@hcwilliams said:

not a big fan of AI but I asked it about my plan to deplete overall pufa stores then refeed with saturated fat to increase sa:pufa ratio

"You Can't Burn Your Way Out of Structural PUFA
Adipose tissue is not just a giant, homogenous bucket of liquid oil where everything mixes together equally.

The "Core" vs. The "Shell": Essential PUFAs (like linoleic acid) are structurally embedded into cell membranes across your entire body—your brain, red blood cells, nerves, liver, and mitochondrial cristae. They are not sitting in your subcutaneous fat depot waiting to be mobilized; they are functional components of tissue architecture.

...

The reason the 2–6 year timeline is stubborn is that true PUFA depletion is a turnover problem, not just a math problem. The cells containing the old, damaged seed oils have to naturally die off, cycle out, and rebuild their phospholipid bilayers using saturated fats and what the body manufactures itself."

this makes sense but not sure what to do about this to speed up the process of cellular pufa

That’s basically what I told you.

Cells will be rebuilt using the available fatty acids (usually in the blood), if you drastically limit n-3/n-6 and maintain an isocaloric diet (i.e., adipose tissue won’t be mobilized as much), your other tissues will generally be built up while depleted of these PUFAs, since the flow of fatty acids will be largely determined by the conversion of carbs into saturated/monounsaturated fat. If, after that, you fast or start losing weight, then n-3/n-6 will be mobilized into the blood, and you’ll see an increase in their levels in the cells of other tissues.

There’s no other way to truly deplete these PUFAs except by drastically restricting in your diet and depleting bodyfat.

In theory, you could set up a “cutting-bulking” cycle with the goal of gradually altering the ratio in adipose tissue while simultaneously depleting total PUFAs.

Let’s assume you have 25% body fat(BF) and have set a goal to reach 10% BF on a PUFA-depletion diet. “Cut” for long enough to achieve a maximum of less 4% BF; once you reach that goal, start “bulking” until you gain a maximum of +2% BF on a diet that is essentially PUFA-free.

This way, you’re losing a total of 2% in each cycle while simultaneously manipulating the SFA/PUFA ratio in adipose tissue.

I don't know how many cycles of gaining 2% body fat and losing 2% body fat it would take to deplete it while maintaining weight nor if it is possible to deplete that way while alive but you can try it too haha

But there are several ways to do cycles like these. I hate long cutting cycles, so when I just want to keep losing weight, I do a "cutting day" every other day until I reach my target weight.

Every time I’ve done it this way, I haven’t experienced any of the negative effects of a long cutting cycle. In fact, quite often the opposite happens: instead of weight loss slowing down over time, the process actually speeds up

"You Can't Burn Your Way Out of Structural PUFA
Adipose tissue is not just a giant, homogenous bucket of liquid oil where everything mixes together equally.

The "Core" vs. The "Shell": Essential PUFAs (like linoleic acid) are structurally embedded into cell membranes across your entire body—your brain, red blood cells, nerves, liver, and mitochondrial cristae. They are not sitting in your subcutaneous fat depot waiting to be mobilized; they are functional components of tissue architecture.

...

The reason the 2–6 year timeline is stubborn is that true PUFA depletion is a turnover problem, not just a math problem. The cells containing the old, damaged seed oils have to naturally die off, cycle out, and rebuild their phospholipid bilayers using saturated fats and what the body manufactures itself."

this makes sense but not sure what to do about this to speed up the process of cellular pufa

Is tren the only feasible way to build muscle during a caloric deficit? Or are there other methods?
………….(( I probably can’t use thyroid with dnp because last time I did that even <3mcg doses would punish my cholesterol and I’d get manic depressed until it came back… I also felt amazing on dnp cus of high temps))

I haven’t lifted in two years so I’m skinny fat but with muscle memory and “newbie” gains I think I can have somewhat decent gains. I just really don’t wanna get low body fat and be gaunt with no muscle

@TexugoDoMel said:

I remember reading that exercise increases unsaturation in muscle tissue,

This would be due to adrenaline right? I know caffeine and thyroid increase SCD 1 levels.

@TexugoDoMel said:

perhaps steroids have a similar effect

Trenbolone can supress SCD 1 levels in animals I have read, and if I remember correctly, so does testosterone.

@TexugoDoMel said:

Androgens seem to me to be more of a structural stabilizer; depending on the animal model of hypertrophy you look at, the (%) hypertrophy is the same in the control animal and in the animal using androgens. The benefit of androgens is solely the reduction of muscle damage, but they do not accelerate hypertrophy; both end up the same.

Oh yeah, I agree. think in endogenous produced amounts, their effects on hypertrophy aren't as they claimed to be. Thanks for the study

@hcwilliams said:

is it true that after a certain dose of testosterone you stop aromatizing into estrogen because the testosterone starts competing for the estrogen or aromatase enzyme/receptors?(I butchered that)

That has not been demonstrated, but it's plausible in theory. Testosterone itself is not the best substrate for aromatase, it's the metabolite, androstenedione, that is a better one. However, the affinity is still moderate - high.

Androgens themselves have neglible affinities for the estrogen receptors. However, especially, exogenously, they circulate at concentrations 100s of fold greater than estrogens. This neglible affinity may become relevant at these concentrations. But again, there are estrogenic metabolites such as the androstenediol and 3a & b androstanediol that have direct and weak affinity for the ERs, and activate them. So I don't think that T directly would have any anti estrogenic effects.

However, genomically, activation of the androgen receptor supresses aromatase and reduces estrogen receptor concentrations. This is why 5 AR androgens were trialed in treating breast cancer. Simply because of their epi genetical anti estrogenic effects. Not because of their direct affinities for aromatase or receptors.

And this is why the 5 AR steroids are ran alongside T - to have an androgen that has no direct estrogenic potential, that has epi genetical anti estrogenic properties, stopping the aromatising and estrogenic effects of T and it's metabolites.

@alfredoolivas said:

@hcwilliams why did you delete your comment bro lol

If you aren't afraid of DNP, you shouldn't be afraid of a low/moderate dose of androgens. They are SUPER effective at preserving lean mass. Especially, if you aren't on thyroid :). I believe they also increase the triene/tetraene ratio Ill try to find the study

Lol my answer didn’t make sense to your question I was responding to.

I’m on testosterone now

@Luke said:

@TexugoDoMel
Macadamia oil is the only oil I can think of that's high in oleic acid and low in PUFA. Downside of course is the high price.

Macadamia oil is good, and I use it sometimes, but since the total percentage of PUFAs in the diet is at the top of the hierarchy, it still contains a lot of linoleic acid. Supplementing with stearic acid doesn't add to that and helps lower the (n-3+n-6)/(SFA+MUFA) ratio even further.

@alfredoolivas said:

@TexugoDoMel these are good theories. Especially the stearate and oleic acid one. PUFA depletion black pill kinda

I’ll personally lean towards more PUFA being burned from a higher metabolic rate. Would I be wrong?

Unrelated, but could you try to explain to me the glycine to methionine ratio? Like why does it matter in terms of protecting against the harmful metabolic effects of methionine.

It’s not exactly a theory, since it’s been demonstrated in animals, haha. You can combine various approaches, but the main thing should be to keep your metabolic rate high, IMO as well.

I’ve never really paid much attention to it, but since glycine is involved in the methionine cycle, I’d expect it to help regulate methyl levels (GNMT?), helping to dissipate excess methyl

From "Protective CO2 and aging"

@hcwilliams said:

well, the inspiration came from this quote on a GE podcast. Georgi: What about chemical interventions? I mean, there is a tremendous track record of things like dinitrophenol being able to cure effectively even extremely morbidly obese people, of course, under medical observation because it can easily kill you if you overheat. Wouldn't something like that be considerable?

Ray: Overdosing on thyroid does the same thing. At the right level, it can increase your safe oxidation of fats while helping to suppress the toxic or random oxidation. Both DNP and thyroid can carefully controlled can reduce the toxicity of getting rid of the fat.

But again thyroid overdose per se would render my cholesterol to undetectable levels. DNP even in high doses doesn’t seem to have that effect on me.

The comparison they make between DNP and thyroid is because DNP increases the metabolic rate exclusively through uncoupling, while thyroid increases both ATP production and uncoupling. He just gave the example of a thyroid overdose to illustrate the ratio of uncoupling to the increase in ATP production.

I still think thyroid is better, and as I said, you don’t need anything close to an overdose

@alfredoolivas said:

alfredoolivas said:

triene/tetraene

Using 20:3/20:4 ratio, (it wasn't clear what 20:3 fatty acid was studied, was it mead or DGLA?)

1.33 Control slow moving lecitihin
0.88 E slow moving lecitihin
1.57 T slow moving lecitihin

1.57 Control fast moving lecitihin
0.97 E fast moving lecitihin
1.3 T fast moving lecithin

https://pubmed.ncbi.nlm.nih.gov/5910280/

Idk if this is substantial. Probably not.

I remember reading that exercise increases unsaturation in muscle tissue, but they used that finding in a questionable way because the increase in unsaturation they mention is a decrease in stearic acid and an increase in oleic acid; perhaps steroids have a similar effect

@alfredoolivas said:

@hcwilliams why did you delete your comment bro lol

If you aren't afraid of DNP, you shouldn't be afraid of a low/moderate dose of androgens. They are SUPER effective at preserving lean mass. Especially, if you aren't on thyroid :). I believe they also increase the triene/tetraene ratio Ill try to find the study

I’m finishing up my research (and testing) on muscle growth, but ever since I started looking at it from a more Lingian perspective, androgens have taken on a more secondary role for these purposes, serving as a sort of workaround to compensate for what actually causes hypertrophy.

Androgens seem to me to be more of a structural stabilizer; depending on the animal model of hypertrophy you look at, the (%) hypertrophy is the same in the control animal and in the animal using androgens. The benefit of androgens is solely the reduction of muscle damage, but they do not accelerate hypertrophy; both end up the same.

In fact, with this model, you can castrate and bring testosterone to nearly 0, you can suppress IGF-1 or insulin to nearly 0, and the (%)hypertrophy remains the same

alfredoolivas said:

triene/tetraene

Using 20:3/20:4 ratio, (it wasn't clear what 20:3 fatty acid was studied, was it mead or DGLA?)

1.33 Control slow moving lecitihin
0.88 E slow moving lecitihin
1.57 T slow moving lecitihin

1.57 Control fast moving lecitihin
0.97 E fast moving lecitihin
1.3 T fast moving lecithin

https://pubmed.ncbi.nlm.nih.gov/5910280/

Idk if this is substantial. Probably not.

If you aren't afraid of DNP, you shouldn't be afraid of a low/moderate dose of androgens. They are SUPER effective at preserving lean mass. Especially, if you aren't on thyroid :). I believe they also increase the triene/tetraene ratio Ill try to find the study

Ray: Overdosing on thyroid does the same thing. At the right level, it can increase your safe oxidation of fats while helping to suppress the toxic or random oxidation. Both DNP and thyroid can carefully controlled can reduce the toxicity of getting rid of the fat.

But again thyroid overdose per se would render my cholesterol to undetectable levels. DNP even in high doses doesn’t seem to have that effect on me.

I’ll personally lean towards more PUFA being burned from a higher metabolic rate. Would I be wrong?

Unrelated, but could you try to explain to me the glycine to methionine ratio? Like why does it matter in terms of protecting against the harmful metabolic effects of methionine.

@Luke said:

Is that the same as High Oleic sunflower oil?

Yes, it is.
Is it suitable in the context of this thread?

@CrumblingCookie said:

Helianthus Annuus Hybrid Oil

Is that the same as High Oleic sunflower oil?

@alfredoolivas said:

@TexugoDoMel said:

Very low-protein days followed by high-protein refeeds—using an alternating schedule (one day restricted, the next not) or a "protein refeed" after every two days of restriction.

As you probably know, there is a study that shows the triene/tetraene ratio rose was inversely correlated to protein intake

https://pubmed.ncbi.nlm.nih.gov/7373431/

Yeah, restricting protein generally reduces desaturase activity. The result is a drastic decrease in unsaturation due to the limitation of PUFAs with multiple double bonds (caused by the downregulation of delta-6 and delta-5 desaturases); consequently, if the restriction continues, delta-9 desaturase activity eventually increases to prevent unsaturation levels from dropping excessively.

With delta-9 desaturase making more oleic acid available, a greater amount of oleic acid proceeds to the delta-6 desaturase, "winning" the competition against linoleic based on sheer quantity.

My theory regarding protein restriction and refeeding is that the refeed phase following restriction causes a massive spike in desaturase activity; if PUFA intake is limited, this creates an excessive flux of oleic acid being converted into Mead acid

@alfredoolivas said:

@TexugoDoMel said:

Stearic acid supplementation, since a significant portion converts to oleic acid, which accelerates tissue PUFA depletion through competition.

Could you expand on this?

Unsaturated fatty acids (UFAs) compete with one another for enzymes and space (such as within cell membranes); therefore, increasing the level of one UFA inevitably reduces that of another once a certain threshold is crossed.

There are basically two ways to accelerate n-3/n-6 depletion, and both involve drastically increasing oleic acid levels:

1. Accelerating delta-9 desaturase activity to boost the conversion of stearic acid to oleic acid; this is typically achieved through cycles of fasting and fat-free refeeding.
2. Increasing oleic acid intake while on a PUFA-restricted diet.

Regardless of the diet, the body converts almost all stearic acid into oleic acid. Since it is generally difficult to find an oleic-rich food that doesn't also contain excessive amounts of linoleic acid, the best approach I’ve found is direct stearic acid supplementation; this allows you to increase oleic acid levels in proportion to the amount of stearic supplemented while adding zero PUFAs.

@TexugoDoMel said:

Stearic acid supplementation, since a significant portion converts to oleic acid, which accelerates tissue PUFA depletion through competition.

Could you expand on this?

@TexugoDoMel said:

Very low-protein days followed by high-protein refeeds—using an alternating schedule (one day restricted, the next not) or a "protein refeed" after every two days of restriction.

As you probably know, there is a study that shows the triene/tetraene ratio rose was inversely correlated to protein intake

https://pubmed.ncbi.nlm.nih.gov/7373431/

@hcwilliams said:

@TexugoDoMel unfortunately I can’t use thyroid here as an uncoupler, it would destroy my cholesterol.

If I understand correctly, the 2-6 year turnover applies to those who go the “safe” route: supporting the metabolism and keeping stress low while lowering pufas. The one year or less route goes for those who choose to literally burn the pufas off, which can be done safely with uncouplers. I understand pufas are preferentially released during stress so it should be easy to accomplish, as long as uncouplers are used. I wonder if it’s possible to get to 2% within a year .

Any holes in my argument?

2.) Do you think omega quant tests are accurate for testing for fat unsaturation?

3.) I don’t mean to bug ya but one last thing. Any general recommendations for speeding up the process? Would you recommend keeping a low fat approach? Or eating something like cocoa butter throughout ? Or low protein? I’ve seen some other posts you’ve made and commented on and you seem to be just as curious of this as I am. I want to guinea pig this

4.) anything to protect me other than Vitamin E?

I should have been more specific; I meant using thyroid hormone as a supplement to keep the metabolic rate high, but not to an uncomfortable degree.

No, actually, the "safe route" is based on a study regarding linoleic acid saturation, not depletion. If you cut back on PUFAs, you will deplete them over time; IMO however, without reducing adipose tissue, you might reach age 80 with enough PUFA stored in your fat tissue to supply your body for another 20 years—that’s what I meant.

Why the focus on uncouplers as protective agents?

2.) OmegaQuant measures fatty acid composition in the blood, so I think it’s great as a "guide." However, you can "fake" an OmegaQuant result showing omega-6 depletion simply by eating a very low-fat diet for a week or two before taking the test. If you’ve stuck to the same diet for years, though, the chances of it reflecting reality are higher.

3.) I think a low-fat approach with focus on restrict omega-6 (since almost all the effects of PUFA depletion stem from depleting omega-6) combined with a slight deficit maintained until reaching low body fat levels is the fastest way to accelerate the process.

I have some posts on speeding up the process; I based them on animal studies showing accelerated results. I was thinking of something like:

• Low fat, max 0.5% of calories from omega-6.
• Stearic acid supplementation, since a significant portion converts to oleic acid, which accelerates tissue PUFA depletion through competition.
• Very low-protein days followed by high-protein refeeds—using an alternating schedule (one day restricted, the next not) or a "protein refeed" after every two days of restriction.

4. I like keeping vitamin E and iodine intake high for protection, though iodine is a controversial topic in the Peaty community and tricky to get right as it requires balancing selenium and other vitamins.

If I understand correctly, the 2-6 year turnover applies to those who go the “safe” route: supporting the metabolism and keeping stress low while lowering pufas. The one year or less route goes for those who choose to literally burn the pufas off, which can be done safely with uncouplers. I understand pufas are preferentially released during stress so it should be easy to accomplish, as long as uncouplers are used. I wonder if it’s possible to get to 2% within a year .

Any holes in my argument?

2.) Do you think omega quant tests are accurate for testing for fat unsaturation?

3.) I don’t mean to bug ya but one last thing. Any general recommendations for speeding up the process? Would you recommend keeping a low fat approach? Or eating something like cocoa butter throughout ? Or low protein? I’ve seen some other posts you’ve made and commented on and you seem to be just as curious of this as I am. I want to guinea pig this

4.) anything to protect me other than Vitamin E?

@hcwilliams said:

@TexugoDoMel thanks for your answer. I wonder why you say that about pufa depletion not being possible if not a low BF. I want to gather as much info as possible because I’m essentially a diabetic from years of pufa consumption and stress (I have bloodwork)

I’m going to attempt the DNP while taking things that keep ETC flowing / other things , diet down to <10% bf then refeed with saturated fat. If my theory is correct , my metabolism should greatly improve and respond better to thyroid

Adipose tissue seems to be able to store PUFAs for long periods—far longer than 2–6 years, even in a fat-free diet(based on animal studies). I still think it’s possible to deplete it in one year (depending on the case) by losing weight—down to about 10% body fat—on a diet low in PUFAs; IMO thyroid would be better than DNP for this purpose.

@alfredoolivas said:

@TexugoDoMel Very interesting stuff thanks. Other omega 9s are created too right? I imagine those are even more understudied.

Omega-9 fatty acids are simply the ones most commonly known, but several endogenous PUFAs are produced. These include omega-5s, omega-7s, and even some that can’t be classified in this way

Some can even be used to produce prostaglandins isomers