Vitamin A (retinol) Is Endotoxin (LPS / TLR4) Antagonist

[haidut]

Another one in the series of endotoxin antagonism featuring so far vitamins D and B2.
Vitamin B2 (riboflavin) Is Endotoxin Antagonist
Vitamin B2 Remarkably Effective Against Endotoxin, Sepsis, And Other Bacterial Infections
Vitamin D Is Endotoxin (LPS / TLR4) Antagonist, May Treat LPS-linked Conditions

This study used plain retinol, which can easily be mimicked by supplementation with retinyl esters like acetate and palmitate, with the acetate ester having higher retinol equivalency and this allowing lower dose to achieve the same effects.

Retinol suppresses the activation of Toll-like receptors in MyD88- and STAT1-independent manners. - PubMed - NCBI
"...However, it has not been fully elucidated how retinol regulates TLR activation in macrophages. Therefore, we investigated the effect of retinol on the activation of TLRs and downstream signaling pathways in macrophages. We found that retinol attenuated TLR2-, TLR3-, and TLR4-mediated production of cytokines and chemokines in macrophages. The inhibitory effects of retinol on TLR activation were still observed in MyD88- or signal transducer and activator of transcription 1 (STAT1)- deficient macrophages, suggesting that MyD88 and STAT1 are dispensable for anti-inflammatory activity of retinol in macrophages. Our study provides new insight in understanding the role of retinol in regulation of immune responses mediated through the inhibition of TLR activation in macrophages."

 

[raypeatclips]

Thank you for posting haidut. It seems the full article costs a fair amount of money to buy. Do you have an opinion on what amount of Vitamin A is needed?

 

[haidut]

Thank you for posting haidut. It seems the full article costs a fair amount of money to buy. Do you have an opinion on what amount of Vitamin A is needed?

The effective concentrations started at a level achievable with as little as 10,000 IU vitamin A.

 

[raypeatclips]

The effective concentrations started at a level achievable with as little as 10,000 IU vitamin A.

Excellent, thank you for the reply.

 

[Area-1255]

This type of research is what perks my eyes and ears and rats eyes and ears right up! :)

 

[artist]

This would explain my experiences with supplementing A

 

[Constatine]

Interesting study, vitamin A reduces the half life of endotoxin by a half: Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits

 

[haidut]

Interesting study, vitamin A reduces the half life of endotoxin by a half: Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits

Great find, thanks. The IV dose of retinyl palmitate used in that study was high but probably worth it for people with acute endotoxin attack. The HED of oral ratinyl palmitate needed to replicate this study would be in the range 250,000 IU - 300,000 IU. It would probably be OK if used sporadically and with 400 IU vitamin E.

 

[Anders86]

When attacking Endotoxin is oral route preferable to topical?

 

[docall18]

When attacking Endotoxin is oral route preferable to topical?

Bump

 

[raypeatclips]

Bump

Interested in this too.

 

[Elephanto]

Great find, thanks. The IV dose of retinyl palmitate used in that study was high but probably worth it for people with acute endotoxin attack. The HED of oral ratinyl palmitate needed to replicate this study would be in the range 250,000 IU - 300,000 IU. It would probably be OK if used sporadically and with 400 IU vitamin E.

Taking that much Vitamin A doesn't seem like a good idea, Peat has mentioned that more than 5000 iU inhibits thyroid function. With low gastric acid output from hypothyroidism/high serotonin as a main factor for pathogenic growth/endotoxin overload, who knows if the long-term effect on endotoxins wouldn't actually be a promoting one. You have posted many substances (coconut oil, B2, D) that would essentially have the same effect without this drawback. Also, before the research on systemic damage from overaccumulation of vitamin A in liver is proven false, caution should be used.

 

[haidut]

Taking that much Vitamin A doesn't seem like a good idea, Peat has mentioned that more than 5000 iU inhibits thyroid function. With low gastric acid output from hypothyroidism/high serotonin as a main factor for pathogenic growth/endotoxin overload, who knows if the long-term effect on endotoxins wouldn't actually be a promoting one. You have posted many substances (coconut oil, B2, D) that would essentially have the same effect without this drawback. Also, before the research on systemic damage from overaccumulation of vitamin A in liver is proven false, caution should be used.

That's why I said "used sporadically and with vitamin E". Most of the toxicity of vitamin A has been shown to be completely preventable by adding E, but with even with adding E I would not use a dose of A that high for more than a few days in a row.

 

[Jem Oz]

So confused about Vitamin A. Doesn't one lone little carrot have around 10,000 iU ?? Surely Peat is saying it's not good to SUPPLEMENT any more than 5000 iU, in addition to diet?

 

[snacks]

So confused about Vitamin A. Doesn't one lone little carrot have around 10,000 iU ?? Surely Peat is saying it's not good to SUPPLEMENT any more than 5000 iU, in addition to diet?

Yeah peat is very conservative about doses with micronutrient supplementation. After fiddling around with this I've found this is the right way to go for most nutrients including vitamin A. Also, if I'm not mistaken a high beta carotene intake isnt ideal

 

[GorillaHead]

Then these studies

Retinoic Acid Facilitates Toll-Like Receptor 4 Expression to Improve Intestinal Barrier Function through Retinoic Acid Receptor Beta - PubMed

Taken together, our results indicate that RARβ enhanced ZO-2 expression by regulating TLR4 to improve intestinal epithelial barrier function in Caco-2 cells, as well as in rat and mouse models, but not in humans.

pubmed.ncbi.nlm.nih.gov

Cutting Edge: All-trans Retinoic Acid Down-Regulates TLR2 Expression and Function

A major consequence of microbial infection is the tissue injury that results from the host inflammatory response. In acne, inflammation is due in part to the ability of Propionibacterium acnes to activate TLR2. Because all- trans retinoic acid (ATRA) decreases inflammation in acne, we...

www.jimmunol.org

Lots of conflicting info. So is atra the issue ? The amount? Hmm

 

[koreus]

So confused about Vitamin A. Doesn't one lone little carrot have around 10,000 iU ?? Surely Peat is saying it's not good to SUPPLEMENT any more than 5000 iU, in addition to diet?

Carrots contain Beta Carotene which is not quite the same thing as retinol and has been linked to more deleterious health outcomes in large quantities. Ray's Carrot Salad is a trade-off, like eggs, good in small amounts.

 

[Dr. B]

So confused about Vitamin A. Doesn't one lone little carrot have around 10,000 iU ?? Surely Peat is saying it's not good to SUPPLEMENT any more than 5000 iU, in addition to diet?

its not that easy to get 10000 IU from carrots. youd need more than one. I thought its like 1000 IU for a large carrot?

The effective concentrations started at a level achievable with as little as 10,000 IU vitamin A.

so can you reduce the vitamin A dosage if you also add C and D? like 5000 IU d3 and A, with 500mg C?

That's why I said "used sporadically and with vitamin E". Most of the toxicity of vitamin A has been shown to be completely preventable by adding E, but with even with adding E I would not use a dose of A that high for more than a few days in a row.

if youre doing 5000 IU vitamin A is E still needed or can you just use 500mg Quali C ascorbic acid instead. to prevent oxidation etc

 

[Dr. B]

Interesting study, vitamin A reduces the half life of endotoxin by a half: Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits

so A actually boosts excretion of endotoxin then? which is different from D3 which is just a TLR4 antagonist?

isnt there something with vitamin C also boosting excretion.

orange juice and activated charcoal are known to boost excretion.

 

[Dr. B]

Interesting study, vitamin A reduces the half life of endotoxin by a half: Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits

@EvanHinkle

Great find, thanks. The IV dose of retinyl palmitate used in that study was high but probably worth it for people with acute endotoxin attack. The HED of oral ratinyl palmitate needed to replicate this study would be in the range 250,000 IU - 300,000 IU. It would probably be OK if used sporadically and with 400 IU vitamin E.

for endotoxin wouldnt oral be more effective than IV since oral will directly reach the gut?

Taking that much Vitamin A doesn't seem like a good idea, Peat has mentioned that more than 5000 iU inhibits thyroid function. With low gastric acid output from hypothyroidism/high serotonin as a main factor for pathogenic growth/endotoxin overload, who knows if the long-term effect on endotoxins wouldn't actually be a promoting one. You have posted many substances (coconut oil, B2, D) that would essentially have the same effect without this drawback. Also, before the research on systemic damage from overaccumulation of vitamin A in liver is proven false, caution should be used.

what about palmitic acid increasing endotoxin absorption and increasing TLR4?
also coconut oil has 5AR inhibiting effects and D3 can also have anti metabolic effects if used improperly, or without A to balance it since it can mess with A and even b vitamins potentially.