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DiscussionLet's talk about it: The science of itUlcerative Colitis and Crohn's ar …

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Ulcerative Colitis and Crohn's are caused by Vitamin A toxicity !

#1 · December 31, 2023, 11:57 am

Quote from r on December 31, 2023, 11:57 am
Hi ,

First of all I am a living example ( n = 1) of someone without any family history of autoimmune ( colitis , eczema , arthritis etc ) not from my mothers side or fathers side since generations ( since we are tribal people we didn't have the luxury of eating so called healthy "exotic" foods ) . Suddenly after 1 year of heavy Vitamin A does I am diagnose with ulcerative Colitus . I never had any intestinal issues no consitpathon , no diarrhea smooth bowel movements all my life . At least I am not accepting that it a glitch in my "immunity " that caused it . I know it was vitamin A . But thank god I found out early that it was vitamin A toxicity . I Know how to fix it , or at-least I wont be looking for cure at wrong places , however I believe Ulcerative to be a colateral damage caused by VA instead of a symptom of it , the symptom of it is toxic bile and presence of huge amount of vitamin A in gut tissue ( as show in a paper below )

I am have been doing some research on potential relationship between VA and UC and I was shocked to see the overwhelming amount of clear research that shows Retinoic acid to be the actual cause of it. I have collected some of the relevant papers and summarized them . Even one of the recent paper proposed inhibition for ALDH1A1 or retinaldehyde dehydrogenase for the treatment of UC and says that even high class biologics ( class of medicine used to suppress immune system to treat severe colitis ) does exactly the same thing .

Another import research paper found out the patients that were in a UC flare had more Retinoic acid in the Gut tissue , but normal levels in the serum and the patients during remission( treated non symptomatic ) had lower amount of Retinoic acid

Isotretinoin-Induced Inflammatory Bowel Disease in an Adolescent

https://www.researchgate.net/profile/Denise-Reniers/publication/11676652_Isotretinoin-Induced_Inflammatory_Bowel_Disease_in_an_Adolescent/links/5747126a08ae707fe21e36ef/Isotretinoin-Induced-Inflammatory-Bowel-Disease-in-an-Adolescent.pdf

Case Report: 17-Year-Old Male with Isotretinoin-Induced Ulcerative Colitis:

Patient Background:

17-year-old male treated with isotretinoin for severe acne.

Developed inflammatory bowel disease (IBD), specifically ulcerative colitis, after a five-month isotretinoin course.

Condition Progression:

Despite conventional treatments, the patient's condition worsened.

Experienced significant weight loss, edema, and anemia.

Subtotal colectomy and ileostomy were eventually performed.

Potential Mechanisms of Isotretinoin-Induced IBD:

Discussion explores mechanisms such as inhibition of epithelial cell growth, interference with glycoprotein synthesis, and stimulation of killer T cells.

Importance of Awareness:

Emphasizes the importance of inquiring about isotretinoin use in patients suspected of having IBD.

Highlights the serious adverse event of isotretinoin-induced IBD.

Additional Cases:

Case 1 (20-Year-Old Man with Crohn's Disease):

Two-year history of Crohn's disease.

Isotretinoin therapy initiated on three occasions, leading to exacerbation of IBD.

Improvement in gastrointestinal symptoms one month after discontinuation of isotretinoin.

Case 2 (17-Year-Old Boy with Acute Proctosigmoiditis):

Developed acute proctosigmoiditis four weeks after starting isotretinoin for cystic acne.

No previous history of bowel disease reported.

Proctosigmoiditis resolved four weeks after isotretinoin discontinuation.

Recurrence observed upon rechallenge with isotretinoin within two weeks.

Two important papers directly descring the role of RA wef Ulcerative colitus

Paper 1: Retinoic Acid and Immune Cells (Th9) https://pubmed.ncbi.nlm.nih.gov/26980802/ :

Topic: The paper talks about a substance called all-trans-retinoic acid and how it affects the immune system, especially in the intestines.

Normal Role: Usually, this substance helps the immune system and prevents inflammation.

Study Focus: Looked at how this substance affects specific immune cells (dendritic cells and CD4+ T cells) in humans in different situations.

Findings: In situations with inflammation, all-trans-retinoic acid may lead to the development of immune cells that contribute to inflammation in the intestines.

Conclusion: The role of this substance is not always straightforward; it can be helpful for the immune system, but in the presence of inflammation, it might have a different, potentially negative, effect in the intestines.

Paper 2: Retinoic Acid in Ulcerative Colitis - https://pubmed.ncbi.nlm.nih.gov/32469071/

Background: All-trans retinoic acid (RA) usually helps in creating immune cells that keep things under control.

Research Objective: Investigated RA levels in the gut of people with ulcerative colitis to see if it is linked to inflammation.

Findings:

People with active disease had more RA in their gut compared to those in remission or without the condition.

Higher RA levels in active disease were linked to more inflammation in different types of immune cells.

RA levels were linked to less of an anti-inflammatory substance (IL-10) and were associated with inhibiting the development of certain immune cells (Th9 cells).

Conclusion: In ulcerative colitis, higher RA levels might worsen inflammation by supporting the creation of certain immune cells and reducing anti-inflammatory substances.

Conclusions: The study confirms what we found in the lab—when there's inflammation, RA seems to play a role in keeping it going by supporting the creation of immune cells that cause inflammation in the gut. This suggests that RA might contribute to ongoing inflammation in the gut during certain conditions.

We studied the connection between a substance called retinoic acid (RA) and the immune responses in the gut. We measured RA levels in the blood and gut lining of people with ulcerative colitis (UC) and those without the condition.

Here's what we found:

In people with UC, RA levels in the gut lining and blood were higher compared to those without UC.

The increase in RA levels was more noticeable in the gut lining of people with UC.

When we looked at different stages of the disease—when inflammation is high (active disease) or low (remission)—we found that RA levels in the gut lining were significantly higher in people with active disease compared to those in remission and those without UC.

However, RA levels in the blood did not show a difference between active and remission states.

Title: Increased Retinoic Acid Production in Crohn's Disease -

https://pubmed.ncbi.nlm.nih.gov/24503130/#:~:text=with%20Crohn's%20disease-,Increased%20production%20of%20retinoic%20acid%20by%20intestinal%20macrophages%20contributes%20to,Gastroenterology.

Summary: The study explores elevated retinoic acid (RA) production, primarily by CD14(+) macrophages, in patients with Crohn's disease (CD). The findings suggest that inhibiting RA generation by these macrophages could be a therapeutic strategy. Two perspectives are discussed:

Higher RA and Inflammation (Undesirable):

In CD, higher RA levels, especially from CD14(+) macrophages, may contribute to an inflammatory phenotype.

If inflammation is linked to the disease, reducing RA levels could be a potential therapeutic approach.

Lower RA for Therapeutic Benefit (Desirable):

Blocking RA receptor signaling might reduce the development of inflammatory macrophages, offering a potential therapeutic benefit.

Lowering RA levels could help mitigate the inflammatory response associated with CD.

Conclusion:

For Crohn's disease, the study suggests that limiting RA generation, particularly by CD14(+) macrophages, could be a beneficial therapeutic approach.

However, considering the broader role of RA in various physiological processes, any therapeutic intervention should be carefully designed to prevent unintended consequences on normal immune function and other RA-regulated biological functions.

The complexity of the immune system and disease-specific details should be considered when interpreting these findings for potential treatments in Crohn's disease.

Title: Retinoic Acid's Impact on Intestinal Mucus and Enterocolitis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380709/

Summary:

Background:

Retinoid medications used for acne treatment are linked to inflammatory bowel disease (IBD).

The intestinal mucus layer is crucial for gut protection, and changes due to retinoid treatment might contribute to IBD, but direct evidence is limited.

Research Approach:

Used zebrafish larvae to create an IBD-like model by exposing them to dextran sodium sulfate (DSS).

This model mimicked aspects of another zebrafish IBD model, allowing the study of mucus changes independently of the adaptive immune system.

Inflammation induced in the gut was dependent on gut bacteria and influenced by drugs.

Findings:

Retinoic acid (RA), a type of retinoid, directly impacted the production of intestinal mucus.

RA suppressed both normal and abnormal mucin production.

Reduction in mucin production by RA made zebrafish larvae more vulnerable to inflammation when exposed to substances causing enterocolitis (inflammation of the intestines).

Implications:

The research establishes a direct influence of retinoid medication, specifically retinoic acid, on the intestinal mucus layer.

This influence may have implications for the development of intestinal inflammation, providing insight into the potential link between retinoid medications and inflammatory bowel disease.

Conclusion: This study using a zebrafish model demonstrates that retinoic acid, a type of retinoid medication, directly impacts intestinal mucus production. The reduction in mucin production induced by retinoic acid makes the gut more susceptible to inflammation, suggesting a potential connection between retinoid medications and the development of inflammatory bowel disease.

Gluten intolerance due to RA

Title: Retinoic Acid and IL-15 Impact on Immune Response in Coeliac Disease

Summary:

Background:

Coeliac disease involves an abnormal immune response to gluten, a wheat protein, disrupting the usual immune tolerance in the gut.

Research Focus:

Experiments with mice investigated the interaction of retinoic acid (a vitamin A metabolite) and IL-15 (elevated in coeliac disease) in the immune system.

Findings:

In the presence of IL-15, retinoic acid quickly activated dendritic cells (immune cells).

This activation resulted in the release of inflammatory substances.

In a stressed intestinal environment, retinoic acid signaled the immune system to react against gluten rather than tolerate it.

Implications:

Retinoic acid, in conjunction with IL-15, disrupts the normal immune tolerance to dietary antigens like gluten.

This unexpected role of retinoic acid provides insights into the mechanisms behind the immune response in coeliac disease.

Conclusion: The study reveals that retinoic acid, particularly in the presence of IL-15, plays an unexpected role in promoting an immune response against gluten in coeliac disease. In a stressed gut environment, retinoic acid signals immune cells to release inflammatory substances, disrupting the usual tolerance to dietary antigens. These findings offer valuable insights into the mechanisms involved in the abnormal immune response seen in coeliac disease.

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice
://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536456/

Summary: Investigating ALDH1A Inhibitor for IBD Treatment Researchers explored an oral treatment option, WIN 18,446, targeting ALDH1A enzymes that produce retinoic acid in inflammatory bowel disease (IBD). The study, conducted in chronic IBD mouse models (Mdr1a−/− mice), demonstrated that initiating WIN 18,446 before inflammation reduced clinical symptoms and improved histological colitis scores. The inhibitor influenced immune cells, particularly decreasing α4ß7 integrin expression on T cells. These findings suggest ALDH1A inhibition as a potential IBD treatment, possibly impacting the efficacy of existing biologics, and future studies aim to assess its effectiveness during active colitis.

Context: Understanding Retinoic Acid's Role in IBD Retinoic acid (RA), a metabolite of vitamin A, plays a dual role in gut inflammation. Reports suggest both beneficial and harmful effects of RA in IBD. The study used WIN 18,446, an ALDH1A inhibitor, to reduce RA synthesis in chronic IBD mouse models (Il10−/− and Mdr1a−/− mice). Treatment initiated before inflammation onset reduced colitis severity.

Notably, ALDH1A inhibition decreased α4ß7 integrin expression on activated T cells, suggesting potential synergy with existing IBD biologics targeting the same protein.

The study represents a step towards developing a new family of oral drugs for IBD treatment.The findings suggest that inhibiting ALDH1A could be a potential new approach for treating IBD.

Hi ,

First of all I am a living example ( n = 1) of someone without any family history of autoimmune ( colitis , eczema , arthritis etc ) not from my mothers side or fathers side since generations ( since we are tribal people we didn't have the luxury of eating so called healthy "exotic" foods ) . Suddenly after 1 year of heavy Vitamin A does I am diagnose with ulcerative Colitus . I never had any intestinal issues no consitpathon , no diarrhea smooth bowel movements all my life . At least I am not accepting that it a glitch in my "immunity " that caused it . I know it was vitamin A . But thank god I found out early that it was vitamin A toxicity . I Know how to fix it , or at-least I wont be looking for cure at wrong places , however I believe Ulcerative to be a colateral damage caused by VA instead of a symptom of it , the symptom of it is toxic bile and presence of huge amount of vitamin A in gut tissue ( as show in a paper below )

I am have been doing some research on potential relationship between VA and UC and I was shocked to see the overwhelming amount of clear research that shows Retinoic acid to be the actual cause of it. I have collected some of the relevant papers and summarized them . Even one of the recent paper proposed inhibition for ALDH1A1 or retinaldehyde dehydrogenase for the treatment of UC and says that even high class biologics ( class of medicine used to suppress immune system to treat severe colitis ) does exactly the same thing .

Another import research paper found out the patients that were in a UC flare had more Retinoic acid in the Gut tissue , but normal levels in the serum and the patients during remission( treated non symptomatic ) had lower amount of Retinoic acid

Isotretinoin-Induced Inflammatory Bowel Disease in an Adolescent

https://www.researchgate.net/profile/Denise-Reniers/publication/11676652_Isotretinoin-Induced_Inflammatory_Bowel_Disease_in_an_Adolescent/links/5747126a08ae707fe21e36ef/Isotretinoin-Induced-Inflammatory-Bowel-Disease-in-an-Adolescent.pdf

Case Report: 17-Year-Old Male with Isotretinoin-Induced Ulcerative Colitis:

Patient Background:
- 17-year-old male treated with isotretinoin for severe acne.
- Developed inflammatory bowel disease (IBD), specifically ulcerative colitis, after a five-month isotretinoin course.
Condition Progression:
- Despite conventional treatments, the patient's condition worsened.
- Experienced significant weight loss, edema, and anemia.
- Subtotal colectomy and ileostomy were eventually performed.
Potential Mechanisms of Isotretinoin-Induced IBD:
- Discussion explores mechanisms such as inhibition of epithelial cell growth, interference with glycoprotein synthesis, and stimulation of killer T cells.
Importance of Awareness:
- Emphasizes the importance of inquiring about isotretinoin use in patients suspected of having IBD.
- Highlights the serious adverse event of isotretinoin-induced IBD.

Additional Cases:

Case 1 (20-Year-Old Man with Crohn's Disease):
- Two-year history of Crohn's disease.
- Isotretinoin therapy initiated on three occasions, leading to exacerbation of IBD.
- Improvement in gastrointestinal symptoms one month after discontinuation of isotretinoin.
Case 2 (17-Year-Old Boy with Acute Proctosigmoiditis):
- Developed acute proctosigmoiditis four weeks after starting isotretinoin for cystic acne.
- No previous history of bowel disease reported.
- Proctosigmoiditis resolved four weeks after isotretinoin discontinuation.
- Recurrence observed upon rechallenge with isotretinoin within two weeks.

Two important papers directly descring the role of RA wef Ulcerative colitus

Paper 1: Retinoic Acid and Immune Cells (Th9) https://pubmed.ncbi.nlm.nih.gov/26980802/ :

Topic: The paper talks about a substance called all-trans-retinoic acid and how it affects the immune system, especially in the intestines.
Normal Role: Usually, this substance helps the immune system and prevents inflammation.
Study Focus: Looked at how this substance affects specific immune cells (dendritic cells and CD4+ T cells) in humans in different situations.
Findings: In situations with inflammation, all-trans-retinoic acid may lead to the development of immune cells that contribute to inflammation in the intestines.
Conclusion: The role of this substance is not always straightforward; it can be helpful for the immune system, but in the presence of inflammation, it might have a different, potentially negative, effect in the intestines.

Paper 2: Retinoic Acid in Ulcerative Colitis - https://pubmed.ncbi.nlm.nih.gov/32469071/

Background: All-trans retinoic acid (RA) usually helps in creating immune cells that keep things under control.
Research Objective: Investigated RA levels in the gut of people with ulcerative colitis to see if it is linked to inflammation.
Findings:
- People with active disease had more RA in their gut compared to those in remission or without the condition.
- Higher RA levels in active disease were linked to more inflammation in different types of immune cells.
- RA levels were linked to less of an anti-inflammatory substance (IL-10) and were associated with inhibiting the development of certain immune cells (Th9 cells).
Conclusion: In ulcerative colitis, higher RA levels might worsen inflammation by supporting the creation of certain immune cells and reducing anti-inflammatory substances.

Conclusions: The study confirms what we found in the lab—when there's inflammation, RA seems to play a role in keeping it going by supporting the creation of immune cells that cause inflammation in the gut. This suggests that RA might contribute to ongoing inflammation in the gut during certain conditions.

We studied the connection between a substance called retinoic acid (RA) and the immune responses in the gut. We measured RA levels in the blood and gut lining of people with ulcerative colitis (UC) and those without the condition.

Here's what we found:

In people with UC, RA levels in the gut lining and blood were higher compared to those without UC.
The increase in RA levels was more noticeable in the gut lining of people with UC.
When we looked at different stages of the disease—when inflammation is high (active disease) or low (remission)—we found that RA levels in the gut lining were significantly higher in people with active disease compared to those in remission and those without UC.
However, RA levels in the blood did not show a difference between active and remission states.

Title: Increased Retinoic Acid Production in Crohn's Disease -

https://pubmed.ncbi.nlm.nih.gov/24503130/#:~:text=with%20Crohn's%20disease-,Increased%20production%20of%20retinoic%20acid%20by%20intestinal%20macrophages%20contributes%20to,Gastroenterology.

Summary: The study explores elevated retinoic acid (RA) production, primarily by CD14(+) macrophages, in patients with Crohn's disease (CD). The findings suggest that inhibiting RA generation by these macrophages could be a therapeutic strategy. Two perspectives are discussed:

Higher RA and Inflammation (Undesirable):
- In CD, higher RA levels, especially from CD14(+) macrophages, may contribute to an inflammatory phenotype.
- If inflammation is linked to the disease, reducing RA levels could be a potential therapeutic approach.
Lower RA for Therapeutic Benefit (Desirable):
- Blocking RA receptor signaling might reduce the development of inflammatory macrophages, offering a potential therapeutic benefit.
- Lowering RA levels could help mitigate the inflammatory response associated with CD.

Conclusion:

For Crohn's disease, the study suggests that limiting RA generation, particularly by CD14(+) macrophages, could be a beneficial therapeutic approach.
However, considering the broader role of RA in various physiological processes, any therapeutic intervention should be carefully designed to prevent unintended consequences on normal immune function and other RA-regulated biological functions.
The complexity of the immune system and disease-specific details should be considered when interpreting these findings for potential treatments in Crohn's disease.

Title: Retinoic Acid's Impact on Intestinal Mucus and Enterocolitis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380709/

Summary:

Background:
- Retinoid medications used for acne treatment are linked to inflammatory bowel disease (IBD).
- The intestinal mucus layer is crucial for gut protection, and changes due to retinoid treatment might contribute to IBD, but direct evidence is limited.
Research Approach:
- Used zebrafish larvae to create an IBD-like model by exposing them to dextran sodium sulfate (DSS).
- This model mimicked aspects of another zebrafish IBD model, allowing the study of mucus changes independently of the adaptive immune system.
- Inflammation induced in the gut was dependent on gut bacteria and influenced by drugs.
Findings:
- Retinoic acid (RA), a type of retinoid, directly impacted the production of intestinal mucus.
- RA suppressed both normal and abnormal mucin production.
- Reduction in mucin production by RA made zebrafish larvae more vulnerable to inflammation when exposed to substances causing enterocolitis (inflammation of the intestines).
Implications:
- The research establishes a direct influence of retinoid medication, specifically retinoic acid, on the intestinal mucus layer.
- This influence may have implications for the development of intestinal inflammation, providing insight into the potential link between retinoid medications and inflammatory bowel disease.

Conclusion: This study using a zebrafish model demonstrates that retinoic acid, a type of retinoid medication, directly impacts intestinal mucus production. The reduction in mucin production induced by retinoic acid makes the gut more susceptible to inflammation, suggesting a potential connection between retinoid medications and the development of inflammatory bowel disease.

Gluten intolerance due to RA

Title: Retinoic Acid and IL-15 Impact on Immune Response in Coeliac Disease

Summary:

Background:
- Coeliac disease involves an abnormal immune response to gluten, a wheat protein, disrupting the usual immune tolerance in the gut.
Research Focus:
- Experiments with mice investigated the interaction of retinoic acid (a vitamin A metabolite) and IL-15 (elevated in coeliac disease) in the immune system.
Findings:
- In the presence of IL-15, retinoic acid quickly activated dendritic cells (immune cells).
- This activation resulted in the release of inflammatory substances.
- In a stressed intestinal environment, retinoic acid signaled the immune system to react against gluten rather than tolerate it.
Implications:
- Retinoic acid, in conjunction with IL-15, disrupts the normal immune tolerance to dietary antigens like gluten.
- This unexpected role of retinoic acid provides insights into the mechanisms behind the immune response in coeliac disease.

Conclusion: The study reveals that retinoic acid, particularly in the presence of IL-15, plays an unexpected role in promoting an immune response against gluten in coeliac disease. In a stressed gut environment, retinoic acid signals immune cells to release inflammatory substances, disrupting the usual tolerance to dietary antigens. These findings offer valuable insights into the mechanisms involved in the abnormal immune response seen in coeliac disease.

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice
://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536456/

Summary: Investigating ALDH1A Inhibitor for IBD Treatment Researchers explored an oral treatment option, WIN 18,446, targeting ALDH1A enzymes that produce retinoic acid in inflammatory bowel disease (IBD). The study, conducted in chronic IBD mouse models (Mdr1a−/− mice), demonstrated that initiating WIN 18,446 before inflammation reduced clinical symptoms and improved histological colitis scores. The inhibitor influenced immune cells, particularly decreasing α4ß7 integrin expression on T cells. These findings suggest ALDH1A inhibition as a potential IBD treatment, possibly impacting the efficacy of existing biologics, and future studies aim to assess its effectiveness during active colitis.

Context: Understanding Retinoic Acid's Role in IBD Retinoic acid (RA), a metabolite of vitamin A, plays a dual role in gut inflammation. Reports suggest both beneficial and harmful effects of RA in IBD. The study used WIN 18,446, an ALDH1A inhibitor, to reduce RA synthesis in chronic IBD mouse models (Il10−/− and Mdr1a−/− mice). Treatment initiated before inflammation onset reduced colitis severity.

Notably, ALDH1A inhibition decreased α4ß7 integrin expression on activated T cells, suggesting potential synergy with existing IBD biologics targeting the same protein.

The study represents a step towards developing a new family of oral drugs for IBD treatment.The findings suggest that inhibiting ALDH1A could be a potential new approach for treating IBD.

Orion, Janelle525 and 5 other users have reacted to this post.

#2 · January 1, 2024, 1:36 am

@r-2 what I don't understand about accutane how is it possible that some people completely crash after even couple of pills and some people take good dose for 6 months or so and they didn't develop any chronic health issues from it.. That is true mistery to me.. Btw what is your diet now?

Deleted user has reacted to this post.

#3 · January 1, 2024, 3:19 am

Hi @r-2 Happy New Year and thank you for this post which should help a good number of people.

I find it interesting that you come from a family background with no former vA consumption. This could bring a vA shock to your system that can make the source of the problem obvious.

I think this is linked to the rapidity with which symptoms developed for you (1 year of heavy vitamin A). Came fast and went away relatively fast too.

I am in the opposite situation, with family exposed to a lot of vitamin A since generations, poor people of the mountains who could survive only on preserved milk in the shape of hard cheese. Two generations before me, uncles and grandparents could not bear dairy in any form, were severly allergic to it, probably a buid up of retinoic acid brought forward by heredity. Some of the cousins did not have this problem but they are all dead alcoholics now. Because we cousins HATED dairy, we would gang up to have a member taste the food. Parents would smoothly lie to us "there is absolutely no milk no cheese in this..." But we knew better.

I was raised without dairy, did not want my mother's milk or any other, survived from the start on a broth of sea water with pureed baby fish. Did not consume a total of one liter of milk in my whole life until I was 50. I was OK but then my husband made me home made yoghurt and kefir and I joined him. BIG MISTAKE. I had no osteoporosis then but my doctor hated my diet and strongly advised for vA poisoning.

Anyway, after 4 years on Grant's diet, I am now perfectly OK. My bones are very strong, my joints supple no arthritis at all (71 1/2 years old now), I can wriggle my ears, make surabhi mudra straight and reverse, have perfect nails on all fingers and toes.

I think we cannot be well until we cancel the hereditary weight we are carrying, and I think the future looks rosy now we know!

Be well!

lil chick and Deleted user have reacted to this post.

#4 · January 1, 2024, 7:18 am

Hi @r-2,

Thanks for putting that information together and sharing it.

I have no doubt that RA is the root cause of IBD, ulcerative Colitus etc.

Wishing everyone the best in 2024.

lil chick, r and 4 other users have reacted to this post.

#5 · January 1, 2024, 9:53 am

Quote from r on January 1, 2024, 9:53 am
I can go on and on , Another one , I mean the data is crystal clear ( even if we dont agree Vitamin A is not a VitaminA , ) Vitamin A is not good for gut at all!! There are liteally hundreds of research papers

IL-15 modulates the effect of retinoic acid, promoting inflammation rather than oral tolerance to dietary antigens
https://digital.csic.es/bitstream/10261/44781/1/egh.11.pdf

Normal Immune Response in the Intestine: The immune response in the intestine against dietary proteins and commensal flora is typically regulated by mechanisms that prevent harmful consequences. This regulation is referred to as tolerance.

Role of Intestinal Dendritic Cells (DCs): Intestinal dendritic cells (DCs) play a crucial role in the development of immunosuppressive regulatory T cells, which contribute to maintaining tolerance. They achieve this by producing TGF-b (Transforming Growth Factor-beta) and retinoic acid (RA).

Unexpected Effect of RA: The evaluated article reveals an unexpected effect of retinoic acid (RA). Instead of promoting tolerance, RA seems to promote a proinflammatory phenotype in intestinal DCs, which are involved in generating inflammatory immune responses to dietary antigens.

Synergistic Effect of RA and IL-15: The study used a double transgenic murine model that mimics human celiac disease. It demonstrated that RA works synergistically with interleukin-15 (IL-15) in promoting the breakdown of gluten tolerance and the development of enteropathy (intestinal disease).

Caution in Immune Therapies: The passage concludes by cautioning that immune therapies based on retinoic acid, which aim to restore oral tolerance, should be used with caution. This is because the presence of IL-15 (and possibly other proinflammatory cytokines) can have undesirable effects, leading to the breakdown of tolerance and the development of inflammatory immune responses to dietary antigens.

In summary, the study suggests that the interaction between retinoic acid and IL-15 in the intestine may have unexpected and potentially harmful effects on the immune response to dietary antigens, particularly in the context of conditions like celiac disease.

I can go on and on , Another one , I mean the data is crystal clear ( even if we dont agree Vitamin A is not a VitaminA , ) Vitamin A is not good for gut at all!! There are liteally hundreds of research papers

IL-15 modulates the effect of retinoic acid, promoting inflammation rather than oral tolerance to dietary antigens
https://digital.csic.es/bitstream/10261/44781/1/egh.11.pdf

Normal Immune Response in the Intestine: The immune response in the intestine against dietary proteins and commensal flora is typically regulated by mechanisms that prevent harmful consequences. This regulation is referred to as tolerance.
Role of Intestinal Dendritic Cells (DCs): Intestinal dendritic cells (DCs) play a crucial role in the development of immunosuppressive regulatory T cells, which contribute to maintaining tolerance. They achieve this by producing TGF-b (Transforming Growth Factor-beta) and retinoic acid (RA).
Unexpected Effect of RA: The evaluated article reveals an unexpected effect of retinoic acid (RA). Instead of promoting tolerance, RA seems to promote a proinflammatory phenotype in intestinal DCs, which are involved in generating inflammatory immune responses to dietary antigens.
Synergistic Effect of RA and IL-15: The study used a double transgenic murine model that mimics human celiac disease. It demonstrated that RA works synergistically with interleukin-15 (IL-15) in promoting the breakdown of gluten tolerance and the development of enteropathy (intestinal disease).
Caution in Immune Therapies: The passage concludes by cautioning that immune therapies based on retinoic acid, which aim to restore oral tolerance, should be used with caution. This is because the presence of IL-15 (and possibly other proinflammatory cytokines) can have undesirable effects, leading to the breakdown of tolerance and the development of inflammatory immune responses to dietary antigens.

In summary, the study suggests that the interaction between retinoic acid and IL-15 in the intestine may have unexpected and potentially harmful effects on the immune response to dietary antigens, particularly in the context of conditions like celiac disease.

Ourania and Deleted user have reacted to this post.

#6 · January 1, 2024, 9:56 am

Quote from Jiří on January 1, 2024, 1:36 am

@r-2 what I don't understand about accutane how is it possible that some people completely crash after even couple of pills and some people take good dose for 6 months or so and they didn't develop any chronic health issues from it.. That is true mistery to me.. Btw what is your diet now?

Sure some of them are find after 6 months , but I believe RA affects people differently . Human body is so complex and the chemical process inside our body is like chaos theory ,where a simple change in small variable can lead to totally random and unexpected results in outcomes.
But we dont get to see those people 10 years down the line after actuate ingestion where they are in terms of health , and they perhaps will never figure out it was accutane

Deleted user and Rebecca3 have reacted to this post.

#7 · January 1, 2024, 10:00 am

Quote from r on January 1, 2024, 10:00 am

Quote from Ourania on January 1, 2024, 3:19 am

Hi @r-2 Happy New Year and thank you for this post which should help a good number of people.

I find it interesting that you come from a family background with no former vA consumption. This could bring a vA shock to your system that can make the source of the problem obvious.

I think this is linked to the rapidity with which symptoms developed for you (1 year of heavy vitamin A). Came fast and went away relatively fast too.

I am in the opposite situation, with family exposed to a lot of vitamin A since generations, poor people of the mountains who could survive only on preserved milk in the shape of hard cheese. Two generations before me, uncles and grandparents could not bear dairy in any form, were severly allergic to it, probably a buid up of retinoic acid brought forward by heredity. Some of the cousins did not have this problem but they are all dead alcoholics now. Because we cousins HATED dairy, we would gang up to have a member taste the food. Parents would smoothly lie to us "there is absolutely no milk no cheese in this..." But we knew better.

I was raised without dairy, did not want my mother's milk or any other, survived from the start on a broth of sea water with pureed baby fish. Did not consume a total of one liter of milk in my whole life until I was 50. I was OK but then my husband made me home made yoghurt and kefir and I joined him. BIG MISTAKE. I had no osteoporosis then but my doctor hated my diet and strongly advised for vA poisoning.

Anyway, after 4 years on Grant's diet, I am now perfectly OK. My bones are very strong, my joints supple no arthritis at all (71 1/2 years old now), I can wriggle my ears, make surabhi mudra straight and reverse, have perfect nails on all fingers and toes.

I think we cannot be well until we cancel the hereditary weight we are carrying, and I think the future looks rosy now we know!

Be well!

Happy new year !

Exacly I am very very lucky that I got quickly hyper toxic (fish oil/ supplements , sweet potatoes and carrots, surpringly I never had liver / cheese in my life ) . This immediately made me realize it there was something wrong in what I was eating / Consuming . Thank go di foudn out it was vitamin A thing . Initially my symptoms matched (http://www.healthextremist.com/how-i-got-vitamin-a-toxicity/#comment-1000047) and thats what confirmed it , but didnt know what to do and I was eating stuff that I wasn't supposed to eat . Eventually someone in the comment mentioned about grants work and I am thankful to you guy for helping me and educating me , I dont know I didn't find this place I would be suffering a lot today!

Thank you all! God Bless!

Quote from Ourania on January 1, 2024, 3:19 am

Hi @r-2 Happy New Year and thank you for this post which should help a good number of people.

I find it interesting that you come from a family background with no former vA consumption. This could bring a vA shock to your system that can make the source of the problem obvious.

I think this is linked to the rapidity with which symptoms developed for you (1 year of heavy vitamin A). Came fast and went away relatively fast too.

I am in the opposite situation, with family exposed to a lot of vitamin A since generations, poor people of the mountains who could survive only on preserved milk in the shape of hard cheese. Two generations before me, uncles and grandparents could not bear dairy in any form, were severly allergic to it, probably a buid up of retinoic acid brought forward by heredity. Some of the cousins did not have this problem but they are all dead alcoholics now. Because we cousins HATED dairy, we would gang up to have a member taste the food. Parents would smoothly lie to us "there is absolutely no milk no cheese in this..." But we knew better.

I was raised without dairy, did not want my mother's milk or any other, survived from the start on a broth of sea water with pureed baby fish. Did not consume a total of one liter of milk in my whole life until I was 50. I was OK but then my husband made me home made yoghurt and kefir and I joined him. BIG MISTAKE. I had no osteoporosis then but my doctor hated my diet and strongly advised for vA poisoning.

Anyway, after 4 years on Grant's diet, I am now perfectly OK. My bones are very strong, my joints supple no arthritis at all (71 1/2 years old now), I can wriggle my ears, make surabhi mudra straight and reverse, have perfect nails on all fingers and toes.

I think we cannot be well until we cancel the hereditary weight we are carrying, and I think the future looks rosy now we know!

Be well!

Happy new year !

Exacly I am very very lucky that I got quickly hyper toxic (fish oil/ supplements , sweet potatoes and carrots, surpringly I never had liver / cheese in my life ) . This immediately made me realize it there was something wrong in what I was eating / Consuming . Thank go di foudn out it was vitamin A thing . Initially my symptoms matched (http://www.healthextremist.com/how-i-got-vitamin-a-toxicity/#comment-1000047) and thats what confirmed it , but didnt know what to do and I was eating stuff that I wasn't supposed to eat . Eventually someone in the comment mentioned about grants work and I am thankful to you guy for helping me and educating me , I dont know I didn't find this place I would be suffering a lot today!

Thank you all! God Bless!

Deleted user and Rebecca3 have reacted to this post.

#8 · January 1, 2024, 10:02 am

Quote from ggenereux on January 1, 2024, 7:18 am

Hi @r-2,

Thanks for putting that information together and sharing it.

I have no doubt that RA is the root cause of IBD, ulcerative Colitus etc.

Wishing everyone the best in 2024.

Absolute no Doubt !

Deleted user has reacted to this post.

#9 · January 8, 2024, 4:09 am

Quote from El on January 8, 2024, 4:09 am

Cita de r el 31 de diciembre de 2023 a las 11:57 am

Hola ,

En primer lugar, soy un ejemplo vivo (n = 1) de alguien sin antecedentes familiares de enfermedades autoinmunes (colitis, eccema, artritis, etc.) ni por parte de mi madre ni de mi padre desde hace generaciones (ya que somos pueblos tribales, no teníamos el lujo de comer los llamados alimentos "exóticos" saludables). De repente, después de 1 año de mucha vitamina A, me diagnostican colitis ulcerosa. Nunca tuve problemas intestinales, ni consitpatía, ni diarrea, deposiciones suaves en toda mi vida. Al menos no acepto que lo haya causado un fallo en mi "inmunidad". Sé que era vitamina A. Pero gracias a Dios descubrí temprano que se trataba de toxicidad por vitamina A. Sé cómo solucionarlo, o al menos no buscaré una cura en los lugares equivocados, sin embargo, creo que la ulcerosa es un daño colateral causado por VA en lugar de un síntoma, el síntoma es la bilis tóxica y la presencia de Gran cantidad de vitamina A en el tejido intestinal (como se muestra en el artículo siguiente)

He estado investigando un poco sobre la posible relación entre VA y CU y me sorprendió ver la abrumadora cantidad de investigaciones claras que muestran que el ácido retinoico es la causa real. He recopilado algunos de los artículos relevantes y los resumí. Incluso uno de los artículos recientes propuso la inhibición de ALDH1A1 o retinaldehído deshidrogenasa para el tratamiento de la CU y dice que incluso los productos biológicos de alta clase (clase de medicamento utilizado para suprimir el sistema inmunológico para tratar la colitis grave) hacen exactamente lo mismo.

Otro artículo de investigación importante descubrió que los pacientes que sufrieron un brote de CU tenían más ácido retinoico en el tejido intestinal, pero los niveles normales en el suero y los pacientes durante la remisión (tratados no sintomáticos) tenían una menor cantidad de ácido retinoico.

Enfermedad inflamatoria intestinal inducida por isotretinoína en un adolescente

https://www.researchgate.net/profile/Denise-Reniers/publication/11676652_Isotretinoin-Induced_Inflammatory_Bowel_Disease_in_an_Adolescent/links/5747126a08ae707fe21e36ef/Isotretinoin-Induced-Inflammatory-Bowel-Disease-in-an-Adolescent.pdf

Informe de caso: Varón de 17 años con colitis ulcerosa inducida por isotretinoína:

Antecedentes del paciente:

Varón de 17 años tratado con isotretinoína por acné severo.

Desarrolló enfermedad inflamatoria intestinal (EII), específicamente colitis ulcerosa, después de un tratamiento con isotretinoína de cinco meses.

Progresión de la condición:

A pesar de los tratamientos convencionales, el estado del paciente empeoró.

Experimentó una pérdida de peso significativa, edema y anemia.

Finalmente se realizó colectomía subtotal e ileostomía.

Mecanismos potenciales de EII inducida por isotretinoína:

La discusión explora mecanismos como la inhibición del crecimiento de las células epiteliales, la interferencia con la síntesis de glicoproteínas y la estimulación de las células T asesinas.

Importancia de la conciencia:

Destaca la importancia de indagar sobre el uso de isotretinoína en pacientes con sospecha de EII.

Destaca el grave evento adverso de la EII inducida por isotretinoína.

Casos adicionales:

Caso 1 (Hombre de 20 años con Enfermedad de Crohn):

Historia de dos años de enfermedad de Crohn.

La terapia con isotretinoína se inició en tres ocasiones, lo que provocó una exacerbación de la EII.

Mejoría de los síntomas gastrointestinales al mes de suspender la isotretinoína.

Caso 2 (Muchacho de 17 años con Proctosigmoiditis Aguda):

Desarrolló proctosigmoiditis aguda cuatro semanas después de comenzar con isotretinoína para el acné quístico.

No se informaron antecedentes previos de enfermedad intestinal.

La proctosigmoiditis se resolvió cuatro semanas después de la interrupción de la isotretinoína.

Se observó recurrencia tras la nueva exposición a isotretinoína en un plazo de dos semanas.

Dos artículos importantes que describen directamente el papel de la AR en el colitus ulceroso

Paper 1: Retinoic Acid and Immune Cells (Th9) https://pubmed.ncbi.nlm.nih.gov/26980802/ :

Topic: The paper talks about a substance called all-trans-retinoic acid and how it affects the immune system, especially in the intestines.

Normal Role: Usually, this substance helps the immune system and prevents inflammation.

Study Focus: Looked at how this substance affects specific immune cells (dendritic cells and CD4+ T cells) in humans in different situations.

Findings: In situations with inflammation, all-trans-retinoic acid may lead to the development of immune cells that contribute to inflammation in the intestines.

Conclusion: The role of this substance is not always straightforward; it can be helpful for the immune system, but in the presence of inflammation, it might have a different, potentially negative, effect in the intestines.

Paper 2: Retinoic Acid in Ulcerative Colitis - https://pubmed.ncbi.nlm.nih.gov/32469071/

Background: All-trans retinoic acid (RA) usually helps in creating immune cells that keep things under control.

Research Objective: Investigated RA levels in the gut of people with ulcerative colitis to see if it is linked to inflammation.

Findings:

People with active disease had more RA in their gut compared to those in remission or without the condition.

Higher RA levels in active disease were linked to more inflammation in different types of immune cells.

RA levels were linked to less of an anti-inflammatory substance (IL-10) and were associated with inhibiting the development of certain immune cells (Th9 cells).

Conclusion: In ulcerative colitis, higher RA levels might worsen inflammation by supporting the creation of certain immune cells and reducing anti-inflammatory substances.

Conclusions: The study confirms what we found in the lab—when there's inflammation, RA seems to play a role in keeping it going by supporting the creation of immune cells that cause inflammation in the gut. This suggests that RA might contribute to ongoing inflammation in the gut during certain conditions.

We studied the connection between a substance called retinoic acid (RA) and the immune responses in the gut. We measured RA levels in the blood and gut lining of people with ulcerative colitis (UC) and those without the condition.

Here's what we found:

In people with UC, RA levels in the gut lining and blood were higher compared to those without UC.

The increase in RA levels was more noticeable in the gut lining of people with UC.

When we looked at different stages of the disease—when inflammation is high (active disease) or low (remission)—we found that RA levels in the gut lining were significantly higher in people with active disease compared to those in remission and those without UC.

However, RA levels in the blood did not show a difference between active and remission states.

Title: Increased Retinoic Acid Production in Crohn's Disease -

https://pubmed.ncbi.nlm.nih.gov/24503130/#:~:text=with%20Crohn's%20disease-,Increased%20production%20of%20retinoic%20acid%20by%20intestinal%20macrophages%20contributes%20to,Gastroenterology.

Summary: The study explores elevated retinoic acid (RA) production, primarily by CD14(+) macrophages, in patients with Crohn's disease (CD). The findings suggest that inhibiting RA generation by these macrophages could be a therapeutic strategy. Two perspectives are discussed:

Higher RA and Inflammation (Undesirable):

In CD, higher RA levels, especially from CD14(+) macrophages, may contribute to an inflammatory phenotype.

If inflammation is linked to the disease, reducing RA levels could be a potential therapeutic approach.

Lower RA for Therapeutic Benefit (Desirable):

Blocking RA receptor signaling might reduce the development of inflammatory macrophages, offering a potential therapeutic benefit.

Lowering RA levels could help mitigate the inflammatory response associated with CD.

Conclusion:

For Crohn's disease, the study suggests that limiting RA generation, particularly by CD14(+) macrophages, could be a beneficial therapeutic approach.

However, considering the broader role of RA in various physiological processes, any therapeutic intervention should be carefully designed to prevent unintended consequences on normal immune function and other RA-regulated biological functions.

The complexity of the immune system and disease-specific details should be considered when interpreting these findings for potential treatments in Crohn's disease.

Title: Retinoic Acid's Impact on Intestinal Mucus and Enterocolitis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380709/

Summary:

Background:

Retinoid medications used for acne treatment are linked to inflammatory bowel disease (IBD).

The intestinal mucus layer is crucial for gut protection, and changes due to retinoid treatment might contribute to IBD, but direct evidence is limited.

Research Approach:

Used zebrafish larvae to create an IBD-like model by exposing them to dextran sodium sulfate (DSS).

This model mimicked aspects of another zebrafish IBD model, allowing the study of mucus changes independently of the adaptive immune system.

Inflammation induced in the gut was dependent on gut bacteria and influenced by drugs.

Findings:

Retinoic acid (RA), a type of retinoid, directly impacted the production of intestinal mucus.

RA suppressed both normal and abnormal mucin production.

Reduction in mucin production by RA made zebrafish larvae more vulnerable to inflammation when exposed to substances causing enterocolitis (inflammation of the intestines).

Implications:

The research establishes a direct influence of retinoid medication, specifically retinoic acid, on the intestinal mucus layer.

This influence may have implications for the development of intestinal inflammation, providing insight into the potential link between retinoid medications and inflammatory bowel disease.

Conclusion: This study using a zebrafish model demonstrates that retinoic acid, a type of retinoid medication, directly impacts intestinal mucus production. The reduction in mucin production induced by retinoic acid makes the gut more susceptible to inflammation, suggesting a potential connection between retinoid medications and the development of inflammatory bowel disease.

Gluten intolerance due to RA

Title: Retinoic Acid and IL-15 Impact on Immune Response in Coeliac Disease

Summary:

Background:

Coeliac disease involves an abnormal immune response to gluten, a wheat protein, disrupting the usual immune tolerance in the gut.

Research Focus:

Experiments with mice investigated the interaction of retinoic acid (a vitamin A metabolite) and IL-15 (elevated in coeliac disease) in the immune system.

Findings:

In the presence of IL-15, retinoic acid quickly activated dendritic cells (immune cells).

This activation resulted in the release of inflammatory substances.

In a stressed intestinal environment, retinoic acid signaled the immune system to react against gluten rather than tolerate it.

Implications:

Retinoic acid, in conjunction with IL-15, disrupts the normal immune tolerance to dietary antigens like gluten.

This unexpected role of retinoic acid provides insights into the mechanisms behind the immune response in coeliac disease.

Conclusion: The study reveals that retinoic acid, particularly in the presence of IL-15, plays an unexpected role in promoting an immune response against gluten in coeliac disease. In a stressed gut environment, retinoic acid signals immune cells to release inflammatory substances, disrupting the usual tolerance to dietary antigens. These findings offer valuable insights into the mechanisms involved in the abnormal immune response seen in coeliac disease.

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice
://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536456/

Summary: Investigating ALDH1A Inhibitor for IBD Treatment Researchers explored an oral treatment option, WIN 18,446, targeting ALDH1A enzymes that produce retinoic acid in inflammatory bowel disease (IBD). The study, conducted in chronic IBD mouse models (Mdr1a−/− mice), demonstrated that initiating WIN 18,446 before inflammation reduced clinical symptoms and improved histological colitis scores. The inhibitor influenced immune cells, particularly decreasing α4ß7 integrin expression on T cells. These findings suggest ALDH1A inhibition as a potential IBD treatment, possibly impacting the efficacy of existing biologics, and future studies aim to assess its effectiveness during active colitis.

Context: Understanding Retinoic Acid's Role in IBD Retinoic acid (RA), a metabolite of vitamin A, plays a dual role in gut inflammation. Reports suggest both beneficial and harmful effects of RA in IBD. The study used WIN 18,446, an ALDH1A inhibitor, to reduce RA synthesis in chronic IBD mouse models (Il10−/− and Mdr1a−/− mice). Treatment initiated before inflammation onset reduced colitis severity.

Notably, ALDH1A inhibition decreased α4ß7 integrin expression on activated T cells, suggesting potential synergy with existing IBD biologics targeting the same protein.

The study represents a step towards developing a new family of oral drugs for IBD treatment.The findings suggest that inhibiting ALDH1A could be a potential new approach for treating IBD.
Are you telling me that colacola that inhibits adlh is good? this doesn't make any sense

Cita de r el 31 de diciembre de 2023 a las 11:57 am

Hola ,

En primer lugar, soy un ejemplo vivo (n = 1) de alguien sin antecedentes familiares de enfermedades autoinmunes (colitis, eccema, artritis, etc.) ni por parte de mi madre ni de mi padre desde hace generaciones (ya que somos pueblos tribales, no teníamos el lujo de comer los llamados alimentos "exóticos" saludables). De repente, después de 1 año de mucha vitamina A, me diagnostican colitis ulcerosa. Nunca tuve problemas intestinales, ni consitpatía, ni diarrea, deposiciones suaves en toda mi vida. Al menos no acepto que lo haya causado un fallo en mi "inmunidad". Sé que era vitamina A. Pero gracias a Dios descubrí temprano que se trataba de toxicidad por vitamina A. Sé cómo solucionarlo, o al menos no buscaré una cura en los lugares equivocados, sin embargo, creo que la ulcerosa es un daño colateral causado por VA en lugar de un síntoma, el síntoma es la bilis tóxica y la presencia de Gran cantidad de vitamina A en el tejido intestinal (como se muestra en el artículo siguiente)

He estado investigando un poco sobre la posible relación entre VA y CU y me sorprendió ver la abrumadora cantidad de investigaciones claras que muestran que el ácido retinoico es la causa real. He recopilado algunos de los artículos relevantes y los resumí. Incluso uno de los artículos recientes propuso la inhibición de ALDH1A1 o retinaldehído deshidrogenasa para el tratamiento de la CU y dice que incluso los productos biológicos de alta clase (clase de medicamento utilizado para suprimir el sistema inmunológico para tratar la colitis grave) hacen exactamente lo mismo.

Otro artículo de investigación importante descubrió que los pacientes que sufrieron un brote de CU tenían más ácido retinoico en el tejido intestinal, pero los niveles normales en el suero y los pacientes durante la remisión (tratados no sintomáticos) tenían una menor cantidad de ácido retinoico.

Enfermedad inflamatoria intestinal inducida por isotretinoína en un adolescente

https://www.researchgate.net/profile/Denise-Reniers/publication/11676652_Isotretinoin-Induced_Inflammatory_Bowel_Disease_in_an_Adolescent/links/5747126a08ae707fe21e36ef/Isotretinoin-Induced-Inflammatory-Bowel-Disease-in-an-Adolescent.pdf

Informe de caso: Varón de 17 años con colitis ulcerosa inducida por isotretinoína:

Antecedentes del paciente:

Varón de 17 años tratado con isotretinoína por acné severo.

Desarrolló enfermedad inflamatoria intestinal (EII), específicamente colitis ulcerosa, después de un tratamiento con isotretinoína de cinco meses.

Progresión de la condición:

A pesar de los tratamientos convencionales, el estado del paciente empeoró.

Experimentó una pérdida de peso significativa, edema y anemia.

Finalmente se realizó colectomía subtotal e ileostomía.

Mecanismos potenciales de EII inducida por isotretinoína:

La discusión explora mecanismos como la inhibición del crecimiento de las células epiteliales, la interferencia con la síntesis de glicoproteínas y la estimulación de las células T asesinas.

Importancia de la conciencia:

Destaca la importancia de indagar sobre el uso de isotretinoína en pacientes con sospecha de EII.

Destaca el grave evento adverso de la EII inducida por isotretinoína.

Casos adicionales:

Caso 1 (Hombre de 20 años con Enfermedad de Crohn):

Historia de dos años de enfermedad de Crohn.

La terapia con isotretinoína se inició en tres ocasiones, lo que provocó una exacerbación de la EII.

Mejoría de los síntomas gastrointestinales al mes de suspender la isotretinoína.

Caso 2 (Muchacho de 17 años con Proctosigmoiditis Aguda):

Desarrolló proctosigmoiditis aguda cuatro semanas después de comenzar con isotretinoína para el acné quístico.

No se informaron antecedentes previos de enfermedad intestinal.

La proctosigmoiditis se resolvió cuatro semanas después de la interrupción de la isotretinoína.

Se observó recurrencia tras la nueva exposición a isotretinoína en un plazo de dos semanas.

Dos artículos importantes que describen directamente el papel de la AR en el colitus ulceroso

Paper 1: Retinoic Acid and Immune Cells (Th9) https://pubmed.ncbi.nlm.nih.gov/26980802/ :

Topic: The paper talks about a substance called all-trans-retinoic acid and how it affects the immune system, especially in the intestines.

Normal Role: Usually, this substance helps the immune system and prevents inflammation.

Study Focus: Looked at how this substance affects specific immune cells (dendritic cells and CD4+ T cells) in humans in different situations.

Findings: In situations with inflammation, all-trans-retinoic acid may lead to the development of immune cells that contribute to inflammation in the intestines.

Conclusion: The role of this substance is not always straightforward; it can be helpful for the immune system, but in the presence of inflammation, it might have a different, potentially negative, effect in the intestines.

Paper 2: Retinoic Acid in Ulcerative Colitis - https://pubmed.ncbi.nlm.nih.gov/32469071/

Background: All-trans retinoic acid (RA) usually helps in creating immune cells that keep things under control.

Research Objective: Investigated RA levels in the gut of people with ulcerative colitis to see if it is linked to inflammation.

Findings:

People with active disease had more RA in their gut compared to those in remission or without the condition.

Higher RA levels in active disease were linked to more inflammation in different types of immune cells.

RA levels were linked to less of an anti-inflammatory substance (IL-10) and were associated with inhibiting the development of certain immune cells (Th9 cells).

Conclusion: In ulcerative colitis, higher RA levels might worsen inflammation by supporting the creation of certain immune cells and reducing anti-inflammatory substances.

Conclusions: The study confirms what we found in the lab—when there's inflammation, RA seems to play a role in keeping it going by supporting the creation of immune cells that cause inflammation in the gut. This suggests that RA might contribute to ongoing inflammation in the gut during certain conditions.

We studied the connection between a substance called retinoic acid (RA) and the immune responses in the gut. We measured RA levels in the blood and gut lining of people with ulcerative colitis (UC) and those without the condition.

Here's what we found:

In people with UC, RA levels in the gut lining and blood were higher compared to those without UC.

The increase in RA levels was more noticeable in the gut lining of people with UC.

When we looked at different stages of the disease—when inflammation is high (active disease) or low (remission)—we found that RA levels in the gut lining were significantly higher in people with active disease compared to those in remission and those without UC.

However, RA levels in the blood did not show a difference between active and remission states.

Title: Increased Retinoic Acid Production in Crohn's Disease -

https://pubmed.ncbi.nlm.nih.gov/24503130/#:~:text=with%20Crohn's%20disease-,Increased%20production%20of%20retinoic%20acid%20by%20intestinal%20macrophages%20contributes%20to,Gastroenterology.

Summary: The study explores elevated retinoic acid (RA) production, primarily by CD14(+) macrophages, in patients with Crohn's disease (CD). The findings suggest that inhibiting RA generation by these macrophages could be a therapeutic strategy. Two perspectives are discussed:

Higher RA and Inflammation (Undesirable):

In CD, higher RA levels, especially from CD14(+) macrophages, may contribute to an inflammatory phenotype.

If inflammation is linked to the disease, reducing RA levels could be a potential therapeutic approach.

Lower RA for Therapeutic Benefit (Desirable):

Blocking RA receptor signaling might reduce the development of inflammatory macrophages, offering a potential therapeutic benefit.

Lowering RA levels could help mitigate the inflammatory response associated with CD.

Conclusion:

For Crohn's disease, the study suggests that limiting RA generation, particularly by CD14(+) macrophages, could be a beneficial therapeutic approach.

However, considering the broader role of RA in various physiological processes, any therapeutic intervention should be carefully designed to prevent unintended consequences on normal immune function and other RA-regulated biological functions.

The complexity of the immune system and disease-specific details should be considered when interpreting these findings for potential treatments in Crohn's disease.

Title: Retinoic Acid's Impact on Intestinal Mucus and Enterocolitis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380709/

Summary:

Background:

Retinoid medications used for acne treatment are linked to inflammatory bowel disease (IBD).

The intestinal mucus layer is crucial for gut protection, and changes due to retinoid treatment might contribute to IBD, but direct evidence is limited.

Research Approach:

Used zebrafish larvae to create an IBD-like model by exposing them to dextran sodium sulfate (DSS).

This model mimicked aspects of another zebrafish IBD model, allowing the study of mucus changes independently of the adaptive immune system.

Inflammation induced in the gut was dependent on gut bacteria and influenced by drugs.

Findings:

Retinoic acid (RA), a type of retinoid, directly impacted the production of intestinal mucus.

RA suppressed both normal and abnormal mucin production.

Reduction in mucin production by RA made zebrafish larvae more vulnerable to inflammation when exposed to substances causing enterocolitis (inflammation of the intestines).

Implications:

The research establishes a direct influence of retinoid medication, specifically retinoic acid, on the intestinal mucus layer.

This influence may have implications for the development of intestinal inflammation, providing insight into the potential link between retinoid medications and inflammatory bowel disease.

Conclusion: This study using a zebrafish model demonstrates that retinoic acid, a type of retinoid medication, directly impacts intestinal mucus production. The reduction in mucin production induced by retinoic acid makes the gut more susceptible to inflammation, suggesting a potential connection between retinoid medications and the development of inflammatory bowel disease.

Gluten intolerance due to RA

Title: Retinoic Acid and IL-15 Impact on Immune Response in Coeliac Disease

Summary:

Background:

Coeliac disease involves an abnormal immune response to gluten, a wheat protein, disrupting the usual immune tolerance in the gut.

Research Focus:

Experiments with mice investigated the interaction of retinoic acid (a vitamin A metabolite) and IL-15 (elevated in coeliac disease) in the immune system.

Findings:

In the presence of IL-15, retinoic acid quickly activated dendritic cells (immune cells).

This activation resulted in the release of inflammatory substances.

In a stressed intestinal environment, retinoic acid signaled the immune system to react against gluten rather than tolerate it.

Implications:

Retinoic acid, in conjunction with IL-15, disrupts the normal immune tolerance to dietary antigens like gluten.

This unexpected role of retinoic acid provides insights into the mechanisms behind the immune response in coeliac disease.

Conclusion: The study reveals that retinoic acid, particularly in the presence of IL-15, plays an unexpected role in promoting an immune response against gluten in coeliac disease. In a stressed gut environment, retinoic acid signals immune cells to release inflammatory substances, disrupting the usual tolerance to dietary antigens. These findings offer valuable insights into the mechanisms involved in the abnormal immune response seen in coeliac disease.

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice
://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536456/

Summary: Investigating ALDH1A Inhibitor for IBD Treatment Researchers explored an oral treatment option, WIN 18,446, targeting ALDH1A enzymes that produce retinoic acid in inflammatory bowel disease (IBD). The study, conducted in chronic IBD mouse models (Mdr1a−/− mice), demonstrated that initiating WIN 18,446 before inflammation reduced clinical symptoms and improved histological colitis scores. The inhibitor influenced immune cells, particularly decreasing α4ß7 integrin expression on T cells. These findings suggest ALDH1A inhibition as a potential IBD treatment, possibly impacting the efficacy of existing biologics, and future studies aim to assess its effectiveness during active colitis.

Context: Understanding Retinoic Acid's Role in IBD Retinoic acid (RA), a metabolite of vitamin A, plays a dual role in gut inflammation. Reports suggest both beneficial and harmful effects of RA in IBD. The study used WIN 18,446, an ALDH1A inhibitor, to reduce RA synthesis in chronic IBD mouse models (Il10−/− and Mdr1a−/− mice). Treatment initiated before inflammation onset reduced colitis severity.

Notably, ALDH1A inhibition decreased α4ß7 integrin expression on activated T cells, suggesting potential synergy with existing IBD biologics targeting the same protein.

The study represents a step towards developing a new family of oral drugs for IBD treatment.The findings suggest that inhibiting ALDH1A could be a potential new approach for treating IBD.

Are you telling me that colacola that inhibits adlh is good? this doesn't make any sense

Deleted user has reacted to this post.

#10 · January 9, 2024, 9:16 am

Quote from r on January 9, 2024, 9:16 am
Quote from El on January 8, 2024, 4:09 am

Cita de r el 31 de diciembre de 2023 a las 11:57 am

Hola ,

En primer lugar, soy un ejemplo vivo (n = 1) de alguien sin antecedentes familiares de enfermedades autoinmunes (colitis, eccema, artritis, etc.) ni por parte de mi madre ni de mi padre desde hace generaciones (ya que somos pueblos tribales, no teníamos el lujo de comer los llamados alimentos "exóticos" saludables). De repente, después de 1 año de mucha vitamina A, me diagnostican colitis ulcerosa. Nunca tuve problemas intestinales, ni consitpatía, ni diarrea, deposiciones suaves en toda mi vida. Al menos no acepto que lo haya causado un fallo en mi "inmunidad". Sé que era vitamina A. Pero gracias a Dios descubrí temprano que se trataba de toxicidad por vitamina A. Sé cómo solucionarlo, o al menos no buscaré una cura en los lugares equivocados, sin embargo, creo que la ulcerosa es un daño colateral causado por VA en lugar de un síntoma, el síntoma es la bilis tóxica y la presencia de Gran cantidad de vitamina A en el tejido intestinal (como se muestra en el artículo siguiente)

He estado investigando un poco sobre la posible relación entre VA y CU y me sorprendió ver la abrumadora cantidad de investigaciones claras que muestran que el ácido retinoico es la causa real. He recopilado algunos de los artículos relevantes y los resumí. Incluso uno de los artículos recientes propuso la inhibición de ALDH1A1 o retinaldehído deshidrogenasa para el tratamiento de la CU y dice que incluso los productos biológicos de alta clase (clase de medicamento utilizado para suprimir el sistema inmunológico para tratar la colitis grave) hacen exactamente lo mismo.

Otro artículo de investigación importante descubrió que los pacientes que sufrieron un brote de CU tenían más ácido retinoico en el tejido intestinal, pero los niveles normales en el suero y los pacientes durante la remisión (tratados no sintomáticos) tenían una menor cantidad de ácido retinoico.

Enfermedad inflamatoria intestinal inducida por isotretinoína en un adolescente

https://www.researchgate.net/profile/Denise-Reniers/publication/11676652_Isotretinoin-Induced_Inflammatory_Bowel_Disease_in_an_Adolescent/links/5747126a08ae707fe21e36ef/Isotretinoin-Induced-Inflammatory-Bowel-Disease-in-an-Adolescent.pdf

Informe de caso: Varón de 17 años con colitis ulcerosa inducida por isotretinoína:

Antecedentes del paciente:

Varón de 17 años tratado con isotretinoína por acné severo.

Desarrolló enfermedad inflamatoria intestinal (EII), específicamente colitis ulcerosa, después de un tratamiento con isotretinoína de cinco meses.

Progresión de la condición:

A pesar de los tratamientos convencionales, el estado del paciente empeoró.

Experimentó una pérdida de peso significativa, edema y anemia.

Finalmente se realizó colectomía subtotal e ileostomía.

Mecanismos potenciales de EII inducida por isotretinoína:

La discusión explora mecanismos como la inhibición del crecimiento de las células epiteliales, la interferencia con la síntesis de glicoproteínas y la estimulación de las células T asesinas.

Importancia de la conciencia:

Destaca la importancia de indagar sobre el uso de isotretinoína en pacientes con sospecha de EII.

Destaca el grave evento adverso de la EII inducida por isotretinoína.

Casos adicionales:

Caso 1 (Hombre de 20 años con Enfermedad de Crohn):

Historia de dos años de enfermedad de Crohn.

La terapia con isotretinoína se inició en tres ocasiones, lo que provocó una exacerbación de la EII.

Mejoría de los síntomas gastrointestinales al mes de suspender la isotretinoína.

Caso 2 (Muchacho de 17 años con Proctosigmoiditis Aguda):

Desarrolló proctosigmoiditis aguda cuatro semanas después de comenzar con isotretinoína para el acné quístico.

No se informaron antecedentes previos de enfermedad intestinal.

La proctosigmoiditis se resolvió cuatro semanas después de la interrupción de la isotretinoína.

Se observó recurrencia tras la nueva exposición a isotretinoína en un plazo de dos semanas.

Dos artículos importantes que describen directamente el papel de la AR en el colitus ulceroso

Paper 1: Retinoic Acid and Immune Cells (Th9) https://pubmed.ncbi.nlm.nih.gov/26980802/ :

Topic: The paper talks about a substance called all-trans-retinoic acid and how it affects the immune system, especially in the intestines.

Normal Role: Usually, this substance helps the immune system and prevents inflammation.

Study Focus: Looked at how this substance affects specific immune cells (dendritic cells and CD4+ T cells) in humans in different situations.

Findings: In situations with inflammation, all-trans-retinoic acid may lead to the development of immune cells that contribute to inflammation in the intestines.

Conclusion: The role of this substance is not always straightforward; it can be helpful for the immune system, but in the presence of inflammation, it might have a different, potentially negative, effect in the intestines.

Paper 2: Retinoic Acid in Ulcerative Colitis - https://pubmed.ncbi.nlm.nih.gov/32469071/

Background: All-trans retinoic acid (RA) usually helps in creating immune cells that keep things under control.

Research Objective: Investigated RA levels in the gut of people with ulcerative colitis to see if it is linked to inflammation.

Findings:

People with active disease had more RA in their gut compared to those in remission or without the condition.

Higher RA levels in active disease were linked to more inflammation in different types of immune cells.

RA levels were linked to less of an anti-inflammatory substance (IL-10) and were associated with inhibiting the development of certain immune cells (Th9 cells).

Conclusion: In ulcerative colitis, higher RA levels might worsen inflammation by supporting the creation of certain immune cells and reducing anti-inflammatory substances.

Conclusions: The study confirms what we found in the lab—when there's inflammation, RA seems to play a role in keeping it going by supporting the creation of immune cells that cause inflammation in the gut. This suggests that RA might contribute to ongoing inflammation in the gut during certain conditions.

We studied the connection between a substance called retinoic acid (RA) and the immune responses in the gut. We measured RA levels in the blood and gut lining of people with ulcerative colitis (UC) and those without the condition.

Here's what we found:

In people with UC, RA levels in the gut lining and blood were higher compared to those without UC.

The increase in RA levels was more noticeable in the gut lining of people with UC.

When we looked at different stages of the disease—when inflammation is high (active disease) or low (remission)—we found that RA levels in the gut lining were significantly higher in people with active disease compared to those in remission and those without UC.

However, RA levels in the blood did not show a difference between active and remission states.

Title: Increased Retinoic Acid Production in Crohn's Disease -

https://pubmed.ncbi.nlm.nih.gov/24503130/#:~:text=with%20Crohn's%20disease-,Increased%20production%20of%20retinoic%20acid%20by%20intestinal%20macrophages%20contributes%20to,Gastroenterology.

Summary: The study explores elevated retinoic acid (RA) production, primarily by CD14(+) macrophages, in patients with Crohn's disease (CD). The findings suggest that inhibiting RA generation by these macrophages could be a therapeutic strategy. Two perspectives are discussed:

Higher RA and Inflammation (Undesirable):

In CD, higher RA levels, especially from CD14(+) macrophages, may contribute to an inflammatory phenotype.

If inflammation is linked to the disease, reducing RA levels could be a potential therapeutic approach.

Lower RA for Therapeutic Benefit (Desirable):

Blocking RA receptor signaling might reduce the development of inflammatory macrophages, offering a potential therapeutic benefit.

Lowering RA levels could help mitigate the inflammatory response associated with CD.

Conclusion:

For Crohn's disease, the study suggests that limiting RA generation, particularly by CD14(+) macrophages, could be a beneficial therapeutic approach.

However, considering the broader role of RA in various physiological processes, any therapeutic intervention should be carefully designed to prevent unintended consequences on normal immune function and other RA-regulated biological functions.

The complexity of the immune system and disease-specific details should be considered when interpreting these findings for potential treatments in Crohn's disease.

Title: Retinoic Acid's Impact on Intestinal Mucus and Enterocolitis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380709/

Summary:

Background:

Retinoid medications used for acne treatment are linked to inflammatory bowel disease (IBD).

The intestinal mucus layer is crucial for gut protection, and changes due to retinoid treatment might contribute to IBD, but direct evidence is limited.

Research Approach:

Used zebrafish larvae to create an IBD-like model by exposing them to dextran sodium sulfate (DSS).

This model mimicked aspects of another zebrafish IBD model, allowing the study of mucus changes independently of the adaptive immune system.

Inflammation induced in the gut was dependent on gut bacteria and influenced by drugs.

Findings:

Retinoic acid (RA), a type of retinoid, directly impacted the production of intestinal mucus.

RA suppressed both normal and abnormal mucin production.

Reduction in mucin production by RA made zebrafish larvae more vulnerable to inflammation when exposed to substances causing enterocolitis (inflammation of the intestines).

Implications:

The research establishes a direct influence of retinoid medication, specifically retinoic acid, on the intestinal mucus layer.

This influence may have implications for the development of intestinal inflammation, providing insight into the potential link between retinoid medications and inflammatory bowel disease.

Conclusion: This study using a zebrafish model demonstrates that retinoic acid, a type of retinoid medication, directly impacts intestinal mucus production. The reduction in mucin production induced by retinoic acid makes the gut more susceptible to inflammation, suggesting a potential connection between retinoid medications and the development of inflammatory bowel disease.

Gluten intolerance due to RA

Title: Retinoic Acid and IL-15 Impact on Immune Response in Coeliac Disease

Summary:

Background:

Coeliac disease involves an abnormal immune response to gluten, a wheat protein, disrupting the usual immune tolerance in the gut.

Research Focus:

Experiments with mice investigated the interaction of retinoic acid (a vitamin A metabolite) and IL-15 (elevated in coeliac disease) in the immune system.

Findings:

In the presence of IL-15, retinoic acid quickly activated dendritic cells (immune cells).

This activation resulted in the release of inflammatory substances.

In a stressed intestinal environment, retinoic acid signaled the immune system to react against gluten rather than tolerate it.

Implications:

Retinoic acid, in conjunction with IL-15, disrupts the normal immune tolerance to dietary antigens like gluten.

This unexpected role of retinoic acid provides insights into the mechanisms behind the immune response in coeliac disease.

Conclusion: The study reveals that retinoic acid, particularly in the presence of IL-15, plays an unexpected role in promoting an immune response against gluten in coeliac disease. In a stressed gut environment, retinoic acid signals immune cells to release inflammatory substances, disrupting the usual tolerance to dietary antigens. These findings offer valuable insights into the mechanisms involved in the abnormal immune response seen in coeliac disease.

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice
://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536456/

Summary: Investigating ALDH1A Inhibitor for IBD Treatment Researchers explored an oral treatment option, WIN 18,446, targeting ALDH1A enzymes that produce retinoic acid in inflammatory bowel disease (IBD). The study, conducted in chronic IBD mouse models (Mdr1a−/− mice), demonstrated that initiating WIN 18,446 before inflammation reduced clinical symptoms and improved histological colitis scores. The inhibitor influenced immune cells, particularly decreasing α4ß7 integrin expression on T cells. These findings suggest ALDH1A inhibition as a potential IBD treatment, possibly impacting the efficacy of existing biologics, and future studies aim to assess its effectiveness during active colitis.

Context: Understanding Retinoic Acid's Role in IBD Retinoic acid (RA), a metabolite of vitamin A, plays a dual role in gut inflammation. Reports suggest both beneficial and harmful effects of RA in IBD. The study used WIN 18,446, an ALDH1A inhibitor, to reduce RA synthesis in chronic IBD mouse models (Il10−/− and Mdr1a−/− mice). Treatment initiated before inflammation onset reduced colitis severity.

Notably, ALDH1A inhibition decreased α4ß7 integrin expression on activated T cells, suggesting potential synergy with existing IBD biologics targeting the same protein.

The study represents a step towards developing a new family of oral drugs for IBD treatment.The findings suggest that inhibiting ALDH1A could be a potential new approach for treating IBD.
Are you telling me that colacola that inhibits adlh is good? this doesn't make any sense
read again it says drugs target aldh inhibition , I never said cola or inhibition is good, however if you are in a severe flare of UC that can end you up with losing your colon ,

are you telling me that time you won’t take Coca-Cola if it hypothetically ( it doesn’t ) rescue yourself and save your colon ?

Quote from El on January 8, 2024, 4:09 am

Cita de r el 31 de diciembre de 2023 a las 11:57 am

Hola ,

En primer lugar, soy un ejemplo vivo (n = 1) de alguien sin antecedentes familiares de enfermedades autoinmunes (colitis, eccema, artritis, etc.) ni por parte de mi madre ni de mi padre desde hace generaciones (ya que somos pueblos tribales, no teníamos el lujo de comer los llamados alimentos "exóticos" saludables). De repente, después de 1 año de mucha vitamina A, me diagnostican colitis ulcerosa. Nunca tuve problemas intestinales, ni consitpatía, ni diarrea, deposiciones suaves en toda mi vida. Al menos no acepto que lo haya causado un fallo en mi "inmunidad". Sé que era vitamina A. Pero gracias a Dios descubrí temprano que se trataba de toxicidad por vitamina A. Sé cómo solucionarlo, o al menos no buscaré una cura en los lugares equivocados, sin embargo, creo que la ulcerosa es un daño colateral causado por VA en lugar de un síntoma, el síntoma es la bilis tóxica y la presencia de Gran cantidad de vitamina A en el tejido intestinal (como se muestra en el artículo siguiente)

He estado investigando un poco sobre la posible relación entre VA y CU y me sorprendió ver la abrumadora cantidad de investigaciones claras que muestran que el ácido retinoico es la causa real. He recopilado algunos de los artículos relevantes y los resumí. Incluso uno de los artículos recientes propuso la inhibición de ALDH1A1 o retinaldehído deshidrogenasa para el tratamiento de la CU y dice que incluso los productos biológicos de alta clase (clase de medicamento utilizado para suprimir el sistema inmunológico para tratar la colitis grave) hacen exactamente lo mismo.

Otro artículo de investigación importante descubrió que los pacientes que sufrieron un brote de CU tenían más ácido retinoico en el tejido intestinal, pero los niveles normales en el suero y los pacientes durante la remisión (tratados no sintomáticos) tenían una menor cantidad de ácido retinoico.

Enfermedad inflamatoria intestinal inducida por isotretinoína en un adolescente

https://www.researchgate.net/profile/Denise-Reniers/publication/11676652_Isotretinoin-Induced_Inflammatory_Bowel_Disease_in_an_Adolescent/links/5747126a08ae707fe21e36ef/Isotretinoin-Induced-Inflammatory-Bowel-Disease-in-an-Adolescent.pdf

Informe de caso: Varón de 17 años con colitis ulcerosa inducida por isotretinoína:

Antecedentes del paciente:

Varón de 17 años tratado con isotretinoína por acné severo.

Desarrolló enfermedad inflamatoria intestinal (EII), específicamente colitis ulcerosa, después de un tratamiento con isotretinoína de cinco meses.

Progresión de la condición:

A pesar de los tratamientos convencionales, el estado del paciente empeoró.

Experimentó una pérdida de peso significativa, edema y anemia.

Finalmente se realizó colectomía subtotal e ileostomía.

Mecanismos potenciales de EII inducida por isotretinoína:

La discusión explora mecanismos como la inhibición del crecimiento de las células epiteliales, la interferencia con la síntesis de glicoproteínas y la estimulación de las células T asesinas.

Importancia de la conciencia:

Destaca la importancia de indagar sobre el uso de isotretinoína en pacientes con sospecha de EII.

Destaca el grave evento adverso de la EII inducida por isotretinoína.

Casos adicionales:

Caso 1 (Hombre de 20 años con Enfermedad de Crohn):

Historia de dos años de enfermedad de Crohn.

La terapia con isotretinoína se inició en tres ocasiones, lo que provocó una exacerbación de la EII.

Mejoría de los síntomas gastrointestinales al mes de suspender la isotretinoína.

Caso 2 (Muchacho de 17 años con Proctosigmoiditis Aguda):

Desarrolló proctosigmoiditis aguda cuatro semanas después de comenzar con isotretinoína para el acné quístico.

No se informaron antecedentes previos de enfermedad intestinal.

La proctosigmoiditis se resolvió cuatro semanas después de la interrupción de la isotretinoína.

Se observó recurrencia tras la nueva exposición a isotretinoína en un plazo de dos semanas.

Dos artículos importantes que describen directamente el papel de la AR en el colitus ulceroso

Paper 1: Retinoic Acid and Immune Cells (Th9) https://pubmed.ncbi.nlm.nih.gov/26980802/ :

Topic: The paper talks about a substance called all-trans-retinoic acid and how it affects the immune system, especially in the intestines.

Normal Role: Usually, this substance helps the immune system and prevents inflammation.

Study Focus: Looked at how this substance affects specific immune cells (dendritic cells and CD4+ T cells) in humans in different situations.

Findings: In situations with inflammation, all-trans-retinoic acid may lead to the development of immune cells that contribute to inflammation in the intestines.

Conclusion: The role of this substance is not always straightforward; it can be helpful for the immune system, but in the presence of inflammation, it might have a different, potentially negative, effect in the intestines.

Paper 2: Retinoic Acid in Ulcerative Colitis - https://pubmed.ncbi.nlm.nih.gov/32469071/

Background: All-trans retinoic acid (RA) usually helps in creating immune cells that keep things under control.

Research Objective: Investigated RA levels in the gut of people with ulcerative colitis to see if it is linked to inflammation.

Findings:

People with active disease had more RA in their gut compared to those in remission or without the condition.

Higher RA levels in active disease were linked to more inflammation in different types of immune cells.

RA levels were linked to less of an anti-inflammatory substance (IL-10) and were associated with inhibiting the development of certain immune cells (Th9 cells).

Conclusion: In ulcerative colitis, higher RA levels might worsen inflammation by supporting the creation of certain immune cells and reducing anti-inflammatory substances.

Conclusions: The study confirms what we found in the lab—when there's inflammation, RA seems to play a role in keeping it going by supporting the creation of immune cells that cause inflammation in the gut. This suggests that RA might contribute to ongoing inflammation in the gut during certain conditions.

We studied the connection between a substance called retinoic acid (RA) and the immune responses in the gut. We measured RA levels in the blood and gut lining of people with ulcerative colitis (UC) and those without the condition.

Here's what we found:

In people with UC, RA levels in the gut lining and blood were higher compared to those without UC.

The increase in RA levels was more noticeable in the gut lining of people with UC.

When we looked at different stages of the disease—when inflammation is high (active disease) or low (remission)—we found that RA levels in the gut lining were significantly higher in people with active disease compared to those in remission and those without UC.

However, RA levels in the blood did not show a difference between active and remission states.

Title: Increased Retinoic Acid Production in Crohn's Disease -

https://pubmed.ncbi.nlm.nih.gov/24503130/#:~:text=with%20Crohn's%20disease-,Increased%20production%20of%20retinoic%20acid%20by%20intestinal%20macrophages%20contributes%20to,Gastroenterology.

Summary: The study explores elevated retinoic acid (RA) production, primarily by CD14(+) macrophages, in patients with Crohn's disease (CD). The findings suggest that inhibiting RA generation by these macrophages could be a therapeutic strategy. Two perspectives are discussed:

Higher RA and Inflammation (Undesirable):

In CD, higher RA levels, especially from CD14(+) macrophages, may contribute to an inflammatory phenotype.

If inflammation is linked to the disease, reducing RA levels could be a potential therapeutic approach.

Lower RA for Therapeutic Benefit (Desirable):

Blocking RA receptor signaling might reduce the development of inflammatory macrophages, offering a potential therapeutic benefit.

Lowering RA levels could help mitigate the inflammatory response associated with CD.

Conclusion:

For Crohn's disease, the study suggests that limiting RA generation, particularly by CD14(+) macrophages, could be a beneficial therapeutic approach.

However, considering the broader role of RA in various physiological processes, any therapeutic intervention should be carefully designed to prevent unintended consequences on normal immune function and other RA-regulated biological functions.

The complexity of the immune system and disease-specific details should be considered when interpreting these findings for potential treatments in Crohn's disease.

Title: Retinoic Acid's Impact on Intestinal Mucus and Enterocolitis - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380709/

Summary:

Background:

Retinoid medications used for acne treatment are linked to inflammatory bowel disease (IBD).

The intestinal mucus layer is crucial for gut protection, and changes due to retinoid treatment might contribute to IBD, but direct evidence is limited.

Research Approach:

Used zebrafish larvae to create an IBD-like model by exposing them to dextran sodium sulfate (DSS).

This model mimicked aspects of another zebrafish IBD model, allowing the study of mucus changes independently of the adaptive immune system.

Inflammation induced in the gut was dependent on gut bacteria and influenced by drugs.

Findings:

Retinoic acid (RA), a type of retinoid, directly impacted the production of intestinal mucus.

RA suppressed both normal and abnormal mucin production.

Reduction in mucin production by RA made zebrafish larvae more vulnerable to inflammation when exposed to substances causing enterocolitis (inflammation of the intestines).

Implications:

The research establishes a direct influence of retinoid medication, specifically retinoic acid, on the intestinal mucus layer.

This influence may have implications for the development of intestinal inflammation, providing insight into the potential link between retinoid medications and inflammatory bowel disease.

Conclusion: This study using a zebrafish model demonstrates that retinoic acid, a type of retinoid medication, directly impacts intestinal mucus production. The reduction in mucin production induced by retinoic acid makes the gut more susceptible to inflammation, suggesting a potential connection between retinoid medications and the development of inflammatory bowel disease.

Gluten intolerance due to RA

Title: Retinoic Acid and IL-15 Impact on Immune Response in Coeliac Disease

Summary:

Background:

Coeliac disease involves an abnormal immune response to gluten, a wheat protein, disrupting the usual immune tolerance in the gut.

Research Focus:

Experiments with mice investigated the interaction of retinoic acid (a vitamin A metabolite) and IL-15 (elevated in coeliac disease) in the immune system.

Findings:

In the presence of IL-15, retinoic acid quickly activated dendritic cells (immune cells).

This activation resulted in the release of inflammatory substances.

In a stressed intestinal environment, retinoic acid signaled the immune system to react against gluten rather than tolerate it.

Implications:

Retinoic acid, in conjunction with IL-15, disrupts the normal immune tolerance to dietary antigens like gluten.

This unexpected role of retinoic acid provides insights into the mechanisms behind the immune response in coeliac disease.

Conclusion: The study reveals that retinoic acid, particularly in the presence of IL-15, plays an unexpected role in promoting an immune response against gluten in coeliac disease. In a stressed gut environment, retinoic acid signals immune cells to release inflammatory substances, disrupting the usual tolerance to dietary antigens. These findings offer valuable insights into the mechanisms involved in the abnormal immune response seen in coeliac disease.

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice
://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536456/

Summary: Investigating ALDH1A Inhibitor for IBD Treatment Researchers explored an oral treatment option, WIN 18,446, targeting ALDH1A enzymes that produce retinoic acid in inflammatory bowel disease (IBD). The study, conducted in chronic IBD mouse models (Mdr1a−/− mice), demonstrated that initiating WIN 18,446 before inflammation reduced clinical symptoms and improved histological colitis scores. The inhibitor influenced immune cells, particularly decreasing α4ß7 integrin expression on T cells. These findings suggest ALDH1A inhibition as a potential IBD treatment, possibly impacting the efficacy of existing biologics, and future studies aim to assess its effectiveness during active colitis.

Context: Understanding Retinoic Acid's Role in IBD Retinoic acid (RA), a metabolite of vitamin A, plays a dual role in gut inflammation. Reports suggest both beneficial and harmful effects of RA in IBD. The study used WIN 18,446, an ALDH1A inhibitor, to reduce RA synthesis in chronic IBD mouse models (Il10−/− and Mdr1a−/− mice). Treatment initiated before inflammation onset reduced colitis severity.

Notably, ALDH1A inhibition decreased α4ß7 integrin expression on activated T cells, suggesting potential synergy with existing IBD biologics targeting the same protein.

The study represents a step towards developing a new family of oral drugs for IBD treatment.The findings suggest that inhibiting ALDH1A could be a potential new approach for treating IBD.
Are you telling me that colacola that inhibits adlh is good? this doesn't make any sense

read again it says drugs target aldh inhibition , I never said cola or inhibition is good, however if you are in a severe flare of UC that can end you up with losing your colon ,

are you telling me that time you won’t take Coca-Cola if it hypothetically ( it doesn’t ) rescue yourself and save your colon ?

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Ulcerative Colitis and Crohn's are caused by Vitamin A toxicity !

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