The Mysterious Case of Pufa Depletion
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@TexugoDoMel Thank you.
Now I have a slightly different question. Is there a benefit to mead acid itself? Or is it simply a fatty acid / biomarker that strongly suggests a linoleic acid depleted organism?
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@TexugoDoMel Thank you.
Now I have a slightly different question. Is there a benefit to mead acid itself? Or is it simply a fatty acid / biomarker that strongly suggests a linoleic acid depleted organism?
Since it hasn’t been studied much, it’s hard to know everything about it, but it’s just as (or more) anti-inflammatory than omega-3, with the added benefit of having 3 double bonds compared to EPA’s 5 and DHA’s 6. IMO phospholipase/COX and leukotriene inhibitors are basically partially mimicking the effects that Mead Acid would have in full.
There are other benefits as well: cartilage is rich in Mead Acid, and it appears that its depletion is one of the causes of cartilage degeneration; there’s even a theory that the depletion of Mead Acid is what causes bones to stop growing
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@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
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@TexugoDoMel Very interesting stuff thanks. Other omega 9s are created too right? I imagine those are even more understudied.
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@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.
@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
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@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 this4.) anything to protect me other than Vitamin E?
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@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 this4.) 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.
- 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.
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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
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Stearic acid supplementation, since a significant portion converts to oleic acid, which accelerates tissue PUFA depletion through competition.
Could you expand on this?
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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
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
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:
- 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.
- 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.
- 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.
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@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.I've never been a big party attender, but I never went to a party where I didn't probably offend most of the people there by talking about what I was interested in. (Ray Peat)
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@Luke Helianthus Annuus Hybrid Oil. Cheap and available. 3% PUFA, 88% MUFA, 9% SFA.
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Helianthus Annuus Hybrid Oil
Is that the same as High Oleic sunflower oil?
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@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.
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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.
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@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 -
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 lecitihin1.57 Control fast moving lecitihin
0.97 E fast moving lecitihin
1.3 T fast moving lecithinhttps://pubmed.ncbi.nlm.nih.gov/5910280/
Idk if this is substantial. Probably not.
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@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.
@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"
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:
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 lecitihin1.57 Control fast moving lecitihin
0.97 E fast moving lecitihin
1.3 T fast moving lecithinhttps://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
@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 studyI’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
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