO WHAT WORKS TODAY; "evolutionary diets" are worthless
This is where I will insert a philosophical assertion: PUFAs being present in "Natural Environments" give absolutely ZERO indication of whether we should be eating them in today's environment.

I absolutely hate arguments that depend on logic: we evolved with X->Y=>Z, and therefore we should do X+Y-somewhat-similar-to->Z.

There are so many exceptions and caveats to this "evolutionary" argument, that it is a completely useless metric to rely on.

Fundamentally, it doesn't matter what we did in the past. "What objectively works today" is the only useful thought pattern to pursue.

Energy Balance is still an Immutable Constraint
For all the talk about PUFA Depletion / Avoidance, Energy Balance still rules at the end of the day.

Provide more substrate than your cells want to deal with, and it will be stored away. Which is to say, that any minute amount of PUFA that you eat that is not immediately oxidised will still be stored in adipose tissue, still be mobilised into circulation when needed, and still be incorporated into the appropriate membranes and tissues when needed.

The only way to force the body into a true "PUFA Depleted" state is with concurrent limitation of PUFAs below the threshold of what the body thinks it needs, AND concurrent substrate limitations to force mobilisation of existing PUFAs in existing structural components.

As an example:

Put someone on a 30% calorie-restricted diet for 8 weeks, while eating a 10% PUFA diet (a lot). They will probably oxidise almost all of that PUFA, lose body fat, and end up with less PUFA than they started with.

Take some on a drunken night pigging out on PUFA-fried nonsense, where they eat 150% of their normal needs. Any dietary PUFA eaten that day WILL be stored ...

And even then, some people may be genetically more prone to make more PUFAs that others. I won't get into the studies, but there is genetic variance in PUFA synthesis, especially in peoples of equatorial latitude ancestry (which makes sense in a way -- less PUFAs and fat in general in ancestral diet, more desaturase activity to provide for endogenous PUFAs).

As far as I'm concerned, people should just chase good body composition (ie: 10-15% body fat for males, 20-30% for females), keep bodyweight at maintenance, don't overeat PUFAs, and let the body distribute Fatty Acids as it sees fit.

ie: All the rambling above just to say nothing (ノಠ益ಠ)ノ彡┻━┻

༼ つ ◕_◕ ༽つ ~~~~ Go eat gummy snakes ~~~~~

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[Mauritio]

This study basically proves peat right , as it shows that mead acid(ETrA), behaves like a saturated fatty acids, in this case not accelerating the inflammatory system (leukotrienes) and even blocking it.

"Thus, dietary ETrA from a biological source can accumulate in leucocytes and suppress inflammatory eicosanoid synthesis. The findings justify further studies into the biochemical and anti-inflammatory effects of dietary ETrA, which could be incorporated into palatable food additives."
(Dietary (n-9) eicosatrienoic acid from a cultured fungus inhibits leukotriene B4 synthesis in rats and the effect is modified by dietary linoleic acid - PubMed)

 

[lamassu]

great thread

 

[LadyRae]

Listening to a Dr. Dom D' agostino interview the other day with the Jay Feldman, he mentioned that there are tons of studies showing that higher levels of Omega-3 in cellular membranes lead to 5 to 10 years longer life...

Jay didn't have a good rebuttal, and I'm not sure what to make of all this

 

[Mauritio]

great thread

Thanks ,one of my favorites too:)

 

[Mauritio]

Listening to a Dr. Dom D' agostino interview the other day with the Jay Feldman, he mentioned that there are tons of studies showing that higher levels of Omega-3 in cellular membranes lead to 5 to 10 years longer life...

Jay didn't have a good rebuttal, and I'm not sure what to make of all this

Feel free to post them , I'll take a look at them.

 

[LadyRae]

Feel free to post them , I'll take a look at them.

Dom speaks at 1:16 about omega-3s and omega-6 for longevity. I can't find actual links to the studies however...


View: https://youtu.be/WbcSRoKYbgQ

 

[Eberhardt]

Listening to a Dr. Dom D' agostino interview the other day with the Jay Feldman, he mentioned that there are tons of studies showing that higher levels of Omega-3 in cellular membranes lead to 5 to 10 years longer life...

Jay didn't have a good rebuttal, and I'm not sure what to make of all this

Im sort of unsure what exactly is said but I would want to see those studies. Is it in humans? Also if you look at pufa saturation in different species the life expectancy of that species is quite in alignment with their lifeexpectancy. The higher Pufa the lower life expectancy. I remember writing with Dr.Peat about it a few years ago and it seems the obnly exception is birds but thats due to the special metabolism in birds (my interpretation)

I think a fair warning is that they say "membranes" - according to Peat and based on the work of Dr.Lings seminal theory on cells and their structures (Pollock has a layman presentation of it - its really dense scientific work- in his book on cells and gels). Basically the socalled cell-membranes are a supposed artifact of the very elaborate process of "documenting" them. So any theory on the basis of that lipid profile os very dubious.

Its also, disregarding all this, not really possible to draw a conclusion even if the studies are real. Its a question of weather EATING pufas are good. The body manufactures our own pufas when we dont eat them. Mainly Mead acid (an omega 9) that makes up the majority of the fat in healthy babies and does not oxidice and become damaging in the same way. So it could even be argued that a healthy pufa"depleted" person could have a high pufa content in some tissue DUE to notvingesting them. Also the Pufa is not equally distributed among tissue.

Anyways. So far there is consistent proof its harmful to ingest in large quantities and is anti-thyroid and immuno-suppresant. And some guys just says in a video that we have lots of proof saying otherwise. :)

Its not a cause for alarm and no way to check the credibilty of such studies (many of them produced by vegetable/fish oil companies)
I am not being sardonic here but if you havent read peats article(s) on fish oil Id give it a try :)

 

[Mauritio]

Dom speaks at 1:16 about omega-3s and omega-6 for longevity. I can't find actual links to the studies however...


View: https://youtu.be/WbcSRoKYbgQ

I did what this guy suggested and googled "pubmed omega 3 longevity "

This is the first result that comes up:

"Could fish oil and its omega-3 fatty acids act as geroprotectors? Probably not. A new study by Strong et al. challenges the role for fish oil supplementation in aging. Using a large cohort of genetically heterogeneous mice in three sites, part of the Interventions Testing Program of the NIA, Strong et al. show that fish oil supplementation at either low or high dosages has no effect on the lifespan of male or female mice. Although it is still possible that fish oil supplementation has health benefits for specific age-related diseases, it does not appear to slow aging or have longevity benefits."
- Fish oil supplements, longevity and aging - PubMed

Here's another one: fish oil fared even worse than the much hated omega 6 fatty acid (safflower oil) which was the control diet. That's says a lot.

"The SAMP8 mice fed fish oil did not have a longer maximum lifespan and had a shorter average lifespan than mice fed safflower oil. To examine the mechanism underlying these results, the effects on oxidative stress of long-term ingestion of fish oil were also examined. SAMP8 mice fed fish oil for 28 wk showed strong oxidative stress that caused hyperoxidation of membrane phospholipids and a diminished antioxidant defense system due to a decrease in tocopherol compared with mice fed safflower oil."
- Long-term intake of fish oil increases oxidative stress and decreases lifespan in senescence-accelerated mice - PubMed

"In conclusion, omega-3 FA over-nutrition or imbalance during pregnancy and lactation had adverse effects on life span and sensory/neurological function in old adulthood."
- Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring - PubMed

Another study showing bad effects from diets high in omega 3s ,done in mice:

"When their effects were analyzed together, the marine oils significantly shortened life span by 6.6 % (P = 0.0321; log-rank test) relative to controls. Individually, Lovaza and krill oil non-significantly shortened median life span by 9.8 and 4.7 %, respectively. Lovaza increased the number of enlarged seminal vesicles (7.1-fold). Lovaza and krill oil significantly increased lung tumors (4.1- and 8.2-fold) and hemorrhagic diathesis (3.9- and 3.1-fold). Analysis of serum from treated mice found that Lovaza slightly increased blood urea nitrogen, while krill oil modestly increased bilirubin, triglycerides, and blood glucose levels. Taken together, the results do not support the idea that the consumption of isolated ω-3 fatty acid-rich oils will increase the life span or health of initially healthy individuals."
- Dietary supplementation with Lovaza and krill oil shortens the life span of long-lived F1 mice - PubMed




Don't get me wrong, there is also evidence for omega 3s increasing lifespan. But I find it not as convincing.

This study was done on flies and given that fact, the increase in life span wasn't that significant. It also reduced mitochondrial uncoupling, which is bad:
- Omega-3 Monoacylglyceride Effects on Longevity, Mitochondrial Metabolism and Oxidative Stress: Insights from Drosophila melanogaster - PubMed

Here's one that looked at the correlation between circurlstinf levels of omega 3s and mortality:

"We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). "
- Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies - Nature Communications

 

[Mauritio]

Dom speaks at 1:16 about omega-3s and omega-6 for longevity. I can't find actual links to the studies however...


View: https://youtu.be/WbcSRoKYbgQ

Having watched it further he does seem to caution about fish oil, which is good.
But the claim that omega 3s are good for a healthy person and bad for a sick person is quite incoherent.
At best a healthy person can burn them quicker and not store them, plus maybe a short term supression of inflammation.

It's like people keep trying to find these small little loopholes, so they can somehow maintain their stance on a topic without losing their face.

It goes from:
Omega 3 is great for everyone --> it's great for almost everyone --> it's only good for healthy people --> it's only good for healthy people if it comes from fish and not in excess ...
Anybody seeing a pattern here ?

Let me finish with a quote from Peat:

"With a strong reason to believe, anything can be believed, and the consequences of holding that belief can be great, seeming to validate the reason for choosing to believe."

 

[LadyRae]

Having watched it further he does seem to caution about fish oil, which is good.
But the claim that omega 3s are good for a healthy person and bad for a sick person is quite incoherent.
At best a healthy person can burn them quicker and not store them, plus maybe a short term supression of inflammation.

It's like people keep trying to find these small little loopholes, so they can somehow maintain their stance on a topic without losing their face.

It goes from:
Omega 3 is great for everyone --> it's great for almost everyone --> it's only good for healthy people --> it's only good for healthy people if it comes from fish and not in excess ...
Anybody seeing a pattern here ?

Let me finish with a quote from Peat:

"With a strong reason to believe, anything can be believed, and the consequences of holding that belief can be great, seeming to validate the reason for choosing to believe."

Wow, so much great stuff here! You really took some time to look into this, and I really appreciate your effort.

Listening to Dom go on and on about himself was really painful during this podcast, and then Jay was hardly given any time to speak... When Jay did get to speak it was like he was only a little added punctuation on the end of whatever Dom was going on about...

 

[Mauritio]

Wow, so much great stuff here! You really took some time to look into this, and I really appreciate your effort.

Listening to Dom go on and on about himself was really painful during this podcast, and then Jay was hardly given any time to speak... When Jay did get to speak it was like he was only a little added punctuation on the end of whatever Dom was going on about...

Well, I thank you for giving me the opportunity to look into this further.

 

[NewACC]

Why PUFA is bad: how high membrane polyunsaturation decreases longevity:



This is probably one of the most interesting papers I've read in a long time . It goes into depth about the danger of PUFA and conncects the dots between PUFA ,membranes ,rate of living theory, life expectancy, and cancer .
They state that PUFA increases lipid peroxidation, yet they still manage to conclude that pufa in membranes is good and a lower metabolic rate increases longevity. So the conclusion is off sometimes but the material in this review is invaluable.

I would advise everyone to read the full study. Especially the parts about membrane fatty acid composition! I have copied the parts that I found most interesting and some conclusions.


1. Rate of living theory doesn't adequately explain maximum lifespan
2. Metabolic rate influences cellular memabrane composition
3. More saturated membranes = longer lifespan
4. Even 5%more PUFA in the membrane means 16x more peroxidative damage
5. The carcinogenic /mutagenic lipid peroxidation end-products can ONLY be derived from PUFA
6. Lipid peroxidation (caused by PUFA) is a self reinforcing process
7. PUFA slows down oxidative metabolism by reducing cytochrome oxidase (amongst others)
8. A cornerstone of the rate of living theory is that increasing size in animals equals a lower metabolic rate . This is true for a very simple reason : "If a mouse increased in size to that of a horse and its BMR increased in direct proportion to the increase in body mass, the horse-sized mouse would need a surface temperature of ∼100°C to rid itself of the heat produced by its BMR (134)."
So to have body temperature of 37° (a little more or less in different mammals) the body MUST slow down metabolism ,because otherwise proteins would start to degrade as in high fever. Which does NOT mean that this "slowing down" of metabolism is what's causing longer lifespan in bigger animals !
9. Especially intraspecific studies have shown that there's a positive correlation between metabolic rate and longevity
10. The lower the peroxidation susceptibility (lower PUFA content = lower peroxidation susceptibility) of the liver and muscle membranes the longer the life span of mammals.



"The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span.


Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate.


When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species.


This means that saturated and monounsaturated fatty acyl chains (SFA and MUFA, respectively) are essentially resistant to peroxidation while PUFA are damaged. Furthermore, the greater the degree of polyunsaturation of PUFA, the more prone it is to peroxidative damage. Holman (148) empirically determined (by measurement of oxygen consumption) the relative susceptibilities of the different acyl chains (see Fig. 1). Docosahexaenoic acid (DHA), the highly polyunsaturated omega-3 PUFA with six double bonds, is extremely susceptible to peroxidative attack and is eight times more prone to peroxidation than linoleic acid (LA), which has only two double bonds. DHA is 320 times more susceptible to peroxidation than the monounsaturated oleic acid (OA) (148).


The peroxidation index of a membrane is not the same as its unsaturation index (sometimes also called its “double bond index”), which is a measure of the density of double bonds in the membrane. For example, a membrane bilayer consisting solely of MUFA will have an unsaturation index of 100 and a peroxidation index of 2.5, while a membrane bilayer consisting of 95% SFA and 5% DHA will have an unsaturation index of 30 and a peroxidation index of 40. This means that although the 5% DHA-containing membrane has only 30% the density of double bonds of the monounsaturated bilayer, it is 16 times more susceptible to peroxidative damage.
View attachment 23703


View attachment 23698

The resulting peroxyl radical is highly reactive: it can attack membrane proteins and can also oxidize adjacent PUFA chains. Thus the initial reaction is repeated and a free radical chain reaction is propagated. Unless quenched by antioxidants, lipid peroxidation is a self-propagating autocatalytic process producing several potent ROS. It can also generate lipid hydroperoxides (124, 335, 336), which are more hydrophilic than unperoxidized fatty acyl chains, and these can thus disrupt the membrane structure, altering fluidity and other functional properties of membranes.

The hydroperoxides and endoperoxides, generated by lipid peroxidation, can undergo fragmentation to produce a broad range of reactive intermediates, such as alkanals, alkenals, hydroxyalkenals, glyoxal, and malondialdehyde (MDA; Ref. 95) (see Fig. 2). These carbonyl compounds (collectively described as “propagators” in Fig. 2) have unique properties contrasted with free radicals. For instance, compared with ROS or RNS, reactive aldehydes have a much longer half-life (i.e., minutes instead of the microseconds-nanoseconds characteristic of most free radicals). Furthermore, the noncharged structure of aldehydes allows them to migrate with relative ease through hydrophobic membranes and hydrophilic cytosolic media, thereby extending the migration distance far from the production site. On the basis of these features alone, these carbonyl compounds can be more destructive than free radicals and may have far-reaching damaging effects on target sites both within and outside membranes.
View attachment 23702

These DNA damage markers are mutagenic and carcinogenic, with powerful effects on signal transduction pathways (217).

Furthermore, they 1) are present in the genome of healthy humans, and other animal species, at biologically significant levels (similar or even higher than oxidation markers sensu stricto) (55), 2) are efficient inducers of mutations frequently detected in oncogenes or tumor suppressor genes from human tumors (254), 3) show increased levels in aged animals (55), 4) can be repaired by nucleotide excision repair systems and metabolized by oxidative pathways (262), 5) correlate with alterations in cell cycle control and gene expression in cultured cells (169), and 6) increase nearly 20-fold with a high-PUFA diet (97).




Thus lipid peroxidation should not be perceived solely in a “damage to lipids” scenario, but should also be considered as a significant endogenous source of damage to other cellular macromolecules, such as proteins and DNA (including mutations). In this way, variation in membrane fatty acid composition, by influencing lipid peroxidation, can have significant effects on oxidative damage to many and varied cellular macromolecules. For example, peroxidized cardiolipin in the mitochondrial membrane can inactivate cytochrome oxidase by mechanisms both similar to hydrogen peroxide and also mechanisms unique to organic hydroperoxides (251).

The variation obvious in Figure 6 is a clear demonstration that the rate-of-living generalization is only a rough predictor of how long a mammal species can maximally live. Its inability to precisely describe the maximum longevity of a mammal suggests other factors are involved in the determination of maximum life span.


"Intraspecific studies on dogs (333), mice (234, 332), and humans (301) reveal a positive association between maximum life span and mass-specific metabolic rate "


Several intraspecific studies using mice and rats (40, 146, 202, 332, 333) have not observed an inverse relationship between mass-specific metabolic rate and MLSP. Indeed, some of these studies show the opposite of rate-of-living predictions, namely, that mice with high mass-specific metabolic rates tend to live longer than those individuals with low metabolic rates.


The liver mitochondrial membrane PI of mammals is proportional to their MLSP−0.40, which means that a 24% decrease in their peroxidative susceptibility is associated with every doubling of maximum life span. For skeletal muscle membranes, the corresponding value is that a 19% decrease in peroxidative susceptibility is associated with every doubling of MLSP in mammals (i.e., muscle PI is proportional to MLSP−0.30).
View attachment 23699

For example, if fed a diet devoid of PUFA, mammals will synthesize an unusual PUFA, mead acid (20:3 n-9) and accumulate it, together with more than normal amounts of MUFA in their membranes. However, with extreme manipulation of dietary fat composition, it is possible to effect small changes in membrane fat composition.

A low PUFA content in cellular membranes (and particularly in the inner mitochondrial membrane) will be advantageous in decreasing the sensitivity of the membrane to lipid peroxidation and would consequently also protect other molecules against lipoxidation-derived damage.

The studies summarized in Table 5 show that there are many reports of 1) an increase in either PUFA content or PI of membranes with age, 2) an increase in both in vitro and in vivo membrane lipid peroxidation with age, as well as 3) age-related changes in physicochemical membrane properties.


In view of these widespread changes in membrane composition and lipid peroxidation with age, it is of interest that in the senescence-accelerated mouse (SAM) strain, those mice that are SAM-prone (SAM-P mice) have greater levels of the highly polyunsaturated peroxidation-prone fatty acids (both 22:6 n-3 and 20:4 n-6) and lower levels of the less peroxidation-prone PUFA (18:2 n-6) in their membranes, and consequently a greater PI, than SAM-resistant mice (59, 281). SAM-prone mice also show greater degrees of lipid peroxides in their tissues than do SAM-resistant mice (221).

Regardless of the factors ultimately responsible for MLSP variation, there are two traits that are often associated with long-lived species: reduced rates of mitochondrial free radical production and reduced susceptibility of membranes to lipoxidation."

https://journals.physiology.org/doi/full/10.1152/physrev.00047.2006?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org

I want to cry!
Here is what is written in the Russian Wikipedia, where, like in Bulgaria and Japan, they are trying to maintain sanity in the study of human biology, about coconut oil:

"Many state and international organizations related to health care, including the US Food and Drug Administration[ 4], World Health Organization[5], US Department of Health and Human Services[6], US Academy of Nutrition and Dietetics[7], American Heart Association[8], UK National Health Service[9] and Dietitians of Canada[10] does not recommend the use of coconut oil due to its high content of saturated fats.

Marketing efforts to promote coconut oil have led to the misconception that it is a "health food"[11]. Whereas studies show that eating coconut oil has similar health effects to other unhealthy fats, including butter, tallow, and palm oil[12]. Coconut oil is high in lauric acid, a saturated fat that raises blood levels of total cholesterol by increasing both high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Due to its high saturated fat content with a corresponding high calorie content, regular use of coconut oil in cooking can contribute to weight gain[13].
"

 

[NewACC]

I want to cry!
Here is what is written in the Russian Wikipedia, where, like in Bulgaria and Japan, they are trying to maintain sanity in the study of human biology, about coconut oil:
"Many state and international organizations related to health care, including the US Food and Drug Administration[ 4], World Health Organization[5], US Department of Health and Human Services[6], US Academy of Nutrition and Dietetics[7], American Heart Association[8], UK National Health Service[9] and Dietitians of Canada[10] does not recommend the use of coconut oil due to its high content of saturated fats.

Marketing efforts to promote coconut oil have led to the misconception that it is a "health food"[11]. Whereas studies show that eating coconut oil has similar health effects to other unhealthy fats, including butter, tallow, and palm oil[12]. Coconut oil is high in lauric acid, a saturated fat that raises blood levels of total cholesterol by increasing both high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Due to its high saturated fat content with a corresponding high calorie content, regular use of coconut oil in cooking can contribute to weight gain[13].
"

Well, that's some kind of abomination. How can you twist the facts like that?

 

[Mauritio]

Alcohol only causes fatty liver when eaten with PUFA not with SFAs

In this study they authors studied how the intake of saturated and unsaturated fats affect the effect of alchohol on the body. They looked at he usual things that alcohol consumption causes in the body (necrosis, fatty liver and inflammation), while also feeding the animals fish oil, corn oil...

raypeatforum.com

 

[Mauritio]

A mutant of C. elegans with a 10-fold increase in lifespan has both increased monounsaturated fatty acids and decreased PUFAS in their membrane.

- Remarkable longevity and stress resistance of nematode PI3K-null mutants - PubMed

The same researcher did a study on the protective effect of aspirin in C. Elegans against oxidative stress. And showed that aspirin increased lifespan by about twenty percent .

- Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans - PubMed

 

[Mauritio]

Yeah, here they are:

Administration of dehydroepiandrosterone enanthate to oophorectomized women--effects on sex hormones and lipid metabolism - PubMed

Eight bilaterally oophorectomized women were given a depot injection of 200 mg DHEA-enanthate to study the effect on endocrine and lipid metabolism. A decrease in sex-hormone binding globulin (SHBG) and an increase in androstenedione was found 14 and 30 days after the injection. No changes could...

www.ncbi.nlm.nih.gov

"...More marked changes were found in the relative fatty acid composition of cholesterol esters, with a decrease in the essential fatty acids linoleic and arachidonic and an increase in non-essential palmitic and oleic acids. In a comparative study between post-menopausal and amenorrhoeic women, women with amenorrhoea were found to have higher levels of testosterone and androstenedione and lower SHBG compared to post menopausal women. Also in this study the essential fatty acids were lower (G. Samsioe and L. Hamberger, to be published). It is therefore suggested that androgens induce changes mainly in the fatty acid composition of cholesterol esters."

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, ...

www.ncbi.nlm.nih.gov

"Hypothyroidism increases the levels of polyunsaturated n − 3 and n − 6 series (e.g., 22: 6n − 3 and 18: 2n − 6) and decreases the levels of monosaturated n − 7 and n − 9 fatty acids.[31] In addition, the change in plasma membrane composition could, in turn, modify the activity of the Na+/K+-ATPase as well as other transmembrane ion exchangers.[103] In fact, it has been described as the reduction of Na+/K+-ATPase activity in the hippocampus of hypothyroid rats.[104,105] The decrease in enzymatic activity might alter the sodium/potassium transmembranal gradient and diminish the uptake of the neurotransmitter glutamate[106] or stimulate the reversed uptake of glutamate.[107] This increase could, in turn, produce mitochondrial calcium overload, decline ATP production, and activate calcium-dependent phospholipases, proteases, and endonucleases.[108] Those biochemical events may increase ROS production and as a result, the lipid peroxidation.[109]”

Accumulation of linoleic and gamma-linolenic acids in tissue lipids of pyridoxine-deficient rats - PubMed

Young male Sprague-Dawley rats were fed diets containing added pyridoxine . HCl at 22 mg/kg (control), 0 mg/kg or 88 mg/kg for 6 weeks. In comparison with control or pyridoxine-supplemented (+PN) rats, growth of the pyridoxine-deficient (-PN) rats was significantly less after 2 weeks. After 6...

pubmed.ncbi.nlm.nih.gov

"...In -PN rats, phospholipid levels of linoleic and gamma-linolenic acids were increased, but arachidonic acid was decreased compared to controls in plasma, liver, thymus and skin. In liver triglycerides from -PN rats, all essential fatty acids (n3 and n6) were increased compared to both control and +PN rats. The n3 essential fatty acids were significantly increased in plasma, liver, and thymus phospholipids in the +PN compared to control rats. These results support previous reports of an effect of pyridoxine on essential fatty acid metabolism and suggest that both linoleic desaturation and gamma-linolenic acid elongation may be impaired in -PN rats. In addition, the accumulation of essential fatty acids in the liver triglycerides of -PN rats suggests that essential fatty acid turnover between triglyceride and phospholipid may be influenced by pyridoxine."

Essential fatty acids in tissue phospholipids and triglycerides of the zinc-deficient rat - PubMed

This study addressed the possibility that zinc deficiency has different effects on the fatty acid composition of triglyceride compared to total phospholipid. Male weanling Sprague-Dawley rats were maintained for 6 weeks on a semisynthetic diet deficient in zinc (3 mg/kg zinc). Control rats (40...

pubmed.ncbi.nlm.nih.gov

"In zinc-deficient rats, the percentage of linoleic acid was increased or that of arachidonic acid was decreased in total phospholipids of plasma, liver, and testis, and in skin total lipids. Saturated and monounsaturated fatty acids were increased in the triglyceride of liver but decreased in the triglyceride of epididymal fat of zinc deficient rats. Essential fatty acids, as a proportion of total fatty acids, were decreased in triglyceride of liver but increased in triglyceride of epididymal fat of zinc-deficient rats."

Dietary fat influences the effect of zinc deficiency on liver lipids and fatty acids in rats force-fed equal quantities of diet - PubMed

Previous studies showed that zinc deficiency influences the fatty acid composition of rat tissues, but the influence of dietary fat on the effects of zinc deficiency was not considered at that time. The present study was therefore conducted to investigate the effect of zinc deficiency on lipid...

pubmed.ncbi.nlm.nih.gov

"The zinc-deficient rats fed the coconut oil diet developed fatty livers, whereas zinc-deficient animals fed the fish oil diet did not. The zinc-deficient rats in both dietary fat groups had lower levels of linoleic acid, arachidonic acid and total (n-6) fatty acids in the liver phospholipids, especially in the phosphatidylcholine, but greater concentrations of (n-3) fatty acids compared with zinc-adequate controls. We conjecture that zinc deficiency influences incorporation of polyunsaturated fatty acids into phosphatidylcholine. The lower levels of arachidonic acid are replaced in the zinc-deficient animals fed a coconut oil diet by docosapentaenoic and docosahexaenoic acids and in the zinc-deficient animals fed a fish oil diet by eicosapentaenoic acid. The replacement of arachidonic acid by other fatty acids in the phospholipids is likely to have implications for prostaglandin synthesis"

 

[Mauritio]

An interesting fact is that queen bees are PUFA depleted .
At least in the sense that their diet that exclusively consists of royal jelly is devoid of fatty acids that can be incorporated into membranes.
Thus they synthesize their own fatty acids which is probably mead acid leading to less oxidative stress and an increase in life expectancy of about 10 fold compared to worker bees.

A similar thing can be seen in queen ants (ants were rays favorite animals) where in some species the queen can life up to 20 years !