THE GREAT PUFA DETOX/DEPLETION MEGA THREAD - SIMPLIFIED

Juri

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Sorry for the all caps title, I want to attract attention with it, simply because i'm counting on your guys' and girls' experiences to be shared here also.
For anyone not that familiar with why one would want to lose PUFA, here is a quick summary by haidut.

That being said, I made this thread primarily to bring together all forms of modern research, peaty advice, anecdotal evidence and success stories, all relating to losing stored (!) PUFA.
I also made a strategy to lose stored PUFA safely, for example geared towards someone that used to be relatively lean in their twenties, but found themselves ballooning after their 30s came into view. I found this to be the most common form of weight gain for people in my age and friend group, and it seems to put a lot of psychological stress on the people affected, further exacerbating the problem. If you reading this are one of those people, take a deep breath and realize: it's going to be okay. Read that again if you want. There is help for you. Just like negativity and problems can often cascade and become self-reinforcing, I believe that positivity, success, breakthroughs, realizations, achievements, however small they may be, can break the cycle very easily. That being said, especially success stories are very welcome to be shared here, as Ray Peat said:
"In one of the studies in which rats had been taught learned helplessness so they would drown in five or six minutes, just being able to see another rat escape would let the informed rat go for days without drowning. Just the recognition that someone else did it can make all the difference."

So, below is what I understand to be the safest way to lose stored PUFA. I made the steps and actions sound a bit militaristic and game-like so the guys among us don't get bored ;)


1. Reconnaissance
Any good offensive battle plan first needs to look at where to strike, with what type of troops, how fast success can be achieved, and if a breakthrough through enemy lines is achieved, how to best exploit it, to turn a tactical victory into a strategic one.
In regards to PUFA, the enemy has been identified as our unsaturated fat stores. As we age, come under stress or are exposed to pathogens, these unsaturated fats get released into our bloodstream. It's almost like one would be "eating them again", and sadly, aging and stress are unavoidable in life. That's why the threat the PUFAs pose doesn't end once the body stores them, although this storage does presumably occur exactly because the body rightly recognizes PUFAs as a toxin. This recognition is also part of the next steps of our plan, but first, let's move on to point 2.


2. Response
Considering the body does recognize PUFA as a toxin, all we need to do is give it the necessary energy and materials to deal with that toxin.
This is primarily achieved through diet and, if necessary, through supplementation.

Before we can do that, it is important to limit the damage it is currently doing. This amounts to "securing the flank" before we go on the offensive.

The process by which PUFAs are usually released into the bloodstream (where they do most of their damage), is called lipolysis. In the blood they are then called "free fatty acids" (FFA). Lipolysis is self-reinforcing because the PUFA metabolites promote further lipolysis. Why this is a bad thing can be seen in haidut's summary above, but for anyone who hasn't done so, please read Peat's article "Fats, functions and malfunctions" for a more thorough understanding.

In essence, because of the Randle cycle, the body needs either fats or glucose as fuel. When we use fats as fuel, we can't use sugar, and vice versa. Because using sugar is safer, more efficient and produces less "waste products", we want to stop the body from using fat.

But, I hear you say, if we use/oxidize fats, won't that help us in getting rid of them?

The answer, surprisingly, is No. This study proved it in rodents and for anyone into maths and some chemistry, below is a basic equation for how much ATP is produced per carbon, in both glucose and fat (assuming an 18-carbon chain).
This is based on my limited understanding of cellular energy, so please do correct me if I got something wrong.
Regarding the little summaries: The higher NADH/FADH2 ratio is, the more electrons are being delivered to the electron transport chain via NADH. Electrons from NADH generally contribute to the pumping of more protons, potentially leading to increased ATP production. ATP is generally recognized as the body's "energy currency".
Mind you, this math is what the textbooks are wrong or even dishonest about. They tell you that oxidizing the unsaturated fats is more "energy-efficient", but then calculate with 15-carbon chains (saturated fat).
When unsaturated fats are oxidized, the math is as follows:
For fatty acid oxidation (per 18-carbon chain):

  • ATP yield: 6 ATP×(18 carbons/16 carbons)=6.75 ATP per carbon
  • NADH yield: 31 NADH×(18 carbons/16 carbons)=34.875 NADH per carbon
  • FADH2 yield: 15 FADH2×(18 carbons/16 carbons)=16.875 FADH2 per carbon

    summary: 6.75 ATP molecules per carbon atom, NADH/FADH2 ratio: 2.06
For glucose oxidation:

  • ATP yield: 4 ATP×(18 carbons/6 carbons)=12 ATP per carbon
  • NADH yield: 10 NADH×(18 carbons/6 carbons)=30 NADH per carbon
  • FADH2 yield: 2 FADH2×(18 carbons/6 carbons)=6 FADH2 per carbon

    summary: 12 ATP molecules per carbon atom, NADH/FADH2 ratio: 5


As one can see, glucose is a much better energy source, without even mentioning the metabolic byproducts of the unsaturated fats.


That is one more reason we don't want to be "fat burning machines". It is misguided to believe that this is the optimal state of the organism. If anything, fat as fuel is widely recognized, by plain logic and complex evolutionary theory, as an emergency method of energy production. That also explains why stress is both a cause and an effect of the release and oxidation of these fats.

Our response to stop the oxidation of these fats must then obviously be to stop consuming them and to get rid of them by a method other than oxidation. The ones in our stores will be oxidized only if the cell can't metabolize glucose. We can restore the cell's ability to oxidize glucose by a variety of means, all of which should be used together.

Among these, one stands out, namely aspirin, of which Ray Peat says:
"Aspirin activates both glycolysis and mitochondrial respiration, and this means that it shifts the mitochondria away from the oxidation of fats, toward the oxidation of glucose, resulting in the increased production of carbon dioxide. Its action on the glycolytic enzyme, GAPDH, is the opposite of estrogen's.

The shift away from fat oxidation under the influence of aspirin doesn't lead to an accumulation of free fatty acids in the circulation, since aspirin inhibits the release of fatty acids from both phospholipids and triglycerides."

If PUFA detox is a war, aspirin is the infantry. It fulfills a variety of roles, it helps where needed and more is usually better. At this point, I wanted to address a concern I hear people express very often when I mention aspirin to them. Peat's article mentions these concerns, about supposed stomach irritation and bleeding problems, but I wanted to address it again here because I feel like it is necessary to repeat important things in different wordings:

Aspirin is a natural product, it's real name is acetylsalicylic acid. It's found in the bark of a tree, the white willow to be exact, and is older than anybody reading this. If you previously thought consuming liters of soybean oil throughout your life is harmless, but one tiny little white pill is harmful, please read up both of these substances and their history. One was made to fatten and poison pigs, the other has a track record literally as old as human history. Herbal medicine used salicylic acid, the natural substance related to synthetic aspirin, from myrtle, willow and meadow sweet, since ancient times (at least 2500 BCE). Ancient history has many examples of humans using salicylic acid for medicinal purposes; there are clay tablets from the Assyrians in the Sumerian period (around 4000 years ago) in which willow leaves are recommended for rheumatic disease, the Egyptians describe the use of willow leaves or myrtle for joint pain or inflammation and Hippocrates (460-377 BCE) recommended an extract of willow bark for fever, pain and child birth. Ancient Chinese, Roman and Native American civilizations have all long recognised the benefits of plants containing salicylic acid for their medicinal benefits. The sources for all of this are the following:​
Jack DB. One hundred years of aspirin. The Lancet 1997:350: 437-39
Elwood P. Aspirin yesterday, aspirin today, aspirin tomorrow: a history of prophylactic aspirin. 2017 International Aspirin Foundation
Goldberg DR. Aspirin: Turn-of-the century miracle drug accessed 12/05/2019 @ https://wwwsciencehistory.org/distillations/aspirin-turn-of-the-centuary-miracle-drug
Schrör K. Acetylsalicylic acid. 2016 Wiley Press

Moving on, other substances commonly used to suppress lipolysis are niacinamide (found in beef liver or OTC at the pharmacy) and obviously, probably most importantly,

SUGAR

If you don't want your mom to drive an unsafe car, you work hard to get her a better one. If you don't want your cells to use an unsafe fuel, you look hard to give them a better one.
Turns out sugar tastes good for a reason. If your skin reacts poorly to sugar, here is a good thread covering why that could be.
So, new fuel source acquired, but what is to be done to the already stored PUFAs?
That will be discussed in step 3.

3. Reinforcement

Two organs are commonly known to be intimately involved with detoxification and excretion, the liver and the kidneys. The liver's role in this is to make things "detectable" for the kidneys to pick up. As the kidneys can only excrete water-soluble compounds (your urine is hopefully somewhat watery), the liver must first make poisons water-soluble. How is that done?

Peat says this about excreting circulating (!) PUFAs:

Ray Peat liver pufa excretion.png


So, according to Peat, there are two ways the liver does its job in detoxifying PUFA. The first is called glucoronidation. The second is called sulfation.
First, about glucoronidation.
Because of their double bonds, PUFAs are already more water-soluble than other fatty acids, but for the kidneys to pick them up, glucoronic acid needs to be attached, making them into a sort of soap, with one end being watery and the other fatty. In this study, It also mentions that this activity is highest in the small intestine, which leads me to believe that supporting the glucoronidase enzyme's activity in that area may yield the best results.
"In general, both PA and DHA were glucuronidated by gastric and intestinal microsomes, and activity toward both substrates was lowest in the stomach, increased in the small intestine, and lower in the colon" is what the study says, for anyone who can't be bothered to read through the whole thing.


This is where I need your input and help: How does one go about maximizing this glucoronidation of PUFAs?
And does this glucoronidation only happen once the PUFA leaves its storage form and enters the blood again?


I know that Peat says the following in Fats, functions and malfunctions: "One of the essential protective functions that decline with aging is the liver's ability to detoxify chemicals, by combining them with glucuronic acid, making them water soluble so that they can be excreted in the urine. The liver (and also the intestine and stomach) efficiently process DHA by glucuronidation (Little, et al., 2002). Oleic acid, one of the fats that we synthesize ourselves, increases (about 8-fold) the activity of the glucuronidation process (Krcmery and Zakim, 1993; Okamura, et al., 2006). However, this system is inhibited by the PUFA, arachidonic acid (Yamashita, et al., 1997), and also by linoleic acid (Tsoutsikos, et al., 2004), in one of the processes that contribute to the accumulation of PUFA with aging."

So, obviously lowering PUFA is once again essential. However, it turns out that most meats, olive oil and also macadamia nut oil, the only oils aside from coconut oil that Peat calls semi-safe, contain oleic acid. Macadamia nut oil specifically only contains about 3% PUFA, which is less than most olive oils. Could this be a viable strategy in optimizing glucoronidation? Genuine question towards experienced readers, as I'm not sure if the downsides of MUFA here may outweigh the benefits.

Moving on, Peat says to keep carbohydrate and thyroid adequate. But is this all that is required?

Logically, keeping the liver free from other jobs, such as detoxing estrogen and the like, would greatly improve this glucoronidation.
"For example, the flavonoids, naringenin, quercetin and kaempherol (kaempherol is an antioxidant, a phytoestrogen, and a mutagen) modify the metabolism of estradiol, causing increased bioavailability of both estrone and estradiol." (W. Schubert, et al., “Inhibition of 17-beta-estradiol metabolism by grapefruit juice in ovariectomized women,” Maturitas (Ireland) 30(2-3), 155-163, 1994.) -Ray Peat

For anyone confused if that's "bad" or "good", the study Peat cited also simply says the following later on: "After administration of grapefruit juice, peak estrone (between 2-6 hours after tablet intake) concentrations increased significantly."

Peat also says this: "And one of the ways that the body safely eliminates the stored PUFA is through the liver. And the ... albumin binds anything that's fat-soluble and carries it to the liver. And the liver, when the albumin arrives carrying either dioxin or one of the toxic environmental estrogenic substances, the liver will capture it and bind it"
(ewh-111215-q-and-a-2.mp3-transcript.txt)

What could impair the liver's ability to detoxify is low albumin. Peat says the following about it in KMUDRAD's show from 09-07-2001 called "Bowel Endotoxin":
"and when the liver is starting to be poisoned and estrogen and radiation can do the same thing as endotoxin, the ability to form albumin decreases. And so looking at the albumin in a blood test is one of the first... indicators of a person's basic resistance. If it's high, their prognosis is usually good. And if it's down around three, where the normal is four and a half, you're going to have to clean out the bowel. I've seen people in just a couple of weeks go from below three, like two and ahalf, up to over four, just by... eating fiber and fruit juice to reduce the absorption of endotoxin."

Make sure albumin is in the proper range, if it's not, try fiber, fruit juice and the like. I would personally also recommend to consider antibiotis. As haidut posted in this excellent article, reducing endotoxin load by reducing bacterial load may significantly lessen the workload of the liver, allowing it to focus on what we are after: excreting the PUFA.

To make sure the other part of excretion, namely the kidneys, are working properly, a high protein diet together with some potato juice should be considered. In this video, Peat talks about it briefly:

View: https://www.youtube.com/watch?v=k_Uzj7vKfXo



The other process mentioned in the screenshot above, by which PUFAs are removed, is sulfation.
A quick refresher on what it is: "Sulfotransferases and UGTs frequently metabolize the same substrates and may cooperate in generating conjugates which are excreted from the liver into the blood, making them available for renal clearance. The human genome contains four Sulfotransferase gene families (SULT1, SULT2, SULT4, and SULT6) with ≥14 members encoding cytosolic 32–36 kD enzymes which use 3′-phosphoadenosine-5′-phosphosulfate as a sulfate donor [29]. They metabolize endogenous biogenic amines and mediate the sulfation of dehydroepiandrosterone and progesterone in the adrenals, after which the sulfated forms are secreted and transported to sites of estrogen/androgen synthesis." Source

So sulfates are used to detoxify metabolites like alcohol, estrogen, phenols etc. They are involved in the production of S-DHEA, which is a steroid precursor. Sulfate production depends on ATP levels, I believe that to be common knowledge but here is a study discussing it. How can the levels of ATP be increased? Obviously through less PUFA consumption, stress, endotoxin and so on, but supplements like creatine monohydrate may also raise ATP levels in cells. This study says: "Creatine supplementation significantly increased the cellular ATP level in neutrophils compared with the control treatment. This ATP increase was due to the phosphocreatine system in the creatine-treated neutrophils".

Therefore, glucoronidation and sulfation are the main "weapons" the body uses to attack PUFAs.
If you have any methods/means/supplements/foods to increase the effectiveness of these two processes, please feel free to share below.


4. Rallying


One of the most asked questions on this forum seems to be about how to speed up PUFA detox or how to get it over with as quickly as possible. Now, aside from our bodies usual detoxifying as described above, there is another one. Those already familiar with the previously mentioned creatine may have heard about bodybuilding, or at least familiar with building muscle in general. Peat himself talks about muscles burning fats at rest, although they preferentially burn saturated fats, I am assuming that they also burn a certain amount of polyunsaturated fats.

Now, how does one build muscle without stressing the body to the point of raising FFA?


Very simple. Train within your glycogen stores, meaning you load up on easily digestible carbs 1h or so before your weightlifting session.
Said weightlifting session should be brief and intense, NOT geared towards building endurance or burning any type of fat.
Rather, you want to build muscle in a way that is not stressful to the entire organism. Now, what is necessary to build muscle then is giving the body the proper stimulus to do so. From my understanding based on simple logic, muscle is a very "expensive" tissue to build and maintain. The body is only going to build it if it is forced to do so. Evolutionarily speaking, it would be a sort of "I need to lift this again tomorrow or I will die" realization that makes the muscle grow during rest. That would be called hyperthrophying of the muscle cells, which is the basic science behind any sort of bodybuilding. Now, for that muscle to get the said stimulus, you need to be taking it sufficiently close to momentary mechanical failure, meaning you simply can't do any more repetitions of whatever specific exercise you are doing, no matter how hard you try. In order for your muscle itself to become the limiting factor here, rather than your ability to breathe or any other sort of endurance, I would recommend a low number of repetitions and sets of any given exercise, but high enough to give the muscle the feeling that it is working. I personally aim for 4-8 repetitions and it has served me quite well.
After the workout, you should again be consuming carbohydrates, in order for your glycogen stores to be replenished. Follow this up with protein in the form of some milk and cheese, or some sort of meat a few hours later, your muscles will grow, and the larger the muscle mass is that one carries around, the higher the metabolic rate, and the higher the ability to burn stored PUFAs.
Especially milk is a very good drink for building muscle. Thinking about it from an evolutionary perspective, it is designed to help a mammal grow, which is exactly what we want in this case.


I hope you found my thread helpful so far.
 

Dapose

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@Juri
Fantastic post Juri! Fun read with lots of questions that you immediately answer yourself! Thank you!
Just a few thoughts to share…
I feel like the Liver and thyroid are the keys to your speedy Pufa removal question. I enjoy Traditional Chinese Pu-erh tea in the morning with sugar and calcium added with breakfast of coarse.
Chamomile tea with honey after lunch helps too.
I do all the usual Peat/Haidut ancestral and metabolic boosting things as well. Aspirin B1,2,3,etc… t3,t4. Lots of collagen glycine milk. Yum yum.

My additional thoughts are… your body is a sacred special garden. Especially your gut. Please consider declaring a truce in this metaphorical War you are in with your body/cells. I get that it’s all fun to use battle talk and I’m not a pacifist even or anti defense or fighting. But I just got to say that the War on Cancer, War on diabetes Alzheimer’s, drugs, poverty… war on yourself is the wrong approach.
Your cells aren’t trying to kill you.
They respond to your mind. To your thoughts. To your energy. Raise your energy, raise your consciousness.
Be a garden, be an ecology. Don’t be a battlefield, there are plenty of those these days. That’s my suggestion. Relax, love life, loving your body is a better way to deplete Pufa then fighting it. I don’t have any studies to prove that I just know it’s true.
💪 ❤️ 🥛
 
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excellent thread and solid advice all around. For anyone interested in learning more about this style of working out look up Mike Mentzer. Thank you very much for the info on glucoronidation and sulfation. The tidbit about glucoronidation turning pufa into a compound that resembles soap is interesting. I found myself looking up why I often had foamy urine. The general consensus found online was protein breakdown, which made sense somewhat because it always seemed foamier after heavy workouts. It did not answer why it seemed foamier in general over the last few years of recomp/fat loss compared to prior years of SAD diet and weight gain. This information is wonderfully useful for this and other questions i've been researching recently!
 

dukesbobby777

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excellent thread and solid advice all around. For anyone interested in learning more about this style of working out look up Mike Mentzer. Thank you very much for the info on glucoronidation and sulfation. The tidbit about glucoronidation turning pufa into a compound that resembles soap is interesting. I found myself looking up why I often had foamy urine. The general consensus found online was protein breakdown, which made sense somewhat because it always seemed foamier after heavy workouts. It did not answer why it seemed foamier in general over the last few years of recomp/fat loss compared to prior years of SAD diet and weight gain. This information is wonderfully useful for this and other questions i've been researching recently!

With the foamy urine, are you aware of an official way of correctly peeing into the toilet, to judge whether the urine is foamy or not?

Whenever I pee directly into the toilet water, it froths up like crazy. When I pee onto the sides of the pan, so the pee trickles down, I get barely any froth at all.

If you shoot any liquid into toilet water at the same projection/pressure/speed, etc, as somebody peeing into toilet water (from that distance away) it's going to 'froth up' the exact same way.

So I've never understood what Peat meant by this.
 
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With the foamy urine, are you aware of an official way of correctly peeing into the toilet, to judge whether the urine is foamy or not?

Whenever I pee directly into the toilet water, it froths up like crazy. When I pee onto the sides of the pan, so the pee trickles down, I get barely any froth at all.

If you shoot any liquid into toilet water at the same projection/pressure/speed, etc, as somebody peeing into toilet water (from that distance away) it's going to 'froth up' the exact same way.

So I've never understood what Peat meant by this.
I just realized this is a rather odd topic to discuss at length but i digress; the change in foaminess is not due to a change in shot placement/aim. I would say as a matter of scientific investigation that we are referring to aiming your stream directly at the water itself, as this disturbs and mixes the urine and the compounds therein more thoroughly in the water, compared to a stream running down the side of the toilet bowl.
 
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