The Travis Corner

Travis

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View attachment 9022

Edit: Also interesting to note the increases of arachidic and behenic in MR
That's a nice shift, and thanks for reminding me of the rare arachidic (20∶0) and behenic acids (22∶0). There are approximately zero studies on giving animals these two fatty acids, and they might perhaps make the membrane 'too stiff.' After reading about the B-series leukotrienes I have decided to go full deficient; the few times I eat eggs the yolks go straight down the sink—no grains, no seeds, no beans (redundant, I know), no avocado, and no nuts besides the coconut.

The B-series leukotrienes were first discovered for their powerful effect on immune cells. This is their canonical function, and in the process of acting upon upon their leukotriene membrane receptors they have been shown to: increase antibody complement affinity sites, initiate the degranulation process, and even serve as very powerful chemoatractants for all polymorphonuclear leukocytes (i.e. neutrophils, eosinophils, and basophils).

The fact that the E-series prostaglandins vary in potency depending on the number of double bonds they have—which, in turn, depends on the diet—is relatively well-known compared to the fact that also do the B-series leukotrienes. There exists only two real E-series prostaglandins on account of Mead acid's (20∶3) cyclooxygenase product not even resembling the other two, completely lacking the cyclopentenone ring structure that puts 'cyclo' in cyclooxygenase—thus being unfit to classified as such. Eicosapentaenoic acid (20∶5) forms the only other cyclopentenone cyclooxygenase products, and these all have one more double bond than the arachidonic acid products (20∶4). The process of endoperoxide cycloaddition of peroxynitrite onto arachidonic acid always desaturates two bonds, giving arachidonic acid products having only two double bonds and a subscript to match. In the very same way, the eicosapentaenoic acid products are denoted by the number three—having this number of double bonds. Prostaglandin E₁ is not the Mead acid product (20∶3ω−9), as you'd might expect, but the dihomo-γ-linolenic acid product (20∶3ω−6). Both the 1-series and 2-series prostaglandins derive from ω−6 fatty acids and both are similarly more potent than the 3-series derived from eicosapentaenoic acid (20∶5ω−3). Most studies geared towards quantifying the differential potency between the three species indicate that the 3-series prostaglandins are approximately four times less potent than the 1-series and 2-series prostaglandins.

But perhaps even more relevant, and what some may even find astonishing, is that the potency of the B-series leukotrienes vary between 10 and 10³-fold. The least potent is the eicosapentaenoic acid (20∶5ω−3) product, having an effect on neutrophils only ¹⁄₁₀₀₀ as great as the arachidonic acid product leukotriene B₄. The leukotriene derived from the ω−3 fatty acids is commonly known as leukotriene B₅, and because the enzyme lipoxygenase does not cyclicize the lipid—or change the double bonds in any way besides stereochemically—the leukotrienes have the same unsaturation index as their parent lipids.

Intermediate in potency is the Mead acid (20∶3ω−9) product, having roughly ten times less the chemoattractant potency on neutrophils. You might assume that this would be called leukotriene B₃ . . . and you'd be right, of course, but this is not what is actually formed.

The lipoxygenase product of Mead acid had been presumed before it's been found in vivo due to the mythological nature of the beast. Since the de novo formation of Mead acid—an elongation product of oleic acid—requires the near-complete avoidance of all ω−6 fatty acids, Mead acid is generally not found in modern humans; nor is this found in lab animals fed the standard diet, and hence neither is its cycloxygenase product or the leukotriene derived from it. For this reason, the chemical structure of leukotriene B₃ was extrapolated from those of leukotrienes B₃ and B₅. This leukotriene has been synthesized, is an available research chemical, and has been used in white blood cell migration assays—among other assay types—where it gives comparable potency as our maligned leukotriene B₄ ultimately derived from linoleic acid.

In the early 1980s, the presumed Mead acid derivative leukotriene B₃ was found to be a unicorn. The structure extrapolated from the other, more common B-series leukotrienes contains one trans double bond; although this molecule is actually made my Mead acid through lipoxygenase, this is a relatively minor isomer. The actual main products of Mead acid + lipoxygenase are two enantiomers both having three cis double bonds having the IUPAC designations of 5S,12R-dihydroxy-6Z,8Z,10Z-eicosatrienoic acid and 5S,12S-dihydroxy-6Z,8Z,10Z-eicosatrienoic acid. I use the term all-cis-leukotriene B₃ to differentiate it from is unphysiological presumption, which goes by the names of: trans-leukotriene B₃, unicorn-leukotriene B₃, or simply leukotriene B₃ (it's too established). All-cis-leukotriene B₃ has approximately ten times less chemoattractant ability as leukotriene B₄, meaning that you'd expect all leukocytes to be inclined to home-in on the arachidonic acid product anywhere from 10 to 10³ times more than our natural eicosapentaenoic and Mead acid products—these being leukotriene B₅ all-cis-leukotriene B₃.

In the absence of dietary ω−6 fatty acids, their formation in the body can still occur. Although humans don't have a Δ⁶-desaturase enzyme, helminths and fungi do. The pathological yeast/fungi Candida albicans is known to synthesize arachidonic acid de novo, which it will even form prostaglandin E₂ with despite not having a genetic sequence homologous to mammalian cyclooxygenase. The B-series leukotrienes would be expected to form in the process, and even nonenzymatically as they are simply hydroxylated lipids (and especially in the presence of a neutrophil attack, which releases superoxide towards the pathogen). Since primate leukocytes have evolved in the tropics where both helminth infections are more common and plants do not synthesize ω−6 fatty acids, I maintain that the relatively potent chemoattraction of leukotriene B₄ on leukocytes had more-or-less evolved as a fungi- and helminth-seeking device. The fact that eosinophils will follow a leukotriene B₄ gradient while also containing a toxic cargo in its cytosol—containing eosinophil basic protein, eosinophil neurotoxin, and eosinophil peroxidase—which has been shown to kill helminths upon degranulation further this idea. Accepting this line of line of thinking eventually leads to the thought that the unnatural ω−6-derived leukotriene B₄ will decrease immunological sensitivity by increasing background levels over that found in the vicinity of helminths and yeast. Eosinophils have also been shown to be attracted to 13-hydroxylinoleic acid with roughly ²⁄₃·leukotriene B₄ potency, but even this reduced attraction is far greater than even the most powerful ω−3 and ω−9 derivatives.

Then comes the avoidance of almonds, grains, seeds, olive oil, avocados . . . and the egg yolks start going down the sink.
 
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Mito

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I have decided to go full deficient; Since the de novo formation of Mead acid—an elongation product of oleic acid—requires the near-complete avoidance of all ω−6 fatty acids,
How long do you think it will take before you start de novo formation of Mead acid?
 

Obi-wan

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@Travis said "In the absence of dietary ω−6 fatty acids, their formation in the body can still occur. Although humans don't have a Δ⁶-desaturase enzyme, helminths and fungi do. The pathological yeast/fungi Candida albicans is known to synthesize arachidonic acid de novo, which it will even form prostaglandin E₂ with despite not having a genetic sequence homologous to mammalian cyclooxygenase."

So getting rid of fungi is just as important as eliminating Linoleic acid. I feel I am having success with oregano oil sublingual (instant effect) along with transdermal Cocoa butter (stearic acid) and Cupuacu butter (arachidic acid) bypassing the liver

Still waiting on the high Gamma dry E that I ordered

The Force is great with Travis!
 
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Travis

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How long do you think it will take before you start de novo formation of Mead acid?
I know most data on this had been compiled from studies done using rats and fast-growing human infants, but I don't see how those could give a reliable time frame for larger animals like us. A person could extrapolate, but I think mathematical models of that sort would be somewhat speculative without clinical or experimental data to cross-verify. But I did find two three studies on a adult humans after a few minutes search, which I will read, and I'm nearly positive there will be yet others in their respective reference sections to add. I will add them below for anyone interested:
Collins, F.. "Plasma lipids in human linoleic acid deficiency." Annals of Nutrition and Metabolism (1971)
Riella, M. "Essential fatty acid deficiency in human adults during total parenteral nutrition." Annals of internal medicine (1975)
Wene, J. "The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally." The Journal of clinical investigation (1975)

I had been planning on to do this for awhile—not 'go fully ω−6 deficient,' but to analyze the clinical data for this purported 'condition.' As you know: Linoleic acid deficiency is framed as an actual pathology—perhaps from help from the oil industry—but as of yet the extent of this 'condition' only hints to minor increases in skin exfoliation (or 'flakiness'), perhaps being merely a symptom of a classic B-vitamin deficiency. This could be a result of a deficiency of lipids in general, and α-linolenic acid (18∶3ω−3) in particular, and its elongation product docosahexaenoic acid powerfully effects steroid partitioning and trans-membrane flux (androgens increase sebum production). We can make both prostaglandins and leukotrienes without arachidonic acid, although of less potency, and there I don't really see how the shift from the 1- and 2-series prostaglandins—and from the 4- to the 3- and 5-series leukotrienes—would do anything besides increase health. Judging by his articles, Ian Prior's Tokelau Islanders must have been all-out 'deficient' or extremely close; over 60% of these islander's energy had come from coconuts with fruit, tubers, and fish contributing nearly the rest. Even the fatty acid composition of the pigs on their island had been mostly saturated (62.2%) while having only 2% linoleic acid, a fatty acid hardly even synthesized on their island.⁽¹⁾⁽³⁾They ate very little meat besides fish—representing about 1% of their total energy—and the surveys indicate that only between 0–2% consume non-fish meat on any given day. But what I just now had realized is that fish actually does contain some linoleic acid (0.6–3.2%)⁽²⁾ . . . and even a bit of pre-formed arachdonic (0.4–4.5%)! This could be a result of algae: Some genera or algae, like fungi, also have a Δ¹²-desaturase which catalyzes the ω−6 desaturation on 18-carbon fatty acids. Some species of helminths also have an enzyme which performs the same function, and there could be a few lower sea creatures which also produce it.
[1] Harding, W. "Dietary surveys from the Tokelau Island migrant study." Ecology of Food and Nutrition (1986)
[2] Gruger, E. "Fatty acid composition of oils from 21 species of marine fish, freshwater fish and shellfish." Journal of the American Oil Chemists Society (1964)

[3] Prior, I. "Cholesterol, coconuts, and diet on Polynesian atolls: a natural experiment: the Pukapuka and Tokelau island studies." The American journal of clinical nutrition (1981)

After thinking about this issue for a bit, I'm getting the impression that all 'essential fatty acid (ω−6) deficient' people either are (1) suffering from a confounding deficiency consequent of being fed intravenously of through a tube, as the majority of cases are; or (2) stemming from the very same condition which had necessitated such unnatural feeding methods; (3) being confused with an actual α-linolenic acid (18∶3ω−3) deficiency—an actual legitimate condition; or (4) are the result of your run-of-the-mill classic B-vitamin deficiency (i.e. biotin) that would be expected from the increased metabolism of the linoleate-'deficient' state—the Ray Peat explanation.
 
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Ledo

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Hi Travis.

Do you know an effective way to test for a metal concentration in a food (liquid)? Take lead for example in homemade gelatin from a chicken carcass. Can the lead somehow be bound and trapped in a reaction of some sort by using a small known amount of the liquid and then weighed after separating to determine concentration per unit vol?

Thx
 

Mito

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We can make both prostaglandins and leukotrienes without arachidonic acid, although of less potency, and there I don't really see how the shift from the 1- and 2-series prostaglandins—and from the 4- to the 3- and 5-series leukotrienes—would do anything besides increase health.
In this post (https://raypeatforum.com/community/...sed-thyroid-function.14245/page-3#post-197825) @haidut noted significant decreases in inflammation markers after measuring high Mead acid levels.

My ESR went down from 8 to 1. It even reached 0 on a few tests. My WBC are in the bottom 10% of the normal range. They used to be consistently in the upper 80%-90% range in my Paleo days. Same thing happened to the guy Peat wrote about who went on the fat free diet for a few months. My CRP levels have always been lowish. A few tests also showed high Mead acid so I am assuming this confirms the EFE deficiency. The problem is that even a few days of being careless about PUFA intake brought back Mead acid in range, just as in the monkey study on 30-day PUFA depletion. So, it seems very easy to replenish PUFA stores (at least for me).”​
 

Travis

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Hi Travis.

Do you know an effective way to test for a metal concentration in a food (liquid)? Take lead for example in homemade gelatin from a chicken carcass. Can the lead somehow be bound and trapped in a reaction of some sort by using a small known amount of the liquid and then weighed after separating to determine concentration per unit vol?

Thx
The lead concentrations should be under the limit of detection for most everything besides electron dispersive spectroscopy. Flame ionization spectroscopy is far more common, but I don't think it would be accurate enough for the amount of lead in those foods; but this would be excellent for things like sodium, potassium, and calcium concentrations.

I think common would be to ash the sample first: This process removes most carbon, nitrogen, and oxygen as it evaporates away. This greatly concentrates the sample and is a good first step for detection.

Perhaps better would be using a blender with gelatin—the sample—and proteolytic enzymes to hydrolyze the peptide bonds. After the entire sample has become mostly all free amino acids, free monosaccharides, and free lipids, then using an excess of EDTA could selectively chelate the divalent ions (i.e. Pb²⁺, Ca²⁺, Fe²⁺, Mg²⁺). After this, then centrifugation could allow the separation of the heavier Pb²⁺–EDTA chelate from everything else. Of course then you'd still have to detect it, but having it all in one density band would make that convenient.
 

Travis

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In this post (The Benefits Of Decreased Thyroid Function) @haidut noted significant decreases in inflammation markers after measuring high Mead acid levels.

My ESR went down from 8 to 1. It even reached 0 on a few tests. My WBC are in the bottom 10% of the normal range. They used to be consistently in the upper 80%-90% range in my Paleo days. Same thing happened to the guy Peat wrote about who went on the fat free diet for a few months. My CRP levels have always been lowish. A few tests also showed high Mead acid so I am assuming this confirms the EFE deficiency. The problem is that even a few days of being careless about PUFA intake brought back Mead acid in range, just as in the monkey study on 30-day PUFA depletion. So, it seems very easy to replenish PUFA stores (at least for me).”​

I read a few articles and Mead acid appears in the blood faster that I'd thought, but levels of linoleic acid in the adipose tissue had remained constant after two weeks. Whole-body ω−6 depletion would take much longer, and I think the length of time needed for this would more-or-less be dependent on adipose tissue levels. A person might have to fast for awhile beforehand, and then eat only very low ω−6 foods.

Last week I'd read study involving a rabbit strain which always gets this autoinmmune nephropathy; the rabbit group which had the ω−6 restricted diet (coconut oil) had greatly outlasted the other groups (control and sunflower oil). The histology confirmed all of this, with far less autoimmune damage in the coconut oil groups. I take this much less leukotriene B₄ acting as little beacons for neutrophils and eosinophils—leukocytes which cause the damage by using peroxynitrite, eosinophil neurotoxin, and eosinophil basic protein.
 

Fractality

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You can so do this, as long as they are short-chained and saturated. Islanders of Tokelau would eat 60% of their daily energy as short-chained fatty acids. They did eat a little fish and pork about once a month, but the pork was actually highly-saturated from the pigs being fed mostly coconut. Ian Prior has published articles will all this information, and I might take another look at them to see the pig analysis; I would like the know what the linoleic acid content had been, specifically, a fatty acid which should be nearly absent on a tropical island (the pigs most surely have a Δ⁹-desaturase so oleic acid would be expected).

I see the short-chained fatty acids as mostly energy that doesn't really get incorporated into structure (but they can be elongated for this purpose). Sure you can find lauric acid on the cell membrane, but only at around 5%. Most membrane lipids range in size from 16–22 carbons; myristic, stearic, and oleic acids form a large percentage and should probably be considered ideal (and with Mead acid). The degree of character of unsaturation varies depending on estrogen concentration, temperature, and diet.

A person certainly can do 50% short-chained fatty acids for decades, as coconut; this much is certain, but I don't think doing this all as dairy products alone would be a grand idea. These fatty acids can also be found in beef and chocolate, and these would contribute less steroids and exorphins. I know of two Peat-friendly plant sources to choose from (chocolate and coconut) and also two animal sources (dairy and beef/lamb). Of course there are probably others I'm not thinking of at the moment . . . but expanding this lost too far and you're running into linoleic acid at some point: eggs have ~22%, olive oil has ~10%, and avocados have ~18%.

Will regular consumption of 100% chocolate displace PUFA from all cells (especially if PUFA is kept very low)? Or does the liver gobble most if it up for energy? Stearic acid has a long enough chain, correct?
 

Koveras

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Wonder if they got this idea from reading the Travis Corner

Cell Metab. 2018 Apr 3;27(4):914-925.e5. doi: 10.1016/j.cmet.2018.02.004. Epub 2018 Mar 15.
Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis.
Ravichandran M1, Priebe S2, Grigolon G3, Rozanov L1, Groth M4, Laube B3, Guthke R2, Platzer M4, Zarse K3, Ristow M5.

Whether and how regulation of genes and pathways contributes to physiological aging is topic of intense scientific debate. By performing an RNA expression-based screen for genes downregulated during aging of three different species, we identified glycine-C-acetyltransferase (GCAT, EC 2.3.1.29). Impairing gcat expression promotes the lifespan of C. elegans by interfering with threonine catabolism to promote methylglyoxal (MGO; CAS 78-98-8) formation in an amine oxidase-dependent manner. MGO is a reactive dicarbonyl inducing diabetic complications in mammals by causing oxidative stress and damaging cellular components, including proteins. While high concentrations of MGO consistently exert toxicity in nematodes, we unexpectedly find that low-dose MGO promotes lifespan, resembling key mediators of gcat impairment. These were executed by the ubiquitin-proteasome system, namely PBS-3 and RPN-6.1 subunits, regulated by the stress-responsive transcriptional regulators SKN-1/NRF2 and HSF-1. Taken together, GCAT acts as an evolutionary conserved aging-related gene by orchestrating an unexpected nonlinear impact of proteotoxic MGO on longevity.​
 

Travis

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Will regular consumption of 100% chocolate displace PUFA from all cells (especially if PUFA is kept very low)? Or does the liver gobble most if it up for energy? Stearic acid has a long enough chain, correct?

Chocolate should help, but some stearic acid is Δ⁹-desaturated into oleic acid; this occurs both in the liver and elsewhere, and the enzyme responsible for this peripherally—stearoly–CoA desaturase—is induced by estradiol (~7×). We are thus necessarily stuck having some oleic acid, but this lipid will not oxidize spontaneously in water (and is safe hormonally). Monounsaturated fatty acids are closer to the saturated fatty acids in this respect, in reactivity, although iodine will add to either one.

We are also stuck with having ω−3 fatty acids in our bodies, and diet, as the lipid α-linolenic acid is the only essential one (unless one eats fish). The characteristic skin changes seen in the 1930's which had been used as a basis of falsely elevating linoleic acid to vitamin status can be reversed by the ω−3 fatty acids (which had been less-characterized back then due to the difficulty in resolving the α and γ isomers, and also due to its assumed irrelevance of this distinction). The 'essential fatty acid deficiency' is not a hormonal condition, or doesn't depend on eicosanoids, but is simply a consequence of physical membrane effects: The skin scaliness observed correlates with increased water loss through same organ (~2×), also observed by Burr & Burr, and this correlates with decreased H₂O membrane flux—this facilitates cell hydration. The most unsaturated membrane lipid, or docosahexaenoic acid (22∶6), increases lipid bilayer water permeability more than any other. Linoleic acid produces elongated and desaturated products (i.e. 20∶4 & 22∶5ω−6) which can also serve this function but at diminished capacity (relative to 22∶6ω−3), and is simply why ω−6 fatty acids will also reverse skin scaling. This simple fact does not make them essential however, as α-linolenic acid works even better; this lipid, it should be known, forms less-carcinogenic prostaglandins and less-chemotactic leukotrienes.

Since the membrane needs some degree of unsaturation, small amounts of linoleic acid will tend to be preserved; I would imagine ω−3 fatty acids more antagonistic to this process more than stearate. Mead acid is a legitimate membrane lipid that I'd consider hormonally-safe, and so is the previously-mentioned DHA (and the similar DPA). These are membrane lipids derived from ω−9 and ω−3 fatty acids, respectively, and have far less hormonal potential than their respective ω−6-derived eicosanoids. I had previously typed a bit about the teleological aspects behind the increased potency of ω−6-derived leukotrienes, but it wasn't until a few minutes ago that I had found a person who had speculated along the very same lines (albeit more briefly):

Preface: The acronym HETE stands for hydroxyeicosatetraenoic acid, which is merely the Greek-ordinal systematic IUPAC name for arachidonic acid. Monohydroxylated forms, such as 5- and 15-HETE, have been long observed to be chemoattractants for white blood cells and approach the potency of leukotriene B₄. In fact: the novel lipid produced by C. albicans mentioned below is very similar to leukotriene B₄, which is also a dihydroxylated arachidonic acid (i.e. 5,12-diHETE). Although not even mentioned in the article, both 3,18-diHETE and 5,12-diHETE (a.k.a. leukotriene B₄) are actually isomers:

Rupal Deva, PhD: Whether the oxylipins produced by C. albicans, including 3,18-diHETE, exert similar biological activities on neutrophils, remains to be examined. If so, the release of these compounds from the fungus would cause a recruitment and activation of neutrophils at the infected site, so that the elimination of the pathogen or the prevention of its invasiveness by phagocytosing neutrophils may be favoured. The observations, that invasive candidiasis is strongly facilitated in systemic neutropenia [1–8], would thus be in line with such an assumption. In summary, our data revealed a novel aspect as to the understanding of the host–pathogen interaction during fungal infections. More reports are required to explore the precise role of 3(R)-hydroxy-eicosanoids and related oxylipins in fungal infections and in general for fungal biology. A deeper insight into the regulation of these processes should open new approaches for the prevention and therapy of fungal diseases.

Deva, R. "Arachidonic acid stimulates cell growth and forms a novel oxygenated metabolite in Candida albicans." Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids (2000)

It is becoming somewhat well
-known now that lauric acid—the main fatty acid in coconut—not only fails to support growth of C. albicans but actually inhibits it. This appears more-or-less particular to short–medium-chained fatty acids, and a phenomenon which certainly cannot be said about all of them: The omega−6 fatty linoleic acid can actually provide the sole carbon source for Candida albicans, with no glucose required:

linoleic.png
 

Travis

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Ha! ― (⟵notice that I'd properly used a horizontal bar and not the very similar em dash) nice find. This is a brand new article, and it's nice seeing people thinking along similar lines. But it had always bothered me when methylglyoxal is framed merely as a 'diabetic complication' because this molecule has a long history in treating cancer (see Albert Szent–Györgyi, Ph.D., and Robert Koch, M.D., Ph.D.) and is likely the causative agent behind myopia (see Travis) on account of its formative role in very same 'diabetic complication'—the well-characterized arginine adduct:

arginine + methygloxal ⟶ cyclic hydroimidazalone ⟶ increase in corneal refractive index ⟶ myopia

Ravichandran: Whether and how regulation of genes and pathways contributes to physiological aging is topic of intense scientific debate. By performing an RNA expression-based screen for genes downregulated during aging of three different species, we identified glycine-C-acetyltransferase (GCAT). Impairing gcat expression promotes the lifespan of C. elegans by interfering with L-threonine catabolism to promote methylglyoxal (MGO) [Why are they abbreviating methylgloxal? and using three letters to do it FFS!] formation in an amine oxidase-dependent manner. MGO Methylgloxal is a reactive dicarbonyl inducing diabetic complicationssuch as myopia—and cancer protection in mammals by causing oxidative stress and damaging modifying cellular components, including mostly proteins at arginine and lysine residues. While high concentrations of MGO consistently exert toxicity in nematodes, we unexpectedly find that low-dose MGO promotes lifespan, resembling key mediators of gcat impairment. These were executed by the ubiquitin-proteasome system, namely PBS-3 and RPN-6.1 subunits, regulated by the stress-responsive transcriptional regulators SKN-1/NRF2 and HSF-1. Taken together, GCAT acts as an evolutionary conserved aging-related gene by orchestrating an unexpected nonlinear impact of proteotoxic MGO on longevity.
 

elundur

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What would be the reason for coffee aggravating psoriasis (or any other autoimmune condition)? I haven't had a cup in close to a year, but I'm searching for ways to bring it back safely ...
 

Wagner83

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Fructose malabsorption is associated with decreased plasma tryptophan. - PubMed - NCBI

CONCLUSIONS: Fructose malabsorption is associated with lower tryptophan levels that may play a role in the development of depressive disorders. High intestinal fructose concentration seems to interfere with L-tryptophan metabolism, and it may reduce availability of tryptophan for the biosynthesis of serotonin (5-hydroxytryptamine). Fructose malabsorption should be considered in patients with symptoms of depression and disturbances of tryptophan metabolism.


I wonder if this suggests anything more about a potential negative correlation between tryptophan effects and fructose in general. Maybe they just had poor absorption and metabolism of everything.
______________________

In an other thread you were talking about casein, I stumbled on this and thought you might find it interesting:

http://journals.sagepub.com/doi/pdf/10.3181/00379727-93-22783
The tryptophan content of casein has been estimated using a rat growth assay method. Whether the results were calculated on the basis of the percentage of tryptophan in the diet or by using food consumption data to calculate the daily intake of tryptophan, essentially the same results were obtained. These animal assays indicate that casein (14.64% N) contains 1.25% tryptophan which is in good agreement with many reports based on microbioassays of alkaline and enzyme hydrolysates of this protein, but much lower than many commonly accepted figures obtained with chemical methods.

https://www.google.com/url?q=http:/...fBd0QFggYMAI&usg=AOvVaw23Uk_8AdGIvweTQ2wchHyd
 
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Travis

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What would be the reason for coffee aggravating psoriasis (or any other autoimmune condition)? I haven't had a cup in close to a year, but I'm searching for ways to bring it back safely ...

Not sure. I've read quite a bit about asthma and type I diabetes, and almost completely certain that I know what the prime underlying agents are, I don't now much about that. But I would be willing to bet that either linoleic acid products (i.e. leukotriene B₄; 15-hydroxylinoleate), autoantibodies, reactive nitrogen species (i.e. nitrogen dioxide; peroxynitrite), or eosinophilic basic protein underlies this.

Coffee has two classes of bio-active molecules: the anti-opiates and the methylxanthines. I think the anti-opiates are easier to understand because they only work on one receptor (μ), and produce noticeable effects easy to measure. Morphine works on the μ-receptor and is unmistakable, although the endogenous peptides which normally act on it (i.e. β-endorphin) exist at far lower concentrations that what opium can deliver. The methylxanthines are complicated by the fact that they work on three adenosine receptors are cyclic-phosphodiesterase, an enzyme which breaks the phosphodiester bridge of cyclic-ATP (and cGTP). The adenosine receptors can be significant, and theophylline has long been used clinically to inhibit them in treating asthma. Theophylline is the most powerful methylxanthine, and although coffee doesn't have any it will be produced regardless; theophylline is simply demethylated caffeine and is one of its metabolites (paraxanthine: ~68%, theobromine: ~23%, theophylline: ~9%).

Neutrophils have adenosine type-1 & -2 receptors while eosinophils have type-3, and adenosine working on its eponymous receptor has been reported to inhibit superoxide generation (superoxide is a free radical produced by NADPH oxidase and made with intent to kill microbes). But not all methylxanthines inhibit all receptor types in a completely predictable way; the additional methyl-groups are situated on all sides of the xanthine ring and can range from zero (xanthine) to three (caffeine). (Although there are four nitrogens in the xanthine ring, the methylation of carbon-9 would destroy the planarity of the imidazole ring and hence it's right to be called a xanthine.)

I think this has something to do with neutrophils, eosinophils, and the skin. I now think the redness is best explained by proteases, which are released both by invaders (i.e. Staphylococcus aureus; Candida tropicalis) and the immune cells which combat them (i.e. neutrophils; macrophages). These could proteolyze the capillary walls and allow heme—the only significant red pigment in the body—to perfuse into the extracellular matrix.

Redness can also be produced by histamine, and mast cells are predictably found near rosacea. A similar small molecule, niacin, also causes redness and skin flushing through either capillary vasodilation or permeability increases. The 'official' mechanism for the niacin flush is overcomplicated, prolix, wrong, and involves both prostaglandin D₂ and serotonin—if Rube Goldberg were a biochemist...—but this mechanism can be simply ignored; niacin has a much greater molecular similarity to histamine, and neither serotonin nor prostaglandin D₂ will cause a flush.

niacin.png


But we must not forget that skin neutrophils, eosinophils, mast cells, and macrophages—which respond to the methylxanthines in coffee—are on the skin for a reason; these are localized in the skin in this condition, in the lungs in asthma, and in the intestines in Crohn's disease. I would say drink coffee and simply let any psoriasis manifest, since doing so will allow a person to pinpoint the precise spots to hit with antimicrobials (such as coconut oil+ lemongrass oil). And also, there are many topical probiotics on the market that can even be found at the grocery store (i.e. kimchi (via L. acidophilus); unpasteurized sauerkraut (via L. acidophilus); apple cider vinergar (via A. pasteurianus).
 

Travis

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Fructose malabsorption is associated with decreased plasma tryptophan. - PubMed - NCBI

CONCLUSIONS: Fructose malabsorption is associated with lower tryptophan levels that may play a role in the development of depressive disorders. High intestinal fructose concentration seems to interfere with L-tryptophan metabolism, and it may reduce availability of tryptophan for the biosynthesis of serotonin (5-hydroxytryptamine). Fructose malabsorption should be considered in patients with symptoms of depression and disturbances of tryptophan metabolism.


I wonder if this suggests anything more about a potential negative correlation between tryptophan effects and fructose in general. Maybe they just had poor absorption and metabolism of everything.
______________________

In an other thread you were talking about casein, I stumbled on this and thought you might find it interesting:

http://journals.sagepub.com/doi/pdf/10.3181/00379727-93-22783
The tryptophan content of casein has been estimated using a rat growth assay method. Whether the results were calculated on the basis of the percentage of tryptophan in the diet or by using food consumption data to calculate the daily intake of tryptophan, essentially the same results were obtained. These animal assays indicate that casein (14.64% N) contains 1.25% tryptophan which is in good agreement with many reports based on microbioassays of alkaline and enzyme hydrolysates of this protein, but much lower than many commonly accepted figures obtained with chemical methods.

https://www.google.com/url?q=http:/...fBd0QFggYMAI&usg=AOvVaw23Uk_8AdGIvweTQ2wchHyd

Most dietary tryptophan ⟶ brain serotonin articles are concerned primarily with the Fernstrom ratio yet give little thought to the absolute amounts. Although independent researchers have found a very high correlation between those two parameters (r≈ .85–.95)—a very reliable indicator—I think the absolute concentrations must also play a role. [It is difficult to measure whole-brain serotonin without first killing the person, so a reliable way to estimate this is needed.] Two people could have identical Fernstrom ratios, and could even have all five Fernstrom-type ratios (i.e. Phe∶Σ(cAA)) identical, and yet one of them could have a 3×-higher absolute amount of these amino acids in their blood. Although the Fernstrom ratio is unique in that it's prime concern—tryptophan, the numerator—is bound to albumin, and hence under the most unusual kinetics, the other amino acids aren't under such constraints. Although sometimes they are all plotted, the Fernstrom-analogous ratios doesn't correlate as the classic tryptophan one.

So although important, the speed of absorption might also play a role. Quickly-absorbable proteins could tend towards bypassing the portal vein, and thus tending less towards liver degradation. When whole-brain serotonin is actually measured afterwards it is generally only done once after a span of hours, meaning that it can be thought of representing an average of instantanous values. Casein is essentially the slowest-absorbing protein on account of its propensity to coagulate in the stomach, forming an agglomerate, meaning that perhaps most tryptophan will be absorbed further down and filtered by the liver—and slower (time-release casein!). Properly-cooked egg white is absorbed much quicker (duodenum), and so quickly that it could even overload the liver. Kinetics like these might account for why egg white leads to high Fernstrom ratio yet doesn't appear to deviate considerably in amino acid ratios when looking at food charts.

Fructose and glucose have surprisingly different effects for being isomers of each-other, especially considering that they will actually inter-convert at a slow rate: Glucose can decyclize and become a straight-chained form, which can then recyclize either as cyclic-glucose or as cyclic-fructose (and vice versa). The differences between these two monosaccharides isn't particularly unique and are shared by monosaccharides in general. Galactose is also an isomer of the two and has differences comparable with them both. I suppose one lesson learned is that lumping all carbohydrates together as one entity ignores the significant biological differences between the two.
 

Koveras

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Not sure. I've read quite a bit about asthma and type I diabetes, and almost completely certain that I know what the prime underlying agents are, I don't now much about that. But I would be willing to bet that either linoleic acid products (i.e. leukotriene B₄; 15-hydroxylinoleate), autoantibodies, reactive nitrogen species (i.e. nitrogen dioxide; peroxynitrite), or eosinophilic basic protein underlies this.

I think you're right about the linoleic

Maybe coffee is releasing some FFAs? @elundur

J Invest Dermatol. 2018 Feb 15. pii: S0022-202X(18)30121-0. doi: 10.1016/j.jid.2018.02.003. [Epub ahead of print]
Bioactive Lipid Mediator Profiles in Human Psoriasis Skin and Blood.
Sorokin AV1, Domenichiello AF2, Dey AK1, Yuan ZX2, Goyal A1, Rose SM3, Playford MP1, Ramsden CE4, Mehta NN5.

Psoriasis is a chronic immune-mediated disease that represents a unique model for investigating inflammation at local and systemic levels. Bioactive lipid mediators (LMs) are potent compounds reported to play a role in the development and resolution of inflammation. Currently, it is not known to what extent these LMs are involved in psoriasis pathophysiology and related metabolic dysfunction. Here, we use targeted and untargeted liquid chromatography-tandem mass spectrometry approaches to quantify LMs in skin and peripheral blood from psoriasis patients and compared them with those of healthy individuals. Lesional psoriasis skin was abundant in arachidonic acid metabolites, as 8-, 12- and 15-hydroxyeicosatetraenoic acid, compared with adjacent nonlesional and skin from healthy individuals. Additionally, a linoleic acid-derived LM, 13-hydroxyoctadecadienoic acid, was significantly increased compared with healthy skin (607.9 ng/g vs. 5.4 ng/g, P = 0.001). These psoriasis skin differences were accompanied by plasma decreases in antioxidant markers, including glutathione, and impaired lipolysis characterized by lower concentrations of primary and secondary bile acids. In conclusion, our study shows that psoriasis skin and blood have disease-specific phenotype profiles of bioactive LMs represented by omega-6 fatty acid-oxidized derivatives. These findings provide insights into psoriasis pathophysiology that could potentially contribute to new biomarkers and therapeutics.

Screen Shot 2018-04-22 at 2.53.58 PM.png Screen Shot 2018-04-22 at 2.52.54 PM.png
 

Travis

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I think you're right about the linoleic

Maybe coffee is releasing some FFAs? @elundur

J Invest Dermatol. 2018 Feb 15. pii: S0022-202X(18)30121-0. doi: 10.1016/j.jid.2018.02.003. [Epub ahead of print]
Bioactive Lipid Mediator Profiles in Human Psoriasis Skin and Blood.
Sorokin AV1, Domenichiello AF2, Dey AK1, Yuan ZX2, Goyal A1, Rose SM3, Playford MP1, Ramsden CE4, Mehta NN5.

Psoriasis is a chronic immune-mediated disease that represents a unique model for investigating inflammation at local and systemic levels. Bioactive lipid mediators (LMs) are potent compounds reported to play a role in the development and resolution of inflammation. Currently, it is not known to what extent these LMs are involved in psoriasis pathophysiology and related metabolic dysfunction. Here, we use targeted and untargeted liquid chromatography-tandem mass spectrometry approaches to quantify LMs in skin and peripheral blood from psoriasis patients and compared them with those of healthy individuals. Lesional psoriasis skin was abundant in arachidonic acid metabolites, as 8-, 12- and 15-hydroxyeicosatetraenoic acid, compared with adjacent nonlesional and skin from healthy individuals. Additionally, a linoleic acid-derived LM, 13-hydroxyoctadecadienoic acid, was significantly increased compared with healthy skin (607.9 ng/g vs. 5.4 ng/g, P = 0.001). These psoriasis skin differences were accompanied by plasma decreases in antioxidant markers, including glutathione, and impaired lipolysis characterized by lower concentrations of primary and secondary bile acids. In conclusion, our study shows that psoriasis skin and blood have disease-specific phenotype profiles of bioactive LMs represented by omega-6 fatty acid-oxidized derivatives. These findings provide insights into psoriasis pathophysiology that could potentially contribute to new biomarkers and therapeutics.

View attachment 9080 View attachment 9081
Koveras has found a massive 112-fold difference, or an 11,200% increase (I attach special significance to even three-fold differences):

Koveras: 'Additionally, a linoleic acid-derived LM, 13-hydroxyoctadecadienoic acid, was significantly increased compared with healthy skin (607.9 ng/g vs. 5.4 ng/g, P = 0.001). ' ―Sorokin

But did you know that 13-hydroxyoctadecadienoic acid—a.k.a. 13-OH-linoleic acid—is characteristic of eosinophils?⁽¹⁾ This also serves as a chemotactic agent and is about ²⁄₃ as powerful as leukotriene B₄.

And I think it's also worth mentioning that even in the absence of diet-derived linoleate, most yeast–fungi have the capacity to synthesize linoleate de novo. The ubiquitous Candida albicans will create it's own prostaglandin E₂ while growing entirely off fatty acid-free growth media. Since epithelial fatty acid distribution doesn't often occur in spots, a person is almost forced into thinking a microbial invader could be what is recruiting the eosinophils, neutrophils, and macrophages. Even on a low linoleate diet: yeast on the skin could produce the linoleic acid required by eosinophils to synthesize to 13-hydroxylinoleic acid detected, and also synthesize the leukotriene B₄ isomer 3,18-diHETE—explaining why the eosinophils are there in the first place.⁽²⁾

[1] Engels, F. "Preferential formation of 13-hydroxylinoleic acid by human peripheral blood eosinophils." Prostaglandins (1996)
[2] The molecule 3,18-diHETE is an isomer of 5,12-diHETE—more commonly-known as leukotriene B₄—and is a suspected chemoattractant for this reason. Leukotriene B₄ the most powerful lipid chemoattractant for neutrophils, and had been discovered on account of its propensity for doing just that.
 
Last edited:

Koveras

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Koveras has found a massive 112-fold difference, or an 11,200% increase (I attach special significance to even three-fold differences):

Koveras: 'Additionally, a linoleic acid-derived LM, 13-hydroxyoctadecadienoic acid, was significantly increased compared with healthy skin (607.9 ng/g vs. 5.4 ng/g, P = 0.001). ' ―Sorokin

But did you know that 13-hydroxyoctadecadienoic acid—a.k.a. 13-OH-linoleic acid—is characteristic of eosinophils?⁽¹⁾ This also serves as a chemotactic agent and is about ²⁄₃ as powerful as leukotriene B₄.

And I think it's also worth mentioning that even in the absence of diet-derived linoleate, most yeast–fungi have the capacity to synthesize linoleate de novo. The ubiquitous Candida albicans will create it's own prostaglandin E₂ while growing entirely off fatty acid-free growth media. Since epithelial fatty acid distribution doesn't often occur in spots, a person is almost forced into thinking a microbial invader could be what is recruiting the eosinophils, neutrophils, and macrophages. Even on a low linoleate diet: yeast on the skin could produce the linoleic acid required by eosinophils to synthesize to 13-hydroxylinoleic acid detected, and also synthesize the leukotriene B₄ isomer 3,18-diHETE—explaining why the eosinophils are there in the first place.⁽²⁾

[1] Engels, F. "Preferential formation of 13-hydroxylinoleic acid by human peripheral blood eosinophils." Prostaglandins (1996)
[2] The molecule 3,18-diHETE is an isomer of 5,12-diHETE—more commonly-known as leukotriene B₄—and is a suspected chemoattractant for this reason. Leukotriene B₄ the most powerful lipid chemoattractant for neutrophils, and had been discovered on account of its propensity for doing just that.

Lauric acid bath?
 

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