Low Toxin Diet Grant Genereux's Theory Of Vitamin A Toxicity

[Tristan Loscha]

The largest trials for beta carotene showing increased mortality from cancer and heart disease in the beta carotene groups, multiple cadaver studies showing high rates of Hypervitaminosis A in western populations, people like myself following low va diets and CURING long standing health problems and normalizing cholesterol and liver panels... What other evidence do you need to BELIEVE?

Hypervitaminosis A was a major problem way before glyphosate appeared on the scene...

I've known a lot of germans and i've never once seen them eat pate or liver?

Liver is one of the most disgusting foods one can ever eat! Kidneys are a close second. Why choose to eat offal when you aren't a starving medieval peasant? If liver is such a natural food for humans why do young humans hate it when young lions and tigers love it?

A low va diet does not have to be beans, rice and beef lol, don't follow that unbalanced diet. It just has to avoid liver, high fat dairy, excess eggs and high carotenoid foods... The low va food I make is the most delicious and nourishing food i've ever eaten. Cheers!

very well,but do not mistake beta-Carotene with Vitamin A,there is only one,Retinol.Pseudovitamin-detox is plausible for disease-reversion.

 

[Orion]

very well,but do not mistake beta-Carotene with Vitamin A,there is only one,Retinol.Pseudovitamin-detox is plausible for disease-reversion.

Vitamin A is a fat-soluble group of unsaturated nutritional organic compounds; that comprises retinol, retinal, retinoic acid, and several pro-vitamin A carotenoids, and beta-carotene. Vitamin A cannot be converted into beta-carotene. Beta-carotene can be converted into vitamin A.

One molecule of beta-carotene can produce two molecules of retinol.

I believe there are studies showing that BC is building up in the liver with other VA storage, and to get it out needs to follow the VA pathway to retinoic acid.

 

[tim333]

Germans eat liverwurst though. Plus dairy and eggs, so... I find liver pate and nicely cooked liver tasty. To each it's own I guess.

Eggs are not that high in VA so you have to consume more than what the general population does to get problems. A few eggs a week and moderate quantities of milk or yoghurt are not problematic in people that are not VA toxic.

Butter, cream, cheese and liver products are problematic though. I doubt most middle aged to elderly germans and french are free of health problems. Serum retinol and liver retinol concentrations rise with age so a diet containing these things will likely lead to health problems, just a matter of time. Their VA intake is nothing like the amount one gets from a diet containing regular liver, cod liver oil, large amounts of high fat diary, large quantities of eggs and lots of high carotenoid foods which is the diet I followed years ago inspired by WAPF. If you analysed the liver retinol concentrations at autopsy of young germans and french you would find higher than desirable retinol levels, many would show Hypervitaminosis but because they aren't consuming extreme amounts of it and if their diet contains plenty of other nutrients then they may be relatively asymptomatic for the most part. Many of the symptoms of Hypervitaminosis A are due to the depletion of other nutrients by VA the most well known of which are: B1, B2, folate, biotin, choline, taurine, C, D, E, K2. So if you follow a high VA diet that is also low in these other nutrients you will notice symptoms more quickly.

We also need to keep in mind that genetic variation in tolerances to VA exist, even betweeen siblings.

very well,but do not mistake beta-Carotene with Vitamin A,there is only one,Retinol.Pseudovitamin-detox is plausible for disease-reversion.

Retinol is understood by scientists to be problematic in amounts over the RDA. Beta-carotene has always been deemed much safer though which is why I mentioned those studies. Even though beta-carotene and its breakdown products are toxic it is still safer than retinol. There are no known examples of acute Hypervitaminosis A occuring from carotenemia. Regardless, high beta-carotene vegetables (herbs are fine) may be best avoided.

In the tropics most starches are low carotene (manioc, plantains, grain, legumes) however in some places they eat a lot of sweet potato. In Papua New Guinea a portion of the population lives largely on them. It seems that they often eat it roasted by itself with no meat or fat or accompany it. If carotene is not consumed with any fat at all the absorption will be far less. Still, they may be getting more than optimal amounts of VA.

 

[Pet Peeve]

Eggs are not that high in VA so you have to consume more than what the general population does to get problems. A few eggs a week and moderate quantities of milk or yoghurt are not problematic in people that are not VA toxic.

Butter, cream, cheese and liver products are problematic though. I doubt most middle aged to elderly germans and french are free of health problems. Serum retinol and liver retinol concentrations rise with age so a diet containing these things will likely lead to health problems, just a matter of time. Their VA intake is nothing like the amount one gets from a diet containing regular liver, cod liver oil, large amounts of high fat diary, large quantities of eggs and lots of high carotenoid foods which is the diet I followed years ago inspired by WAPF. If you analysed the liver retinol concentrations at autopsy of young germans and french you would find higher than desirable retinol levels, many would show Hypervitaminosis but because they aren't consuming extreme amounts of it and if their diet contains plenty of other nutrients then they may be relatively asymptomatic for the most part. Many of the symptoms of Hypervitaminosis A are due to the depletion of other nutrients by VA the most well known of which are: B1, B2, folate, biotin, choline, taurine, C, D, E, K2. So if you follow a high VA diet that is also low in these other nutrients you will notice symptoms more quickly.

We also need to keep in mind that genetic variation in tolerances to VA exist, even betweeen siblings.



Retinol is understood by scientists to be problematic in amounts over the RDA. Beta-carotene has always been deemed much safer though which is why I mentioned those studies. Even though beta-carotene and its breakdown products are toxic it is still safer than retinol. There are no known examples of acute Hypervitaminosis A occuring from carotenemia. Regardless, high beta-carotene vegetables (herbs are fine) may be best avoided.

In the tropics most starches are low carotene (manioc, plantains, grain, legumes) however in some places they eat a lot of sweet potato. In Papua New Guinea a portion of the population lives largely on them. It seems that they often eat it roasted by itself with no meat or fat or accompany it. If carotene is not consumed with any fat at all the absorption will be far less. Still, they may be getting more than optimal amounts of VA.

There are no betacarotene or retinol receptors, only retinoic acid receptors. Carotenes and retinol only become problematic when they are metabolised to retinoic acid. You detox retinoic acid (accutane) through glucuronidation. This is copied directly from Gbolduev at hackstasis:

"retinoic acid is ACTI|VE FORM of vitamin A)))


it is accutane))

so taking b2 is same as taking accutane.



Retinoic ACID is ACCUTANE



ADH - ALDH make ACCUTANE in the body )))

it is not excretion))


you need stop mixing vitamin A overload in the liver as retinol

and retinoic acid.


people take accutane, since they cant make retinoic acid))

they dont have cofactors to make it))


and thus their vitamin A does not work in the body))

retinol has no receptors in the body)) it DOES NOTHING|


retinoic acid has receptors.


so increasing the cofactors to make retinoic acid, you are basically TAKING ACCUTANE)


Only accutane, bypasses glutathione regulation which is why it is bad.

you need FAD and NAPH for retinoic acid to be formed

since it will cause oxidation problems.

this is why enzymes that make retinoic acid could depend on b2 .


but also you need to realize that ALDH has nothing to do with FAD and molydenum


ALDH is NAD and cysteine enzyme. and magnesium and b6))

the second enzyme in aldehyde breakdown is AD which aldehyde oxidase, which is moly and FAD enzyme,

which is secondary enzyme. when ALDH goes down."

"It is not detox path)) it i the same as you can say that cholesterol to testosterone to DHT to excretion as glucucoranates are Detox pathway for cholesterol HAHA


it is the same as saying cholesterol is bad since it makes DHT)) LOL DHT in this case is accutane.


if you take DHT your cholesterol is not used. you inhibit the axis))


same as with vitamin A


vitamin A makes retinoic acid. which acts as a hormone and has specific receptors for it.

so taking ACCUTANE is like taking DHT)) it inhibits the axis of vitamin A>



if you want to totally kill vitamin A stores in the body ))) just block RAR and RXR receptors))

and your vitamin A will be gone all the pathway will be restored))



BUT If you think that you have accutane overload in TISSUES< that is what you are saying.

that means you are overloaded with RETINOIC ACID.

you surely dont want to make more retinoic acid. with any pathways in this case. You want to deplete retinoic acid

USE it up. in metabolism , before you make more of it from vitamin A.

This is why low A diet is good in this case.


I am not sure this is the case, but if your idea is that you are overloaded with accutane, that means you are overloaded with retinoic acid.

And retinoic acid can't be detoxed with any pathways))

it can be only detoxed with glucuronidation. same as DHT.


or you can use it up, with stuff like thyroid. which uses it up."

 

[tim333]

There are no betacarotene or retinol receptors, only retinoic acid receptors. Carotenes and retinol only become problematic when they are metabolised to retinoic acid. You detox retinoic acid (accutane) through glucuronidation. This is copied directly from Gbolduev at hackstasis:

"retinoic acid is ACTI|VE FORM of vitamin A)))


it is accutane))

so taking b2 is same as taking accutane.



Retinoic ACID is ACCUTANE



ADH - ALDH make ACCUTANE in the body )))

it is not excretion))


you need stop mixing vitamin A overload in the liver as retinol

and retinoic acid.


people take accutane, since they cant make retinoic acid))

they dont have cofactors to make it))


and thus their vitamin A does not work in the body))

retinol has no receptors in the body)) it DOES NOTHING|


retinoic acid has receptors.


so increasing the cofactors to make retinoic acid, you are basically TAKING ACCUTANE)


Only accutane, bypasses glutathione regulation which is why it is bad.

you need FAD and NAPH for retinoic acid to be formed

since it will cause oxidation problems.

this is why enzymes that make retinoic acid could depend on b2 .


but also you need to realize that ALDH has nothing to do with FAD and molydenum


ALDH is NAD and cysteine enzyme. and magnesium and b6))

the second enzyme in aldehyde breakdown is AD which aldehyde oxidase, which is moly and FAD enzyme,

which is secondary enzyme. when ALDH goes down."

"It is not detox path)) it i the same as you can say that cholesterol to testosterone to DHT to excretion as glucucoranates are Detox pathway for cholesterol HAHA


it is the same as saying cholesterol is bad since it makes DHT)) LOL DHT in this case is accutane.


if you take DHT your cholesterol is not used. you inhibit the axis))


same as with vitamin A


vitamin A makes retinoic acid. which acts as a hormone and has specific receptors for it.

so taking ACCUTANE is like taking DHT)) it inhibits the axis of vitamin A>



if you want to totally kill vitamin A stores in the body ))) just block RAR and RXR receptors))

and your vitamin A will be gone all the pathway will be restored))



BUT If you think that you have accutane overload in TISSUES< that is what you are saying.

that means you are overloaded with RETINOIC ACID.

you surely dont want to make more retinoic acid. with any pathways in this case. You want to deplete retinoic acid

USE it up. in metabolism , before you make more of it from vitamin A.

This is why low A diet is good in this case.


I am not sure this is the case, but if your idea is that you are overloaded with accutane, that means you are overloaded with retinoic acid.

And retinoic acid can't be detoxed with any pathways))

it can be only detoxed with glucuronidation. same as DHT.


or you can use it up, with stuff like thyroid. which uses it up."

Carotenoid breakdown products are genotoxic and cytotoxic, google it for studies...

It is not accurate to say that retinoic acid is Accutane. Accutane is 13-cis-retinoic acid. The useful form of retinoic acid in our body and the one most commonly discussed is all-trans-retinoic acid. After a meal of beef liver, any absorbed retinol not stored away in the liver is converted into a mix of all-trans and 13-cis.

B2 is needed to convert retinol to retinoic acid and it is also needed to convert retinoic acid to water soluble retinoids that get excreted in the urine. It is misleading to claim that taking B2 is the same as taking Accutane.

Never heard of Gbolduev, usually best to assume that any internet health guru is wrong.

 

[Vinero]

I think the reason it takes a long time is because it gets stuck at certain bottlenecks. You need FAD to convert retinol to retinoic acid. Then you need glucuronidation to transport the retinoic acid out of your body. Unless you supplement these bottlenecks can get overwhelmed. I was one month in eating rice, beef and beans, supplementing b2 and molybdenum and feeling worse than ever before, because I was converting a lot of VA to RA and not getting rid of it. Once I took the sulforaphane, dim, cdg combo it only took a few hours to feel good again. I think you should try this if you have a flare up.

Interesting. I am glad you are feeling better. I have also been experiencing increased detox symptoms from taking b2, molybdenum and also increasing my soluble fiber intake. Can you provide any evidence or more information as to why sulforaphane, dim, and cdg would help to excrete retinoic acid? I would like to learn more about it.

 

[LLight]

Talking about glucuronidation:

The Liver X-receptor Alpha Controls Hepatic Expression of the Human Bile Acid-Glucuronidating UGT1A3 Enzyme in Human Cells and Transgenic Mice - PubMed

"Glucuronidation, an important bile acid detoxification pathway, is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase (UGT) family. Among UGT enzymes, UGT1A3 is considered the major human enzyme for the hepatic C24-glucuronidation of the primary chenodeoxycholic (CDCA) and secondary lithocholic (LCA) bile acids. We identify UGT1A3 as a positively regulated target gene of the oxysterol-activated nuclear receptor liver X-receptor alpha (LXRalpha)."​

Water restriction could induce the upregulation of the CYP3A4 enzyme in the liver.
This enzyme seems to be able to convert cholesterols into oxysterols (25-hydroxycholesterol and 4β-hydroxycholesterol).

Moreover, these oxysterols are known to be ligands for the Liver X Receptor (LXR). What is interesting is that the LXR seems to be involved in testosterone synthesis in testis:
Liver X Receptor: A Cardinal Target for Atherosclerosis and Beyond

 

[Pet Peeve]

Interesting. I am glad you are feeling better. I have also been experiencing increased detox symptoms from taking b2, molybdenum and also increasing my soluble fiber intake. Can you provide any evidence or more information as to why sulforaphane, dim, and cdg would help to excrete retinoic acid? I would like to learn more about it.

Sure, wikipedia: Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids.

This means that if you experience VA detox symptoms you will most likely be full of estrogen and toxins as you are deficient in glucuronidation.

Selfhacked: Sulforaphane, found in cruciferous vegetables (with the highest levels in broccoli sprouts), increases glucuronidation. Research suggests It’s the most potent inducer of phase 2 detox enzymes (including UGTs) identified to date.

Beta-glucuronidase is an enzyme produced by gut bacteria (such as E. coli) and gut cells. This enzyme reverses the glucuronidation reaction and reactivates the inactivated toxins to their previous active form. Calcium-D-glucarate (D-glucaric acid) is found in many fruits and vegetables, with the highest levels in grapefruit, apples, oranges, and cruciferous vegetables. It is transformed in the stomach into D-glucaro-l,4-lactone, a natural inhibitor of beta-glucuronidase activity.

Sulforaphane and cdg often come together with dim in supplements, but it seems that dim mostly affects phase 1 estrogen metabolism and not glucuronidation (phase 2) so it might not be needed.

 

[tim333]

This means that if you experience VA detox symptoms you will most likely be full of estrogen and toxins as you are deficient in glucuronidation.

If one experiences VA detox symptoms the most likely reason is that one is toxic with retinoic acid, a substance that has a long and terrible list of symptoms when it is present in excess.

Selfhacked: Sulforaphane, found in cruciferous vegetables (with the highest levels in broccoli sprouts), increases glucuronidation. Research suggests It’s the most potent inducer of phase 2 detox enzymes (including UGTs) identified to date.

Sulphoraphane is an isothiocyanate, in other words it's a thyroid inhibiting toxin. Being a potent inducer of Phase II enzymes indicates that the liver identifies it as an important toxin. You know smoking induces Phase II enzymes as well? Inducing != supporting. Sulphoraphane supplements are a form of health fraud. The healthiest cruciferous vegetables are the ones that contain the lowest concentrations of isothiocyanates.

 

[Tristan Loscha]

There are no betacarotene or retinol receptors, only retinoic acid receptors. Carotenes and retinol only become problematic when they are metabolised to retinoic acid. You detox retinoic acid (accutane) through glucuronidation. This is copied directly from Gbolduev at hackstasis:

"retinoic acid is ACTI|VE FORM of vitamin A)))


it is accutane))

so taking b2 is same as taking accutane.



Retinoic ACID is ACCUTANE



ADH - ALDH make ACCUTANE in the body )))

it is not excretion))


you need stop mixing vitamin A overload in the liver as retinol

and retinoic acid.


people take accutane, since they cant make retinoic acid))

they dont have cofactors to make it))


and thus their vitamin A does not work in the body))

retinol has no receptors in the body)) it DOES NOTHING|


retinoic acid has receptors.


so increasing the cofactors to make retinoic acid, you are basically TAKING ACCUTANE)


Only accutane, bypasses glutathione regulation which is why it is bad.

you need FAD and NAPH for retinoic acid to be formed

since it will cause oxidation problems.

this is why enzymes that make retinoic acid could depend on b2 .


but also you need to realize that ALDH has nothing to do with FAD and molydenum


ALDH is NAD and cysteine enzyme. and magnesium and b6))

the second enzyme in aldehyde breakdown is AD which aldehyde oxidase, which is moly and FAD enzyme,

which is secondary enzyme. when ALDH goes down."

"It is not detox path)) it i the same as you can say that cholesterol to testosterone to DHT to excretion as glucucoranates are Detox pathway for cholesterol HAHA


it is the same as saying cholesterol is bad since it makes DHT)) LOL DHT in this case is accutane.


if you take DHT your cholesterol is not used. you inhibit the axis))


same as with vitamin A


vitamin A makes retinoic acid. which acts as a hormone and has specific receptors for it.

so taking ACCUTANE is like taking DHT)) it inhibits the axis of vitamin A>



if you want to totally kill vitamin A stores in the body ))) just block RAR and RXR receptors))

and your vitamin A will be gone all the pathway will be restored))



BUT If you think that you have accutane overload in TISSUES< that is what you are saying.

that means you are overloaded with RETINOIC ACID.

you surely dont want to make more retinoic acid. with any pathways in this case. You want to deplete retinoic acid

USE it up. in metabolism , before you make more of it from vitamin A.

This is why low A diet is good in this case.


I am not sure this is the case, but if your idea is that you are overloaded with accutane, that means you are overloaded with retinoic acid.

And retinoic acid can't be detoxed with any pathways))

it can be only detoxed with glucuronidation. same as DHT.


or you can use it up, with stuff like thyroid. which uses it up."

Retinoic Acid is not Accutane.They have siimilar chemical form and struc,but having differing affinity for the numerous retinX receptors.

 

[Pet Peeve]

@Vinero btw, you should consider cutting oxalates and test later if you react.

I also found this study: The exposed level of vitamin A in plasma might be exceeded due to the both inadvertent and clinical utilization. The adverse effects of vitamin A have been frequently reported, however, the mechanism remains unclear. The inhibition of vitamin A on the activity of UDP-glucuronosyltransferases (UGTs) was determined using in vitro incubation system to explain the adverse effects of vitamin A from a new perspective.

vitamin A significantly inhibited the activity of all the tested UGT isoforms.

The present study provides a new perspective for the adverse effects of vitamin A through reporting the inhibition of vitamin A on the activity of important phase II drug-metabolizing enzymes UGTs, which benefits our deep understanding of mechanism of vitamin A's adverse effects when high exposure of vitamin A occurs.

 

[Tristan Loscha]

If one experiences VA detox symptoms the most likely reason is that one is toxic with retinoic acid, a substance that has a long and terrible list of symptoms when it is present in excess.



Sulphoraphane is an isothiocyanate, in other words it's a thyroid inhibiting toxin. Being a potent inducer of Phase II enzymes indicates that the liver identifies it as an important toxin. You know smoking induces Phase II enzymes as well? Inducing != supporting. Sulphoraphane supplements are a form of health fraud. The healthiest cruciferous vegetables are the ones that contain the lowest concentrations of isothiocyanates.

indeed.In Germany,they actually put isothiocyanate and Fluoride in almost all commercial salts,which are often fortified with iodine,a desperately needed supplementation,European soils are rendered iodine deficient by some kind of prehistoric weather or climate event,maybe it was an Iceage,which eroded the soilbound iodine by washing it out into rivers and then into the larger bodies of water like seas and oceans.

 

[tim333]

indeed.In Germany,they actually put isothiocyanate and Fluoride in almost all commercial salts,which are often fortified with iodine,a desperately needed supplementation,European soils are rendered iodine deficient by some kind of prehistoric weather or climate event,maybe it was an Iceage,which eroded the soilbound iodine by washing it out into rivers and then into the larger bodies of water like seas and oceans.

Why are they adding isothiocyanate? Do you have a link?

Swiss soils can be very iodine deficient, I think that that is why dairy is popular there, it was the only accessible food (aside from animal thyroid) that contained iodine, non dairy consumers would have got goiter and died off.

I don't use iodized salt and I dont eat much bread which is the food item iodized here. I eat fish everyday which supplies iodine, selenium and dha. Iodine and selenium content of terrestrial foods is very variable. Tuna is the only common species that needs to be avoided due to mercury content. I eat mostly hoki and whiting. It amazes me how many health conscious people avoid fish.

 

[Tristan Loscha]

Why are they adding isothiocyanate? Do you have a link?

Swiss soils can be very iodine deficient, I think that that is why dairy is popular there, it was the only accessible food (aside from animal thyroid) that contained iodine, non dairy consumers would have got goiter and died off.

I don't use iodized salt and I dont eat much bread which is the food item iodized here. I eat fish everyday which supplies iodine, selenium and dha. Iodine and selenium content of terrestrial foods is very variable. Tuna is the only common species that needs to be avoided due to mercury content. I eat mostly hoki and whiting. It amazes me how many health conscious people avoid fish.

They do not have good reasons,same for the Fluorine.And sorry,I remembered it wrongly,it is a different cyanide containing compound,namely Sodium ferrocyanide.iirc,this and related compounds outcompeting iodine for uptake in the thyroidea,just like Fluorine,which also has deiodinase-inhibiting action,but not so sure.

 

[Amazoniac]

- The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation

Spoiler

"Aldehydes, such as formaldehyde, acetaldehyde, and acrolein, are ubiquitous in nature,[3] as byproducts of photochemical oxidation of plants and fuels, as by-products of industrial manufacturing, and as components in foods. The primary source of aldehydes in the outdoors is motor vehicle exhaust, which emits either aldehydes directly or compounds that can be photochemically oxidized to aldehydes. The indoor concentration of aldehydes, particularly in confined or poorly ventilated areas, is 4- to 10-fold higher and is attributed to smoking, cooking fumes, and industrial products, such as furniture, carpets, fabrics, disinfectants, perfumes, cosmetics, and salon products.[3] Particularly noteworthy, are that many foods, including fruits and vegetables, as well as natural food flavorings, such as vanilla, cinnamon, spearmint, peppermint, citrus, and cocoa, contain aldehydes.[3] Cooking at temperatures high enough to brown food also increases the concentration of aldehydes. Moreover, numerous pharmaceuticals and xenobiotics either contain aldehydes or are metabolized through aldehyde intermediates. Individuals with normal metabolisms generally have suitable in vivo mechanisms to rapidly detoxify the environmental onslaught of aldehydes. Those with abnormal metabolic antioxidant defense mechanisms or those low in detoxifying sulfurcontaining antioxidants are likely to suffer more immediate negative reactions to the environmental toxins."

"One source of endogenous aldehydes is that generated by the nonenzymatic oxidation of lipids and carbohydrates by the superoxide anion radical (•O2-) and other reactive oxygen species (ROS). Particular examples related to ASD are the lipidic aldehydes generated as a result of ROS attack on PUFAs as shown in Figure 1."

"Most endogenous aldehydes are quickly reduced, oxidized, or neutralized by the cellular antioxidant defense system to prevent the random interactions with surrounding biomolecules. Enzymes that reduce the aldehyde moiety to an alcohol (OH) group are members of the alcohol dehydrogenase (ADH), the aldo-keto reductase, or the shortchain dehydrogenase/reductase superfamilies.[3] Enzymes that oxidize the aldehyde moiety to an acid group include aldehyde dehydrogenase (ALDH) superfamily members as well as a few other miscellaneous enzymes, such as aldehyde oxidase, xanthine oxidase, and molybdenum hydroxylases.[3] Of note, some endogenous aldehydes are first conjugated with glutathione, before being detoxified by specific enzymes in the cellular antioxidant defense system.[3]"

"Gastrointestinal abnormalities are common among those suffering from neurodevelopmental disorders, including ASD. In addition to malabsorption problems in unhealthy intestines, abnormal microbiota of the gut appear to be contributing factors in ASD mouse models[28] as well as in humans.[29] One suggested explanation is that yeast and bacterial gut flora generate toxins, including alcohols and aldehydes, such as methylglyoxal, [30] during the metabolism of various carbohydrates. Methylglyoxal is a potent aldehyde implicated in numerous disorders.[3] Certainly, Candida infections common in ASD[31] have long been suspected of converting carbohydrates into ethanol,[32] which is subsequently metabolized to the potent neurotoxin, acetaldehyde. Alterations in the normal gut microflora of mice have also been linked to oxidative stress.[33] Research into the microbiota–gut–brain axis in neurodevelopmental disorders is in its earliest stages, but aldehydes may play an important role."

"Ethanol is known to compete directly for the retinol-binding site on the ADHs involved in the rate-limiting step of retinol oxidation, thereby decreasing the amount of retinal and retinoic acid that is ultimately produced."

"The lack of night blindness in ASD cases of vitamin A deficiencies suggests that retinal is present, but conversion to retinoic acid is blocked. An accumulation of retinal would have the same toxicity consequences as other endogenous aldehydes but with the added problem that a deficiency in retinoic acid would disrupt the retinoic acid response element (RARE)-dependent transcription of many key proteins in embryonic and neuronal development."

@ecstatichamster​

"In addition to reacting with small molecules, acetaldehyde is believed to cause long-term cellular damage in chronic alcoholism by reacting with macromolecules.[55,56] Acetaldehyde and other types of endogenous aldehydes cause disruptive tissue damage by reacting with accessible lysines, histidines, cysteines, and arginines on proteins[57] as well as by forming adducts with mainly deoxyguanine bases of DNA, promoting strand breakage and mutagenesis.[7] Curiously, although most proteins contain these amino acids, certain proteins are preferentially modified by acetaldehyde, including hemoglobin, albumin, tubulin, lipoproteins, collagen, cytochrome P450 2E1 (CYP2E1), and ketosteroid reductase.[58]"

"Moreover, the targets of lipid peroxidation-generated aldehydes are specific to cell types, aldehyde concentration, and the pattern of proteins expressed, giving rise to differential effects upon cell function.[5] The lipid peroxidation-derived aldehydes have been implicated in cardiovascular, neurodegenerative, chronic inflammatory, and autoimmune diseases as well as cancer and aging.[8] In addition to macromolecular damage, Hao and Maret[59] have shown how the lipid peroxidation-generated aldehydes release Zn2+ from proteins by binding to cysteines typically found in Zn2+-binding sites. In this regard, it is noteworthy that zinc supplementation attenuates oxidative stress in mice by suppressing the ethanol-induced CYP2E1 activity but increasing the activity of liver ADH.[60]"

"Most of the evidence for selective, aldehyde-induced micronutrient deficiencies arises from the alcoholism literature and the study of acetaldehyde, the intermediate of ethanol metabolism. Prolonged ethanol consumption is known to cause oxidative stress[35] and induce deficiencies in a number of key nutrients, including but not limited to retinol, glutathione, Zn2+, B1, B6, and folate.[36] Although the nutrient-deficient status of an alcoholic is often attributed to a nutrient-poor diet or to ethanol-induced malabsorption, the reality is much more complex.[37] The mechanism for some micronutrient deficiencies includes direct reactions with the electrophilic acetaldehyde generated during ethanol metabolism. For example, ethanol is known to induce B1[38] and B6[39] deficiencies and to lower hepatic glutathione levels in alcoholics by several mechanisms. In one B1 mechanism demonstrated in vitro, the electrophilic acetaldehyde attacks the C2 adjacent to the sulfur in the thiophene ring of B1, thereby lowering the bioavailability of B1.[40]"

- Comprehensive Biochemistry for Dentistry (978-981-13-1035-5) - 11. Vitamins

"One mechanism for the decrease in hepatic glutathione levels involves the binding of the reactive acetaldehyde, not to glutathione directly, but to the glutathione intermediate cysteinylglycine.[41] Similarly, acetaldehyde also reacts directly with selective amino acids and sulfur-containing antioxidants, such as N-acetylcysteine (NAC) and taurine.[42] Ethanol ingestion is also known to induce folate deficiencies, with one mechanism demonstrating the acetaldehyde-induced cleavage of folate by xanthine oxidase.[43] Although there are no reports of B6-acetaldehyde adducts, the activated form of B6, pyridoxal-5-phosphate (P5P), is a type of aldehyde, which is known to form condensation products with other aldehydes, thereby decreasing the bioavailability of B6. In fact, the evidence for B6-aldehyde condensation products formed in vivo in localized intracellular regions is the strongest and most convincing of all micronutrient studies.[44] Two well-established examples include LoF mutations in pyrroline-5-carboxylate dehydrogenase[45] and in a-aminoadipic semialdehyde dehydrogenase,[24,46,47] also known as antiquitin, which cause the intermediate aldehydes to accumulate. In both examples, the aldehyde intermediates react irreversibly with P5P, forming condensation products that are subsequently detected in the urine. Although a global B6 deficiency is not detected by standard clinical assays, the ensuing, cell-localized B6 deficiency causes atypical B6-dependent seizures in both disorders. The reaction is shown in Figure 3 for antiquitin. Although the investigators show only hydrogen atoms neutralizing the double negative charges on the P5P in their original literature reports, this author suggests that neutralization of the double charge by hydrogen atoms is unlikely at the typical cellular pH. The charge is more likely to be neutralized by divalent metal ions, such as Mg2+ or Zn2+, creating a localized deficiency in the neutralizing atoms. B6 and folate are cofactors in methylation reactions; so chronic deficiencies in one or both disrupt the methylation of DNA,[48] which subsequently alters certain transcriptional signaling, DNA repair mechanisms, and chromatin remodeling.[49] In addition to these micronutrients, there are suggestions that acetaldehyde [] may also react with ["cobalamin, inositol, and other carbohydrate aldoses"], but at present, there is a paucity of chemical data to confirm such reactions. Moreover, there are no systematic studies that address the interaction of reactive aldehydes with other micronutrients. Taken together, aldehyde toxicity induces micronutrient deficiencies in sulfur-containing antioxidants, Zn2+, B6, B1, Mg2+, and folate, creating oxidative stress and disruptions in a cascade of metabolic reactions."

"With all the cellular damage done by accumulated endogenous aldehydes, it is not surprising that some types of treatment are being devised to counteract the damage."

"Until targeted pharmacological therapies become available, the alternative treatment is the use of commercially available antioxidants. The best appear to be the sulfur-containing antioxidants: taurine and the bioavailable form of cysteine, N-acetyl cysteine (NAC)."

"Some research indicates that taurine interacts directly with aldehydes[42] and potentially with some free radicals at physiological concentrations.[64]"

"Lipoic acid, another sulfur-containing antioxidant, also seems to be effective in protecting against 4-HNE-mediated oxidative stress.[72]"

"There are a myriad of studies in which single micronutrient supplementation has been assessed, with several reporting mitigation, but not complete elimination, of some ASD symptoms. Many of the micronutrients studies have been based on plasma and urinary clinical results, which suggest the elevation of lipid peroxide-generated aldehydes (HNE, MDA)[84–86] as well as deficiencies in antioxidants, such as vitamin E, sulfur-containing compounds, such as cysteine, methionine, and GSH,[119] carnitine,[120] biotin,[121] and (n-3) PUFAs.[122] Given the depressed levels of sulfur-containing compounds in ASD individuals, it is not surprising that these children are more sensitive than neurotypicals to the exposure of mercury and other heavy metals.[78] The antioxidant supplements, which show symptom improvements include, but are not limited to ubiquinol,[123] NAC,[124] carnosine, and vitamin C.[125] Other micronutrients, including B1,[126] B6-Mg2+,[127] folate, vitamin E, retinol, and Zn2+, have been selected for a variety of reasons relating to the involvement in abnormal metabolic pathways implicated in ASD,[1] even though the clinical assays do not always show a deficiency in ASD individuals compared to neurotypical controls.[119]"

"Unless one is using supplements containing an extended-release compound, it is best to administer water-soluble micronutrients thrice a day to a child as 50% of water-soluble vitamins pass into the urine within four hours."

"It may take several months to observe a positive response with a low-dose supplementation regimen due to the up- and downregulation of genes as enzymes adjust to new micronutrient levels. With higher pharmacological doses of micronutrients, definitive improvement may be observed within days. However, it must be noted that very high micronutrient doses are absorbed by passive diffusion mechanisms, while the active diffusion mechanisms are inactivated by the downregulation of nutrient transporters.[147] Thus, an individual must be weaned slowly from high micronutrient doses to allow enough time to upregulate the active transporter mechanisms again. Obviously, before any supplement plan is initiated, triggers of symptoms including infections, allergens, and environmental risk factors, should be identified, if possible, and eliminated."

- Aldehyde oxidase and its role as a drug metabolizing enzyme
- Aldehyde Oxidase: Reaction Mechanism and Prediction of Site of Metabolism
- Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily

- Aldehyde oxidase - Wikipedia
- Aldehyde dehydrogenase - Wikipedia
- Retinal dehydrogenase - Wikipedia


- Influence of food commodities on hangover based on alcohol dehydrogenase and aldehyde dehydrogenase activities

Check out tables 2 and 3. It was a realistic experiment of combining foods' juices or extracts with the enzymes, adequate temperature, pH, and so on. There's expression in the upper gut and some of the responsible compounds might also reach places where they can inhibit them (promotion is trickier, can be by traces of substrates in which they're supposed to act), but it's more out of curiosity.​

 

[mrchibbs]

Germans eat liverwurst though. Plus dairy and eggs, so... I find liver pate and nicely cooked liver tasty. To each it's own I guess.

Most cultures eat organs. In fact the glands/offals are often mixed up in some sort of product like liverwurst. Good liver pate on sourdough bread is extremely tasty.

 

[tim333]

Most cultures eat organs. In fact the glands/offals are often mixed up in some sort of product like liverwurst. Good liver pate on sourdough bread is extremely tasty.

They ate nose to tail for economic reasons. Despite having liver in their diet they had a tendency towards VA deficiency rather than excess. Meaning they didn't eat liver much and there were factors that lowered VA such as parasitic and viral infection.

Today Hypervitaminosis A is common so it makes no sense to appeal to historical liver consumption.

 

[mrchibbs]

They ate nose to tail for economic reasons. Despite having liver in their diet they had a tendency towards VA deficiency rather than excess. Meaning they didn't eat liver much and there were factors that lowered VA such as parasitic and viral infection.

Today Hypervitaminosis A is common so it makes no sense to appeal to historical liver consumption.

Not sure I follow your perspective

 

[Amazoniac]

- Enzyme Commission number - Wikipedia
Check out the Wikipedia links on my previous post and the identifiers on the right box. It can avoid confusion since there are various synonyms and the enzymes are also related.

They used to refer to 'Retinol Dehydrogenase' as 'Retinene Reductase', but the problem persists: defining substrate and function. In Prolactinese we would settle it as Poisonoid Cyclase. It can't be Intoxicase, Profitase or Shitinase because we don't know its origin and fate, the body may be defending towards excretion while you're accusing storage. But Poisonoid Cyclase may be too appropriate for Prolactinese, Satanase could work since it doesn't matter the substrate and product, we know it's evil on both ends.

I was charnathaning in using the term 'symmetric cleavage' of carotenoids because it's not always mirrored, centric is better. But then there's eccentric, which we don't associate with ex-centric or away from the center. Noncentric could be the alternative of choice for Prolactinese nomenclature. Again, too correct; isntiscenter shattering.


- BRENDA - Information on EC 1.2.1.36 - retinal dehydrogenase (useful website, click on 'show all')
When you spot 'retinoate', it's the deprotonidizated/conjugated base of poisonoic acid, amalogous to acetate and acetic acid (or ethanoate and ethanoic acid).

Poisonyl is for poisonol, poisonoyl is for poisonoic acid.

• Retinyl beta-glucuronide (C26H38O7)
• Retinoyl beta-glucuronide (C26H36O8)

With the attached molecule conserved, the difference matches the conversions:

• C20H30O - Poisonol
• C20H28O - Poisonal
• C20H28O2 - Poisonoic acid

Next time you find someone suggesting that it's dispensable, seek a specific and atoxic inhibitor of the enzyme that produces the metabolite in question and tell the person to take it as proof.

 

[Amazoniac]

Since the idea that these toxins are funneled and has to necessarily go through the classic pathway for excretion continues to circulate, below are some known alternative routes where each major metabolite can be made weaker and primed for elimination without having to be metabolized further down the expected course, changes are equivalent to those on poisonoic acid (gluscuronidization, oxidation of the ring by P450 enzymes, and so on).

- The Vitamins: Fundamental Aspects in Nutrition and Health (978-0-12-802965-7) - Gerald F. Combs and James P. McClung

Spoiler

- Dissecting Germ Cell Metabolism through Network Modeling

Spoiler

- Elevated serum concentrations of β-glucuronide metabolites and 4-oxoretinol in lactating sows after treatment with vitamin A: a model for evaluating supplementation in lactating women