The Travis Corner

[Travis]

Although rare, prostaglandin‐like molecules can occur spontaneously from oxygen and linoleic acid. I don't think this would surprise many enzymologists, who might tell you that many enzymes only lower the energy barrier for reactions that would otherwise occur.

Gunstone, F. D. "Reaction of oxygen and unsaturated fatty acids." Journal of the American Oil Chemists’ Society (1984)​

 

[Terma]

Well I can't comment on microtubules, out of context I would have assumed that was something from star trek.

I liked your idea about polyamines contributing to fat mass, and yeah either way methionine contributes to them significantly. Methionine depletion would certainly stop the synthesis. However I wonder if there wouldn't also be any negative feedback regulation to high levels of polyamines (I forgot the word), or if polyamine synthesis will really overproduce enough to cause fat gain. (Perhaps potential for a disorder here?)

Methionine is so generic it could contribute to weight gain (and loss) in 10 different ways, so as always it's a question of trying to figure out the proportional contributions of the pathways rather than yes/no. Seems impossible to me in current articles but maybe you can do better.

In any case this is thrilling because specific amino restriction was exactly my plans. I think you only need to restrict one or two to achieve the effects on mTor, but something like polyamines throws another wrench into the mix.

 

[eddiem991]

What do you think about the paleo/stone age/ketogenic diet? And their explanations saying our bodies are "evolutionary tuned" for eating a high fat, low carb diet.

I know someone on this forum explained the benefits of the state of ketosis: [Non Peat] Undermethylators, Ketogenesis

Stating that beta-Hydroxybutyric acid is a more effective fuel for the body compared to glucose because it creates less end-products and free radicals.

What's your take on this?

 

[Koveras]

Hey @Travis @Amazoniac

Some of the discussion here around schizophrenia, histamine, etc had me interested - and one book I happened to be reading was 'Nutrient Power: Heal Your Biochemistry and Heal Your Brain'

The book discusses a somewhat contentious condition called pyroluria - excess pyrroles in the urine - described lay-ly here and here:

"Pyroluria is a genetically determined chemical imbalance involving an abnormality in hemoglobin synthesis. Hemoglobin is the protein that holds iron in the red blood cell. Individuals with this disorder produce too much of a byproduct of hemoglobin synthesis called “kryptopyrrole” (KP) or “hemepyrrole.” Kryptopyrrole has no known function in the body and is excreted in urine. Kryptopyrrole binds to pyridoxine (vitamin B6) and zinc and makes them unavailable for their important roles as co-factors in enzymes and metabolism. These essential nutrients when bound to kryptopyrrole are removed from the bloodstream and excreted into the urine as pyrroles. Arachidonic acid (an omega-6 fatty acid) also becomes deficient. The effect of pyroluria can have a mild, moderate, or severe depending on the severity of the imbalance. Most individuals show symptoms of zinc and/or B6 deficiencies, which include poor stress control, nervousness, anxiety, mood swings, severe inner tension, episodic anger (an explosive temper), poor short-term memory and depression. "​

Irving DG: Apparent non-indolic ehrlich-positive substances related to Mental illness. JNeuropsychiat, 1961;2:292-305.
Hoffer A, Mahon M: The presence of unidentified substances in the urine of psychiatric patients. JNeuropsychiat, 1961;2:331-397.
Irvine DG, Bayne W, et al: Identification of kryptopyrrole in human urine and its relationship to psychosis. Nature, 1969;224:811-813.
Pfeiffer CC, Lliev V: Pyrroluria, urinary mauve factor, causes double deficiency of B6 and zinc in schizophrenics. Fed Proc, 1973;32:276.
Jackson JA, Riordan HD, Neathery S: Vitamins, blood lead and urine pyrroles in Down Syndrome patients.Amer Clin Lab, 1990:Jan- Feb:8-9.
Jackson JA, Riordan HD, Neathery S, Riordan N: Urinary pyrroles in health and disease. J Orthomol Med, 1997: 12;2:96-98.​

Less supportive papers

Gendler PL, Duhan, HA, Rapoport H. Hemopyrrole and kryptopyrrole are absent from the urine of schizophrenics and normal persons. Clin Chem. 1978 Feb;24(2):230-3.
Jacobson SJ, Rapoport H, Ellman GL. The nonoccurrence of hemo- and kryptopyrrole in urine of schizophrenics. Biol Psychiatry. 1975 Feb;10(1):91-3.
Irvine DG. Hydroxy-hemopyrrolenone, not kryptopyrrole, in the urine of schizophrenics and porphyries. Clin Chem. 1978 Nov;24(11):2069-70.​

This had me thinking about Ray's discussion around essential fatty acids in a few articles

"In 1929 George and Mildred Burr published a paper claiming that unsaturated fats, and specifically linoleic acid, were essential to prevent a particular disease involving dandruff, dermatitis, slowed growth, sterility, and fatal kidney degeneration."

Unsaturated fatty acids: Nutritionally essential, or toxic?​

"Several publications between 1936 and 1944 made it very clear that Burr's basic animal diet was deficient in various nutrients, especially vitamin B6. The disease that appeared in Burr's animals could be cured by fat free B-vitamin preparations, or by purified vitamin B6 when it became available. A zinc deficiency produces similar symptoms, and at the time Burr did his experiments, there was no information on the effects of fats on mineral absorption. If a diet is barely adequate in the essential minerals, increasing the metabolic rate, or decreasing intestinal absorption of minerals, will produce mineral deficiencies and metabolic problems."

Fats and degeneration
​

As well as Chris Masterjohn's take on the EFA debate

"The Burrs cured essential fatty acid deficiency in young, growing rats using 0.4 percent of calories as polyunsaturated fatty acids (PUFA) when provided by lard and 0.1 percent of calories when provided by liver.7 Evidence suggests the requirement is similar in human infants. This is discussed in more detail in the sidebar below. The essential fatty acid requirement, however, is influenced by other factors. The refined sugar used in these experiments increases the requirement.18 Vitamin B6 alone resolved the deficiency in later experiments by dramatically increasing the synthesis of arachidonic acid from linoleic acid stored in the tissues.19 Diets low in refined sugar and rancid vegetable oils, adequate in protein and total energy, and rich in vitamin B6, biotin, magnesium, and whole, fresh foods abundant in natural antioxidants are likely to reduce the essential fatty acid requirement to such a degree that it is impossible for a healthy, growing child under ordinary circumstances to develop a deficiency."

Understanding the Essential Fatty Acids​

["19"]

Witten, P. W., & Holman, R. T. (1952). Polyethenoid fatty acid metabolism. VI. Effect of pyridoxine on essential fatty acid conversions. Arch Biochem Biophys, 41(2), 266-273. ​

Have you looked into these pyrroles/kryptopyrrole and the relationship with vitamin B6, zinc, and fatty acids?

 

[Amazoniac]

Hey @Travis @Amazoniac

Some of the discussion here around schizophrenia, histamine, etc had me interested - and one book I happened to be reading was 'Nutrient Power: Heal Your Biochemistry and Heal Your Brain'

The book discusses a somewhat contentious condition called pyroluria - excess pyrroles in the urine - described lay-ly here and here:

"Pyroluria is a genetically determined chemical imbalance involving an abnormality in hemoglobin synthesis. Hemoglobin is the protein that holds iron in the red blood cell. Individuals with this disorder produce too much of a byproduct of hemoglobin synthesis called “kryptopyrrole” (KP) or “hemepyrrole.” Kryptopyrrole has no known function in the body and is excreted in urine. Kryptopyrrole binds to pyridoxine (vitamin B6) and zinc and makes them unavailable for their important roles as co-factors in enzymes and metabolism. These essential nutrients when bound to kryptopyrrole are removed from the bloodstream and excreted into the urine as pyrroles. Arachidonic acid (an omega-6 fatty acid) also becomes deficient. The effect of pyroluria can have a mild, moderate, or severe depending on the severity of the imbalance. Most individuals show symptoms of zinc and/or B6 deficiencies, which include poor stress control, nervousness, anxiety, mood swings, severe inner tension, episodic anger (an explosive temper), poor short-term memory and depression. "​

Irving DG: Apparent non-indolic ehrlich-positive substances related to Mental illness. JNeuropsychiat, 1961;2:292-305.
Hoffer A, Mahon M: The presence of unidentified substances in the urine of psychiatric patients. JNeuropsychiat, 1961;2:331-397.
Irvine DG, Bayne W, et al: Identification of kryptopyrrole in human urine and its relationship to psychosis. Nature, 1969;224:811-813.
Pfeiffer CC, Lliev V: Pyrroluria, urinary mauve factor, causes double deficiency of B6 and zinc in schizophrenics. Fed Proc, 1973;32:276.
Jackson JA, Riordan HD, Neathery S: Vitamins, blood lead and urine pyrroles in Down Syndrome patients.Amer Clin Lab, 1990:Jan- Feb:8-9.
Jackson JA, Riordan HD, Neathery S, Riordan N: Urinary pyrroles in health and disease. J Orthomol Med, 1997: 12;2:96-98.​

Less supportive papers

Gendler PL, Duhan, HA, Rapoport H. Hemopyrrole and kryptopyrrole are absent from the urine of schizophrenics and normal persons. Clin Chem. 1978 Feb;24(2):230-3.
Jacobson SJ, Rapoport H, Ellman GL. The nonoccurrence of hemo- and kryptopyrrole in urine of schizophrenics. Biol Psychiatry. 1975 Feb;10(1):91-3.
Irvine DG. Hydroxy-hemopyrrolenone, not kryptopyrrole, in the urine of schizophrenics and porphyries. Clin Chem. 1978 Nov;24(11):2069-70.​

This had me thinking about Ray's discussion around essential fatty acids in a few articles

"In 1929 George and Mildred Burr published a paper claiming that unsaturated fats, and specifically linoleic acid, were essential to prevent a particular disease involving dandruff, dermatitis, slowed growth, sterility, and fatal kidney degeneration."

Unsaturated fatty acids: Nutritionally essential, or toxic?​

"Several publications between 1936 and 1944 made it very clear that Burr's basic animal diet was deficient in various nutrients, especially vitamin B6. The disease that appeared in Burr's animals could be cured by fat free B-vitamin preparations, or by purified vitamin B6 when it became available. A zinc deficiency produces similar symptoms, and at the time Burr did his experiments, there was no information on the effects of fats on mineral absorption. If a diet is barely adequate in the essential minerals, increasing the metabolic rate, or decreasing intestinal absorption of minerals, will produce mineral deficiencies and metabolic problems."

Fats and degeneration
​

As well as Chris Masterjohn's take on the EFA debate

"The Burrs cured essential fatty acid deficiency in young, growing rats using 0.4 percent of calories as polyunsaturated fatty acids (PUFA) when provided by lard and 0.1 percent of calories when provided by liver.7 Evidence suggests the requirement is similar in human infants. This is discussed in more detail in the sidebar below. The essential fatty acid requirement, however, is influenced by other factors. The refined sugar used in these experiments increases the requirement.18 Vitamin B6 alone resolved the deficiency in later experiments by dramatically increasing the synthesis of arachidonic acid from linoleic acid stored in the tissues.19 Diets low in refined sugar and rancid vegetable oils, adequate in protein and total energy, and rich in vitamin B6, biotin, magnesium, and whole, fresh foods abundant in natural antioxidants are likely to reduce the essential fatty acid requirement to such a degree that it is impossible for a healthy, growing child under ordinary circumstances to develop a deficiency."

Understanding the Essential Fatty Acids​

["19"]

Witten, P. W., & Holman, R. T. (1952). Polyethenoid fatty acid metabolism. VI. Effect of pyridoxine on essential fatty acid conversions. Arch Biochem Biophys, 41(2), 266-273. ​

Have you looked into these pyrroles/kryptopyrrole and the relationship with vitamin B6, zinc, and fatty acids?

Grand leader, Google results for those terms narrowing the search to orthomolecular.org might interest you.

 

[Travis]

Hey @Travis @Amazoniac

Some of the discussion here around schizophrenia, histamine, etc had me interested - and one book I happened to be reading was 'Nutrient Power: Heal Your Biochemistry and Heal Your Brain'

The book discusses a somewhat contentious condition called pyroluria - excess pyrroles in the urine - described lay-ly here and here:

"Pyroluria is a genetically determined chemical imbalance involving an abnormality in hemoglobin synthesis. Hemoglobin is the protein that holds iron in the red blood cell. Individuals with this disorder produce too much of a byproduct of hemoglobin synthesis called “kryptopyrrole” (KP) or “hemepyrrole.” Kryptopyrrole has no known function in the body and is excreted in urine. Kryptopyrrole binds to pyridoxine (vitamin B6) and zinc and makes them unavailable for their important roles as co-factors in enzymes and metabolism. These essential nutrients when bound to kryptopyrrole are removed from the bloodstream and excreted into the urine as pyrroles. Arachidonic acid (an omega-6 fatty acid) also becomes deficient. The effect of pyroluria can have a mild, moderate, or severe depending on the severity of the imbalance. Most individuals show symptoms of zinc and/or B6 deficiencies, which include poor stress control, nervousness, anxiety, mood swings, severe inner tension, episodic anger (an explosive temper), poor short-term memory and depression. "​

Irving DG: Apparent non-indolic ehrlich-positive substances related to Mental illness. JNeuropsychiat, 1961;2:292-305.
Hoffer A, Mahon M: The presence of unidentified substances in the urine of psychiatric patients. JNeuropsychiat, 1961;2:331-397.
Irvine DG, Bayne W, et al: Identification of kryptopyrrole in human urine and its relationship to psychosis. Nature, 1969;224:811-813.
Pfeiffer CC, Lliev V: Pyrroluria, urinary mauve factor, causes double deficiency of B6 and zinc in schizophrenics. Fed Proc, 1973;32:276.
Jackson JA, Riordan HD, Neathery S: Vitamins, blood lead and urine pyrroles in Down Syndrome patients.Amer Clin Lab, 1990:Jan- Feb:8-9.
Jackson JA, Riordan HD, Neathery S, Riordan N: Urinary pyrroles in health and disease. J Orthomol Med, 1997: 12;2:96-98.​

Less supportive papers

Gendler PL, Duhan, HA, Rapoport H. Hemopyrrole and kryptopyrrole are absent from the urine of schizophrenics and normal persons. Clin Chem. 1978 Feb;24(2):230-3.
Jacobson SJ, Rapoport H, Ellman GL. The nonoccurrence of hemo- and kryptopyrrole in urine of schizophrenics. Biol Psychiatry. 1975 Feb;10(1):91-3.
Irvine DG. Hydroxy-hemopyrrolenone, not kryptopyrrole, in the urine of schizophrenics and porphyries. Clin Chem. 1978 Nov;24(11):2069-70.​

This had me thinking about Ray's discussion around essential fatty acids in a few articles

"In 1929 George and Mildred Burr published a paper claiming that unsaturated fats, and specifically linoleic acid, were essential to prevent a particular disease involving dandruff, dermatitis, slowed growth, sterility, and fatal kidney degeneration."

Unsaturated fatty acids: Nutritionally essential, or toxic?​

"Several publications between 1936 and 1944 made it very clear that Burr's basic animal diet was deficient in various nutrients, especially vitamin B6. The disease that appeared in Burr's animals could be cured by fat free B-vitamin preparations, or by purified vitamin B6 when it became available. A zinc deficiency produces similar symptoms, and at the time Burr did his experiments, there was no information on the effects of fats on mineral absorption. If a diet is barely adequate in the essential minerals, increasing the metabolic rate, or decreasing intestinal absorption of minerals, will produce mineral deficiencies and metabolic problems."

Fats and degeneration
​

As well as Chris Masterjohn's take on the EFA debate

"The Burrs cured essential fatty acid deficiency in young, growing rats using 0.4 percent of calories as polyunsaturated fatty acids (PUFA) when provided by lard and 0.1 percent of calories when provided by liver.7 Evidence suggests the requirement is similar in human infants. This is discussed in more detail in the sidebar below. The essential fatty acid requirement, however, is influenced by other factors. The refined sugar used in these experiments increases the requirement.18 Vitamin B6 alone resolved the deficiency in later experiments by dramatically increasing the synthesis of arachidonic acid from linoleic acid stored in the tissues.19 Diets low in refined sugar and rancid vegetable oils, adequate in protein and total energy, and rich in vitamin B6, biotin, magnesium, and whole, fresh foods abundant in natural antioxidants are likely to reduce the essential fatty acid requirement to such a degree that it is impossible for a healthy, growing child under ordinary circumstances to develop a deficiency."

Understanding the Essential Fatty Acids​

["19"]

Witten, P. W., & Holman, R. T. (1952). Polyethenoid fatty acid metabolism. VI. Effect of pyridoxine on essential fatty acid conversions. Arch Biochem Biophys, 41(2), 266-273. ​

Have you looked into these pyrroles/kryptopyrrole and the relationship with vitamin B6, zinc, and fatty acids?

Well, it's quite obvious that pyrroles can chelate zinc. Histidine has an imidizole ring, which is similar to the pyrrole ring, and is the second best‐known endogenous zinc chelator behind picolinate. Vitamin B₆, or pyridoxal, has the same pyridine ring that picolinate has. The universal zinc chelator has certain characteristics. Perhaps it can be stated this way:

'Aberrations in the heme biosynthetic pathway can produce urinary metabolites resembling incomplete porphyrin ring fragments such as kryptopyrrole and pyrrole-3-propanoic acid, the latter being capable of complexing zinc between its cyclic amine and terminal carboxyl group—analogous to the Zn²⁺‐histidine complex.'​

The heme fragment pyrrole-3-propanoic acid looks to be a good zinc chelator, but straight pyrrole doesn't seem like it would work very well. There are some lazy depictions online, but I think this one is convincing (for zinc picolinate):

The second one not so much, because if all it took was a carboxyl group then why wouldn't glutamate be the 'classic zinc chelator?' The cyclic nitrogen must play a fundamental role since molecules known specifically for their zinc affinity all have a cyclic nitrogen (and a carboxyl).

Since these zinc complexes always appear in pairs, perhaps Zn²⁺ is being pulled out of the body by an oxygenated heme fragment (a substituted pyrrole) in association with pyridoxal—being the second ligand? I can see how heme fragments would have the capacity to chelate zinc, but not sure how pyridoxal becomes involved in this..

So are there skin problems seen in pyroluria?

I liked your idea about polyamines contributing to fat mass, and yeah either way methionine contributes to them significantly. Methionine depletion would certainly stop the synthesis. However I wonder if there wouldn't also be any negative feedback regulation to high levels of polyamines (I forgot the word), or if polyamine synthesis will really overproduce enough to cause fat gain. (Perhaps potential for a disorder here?)

I know of two enzymes named after their ability to oxidize polyamines, and I think even monoamine oxidase can do it. I just read something today about polyamine injections producing acrolein.

Here it is, I just found the quote:

'The toxicity of by-products of polyamine oxidation by serum amine oxidases interacting with exogenous polyamine administration is evident and has been attributed to the amino aldehydes, H₂O₂, acrolein, or a combination thereof (24).' ―Redman​

So there are two dedicated ones, named for this, but also monoamine oxidase to consider. You might think that high levels of methylglyoxal would disable polyamines directly through a Schiff base. Aromatic diamines like phenylenediamine are commonly used to detect methylgloxal; the two carbonyls condense with two perfectly‐spaced amines producing a new fluorophore that absorbs light at a new frequency—allowing detection. Other diamines perfectly‐spaced in allowing methylgloxal cycloaddition are arginine and urea.

Redman, Claire. "Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells." Carcinogenesis (1997)​

Methionine is so generic it could contribute to weight gain (and loss) in 10 different ways, so as always it's a question of trying to figure out the proportional contributions of the pathways rather than yes/no. Seems impossible to me in current articles but maybe you can do better.

I did think about the other ways, but am convinced that only polyamines can explain this. There isn't much of a reason to think glutathione is involved since cysteine—and even glutathione itself—does not cause weight gain and kill rats. I think general methylation would be more convincing . . . if it weren't for the fact that betaine, creatine, or choline cannot do this.

Androgens induce ornithine decarboxylase, which could be partially responsible for their anabolic effects.

If you read that study, you can see how selenomethionine inhibits polyamine production and proliferation—an effect reversed by added spermine. I see polyamines as synonymous with growth since nothing appears capable of unfurling DNA to the same extent. In fact, nothing else can really induce the Z‐DNA configuration besides polyamines and a few synthetic metal triamines.

The interaction with microtubules is interesting, but I'm not certain what role they have. I do know that they microtubule cytoskeleton needs to be disassembled for mitosis to occur . . . somehow (I'm laying my bet on Ca²⁺ at the moment).

In any case this is thrilling because specific amino restriction was exactly my plans. I think you only need to restrict one or two to achieve the effects on mTor, but something like polyamines throws another wrench into the mix.

I think they are certainly anabolic, but you can replace them with Se‐methionine. Plants and mammals incorporate these without discretion and cannot tell the difference, yet Se‐methionine cannot become polyamines. You could potentially shift polyamine‐induced replication (growth) by modifying the Se‐methionine/S‐methionine ratio in addition to the leucine/isoleucine ratio. I know that tryptophan converts to serotonin, which then releases growth hormone from the pituitary. So the most anabolic amino acids—I think you could almost say hormonally anabolic—appear to be S‐methionine, ornithine, leucine, and tryptophan.

 

[Terma]

I know of two enzymes named after their ability to oxidize polyamines, and I think even monoamine oxidase can do it. I just read something today about polyamine injections producing acrolein.

Here it is, I just found the quote:

'The toxicity of by-products of polyamine oxidation by serum amine oxidases interacting with exogenous polyamine administration is evident and has been attributed to the amino aldehydes, H₂O₂, acrolein, or a combination thereof (24).' ―Redman​

Redman, Claire. "Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells." Carcinogenesis (1997)​

I was thinking in terms of negative feedback regulation on the decarboxylases, but actually that's even more interesting... and concerning.

That article is quite dense too so a lot of food for thought. Thanks.

I did think about the other ways, but am convinced that only polyamines can explain this. There isn't much of a reason to think glutathione is involved since cysteine—and even glutathione itself—does not cause weight gain and kill rats. I think general methylation would be more convincing . . . if it weren't for the fact that betaine, creatine, or choline cannot do this.

Well, for example, there's quite an association between SAMe and mTORC1.
This was just published but it was clear from other articles there was a strong link in several parts of the body: SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
Of course what really matters is the localization of the final effect, i.e. in adipocytes or in fatty liver hepatocytes.

I think they are certainly anabolic, but you can replace them with Se‐methionine. Plants and mammals incorporate these without discretion and cannot tell the difference, yet Se‐methionine cannot become polyamines. You could potentially shift polyamine‐induced replication (growth) by modifying the Se‐methionine/S‐methionine ratio in addition to the leucine/isoleucine ratio. I know that tryptophan converts to serotonin, which then releases growth hormone from the pituitary. So the most anabolic amino acids—I think you could almost say hormonally anabolic—appear to be S‐methionine, ornithine, leucine, and tryptophan.

Exactly, leucine and tryptophan were the ones I had in mind. It appears the tryptophan also has more direct effects on cells, not only through IGF-1, hinted to for muscle cells in the in vitro part of The aromatic amino acid tryptophan stimulates skeletal muscle IGF1/p70s6k/mTor signaling in vivo and the expression of myogenic genes in vitro (likely was posted here somewhere, it made the rounds) and also from its use by T-cells (several articles). [As an aside, there's an interesting part of that article where Kynurenine prevented lean mass gain while maintaining fat mass - this also motivates me *edit: I wrote this all wrong, but you'll get what I mean]

This is good, but I'm not completely sure how to exploit this knowledge of Se-methionine further, other than restricting methionine; I've been taking selenomethionine for years!

 

[Terma]

Not to mention, I plan on looking deeper into the putrescine/polyamine content of foods I eat thanks to this.

 

[Tarmander]

Big picture question for you Travis. What do you consider the proper direction to head in while looking for health? Meaning, if I am "working on my health," what am I working on in your world? In some ways, Peat's contribution to my life was simply orienting myself towards robust metabolism. The details along the way overall head in that direction. When you are orienting yourself, do you think to yourself "Man I really have to get more micro-tubes going here," or what?

 

[Travis]

Big picture question for you Travis. What do you consider the proper direction to head in while looking for health? Meaning, if I am "working on my health," what am I working on in your world? In some ways, Peat's contribution to my life was simply orienting myself towards robust metabolism. The details along the way overall head in that direction. When you are orienting yourself, do you think to yourself "Man I really have to get more micro-tubes going here," or what?

I think people should just be unbiased and honest (i.e. boring). Many people come across compelling information and ignore it, or disregard information that implicates their favorite food. It's easy to become attached to certain foods, and especially the ones with opiates and high‐tryptophan. I have a theory that some people eat immunogenic foods (i.e. oats) as an 'immune stimulant,' to release histamine. The reason I think this is because I find them addictive, and a mild stimulant, yet they have no exorphins. I think some people toss‐aside these effects as being 'only hungry,' but certain foods do seem far more addictive than others.

I am mostly vegan but I think that beef is the best nonvegan food, so this is an unbiased opinion. Beef has ~15% stearic acid, which has actually been shown to inhibit cancer. Unlike eicosapentaenoic acid, stearic acid has no double bond and hence no kink; saturated acids are unable to inhibit cyclooxygenase for this reason. Instead, stearic acid has been shown to displace arachidonic acid and linoleic acid from the cell membrane. The shorter chained fatty acids myristic and palmitic are oxidized for energy much quicker and don't persist to the extent in which stearic acid does, explaining why these fatty acids don't greatly reduce cancer.

click to embiggen: Chart indicates stearic acid most cancer‐protective (Tinsley, 1981).​

Injections of stearic acid have been shown to protect rats against a carcinogen (Habib, 1997).

And the feeding of stearic acid at 13% of energy, to rats, has been found to reduce tumors compared to the control—being fed low‐fat rat kibbles (~4.5%).

click to embiggen: Graph proving anticancer effect of stearic acid (black bars). ​

Total rat linoleic arachidonic acid contents were reduced on the plasma membrane (Bennett, 1984).

In 'essential fatty acid deficiency,' arachidonic acid levels are low; total prostaglandins are low. This has been observed in newborns—having less fatty acid stores and more cell division, acting to lower the density of fatty acids at each cell cycle.

click to embiggen: Graph showing reduced linoleic and arachidonic acid in newborns.​

Mead acid is synthesized by the body in the event on low linoleic acid (pink highlight). This is our body's own membrane lipid, unique in that it cannot form prostaglandins like arachidonic acid can. The eicosanoid produced by the Mead acid is simply a hydroxylated product, either of lipoxygenase or cycooxygenase. The term 'Mead acid' was named in honor of the man who had discovered it, and could represent the ideal membrane lipid.

Urinary prostaglandin E₂ levels are lower in so‐called 'essential fatty acid deficiency.'

So I think to be healthy one needs chocolate (stearic acid), coffee, fruit, leaves, tubers, coconuts, and perhaps some beef for people who like it. Beef has roughly 15% stearic acid and only 2% linoleic acid—perhaps the best fatty acid ratio among animal foods. But since methionine creates polyamines, one should restrict it in the event self‐perceived 'excessive growth' or 'excessive weight gain.' Anabolic foods shouldn't be considered harmful, for this reason alone, but grown adults can only occupy so much space. Some foods stimulate growth more than others.

Wheat is a food from hell with an immunogenic peptide, but there are ways to circumvent this with proper preparation. Unless someone is serious about detoxifying gluten with enzymes or preparation techniques, it should probably be avoided. Oats and soy can also be immunogenic, but corn and rice are safe in this respect. Large immunogenic peptides can release cytokines within the body, and these can induce cells to produce additional cytokines—a self‐amplification positive‐feedback cascade which only stops after cortisol has been raised through the roof (negative feedback, but we have other ones; we even have negative feedback cytokines (i.e. IL‐4)). These cytokines increase prostaglandin flux, lower tryptophan by activated the kyneurenine pathway, increase histamine for weeks by inducing mast cells, and can even effect polyamines; under the control of cytokines are iNOS and arginase: two enzymes which decide whether arginine becomes nitric oxide or becomes ornithine. An enzyme in the bloodstream called delta nine desaturase (Δ⁹‐desaturase) converts stearic acid into oleic acid, and this has been shown to be under the control of α-interferon (Habib, 1987). This would lead me to assume that other cytokines can also affect this enzyme, perhaps creating more double=bonds in the event of immune activation—such as seen during during infection and after the ingestion of immunogenic peptides. Although oleic acid cannot become arachidonic acid and hence cannot become an 2‐series prostaglandin,* it can eventually become less-harmful eicosanoids through the action elongases and additional desaturases.

People with so-called 'HIV infection' have higher Δ⁹‐desaturase activity.

Habib, N. A. "Stearic acid and carcinogenesis." British journal of cancer (1987)
Friedman, Z. V. I. "Decreased prostaglandin E turnover in infants with essential fatty acid deficiency." Pediatric research (1978)
Tinsley, Ian J. "Influence of dietary fatty acids on the incidence of mammary tumors in the C3H mouse." Cancer research (1981)
Bennett, Alice S. "Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice." International journal of cancer (1984)
[*] Eicosapentaenoic acid (EPA) technically can become a 3‐series prostaglandin, such as prostaglandin E₃. Though quite similar in structure, the 3‐series prostaglandins are far less potent biologically; prostaglandin E₃ represents merely ~¹⁄₄ the activity of prostaglandin E₂.​

 

[Tarmander]

I think people should just be unbiased and honest (i.e. boring). Many people come across compelling information and ignore it, or disregard information that implicates their favorite food. It's easy to become attached to certain foods, and especially the ones with opiates and high‐tryptophan. I have a theory that some people eat immunogenic foods (i.e. oats) as an 'immune stimulant,' to release histamine. The reason I think this is because I find them addictive, and a mild stimulant, yet they have no exorphins. I think some people toss‐aside these effects as being 'only hungry,' but certain foods do seem far more addictive than others.

I am mostly vegan but I think that beef is the best nonvegan food, so this is an unbiased opinion. Beef has ~15% stearic acid, which has actually been shown to inhibit cancer. Unlike eicosapentaenoic acid, stearic acid has no double bond and hence no kink; saturated acids are unable to inhibit cyclooxygenase for this reason. Instead, stearic acid has been shown to displace arachidonic acid and linoleic acid from the cell membrane. The shorter chained fatty acids myristic and palmitic are oxidized for energy much quicker and don't persist to the extent in which stearic acid does, explaining why these fatty acids don't greatly reduce cancer.

View attachment 7889 click to embiggen: Chart indicates stearic acid most cancer‐protective (Tinsley, 1981).​

Injections of stearic acid have been shown to protect rats against a carcinogen (Habib, 1997).

And the feeding of stearic acid at 13% of energy, to rats, has been found to reduce tumors compared to the control—being fed low‐fat rat kibbles (~4.5%).

View attachment 7890 click to embiggen: Graph proving anticancer effect of stearic acid (black bars). ​

Total rat linoleic arachidonic acid contents were reduced on the plasma membrane (Bennett, 1984).

In 'essential fatty acid deficiency,' arachidonic acid levels are low; total prostaglandins are low. This has been observed in newborns—having less fatty acid stores and more cell division, acting to lower the density of fatty acids at each cell cycle.

View attachment 7891 click to embiggen: Graph showing reduced linoleic and arachidonic acid in newborns.​

Mead acid is synthesized by the body in the event on low linoleic acid (pink highlight). This is our body's own membrane lipid, unique in that it cannot form prostaglandins like arachidonic acid can. The eicosanoid produced by the Mead acid is simply a hydroxylated product, either of lipoxygenase or cycooxygenase. The term 'Mead acid' was named in honor of the man who had discovered it, and could represent the ideal membrane lipid.

Urinary prostaglandin E₂ levels are lower in so‐called 'essential fatty acid deficiency.'

So I think to be healthy one needs chocolate (stearic acid), coffee, fruit, leaves, tubers, coconuts, and perhaps some beef for people who like it. Beef has roughly 15% stearic acid and only 2% linoleic acid—perhaps the best fatty acid ratio among animal foods. But since methionine creates polyamines, one should restrict it in the event self‐perceived 'excessive growth' or 'excessive weight gain.' Anabolic foods shouldn't be considered harmful, for this reason alone, but grown adults can only occupy so much space. Some foods stimulate growth more than others.

Wheat is a food from hell with an immunogenic peptide, but there are ways to circumvent this with proper preparation. Unless someone is serious about detoxifying gluten with enzymes or preparation techniques, it should probably be avoided. Oats and soy can also be immunogenic, but corn and rice are safe in this respect. Large immunogenic peptides can release cytokines within the body, and these can induce cells to produce additional cytokines—a self‐amplification positive‐feedback cascade which only stops after cortisol has been raised through the roof (negative feedback, but we have other ones; we even have negative feedback cytokines (i.e. IL‐4)). These cytokines increase prostaglandin flux, lower tryptophan by activated the kyneurenine pathway, increase histamine for weeks by inducing mast cells, and can even effect polyamines; under the control of cytokines are iNOS and arginase: two enzymes which decide whether arginine becomes nitric oxide or becomes ornithine. An enzyme in the bloodstream called delta nine desaturase (Δ⁹‐desaturase) converts stearic acid into oleic acid, and this has been shown to be under the control of α-interferon (Habib, 1987). This would lead me to assume that other cytokines can also affect this enzyme, perhaps creating more double=bonds in the event of immune activation—such as seen during during infection and after the ingestion of immunogenic peptides. Although oleic acid cannot become arachidonic acid and hence cannot become an 2‐series prostaglandin,* it can eventually become less-harmful eicosanoids through the action elongases and additional desaturases.

People with so-called 'HIV infection' have higher Δ⁹‐desaturase activity.

Habib, N. A. "Stearic acid and carcinogenesis." British journal of cancer (1987)
Friedman, Z. V. I. "Decreased prostaglandin E turnover in infants with essential fatty acid deficiency." Pediatric research (1978)
Tinsley, Ian J. "Influence of dietary fatty acids on the incidence of mammary tumors in the C3H mouse." Cancer research (1981)
Bennett, Alice S. "Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice." International journal of cancer (1984)
[*] Eicosapentaenoic acid (EPA) technically can become a 3‐series prostaglandin, such as prostaglandin E₃. Though quite similar in structure, the 3‐series prostaglandins are far less potent biologically; prostaglandin E₃ represents merely ~¹⁄₄ the activity of prostaglandin E₂.​

Thank you for the response. If I could attempt to sum it up, you seem very oriented towards fatty acid profiles, immunologic ingredients and their stimulation of histamine, and different amino acids and their neurotransmitters.

How do you think lamb compares to Beef? Lamb usually has a higher zinc content which I think can be valuable, although I am not sure how its stearic acid content measures up. Do you buy into the stressed state vs relaxed state that Ray talks about? Thanks man!

 

[Amazoniac]

I have a theory that some people eat immunogenic foods (i.e. oats) as an 'immune stimulant,' to release histamine.

And there's one about heavy meals, such as rice with meat, stimulating insulin so much that angelords crave sweet desserts right afterwards based on a dip feeling.

 

[Amazoniac]

Herb Doctors: The Metabolism Of Cancernew

cysteine, tryptophan, and methionine are the ones that most easily promote cancer growth and development but glutamine and several of the easily metabolized amino acids are the ones that fuel the production of lactate even when glucose is not available or is currently being depleted.

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Herb Doctors: You Are What You Eat 2

I don't know anything about mushrooms, actually, except that principle - they are antiseptic. They have a high- value protein, and the protein happens to be pretty low in methionine which is the most toxic of the amino acids. Cysteine and methionine are the amino acids that most slow your metabolism, so you're getting two of the metabolic stimulants - lowering the estrogen, disinfecting your intestine.

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Politics & Science: Biochemical Health

And probably a fairly low protein diet is very good for health, in the sense of living longer. But for maintaining tissue renewal, you can’t go below a certain amount of tryptophan, cysteine and methionine. Those are rapid turnover proteins.

 

[raypeatclips]

@Travis How much chocolate do you think is reasonable amount to eat solely for health benefits, do you favour the high cocoa types?

Edit: I think I answered my own question here about milk vs dark chocolate. They both seem pretty good, not too different stearic acid amounts, I was expecting a lot less from milk chocolate in comparison, as all the stearic acid I believed was in the cocoa butter. Still unsure how much would be a good amount to eat daily though.

http://www.agriculturejournals.cz/publicFiles/22721.pdf

 

[CLASH]

@Travis
Thanks for your replies, knowledge and time.

A few queries on your list of "ideal "foods for lack of a better term (im not intending to argue with you, actually im interested in your opinion more than anything):

1) tubers: from what I understand most tubers with the exception of some white potatoes contain a decent amount of amylose starch. In my experience and the experience of quite a few people around me, amylose starch seems to induce bloating, gas, and some psychological issues like brain fog (it could be fodmaps in the tubers as well). Meanwhile amylopectin from certain varieties of white rice seems to cause no issues at all.

2) coconut: many people that I know seem to have issues with coconut pulp, some even coconut oil, and others even hydrogenated from quality sources

3) fruit: besides most fruit in some parts of the world being poorly produced, in my experience and others that im close with, fruit also induces digestive issues, makes the body cold compared to sucrose and honey and far too much has to be eaten to meet caloric needs based on quantity (and cost but the argument is secondary to this context).

4)leaves: many leaves contain metabolic inhibiting compounds, specifically the brassica family, which is most common contains goitrogens. The other major group including Spinach, chard etc contains exceedingly high levels of oxalate

What do you think about the above in lieu of the other contextual pieces in place (polyamines, linoleic acid, immunogenic proteins, tryptophan etc)? Many i know seem to well on a diet of beef, white rice, butter/tallow/coconut oil/ olive oil and spinach with some fruit juice periodically (i.e. Basic bodybuilding stuff).

 

[Travis]

@Travis How much chocolate do you think is reasonable amount to eat solely for health benefits, do you favour the high cocoa types?

Edit: I think I answered my own question here about milk vs dark chocolate. They both seem pretty good, not too different stearic acid amounts, I was expecting a lot less from milk chocolate in comparison, as all the stearic acid I believed was in the cocoa butter. Still unsure how much would be a good amount to eat daily though.

http://www.agriculturejournals.cz/publicFiles/22721.pdf

Since many people take issue with refined sugar, a person could perhaps head to the baking aisle where 100% chocolate is sold. Also found in in the baking aisle are dates, which can be stuffed with chocolate or dipped in it (a double water contraption on the stove‐top works good for melting chocolate.)

Chocolate‐eating seems unhealthy, but probably only because it is associated with candy. But I don't think anyone who's tried 100% chocolate would consider it candy, in any sense of the word. Pure chocolate is bitter, so bitter that I find it difficult to eat very much of it.

But the evidence is unanimous: Stearic acid occupies a niche on the cell membrane, reducing prostaglandin potential by displacing linoleic and arachidonic while reducing fluidity. It could perhaps be argued that 'fluidity' is associated with cancer because fluidity is caused by arachidonic and linoleic acids, but you'd think EPA and DHA would reduce fluidity to the same extent—perhaps making stearic acid's ability to displace arachidonic acid seem the primary mechanism.

One of those articles above has citations for 'membrane rigidity' articles. This is an interesting concept that might be fun to read about. I think I remember Ray Peat talking about this.. .

'Another argument is that "membrane fluidity" is a good thing, and that unsaturated essential fatty acids make the membranes more fluid and thus better--by analogy with their lower bulk-phase melting temperature. (But the measure of fluidity is a very limited thing on the molecular level, and this fluidity may be associated with decreased cellular function, instead of the postulated increase.)' ―Peat​

Peat, Ray. "Membranes, plasma membranes, and surfaces." raypeat.com (2009)
​

So this membrane fluidity idea seems a bit esoteric ―Which is good! because that means its interesting and exciting to read about.

Cooper, Richard A. "Abnormalities of cell-membrane fluidity in the pathogenesis of disease." New England Journal of Medicine (1977)
​

And it appears that cholesterol stiffens membranes. Also interesting is that fluidity does change through the cell cycle but he doesn't say why. Perhaps desaturase enzymes are involved in the cell cycle? upregualted in response to certain signals?

Macrophages engulf foreign particles in the body, a process dependent on the rigidity of the macrophage. For this to occur membrane fluidity must be kept in range; not too stiff and not too fluid.

As of 1977 there'd been interesting observations regarding membrane fluidity, but exactly how this effects steroid transfer and membrane receptor function had remained theoretical. You would think that a more fluid membrane would increase steroid flux, allowing more lipids to pass into the cell. He did mention that enzymes of the membrane were influenced by fluidity, yet had said nothing about phospholipase A₂. I think it would be interesting to know if membrane fluidity increases the catalytic rate of this enzyme, since this would lead to more prostaglandins.

Herb Doctors: The Metabolism Of Cancernew

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Herb Doctors: You Are What You Eat 2

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Politics & Science: Biochemical Health

It look like the herb doc is on the same page.

Does the cronometer compile the amino acid ratio? I think perhaps a computer programmer should make a spin‐off which also shows you the Fernstrom ratio and the 'membrane fluidity index'—essential values for the Peatarian.

Thank you for the response. If I could attempt to sum it up, you seem very oriented towards fatty acid profiles, immunologic ingredients and their stimulation of histamine, and different amino acids and their neurotransmitters.

How do you think lamb compares to Beef? Lamb usually has a higher zinc content which I think can be valuable, although I am not sure how its stearic acid content measures up. Do you buy into the stressed state vs relaxed state that Ray talks about? Thanks man!

Yes. I think immunogenic proteins are important, and I think they're easier to understand when considering histamine. I would sometimes eat food that others had left around when I'd been out, or the day before I would go shopping, and I could never understand why oats had made me feel like they had. I had read many articles on exorphins and oats have none, absolutely no opiate function as tested by protein hydrolysates on mice nerves; basically only spinach, wheat, and dairy have exorphins.

Once I started reading about histamine I knew I was on to something. This is a real neurotransmitter produced in the brain by the tuberomammillary nucleus, similar in scope of the serotonergic system yet rarely talked about. Mast cells have been shown to migrate to the brain where they can produce up to 90% of total brain histamine (in rats). This is some serious histaminergic crosstalk, so anything which induces mast cells could potentially affect psychology.

Schizophrenics had been shown to have 2.6× the brain histamine as controls. ​

So I used to imagine that all the psychological effects from eating wheat were due to the exorphins with δ-opioid activity, but now I think it has more to do with histamine from mast cells.

And prostaglandins are strongly hormonal, acting on DNA through the PPAR receptor/transcription factors in the cell nucleus. Prostaglandins also have G protein‐coupled receptors on the cell membrane, where they act to control Ca²⁺ and constrict/relax the blood vessels. But unlike steroid hormones, these powerful lipid hormones can be greatly controlled through diet. As you can see from above, a linoleic acid‐deficient infant had less arachidonic acid and produced only a fraction of urinary prostaglandin E₂.

Prostaglandin D₂ causes hair loss, another reason to avoid linoleic acid. ​

The 3‐series prostaglandins can be made from eicosapentaenoic acid (EPA) and could be the main prostaglandins in linoleic acid‐deficient people. These prostaglandins have less biological activity and are not nearly as effective at inducing cancer in vitro.

@Travis
Thanks for your replies, knowledge and time.

A few queries on your list of "ideal "foods for lack of a better term (im not intending to argue with you, actually im interested in your opinion more than anything):

1) tubers: from what I understand most tubers with the exception of some white potatoes contain a decent amount of amylose starch. In my experience and the experience of quite a few people around me, amylose starch seems to induce bloating, gas, and some psychological issues like brain fog (it could be fodmaps in the tubers as well). Meanwhile amylopectin from certain varieties of white rice seems to cause no issues at all.

2) coconut: many people that I know seem to have issues with coconut pulp, some even coconut oil, and others even hydrogenated from quality sources

3) fruit: besides most fruit in some parts of the world being poorly produced, in my experience and others that im close with, fruit also induces digestive issues, makes the body cold compared to sucrose and honey and far too much has to be eaten to meet caloric needs based on quantity (and cost but the argument is secondary to this context).

4)leaves: many leaves contain metabolic inhibiting compounds, specifically the brassica family, which is most common contains goitrogens. The other major group including Spinach, chard etc contains exceedingly high levels of oxalate

What do you think about the above in lieu of the other contextual pieces in place (polyamines, linoleic acid, immunogenic proteins, tryptophan etc)? Many i know seem to well on a diet of beef, white rice, butter/tallow/coconut oil/ olive oil and spinach with some fruit juice periodically (i.e. Basic bodybuilding stuff).

The difference between amylopectin and amylose lies in the branching of the glucose chains. I can see this having an effect on absorption rate and the pancreatic hormones.

Fruit has glucose. I had read a study where sucrose was metabolized quicker than either fructose of glucose alone, perhaps implying that we have a separate enzymatic system for each one. The fruits that I remember looking at were about 70/30 – 50/50 fructose to glucose. Since the study I had read indicated a 1:1 ratio metabolizing the quickest, this is the ratio that I think is best. Starch represents all glucose and I don't really eat it; the only significant amount of carbohydrates I normally eat comes from fruit.

Fruit is also the most natural primate food, and appears beyond criticism for me. I can't see how it could cause a problem that would be more easily caused by something else.

Oxalate is produced in the body during the citric acid cycle, and there's no reason to fear it. But as a dicarboxylic acid it can chelate calcium. The body has a similar way to bind calcium to proteins by carboxylating glutamate, forming the Ca²⁺‐chelating dicarboxylic amino acid called γ-carboxyglutamate. Vitamin K is a necessary cofactor to produce this nonconventional amino acid, or post-translational modification (depending on how you want to look at it.) In a similar way, the tricarboxylic acid citrate strongly chelates the trivalent aluminum ion (Al³⁺). [as seen here] So eating calcium oxalate is safe and simply means less Ca²⁺ bioavailability. It has been demonstrated that spinach calcium is less absorbable than kale, yet still significant (~30%). On to kale: it does have certain gylcosides that release the thiocyanate ion (S–C≡N⁻) after ingestion, a molecule which has about the same affinity for the thyroid than has iodide (I⁻). Perchlorate binds the thyroid I⁻ domains much more strongly, but the thiocyanate ion can catalyze goitre. However, everyone has the thiocyanate ion in their bodies to some degree; smokers have more of this but everyone has some. So the induction of goitre depends on the thiocyanate:iodide ratio. Goitre only happens in iodine-deficient regions, the thiocyanates reducing I⁻ uptake and enhancing its elimination. This will not be as strongly-induced by normal kale since it's been bred to have reduced amounts. Cassava and purple-stem Russian kale have the most, but the amount in broccoli is barely significant. I'm not sure if thiocyanate ion has other effects.

I think the people you know eating beef/rice/spinach are certainly avoiding the worst foods.

 

[Mito]

The shorter chained fatty acids myristic and palmitic are oxidized for energy much quicker and don't persist to the extent in which stearic acid does,

Do you think methyl palmitate and methyl myristate would be able to displace arachidonic acid and linoleic acid from the cell membrane similar to stearic acid since apparently methyl palmitate and methyl myristste are more resistant to metabolism?

 

[Travis]

Do you think methyl palmitate and methyl myristate would be able to displace arachidonic acid and linoleic acid from the cell membrane similar to stearic acid since apparently methyl palmitate and methyl myristste are more resistant to metabolism?

The chart I had looked at did have 16:0 in the membrane, as well as the undifferentiated category <14:0. So these are membrane lipids, but they have not been consistently associated with a reduced risk in cancer as has stearic acid—despite being a greater constituent of most diets.

A certain degree of oleate on the lipid membrane could have initially come from stearate, through Δ⁹‐desaturase. ​

The methyl groups you speak of . . . are they on an oxygen or a carbon? Are these methyl esters or branched alkanes?

 

[Mito]

The chart I had looked at did have 16:0 in the membrane, as well as the undifferentiated category <14:0. So these are membrane lipids, but they have not been consistently associated with a reduced risk in cancer as has stearic acid—despite being a greater constituent of most diets.

A certain degree of oleate on the lipid membrane could have initially come from stearate, through Δ⁹‐desaturase. ​

The methyl groups you speak of . . . are they on the oxygen? Are these methyl esters or branched alkanes?

methyl esters Methyl palmitate 1431603

Metabolism of topically applied fatty acid methyl esters in BALB/C mouse epidermis. - PubMed - NCBI

 

[Mito]

Oxalate is produced in the body during the citric acid cycle, and there's no reason to fear it.

What about calcium oxalate kidney stones? And oxalates in the urine are much higher in individuals with autism than in normal children (Figure 1)?

OXALATES CONTROL IS A MAJOR NEW FACTOR IN AUTISM THERAPY