Generative Energy #7: Polyunsaturated Fats in The Real Organism

 
 

Listen to Georgi (aka Haidut) and I discuss polyunsaturated fats in the real organism on Episode #7 of The Generative Energy Podcast!

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01:12 - From Paleo to Peat
05:22 - Georgi’s work on raypeatforum.com
07:14 - Aspirin and free fatty acid inhibition
11:00 - PUFA metabolism, inflammation, and growth
13:35 - PUFA increases histamine and serotonin
15:25 - Brain vs. gut serotonin
16:37 - Lower serotonin is better? Is that right?
18:06 - PUFA inhibit cytochrome c oxidase
19:42 - Warburg’s 1931 nobel prize discovery
21:04 - Mitochondria, 5-alpha-reductase, baldness, and BPH
23:40 - Are androgens to blame or are they protective?
28:05 - Radiation and PUFA - are they hormetic?
29:51 - Resilient “EFA” deficient animals
30:55 - What is endotoxin and how it relates to serotonin
33:29 - PUFA and immunosuppression
36:09 - PUFA inhibits endogenous cholesterol production
39:10 - PUFA shifts the balance between NAD+/NADH towards NADH
41:30 - The true method of knowledge is experiment
43:15 - Mitigating the damage from PUFA when dining out
44:30 - Where can we find you on the internet Georgi (“Haidut”)?
46:00 - Did you like the show? Let us know!

Transcript

d: Hello Everyone, welcome to the Generative Energy Podcast. I'm Danny Roddy at dannyroddy.com and today I'm talking with Georgi (aka haidut) of raypeatforum.com.

Georgi is an independent health researcher and owner of IdealLabs - a small company producing high-quality boutique supplements - with a focus on supporting a healthy metabolism. Today, Georgi and I will present a physiological argument against the so-called Essential Polyunsaturated Fats (or PUFA), and we'll detail why we think that they are the main promoters of inflammation, stress and aging. In addition to thanking Georgi for talking with me today I wanted to thank my Patreons, and you can become a Patreon by going to patreon.com/dannyroddy

And my heart goes out to all those people supporting me and making this content possible. So, without further ado, let's talk with Georgi (aka haidut). And Georgi, I just wanted to say I found your posts a few years ago, they were so filled with content and they were so clear; it was obvious that you had a zest for learning on your own and confirming a lot of things Ray has said in interviews and his newsletters. I was curious how your own journey started.

h: Finding Ray Peat: it all started back in 2009. I was a little bit into health even before that. I was an active athlete in college and I was always mindful of what I ate. I got influenced unfortunately like many people I think, by the whole Paleo diet circle and I went low-carb for a long time, between 2006-2009 I was eating pretty strict hardcore Paleo diet. While that initially gave me a lot of energy, I felt that something was just not right. It was taking me a lot longer to recover from workouts, I wasn't sleeping well, things like that, but anybody that I talked to they basically said “Well, what do you care, this is like the most energetic you've ever felt, so it must be a good thing”. Only later I realized that cortisol is this thing (cortisol and estrogen) that will make you feel energized, but they're really sort of the devil in a mask, because eventually they do contribute to the pathology of most degenerative conditions that we're witnessing nowadays. So between 2006-2009 I was sticking to the paelo diet and around 2009 I started getting these weird sinus infections, unfortunately spread to my ear, I started having balance issues, you know, I kept seeing [???] I saw my private care physician at least once a week; I went on several rounds of antibiotics, which seemed to clear things up but then invariably they'd still come back, and you know and ultimately it all came down to cortisol because given how high it was, it was supressing my immune system. I started to get this weird neurological symptoms, so I got referred to a neurologist, I got a lot of MRI scans, all kind of scans; I knew radiation was bad even before that so I managed to avoid most of the X-Rays and CT scans that were offered to me; so I mostly got MRIs.

But it basically, long story short, after about a year and a half of testing, everybody said that there's nothing structurally wrong with you, but I kept deteriorating. I think the first time I heard about Ray Peat was on Reddit, I was commenting on some studies that showed basically that the paleo diet was good for you and things like that, and then some random user, I don't think he or she is even a member of Reddit anymore, said: “Well, I think all you guys are wrong”, this thread is full of BS, you should really read more, check out this guy, he knows his stuff”. <I think he/she was mentioning pboy back then>. I just clicked on that link and the first article from the very top, from the moment I started reading I realized: this guy, he knows his stuff. It's not so much about being right, but everything that he says makes sense, and everything that I managed to check made sense. So that was really how it all started. So, between 2009-2011, I was essentially focused on regaining my health and knock on wood since I would say since 2011/12, I have not had any of this weird neurological symptoms.

I don't want to say that it convinced me that Ray Peat is right but it convinced me that the guy has a point. That got me researching even more and I was naturally curious, got interested in this stuff and I found this nice hobby, so to speak, which is so different from my day job, but it gives me a way of recovering from the travails of the day job by researching and getting involved with Ray Peat ideas. And also of all the people that reached out to me for advice, I feel good about knowing that I've managed to help some people, even though the FDA doesn't wanna hear that.

d: Well, you helped me too. You're a prolific poster on Ray Peat Forum. And the way you kinda of highlight and make the studies - truth be told, I sometimes can't interpret the really complex studies and they're just over my head - but you have a way of presenting things, its like: Oh, I can understand that. But I was curious, what was like the giveaway when you went to Ray's site, were you like: Oh this guy has something different to say about cortisol that made you interested in them?

h: No, It was actually aspirin, because I known for a long time - I'm originally from Bulgaria, and in Eastern Europe aspirin has this reputation of a drug that cures it all. And I've always thought that it was just what old people say, modern medicine really has an answer for all this things; they just think aspirin cures it all, but its really you know, it's just old-people stuff, they don't really know what they're talking about. But when I read his (RP) article on aspirin, I think it's called Aspirin, Brain, and Cancer. I started reading it and it backs up everything that I've been hearing since very early childhood. Aspirin is the best thing that you can do for heart attack preventions, for stroke prevention, for even for like basically slowing down the aging process, so to speak. Both of my grandmothers are still alive, they're both on their late eighties, and they're very active. I wanna say that they're more active now than I was back in my paleo diet phase, and both of them take aspirin on a daily basis, they've done so over the last 60 years and they started back on their twenties. So after I started reading his articles, followed up on all of the links, checked the research; if you go to PubMed, there are like literally millions of articles on aspirin and not a single one is negatively framed. That must tell you something!

d: Was it aspirin that made you more curious about the PUFAs and their role in inflammation, stress and aging?

h: Yeah, basically what I did is there are several inflammation markers, so basically after I quite going to doctors - I still see my primary care physician once a year to sort of just to keep him happy because he's a nice guy, he does agree with a lot of what Ray Peat has to say - but basically started doing my own blood tests and I noticed that initially my inflammation markers, they weren’t elevated but they were close to their upper range, like the C-reactive Protein (CRP), the Erythrocyte sedimentation rate (ESR) and I also measured some of the prostaglandins; so basically they were all borderline high. And then I noticed that after taking aspirin - which is actually really to summarize what got me into Ray Peat and got me out of my “troubles”, for the biggest part it was probably aspirin.  I was taking high doses and then I noticed within a month all of these inflammation markers went down. Officially aspirin is just a COX inhibitor and none of these things that aspirin manage to do are explainable by the COX mechanism, so there must've be something else that aspirin was doing. As I started researching I noticed that one of the things that aspirin does is that it inhibits lipolysis, it will lower the elevated free fatty acids (FFA) in the blood. Ray says saturated fat is fine if those are the fatty acids in the blood but its still not a good thing. So I noticed that aspirin is helping and then I did some experiments; I would stop aspirin and I would only eat coconut oil and I noticed that my inflammation markers would stay low; but if I started eating "regular foods" because it's not really regular, it's poison but if you want to eat commercial food you don't have much of a choice, whenever I would eat even a tiny little bit of commercial foods, like something you buy from 7-eleven, CVS or Safeway; my inflammation markers would immediately jump, even from a tiny amount, so I think, this guy has a point. Basically, without aspirin, saturated fat kept my inflammation markers down, and then PUFAs raised them, even a very small amount. So I would say around 2013 I started consciously avoiding any kind of PUFA (including fish oil).

d: And you list 1-2g. Is that based on research that you've done?

h: Yeah, I have provided the link on the forum but the bottom line is: there have been a lot of disagreements over the essentiality of PUFA going back to the 1950s, and even to this day, occasionally there are PubMed studies that pop-up that say: look, even if we assume that PUFA is essential, I think you guys (by you meaning the FDA, the USDA have determined the dietary requirements per day) you are vastly overestimating the essentiality of PUFA. It was shown that even in situations when you feed the rats just a little bit of PUFA, all of these symptoms that are claimed to be caused by EFA deficiency disappear immediately, any intake on top of that was not shown to be beneficial; at the very best you can say, if you believe that PUFA is essential - and I don't - you can get away with eating no more than a gram or two of PUFA per day, which you can get from just eating the eggs, just like you mentioned. Anything on top of that eating non-essential fats and knowing how fat metabolism contributes to the degenerative diseases, even if we're assuming it’s not bad, having more fat than what is necessary and essential is not a good idea in my opinion.

d: So, Georgi, you mentioned that the metabolism of the unsaturated fats or the PUFA, they're synthesized into the eicosanoids and the leukotrienes and that these are major pathways to inflammation.

h: Basically, eicosanoids and leukotrienes are types of prostaglandins, and they're mostly derived from arachidonic acid, which is one of the Omega 6 acids and it's widely known ever since the early 20th century to be the main mediator of inflammation, and actually cellular growth and division.

Believe it or not, in some circles of bodybuilders, arachidonic acid is injected intravenously so that they can spare muscle growth. This tells you immediately that both Ray is right and how stupid some people are. The primary purpose of every cell is to grow, all primitive cellular life forms that is really all they do: they just eat and grow. We are in a sense a mechanism for supressing excessive growth, and excessive growth is mainly due to inflammation. So if PUFA are the main driver, if not the only driver of inflammation, then basically PUFA are the main driver of cellular growth and dead differentiation. In other words, they cause you to revert to a primitive organism, like a yeast or some kind of bacteria, that all it does is eats and as a primitive metabolism it divides, because that's the only energy from a primitive metabolism is sufficient only for that. If you eat PUFA, this means high inflammation, this means your cells will prefer to divide versus to differentiating; in other words, you're getting closer to a cancer metabolism.

d: And the problem with the growth and not differentiating the cells is that it interferes with renewal of the organism, correct?

h: Exactly yes.  Cells they act as a part of a field as Ray said, and by reverting them back to their growth potential, in other words, due to high inflammation or intake of PUFA, essentially the organism loses its coherence; in other words you're no longer a human, you're just a collection of cells but they're not guided by any coherent field. We’re all a collection of cells but these cells every human being is perceived as a coherent field [?] very powerful with coherence so there is no field, just a collection of cells, they're independent of each other and their only purpose is survival, and how to survive is by dividing and growing.

d: You mentioned that the PUFAs, the products that they're metabolizing into, the eicosanoids and leukotrienes, are major triggers of histamine; which might be agreed upon that histamine is a problem in excess, but also serotonin and serotonin will probably have to demystify this until the end of our lives, but that is also a problem: increasing serotonin synthesis.

h: Yeah, it's a huge problem because you can look at the organism in two ways: a low metabolism, in other words glycolysis; versus high metabolism, through the phosphorylation. It has been shown that in animals that hibernate, serotonin is the primary driver of hibernation. Serotonin actually causes their metabolism to slow down and it increases the activity of glycolysis versus oxidative phosphorylation. So in other words, the mechanism by which PUFA increase histamine. So, histamine drives serotonin synthesis directly but PUFA have another way of increasing serotonin. First of all, it interferes with Cytochrome c oxidase, which we'll talk about later, and also another thing it does is that it displaces tryptophan from albumin. Normally tryptophan in the blood is bound to albumin and tryptophan gets to the blood-brain barrier. The levels of serotonin in the brain is determined by the ratio of tryptophan versus the so-called large neutral amino acids, in other words the branched-chain amino acids tyrosine and phenylalanine. So, the more tryptophan you get to the brain and the lower of the other amino acids you get to the brain, the more serotonin you'll synthesize and PUFAs is the main driver of increased tryptophan availability in the brain. So more PUFAs means more tryptophan and more serotonin in the brain; it means lower metabolism.

d: And that's independent of the serotonin's production in the bowel, is that right?

h: That's correct.  Basically 90% of the serotonin is produced in the bowel and I posted a study that showed that this production in the bowel is mainly driven by bacteria in the gut. Animals that had their gut bacteria killed by antibiotics produced about 90% less serotonin in their gut than other animals. However, brain serotonin is separate, it's synthesized by the enzyme called tryptophan hydroxylase 1 (TPH1).

The peripheral serotonin, the one in the gut, is synthesized by tryptophan hydroxylase 2 (TPH2). When tryptophan floats around freely in the blood, it gets to the brain and there's nothing there to inhibit it, unless you take a specific tryptophan hydroxylase 1 inhibitor such as Fenclonine, which Ray also talked about. In other words, the brain serotonin production is independent of the gut serotonin production, even though the two are related. If you have high brain serotonin this will slow down metabolism, make the gut bacteria more active, so you'll end up with high gut serotonin as well; but the production of the two is generally separate.

d: And so for the people that are doubting the veracity of the problematic serotonin, they can look into effectiveness of Cyproheptadine as pretty much a wonder drug, in addition to Ondansetron, which can treat a lot of different problems. You mentioned a couple of other anti-serotonin drugs.

h: <???> likes to call them serotonin recepetor antagonists. In reality, there's no such thing as the receptor; like Ray said, the entire cell is the receptor. What gets into the cell and what is kept out is determined primarily by the energetic status of the cell. So, if a cell is low on energy so to speak, more bad stuff will get in and the cell will have a hard time getting it out. But some of the other anti-serotonin drugs that have been found to be beneficial includes Ketanserin, Ritanserin, Mianserine all of the “rins” the way I’d like to call them. They all act mostly on the so-called Serotonin receptor Type 2, and then there are some of the older drugs that were derived from LSD such as Bromocriptine, Cabergoline, Lisuride, they're considered to be more dopamine agonists. However, it was just recently discovered that dopamine itself, inhibits the enzyme tryptophan hydroxylase 1 so, taking a dopamine drug actually means that you'll synthesize less serotonin in the brain as well.

d: You mentioned keeping the cell in its high oxidative-metabolism state was essential for it being able to maintain its coherence and structure, and a main part of that is by the activity of Cytochrome c oxidase. An easy argument against the PUFAs is that they're extremely detrimental to this enzyme. Do you want to talk about that?

h: Sure. It was shown that whenever animals were fed a diet high in PUFA, and what the studies determine as high is really what constitutes the average intake of most human beings in the Western world, so basically your regular Western diet dramatically decreased the levels of Cytochrome c oxidase, which is a copper-dependent enzyme in the organism by up to 90%, without that you cannot have oxidative phosphorylation. It was just discovered many brain diseases are actually symptoms of COX deficiency. I posted some studies that showed that animal models of diseases like ALS (Amyotrophic lateral sclerosis), Parkinson's, Alzheimer's, were all greatly helped and survival was extended by adding supplemental copper to the diet. Now basically, the more PUFA you eat, the less COX you'll have, and the less oxidative phosphorylation your cells can perform. In the absence of that, the only other thing your cells can do is glycolysis. So, eating a diet chronically high in PUFA will force your cells to essentially adopt a cancer metabolism.

d: And that's Warburg's discovery I think in 1931, I think he got the Nobel Prize for discovering COX.

h: Yeah, that's correct. What's stunning to me is that even though the guy had (Warburg) at least two Nobel Prizes, he's virtually unknown. If you talk to anybody with a medical degree, the only thing they know about it is the Warburg effect even though Warburg talked a lot more about, including things that can inhibit, not so much inhibit glycolysis but prevents glycolysis from becoming excessive. Some of those things Ray touched upon but they're really coming from Warburg's original research; and these include thiamine (which is vitamin B1), biotin (which is another one of the B vitamins), and niacinamide. So it is amazing that the combination of PUFAs and the suppression of COX, plays such a large role in health and metabolism in general, and it was known back in the 1930s.  But to this day, it's largely brings an area of risk if you want to do research on metabolic cause of diseases. And I've actually talked to some people that worked with NIH, they've told me that unofficially is considered largely a dead end. If you really want funding from the government, you should not be working on metabolic causes of diseases; genetics is a preferred field.

d: The mitochondrion of the cell is not only where energy is produced along with CO2 but it's also where steroids are produced. You don't often hear some of the pro-PUFA people ever talk about steroids in general, let alone the idea that PUFA damages the mitochondria and inhibits steroids synthesis.

h: Yeah, it was discovered as soon as some of the drugs that were currently available on the market to treat the so-called treat because I don't believe in treating it - to treat hair loss and a condition called benign prostate hyperplasia (BPH), in other words, enlarged prostate but it's not cancerous yet; so these drugs what they do is they inhibit the enzyme 5-alpha reductase. That enzyme is well known, again in the bodybuilding world, it’s an enzyme that to converts testosterone into its more powerful androgen cousin, dihydrotestosterone. In addition, this is also the enzyme that converts progesterone into another neurosteroid called allopregnanolone. As soon as these drugs were approved, even during the clinical trials two things were noticed: one is that the people who were on these drugs suffered from some kind of a depression which was really not amenable to treatment with the current available SSRI drugs - that's a whole other story whether they are effective or not - but these people immediately started suffering from depression and also they started suffering from muscle loss. This tells you basically that the drug interferes with an enzyme that is very important for both your brain and your musculature, and how muscle you have largely determines how fast your metabolism is. You can say in effect that  [?] and PUFA basically destroys your muscles and destroys your brain. Allopregnanolone is one of the most powerful steroids - protective steroids - in the brain together with its precursors pregnenolone, progesterone, there's also pregnenolone, premenedione, there are a number of steroids that are all derived from pregnenolone and 5-alpha reductase is a crucial enzyme into converting them from one to the other, and without that enzyme we're inhibiting strongly; essentially means suboptimal brain function, which the designers of the drug freely admitted upon applying for approval of the FDA, they said that for unknown reasons at that time, the drug causes severe depressive symptoms in the majority of the population that was studied.

d: In medical culture there's a widespread belief that androgens are involved with acne, baldness, PCOS; is that a mistaken belief do you think?

h: I don't know about PCOS but I think that as far as baldness, prostate cancer, I think this is actually in my opinion is close to a criminal negligence. Ray wrote in one of his earlier articles that not only does he disagree that androgens are the cause of prostate cancer but he thinks that they should be used as a treatment. And lo and behold, about two years after he wrote that article the popular press published a reference to a study in which they showed that patients with terminal prostate cancer, in other words these were people who were told they had no more than 3-4 months to live, when they got testosterone injections directly into their prostate, they all fell into remission. Not only that but the metastatic masses that grew in their livers and lungs, they all disappeared. So, I don't know what else will tell you that this theory of the androgens causing prostate cancer is wrong, other than showing that using an androgen in a disease that is terminal, stops it in its tracks.

So, as far as prostate cancer is concerned I think that the medical field is dead wrong with that. I also think that the medical field is wrong on the cause of baldness because if testosterone and the androgens were the cause of baldness, 20-year-old men would be bald and 60 years old men would have a full stock of hair.

d: ~Cracking~ That's the most simple observation, when I frequently go to baldness forums and every now and then somebody will say that exact thing and they'll just be crucified in the forum for how stupid that sentiment is, which boggles the mind.

h: I'll be curious to see what the argument against the androgens is because frankly, even if you look at the official studies they'll admit at this point that androgens are not the only agent. Now they're saying estrogen, prolactin and cortisol, things that Ray said 20 years ago, that they also play a part but they are still claiming that the androgens are involved. The funny thing is, in the simplistic medical theory here that's saying that the elevation of these agents causes baldness, right? Well, a lot of them are actually inversely correlated. You can’t really have a high estrogen in a high dihydrotestosterone at the same time, I just don't know of a case like that, there's a good physiological reason; usually, people with high androgens, because androgens like dihydrotestosterone themselves are actually estrogen receptors antagonists and aromatase inhibitors. So, if you have a high dihydrotestosterone you'll have low estrogen, so something there doesn't add up, it's one or the other or the whole theory is wrong.

d: The DHT increasing, if that were to happen, that would be a protective mechanism, do you think?

h: I think this is one of the most protective steroids that both a man and women can produce. There were recently some studies, originally they were done in rats but recently they were repeated in humans, and were repeated successfully. They showed that basically that it has been known that the steroid Dehydroepiandrosterone (or DHEA), which is also precursor to DHT, works really well in preventing and even treating osteoporosis in postmenopausal women. Now, the official statement is that the osteoporosis in these patients is caused because of low estrogen; however, when one group was given estrogen and the other one was given DHT, the estrogen group had actually had higher rates of fractures versus the DHEA group, and when they measured the blood level of the hormones they found that people supplementing with DHEA had a "abnormally" high levels of DHT. When they administered an androgen receptor antagonist, in other words, when they blocked the effects DHT, the women that were given DHEA also had fractures. It shows you that DHT like the androgens in general are crucial for bone health, and they're also active neurosteroids. It's well known that men with low testosterone, actually both men and women with lower levels of androgens, are much more prone to depression and other psychiatric conditions.

d: You mentioned osteoporosis and something that might surprise some people is that serotonin is involved in osteoporosis not an estrogen. And you compared the PUFAs ability to activate tryptophan hydroxylase to radiation. I thought that was an interesting comparison and if someone were to try to explain the benefits of PUFAs, they have to explain the benefits of radiation - which I've actually ironically heard. I think a paleo advocate once, I had an email back and forth with them, and they were telling me that radiation was hormesis. Which seems to be kind of like the standard argument for anything that's slightly toxic or overtly toxic. They'll say: oh, it's hermetic and you should still take it!

h: The "funny" part, because it's really not funny at all, but the funny part about all these people is that they say, “Oh yeah, low dose radiation is hormesis” and at the same time they'd admit that radiation, the danger of radiation is cumulative. So, how can something be hormetic if I keep doing it, in theory if its hormetic, and I keep using low doses it should be beneficial; but at the same time if I cross a sort of threshold - which by the way turned out to be fraudulent, and I posted a study about it on the forum as well – so if I cross a threshold and suddenly it becomes carcinogenic. You can’t have it both ways, if its cumulative and it cannot be good for you in the long run. So, any talk about hormesis, even if it was proved can only apply to a single or at most just a few times a lifetime, of exposure not like these hundreds of X-Rays, CT scans that people are having on an annual basis to "prevent disease".

d: So, another strike against the essentiality of the unsaturated fats is that animals made deficient in the so-called essential fatty acids have extremely high metabolic rates and they're really hard to kill with things like endotoxins.

h: Yeah, that's right. One of the reasons is that basically one of the main mechanisms for which endotoxin causes its detrimental effects on the body is because it raises the production of serotonin itself. You can actually get a serotonin syndrome if you get a decent dose of endotoxins in your blood stream. What happens is that because the animals that are deficient in PUFA, in these animals the enzyme tryptophan hydroxylase is really low, both in the gut and in the brain, so, even if you give them endotoxins it won't trigger the production of serotonin that it does in animals that eat a normal PUFA laden diet. That's one of the main mechanisms why a PUFA deficiency will protect you from endotoxins. There are others as well.

d: Back up just a second, what is endotoxin producing in a person?

h: Endotoxin is produced by bacteria, basically when bacteria digest food, it's a by-product of bacterial digestion, its official name is Lipopolysaccharide. So, in a sense, it's a type of sugar; however, when the white blood cells in the blood stream sense that, they interpret this as a sign of infection; you get an immune response whenever there's a significant dose of endotoxins in your blood stream. People with good immune system they can probably brush it off pretty easily or at most get a symptom of a mild flu - which is also another topic that we can talk about, whether the flu is really caused by virus or it's a symptom of endotoxin poisoning - basically people with good immune systems can brush it off, but people with compromised immune system they cannot really muster up an immune response and also the overload of serotonin can cause their lungs to fail and their heart. Serotonin is one of the primary mediators of fibrosis in the human body, antiserotonin drugs are currently actually getting approved and pretty quickly so could be treating things like cystic fibrosis, heart failure, liver cirrhosis (which is actually fibrosis); it shows that serotonin has a very quick and detrimental effect on many organs and tissues, and endotoxins raise serotonin tremendously in people who eat a decent amount of PUFA.

d: The fibrosis is an excess production of collagen within the tissue and the tissue is presumably being de-energized by serotonin..?

h: Yeah, basically you can think of collagen as type of scar, which it really is, it's like when you get a wound on your skin, on the surface of the skin, the cells around it in the process of healing sort of over divide and overgrow, that's really why you get a scar. The scar is a tissue that is not permeated well by blood vessels, so it doesn't get good nutrition, and in absence of good nutrition it just solidifies and hardens, even calcifies at some point. The calcification thing is one of the hallmarks of cancer. Anything that has a fibrotic effect, and PUFA does have that effect, ultimately will cause at the very least fibrosis and at worst will cause some sort of undivided and uncontrolled growth, in other words, cancer.

d: You mentioned previously but the PUFAs are strongly immunosuppressive, they're found in higher levels in AIDS patients and then they're used to suppress the immune system for organ transplants?

h: That's correct. First started in the 1960s, in the UK, I forgot the name of the researcher but I can provide it to you later, but what he noticed was that as he was doing experiments with rats and doing kidney, liver transplants, he noticed that whenever the rats where fed on a high PUFA diet, specifically linoleic acid, one of the many examples of omega 6 PUFAs, whenever he fed a diet high - and again, when I say high, it's high by the animal standards, when you really look at it and convert it to a human dosage it comes down to about 10g per human per day, which is probably what most people end up getting nowadays anyways - anyway what he fed these rats they did not reject the organs and when he investigated further, he found that this was due to the fact that in these animals the PUFA raised the production of cortisol and serotonin, and both of these substances are immunosuppressive, so it's a well established practice in transplantations to administer immunosuppressive drugs, sometimes for life. Now I guess this is probably one of the few, so to speak “valid reasons” for using PUFA in a person who has had liver transplant, but even that I think there are other ways to achieve the same with less side effects. Anything that supresses your immune system ultimately will give you a life threatening infection. Recently there has been a huge increase in cases of so called PML (Progressive multifocal luekoencephalopathy) and it's caused by the JCV (John Cunningham virus) - about 90% of the population carries it but in the vast majority of people it's kept under control by the immune system - but in immunosuppressed people this virus gets activated and essentially causes a very rapid deterioration of the nervous system, with invariably lethal effects. It was noticed by the same researcher that these rats, even though they did not reject the organs that were transplanted, they died of some kind of neurological deterioration, and I don't know if it was PML but it matches with the current data that is known on humans, that immunosuppressed people have a much higher chance of dying from a viral encephalitis disease like PML.

d: So, some of the people that are advocating PUFA intake or think that restriction is ridiculous, these are some of the same people that advocate lowering the cholesterol, and you've noted that an accumulation of PUFAs inhibits endogenous cholesterol production, so perhaps if you paint this picture - which I think is incorrect - if you're consuming PUFAs you're ~vibrato starts~ decreasing your endogenous cholesterol production, you're lowering your so-called bad cholesterol LDL, and increasing your so called good cholesterol HDL, and perhaps this is a reason to consume PUFAs.

h: Yeah in that context, sure, if you believe this things, but even the main medical establishment has already admitted that cholesterol, at least dietary cholesterol, is no longer of concern. They haven't gone as far as to say that endogenous cholesterol production is not a concern but the FDA officially about two months ago said: “You can eat all the cholesterol you want, it really doesn't matter in terms of cardiovascular disease, stroke and things like that”. So, 30 years of spending billions of dollars of research and producing all of these drugs, and now they're saying that it just doesn't matter, it's not that important, at best, right? And we know that cholesterol is the precursor for all of your steroids. If you lower your cholesterol, which by the way the cholesterol production in hypothyroid people is already low, so if you deprive them of the nutrient that has many other properties on its own - Ray talks about some of them such as protection against viral infections, it can neutralize some pathogens that enter the system if their white blood cells count is not high enough - anyways, so in compromised people, if you lower their cholesterol even more, you're exposing them to all kinds of sort of assaults from the environment, and even internally, that they would have been able to handle better if their cholesterol levels were higher. I provided a study, which shows that low levels of LDL predate a cancer diagnosis by more than a decade. And that was independent of any other lifestyle choices such as smoking, drinking excessively, doing drugs, living next to a power plant - I don't know if the researchers had control over that but they claimed to have control over a lot of lifestyle factors. So it shows that it's a pretty powerful thing, it's probably not a good idea to blindly lower especially considering the fact that the official period doesn't say that we know with certainty that cholesterol is causing these plaques to form on the arteries. If you actually take these plaques, you really see that it's a combination of PUFA and calcium and a few other things; cholesterol may be there, but it's more like to protect from the damage and inflammation in vessel wall that the PUFA and calcium deposits are causing, so it's there by accident not as a causative agent.

d: Were the fats damaging the ability of the cell to make the steroids, is it the reducing agent like NADH?

h: Yeah, basically, if you eat a diet high in PUFA - and actually there's some evidence that excess fat intake, whether is saturated or not, will do the same but to a much smaller degree. But if you load up on PUFA, which will raise your inflammatory markers, in order for the body to sort of quench them, it uses the substance called NAD (Nicotinamide adenine dinucleotide), NADH is the reduced version of it, so, NAD is the oxidized and NADH is the reduced version of it; and it has been shown that the NAD to NADH ratio is perhaps the best health biomarker currently available. The higher the ratio is, the healthier you are, the longer you'll live, and the more resistant you'll be to a disease; the lower the ratio, the more prone you are to a disease, as a matter of fact high NADH levels are one of them (and not the only) a diagnostic biomarker for several Cancers, for Parkinson's disease, for Alzheimer's disease, in other words, they show that your body is in a reduced state, and PUFA is one the most powerful substances that lowers the NAD to NADH ratio, in other words, it raises the levels of NADH, it puts you in a reduced state. You don't want to be there.

d: The growth cancer state.

h: Exactly. So, in a reduced state, with not enough oxygen, basically the NAD to NADH ratio determines how well your body is oxidizing, how much oxygen is available to the cells; actually, how well they're using it because just providing oxygen to the cells is very often counter-productive. So it shows you how much CO2 you're producing and how well your tissues are oxygenated. PUFAs really put you far away from that state and is one of the few agents that - also radiation does the same, I think it's one of the reasons why I compare PUFA to radiation, because the two are very powerfully at lowering the NAD to NADH ratio, putting you in a disease state, and they've done, I don't know for how long, but you don't want to be in that state, is a disease state even if it's there temporarily.

d: My absolute favorite thing you listed on this post that kind of inspired us to chat was: you can take all this information but ultimately experiment is the ultimately arbiter and no amount of bickering or arguing over this or that study is going to make any difference if you don't test it out yourself and try to gather information about yourself to get a better understanding of what's going on your own body.

h: Yeah, I strongly encourage everybody to really do that.

I mean, I don't wanna sound like Ray, I'm sure he doesn't wanna sound like the ultimate authority on the subject. He does say that something along the lines of the ultimate human faculty is the one that experiences then experiment is the ultimate knowledge, something along those lines.

So go ahead, try it out yourself, and see how it makes you feel and if possible try to confirm that with some tests. I do have some suggested tests on the forum and I'm sure Danny, you also provide a list of valuable tests to people that they can do themselves. But you'll see the results yourselves I'm pretty confident, in as little as one month which is one study done with monkeys [??] which is relative to humans that I have seen a study with, as little as two weeks on a fat free diet, and one month on a very low fat diet, their tissues got fully depleted of PUFA and their metabolism basically increased two-fold, all the animals lost all the excessive fat that they had and essentially their respiration became uncoupled. I think it's not that difficult for people to actually experiment and find it out for themselves, I think that that is the ultimate goal, you should find out what works for you. Or Ray Peat and I personally am doing is trying to provide some directions for personal experimentation. I really don't mean to sound like I know it all, I really don’t.

d: That was amazing. The last part I wanted to touch upon was, say you are going out, say you have to eat PUFAs, what are some things that you can do to mitigate the damage of a high PUFA meal?

h: Some of the best things that you can do to prevent the damage from even occurring is probably take a little dose of vitamin E; Ray has said that as little as 200IU would be sufficient, there'll be about 2/3 of 200 is about 150mg would be sufficient if you prefer in mg. Most capsules on the market provide 400IU or above, that should be enough to prevent the damage that PUFA does, and one of the ways that vitamin E prevents the damage is that it turns the PUFA into saturated fat, the exact mechanism is still not known, but it's known that it happens. So, when you eat this PUFA and you take vitamin E, even if you end up storing that fat, it should be stored as saturated fat which is a lot more benign, both as stored fat and as actively burned fat than PUFA.

d: Georgi, thank you so much for chatting with me. That was extremely informative and I'm gonna have to chew on a lot of it, before you go, go ahead and let everyone know where they can find you on Ideal Labs as well as raypeatforum.com.

h: Sure. My information is pretty easy for people that are members of the forum - user forum member, haidut – when you log into the forum you'll be able to find me very easily, I comment on a lot of posts, I put a lot of new posts, to get to one in special just use the search box and search for haidut and you'll find me. My profile on the forum has a link to my website where I sell some supplements, I would like to point out that I'm not a salesman, I don't want you to buy my supplements, they are there simply to let you experiment if you don't have the time to experiment for yourself, but I actively encourage you to go out there, if you're willing to and you have the time, find the ingredients yourself and perform the experiments yourself and make your own supplements if you want to. But if you're interested in my supplements, you can find them in the profile of the forum. The forum is really the best because whenever I have a discussion with people I would like to be possible for the rest of the forum members to see it because it gives them additional knowledge, some people might have the same issue, some people might have additional comments and suggestions. Really, the purpose of the forum is to spread the discussion and get the collective knowledge going, not so much to help one individual person or listen to only one member of the forum.

d: Georgi, thank you so much for talking with me today.

h: Thank you, Danny. I really appreciate it and good luck with all of your endeavors; I look forward to speak to you again soon!

d: <Wrap up summary: Leave comments with suggestions for future podcasts using via his social media or whatever>