Crohn’s Disease: Is the Cold Chain Hypothesis Still Hot?

[asadmom]

Abstract

Crohn’s disease [CD] is an inflammatory bowel disease of unknown aetiology. During recent decades, significant technological advances led to development of -omic datasets allowing a detailed description of the disease. Unfortunately these have not, to date, resolved the question of the aetiology of CD. Thus, it may be necessary to [re]consider hypothesis-driven approaches to resolve the aetiology of CD. According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. We discuss the consistency of this working hypothesis in light of recent data from epidemiological, clinical, pathological, microbiological, and molecular studies

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023829/pdf/jjaa192.pdf

 

[kiny]

Fibres, particularly fruit, have been inversely associated with the risk of CD in America but not in Europe

Finally, a recent prospective cohort study found no association between ultra-processed food and CD.

Rapid sugars have been suspected but not confirmed in a randomised clinical trial

The total amount of fat ingested does not seem to have a major role either, and enteral nutrition solutions, in particular those rich in fatty acids, still have a beneficial effect

Although food additives are likely candidates, it should be noted that most enteral nutrition formulas used for the treatment of CD contain such addditives. Among the 61 products studied by Logan
et al. 17 , all contained several food additives. Modified starch, including maltodextrin, was present in all formulas, carrageenan was present in 12/55 [22%], carboxymethyl cellulose was present in 7/55 [13%], and sucralose and polysorbate 80 were present in 3/55 [5%] formulas 17.

The number of contradicitons is staggering. EN has upended everything we thought we knew about diet and crohn's disease. EN is by far the most effective treatment for ileal crohn's disease and contradicts everything.

EN contains rapid sugars.
EN contains emulsifiers to integrate MCT into the formula.
EN contains lots of maltodextrin.
EN contains no fiber.
EN is ultra processed.

The opposite of what every dietician and study would recommend, is omnipresent in EN. That "unhealthy Western diet" full of simple sugars, emulsifiers, lack of fibers, with lots of fat, is omnipresent in EN, and is the most effective means of inducing remission.

 

[asadmom]

The number of contradicitons is staggering. EN has upended everything we thought we knew about diet and crohn's disease. EN is by far the most effective treatment for ileal crohn's disease and contradicts everything.

EN contains rapid sugars.
EN contains emulsifiers to integrate MCT into the formula.
EN contains lots of maltodextrin.
EN contains no fiber.
EN is ultra processed.

The opposite of what every dietician and study would recommend, is omnipresent in EN. That "unhealthy Western diet" full of simple sugars, emulsifiers, lack of fibers, with lots of fat, is omnipresent in EN, and is the most effective means of inducing remission.

It feels like these ingredients are illegal when they are in the form of solids but have no bearing when they are presented in the liquid form?

 

[kiny]

They're soluble so it shouldn't make a difference.

What really sets EN apart is a complete lack of fermentable energy like starch.

 

[kiny]

The study's argument ties in EN with the cold chain hypothesis. EN is free from foodborne pathogens like Yersinia and therefore doesn't invoke an immune response. I don't know, Yersinia species recovered from CD patients aren't that virulent usually. Most people have Yersinia present in the ileum, they don't translocate that easily across the epithelial barrier, they interact with M cells but are not nearly as pathogenic as invasive E Coli.

 

[asadmom]

The study's argument ties in EN with the cold chain hypothesis. EN is free from foodborne pathogens like Yersinia and therefore doesn't invoke an immune response. I don't know, Yersinia species recovered from CD patients aren't that virulent usually. Most people have Yersinia present in the ileum, they don't translocate that easily across the epithelial barrier, they interact with M cells but are not nearly as pathogenic as invasive E Coli.

This article doesn't repeat the mainstream belief so I had to read it a few times. If the cold chain theory is true then produce fresh from the garden as the only source of food should be equally effective however the fiber part of this diet is problematic.

 

[kiny]

Crohn's disease has always been a bit more prevalent in urban areas than rural areas. When areas that were previously rural become urbanized, the rates of crohn's disease increase.

Do farmers refrigerate food less. Are they less exposed to foodborne infections. I have no idea, I am not a farmer. But I'm all in to become one if it cures crohn's disease.

A study showed that if people with crohn's disease move to an area where crohn's disease is less prevalent, people with crohn's disease have a slightly smaller chance to relapse and remain in remission slightly longer. Why, we have no idea.

We know when moroccan migrants moved to Europe, they developed crohn's disease at rates similar to the local population. Moroccan family members who stayed in Northern Africa however, saw no such increase.

When countries develop and increase living standards, the rates of crohn's disease increase. It coincides with increased refrigeration because these communities now have electricity and the financial means to refrigerate food. But lots of other things coincide with increasing standards of living and westernization, refrigeration of food is just one factor.

 

[kiny]

Like this study pointed out. Refrigeration can be associated with crohn's disease, but so can having a car and a television.

In countries and areas where living standards increase, the rate of crohn's disease increases. That could be due to refrigeration, or many other factors.

 

[kiny]

The number of contradicitons is staggering.

EN contains rapid sugars.
EN contains emulsifiers to integrate MCT into the formula.
EN contains lots of maltodextrin.
EN contains no fiber.
EN is ultra processed.

The opposite of what every dietician and study would recommend, is omnipresent in EN. That "unhealthy Western diet" full of simple sugars, emulsifiers, lack of fibers, with lots of fat, is omnipresent in EN, and is the most effective means of inducing remission.

It finally dawned on GI and dieticians recommending CDED that there might be some major contradictions.

We have 4 decades worth of studies that show elemental nutrition is effective. We have 1 Israli study that claims CDED (exclusion+PEN) is effective, but 2 studies that show PEN was not effective at all.

Instead of calling it a "paradox", the claims the Israeli CDED study made should be heavily scrutinized.

 

[asadmom]

It finally dawned on GI and dieticians recommending CDED that there might be some major contradictions.

Instead of calling it a "paradox", the claims the Israeli CDED study made should be heavily scrutinized.


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MD is not right either.

It's interesting the title has the word "Prevention"

 

[kiny]

It's interesting the title has the word "Prevention"

Right. It's the argument that dietary fiber could be preventative for Crohn's.

But I have shown lack of fiber intake is not linked to crohn's disease in Europe, in previous posts. So have several studies.

Crohn's disease in the US and in Europe are similar, genetic overlap is similar, there's no reason why there should be any different conclusion. The link between fiber intake and subsequent development of CD is extremely weak, there is no such association in European studies.

Largest study in Europe. 401,326 participants in Europe. A study spanning a decade of data. No association whatsoever between low fiber intake and subsequent development of crohn's was found.

https://academic.oup.com/ecco-jcc/article/12/2/129/4372232?login=false

The main finding of this study was that there were no associations in the whole cohort with the intakes of total fibre, or fibre from fruit, vegetables or cereals, and the subsequent development of either CD or UC.

 

[kiny]

The concept of CDED, which is PEN+exclusion diet, comes from someone named Arie Levine.

It's the study that is wildly shared online. The exclusion diet, the CDED diet, whatever you want to call it.

Arie Levine, a pediatric gastro from Israel. You'll see his name quoted in the bottom of that ECCO presentation. He's no longer a working GI, because he was accused of sexual assault on his patients. These CDED studies happened at a private clinic, he was arrested, and that's the extent of the CDED data.





The other claims come from Mitsuro Chiba, a PhD is a gastroenterologist and researcher at Akita City Hospital in Japan. He has been advocating for plant based high fiber diets in Japan for years.

Take note that no one in Japan follows these recommendations. Most hospitals in Japan just do standard EN treatments.


These studies are interesting to some, especially to dieticians, because they can sell the idea that EN does not need to be strictly followed. But they contradict 4 decades of studies we have about EN. Including studies from the US, UK and France that show PEN is not effective in inducing remission, and studies from Japan that show total nitrogen utilization and total EN intake matters.

 

[asadmom]

CDED uses Modulen as its standard drink of choice. I always thought CDED is Nestle's home-grown diet plan. Maybe Nestle hired Arie Levine to create the diet plan?

BTW, didn't know about the background of Levine. That's appalling.

 

[kiny]

CDED uses Modulen as its standard drink of choice. I always thought CDED is Nestle's home-grown diet plan. Maybe Nestle hired Arie Levine to create the diet plan?

Nestlé did sponsor the CDED study. They built the whole Modulife site around it. The idea that you only need to use EN half of the time is very attractive to patients and especially parents.

Mind you...do not let that persuade you not to use Modulen. Modulen has been shown to be effective in many studies. EN in general has been shown to be very effective.

People like Anthony Segal are people you can fully trust. And the studies from the 80s and 90s posted in the British Medical Journal showing the effectiveness of Nestlé's formula are studies you can fully trust.

But, Nestlé should have never sponsored this Israeli study. The data behind CDED is very weak, and the person behind it is a very questionable individual.

PEN, partial elemental nutriton, has been shown not to be effective. There's no logical reason why it would be.

 

[kiny]

I often quote old BMJ and The Lancet studies. The reason for this is that the BMJ and the Lancet are a library full of valuable information. They were made in a time where studies were not sponsored by corporations and the individuals behind the studies are often retired, and they love to chat about their studies. These studies were well done and they were made in a time where studies were repeated by other researchers to ensure their validity. The BMJ especially is a trove of valuable information.