Posts made by TexugoDoMel

@yerrag

That general view of some peaters about lipolysis that you quoted in your reply probably stems from a misinterpretation of what Ray said about it. The emphasis he places on inhibiting lipolysis is in the context of too much PUFA stored in the tissues, which becomes less and less necessary as you become “PUFA depleted”. After that, inhibiting lipolysis becomes more of a therapeutic tool to be used in appropriate contexts, such as in some pathologies.

He even mentions that in healthy people (especially children) stress hormones are only produced in the amount needed because free saturated fatty acids serve as negative feedback, not allowing them to rise beyond what is necessary.

In good health, especially in children, the stress hormones are produced only in the amount needed, because of negative feedback from the free saturated fatty acids, which inhibit the production of adrenalin and adrenal steroids, and eating protein and carbohydrate will quickly end the stress. But when the fat stores contain mainly PUFA, the free fatty acids in the serum will be mostly linoleic acid and arachidonic acid, and smaller amounts of other unsaturated fatty acids. These PUFA stimulate the stress hormones, ACTH, cortisol, adrenaline, glucagon, and prolactin, which increase lipolysis, producing more fatty acids in a vicious circle. In the relative absence of PUFA, the stress reaction is self limiting, but under the influence of PUFA, the stress response becomes self-amplifying.

This misinterpretation is probably one of the bases for the idea that moderately high insulin several times a day is beneficial (because it inhibits lipolysis and increases glucose oxidation). I don't particularly consider insulin to be a “stress hormone”, but high insulin several times a day and for long periods is obviously a bad sign; insulin plays an “enhancing” role and not the main role.

Keto diets, a very low fat and/or very low protein diet, exercise, ACV before meals, walking after meals, and other similar tools aimed at reducing insulin are only necessary if metabolic dysfunction is already present. Is it good to have these options available with the constant attacks on our health? Yes, but the more miraculous a therapeutic tool is, the more likely it is that your health isn't as good as you think.

@Ancap

How is your sun exposure in summer compared to winter? Assuming nothing else changes...

If we use hibernating animals as an example, one of the reasons these animals develop insulin resistance and become “diabetic” is the absence of sunlight, since the sun is 50%+ infrared light and it stimulates the mitochondria. In a natural environment, the increasing absence of sunlight makes them prone to increased blood glucose (and insulin), and the less exposure to sunlight, the greater the response to carbohydrates.

A 15 min exposure to 670 nm light reduced the degree of blood glucose elevation following glucose intake by 27.7%, integrated over 2 h after the glucose challenge. Maximum glucose spiking was reduced by 7.5%.
Light stimulation of mitochondria reduces blood glucose levels

Whenever possible I like to eat outdoors, or stay outdoors after meals. On days when I can't, I always “simulate” this study and eat with the “chicken lamp” turned on towards me.

@alex155 But it has the same effect as taking t3 and t4, as long as you take it it will suppress the thyroid until you stop, at least that's what the studies say.

@alex155

I remember seeing that there's 1 or 2% T4 in iodocasein, Ray said that it's possible to consume some when you boil oysters in milk (I don't actually remember if it got to the point of boiling).

Iodine has other interactions that can be interesting too. Saturating the double bounds of PUFAs with iodine (and this can happen naturally inside the body) converts them into something closer to a saturated fat. Linoleic acid is converted into tetraiodostearic acid, oleic acid is converted into diiodostearic acid...

PRESS, M. (1974). CORRECTION OF ESSENTIAL FATTY-ACID DEFICIENCY IN MAN BY THE CUTANEOUS APPLICATION OF SUNFLOWER-SEED OIL. The Lancet, 303(7858), 597–599. doi:10.1016/s0140-6736(74)92653-1

@LucH said in New study says increased circulating levels of O6 PUFA arachidonic acid is fasting's mechanism for lowering inflammation (30 Jan 2024):

Hi,
Thanks for posting but I won’t take these studies for granted findings. Deductions are no valid arguments, for me, here. Why?
Main points in the first study:

• AA reduces inflammasones (it turns down the activity of the NLRP3 inflammasome in cell culture and in mouse).
• We already know fasting improves brain biology. Of course if we fast 24 H after a meal of 500 K/cal, it will induce lipogenesis, and thus fat that has been stored, often AA, supposed to be pro-inflammatory because training a cascade reaction. We make a statement but we don’t know how or why in some ways.
  But we know too that very long PUFAs depress the system and the thyroid if prolonged.
  The only interesting thing in this first study is the conclusion, not oriented:
• “There could be a yin and yang effect going on here, whereby too much of the wrong thing is increasing your inflammasome activity and too little is decreasing it,” said Professor Bryant. “Arachidonic acid could be one way in which this is happening.”

You can basically abolish the “brain improvements” of fasting just by consuming tryptophan, even if you don't consume anything else.

We found that adding back carbohydrate or fat did not affect Dietary Restricted(DR)-induced memory retention of mice in the NOR test (Fig 2A), indicating that these constituents do not limit memory performance during DR. In contrast, addition of protein to the DR diet attenuated DR-induced memory performance, bringing it back to alevel comparable to that for AL mice (Fig 2A). We next determined which amino acid affected memory function in this context....

Our results demonstrated that adding back tryptophan, but not glutamate, cysteine, or tyrosine, attenuated DR-induced memory retention (Fig 2B). Tryptophan alone is thus limiting for memory retention during DR. Although adding back carbohydrate and fat, but not protein or individual amino acids, significantly increased the body weight of DR mice (S2A and S2D Fig), none of these dietary manipulations affected general locomotor activity or total time spent on object exploration, compared to either the AL or DR group in the open field test or NOR test, respectively

I'm not sure what they were trying to see in relation to NSAIDs like aspirin, but they inhibit COX-1/2, for them to decrease the level of AA they would have to inhibit Phospholipase A2, which is the enzyme that releases AA from the membrane to be processed by COXs.

It wouldn't be surprising to see a negative feedback mechanism in relation to AA levels in an isolated variable like the one in this study, and there are other ways in which AA can influence this, after all, an increase in AA means more substrate for other things. I remember Travis commenting on AA influencing PPARδ and it also participates in inflammation, so maybe it's responsible for the negative feedback? haha

These findings indicate that PPARδ agonists have the potential to suppress the inflammatory response that triggers atherosclerosis

Some of Travis' mentions of Phospholipase A2:

Han starts off his article quite appropriately by mentioning phospholipase A₂. This is a real enzyme, and can cleave arachidonic acid from membrane phospholipids in vitro. It cannot do this at low lipid concentrations, but once a micelle is formed it will stick to it and start cleaving. The cell membrane is presumed to be similar to a phospholipid micelle. Phospholipase A₂ can cleave phosphotidylethanolamine, but needs to be anchored to phosphotidylcholine to do so. It will not anchor to an in vitro micelle composed exclusively of phosphotidylethanolamine.

By the way, another thing that Click mentioned in X in relation to a possible anti-inflammatory mechanism of fasting is the very restriction of methionine, which is a component of COX-2. One might expect a reduction in inflammation just by restricting some amino acids, on top of restricting other elements that can contribute.

@Insomniac said in I remember Ray Peat saying he used to eat lowish carb. Does anyone know around what age he switched to favoring carbs/sugar?:

@TexugoDoMel Thank you. That's the quote I remembered. I doubt I ever read he ate 50% calories as fat.

But 35 percent is just slightly less than a standard American diet. I remembered him talking about making food from coconut oil like he was at least experimenting with high saturated fat diets.

I think he was only low fat for a few years.

Perhaps because english isn't my first language, the first time I read this quote, especially the “little less fat, maybe 30 to 35%” part, I interpreted it as “little less fat, maybe 30 to 35% less”.

The few times I've seen him comment on his diet, he didn't seem to be eating all that much fat

That's all I remember

"Sugar helps the liver to make cholesterol, switching from starchy vegetables to sweet fruits will usually bring cholesterol levels up to normal. If the fat is mostly saturated, from milk, cheese, butter, beef, lamb or coconut oil, I think it's usually o.k. to get about 50% of the calories from fat, but since those natural fats typically contain around 2% polyunsaturated fats, I try to minimize my PUFA intake by having more fruit, and a little less fat, maybe 30 to 35%." -Ray Peat

Now I don't eat as much because I'm testing very low-fat, but I used to like to eat shredded coconut with sugar in a 1:1 ratio, especially before going to the gym. I never had any problems.

There are some studies saying that uncoupling protects the muscles, so I imagine it's something related. I think it's common knowledge that DNP seems to preserve a lot of muscle mass even if you lose a lot of weight (compared to fat loss with ozempic for example). When protein is restricted there is an increase in T3, uncoupling, brown fat... So this could be one of the reasons, but I don't know if it would preserve it for long

Low protein has twice as much t3

I don't think it's worth it, since it's only a “pseudo depletion”.

In animals, a diet where most of the fat was oleic acid depleted PUFAs (omegas-6 and omegas-3) faster than a diet with no fat or hydrogenated coconut oil.

If I were to try a diet for rapid depletion, it would be a low-fat one supplemented with stearic acid, since most of the stearic is converted to oleic by our delta-6 desaturase (high carbohydrates also increase its activity). The higher the ratio of Oleic to Linoleic the better

Carbohydrates alone raise serotonin through the effect that insulin has on amino acids, increasing the proportion of tryptophan in the blood in relation to other amino acids (which insulin removes from the blood). It would basically be the same if you supplemented tryptophan alone.

But although it seems that carbohydrates are a problem in this case, the real problem is the ratio of amino acids. If you consumed the same amount of sucrose but added some gelatin/collagen or even BCAAs, this effect on increasing serotonin would be abolished. This is even the basis for the “acute serotonin depletion” technique

John D. Fernstrom has several studies on amino acids ratio and serotonin

When plasma tryptophan is elevated by the injection of tryptophan or insulin, or by the consumption of carbohydrates, brain tryptophan and serotonin also rise; however, when even larger elevations of plasma tryptophan are produced by the ingestion of protein-containing diets, brain tryptophan and serotonin do not change. The main determinant of brain tryptophan and serotonin concentrations does not appear to be plasma tryptophan alone, but the ratio of this amino acid to other plasma neutral amino acids (that is, tyrosine, phenylalanine, leucine, isoleucine, and valine) that compete with it for uptake into the brain.

Fernstrom, J. D., & Wurtman, R. J. (1997). Brain Serotonin Content: Physiological Regulation by Plasma Neutral Amino Acids. Obesity Research, 5(4), 377–380. doi:10.1002/j.1550-8528.1997.tb00567.x

Choi, S., DiSilvio, B., Fernstrom, M. H., & Fernstrom, J. D. (2009). Meal ingestion, amino acids and brain neurotransmitters: Effects of dietary protein source on serotonin and catecholamine synthesis rates. Physiology & Behavior, 98(1-2), 156–162. doi:10.1016/j.physbeh.2009.05.004

The amount of studies producing EFA deficiency with fat-free or Hydrogenated Coconut Oil-added diets are the majority, but apparently not the fastest to deplete EFAs.

I posted a few days ago how Oleic acid (MUFA) accelerates EFA deficiency, in the simplest study below 0.8% linoleic and a 20:1 Oleic:Linoleic ratio accelerated depletion. Apart from macadamias, I don't know of anything that has a good OA:LA ratio and little PUFA or is pure Oleic, so I think supplementing with Stearic Acid may be even better, since it is well known and used and has no PUFA, it is also widely converted into Oleic Acid within the body (Rats on a diet rich in Oleic vs Stearic have basically the same amount of Oleic in the tissues).

It would be nice to do an OmegaQuant to see if the depletion is working.

@jamezb46

I usually control my breathing and do a few breath holds, maintaining between 85~90% SpO2 for a few minutes, I know it's not the best way to measure hypercapnia, but it's the most practical for me. Bag breathing is one option, a CO2 bath is another.

For a more localized effect, those who are more creative can create a "homemade paste" of CO2 (paste/hydrogel, baking soda and some acid) and seal the desired area for a few minutes. Animal studies have shown good results from doing this for 10 minutes over a few days.

In conclusion, our study demonstrates that the CO2 paste prevents excessive scarring and accelerates muscle regeneration. This may be due to the induction of an artificial Bohr effect, which leads to the upregulation of MyoD and myogenin, and the downregulation of IL-1β, IL-6, and TGF-β. The CO2 paste is inexpensive and non-invasive. Therefore, it may be the treatment of choice for patients with muscle damage. Further research should be conducted to confirm our findings.

@brad bloo co2 paste when

@thyroidchor27

I don't see a problem with a little olive oil, but if you want to tip the scales to the "peaty side", macadamia is probably a better option due to the Oleic:Linoleic ratio.

When I say PUFA in this article, I'm referring mainly to omegas-6, as they are responsible for most of what is known as essential fatty acid deficiency(EFAD). Omegas-3 deficiency causes other effects, which I won't cover here.

On Mead Acid(MA)

That MA is produced in large quantities in a state of Linoleic(LA)/Arachidonic(ARA) deficiency is already known (The other post in which I talk about this and mention a few more things can be found here), but what is little known is that MA also has the ability to deplete other PUFAs by competition, either by "metabolic pathways" or structurally (taking the place of other PUFAs in membranes).

Below is a table showing the proportion of fatty acids in plasma phospholipids in diets with different Mead:Linoleic ratios

Regardless of the proportions, the presence of LA in the diet seems to be the determining factor in the minimum levels of LA/ARA in phospholipids, but that's not what matters here, what we can see is that the increase in the proportion of MA affects the levels of LA/ARA as well, clearly demonstrating a competition between these PUFAs for the same positions in the membrane. MA(20:3 ω-9) is a "substitute" for ARA(20:4 ω-6), so the effects will be more noticeable at the ARA level than LA.

The conclusion seems to be the same:

Nice to know, but if MA is produced in large quantities only in EFAD, what relevance does it have for us? It's not as if there's a significant external source of MA.

Indeed, but considering that MA is produced from Oleic Acid (OA), I've been thinking for some time about the possibility of manipulating levels through diet. In theory, if the LA:ALA ratio, which is usually much higher than 1, hinders the conversion of ALA (even though it has priority compared to LA) to EPA/DHA, the same would be possible with the OA:LA ratio, favoring OA. I always thought it curious that MA was produced from OA but most studies only induce EFAD with a fat-free diet or hydrogenated coconut oil.

Does consuming more OA increase MA production?

Apparently yes. Below is the difference between the levels of MA derivatives in a diet rich in LA vs rich in OA:

Unfortunately in this study I didn't find the information on how much OA was in the high LA diet so I could get a better idea, but in this other study there are more details:

Influence of diets on MA(20:3 ω-9)

We saw before that the amount of LA is the biggest influence on MA limits, but take a look at the graph and compare it with the diets and their OA:LA ratios.

• Soybean Oil: 0.4
• Fish Oil: 13.3
• Lard: 4.6

Although Fish Oil(omega-3 has the aggravating factor of reducing Δ-6 desaturase) has the best OA:LA ratio, the amount of MA is still less than that of Soybean oil with 50% LA and a ratio of 0.4! OA seems to increase MA regardless of LA.

Is the presence of OA/MA able to help deplete EFAs?

Apparently, not only is it able to help, but it happens much faster than a fat-free or coconut oil diet.

SF(OA=14.2%/LA=75.5%) - CO(OA=2.63%/LA=0.45%) - OA(OA=69%/LA=3.54%)

Trienes* = Mead Acid(20:3 ω-9)

Within 21 days MA was found in the brain, liver and serum in the OA group, even though the diet with the lowest LA was CO.

After 90 days, the intensity of EFAD was greater in the OA group

Curiosity: Usually EFAD at these levels is enough to cause growth stunting, but apparently OA didn't have as much of this, at least in this study. Study with too little time to find out.

Other studies seem to confirm OA ability to increase MA independently of LA:

Others point to OA ability to interfere with LA levels:

Attention was thus focused on the possibility that oleic acid interfered with the normal utilization of some other component in coconut oil. As we were dealing with essential fatty acid deficiency symptoms, this component might be linoleic acid. Gas-liquid chromatographic analysis of coconut oil showed that it contained 1.5% of linoleic acid, furnishing about 20 mg. of linoleic acid per day per guinea pig. This amount, although small, can support almost normal growth without any deficiency symptoms as shown by feeding coconut oil alone. However, when comparatively large amounts of oleic acid are included in the diet, the animals no longer can utilize the small but significant amount of linoleic acid and deficiency symptoms are observed.

It may be possible that under these circumstances oleic acid competes with linoleic acid and acts as an inhibitor with some of the enzymes involved in arachidonic acid formation. If such is the case, metabolites of oleic acid would accumulate in the oleic acid-fed group. Eicosatrienoic acid, which is formed from oleic acid under conditions of fat deficiency, was found in the oleic acid-fed group and was absent in the other groups.

To produce MA, it seems that the amount of oleic matters in an "acute" way, and the limits and intensity with which it can increase seem to be defined by the OA:LA ratio at the moment.

The way I see it, for those who strive to deplete PUFA, there's no reason why someone can't reach this EFAD status or can't accelerate this state to happen in less than 4 years. Considering depletion as something that happens in a linear way is the reason many peaters find it impossible outside of laboratory environments.

REFERENCES

Cleland, L. G., Neumann, M. A., Gibson, R. A., Hamazaki, T., Akimoto, K., & James, M. J. (1996). Effect of dietary n-9 eicosatrienoic acid on the fatty acid composition of plasma lipid fractions and tissue phospholipids. Lipids, 31(8), 829–837.

Nada Birkic, Toni Azar, Krishna Rao Maddipati, Zeljka Minic & Christian A. Reynolds. Excessive dietary linoleic acid promotes plasma accumulation of pronociceptive fatty acyl lipid mediators

Mizunoya, W., Iwamoto, Y., Shirouchi, B., Sato, M., Komiya, Y., Razin, F. R., … Ikeuchi, Y. (2013). Dietary Fat Influences the Expression of Contractile and Metabolic Genes in Rat Skeletal Muscle. PLoS ONE, 8(11), e80152.

Menon, N. K., & Dhopeshwarkar, G. A. (1981). Essential fatty acid deficiency and lipid metabolism of the developing brain. Progress in Lipid Research, 20, 129–134.

Lowry, R. R., & Tinsley, I. J. (1966). Oleic and Linoleic Acid Interaction in Polyunsaturated Fatty Acid Metabolism in the Rat. The Journal of Nutrition, 88(1), 26–32.

Mohrhauer, H., Rahm, J. J., Seufert, J., & Holman, R. T. (1967). Metabolism of Linoleic Acid in Relation to Dietary Monoenoic Fatty Acids in the Rat. The Journal of Nutrition, 91(4), 521–527.

I've never looked that deeply in this context, but cortisol is just one of the hormones involved in glucose regulation.

The hormones glucagon, glucocorticoids and adrenaline are all increased in catabolic states and may work in concert to increase protein breakdown in muscle tissue and to increase amino acid uptake in liver for gluconeogenesis.

Although glucagon is regarded as a major hormone that activates gluconeogenesis during fasting, fasting-induced gluconeogenesis is reduced in adrenalectomized mice, an effect that is restored by treating mice with GC [ 40 – 42 ]. In fact, glucagon-, epinephrine-, or cyclic AMP(cAMP)-induced gluconeogenesis are all attenuated in adrenalectomized mice. Giving GC to adrenalectomized mice restores the ability of these hormones to induce gluconeogenesis. Thus, GC play a “permissive” role promoting the optimal ability of these hormones in gluconeogenesis.

So if cortisol is not close to 0, and their bodies are already adapted to a high level of fatty acid oxidation and they are maintaining a constant flow of ketones, it is unlikely that they will experience severe hypoglycemia since ketones are glucose sparing.

ketogenesis can be upregulated by hormones such as glucagon, cortisol, thyroid hormones, and catecholamines by causing a more significant breakdown of free fatty acids, thus increasing the amount available to be used in the ketogenic pathway. However, insulin is the primary hormonal regulator of this process.

Basically everything Peat says to keep the metabolism healthy is good for bringing the body back to that state after training, with the exception of aspirin, which is considered to be detrimental to gains due to its effect on prostaglandins.

In particular, I like to drink plenty of low-fat or skim milk/kefir after a workout, use red/infrared light (sun is better) and finish with a buteyko/CO2 bath.

CO2 seems to be a great addition post-workout, as it increases the number of mitochondria (PGC-1α), angiogenesis (VEGF) and O2 availability to the tissues.

In episode 53 of “Generative Energy Ray talks about a study in which scientists took EFAD rats and threw them against the furniture, but even after that the scientists were unable to observe any damage. Ray also mentioned this in the interview with Tucker Goodrich and David Gornoski

Furthermore, in episode 64 of Generative Energy (Life | Energy | Estrogen | Fibrosis | Calcification | Process Theology | Altruism with Ray Peat), haidut comments on studies of EFAD rats regenerating wounds without any scarring.

I couldn't find it, does anyone have these studies? I don't know if @haidut has kept the one about the scar in efad

“The enzyme that produces the Mead fatty acid is strongly inhibited by PUFA seed oils (less strongly by fish oils), and so the presence of the Mead acid in the tissues is taken as evidence that the animal is suffering damage resulting from the absence of PUFA. The Mead acid happens to have some valuable anti-inflammatory effects, and is associated with many biological advantages, but research in that direction is prevented by the lack of funding.” Ray Peat

When Ray mentions the ability of EFAs to suppress the production of Mead Acid, he is talking about the effects they have on desaturases, and although ω-3 has the ability to suppress Mead acid this would probably only happen if ingested in large quantities, the biggest reason for the increase in Mead acid production is ω-6 restriction.

So first of all, you should know that desaturases "add 1 double bound" and elongases "add 2 carbons". Let's take stearic acid as an example, it has an 18-carbon chain and because it is saturated it has no double bounds, so we classify it as 18:0. When it is used as a substrate by the enzyme ∆-9 desaturase (D9D) a double bound is added and it becomes 18:1, so stearic acid (18:0) has been converted into the monounsaturated oleic acid (18:1). The logic is similar for elongases, if 18:1 is used as a substrate by an elongase it would be converted into a 20:1 fatty acid.

To produce Mead's acid, oleic acid (18:1ω-9) is the substrate for the enzyme ∆-6 desaturase (D6D), which transforms it into 6-9-octadecadienoic acid (now 18:2ω-9) which then undergoes the effects of an elongase and is converted into 8-11-eicosadienoic acid (now 20:2ω-9). The last step after this is to pass through ∆-5 desaturase (D5D), converting it into Mead acid(5-8-11-eicosatrienoic acid) with 3 double bounds (20:3ω-9).

The strong inhibition of Mead acid production by EFAs is due to their affinity for the D6D enzyme. α-linolenic acid has priority, followed by linoleic acid and then oleic acid.

The increase of the affinity of the ∆6-desaturase from oleic to linoleic and α-linolenic acid, as well as the correlative increase of the rate of their desaturating reactions explain the predominance of the polyunsaturated acids of the linoleic family or α-linolenic family over the acids of the oleic family in animals fed a complete diet.

For this reason, I can only see two ways of producing Mead's acid in larger quantities:

• By elimination: As Ray suggests, eliminating "essential" fatty acids (focus on eliminating ω-6) from the diet and accumulated in the body, thus releasing D6D for oleic acid.

• By competition: A greater flow of oleic acid in "unusual" situations. Just eating more MUFA won't make you produce more Mead's acid (unless perhaps you were already depleted of EFAs), but there are studies on rats that show that fasting for 3 days and refeed even with an ordinary diet will make the level of Mead's acid rise. The supposed reason? Fasting partially suppresses the desaturases and there is an overcompensation in refeed, apparently for brief moments there is an insufficiency of EFAs and an abundance of MUFAs such as Oleic, available to desaturases.
  
  Control(normal), control-induced(fasting+refeed)

Accelerating pufa depletion through desaturases

In addition to the affinity factor, different macros exert different effects on desaturases, which in theory makes it possible to accelerate EFA depletion by manipulating desaturases. If we consider cystic fibrosis(CF) as an example, Mead's acid is common and is not always due to super low levels of linoleic acid (although they are almost always low), but rather to an increase in the expression of desaturases.

CF: Among these abnormalities are increases in the levels of n-7 and n-9 fatty acids, particularly palmitoleate (16:1n-7), oleate (18:1n-9), and eicosatrienoate or mead acid (20:3n-9)

Work from our laboratory provided correlative data suggesting that these metabolic changes were due to increased expression and activity of fatty acid desaturases ( 23, 24 ). The current study demonstrates that treatment of CF cells with exogenous DHA reverses the metabolic changes by suppressing expression of these enzymes. Specifically, DHA decreases expression of 5- and 6-desaturases.

I found a study in which they accelerated "essential" fatty acid deficiency by inducing D9D, fasting for 3 days + 4 days of refeed.

Biochemical indicator of "essential" fatty acid deficiency is a triene:tetraene ratio (20:3n-9:20:4n-6) greater than 0.4, and below is the difference between EFAD (fat-free diet without fasting) vs EFAD-Induced (fasting+refeed with fat-free diet) over 3 weeks.

Comparing the two, EFAD has a T:T ratio of 1.55 while EFAD-induced has a ratio of 2.60. The former's ratio seems to be more influenced by the increase in Mead Acid (20:3) with almost 60% more compared to EFAD-Induced, which seems to have a high ratio due to the depletion of Linoleic (18:2) and Arachidonic (20:4). This T:T ratio doesn't reflect all the tissues in the body, so this highlight is from the serum.

Do you remember that different macros influence enzymes in different ways? So.

Example 1:

Obs.: G= Glucose, C = Casein, HCO = Hydrogenated coconut oil, SFO = Sunflower Oil.

Example 2:

While fasting is not "peaty" I have the impression that a similar or superior result can be achieved with a protein restriction replacing these 3 days of fasting. Protein restriction seems to have the same effects on desaturases, combined with carbohydrate increasing D9D and low fat (close to 0 PUFA) might be better.

In monkeys:

In rats:

In the present work a time-course study with young rats fed on a low-protein diet was an original approach for protein restriction, providing evidence that ∆-9 desaturase activity is impaired, as indeed are ∆6 and ∆5 desaturase activities, during growth under such a dietary regimen.

The effects of this cyclical approach, which accelerates the depletion of EFAs, are more localized:

The mol% of 20 : 3(n - 9) in serum was not increased by ∆9 desaturase induction and the 20 : 3(n - 9) to 20 : 4(n - 6) ratio was only modestly increased. The effects of ∆9 desaturase induction were even more attenuated in tissues other than the liver.

The liver is not the only tissue that shows changes in fatty acid composition. It has been noted, however, that the extent of change is much more profound in liver during the limited 48 hr refeeding period. In Table 5 it is seen that adipose tissue (epididymal fat pad), heart tissue, and the remaining carcass also reflect the variations noted with liverr, but the extent of change is less in the period studied.

So I think you can still expect a general acceleration on a diet with <0.8% linoleic acid, since even those on the control diet produced a small amount of Mead's acid, I suppose that some of it is transported out of the liver and what would take 4 years could be reduced to less due to competition, who knows.

The above studies showed that the concentrations of other PUFAs, such as ARA, EPA and DHA, decreased due to their partial displacement by Mead Acid(MA). The results suggest that MA competes with other long chain PUFAs in PUFA metabolism, and that the presence of MA is not solely due to the decrease in ARA in patients with EFA deficiency. The competition of MA with other PUFAs, especially ARA, is a main mechanism underlying its various physiological and pathological activities, as described below.

Besides, considering that simple approaches can have this influence opens up new possibilities for experimentation: would restricting calories a little on restriction days also increase overcompensation in refeed? And if I use niacinamide/aspirin on restriction days to decrease de novo lipogenesis, what would be the effect?

References

DAVID W. ALLMA, DOROTHY D. HUBBARD, and DAVID M. GIBSON. "Fatty acid synthesis during fa t-free refeeding of starved rats"

Hui Gyu Park, Matthew G. Engel,Kyle Vogt-Lowell, Peter Lawrence, Kumar S. Kothapalli, and J. Thomas Brenna. "The Role of Fatty Acid Desaturase (FADS) Genes in Oleic Acid Metabolism: FADS1 Δ7 desaturates 11-20:1 to 7,11-20:2"

J B Lefkowith. "Accelerated essential fatty acid deficiency by ∆9 desaturase induction: dissociation between the effects on liver and other tissues".

CAROL A. INKPEN, ROBERT A. HARRIS and FORREST W. QUACKENBUSH. "Differential responses to fasting and subsequent feeding by microsomal systems of rat liver: 6- and 9-desaturation of fatty acids"

Rodolfo R. BRENNER "The oxidative desaturation of unsaturated fatty acids in animals"

María C. Marína, Héctor M. Pucciarellib, and María J.T. de Alaniza. "Liver Desaturase Activities and FA Compositionin Monkeys. Effect of a Low-Protein Diet".

Victoria Ayala, Alba Naudí, Alberto Sanz, Pilar Caro, Manuel Portero-Otin, Gustavo Barja, Reinald Pamplona. "Dietary Protein Restriction Decreases Oxidative Protein Damage, Peroxidizability Index, and Mitochondrial Complex I Content in Rat Liver"

Hiroshi Kawashima and Katsuhiko Yoshizawa. "The physiological and pathological properties of Mead acid, an endogenous multifunctional n-9 polyunsaturated fatty acid"

Sarah W Njoroge, Michael Laposata, Waddah Katrangi, Adam C Seegmiller. "DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity"

Kelly F Thomsen, Michael Laposata, Sarah W Njoroge, Obi C Umunakwe, Waddah Katrangi, Adam C Seegmiller. "Increased elongase 6 and Δ9-desaturase activity are associated with n-7 and n-9 fatty acid changes in cystic fibrosis"*