Need Thyroid Med HELP!

[Mito]

PUFA will generally be preferentially used in any context in which they are available.

Is your statement contrary to Ray's ideas?

In Herb Doctors - Weight Gain, Ray said "The natural foods milk, beef, lamb, coconut oil, these all have 2 – 3% unsaturated, polyunsaturated fats and if you eat a tiny bit more than you are going to burn right away, some of it is going to be stored in your fat tissue and what is stored is preferentially polyunsaturated fat. Your body recognises that the good stuff to burn right away is the saturated fat, right after the sugars so it selectively doesn’t burn the poly unsaturated fats quickly and so it is the most likely to be stored but then your fat is the same way, the fat cells prefer to burn saturated fats so whatever you have stored in your fats by eating more than you needed, over time your fat cells use up a percentage of the stored saturated fats and increase the storage of the percentage polyunsaturated fats so as you get older and fatter or even if you don’t get fatter your fat tissue becomes more polyunsaturated, so each time you become hungry or stressed and draw on your fat stores for energy, it is more anti thyroid and pro estrogenic because of its increased polyunsaturation in time."

 

[tyw]

Is your statement contrary to Ray's ideas?

In Herb Doctors - Weight Gain, Ray said "The natural foods milk, beef, lamb, coconut oil, these all have 2 – 3% unsaturated, polyunsaturated fats and if you eat a tiny bit more than you are going to burn right away, some of it is going to be stored in your fat tissue and what is stored is preferentially polyunsaturated fat. Your body recognises that the good stuff to burn right away is the saturated fat, right after the sugars so it selectively doesn’t burn the poly unsaturated fats quickly and so it is the most likely to be stored but then your fat is the same way, the fat cells prefer to burn saturated fats so whatever you have stored in your fats by eating more than you needed, over time your fat cells use up a percentage of the stored saturated fats and increase the storage of the percentage polyunsaturated fats so as you get older and fatter or even if you don’t get fatter your fat tissue becomes more polyunsaturated, so each time you become hungry or stressed and draw on your fat stores for energy, it is more anti thyroid and pro estrogenic because of its increased polyunsaturation in time."

I do not see how cells in the body could magically know that saturated fat is the "good stuff to burn right away".

NOTE: maybe (MAYBE!) an exception are dietary medium and short chain saturated fatty acids, and that is due to direct hepatic transport (no chylomicrons required for absorption).

Otherwise, when fat is eaten, it needs to be taken into chylomicrons, transported around the blood and off-loaded to tissues, and then back to the liver, all the while competing with oxidation with available carbohydrates (tissue-differentiated as per the Randle effect), and then stored in adipose tissue if the fat is not required to be used.

All mechanisms point to PUFAs being "more reactive", and that applies also to the susceptibility for them to be transported into the mitochondrial matrix for beta oxidation. NOTE: see paper -- Fatty acid transport: difficult or easy? . Figure 6 shows the relation between number of double bonds and free energy required for transport. This is going to apply regardless of whether a cell receives fatty acid triglycerides from chylomicrons or free triglycerides (ie: regardless of immediate dietary intake or mobilisation from adipose stores).

Another article talking about preference of PUFA oxidation over SFA oxidation in the context of mixed meal intake -- Postprandial metabolism of meal triglyceride in humans,

I've also elaborated before on how PUFA allow for insulin sensitivity to be maintained -- Hey My Dudes [PUFA, Ketosis, Insulin Resistance] . We can simplistically view this as PUFA allowing the "mitochondrial overload condition" to be sustained, which would then allow for more oxidation of substrate (including more PUFA). Note that this is purely mechanical, and does not say whether or not this higher energy state is helpful or hurtful or useless.

As mentioned in the last hyperlink, these PUFA oxidation mechanics may explain why in overfeeding scenarios with PUFA vs SFA, the PUFA groups gain less fat -- Diabetes . As I've stated many times, the operative word is "overfeeding", and cannot be interpreted to mean that "PUFA is good", when harm is already being done to all groups in such scenarios (who gain fat and have poorer body composition).​

But as stated above, I do not see how and why saturated fat would be preferentially used by any cell, and the studies and observations that I've provided don't seem to support that fact either.

As a final funny aside, Dave Valentine, author of "Human Longevity", had chapter 14 titled, "Selective Targeting of HUFAs (Highly Unsaturated Fatty Acids) Away from Cardiolipin and Beta-Oxidation Combine to Protect Mitochondrial Membranes against Oxidative Damage", and has subsections:

- 14.3 Beta-oxidation is Responsible for degrading a vast majority of DHA in the Body, thus minimizing DHA incorporation into most cellular Membranes
- 14.4 Comparative Biochemistry of DHA Detoxification

there is evidence of mechanisms for disposal of unneeded PUFAs, and the molecules themselves are reactive to begin with, and lend themselves to be gotten rid off.​

....

 

[Mito]

I do not see how cells in the body could magically know that saturated fat is the "good stuff to burn right away".
I do not see how and why saturated fat would be preferentially used by any cell, and the studies and observations that I've provided don't seem to support that fact either.

Do you know what Ray Peat's logic is for thinking that saturated fat is preferentially used over PUFA? I'm just asking because I don't know where (or if) he has articulated the reason he believes it.

 

[tyw]

Do you know what Ray Peat's logic is for thinking that saturated fat is preferentially used over PUFA? I'm just asking because I don't know where (or if) he has articulated the reason he believes it.

No clue where Peat got the idea that saturated fat is used first. This topic has been raised before, and I fully agree with what Steffi said in this thread -- Peat got the fats quite wrong

Again, all the real-world observed evidence shows that PUFA are used first. Whether or not this is "preferred" or "desirable" is a separate question ..... PUFAs are simply more likely to be oxidised before saturated fat.

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[Tourist]

Some follow up questions based on added information:

1.) Can the thyroid tissue regenerate after a thyroidectomy where there is residual thyroid tissue (a sliver)? AND, if there was later RAI given; would regenreation mean that radiated tissue is growing or would new tissue be free of RAI?

2.) By reducing PUFA intake and restoring metabolic "harmony" could someone without a thyroid greatly reduce--or eliminate their need for T3/4?

3.) Could someone PLEASE translate the back and forth posts for the dim witted readers ':)

Thanks!

 

[HDD]

Do you know what Ray Peat's logic is for thinking that saturated fat is preferentially used over PUFA? I'm just asking because I don't know where (or if) he has articulated the reason he believes it.

"Despite the instability of polyunsaturated fatty acids, which tend to break down into toxic fragments, and despite their tendency to be preferentially liberated from fat cells during stress, the proportion of them in many tissues increases with age (Laganiere and Yu, 1993, 1987; Lee, et al., 1999; Smidova, et al., 1990;Tamburini, et al., 2004; Nourooz-Zadeh J and Pereira, 1999 ). This progressive increase with age can be seen already in early childhood (Guerra, et al., 2007). The reason for this increase seems to be that the saturated fatty acids are preferentially oxidized by many types of cell, (fat cells can slowly oxidize fat for their own energy maintenance). Albumin preferentially delivers saturated fatty acids into actively metabolizing cells such at the heart (Paris, 1978) for use as fuel. This preferential oxidation would explain Hans Selye's results, in which canola oil in the diet caused the death of heart cells, but when the animals received stearic acid in addition to the canola oil, their hearts showed no sign of damage."

http://raypeat.com/articles/articles/fats-functions-malfunctions.shtml

 

[Mito]

No clue where Peat got the idea that saturated fat is used first. This topic has been raised before, and I fully agree with what Steffi said in this thread -- Peat got the fats quite wrong Again, all the real-world observed evidence shows that PUFA are used first. Whether or not this is "preferred" or "desirable" is a separate question ..... PUFAs are simply more likely to be oxidised before saturated fat.....

"Despite the instability of polyunsaturated fatty acids, which tend to break down into toxic fragments, and despite their tendency to be preferentially liberated from fat cells during stress, the proportion of them in many tissues increases with age (Laganiere and Yu, 1993, 1987; Lee, et al., 1999; Smidova, et al., 1990;Tamburini, et al., 2004; Nourooz-Zadeh J and Pereira, 1999 ). This progressive increase with age can be seen already in early childhood (Guerra, et al., 2007). The reason for this increase seems to be that the saturated fatty acids are preferentially oxidized by many types of cell, (fat cells can slowly oxidize fat for their own energy maintenance). Albumin preferentially delivers saturated fatty acids into actively metabolizing cells such at the heart (Paris, 1978) for use as fuel. This preferential oxidation would explain Hans Selye's results, in which canola oil in the diet caused the death of heart cells, but when the animals received stearic acid in addition to the canola oil, their hearts showed no sign of damage." Fats, functions and malfunctions.

From this is seems Peat's main reason for believing saturated fat is preferentially burned over polyunsaturated fat is that PUFA tends to increase in tissues with age (despite the fact that it is preferentially liberated and oxidized during stress). This is somewhat intuitive to me because why would PUFA tend to increase in tissues as we age if it is the first fat that the cells prefer to burn for energy? If PUFA is preferentially burned, shouldn't saturated fat be the one accumulating in tissues as we age?

 

[tyw]

From this is seems Peat's main reason for believing saturated fat is preferentially burned over polyunsaturated fat is that PUFA tends to increase in tissues with age (despite the fact that it is preferentially liberated and oxidized during stress). This is somewhat intuitive to me because why would PUFA tend to increase in tissues as we age if it is the first fat that the cells prefer to burn for energy? If PUFA is preferentially burned, shouldn't saturated fat be the one accumulating in tissues as we age?

PUFA tend to accumulate with age in some tissues because they are essential to those tissues , while also being reactive, and therefore prone to much endogenous regulation. ie: there are specific pathways designed to accumulate specific amounts of specific PUFAs in specific locations in specific cells.

If there is one central message from my article on DHA, it is that this very unstable and very essential highly unsaturated fatty acid, requires very finely tuned regulation to be used properly -- Docosahexaenoic Acid (DHA)

When this PUFA is used properly, we get the extreme kinetics that are required to run highly complex tissues like the retina (and all its connections to the brain). When this PUFA is not used properly, we get toxic breakdown products.

The same principles apply to all PUFA (though more so to the highly unsaturated AA and DHA) -- Tight Endogenous regulation is required. Now, what happens when the ability to maintain such tight endogenous regulation is slowly lost during the ageing process? .... you get more PUFA is some places which they shouldn't be, and less in places where they should be ... This is exactly what we see -- lost of regulation, not just accumulation.

All of this has nothing to do with the relative ease of (beta) oxidising PUFA over SFA as an energetic substrate, which is always true, and not just in the "stress state".

And in any case, beta oxidation of fatty acids breaks them down into NADH and FADH2; there is no "toxic waste products" from complete beta oxidation.

....

 

[Mito]

PUFA tend to accumulate with age in some tissues because they are essential to those tissues
Now, what happens when the ability to maintain such tight endogenous regulation is slowly lost during the aging process? .... you get more PUFA is some places which they shouldn't be, and less in places where they should be ... This is exactly what we see -- lost of regulation, not just accumulation.

The above two sentences seem to contradict each other (if my interpretation is correct ). The first sentence states that PUFAs only accumulate in places were they are essential (only some tissues but not all tissues). The second sentence seems to state PUFA accumulates in all tissues (the tissues in which they are essential AND places they shouldn't be or nonessential) as we age. I understand the accumulation may be due to disregulation but never the less it is accumulation. This accumulation in all tissues is consistent with Peat's statements.

All of this has nothing to do with the relative ease of (beta) oxidising PUFA over SFA as an energetic substrate, which is always true, and not just in the "stress state"And in any case, beta oxidation of fatty acids breaks them down into NADH and FADH2; there is no "toxic waste products" from complete beta oxidation.

Yes but isn't this risky because some (most??) PUFA's don't make it through complete beta-oxidation (to make energy) before they interact with oxidants creating lipid radicals, lipid peroxide radicals, lipid peroxide, and other highly damaging compounds?

 

[tyw]

The above two sentences seem to contradict each other (if my interpretation is correct ). The first sentence states that PUFAs only accumulate in places were they are essential (only some tissues but not all tissues). The second sentence seems to state PUFA accumulates in all tissues (the tissues in which they are essential AND places they shouldn't be or nonessential) as we age. I understand the accumulation may be due to disregulation but never the less it is accumulation. This accumulation in all tissues is consistent with Peat's statements.

Yes but isn't this risky because some (most??) PUFA's don't make it through complete beta-oxidation (to make energy) before they interact with oxidants creating lipid radicals, lipid peroxide radicals, lipid peroxide, and other highly damaging compounds?

No. My statements are not contradictory.

PUFA is essential for particular functions in a cell. There are many examples. DHA in the retina, Linolenic acid in cardiolipin, etc ..... But they are highly regulated, with very specific enzymes governing incorporation into very specific structures (be it a specific section on retinal ganglion cells, or specific concentrations of cardiolipin in cardiac tissue).

I have discussed some of these specific mechanisms in my posts on this thread -- Haidut's Summary Of PUFA . Again, these are highly regulated mechanism with multiple systems and enzymes working together.

PUFAs do not accumulate at will in the structures that are meant to use it. I have written about that at length on this forum, though many of the mechanisms are summarised in my article on PUFA in birds -- PUFA, Birds, and Genetics . In short, amount of PUFA incorporation into important structures like mitochondrial membranes, is governed and regulated heavily by endogenous mechanisms. So much so that if you feed birds a ton of PUFA, they do not accumulate it on their membranes at all (in fact, the high-PUFA-seed-eating birds lived longer)

We cannot just look at a simplistic mechanic like "PUFA breakdown products bad, therefore PUFA bad", and come to conclusions about PUFA consumption.

The first question is "why would PUFA be in excess quantities in the first place?" I am no fan of excessive consumption, and have consistently called for a reduction in PUFA consumption. That is still completely consistent with the fact that some PUFA is necessary.

Though "how much PUFA is the minimum?" is a question that needs to be answered by each individual. Personally, so long as I keep fat intake low to begin with, I don't really care about controlling for PUFA, because:

- I have very low fat intake to begin with, which is rarely above 15g total fat in a day.
- I rarely eat more than I need, evidenced by the fact that I have not gained any bodyweight in the last 3 years (in fact, I got leaner / lost fat)​

The next question is "Why, where, and how is PUFA oxidation going to cause damage?". It is clear that some generic breakdown of PUFA in the GI tract isn't going to be doing as much harm as lost of cardiolipin function in the heart (due to peroxidation of PUFA). In fact, almost all the loci whereby damage to PUFA causes systemic damage to the organism, are all referring to intra-cellular mechanisms, which are all guarded by endogenous mechanisms, which do not fail if the organism is functioning normally.

We're referring to mechanics like peroxidation of DHA on the retina without adequate recycling mechanisms, or the same in the membranes synapses of the brain leading to improper firing, or Apolipoprotein D (ApoD) malfunctions causing lack of Arachidonic Acid (ARA) clearance from the brain, or peroxidation of cardiolipin causing detachment from Cytochrome C and thus apoptosis of the cell, etc ....

While numerous, these are very specific points of damage, each of which in which the particular PUFA performs a particular role, and whereby there is a unique failure mode that isn't related to the PUFA itself whatsoever.

As an example:

- If there is excess ARA in the brain, why did the brain want to upregulate ARA transport there to begin with? Obviously there must have been an inflammatory driver for this pathway to be over-expressed.

- Why did ApoD malfunction? And How?​

Inevitably, if PUFAs are not in major excess to begin with, when we drive down into the details, it is always going to be some other pathogenesis driving PUFA dysregulation, and not because PUFAs are intrinsically bad.

Cases like "body sees peroxidised PUFA in chylomicrons in bloodstream" are the easy cases that can be dealt with by the immune system. Note that this is the case that will be seen even if PUFA is mobilised from stored tissue.

Cases like "Insulin signalling pathology driving excess fatty acids into liver cells and saturating their energy-producing mitochondrial membranes with PUFA", are the truly harmful ones, in which one should ask, "Why is insulin signalling screwed up in the first place?" (which often requires solutions like "improve body composition")

"Risk" must be defined specifically, and in the case of PUFA, many of these risks are known.

Also, I already noted that in all the experiments cited, it is exactly because they are more reactive, that most PUFAs are pre-disposed to be transported into mitochondria, and put through beta-oxidation quickly, instead of being stored.

Which also means that fixing poor body composition alone fixes many of those risks -- stored PUFAs get mobilised and oxidised for energy.

Dietary PUFA restriction is still generally a good thing to do, and it is still my position that almost everyone in the world eats too much. People would be better off with the 4-5g / day PUFA intake of the traditional Okinawans.

.....

 

[Koveras]

No. My statements are not contradictory.

PUFA is essential for particular functions in a cell. There are many examples. DHA in the retina, Linolenic acid in cardiolipin, etc ..... But they are highly regulated, with very specific enzymes governing incorporation into very specific structures (be it a specific section on retinal ganglion cells, or specific concentrations of cardiolipin in cardiac tissue).

I have discussed some of these specific mechanisms in my posts on this thread -- Haidut's Summary Of PUFA . Again, these are highly regulated mechanism with multiple systems and enzymes working together.

PUFAs do not accumulate at will in the structures that are meant to use it. I have written about that at length on this forum, though many of the mechanisms are summarised in my article on PUFA in birds -- PUFA, Birds, and Genetics . In short, amount of PUFA incorporation into important structures like mitochondrial membranes, is governed and regulated heavily by endogenous mechanisms. So much so that if you feed birds a ton of PUFA, they do not accumulate it on their membranes at all (in fact, the high-PUFA-seed-eating birds lived longer)

We cannot just look at a simplistic mechanic like "PUFA breakdown products bad, therefore PUFA bad", and come to conclusions about PUFA consumption.

The first question is "why would PUFA be in excess quantities in the first place?" I am no fan of excessive consumption, and have consistently called for a reduction in PUFA consumption. That is still completely consistent with the fact that some PUFA is necessary.

Though "how much PUFA is the minimum?" is a question that needs to be answered by each individual. Personally, so long as I keep fat intake low to begin with, I don't really care about controlling for PUFA, because:

- I have very low fat intake to begin with, which is rarely above 15g total fat in a day.
- I rarely eat more than I need, evidenced by the fact that I have not gained any bodyweight in the last 3 years (in fact, I got leaner / lost fat)​

The next question is "Why, where, and how is PUFA oxidation going to cause damage?". It is clear that some generic breakdown of PUFA in the GI tract isn't going to be doing as much harm as lost of cardiolipin function in the heart (due to peroxidation of PUFA). In fact, almost all the loci whereby damage to PUFA causes systemic damage to the organism, are all referring to intra-cellular mechanisms, which are all guarded by endogenous mechanisms, which do not fail if the organism is functioning normally.

We're referring to mechanics like peroxidation of DHA on the retina without adequate recycling mechanisms, or the same in the membranes synapses of the brain leading to improper firing, or Apolipoprotein D (ApoD) malfunctions causing lack of Arachidonic Acid (ARA) clearance from the brain, or peroxidation of cardiolipin causing detachment from Cytochrome C and thus apoptosis of the cell, etc ....

While numerous, these are very specific points of damage, each of which in which the particular PUFA performs a particular role, and whereby there is a unique failure mode that isn't related to the PUFA itself whatsoever.

As an example:

- If there is excess ARA in the brain, why did the brain want to upregulate ARA transport there to begin with? Obviously there must have been an inflammatory driver for this pathway to be over-expressed.

- Why did ApoD malfunction? And How?​

Inevitably, if PUFAs are not in major excess to begin with, when we drive down into the details, it is always going to be some other pathogenesis driving PUFA dysregulation, and not because PUFAs are intrinsically bad.

Cases like "body sees peroxidised PUFA in chylomicrons in bloodstream" are the easy cases that can be dealt with by the immune system. Note that this is the case that will be seen even if PUFA is mobilised from stored tissue.

Cases like "Insulin signalling pathology driving excess fatty acids into liver cells and saturating their energy-producing mitochondrial membranes with PUFA", are the truly harmful ones, in which one should ask, "Why is insulin signalling screwed up in the first place?" (which often requires solutions like "improve body composition")

"Risk" must be defined specifically, and in the case of PUFA, many of these risks are known.

Also, I already noted that in all the experiments cited, it is exactly because they are more reactive, that most PUFAs are pre-disposed to be transported into mitochondria, and put through beta-oxidation quickly, instead of being stored.

Which also means that fixing poor body composition alone fixes many of those risks -- stored PUFAs get mobilised and oxidised for energy.

Dietary PUFA restriction is still generally a good thing to do, and it is still my position that almost everyone in the world eats too much. People would be better off with the 4-5g / day PUFA intake of the traditional Okinawans.

.....

Late to reply

And no, cardiolipin with 4 units of linoleic acid (18:2) is the most common form of cardiolipin in the human body. It is particularly concentrated in the heart.

The proof that 18:2 is absolutely necessary in a healthy human heart is found by examining the case of Barth's Syndrome, which is a genetic disorder that causes Heart Cardiolipin to be altered -- Barth syndrome - Wikipedia

Studies like this show the alteration, in which there is a loss of cardiolipin with 18:2, in favour of cardiolipin with 18:1 -- Bloodspot Assay Using HPLC–Tandem Mass Spectrometry for Detection of Barth Syndrome | Clinical Chemistry

The result are all the diseases of the heart and subsequent functionality in the humans born with this defect, which is very much fatal.

Dave Valentine (author of 'Human Longevity') has this to say:

The major molecular species of CL in cardiac cells is (18:2)4-CL, in which linoleic acid (18:2) occupies all four acyl positions. In Barth’s syndrome the trend is that the 18:2 chains are replaced with more saturated fatty acids, including 18:1.

Studies of Barth’s syndrome establish the essential role of cardiolipin in energy transduction in human mitochondria. CL is primarily located in the inner membrane but is distributed in both leaflets

The universality, localization, amounts, and structure of CL suggest multiple beneficial roles, including formation of supramolecular complexes enhancing energy efficiency as well as appropriate membrane motion and permeability.

These benefits are balanced against risks associated with membrane integrity and oxidative stability.
​

The risks that are mentioned are very clear -- Influence of cardiolipin remodeling on mitochondrial respiratory function in the heart

That last study shows that excess Delta-6 desaturase activity, presumably causing more unsaturated fatty acids in the heart, is directly harmful. That is, once you get cardiolipin that is unsaturated beyond the 2 double bonds in 18:2, peroxidative stress outweighs any benefit of better energetics.

This is very clearly a case of the body having to balance the fast and furious needs of a very active tissue like the Heart, while trying to minimise the downsides. It is clear that without these PUFA on cardiolipin, the heart fails to function, and it is clear that more than the required unsaturation causes damage over time.

Balance is key.

-----

We see the same with other animals (quotes inline):

- Running Speed in Mammals Increases with Muscle n-6 Polyunsaturated Fatty Acid Content

it has been shown that experimentally n-6 PUFA-enriched diets increase the maximum swimming speed in salmon.

the proportion of PUFAs in the muscle phospholipids of an extremely fast runner, the brown hare (Lepus europaeus), are very high compared to other mammals

We found that there is indeed a general positive, surprisingly strong relation between the n-6 PUFAs content in muscle phospholipids and maximum running speed of mammals.​

- Fatty acid composition of pectoralis muscle membrane, intramuscular fat stores and adipose tissue of migrant and wintering white-throated sparrows (Zonotrichia albicollis) | Journal of Experimental Biology

During migratory seasons there was an increase in the n-6:n-3 ratio of muscle membrane phospholipid fatty acids without a change in the proportion of unsaturated fatty acids. This change was driven mainly by an increase in the proportion of 18:2n-6 and a decrease in the proportion of 22:6n-3. An increase in the proportion of 18:2n-6 was also observed in the intramuscular and adipose tissue triglyceride stores during the migratory seasons

These increases in 18:2n-6 were offset by a decrease in 16:0; resulting in an elevated proportion of unsaturated fatty acids and elevated double bond index in both fat stores of migrants

Previous studies on mitochondrial membrane composition report high levels of n-6 PUFA that were associated with an increased oxidative capacity of mitochondria (Guderley et al., 2005). However, a recent study by Maillet and Weber (Maillet and Weber, 2007) found a positive correlation between increased citrate synthase activity (a measure of mitochondrial activity) and high levels of n-3 PUFA in muscle membrane PL in migrating shorebirds.
​

- Performance-enhancing role of dietary fatty acids in a long-distance migrant shorebird: the semipalmated sandpiper | Journal of Experimental Biology

Birds were collected at various stages of fat loading to examine changes in the composition of tissue PL (membranes) and NL (fuel stores). Results show that dietary n-3 PUFA are incorporated in tissue lipids in less than 2 weeks. During the stopover, the double bond index of muscle PL increases by 25% and the fatty acid profiles of both muscle PL and adipose NL converge with that of the die

This study shows that long-distance migrant birds can (1) use natural diets rich in specific lipids to prime flight muscles for endurance exercise, and (2) modify dietary fatty acids before storing them as fuel.

In addition to membrane-related effects, EPA and DHA are also known to trigger mitochondrial and peroxisomal proliferation (Froyland et al., 1997; Jump, 2002a; Jump, 2002b; Totland et al., 2000;Yamazaki et al., 1987), and to increase the activities of key Krebs Cycle and β-oxidation enzymes (Froyland et al., 1997; Guo et al., 2005; Jump and Clarke, 1999; Sanz et al., 2000; Yamazaki et al., 1987).

This study shows that massive consumption of n-3 PUFA causes a rapid increase in the unsaturation levels of muscle PL and adipose tissue NL. However, a significant fraction of the dietary n-3 PUFA consumed is modified before storage to maintain high MUFA levels in the fuel reserves used for migration.

(TYW note: see section 'Flight muscle membranes are modified' for the context of this quote) It is therefore premature to determine whether n-3 or n-6 PUFA are most beneficial, or to generalize to all animals.

In this study, we show that semipalmated sandpipers modify their muscle membranes by feeding on Corophium as they prepare for long-distance flight.​

We can go on, but it is very clear that specific species decide to incorporate specific PUFAs on specific tisue membranes, in order to maximise raw energetic performance in those tissues. It is clear that these PUFAs are not just meant as fuel, but are specifically incorporated into membranes where they are not the targets of Mitochondrial oxidation, and are instead used for the functional purpose of "increasing rate of action" in those cells.

This comes with tradeoffs, and it is clear that each species is designed to work their tradeoffs based on species-specific needs.

This is also why I have said that when comparing any the way any other species uses PUFAs to the way that Humans use PUFAs has very little utility.

The only thing that we can discuss as a cross-species mechanism are the very-low-level mechanisms that PUFAs have at the eukaryotic and mitochondrial membrane level.

-----

I stand by my comments in my post above, and will say that in Humans, some level of PUFA is necessary, and that it should be endogenously regulated as much as possible.

IMO, this applies to all PUFAs, and the more unsaturated the PUFA, the more you want endogenous regulation (which was the entire point I tried to make in my DHA article).

Practically speaking, this still means that one should try to avoid any significant sources of dietary PUFA, since these fatty acids are very readily available in almost any whole food. But neither would I worry about being militant about reducing PUFA to zero.

.....

In the post above you discussed PUFAs increasing the 'rate of action' of certain tissues.

Andrew Kim discussed awhile how thyroid hormone increases the activity of desaturase enzymes:

"Thyroid hormone, in parallel with insulin, decreases the saturation indices of membranes by activating certain desaturase enzymes (Δ5- and Δ6-desaturases), thereby increasing the proportion of the highly unsaturated fats, like arachidonate, to their parents, like linoleate (Van Doormaal, Muskiet, Martini, & Doorenbos, 1986)."

Do you think that's one of the mechanisms where by thyroid hormone increases the 'rate of action' of cells?

 

[tyw]

In the post above you discussed PUFAs increasing the 'rate of action' of certain tissues.

Andrew Kim discussed awhile how thyroid hormone increases the activity of desaturase enzymes:

"Thyroid hormone, in parallel with insulin, decreases the saturation indices of membranes by activating certain desaturase enzymes (Δ5- and Δ6-desaturases), thereby increasing the proportion of the highly unsaturated fats, like arachidonate, to their parents, like linoleate (Van Doormaal, Muskiet, Martini, & Doorenbos, 1986)."

Do you think that's one of the mechanisms where by thyroid hormone increases the 'rate of action' of cells?

IMO, this mechanic is not applicable to humans.

For an overview of the effects of thyroid hormone in other animals, see -- http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1029&context=scipapers

We find that:

(11) Thyroid hormones result in an increased degree of unsaturation of membrane acyl chains (especially in the omega-6 PUFAs). The mechanism of this effect is unknown. It is proposed that the normal phospholipid remodelling mechanisms (largely deacylation}reacylation) present in animal cells respond in a ‘homeoviscous’ manner to the thyroid-hormone-induced membrane rigidification by altering the acyl composition of the membrane.
​

Why the author says that the mechanism is unknown is because:

Direct measurement of ∆6 desaturase activity in rat liver microsomes has shown that it is significantly decreased in hypothyroidism (Faas & Carter, 1982). However, the same authors in the previous year (Faas & Carter, 1981) reported a significant decrease in ∆6 desaturase activity following T3 injections in normal rats.

Curiously, the same study found that although measured ∆6 desaturase activity was reduced, the 18: 2 content of the liver microsomes was significantly decreased and the 20: 4 content significantly increased, which is the opposite of what one would expect from the reported changes in enzyme activity​

(SIDENOTE: this is the original paper by Hoch -- https://deepblue.lib.umich.edu/bitstream/handle/2027.42/24531/0000810.pdf?sequence=1&isAllowed=y)

In any case, regardless of whether the Thyroid hormones have an effect on the delta-5 and delta-6 desaturases, they clearly cause more Membrane Unsaturation in Rat Liver Mitochondria.

This is not applicable to humans. Rats rely on highly unsaturated mitochondrial membranes for increased metabolic activity. The more unsaturated their membranes are, the lower the proton leak (ie: more ATP production) -- http://www.sciencedirect.com/scienc...b1f7edee1c10e685f4d8ed42dfad9b60ae27ce2b05e92

A prior post of mine already raised this point -- Haidut's Summary Of PUFA

IMO, what we are seeing is a generalised call for more metabolic activity. This is signalled via the Thyroid Hormones (and remember that hormones are nothing but messages / requests to get something done; it is still up to the individual cells to actually fulfil their end of the hormone contract).

Then, in rats, the way their cells choose to increase metabolic rate is to increase membrane unsaturation (to a certain limit). There is little evidence that human liver mitochondria, much less the mitochondria of other cells, will respond in this fashion; Humans are a "low mitochondrial PUFA species" to begin with.

Yes, the thyroid hormones provide a generic signal for even human cells to raise their metabolic rate. This is a simple mechanical contract, and does not exactly specify the means in which said metabolic rate must be increased (nor does the contract care if raising metabolic rate is a good thing to begin with).

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[m_arch]

Yew going next level