The Travis Corner

[Koveras]

I was thinking just as a one‐time experiment. I would like to match each neurotransmitter to the thought processes, feelings, and idiosyncracies which characterize them; dopamine, histamine, and serotonin are neurotransmitters that I'd like to get a feel for.

Yesterday, I think the serotonin from the massive amounts of chicken eggs had become melatonin—basicially methylated and acetylated serotonin—despite having been in a well‐lit environment. [Now, I do know exactly what melatonin feels like since I have it in the cabinet, and had taken it twice.] It's rather clownish; I had found myself watching music videos on YouTube from the '80s, but actually enjoying them! [⁉]

I usually hate '80s music, but for some reason David Bowie's Let's Dance, Queen's Under Pressure, and even the Talking Heads' Burning Down the House seemed like good things to watch. But thankfully, I'm feeling much better now.

[And also thankful that it wasn't bad enough to watch this.]

Maybe you do know what serotonin feels like

Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content

"Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. "

 

[Koveras]

But it would be interesting to know what the most specific inhibitor of this enzyme is, perhaps for people in the process of weaning themselves off of immunogenic peptides which are also somewhat addictive.

Eur J Med Chem. 2018 Jan 1;143:1858-1868. doi: 10.1016/j.ejmech.2017.10.078. Epub 2017 Nov 11.
Synthesis and biological evaluation of new berberine derivatives as cancer immunotherapy agents through targeting IDO1.
Wang YX1, Pang WQ1, Zeng QX1, Deng ZS2, Fan TY1, Jiang JD1, Deng HB3, Song DQ4.

To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71-90% compared with BBR. Their effects on IDO1 expression were further confirmed by protein level as well. Furthermore, compounds 2i and 2n exhibited anticancer activity by enhancing the specific lysis of NK cells to A549 through IDO1, but not cytotoxicity. Preliminary mechanism revealed that both of them inhibited IFN-γ-induced IDO1 expression through activating AMPK and subsequent inhibition of STAT1 phosphorylation. Therefore, compounds 2i and 2n have been selected as IDO1 modulators for small-molecule cancer immunotherapy for next investigation.

 

[Diokine]

what does serotonin feel like

​

I really hate it when my mountains get all stretchy :/ much more of a challenge to climb

 

[Wagner83]

@Travis you have said a few times that corn could much safer than most of the other grains (lowered tryptophan/serotonin etc..), what are your thoughts on the necessity or use of nixtamalization? Generally speaking do you have any opinion on the importance of the calcium/phosphate ratio in the diet?

 

[Travis]

I have measured all three (not the same day but within 6 months) but the results seem somewhat contradictory. 5-HIAA was very low and serotonin in urine was low (slightly below low end of reference range) so they match pretty well. But whole blood serotonin was close to the top of the reference range.

Well that's enigmatic. Perhaps you have especially powerful platelets: capable of binding more serotonin, or serotonin more strongly?

But I'd go with Fernstrom, personally, over urinary values. I think plasma tryptophan/Σ·CAA could have more to with brain serotonin at the present moment than any other measurement. Fernstom's graphs were particulary convincing.

Eur J Med Chem. 2018 Jan 1;143:1858-1868. doi: 10.1016/j.ejmech.2017.10.078. Epub 2017 Nov 11.

Synthesis and biological evaluation of new berberine derivatives as cancer immunotherapy agents through targeting IDO1.
Wang YX1, Pang WQ1, Zeng QX1, Deng ZS2, Fan TY1, Jiang JD1, Deng HB3, Song DQ4.

To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71-90% compared with BBR. Their effects on IDO1 expression were further confirmed by protein level as well. Furthermore, compounds 2i and 2n exhibited anticancer activity by enhancing the specific lysis of NK cells to A549 through IDO1, but not cytotoxicity. Preliminary mechanism revealed that both of them inhibited IFN-γ-induced IDO1 expression through activating AMPK and subsequent inhibition of STAT1 phosphorylation. Therefore, compounds 2i and 2n have been selected as IDO1 modulators for small-molecule cancer immunotherapy for next investigation.

View attachment 7763 View attachment 7764 View attachment 7765 View attachment 7766 View attachment 7767 View attachment 7768 View attachment 7769 View attachment 7770 View attachment 7771 View attachment 7772

Watch out: compound JTH looks like it could be a microtubule depolymerizer. Nearly all the microtubule inhibitors—including the classic one: colchicine—are planar ring structures characterized by multiple methoxy groups.

Serotonin in the microgram range could be bioactive, although monoamine oxidase purportedly deaminates this. But since I can feel just 1·mg melatonin + x·μg serotonin, I'm starting to wonder. Does the acetyl group of melatonin protect it from monoamine oxidase?

How much melatonin had resulted in those figures for serotonin, as adulterant?

@Travis you have said a few times that corn could much safer than most of the other grains (lowered tryptophan/serotonin etc..), what are your thoughts on the necessity or use of nixtamalization? Generally speaking do you have any opinion on the importance of the calcium/phosphate ratio in the diet?

The process of nixtamalization has actually been shown to partially equalize the amino acid imbalance in corn. Boiling corn in water and calcium hydroxide (or carbonate) makes some proteins less‐soluble, in which they then precipitate to the bottom of the pot. Leucine, considered a factor in pellagra, has shown the greatest reductions relative to other amino acids (~21%). Leucine is also the amino acid found in excess in corn and sorghum—also shown to initiate pellagra. Feeding straight leucine to rats results in an increased excretion of N¹‐methylniacin, perhaps by activating the mTOR pathway, and has also been shown to shift the kyneurine pathways more towards picolinate—at the expense of de novo niacin biosynthesis. The amino acid leucine is unique for being capable of more‐or‐less direct incorporation into the steroid skeleton; if you look at its structure, it's easy to see it nearly as a carboxylated isoprene.

The idea that nixtamalization liberates niacin is a tough sell, since any liberated niacin would of course lost in the water. While true that much niacin is corn is bound to an indigestible polysaccharide (cellulose‐like), this is certainly not unique to corn. All of the rat feeding studies showing increased plasma niacin levels after feeding corn which had been nixtamalized, compared to that which hadn't, could have simply been measuring the effects of ~21% lowered leucine. Thus: the assumed increase in bioavailabilty in such studies could simply be a faiure to understand the mTOR pathway, or actually discovering it without realizing it. The liver has a very specific leucine‐binding protein: a sensor for dietary leucine intake which causes a shift towards cholesterol biosynthesis, ostensibly to make efficient use of excessive dietary leucine by synthesizing cholesterol. I think perhaps the shift in the kyneurenine pathway resulting from excessive leucine could be seen as the body attempting to increase zinc absorption—by synthesizing picolinate—in anticipation of more cholesterol. Either that, or you probably have to assume the body simply malfunctions as a result of excessive leucine—something harder to imagine when realizing that the body has it's own sensor for dealing with this essential amino acid.

 

[Travis]

​

I really hate it when my mountains get all stretchy :/ much more of a challenge to climb

That bottom image reminded me of the band Meat Puppets. Their second album has a song called Plateau, and another song called Climb. Kurt Cobain had liked this album, and Nirvana had covered three songs off that album during their famous MTV Unplugged in New York album (see aforelinked hyperlink).

I had eaten mushrooms a few years ago, and had imagined many geometrical shapes. Upon closing the eyes, mental images reminiscent of Aztek art—or those blankets sold in Tijuana—were observed. Psilicybin is of course an indole, and has two N‐methyl groups (perhaps responsible for the changes in gait noted.)



There is a good study correlating psychedelic potency with serotonin receptor binding affinity, but also convincing data showing that it corresponds with the highest occupied molecular orbital [Acronym removed by editor. Reason: exceeds PG rating] Lysergic acid N‐dimethyl has a peculair affinity for the serotonin receptor yet also an unusually high molecular orbital energy. I'm not sure exactly what to think (actually, I know exactly what to think). Perhaps the seronotin receptor binding capacity is necessary to open the G protein‐coupled receptors (perhaps allowing fluorescence to bridge the gap from one receptor to another, similar to how the protein connexin makes a link between corresponding microtubules of hard‐wired neurons) and the higher molecular orbital necessary to shift the frequency of light emitted?

I think our eyes had historically funneled light through the optic nerve into the brain, and this light is basically consciousness itself. Only later, by using heme, our bodies have found a ways to create light chemically so we can think in the dark. Bio‐chemiluminescence is a well‐known phenomenon, and ultra‐weak fluorescence has been observed emanating from living cells for over a century.

Observing the structure of microtubules usually leads to the conclusion they'd been designed for this very purpose. You are almost forced into thinking their interiors transmit light after the realization that nothing else can explain the 100·m/s nerve conduction velocity. I refuse to believe an 'ionic wave' could possible travel so far along the outside of myelinated microtubules (i.e. what are nerves). All other explanations fail.

And the canonical explanations for photoreception are frankly absurd. I just found one on Wikipedia.org:

• A light photon interacts with the retinal in a photoreceptor cell. The retinal undergoes isomerisation, changing from the 11-cis to all-transconfiguration [The cis–trans isomerization of retinol could simply represent a 'shade,' or a way to block excessive light. This is the impression I had got from George Wald's pioneering articles.]
• Retinal no longer fits into the opsin binding site.
• Opsin therefore undergoes a conformational change to metarhodopsin II. [The term 'confomational change' is a lazy an vague way to explain a chemical mechanism. When encountering something they cannot explain, lazy chemists just mumble lazy and invoke the 'confomational change'.]
• Metarhodopsin II is unstable and splits, yielding opsin and all-trans retinal. [They think retinal is dissociated every time a photon hits it. I think you could show by counting both photons and retinal that we then should then have no bound retinal. Moreover: free retinal has a reactive aldyhyde group, leading to the more‐than‐remote possibility of spontaneous dimers and random protein adducts.]
• The opsin activates the regulatory protein transducin. This causes transducin to dissociate from its bound GDP, and bind GTP, then the alpha subunit of transducin dissociates from the beta and gamma subunits, with the GTP still bound to the alpha subunit. [Guansine triphosphate is in this ridiculous Rube Goldberg series of event because its associated with microtubules. Guansine triphosphate greatly increases polymerization rates in vitro, and nothing else really comes close. The enzyme GTPase is probably the same microtubule constituent shown to do this in the lengthening polymer.]
• The alpha subunit-GTP complex activates phosphodiesterase or PDE.
• PDE breaks down cGMP to 5'-GMP. This lowers the concentration of cGMP and therefore the sodium channels close. [Exactly why sodium chloride makes people see white spots.]
• Closure of the sodium channels causes hyperpolarization of the cell due to the ongoing efflux of potassium ions.
• Hyperpolarization of the cell causes voltage-gated calcium channels to close.
• As the calcium level in the photoreceptor cell drops, the amount of the neurotransmitter glutamate that is released by the cell also drops. This is because calcium is required for the glutamate-containing vesicles to fuse with cell membrane and release their contents. [Exactly why MSG is hallucinogenic.]
• A decrease in the amount of glutamate released by the photoreceptors causes depolarization of On center bipolar cells (rod and cone On bipolar cells) and hyperpolarization of cone off-center bipolar cells. [They still don't explain how the signal is transmitted so quickly. Their explanation has both binary signals and analogue symbols (glutamate), ostensibly only because there were terrible biologists both in the '70s and the '80s which had contributed to this (by killing trees, and then writing bad ideas on them). Any chemical phototransduction cascade of similar mechanics as written above would lead to a very low-fidelity, and slow signal. The above mechanism is absurd.]

 

[Travis]

Rotenoids have been shown to downregulate ornithine decarboxylase, which of course inhibits cancer.

Gerhäuser, Clarissa. "Rotenoids mediate potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase." Nature medicine (1995)​

But they weren't able to detect an inhibition of either cycooxygenase or phase II enzymes like NADH:quinone oxidoreductase. So how does this drug do it? what do the rotenoids act on?

There are two methoxy groups on the planar rotenone ring, leading one to suspect that it's a microtubule inhibitor.

click to embiggen​

And rotenone it is, in fact, a microtubule inhibitor. This is easy to confirm, as there has been plenty of studies verifying this; below is one:

Marshall, Laura E. "Rotenone inhibition of tubulin self-assembly." Biochimica et Biophysica Acta (BBA)-General Subjects (1978)​

Microtubules can be polymerized (grown) in vitro using only their monomer proteins—α- and β-tubulin—and guanisine triphosphate. A chelator like EDTA is always used because calcium has a peculiar ability to inhibit this growth process. Polymerization is usually detected spectrophotometrically, by either light absorption or scattering.

click to embiggen​

The fact that rotenone has two methoxy groups was not lost by this researcher—though he doesn't stress it:

'...suggesting that rotenone and colchicine bind to the same or to structurally close sites on the tubulin dimer. Structurally the two drugs do not have much in common except perhaps the methoxy-substituted benzene ring. [¶] Rotenone, a potent anti-tubulin agent, inhibits microtubule formation by binding to tubulin in a reversible fashion.' ―Marshall​

In the beginning of the article, the author lists a few microtubule inhibitors.

'In recent years a number of compounds have been shown to act as inhibitors of tubulin self-assembly. In addition to the well known vinca alkaloids and colchicine the list now includes methyl-benzimidazolyl carbamates [1], griseofulvin [2], maytansine [3], barbituates [4], psychotropic drugs [5] and rotenone [6--8]. Some of the compounds may bind to the same sites as vincristine [9] and colchicine [1].' ―Marshall​

He lists a few general classes such the 'barbituates' and 'pscyhotropic drugs,' but only the barbituates represent a class which can be chemically characterized; the 'vinca alkaloids' are essentially synonymous with 'vincristine,' which is also on the list. With this redundancy removed—as with the vague, unspecific class 'psychotropic drugs'—six out of these seven drugs have methoxy groups on the planar ring. The most powerful microtubule inhibitors have multiple methoxy groups. [depicted in the order mentioned]

The only exception are barbituates, which have no methoxy groups. The quote above is in line with my previous observation that an alarming majority of microtubule inhibitors have methoxy groups on a planar ring.

One other one not mentioned is methoxyestradiol, which has been shown to inhibit microtubule formation. Estrogen is the only steroid capable of doing this since it's the only steroid with a planar (aromatic) ring. The enzyme aromatase makes it planar, and the O‐methyl group—perhaps not surprisingly—is donated by SAM through the enzyme catechol‐O‐methyltransferase; estradiol is indeed a catechol, making this an intuitive—and tautological—reaction.

D'Amato, Robert J. "2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site." Proceedings of the National Academy of Sciences (1994)​

So if >90% of micrtobule inhibitors have methoxy groups, the what does this say about melatonin? You might think, at night, that microtubules would grow as a reparative process. But perhaps not so, as growing microtubules could represent memory consolidation. Would it really make sense to form strong memories of dreams?

Huerto‐Delgadillo, Lourdes. "Effects of melatonin on microtubule assembly depend on hormone concentration: role of melatonin as a calmodulin antagonist." Journal of pineal research (1994)​

Melatonin does appear to be a microtubule disruptor in nanomole concentrations:

'Reaction mixtures were pre-incubated 1 min at 30°C, and after the pre-incubation period, polymerization was started by the addition of GTP to a final concentration of 1 mM. Turbidity changes were monitored every 2 min and up to 30 min after GTP addition. The change in turbidity was assessed at 350 nm (Beckman DU-7 Spectrophotometer with 1 cm path length cells). Polymerization rates were calculated from the slopes of the kinetic curves, and microtubule formation was estimated by the optical density registered at equilibrium.' ―Huerto‐Delgadillo​

'In the absence of Ca²⁺, GTP addition was followed by tubulin polymerization that progressed steadily after a 2 min lag and reached equilibrium 18 min later. Calculated polymerization rate was 0.016 OD/min.' ―Huerto‐Delgadillo​

'The distinct melatonin effects on tubulin polymerization at nanomolar and micromolar concentrations were also observed when the same melatonin concentrations were studied in cytoskeletons in situ.' ―Huerto‐Delgadillo​

​

'In the absence of Ca²⁺, 10⁻⁵ M melatonin disrupts the fine microtubule network observed in control conditions.' ―Huerto‐Delgadillo​

'Secondly, melatonin administration at micromolar concentrations is followed by functional changes consistent with microtubule disruption, i.e., melatonin arrests granule movement in B6 melanoma cells [Funan 19661; inhibits microtubule reassembly in sciatic nerve of toad [Piezzi and Cavicchia, 198 11, reduces melanin granule dispersion in various fish species [Reed et al., 19691, inhibits rapid axonal flow in the rat hypothalamus [Cardinali and Freire, 19751, disrupts the mitotic apparatus in onion root tips [Banerjee and Margulis, 19731, and delays oral band regeneration in Stentor coeruleus [Banerjee et al., 19721].' ―Huerto‐Delgadillo
​

I don't think we should underestimate melatonin. One could argue that excessive serotonin would lead to excessive melatonin, microtubule inhibition, and less efficient memory formation.

 

[Such_Saturation]

The rat experiments measure‐whole brain serotonin after they're Lennied, so there is no ambiguity there.

Funny that you mention, serotonin was depleted in frozen homogenized rat brain after MDMA

http://www.maps.org/images/pdf/1996_chu_1.pdf

 

[Nighteyes]

Your diet (based on your posted screen shots from cronometer) seems really on point theoretically. I think a healthy body would get all it needs from those foods. I do wonder if it wouldn't be beneficial to add a safe source of clean protein and B12, something like scallops maybe. This might mitigate need for occational B12 supplementation. Do you never have cravings for warm proteiny foods? I know I do no.. matter what my diet looks like and I think scallops might do the job.

But the coconut stuffed dates are a neat idea and you are right, they do taste like cup cakes! Like a tiny dessert that is available all day long - brilliant.

How do you tell if a coconut is at it's prime? I seem to either get really hard ones (the flesh) or moldy/mushy ones.

 

[Amazoniac]

I do wonder if it wouldn't be beneficial to add a safe source of clean protein and B12, something like scallops maybe.

What if Travisord's amino acids experiments are his unconscious petting his reason with an excuse to increase a bit protein consumption?

 

[Travis]

Your diet (based on your posted screen shots from cronometer) seems really on point theoretically. I think a healthy body would get all it needs from those foods. I do wonder if it wouldn't be beneficial to add a safe source of clean protein and B12, something like scallops maybe. This might mitigate need for occational B12 supplementation. Do you never have cravings for warm proteiny foods? I know I do no.. matter what my diet looks like and I think scallops might do the job.

But the coconut stuffed dates are a neat idea and you are right, they do taste like cup cakes! Like a tiny dessert that is available all day long - brilliant.

How do you tell if a coconut is at it's prime? I seem to either get really hard ones (the flesh) or moldy/mushy ones.

The last five coconuts I bought were *λ*τ, which really makes me angry. Good thing that I have extra dates, coffee, oranges, and spinach to make up for the difference or I'd be even more upset. Looks like this week will be essentially fat free, with the highest amount of fatty acids coming from spinach.

I do wonder if it wouldn't be beneficial to add a safe source of clean protein and B12, something like scallops maybe.

Around Jews, never use the word 'clean' and 'scallops' in the same sentence. Kosher laws forbid such things, perhaps because of the paralytic toxins contained therein.⁽¹⁾ Although historical dietary laws should necessarily be considered logical, the Kosher laws do appear to have some logic to them. They do focus on the low linoleic acid ruminants, as well as forbid the Trichinella infested pig. Besides that infamous muscle‐bound parasite, the pork tapeworm is far more dangerous than the beef tapeworm. The reason for this is that the digestive tract of the pig is similar to the human, allowing the life cycle of the tapeworm from this animal to superimpose itself onto the digestive idiosyncrasies of the human in such a way as to permit more serious infection. Although the beef tapeworm is infectious, it will not enter the brain.⁽²⁾

'However, the scallop retained a fairly high level of toxin even after three months. The maximum toxicity level of oyster was lower than that of scallop and mussel. The toxin compositions of oyster, scallop and mussel were analyzed by means of high-performance liquid chromatography. The toxin compositions were different among the species.' ―Takata​

I find the sum total of amino acids from everything I eat to be sufficient for protein turnover as well as supplying a minimum of tryptophan. I think this would lead to a lower steady‐state serotonin concentration, which would lower growth hormone. In the pituitary, dopamine suppresses prolactin and serotonin releases growth hormone. It is likely for this reason that tryptophan is the second most lifespan‐decreasing amino acid behind methionine, shown to increase cancer incidence and lower the lifespan of rats by ~12% (on average). Even worse than tryptophan is methionine, which generally exists in a lower ratio in vegan foods.⁽³⁾

I don't think that cravings, however strong, can be said to represent inherent bodily wisdom. I've craved some seriously terrible foods in the past. I find wheat—perhaps the world's most terrible food—especially addictive.

[1] Takata, K. "Differences in accumulation and elimination of paralytic shellfish toxins among oyster [Crassostrea gigas], scallop [Patinopecten yessoensis] and mussel [Mytilus edulis]." Bulletin of the Japanese Society of Scientific Fisheries (Japan) (2004).
[3] Despomier, Dickson. "TWIP podcasts." The World Wide Web (2010)
[2] McCarty, Mark F. "The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy." Medical hypotheses (2009)​

 

[DaveFoster]

Kosher laws forbid such things, perhaps because of the paralytic toxins contained therein.⁽¹⁾ Although historical dietary laws should necessarily be considered logical, the Kosher laws do appear to have some logic to them. They do focus on the low linoleic acid ruminants, as well as forbid the Trichinella infested pig.

But you do forget their allowances for the use of oils as foodstuffs:

"OILS (Heb. יִצְהָר ;שֶׁמֶן, "new oil"; תַּמְרוּק, מֶרְקָחָה, "ointment"), unctuous, inflammable substances, usually liquid, obtained from animal, vegetable, or mineral matter. In Job 29:6 and Deuteronomy 32:13, the references to oil flowing from rocks are hyperboles for fertility or prosperity.

Regarded as one of the characteristic products of the Land of Israel (II Kings 18:32; Jer. 40:10), oil served as an element in food (I Kings 17:12), as a cosmetic (Eccles. 9:7–8), as a fuel for lamps (Ex. 25:6), as a medicine (Isa. 1:6), and as a principal export in foreign trade (I Kings 5:25). As oil was apparently applied to leather shields to keep them supple, the expression "to oil a shield" (mashaḥ magen) came to be an idiom for "to make war" (Isa. 21:5). As an extension of its use in the preparation of food, oil occupied a place in sacrifices. As an extension of its cosmetic function, it played a role in various investiture proceedings."

 

[Amazoniac]

Dairy opioids:
A1 Vs A2 Milk - Is The Devil Really In The Milk?

Homocysteine and pyridoxine:
I think gilson would benefit a lot from your posts. His case was interesting though. You often mention pyridoxine being important in normalizing homocysteine levels yet he had both elevated in blood. burtlan trained the forum that perhaps it was a case of leakage, similar to the magnesium discussion at the buttzord thread.
Vitamin B6 Very High!
Homocysteine Never Goes Down

Coffee and choline:
"I Have Liver Issues And I Am Not Making Progress"
Choline
It's very difficult to get enough choline without eggs. You can get away with a mild choline insufficiency if you consume coffee but I never understood why. And I'm not even sure if it actually enhances the internal synthesis of choline or the protective actions come by other means.
On a side note the immediate mental clarity that it gives is impressive but I could never deal with the consequences that appear for me on the following days. 1-3 days of extreme anxiety from just a modest.. shot.

gbolduev:
I realized that he has a corner as well, so it's official: I'm a plagiarist. But I think it was more a case of impregnation. Zeus has a "It's official" thread series, I would say my case is doublebad, but after this one I have to say it's doubleplusbad.

 

[Travis]

It's very difficult to get enough choline without eggs.

Tell me then, where do most animals get choline? How does, say a deer or squirrel, exactly 'get enough choline' without eating eggs?

In the rat, it can be biosynthesized by serine!

'When [¹⁴C]serine was injected into intact rats, radioactive aminoethanol as well as radioactive choline labeled in both the hydroxyethyl‐ and in the methyl groups, were isolated. Turnover and specific activity studies showed that phosphoaminoethanol and cytidinediphosphoaminoethanol are unlikely intermediates in the formation of phospholipid aminoethanol from serine.' ―Bremer​

And what perhaps could be important in cancer proliferation and hyperhomocyseinemia, choline is biosynthesized by methionine‼

'When [¹⁴C]methionine was given, radioactive mono‐ and dimethylaminoethanol, as well as radioactive choline, were isolated from the liver phospholipids. The mono‐ and dimethylaminoethanol had much higher turnover rates than had the choline.' ―Bremer​

So perhaps the ingestion of choline could spare methionine, subsequent polyamines, and damaging homocysteine—as it's deftly converted into choline!

'On the basis of these results it is concluded that phosphatidylserine is decarboxylated to phosphatidylaminoethanol and that the latter compound is methylated to form lecithin. In this reaction all the methyl groups of choline are incorporated by transmethylation from S-adenosylmethionine.' ―Bremer​

Nicotine acts as a proxy for acetylcholine, perhaps sparing it a bit (although the choline formed through the disociation of acetylcholine is thought to be recycled.) Since choline is necessary for this neurotransmitter, I would consider it essential. However, anyone ingesting eggs does have to overcome the ~15–20% linoleic acid yolk content (as a fraction of total fatty acids.)

I think we're going to have to post a recipe for the coconut and goat cheese omelet, to provide enough stearic acid to counter the linoleic acid—as well as lowering the Fernstrom ratio (egg white albumin is high in tryptophan, second only to whey lactalbumin.)

Bremer, Jon. "The biosynthesis of choline and its relation to phospholipid metabolism." Biochimica et Biophysica Acta (1960)​

 

[Amazoniac]

Really? Tell me then, where do most animals get choline? How does, say a deer or squirrel, exactly 'get enough choline' without eating eggs?

In the rat, it can be biosynthesized by serine:

'When [¹⁴C]serine was injected into intact rats, radioactive aminoethanol as well as radioactive choline labeled in both the hydroxyethyl‐ and in the methyl groups, were isolated. Turnover and specific activity studies showed that phosphoaminoethanol and cytidinediphosphoaminoethanol are unlikely intermediates in the formation of phospholipid aminoethanol from serine.' ―Bremer​

And what perhaps could be important in cancer proliferation and hyperhomocyseinemia, choline is biosynthesized by methionine:

'When [¹⁴C]methionine was given, radioactive mono‐ and dimethylaminoethanol, as well as radioactive choline, were isolated from the liver phospholipids. The mono‐ and dimethylaminoethanol had much higher turnover rates than had the choline.' ―Bremer​

The ingestion of choline could spare methionine, subsequent polyamines, and damaging homocysteine.

'On the basis of these results it is concluded that phosphatidylserine is decarboxylated to phosphatidylaminoethanol and that the latter compound is methylated to form lecithin. In this reaction all the methyl groups of choline are incorporated by transmethylation from S-adenosylmethionine.' ―Bremer​

Nicotine acts as a proxy for acetylcholine, perhaps sparing it a bit (although the choline formed through the disociation of acetylcholine is thought to be recycled.)

Bremer, Jon. "The biosynthesis of choline and its relation to phospholipid metabolism." Biochimica et Biophysica Acta (1960)​

The rats still develop liver problems on the typical methionine-choline deficient diet. So you believe that our needs aren't that high, correct? Eggs are more than choline but why would eggs be featured often on this list if more of it wasn't beneficial? It should be one of the main reasons why people consume it.
Long-lived Compilation Facts
The reason why I link it a lot of times is that it should be viewed as thriving habits list, rather than just getting by. All complex interactions are reflected there, unless the person believes that habits had no influence on their longevity.

 

[Travis]

From your list: I had counted eight instances of egg yolk eating, one of egg white eating (inapplicable: no linoleic acid), and one of 'fondness for custard' (inapplicable: proclivity for dessert ≠ dietary staple). Confirmed cases of daily, or near daily, egg‐eating represents the following centenarians:

Besse Cooper - 116 years, 100 days
Charlotte Hughes - 115 years, 228 days
Edna Parker - 115 years, 220 days
Gertrude Baines - 115 years, 158 days
Walter Breuning - 114 years, 205 days
Florrie Baldwin - 114 years, 38 days
Emma Morano - 113 years, 231 days
George Francis - 112 years, 204 days​

I had also found three so‐called vegetarians, those who ostensibly avoid eggs entirely.

Marie-Louise Meilleur - 117 years, 230 days
Christian Mortensen - 115 years, 252 days
Reg Dean - 110 years, 62 days​

Eggs do not appear to be required to live 117 years.

The NIH reports the prevalence of 'vegetarianism' to be quite low really. Even among people claiming only 4–6 days of vegetarianism per week, the prevalence was only 3.5–4.2% (depending on year; Table 1). Naturally, the prevalence of strict vegetarians are even lower.

'A 1980 study of 605 Massachusetts physicians and lawyers, however, found that 1.5% called themselves vegetarian (although this population is also atypical).' ―White​

Are these people deluded? Well, here are some characteristics of of those who claim to be vegetarians:

'We found that vegetarians were rare in the population, and there was no change in prevalence during the 1980s (P > .25 for a logistic regression with a y variable of >0 vegetarian days per week) (Table 1). Those with more vegetarian days in the previous week were significantly (P < .05) more likely to be younger, female, more educated, and of higher household income. Those with more vegetarian days had lower weight, plasma cholesterol levels, systolic and diastolic blood pressures, and lower (better) Framingham risk scores. Regarding their health and dietary habits, they had higher health knowledge scores, exercised more, and consumed fewer calories and less fatty food.' ―White​

No mention of choline deficiency was made among this cohort.

Since linoleic acid becomes prostaglandin E₂, and prostaglandin E₂ upregualtes ornithine decarboxylase, you might expect higher cancer rates among egg eaters. This has in fact been found by some researchers.

Among inhabitants of Uraguay, a dose‐dependent effect had been found in a case–control study:

'A high intake of eggs has been associated with increased risk of colorectal cancer in several previous studies (Steinmetz and Potter, 1994).' ―Aune​

​

'Conclusions: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.' ―Aune
​

I think you'd have to expect this based on the proliferative effects of prostaglandin E₂. I have yet to see any indication that linoleic acid found in eggs is less carcinogenic than the linoleic acid found in corn oil.

But, of course, linoleic acid alone is not sufficient for particularly high prostaglandin E₂ levels. The expression of induced phospholipase A and cyclo‐oxygenase play a considerable role, and this is powerfully effected by cytokine levels. Other fatty acids will compete for this pathway, and the higher incidence of chocolate eating—a low ω−6 vegan food mentioned by ten centenarians—could have relevance. Stearic acid is the fatty acid historically found most protective, likely on account of its persistence. The short chained fatty acids are metabolized quickly, and only palmitic and stearic acids are long enough to be incorporated into membrane phospholipids:

​

This means that caproic, caprilic, and myristic acids wouldn be expected to prevent cancer since the neither displace linoleic acid from the cell membrane or significantly compete with cyclooxygenase. These short‐chained fatty acids undergo β-oxidation quickly and represent a great source of energy. Coconuts and goat cheese appear to be more Peat-friendly than eggs, both due to the lower Fernstrom ratios and their ω−6 contents.

The centenarians prove that you can still live a long time eating linoleic acid, but I am willing to bet that these people didn't eat very many calories. More highly active people, both physically and intellectually, simply must eat more food—upwards of 3000–4000·Cal·d⁻¹. Although eggs are fun to eat and cook with, I think logic would tend towards more beef and less eggs for those concerned about choline. Compared with eggs, beef is both more saturated and has a lower Fernstrom ratio: W/(T+V+I+L+F).

Beef has much less linoleic acid. Even its total PUFA% is less than the total linoleic acid% found in eggs.

White, Randall. "Health effects and prevalence of vegetarianism." Western Journal of Medicine (1994)
Raes, Katleen. "Meat quality, fatty acid composition and flavour analysis in Belgian retail beef." Meat science (2003)
Aune, Dagfinn. "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay." Asian Pac J Cancer Prev (2009)
Borkman, Mark. "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids." New England Journal of Medicine (1993)​

 

[Amazoniac]

anyone ingesting eggs does have to overcome the ~15–20% linoleic acid yolk content

Travisord, this would make a good thread title: is choline worth the linoleic acid in eggs?

From your list: I had counted eight instances of egg yolk eating, one of egg white eating (inapplicable: no linoleic acid), and one of 'fondness for custard' (inapplicable: proclivity for dessert ≠ dietary staple). Confirmed cases of daily, or near daily, egg‐eating represents the following centenarians:

Besse Cooper - 116 years, 100 days
Charlotte Hughes - 115 years, 228 days
Edna Parker - 115 years, 220 days
Gertrude Baines - 115 years, 158 days
Walter Breuning - 114 years, 205 days
Florrie Baldwin - 114 years, 38 days
Emma Morano - 113 years, 231 days
George Francis - 112 years, 204 days​

I had also found three so‐called vegetarians, those who ostensibly avoid eggs entirely.

Marie-Louise Meilleur - 117 years, 230 days
Christian Mortensen - 115 years, 252 days
Reg Dean - 110 years, 62 days​

Eggs do not appear to be required to live 117 years.

The NIH reports the prevalence of 'vegetarianism' to be quite low really. Even among people claiming only 4–6 days of vegetarianism per week, the prevalence was only 3.5–4.2% (depending on year; Table 1). Naturally, the prevalence of strict vegetarians are even lower.

'A 1980 study of 605 Massachusetts physicians and lawyers, however, found that 1.5% called themselves vegetarian (although this population is also atypical).' ―White​

Are these people deluded? Well, here are some characteristics of of those who claim to be vegetarians:

'We found that vegetarians were rare in the population, and there was no change in prevalence during the 1980s (P > .25 for a logistic regression with a y variable of >0 vegetarian days per week) (Table 1). Those with more vegetarian days in the previous week were significantly (P < .05) more likely to be younger, female, more educated, and of higher household income. Those with more vegetarian days had lower weight, plasma cholesterol levels, systolic and diastolic blood pressures, and lower (better) Framingham risk scores. Regarding their health and dietary habits, they had higher health knowledge scores, exercised more, and consumed fewer calories and less fatty food.' ―White​

No mention of choline deficiency was made among this cohort.

Since linoleic acid becomes prostaglandin E₂, and prostaglandin E₂ upregualtes ornithine decarboxylase, you might expect higher cancer rates among egg eaters. This has in fact been found by some researchers.

Among inhabitants of Uraguay, a dose‐dependent effect had been found in a case–control study:

'A high intake of eggs has been associated with increased risk of colorectal cancer in several previous studies (Steinmetz and Potter, 1994).' ―Aune​

View attachment 7817 ​

'Conclusions: We found an association between higher intake of eggs and increased risk of several cancers. Further prospective studies of these associations are warranted.' ―Aune
​

I think you'd have to expect this based on the proliferative effects of prostaglandin E₂. I have yet to see any indication that linoleic acid found in eggs is less carcinogenic than the linoleic acid found in corn oil.

But, of course, linoleic acid alone is not sufficient for particularly high prostaglandin E₂ levels. The expression of induced phospholipase A and cyclo‐oxygenase play a considerable role, and this is powerfully effected by cytokine levels. Other fatty acids will compete for this pathway, and the higher incidence of chocolate eating—a low ω−6 vegan food mentioned by ten centenarians—could have relevance. Stearic acid is the fatty acid historically found most protective, likely on account of its persistence. The short chained fatty acids are metabolized quickly, and only palmitic and stearic acids are long enough to be incorporated into membrane phospholipids:

View attachment 7820 ​

This means that caproic, caprilic, and myristic acids wouldn be expected to prevent cancer since the neither displace linoleic acid from the cell membrane or significantly compete with cyclooxygenase. These short‐chained fatty acids undergo β-oxidation quickly and represent a great source of energy. Coconuts and goat cheese appear to be more Peat-friendly than eggs, both due to the lower Fernstrom ratios and their ω−6 contents.

The centenarians prove that you can still live a long time eating linoleic acid, but I am willing to bet that these people didn't eat very many calories. More highly active people, both physically and intellectually, simply must eat more food—upwards of 3000–4000·Cal·d⁻¹. Although eggs are fun to eat and cook with, I think logic would tend towards more beef and less eggs for those concerned about choline. Compared with eggs, beef is both more saturated and has a lower Fernstrom ratio: W/(T+V+I+L+F).

Beef has much less linoleic acid. Even its total PUFA% is less than the total linoleic acid% found in eggs.

White, Randall. "Health effects and prevalence of vegetarianism." Western Journal of Medicine (1994)
Raes, Katleen. "Meat quality, fatty acid composition and flavour analysis in Belgian retail beef." Meat science (2003)
Aune, Dagfinn. "Egg consumption and the risk of cancer: a multisite case-control study in Uruguay." Asian Pac J Cancer Prev (2009)
Borkman, Mark. "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids." New England Journal of Medicine (1993)​

Thanks for the class and for training me that it's possible to change the color of the highlights.
Those cases are somewhat suspicious, perhaps they did eat eggs and likely many more others that omitted than those who didn't consume.
What do you think about this?
The Healthfulness of Eggs - Perfect Health Diet | Perfect Health Diet "Positive associations with diseases exist for every food."

 

[Tenacity]

@Amazoniac Health Correlator: The man who ate 25 eggs per day: What does this case really tell us?

 

[Travis]

Ian Prior studied the diet of South Pacific islanders to examine the effects of saturated fat on cardiovascular disease. He chose to study these islanders for the reason of their unusually‐high saturated fat consumption; these islanders ate coconuts, tubers, and fruit. Although they ate pork, the pigs were reserved for special occasions. Moreover, the pigs were fed actually fed coconuts and had a fatty acid composition to match:

​

These pigs were only 2% linoleic acid, as expressed as a percentage of total fatty acids. This goes to show that even a high‐linoleate animal can be made low on an island devoid of the high‐linoleate seeds and grasses found in the more temperate climates.

Commercial egg production is industrialized and chickens are largely fed the same thing, a fact with likely gives a false sense of concreteness to the linoleic acid concentrations of their eggs. Little can be said of the eggs of the centenarians, but it is theoretically possible that they were eating low‐linoleate eggs. It is actually a statistical likelihood that some people do in fact eat low‐linoleate eggs; and as representing less than one tenth of one percent of all egg‐eaters, those eight centenarians above could very well have been those people.

People raising chickens in non‐industrialized settings would likely be eating eggs with an uncommon fatty acid profile.

 

[Travis]

@Amazoniac Health Correlator: The man who ate 25 eggs per day: What does this case really tell us?

I think it tells us that it's a complete food, yet has a relatively high tryptophan ratio:

'This man ate 25 eggs per day apparently due to an obsession tied to mental problems. Repeated attempts at changing his behavior were unsuccessful. He said: “Eating these eggs ruins my life, but I can't help it.”' ―Ned Kock​

'He was an articulate, well-educated elderly man, healthy except for an extremely poor memory without other specific neurologic deficits...' ―Ned Kock
​

Eggs are low in aluminum, and not especially immunogenic, so any mental problems could very well have been due to either serotonin (tryptophan) or homocysteine (methionine).

Given, he was 88 years old—but this man here is 98:



And still performing surgery into his 90s! (A low tryptophan and methionine diet can help you do this.)