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

[tim333]

Methanol is definitely something we want to minimise in our diet. Surprisingly the most important source of methanol and formaldehyde is fruit and vegetable consumption. I did a yt video on it:

 

[mmb82]

Methanol is definitely something we want to minimise in our diet. Surprisingly the most important source of methanol and formaldehyde is fruit and vegetable consumption. I did a yt video on it:

I watched your "Vitamin A toxicity, a Hidden Epidemic" video as well. It sounds like you are a believer that vitamin A toxicity is real, but aren't fully convinced it is a toxin/poison like Grant does. Am I interpreting that correctly?

I find your approach much more realistic than Grant and Dr. Smith's.

 

[md_a]

Methanol is definitely something we want to minimise in our diet. Surprisingly the most important source of methanol and formaldehyde is fruit and vegetable consumption. I did a yt video on it:

I've asked Travis about methanol in the past. His answer refers to folic acid as protection against the toxicity of methanol which also seems to provide protection against vitamin A toxicity as shown in this study.

`Here we have a study that proved folic acid also prevented birth defects caused by retinoic acid.`

“Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused se- vere ultrastructural damages in Meckel’s cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg.”

http://www.journal.med.tohoku.ac.jp/2051/TJ2051_04.pdf

...
md_a, Apr 10, 2018

`Hello Travis, do you have any opinion about methanol exposure after ingestion of pectin fruits like apple, as I understand methanol is very toxic to the human body because it is metabolized into formaldehyde and then to formic acid or formate salts. These are poisonous to the central nervous system. Thanks`

Formate as an inhibitor of cytochrome C oxidase..

https://www.researchgate.net/publication/240197119_Formate_as_an_inhibitor_of_cytochrome_C_oxidase

Travis:
What is the lowest concentration shown to be poisonous?

The reason I say that is that methanol and formate are both one-carbon units and we do need those too; we produce methanol naturally even in the absence of pectin (Lindinger, 1997). Considering one-carbon units: Methyl groups can come from many sources, such as methionine and choline, but they can also be liberated from serine's carbon backbone by enzymes having a folic acid cofactor. Folate-containing enzymes can use formate directly—sparing the amino acid serine. Below is a graph illustrating how folate keeps methanol levels in range, even after a massive 4·g/kg i.p. injection (the solid lines):

Now the study that had demonstrated a roughly tenfold increase of expired methanol consequent of the consumption of 1·kg apples did not report folate levels of the four test subjects (Lindinger, 1997); in fact, the authors hadn't even mentioned them . . . and ostensibly hadn't even considered them. They had simply used four people—perhaps with varying stages of folate deficiency—and had explained the variability in expired methanol by 'differences in enteric bacteria,' even though the amount of methoxy-pectin not absorbed had not been determined.

I'm not too concerned about pectin-derived methanol. First of all: I very rarely eat one kilo of apples at one time but about half that amount (I'd expect half the increase; in addition, I eat enough enough leaves to absorb more folate than I know what to do with—likely far more than the four random Austrians* depicted above. The graph above should represent the worst-case scenario and cannot be logically extrapolated to routine fruit consumption for the following reasons: (1) apples have more methoxylated pectin than has any other common fruit; (2) the above graph depicts methanol concentrations after the consumption of relatively large amounts (~1·kg) of apples; and (3) no indication of folate status was given, Austrians can be logically presumed to have lower than global mean intakes, and having adequate levels of this cofactor (folate)—as shown above—allows one to assimilate formate at a greatly accelerated rate.

*How much folate is in beer, sausage, and cheese?
Makar, A. "Methanol poisoning in the folate-deficient rat." Nature (1976)
Lindinger, W. "Endogenous production of methanol after the consumption of fruit." Alcoholism: clinical and experimental Research (1997)

 

[rob]

Really interesting contributions on the aldehyde front.

Worth noing the contribution of molybdo-flavoenzymes. They've been indicated to play a role in the metabolism of aromatic aldehydes, as per drug metabolism and biogenic amine catabolism (see Contribution of Aldehyde Oxidase, Xanthine Oxidase, and Aldehyde Dehydrogenase on the Oxidation of Aromatic Aldehydes - PubMed).

On the aldehyde dehydrogenases, Nrf2 seems a significant regulator with potent agonists, such as sulforaphane, possibly helping alcohol intolerance (see Sulforaphane Accelerates Acetaldehyde Metabolism by Inducing Aldehyde Dehydrogenases: Relevance to Ethanol Intolerance).

 

[Svdmeere]

I found this blog and I find it interesting in terms of the idea of aldehyde toxicity from an dehydrogenase system unable to function properly due to lack of cofactors.

My Blog — Eric Levinson Health Coaching

From: Eric Justin Levinson

Folic acid is known to prevent birth defects.

How does one become deficient?

Methanol and formaldehyde require the same dehydrogenase enzymes to be oxidized into formic acid.

Retinol > retinaldehyde > retinoic acid (vitamin A)

Alcohol > acetaldehyde > acetic acid

Same pathway.

The acid forms require a oxidizing agent to eliminate them safely.

Acetic acid requires a mineral base.

Retinoic acid requires taurine.

Formic acid requires folinic acid.

Folinic acid is the fully reduced folic acid, ready for the body to use.
View attachment 18299
Formaldehyde/methanol exposure is going to deplete folic acid. And aldehydes, including formaldehyde, acetaldehyde, and retinaldehyde cause birth defects.

Here we have a study that proved folic acid also prevented birth defects caused by retinoic acid.

“Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused se- vere ultrastructural damages in Meckel’s cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg.”

http://www.journal.med.tohoku.ac.jp/2051/TJ2051_04.pdf

Now you know why, women supplementing with vitamin A in a prenatal multi, in addition to their dietary and fortified vitamin A, need very high doses of folic acid to compensate for the dangers of the high vitamin A intake.

...

Retinol is actually "vitamin A alcohol," and causes similar problems as alcohol, including birth defects known as fetal retinoid syndrome.

It's metabolized by the same dehydrogenase enzymes as alocohol and methanol, which creates aldehydes.

Much better would be to support the dehydrogenase system and eliminate the build up of toxic aldehydes.


Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities

...

When our dehydrogenase system is inhibited, we build up aldehydes, like vitamin A, which cause headaches.

Our dehydrogenase turns alcohol into acetaldehyde, and that gets turned into acetic acid.

Same pathway for vitamin A and formaldehyde.


Retinaldehyde is made when we split a beta-carotene molecule in half, or when vitamin A alcohol (retinol) is metabolized into an aldehyde in the process of eliminating it form the body.


Some of our most important neurotransmitters like dopamine, and other important chemicals like pyruvate, depend on this system to prevent the build up of aldehydes that are created when these chemicals are used up in the body.[1]

However, dehydrogenase is a finite resource.

It is easily overwhelmed by to much aldehyde exposure from things like air pollution, or when they build up in the body.

The resources required to make it are also easily depleted.

Like zinc, for example.[2]

Now you know why everyone with coronavirus does so much better when they supplement with zinc.

Because without zinc, they can't make dehydrogenase to get rid of the aldehydes that are damaging their lungs.

Aldehydes are also released from combustion of fossil fuels, including natural gas from our stoves.

Interestingly, ethanol blend fuels, like the 10% ethanol we use in the US, releases more aldehydes than straight petroleum gasoline.

Adding ethanol increases the aldehyde emissions 40%![3]

So what does the EPA say about inhalation of aldehydes?

Aldehydes constrict airway passages, and "can also damage cells lining the airways, prompting white blood cells to enter the lungs."[4]

What happens when white blood cells enter the lungs?

Well, that's pneumonia.[5]

And all those aldehydes our bodies make, one of the ways we get rid of them is by our breath.

That's why people have that distinctive breath in the morning after a long night of drinking.

It's aldehydes.


Our dehydrogenase turns alcohol into acetaldehyde.

Methanol becomes formaldehyde.

Retinol becomes retinaldehyde.

That's the process our bodies use to break down retinoids, also known as vitamin A and beta carotene.

So if we are consuming high amounts of retinoids in our diets, we are depleting that vital resource our bodies produce to protect us from the aldehydes from air pollution.

So, many sources of aldehydes in our air cannot be avoided, neither can our endogenous aldehydes.

We can learn to effectively limit them in our diets.

And then our zinc supplementation can do much more to protect our lungs from air pollution.

My Blog — Eric Levinson Health Coaching

Dehydrogenase - Wikipedia

Does anyone know if this Eric Levinson is legit? From what I can make out of his blog and testimonials, he has found some way of speeding up recovery on the low-vitamin A diet (primarily weight loss). I watched one of his webinars but no specifics regarding therapy are mentioned.

 

[tim333]

I watched your "Vitamin A toxicity, a Hidden Epidemic" video as well. It sounds like you are a believer that vitamin A toxicity is real, but aren't fully convinced it is a toxin/poison like Grant does. Am I interpreting that correctly?

I find your approach much more realistic than Grant and Dr. Smith's.

Thanks for checking it out. Yes, there is extensive evidence that vA is a vitamin and in my opinion nobody including Grant has shown any convincing evidence that it is not a vitamin.

The science is clear that chronic subclinical Hypervitaminosis A is an epidemic in modern Western nations. Retinol supplementation, cod liver oil consumption or liver consumption fast tracks it.

Thanks, I'm science based and very much about avoiding logical fallacies.

 

[tim333]

I've asked Travis about methanol in the past. His answer refers to folic acid as protection against the toxicity of methanol which also seems to provide protection against vitamin A toxicity as shown in this study.

`Here we have a study that proved folic acid also prevented birth defects caused by retinoic acid.`

“Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused se- vere ultrastructural damages in Meckel’s cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg.”

http://www.journal.med.tohoku.ac.jp/2051/TJ2051_04.pdf

...
md_a, Apr 10, 2018

`Hello Travis, do you have any opinion about methanol exposure after ingestion of pectin fruits like apple, as I understand methanol is very toxic to the human body because it is metabolized into formaldehyde and then to formic acid or formate salts. These are poisonous to the central nervous system. Thanks`

Formate as an inhibitor of cytochrome C oxidase..

https://www.researchgate.net/publication/240197119_Formate_as_an_inhibitor_of_cytochrome_C_oxidase

Travis:
What is the lowest concentration shown to be poisonous?

The reason I say that is that methanol and formate are both one-carbon units and we do need those too; we produce methanol naturally even in the absence of pectin (Lindinger, 1997). Considering one-carbon units: Methyl groups can come from many sources, such as methionine and choline, but they can also be liberated from serine's carbon backbone by enzymes having a folic acid cofactor. Folate-containing enzymes can use formate directly—sparing the amino acid serine. Below is a graph illustrating how folate keeps methanol levels in range, even after a massive 4·g/kg i.p. injection (the solid lines):

Now the study that had demonstrated a roughly tenfold increase of expired methanol consequent of the consumption of 1·kg apples did not report folate levels of the four test subjects (Lindinger, 1997); in fact, the authors hadn't even mentioned them . . . and ostensibly hadn't even considered them. They had simply used four people—perhaps with varying stages of folate deficiency—and had explained the variability in expired methanol by 'differences in enteric bacteria,' even though the amount of methoxy-pectin not absorbed had not been determined.

I'm not too concerned about pectin-derived methanol. First of all: I very rarely eat one kilo of apples at one time but about half that amount (I'd expect half the increase; in addition, I eat enough enough leaves to absorb more folate than I know what to do with—likely far more than the four random Austrians* depicted above. The graph above should represent the worst-case scenario and cannot be logically extrapolated to routine fruit consumption for the following reasons: (1) apples have more methoxylated pectin than has any other common fruit; (2) the above graph depicts methanol concentrations after the consumption of relatively large amounts (~1·kg) of apples; and (3) no indication of folate status was given, Austrians can be logically presumed to have lower than global mean intakes, and having adequate levels of this cofactor (folate)—as shown above—allows one to assimilate formate at a greatly accelerated rate.

*How much folate is in beer, sausage, and cheese?
Makar, A. "Methanol poisoning in the folate-deficient rat." Nature (1976)
Lindinger, W. "Endogenous production of methanol after the consumption of fruit." Alcoholism: clinical and experimental Research (1997)

Interesting, thanks for that.

With methanol I think a balanced approach is best, we've consumed pectin for millions of years yet it does convert into methanol, one dessertspoon of which can cause permanent blindness. Conservative fruit and vegetable consumption seems like the most optimal approach to me.

"I'm not too concerned about pectin-derived methanol. First of all: I very rarely eat one kilo of apples at one time but about half that amount (I'd expect half the increase; in addition, I eat enough enough leaves to absorb more folate than I know what to do with—likely far more than the four random Austrians* depicted above. The graph above should represent the worst-case scenario and cannot be logically extrapolated to routine fruit consumption for the following reasons: (1) apples have more methoxylated pectin than has any other common fruit; (2) the above graph depicts methanol concentrations after the consumption of relatively large amounts (~1·kg) of apples; and (3) no indication of folate status was given, Austrians can be logically presumed to have lower than global mean intakes, and having adequate levels of this cofactor (folate)—as shown above—allows one to assimilate formate at a greatly accelerated rate."

This paragraph feels like he is trying to rationalize his fruit consumption! Apples aren't an especially high source of pectin, most fruit has quite similar levels. He's also making the assumption that folate status has a significant effect on breath methanol levels without evidence. Yep they consumed 1kg of apples to make the effect more significant but so what? He admits to consuming just half that amount which will definitely lead to a significant increase in blood methanol. And why is he discussing how many leaves he personally eats? Imagine an alcohol drinker justifying ethanol in general by saying they personally consume a B complex every day... fortifying one's diet with nutrients that are depleted during the metabolism of a given toxin does not completely protect against the toxic effects of that given toxin anyway.

 

[Tarmander]

Hey guys,

I did an interview with Dr. Garrett Smith on my podcast: Ep. 63 Interview Dr. Garrett Smith: Vitamin A is Still a Poison and Other Discoveries - Quax Podcast

I know some of you guys can't stand him, but I respect his willingness to commit to an idea, make predictions, and admit when he is wrong.

In this interview he definitely admits to giving people supplements he now thinks are disastrous

Definitely a controversial figure. Let me know what you think.

 

[tallglass13]

Here are some quotes from Ray Peat about vitamin A. I find the last quote particularly interesting. So Ray does knows about the toxic effects of vitamin A.
"Since vitamin A is highly unsaturated, in excess it suppresses the thyroid."
"I avoid carotene, because it blocks thyroid and steroid production, and very large, excessive, amounts of vitamin A, retinol, can do the same."
"Vitamin A oxidizes easily and an excess can create symptoms of a deficiency, so vitamin E is the most important thing for correcting it; excess vitamin A, like PUFA, interferes with thyroid hormone transport, so it’s important to balance the two."

 

[Sulcuscentralis]

Here are some quotes from Ray Peat about vitamin A. I find the last quote particularly interesting. So even Ray knows about the toxic effects of vitamin A.
"Since vitamin A is highly unsaturated, in excess it suppresses the thyroid."
"I avoid carotene, because it blocks thyroid and steroid production, and very large, excessive, amounts of vitamin A, retinol, can do the same."
"Vitamin A oxidizes easily and an excess can create symptoms of a deficiency, so vitamin E is the most important thing for correcting it; excess vitamin A, like PUFA, interferes with thyroid hormone transport, so it’s important to balance the two."

So the question follows - what would be a "toxic" dose? Probably highly individual.

 

[tallglass13]

So the question follows - what would be a "toxic" dose? Probably highly individual.

To me it seems that having good thyroid function is able to handle the vitamin A in the diet. Whether it be a natural slightly hyperthyroid state or supplementing with thyroid. From what Ray is saying that if you have low thyroid then you shouldn't eat a lot of vitamin A. I think all of this coincides with the vitamin A toxicity Theory. If one is able to handle the vitamin A with very good thyroid and and use it to turn it into steroids then it's okay. I still won't be eating liver or supplementing any vitamin A of course. But I seem to handle cheese and skim milk that is un-fortified very well. And I think since starting a desiccated thyroid supplement, I may even see more Improvement. Bright light and staying in the sun is important to burnout extra vitamin A as well. So without sunlight or incandescent lights in the home, and with low thyroid function, vitamin A can build up and do damage as Grant is proving.

 

[Tarmander]

To me it seems that having good thyroid function is able to handle the vitamin A in the diet. Whether it be a natural slightly hyperthyroid state or supplementing with thyroid. From what Ray is saying that if you have low thyroid then you shouldn't eat a lot of vitamin A. I think all of this coincides with the vitamin A toxicity Theory. If one is able to handle the vitamin A with very good thyroid and and use it to turn it into steroids then it's okay. I still won't be eating liver or supplementing any vitamin A of course. But I seem to handle cheese and skim milk that is un-fortified very well. And I think since starting a desiccated thyroid supplement, I may even see more Improvement. Bright light and staying in the sun is important to burnout extra vitamin A as well. So without sunlight or incandescent lights in the home, and with low thyroid function, vitamin A can build up and do damage as Grant is proving.

I think thats true

I also think something changed in the 1970s and 1980s that made dealing with VA and a host of other chemicals much harder. People who were born before that time seem to have little problem dealing with VA overload

 

[tallglass13]

I think thats true

I also think something changed in the 1970s and 1980s that made dealing with VA and a host of other chemicals much harder. People who were born before that time seem to have little problem dealing with VA overload

Yes and thank you tarmander.
It seems that there is over fortification in the milk and of course it's a synthetic supplement, not a natural form anyways. I have been lucky enough to find raw organic skimmed milk that has virtually no vitamin A. If there is raw cheese that's white that's not colored with beta-carotene.
Ray has talked about the vaccines starting around 1980 or maybe a little earlier, and that seems to correlate with what Grant talks about and how vaccines May make it difficult to use vitamin A properly.

 

[Diokine]

I also think something changed in the 1970s and 1980s that made dealing with VA and a host of other chemicals much harder.

I think it's interesting to examine the links between vaccination scheduling, effects of vaccination on the HPA axis, glucocorticoid dysregulation, and insulin resistance as a consequence of disrupted mitochondrial "membrane." It is not hard to imagine a scenario where persistent exposure to glucocorticoids induces an inability to oxidize fats, leading to an accumulation of FFA, glucose intolerance and an inability to handle, process, or incorporate unsaturated fatty acids like retinol.

 

[tim333]

Here are some quotes from Ray Peat about vitamin A. I find the last quote particularly interesting. So Ray does knows about the toxic effects of vitamin A.
"Since vitamin A is highly unsaturated, in excess it suppresses the thyroid."
"I avoid carotene, because it blocks thyroid and steroid production, and very large, excessive, amounts of vitamin A, retinol, can do the same."
"Vitamin A oxidizes easily and an excess can create symptoms of a deficiency, so vitamin E is the most important thing for correcting it; excess vitamin A, like PUFA, interferes with thyroid hormone transport, so it’s important to balance the two."

What does the saturation of vA have to do with it's thyroid toxicity? 10 grams of Accutane will significantly shrink a thyroid, this is because of the molecule's level of saturation?

Carotenoids are problematic but are way safer than retinol.

Excess vA never creates symptoms of a vA deficiency! VAD causes xeropthalmia from dry eyes all the way through to blindness. Accutane can cause the initial stages of xeropthalmia because 13-cis-retinoic acid inhibits the enzymatic production of retinal in the eye. Someone would have to have severe Hypervitaminosis A to create the same effect. With Accutane and Hypervitaminosis A it can only go as far as dry eyes whereas VAD causes xeropthalmia, a term which describes the progression of dry eyes through to total blindness.

 

[tim333]

I think thats true

I also think something changed in the 1970s and 1980s that made dealing with VA and a host of other chemicals much harder. People who were born before that time seem to have little problem dealing with VA overload

Probably. However there is more than one study from around the sixties showing high levels of Hypervitaminosis A in the general population. Garrett Smith discusses them in a recent video he did.

 

[Blossom]

Hey guys,

I did an interview with Dr. Garrett Smith on my podcast: Ep. 63 Interview Dr. Garrett Smith: Vitamin A is Still a Poison and Other Discoveries - Quax Podcast

I know some of you guys can't stand him, but I respect his willingness to commit to an idea, make predictions, and admit when he is wrong.

In this interview he definitely admits to giving people supplements he now thinks are disastrous

Definitely a controversial figure. Let me know what you think.

Thank you for posting the interview.

 

[Amazoniac]

Below, they labeled oxygen atoms in water (left side of the tables) or oxygen (right side of the tables) molecules to track their incorporation into poisonals when carotenes are cleaved. It's the 18 variant that they were following.

- The Human Enzyme That Converts Dietary Provitamin A Carotenoids to Vitamin A Is a Dioxygenase

Spoiler: Figure 1. Human BCO1 is a dioxygenase

 

[Amazoniac]

- The multifaceted nature of retinoid transport and metabolism

Spoiler

"[..]with the completion of the Human Genome Project, the gene encoding RBP, the serum/plasma transport protein for retinol, was given the designation RBP4. Classically though, this protein has been known as RBP. Both RBP and RBP4 appear in current literature, with RBP4 being commonly used in the literature focused on its role in metabolic disease. However, both RBP and RBP4 refer to the same protein, encoded by the same gene."

"Until recently, it was generally thought that the sole important retinoid delivery pathway to tissues involved retinol transported throughout the circulation bound to RBP4. Indeed, in the fasting human circulation, approximately 95% of the retinoids present exists as retinol bound to RBP4, with normal adult concentrations of approximately 2-4 µM (38-40). The retinol-RBP4 complex is secreted from the hepatocyte into the circulation to allow for retinol delivery to retinoid-dependent peripheral tissues, where it can be oxidized to retinoic acid (41). Retinol-RBP4 is found in the circulation as a complex with another protein, transthyretin (TTR). Binding to TTR stabilizes the retinol-RBP4 complex, thereby reducing renal filtration of RBP4 and allowing for RBP4 to be recycled after retinol is taken into cells (41)."

"Another pathway for retinoid delivery to peripheral tissues—known for many years but the true significance of which has gone unrecognized—involves transport of dietary retinyl esters in chylomicrons (as depicted in Figure 2). Retinyl esters are packaged in chylomicrons along with other dietary fat (including cholesterol and triglyceride). Chylomicrons are secreted into the lymphatic system and eventually enter the general circulation through the thoracic duct (41). Before clearance by peripheral tissues, retinyl esters must first be hydrolyzed to retinol by lipoprotein lipase (LPL) (42). This newly formed retinol is thought to bind to cellular retinol-binding protein, type I (CRBPI) present in most peripheral tissues, which transports retinol within these tissues (43,44)."

- The Physiology Of Digestion (1840)

- Retinoids in health and disease: A role for hepatic stellate cells in affecting retinoid levels

Spoiler

"After consumption of a retinoid-rich meal, the postprandial circulation may contain levels of retinyl esters as high as 5-10 µM, with exact concentrations directly depending on the quantity of retinoid consumed, while retinyl ester concentrations in the fasting circulation vary but are generally found within the 100-200 nM range (19). Studies in the 1960s in rodents established that approximately 66-75% of chylomicron retinyl ester is taken up by the liver, while the remaining 25-33% of chylomicron retinyl ester is delivered to peripheral tissues, bypassing the liver and its stores (21). A generalized summary of this classical understanding of retinoid transport is presented in Figure 3."

"For the last ten or fifteen years, it has been increasingly recognized that a number of different forms of retinoid, in addition to retinol-RBP4, are found in the circulation at varying levels, depending on the dietary status of the individual. As summarized in Figure 4 and Table 1, these include retinyl esters transported in lipoproteins derived from the small intestine, in chylomicrons and chylomicron remnants, as well as from the liver, in very low density lipoprotein (VLDL) and low density lipoprotein (LDL); retinoic acid transport bound to albumin; and retinol and retinoic acid transported in the form of water-soluble retinyl- and retinoyl-β-glucuronides (19). We propose that all of these pathways can be important for assuring normal retinoid actions within the body and for contributing to tissue retinoid pools."

"The older literature emphasized the importance of the retinol-RBP4 transport pathway for assuring retinoid delivery to tissues, although it had been known for some time that retinyl esters can be found in the postprandial circulation transported in chylomicrons (65). As noted above, although the retinol-RBP4 pathway is the major pathway for retinoid transport in the circulation, it is not an essential pathway. This is evidenced by the fact that humans who do not express RBP4 have impaired vision and possible eye defects, but are otherwise normal when they regularly consume a retinoid-sufficient diet (53,54,66). Therefore, there must be other mechanisms to account for retinoid transport in the body. As discussed earlier, relatively high levels of retinyl esters are transported in chylomicrons following a vitamin-A rich meal. Even though postprandial clearance of retinyl esters by peripheral tissues had been known fairly early on, researchers did not make the connection that this was an important route for vitamin A delivery to tissues. However, when it became clear that humans lacking RBP4 have relatively mild phenotypes, ones not resulting in mortality, this delivery pathway began to be recognized as a major contributor to retinoid delivery to tissues. In other words, the present understanding is that RBP4 exists to allow for retinoid stores to be mobilized from the liver, thus enabling the body to store vitamin A for use in times of dietary insufficiency. However, individuals can survive without RBP4, as long as they consume sufficient quantities of dietary retinoid. This is because postprandial retinoid is delivered effectively to extrahepatic tissues that are vitamin A-dependent, aside for the eye. At present it is not understood whether this process is regulated and responsive to tissue retinoid needs and/or intake levels or whether this is simply an unregulated process. It is, however, now generally believed that delivery of postprandial retinoid to tissues via chylomicrons allows for humans lacking RBP4 to survive and live relatively normal lives, albeit with diminished or impaired vision (53-56,65)."

 

[Amazoniac]

- Vitamins in Animal and Human Nutrition (0-8138-2630-6) (A/D in feed)