Increased Mucin Production With Supplementation Of Certain Amino Acids May Help Digestive Isssues

DrJ

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As someone who struggles with digestive problems, I have come across the production of mucin in the intestine to be important in protecting it. Through reading, I've found that a healthy intestine has 1-2 layers of mucus protecting the lining of the intestine (depending on where in the intestine), and those layers are often degraded or missing in intestinal maladies such as IBD or colitis. It seems that an adequate mucus layer can protect against and heal problems in the intestine. Until now, I've found that the amino acid, threonine, is an important component of mucin, but this study I found to be very informative on how one might go about restoring the mucus layer of the intestine by supplementing certain amino acids that help increase mucin production in the intestine:

Specific Amino Acids Increase Mucin Synthesis and Microbiota in Dextran Sulfate Sodium–Treated Rats | The Journal of Nutrition | Oxford Academic

Some key quotes:

During the anabolic response associated with inflammation, mucin synthesis and colonic protection may be compromised by the limited availability of specific amino acids.

The higher dose of amino acids increased the number of Muc2-containing goblet cells in the surface epithelium of the ulcerated area, stimulated mucin production in the colon, and restored the mucin amino acid composition and mucosal content to healthy, control values. The colonic mucin synthesis rate was specifically stimulated by 95%, whereas the protein turnover was unchanged. All bacterial populations, markedly altered by the DSS treatment, were promoted. In conclusion, in inflammatory situations, an increase in threonine, serine, proline, and cysteine dietary supply can promote mucin synthesis, reequilibrate the gut microbiota, and thus favor colonic protection and mucosal healing.

Basically, in the study they induced colitis in rats and then gave them the amino acids threonine, serine, proline, and cysteine in a 'small' dose dubbed DSSM1 and a 'large' dose dubbed DSSM2. The large dose DSSM2 group was able to completely recover from the colitis/ulcers induced which I think is pretty remarkable. The no-supplementation and DSSM1 rats ('small' supplementation) did not recover.

The dosage for the DSSM2 (recovered) group was:
  • Threonine: 15g/kg
  • Serine: 7.2g/kg
  • Proline: 15g/kg
  • Cysteine: 10g/kg
Which is a pretty huge amount! (And almost makes me wonder if they typo'd somwhere). In a 75kg (165lb) human, this would be:
  • Threonine: 1125g
  • Serine: 540g
  • Proline: 1125g
  • Cysteine: 750g
That would be like supplementing POUNDS of amino acids in a human (if they didn't mean mg/kg somehow), but it did basically cure ulcerative colitis in the rats.

I note that in the study, the fats of the diet fed to the rats were highly unsaturated consisting of groundnut oil, sunflower oil, and rapeseed oil. So one might say this worked in spite of that situation.

For those contemplating between supplementing glycine or gelatin, this would argue for trying gelatin to get the proline.

I wish they would do the same study with only threonine and proline since some of my other reading suggests those are probably the key to this. Cysteine is probably already over-represented in the modern diet due to lots of muscle meat consumption.

This paper is pretty informative to read, even if that level of supplementation (if correct units) is extreme. One thing they noted is that the rats that had colitis induced (vs. control with no colitis induced) had significantly reduced amounts of the amino acids studied in their mucins (DSS means colitis was induced):

In all segments of the intestine, the mucins synthesized in rats of the DSS group had significantly reduced proline, serine, and threonine content compared with the control rats

So it's a clue that an outcome of intestinal damage is lack of adequate certain amino acids to remedy the problem. Also a clue that if you have poor digestion/assimilation of protein (as in hypothyroidism) it might be a factor leading to intestinal problems through lack of an adequate mucus layer provided by the mucins.

But, as mentioned, the high-dosage DSSM2 group basically recovered:

The colonic damage in the DSSM1 group (Figure 2, C, G) was similar to that of the DSS group. In contrast, ulcerated areas in the colons of DSSM2 rats were generally completely recovered by a monolayer of cells containing MUC2-expressing goblet cells

If you read in the paper, both small (DSSM1) and large (DSSM2) supplement groups were able to recover a normal microbiota.

Highly recommended to read if you have intestinal issues. I've obtained some powdered threonine and might experiment with it to see if it qualitatively helps, but not in the doses implied by the study.
 
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I think you have to divide by 6 to get the human dosage (60kg) based on the relative surface area of rat to human. :)
Then you get this:
  • Threonine: 2.4g/kg
  • Serine: 1.7g/kg
  • Proline: 2.4g/kg
  • Cysteine: 1.6g/kg
 
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DrJ

DrJ

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@General Orange Thanks for that! I did not know. If anyone else would find it handy, then based on that conversion, the human doses for a 75kg human (165 lb) would be:
  • Threonine: 180g
  • Serine: 127.5g
  • Proline: 180g
  • Cysteine: 120g
Still quite a bit! But it is probably extreme therapy to heal ulcerative colitis.
 

800mRepeats

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I'm not certain, but, judging by this quote, I reckon they were talking about g/kg of diet (not rat weight) ...

Two groups, healthy rats (control group) and dextran sulfate sodium (DSS)-treated rats (DSS group), were fed the control diet, a dry semisynthetic powder consisting of (g/kg): carbohydrates 646 (wheat starch), proteins 120 (supplied by herring meal balanced to meet all amino acid requirements), lipids 64 (groundnut oil 45, sunflower oil 10, rapeseed oil 9), agar-agar 30, mineral mix 70 (UAR 205b: CaHPO4, 30.1; KCl, 7; NaCl, 7; MgO, 0.735; MgSO4, 3.5; Fe2O3, 0.21; FeSO4·7H2O, 0.35) and vitamin mix 10 [UAR 200, (24)]. The threonine, cysteine, proline, and serine concentrations of the control diet were 5.7, 1.2, 5, and 5 g/kg (dry matter), respectively. Two additional DSS-treated groups were fed the control diet supplemented with amino acids highly represented in mucins (20,21) and whose requirement was shown to be increased after an inflammation-induced anabolic response in liver and gut tissues (18,19). The supplementation levels of threonine, cysteine, proline, and serine were 5, 4, 5, and 5 g/kg (DSSM1 group) and 15, 7.2, 15, and 10 g/kg (DSSM2 group), respectively.
 

A.R

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Messages
896
As someone who struggles with digestive problems, I have come across the production of mucin in the intestine to be important in protecting it. Through reading, I've found that a healthy intestine has 1-2 layers of mucus protecting the lining of the intestine (depending on where in the intestine), and those layers are often degraded or missing in intestinal maladies such as IBD or colitis. It seems that an adequate mucus layer can protect against and heal problems in the intestine. Until now, I've found that the amino acid, threonine, is an important component of mucin, but this study I found to be very informative on how one might go about restoring the mucus layer of the intestine by supplementing certain amino acids that help increase mucin production in the intestine:

Specific Amino Acids Increase Mucin Synthesis and Microbiota in Dextran Sulfate Sodium–Treated Rats | The Journal of Nutrition | Oxford Academic

Some key quotes:





Basically, in the study they induced colitis in rats and then gave them the amino acids threonine, serine, proline, and cysteine in a 'small' dose dubbed DSSM1 and a 'large' dose dubbed DSSM2. The large dose DSSM2 group was able to completely recover from the colitis/ulcers induced which I think is pretty remarkable. The no-supplementation and DSSM1 rats ('small' supplementation) did not recover.

The dosage for the DSSM2 (recovered) group was:
  • Threonine: 15g/kg
  • Serine: 7.2g/kg
  • Proline: 15g/kg
  • Cysteine: 10g/kg
Which is a pretty huge amount! (And almost makes me wonder if they typo'd somwhere). In a 75kg (165lb) human, this would be:
  • Threonine: 1125g
  • Serine: 540g
  • Proline: 1125g
  • Cysteine: 750g
That would be like supplementing POUNDS of amino acids in a human (if they didn't mean mg/kg somehow), but it did basically cure ulcerative colitis in the rats.

I note that in the study, the fats of the diet fed to the rats were highly unsaturated consisting of groundnut oil, sunflower oil, and rapeseed oil. So one might say this worked in spite of that situation.

For those contemplating between supplementing glycine or gelatin, this would argue for trying gelatin to get the proline.

I wish they would do the same study with only threonine and proline since some of my other reading suggests those are probably the key to this. Cysteine is probably already over-represented in the modern diet due to lots of muscle meat consumption.

This paper is pretty informative to read, even if that level of supplementation (if correct units) is extreme. One thing they noted is that the rats that had colitis induced (vs. control with no colitis induced) had significantly reduced amounts of the amino acids studied in their mucins (DSS means colitis was induced):



So it's a clue that an outcome of intestinal damage is lack of adequate certain amino acids to remedy the problem. Also a clue that if you have poor digestion/assimilation of protein (as in hypothyroidism) it might be a factor leading to intestinal problems through lack of an adequate mucus layer provided by the mucins.

But, as mentioned, the high-dosage DSSM2 group basically recovered:



If you read in the paper, both small (DSSM1) and large (DSSM2) supplement groups were able to recover a normal microbiota.

Highly recommended to read if you have intestinal issues. I've obtained some powdered threonine and might experiment with it to see if it qualitatively helps, but not in the doses implied by the study.
This is an interesting study. Have you personally found any health benefit from supplementing with amino acids?
 
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DrJ

DrJ

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This is an interesting study. Have you personally found any health benefit from supplementing with amino acids?
I supplement gelatin every day which has the proline. It also has glycine which is nice.
 

A.R

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Messages
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I supplement gelatin every day which has the proline. It also has glycine which is nice.
Gelatine doesn’t contain much threonine, and threonine was an important factor in the study
 
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