Transforming growth factors and EN.

[kiny]

 

[kiny]

 

[kiny]

 

[kiny]

In case anyone reads all this stuff. There was a bit of early apprehension regarding enriching EN with TGF-β because of its involvement in fibrosis. But fibrosis is not worsened with EN, or with EN with TGF-β, quite the opposite.

 

[asadmom]

Modulen is the only formula that I can find in the US that has the growth factor. I wonder if this is the main differentiation between Modulen and all others (like Neocate Jr.) and what brands Modulen as the drink for Crohn's treatment.

We are using Neocate Jr. at the moment. Just ordered a ton of Modulen with a coupon code.

 

[kiny]

Some studies differentiate EN based on the type of protein. They'll call some polymeric due to the length of the protein and others with broken down peptides elemental. I don't care about this distinction, the nitrogen source has no impact whatsoever on the effectiveness of the EN. There's also no rule on what these peptides should look like because the hydrolysis process differs from manufacturer to manufacturer.

Same with maltodextrins found in EN, they all have a slightly different DE equivalent due to differences in hydrolysis times. Maltodextrin is made from starch hydrolysis, but it is nothing like starch anymore after the process. You could differentiate EN on that basis, but it serves little point, because it doesn't affect how well EN works at all.

Enriched TFG-b and MCT content possibly has an impact on the effectiveness.

 

[kiny]

Btw, don't do fasting before you start EN. Refeeding syndrome is very rare, but you shouldn't fast and then suddenly take a lot of EN.

Intermittent fasting is fine, but people who fast for several days, or people who do Ramadan, should build up EN a bit more slowly. Anyway, not a big fan of fasting, the small intestine needs a lot of nutrients to maintain barrier integrity.

 

[kiny]

Was reading over some studies. Modulen was called CT3211 in experimental studies.

It's a derivative of Nestlé AL110. AL110 is for kids with severe lactose intolerance and malnutrition.

Most of these formulas from companies aren't particularly high transforming growth factor, but AL110 is. AL110 had previously been shown to be effective in treating crohn's disease in children, but was never particularly designed for crohn's disease. Because Nestlé knew how to get these growth factors into formulas, they made a version of AL110 with concentrated TGFβ, called Modulen. Nestlé tested this with Tom MacDonald, Professor of Immunology, in the St Bartholonew's hospital in the UK. In the first trial, they achieved 90% remission rates in children with crohn's disease, which was good enough for Nestlé Science to start producing it en masse.

 

[kiny]

You can find many "Documents of application" in Europe where companies have to register a baby formula with all ingredients, it's much more extensive than just the ingredient list on products. Most infant formula actually lack TGFβ, because they're made to be hypoallergenic. The TGFβ is mostly concentrated in bovine milk, it's an immune tolerance factors for the calves. When a company extracts protein from skimmed milk, it is rich in TGFβ, but it is no longer present in the hypoallergenic formulas. I don't follow anything about infant formulas, but TGFβ is also found in human breast milk, and I assume these kids getting fed hypoallergenic infant formulas lacking in TGFβ, instead of breast milk rich in TGFβ, is probably not that great, their intolerance to dietary antigens could just worsen.

 

[westernbuddy]

@kinny

I take 1 x sachet of elemental 028 per day, I also eat food and I also take protein shakes as I go to the gym.

I seam to be able to tolerate protein shakes, the gym seams to do me really great also.


Do you have a protein shake that you have studied and would be best for crohns ?

I take all these drinks eat all this food around 2.2k calories per day and trying to put on weight is almost impossible.

My fitness pal app is well worth trying for anyone with crohns, even if it's only for a week.

 

[kiny]

I add whey isolate and a daily tablespoon of MCT to my EN. Because there is lecithin in EN it mixes without a problem. If I can find 028 for cheap I will go buy it, otherwise I use Modulen which is usually cheaper.

EN are relatively low on protein and the small intestine needs a lot of glutamine. L-glutamine is very unstable, adding a bit of whey to EN makes much more sense. It should be appreciated that the small intestine is a muscle.

 

[asadmom]

I add whey isolate and a daily tablespoon of MCT to my EN. Because there is lecithin in EN it mixes without a problem. If I can find 028 for cheap I will go buy it, otherwise I use Modulen which is usually cheaper.

EN are relatively low on protein and the small intestine needs a lot of glutamine. L-glutamine is very unstable, adding a bit of whey to EN makes much more sense. It should be appreciated that the small intestine is a muscle.

Can we supplement with l-glutamine powder?

 

[kiny]

Can we supplement with l-glutamine powder?

You can, several studies have done this. But you can just as easily consume enough protein. The body is more than capable of making glutamine, it's the most abundant amino acid in the body, all immune cells need it to function. The body just needs enough protein intake to make it.

The glutamine you buy in the store isn't as stable as other amino acids, it becomes unstable in solutions and higher temperatures. It can also cause diarrhea, you need to dose it right, etc, it's just much easier and safer to just consume enough protein.

 

[patulsius]

I add whey isolate and a daily tablespoon of MCT to my EN. Because there is lecithin in EN it mixes without a problem. If I can find 028 for cheap I will go buy it, otherwise I use Modulen which is usually cheaper.

EN are relatively low on protein and the small intestine needs a lot of glutamine. L-glutamine is very unstable, adding a bit of whey to EN makes much more sense. It should be appreciated that the small intestine is a muscle.

@kiny I was doing some testings with EEN mixing some ingredients on my own. I've bought hydrolyzed whey to get protein, now I wonder if there is any difference between isolate and hydrolyzed whey and what is more convenient for our dietary needs.

 

[kiny]

I don't think it matters. Isolate is much cheaper so I use that. Most protein is absorbed at the proximal jejunum. Crohn's disease manifests itself much more distally, at the ileum. We can absorb protein just fine.

Whey concentrate is still full of fats and carbs. We just want the protein and isolate is only slightly more expensive than concentrate, it's just a cheap extra filtering process to remove the lactose and fat. I see no reason for hydrolysed whey, it's way more expensive because of the extra hydrolysis step and there's no reason why we would absorb it better, it likely only affects the speed of absorption.

 

[kiny]

I said that it is underappreciated that the small intestine is a muscle. I think it is generally underappreciated that the small intestine is the fastest regenerating organ in the body.

When people on EN + anti-TNF somehow heal from fibrosis and fistula, it has surely a lot to do with the fact the epithelial barrier renews itself in a few days and the fact the small intestine is programmed to do this faster than any other organ. The very fast turnover of these epithelial cells was confirmed in recent studies.

If inflammation is kept at bay, the small intestine is very good at reversing tissue damage, if you give it the nutrients to do this.

 

[asadmom]

Transient Suppression of Bacterial Populations Associated with Gut Health is Critical in Success of Exclusive Enteral Nutrition for Children with Crohn’s Disease

https://academic.oup.com/ecco-jcc/a...rom=fulltext&login=false#.ZB1ir5q_CxY.twitter

 

[kiny]

These observations taken together suggest that successful outcomes of EEN are marked by a temporary emergence of microbial populations that are rare in healthy individuals, and a concomitant reduction in microbes that are commonly associated with gut homeostasis.

Thanks.

It has been shown several times that EN not only brings down bacterial load, but also increases dysbiosis. The microbiome signature of people on EN in remission is not a microbiome which researchers associate with health.

Research is far too focused on trying to link microbiomes to health and disease. EN decreases the fecal stream and bacterial load, which lowers the amount of antigen that comes into contact with the epithelial barrier, leading to remission. Whatever changes we see to the microbiome could be a result of the decrease in inflammation and the dietary changes of EN, and likely has no direct impact on the effectiveness of EN.

It's not that out of the ordinary that EN results in a rare microbiome signature that is not associated with controls, considering what a drastic dietary change EN entails.

The microbiome adapts to inflammatory conditions and dietary changes. Trying to use the microbiome as a marker for disease or health, is fraught with problems. If we relied on that type of research, EN should not be used to treat patients. Thankfully we use inflammatory markers to judge disease in crohn's disease, and not a microbiome signature.

 

[asadmom]

My son finally finished the crate of Neocate and started on Modulen today. He loves Modulen compared with the Neocate drinks. Since he just needs to grow and gain weight, do you think Neocate is better for absorption compared with Modulen?

 

[kiny]

I don't think so. Modulen is effective in improving nutritional status too, almost all of it is absorbed proximally.

What has to be absorbed in the ileum is B12.

But glucose, amino acids, lipids, iron, etc, these can all be absorbed higher up in the jejunum and duodenum, on the condition they come in bioavailable forms like they are found in EN.

 

[asadmom]

I don't think so. Modulen is effective in improving nutritional status too, almost all of it is absorbed proximally.

What has to be absorbed in the ileum is B12.

But glucose, amino acids, lipids, iron, etc, these can all be absorbed higher up in the jejunum and duodenum, on the condition they come in bioavailable forms like they are found in EN.

OK, so you don't think that the protein needs to be broken down completely for the EN to have an advantage, right?

What do you mean by "What has to be absorbed in the ileum is B12"?

 

[kiny]

OK, so you don't think that the protein needs to be broken down completely for the EN to have an advantage, right?

No, the casein protein in Modulen is fine, it's also lactose free.

Ideally Modulen would be based on whey protein, but it would be more expensive and I don't know if it would allow them to add the growth factors. It would also affect the taste.

What do you mean by "What has to be absorbed in the ileum is B12"?

Meaning B12 needs to be absorbed in the ileum, you can't formulate it in any way that would cause uptake in the jejunum or duodenum.

This is in contrast to all other nutrients that can be taken up by other parts of the small intestine. B12 is the exception.

 

[kiny]

Regarding protein. Most of the protein is going to be taken up before it reaches the distal end of the small intestine (ileum), regardless of the source of protein. If you consume 20 grams of protein, maybe 1 or 2 grams would escape digestion and ends up in the colon.

If given the choice, of course you would pick whey isolate to bring down the content that escapes absorption even further and to increase proximal absorption as high up in the intestine as possible. But the casein in Modulen is just fine too.

What escapes digestion is fiber, which has no nutritional value. EN is very low in fiber and dietary particles that could unwillingly cross the epithelial barrier and cause an immune response.

It's really a non-issues for protein, we are (thankfully) able to absorb almost all protein before it reaches the most distal part of the ileum.

The mechanic behind EN is really:
-decrease the fecal stream
-correct any nutritonal deficiencies through bioavailable formulation of nutrients
-deprive bacteria of nutrients which brings down bacterial load

This results in bringing down inflammation. Research can argue all day how exactly EN does this, it's important that we know it is highly effective.

 

[Andersen007]

I was very determined to make EN work, I had a mild case of terminal ileitis recently diagnosed as Crohn's, however immediately as I switched to Modulen 100%, really liked the taste, but I started experiencing bad stomach cramps along with diarrhea 4-5x a day. After a week of soldiering through it, my calprotectin was up 3x my starting value. Since then I have switched to whole foods based exclusion diet using SCD (but even more restricted than that), increased fiber intake, take VSL3 probiotics, and for the first time in years I am experiencing solid stools once a day, no longer having any cramps or pain, and dont have to run to the bathroom. At some point I will try Elemental 028, although my IgE test for milk protein was negative, I still have to exclude all dairy as they cause me symptoms (e.g. a few pieces of aged cheese with no lactose 2 weeks ago) . And when I am in the US I will try the Kate Farms formulation, but very unfortunately they are not shipping to Europe and I am not able to get them here to Spain in any way. It also could be something else in these formulas, as Ensure's non-milk based Almond flavour also didnt sit very good with me (but I didnt stick long with that to be fair, and it did feel better than Modulen). Perhaps its the corn syrup.

I guess what I am trying to say is, compliance is not the only thing in the way of EEN adoption, and in my case made symptoms and inflammation significantly worse than before - and then probiotics, whole food based diet, excluding complex carbohydrates, and indirectly more fiber, is what has helped. Diet has a role to play, but I am still not convinced we understand exactly how. And perhaps the case of Crohn's is actually a combination of different diseases. I wish we would understand more, as I would be very willing to experiment with some home-made shakes, but currently as my symptoms are better than ever I am a bit reluctant to do so.

 

[kiny]

The effect of TGF-β2 growth factor in some EN like Modulen is relevant if it is part of the mechanic of action of Modulen EN, because it indicates total intake matters.

I am only aware of 1 study from Japan that compared different levels of intake of EN containing TGF-β2. Subjects that consumed slightly more had slightly higher reductions in CRP and calprotectin, but it wasn't a large difference.

Effect of Oral Nutrition Supplements and TGF-β2 on Nutrition and Inflammatory Patterns in Patients With Active Crohn's Disease.[/QUOTE]

Department of Pathology, Universidade Federal de Minas Gerais, Medical School, Belo Horizonte, Brazil

Background: Crohn's disease (CD) is often associated with nutrition disorders. Many nutrition therapeutic alternatives have been studied. Nevertheless, the actual role of nutrition therapy is still controversial. The objective of this study was to assess the effects of nutrition supplementation with and without transforming growth factor-beta 2 (TGF-β2) on inflammatory, endoscopic, histopathologic, and nutrition parameters in active CD.

Materials and methods: Thirty-eight patients were allocated into 3 groups: group 1 (patients who received only nutrition orientation), group 2 (nutrition orientation and a normoproteic, normocaloric nutrition supplement), and group 3 (nutrition orientation and the nutritional supplement with TGF-β2). Clinical and nutrition evaluation, C-reactive protein (CRP) levels, and assessment of endoscopic and histologic parameters in the intestinal mucosa were performed before and after nutrition intervention.

Results: The mean follow-up period was 3 months. In the beginning of the study, groups were homogeneous regarding age, gender, CD behavior and localization, and medication in use. In the end of the study, the Clinical Disease Activity Index score was reduced in groups 2 and 3; in group 3, a reduction in CRP levels and an improvement in histologic findings were observed. Among patients who received nutritional supplement, some anthropometric patterns were improved.

Conclusion: The results of the study indicate that nutritional supplementation improved nutrition and inflammatory patterns in patients with active CD. However, only patients receiving TGF-β2-enriched formula showed improvement in histologic parameters and significant reduction in CRP levels.