Protein Metabolism And Organ Injury

[Amazoniac]

Gaylords,
Members that can only name 2 or less Katy Perry songs;

Protein Deficiency and Liver Injury

• Protein deficiency affects humans differently than in lab experiments because there are many variables that must be taken in consideration. An example would be meal timing and protein intakes, that alone can modify how the protein that you eat is utilized.
• Fatty liver doesn’t develop as long as overall calorie intake is kept low along with protein, as in marasmus; and unlike in Kwashiorkor, that there are enough calories, but not enough protein.
• Chronic alcohol intake/abuse (usually a lot of calories without enough protein) can potentiate liver problems because it also affects indirectly by interfering with other micronutrients involved in protein metabolism and liver protection.
• Choline and betaine were the first compounds discovered to protect the liver from fat accumulation. The discovery of methionine and its protective effects came later. They also mentioned orotic acid, that seems present when there’s liver injury.
• Starvation [low everything] depletes fat accumulation in the liver. In lab experiments it requires less measures to counteract the fat deposition on the liver compared to normal caloric intake and protein deficiency. But fat accumulation still occurs even when the carbohydrate or fat intakes are somewhat low and protein intake is not matching. #westsfastinganddiabeteshealingcentre
• Not only methionine, but lysine, glycine, tryptophan and threonine demonstrated to reduce the accumulation of fat in livers of rats on a diet low in proteins.
• Accumulation was observed to be much worse in choline-deficient diets than on insufficient protein alone.
• There was an experiment comparing low-protein on either high-carb or low-carb and a normally partitioned diet. As expected, the rats on a decent protein intake had normal livers; whereas the others, both of them demonstrated accumulation of fat (3-4 fold increase in triglycerides, values were higher in the high-carb group). On both extreme groups they noted that the “mitochondria were greatly enlarged and adopted bizarre shapes”, their number per cell in the liver of those animals also reduced; something that they commented that is common in protein deficiency. And it doesn’t stop there, other parts of the cells are also affected.
• “Increased synthesis of hepatic triglycerides from carbohydrates, increased output of free fatty acids from the fat depots, which in turn causes excess fat deposition in the liver, and impairment of triglyceride secretory mechanism of the liver have been suggested as pathogenic mechanisms (47, 49, 50).”
• It’s common to find swelling of the animals’ cell when on a low-protein high-carb diet. “Intracellular overhydration is also favored by the potassium loss and its replacement by sodium and hydrogen ions, plus a suggested increase in free amino acids (8).”
• Also common to have excess glycogen accumulation under those circumstances.
• The activity of an enzyme involved in glycogen metabolism was noted to be diminished in protein-deficient dogs.
• Protein-deficiency seems to affect more the liver enzymes than other organs. Within the liver, when protein is scarce, the resources are prioritized accordingly to the importance of the enzyme and its activity.
• Rats fed a protein-free diet for 8 weeks lost their mitochondrial cytochromes b, c1 and c by about 50%. They commented that that means for sure an impairment of respiration and oxidative phosphorylation. However, that doesn’t happen when there’s at least some protein present and carbohydrates available. They suggested a compensatory mechanism: when protein is insufficient, the number of mitochondrias diminishes however they swell and compensate in activity, occupying virtually the same volume.
• Choline prevented fibrosis and cirrhosis during 1 year in rats fed a low-protein diet.

On the first paragraph, they mentioned that a protein deficiency can occur even when there’s enough protein ingested.
What’s interesting is that Ray mentions in most of his articles that address autoimmunity that there’s at least some sort of protein derangement:

Multiple sclerosis, protein, fats, and progesterone

“People with MS have chronically increased production of cortisol. This creates a distortion of protein assimilation, resembling a nutritional protein deficiency. Excessive serotonin and estrogen cause a relatively uncontrolled production of cortisol. A vicious circle of inflammatory mediators and amino acid imbalance can result.”

“High quality protein, thyroid, pregnenolone and progesterone tend to correct the underlying pathology. These are antiinflammatory, but they are not immunosuppressive or catabolic.”

“A simple protein deficiency has many surprising effects. It lowers body temperature, and suppresses the thyroid, but it increases inflammation and the tendency of blood to clot. Since the brain and heart and lungs require a continuous supply of essential amino acids if they are to continue functioning, in the absence of dietary protein, cortisol must be produced continuously to mobilize amino acids from the expendable tissues, which are mainly the skeletal muscles. These muscles have a high concentration of tryptophan and cysteine, which suppress the thyroid. Cysteine is excitoxic, and tryptophan is the precursor for serotonin. Presumably, their presence in, and stress-induced release from, the muscles is one of the mechanisms that reduce metabolic activity during certain types of stress.”

“Unsaturated fats inhibit the enzymes that digest protein, and MS patients have been reported to have poor digestion of meat (Gupta, et al., 1977).”


--
Related to the issue:
Atrophied thymus-generated Th17 cells have tissue-specific involvement in autoimmunity.

--
Vitamin A And (Auto)immunity

--
On collagen being susceptible in autoimmunity.

When researchers decellularize organs, what’s left is the extracellular matrix that still has the shape of the organ and can provide sufficient information for a stem cell to regenerate it.
http://guardianlv.com/wp-content/uploads/2014/04/Ghost-Heart-Miracle-in-Medicine.jpg
Organ decellularization, ghost <organ>, etc.

I wonder if all this is connected.

 

[Mjhl85]

Gaylords,
Members that can only name 2 or less Katy Perry songs;...

huh?

 

[Mjhl85]

Gaylords,
Members that can only name 2 or less Katy Perry songs;

Protein Deficiency and Liver Injury

• Protein deficiency affects humans differently than in lab experiments because there are many variables that must be taken in consideration. An example would be meal timing and protein intakes, that alone can modify how the protein that you eat is utilized.
• Fatty liver doesn’t develop as long as overall calorie intake is kept low along with protein, as in marasmus; and unlike in Kwashiorkor, that there are enough calories, but not enough protein.
• Chronic alcohol intake/abuse (usually a lot of calories without enough protein) can potentiate liver problems because it also affects indirectly by interfering with other micronutrients involved in protein metabolism and liver protection.
• Choline and betaine were the first compounds discovered to protect the liver from fat accumulation. The discovery of methionine and its protective effects came later. They also mentioned orotic acid, that seems present when there’s liver injury.
• Starvation [low everything] depletes fat accumulation in the liver. In lab experiments it requires less measures to counteract the fat deposition on the liver compared to normal caloric intake and protein deficiency. But fat accumulation still occurs even when the carbohydrate or fat intakes are somewhat low and protein intake is not matching. #westsfastinganddiabeteshealingcentre
• Not only methionine, but lysine, glycine, tryptophan and threonine demonstrated to reduce the accumulation of fat in livers of rats on a diet low in proteins.
• Accumulation was observed to be much worse in choline-deficient diets than on insufficient protein alone.
• There was an experiment comparing low-protein on either high-carb or low-carb and a normally partitioned diet. As expected, the rats on a decent protein intake had normal livers; whereas the others, both of them demonstrated accumulation of fat (3-4 fold increase in triglycerides, values were higher in the high-carb group). On both extreme groups they noted that the “mitochondria were greatly enlarged and adopted bizarre shapes”, their number per cell in the liver of those animals also reduced; something that they commented that is common in protein deficiency. And it doesn’t stop there, other parts of the cells are also affected.
• “Increased synthesis of hepatic triglycerides from carbohydrates, increased output of free fatty acids from the fat depots, which in turn causes excess fat deposition in the liver, and impairment of triglyceride secretory mechanism of the liver have been suggested as pathogenic mechanisms (47, 49, 50).”
• It’s common to find swelling of the animals’ cell when on a low-protein high-carb diet. “Intracellular overhydration is also favored by the potassium loss and its replacement by sodium and hydrogen ions, plus a suggested increase in free amino acids (8).”
• Also common to have excess glycogen accumulation under those circumstances.
• The activity of an enzyme involved in glycogen metabolism was noted to be diminished in protein-deficient dogs.
• Protein-deficiency seems to affect more the liver enzymes than other organs. Within the liver, when protein is scarce, the resources are prioritized accordingly to the importance of the enzyme and its activity.
• Rats fed a protein-free diet for 8 weeks lost their mitochondrial cytochromes b, c1 and c by about 50%. They commented that that means for sure an impairment of respiration and oxidative phosphorylation. However, that doesn’t happen when there’s at least some protein present and carbohydrates available. They suggested a compensatory mechanism: when protein is insufficient, the number of mitochondrias diminishes however they swell and compensate in activity, occupying virtually the same volume.
• Choline prevented fibrosis and cirrhosis during 1 year in rats fed a low-protein diet.

On the first paragraph, they mentioned that a protein deficiency can occur even when there’s enough protein ingested.
What’s interesting is that Ray mentions in most of his articles that address autoimmunity that there’s at least some sort of protein derangement:

Multiple sclerosis, protein, fats, and progesterone

“People with MS have chronically increased production of cortisol. This creates a distortion of protein assimilation, resembling a nutritional protein deficiency. Excessive serotonin and estrogen cause a relatively uncontrolled production of cortisol. A vicious circle of inflammatory mediators and amino acid imbalance can result.”

“High quality protein, thyroid, pregnenolone and progesterone tend to correct the underlying pathology. These are antiinflammatory, but they are not immunosuppressive or catabolic.”

“A simple protein deficiency has many surprising effects. It lowers body temperature, and suppresses the thyroid, but it increases inflammation and the tendency of blood to clot. Since the brain and heart and lungs require a continuous supply of essential amino acids if they are to continue functioning, in the absence of dietary protein, cortisol must be produced continuously to mobilize amino acids from the expendable tissues, which are mainly the skeletal muscles. These muscles have a high concentration of tryptophan and cysteine, which suppress the thyroid. Cysteine is excitoxic, and tryptophan is the precursor for serotonin. Presumably, their presence in, and stress-induced release from, the muscles is one of the mechanisms that reduce metabolic activity during certain types of stress.”

“Unsaturated fats inhibit the enzymes that digest protein, and MS patients have been reported to have poor digestion of meat (Gupta, et al., 1977).”


--
Related to the issue:
Atrophied thymus-generated Th17 cells have tissue-specific involvement in autoimmunity.

--
Vitamin A And (Auto)immunity

--
On collagen being susceptible in autoimmunity.

When researchers decellularize organs, what’s left is the extracellular matrix that still has the shape of the organ and can provide sufficient information for a stem cell to regenerate it.
http://guardianlv.com/wp-content/uploads/2014/04/Ghost-Heart-Miracle-in-Medicine.jpg
Organ decellularization, ghost <organ>, etc.

I wonder if all this is connected.

I think the elephant in the room is the unsaturated Fats quote. To me at least, swank's treatment of MS involved high amounts of unsaturated fats.
And I know myself and others are confused by that.

 

[Amazoniac]

huh?

Yeah, it’s a disclaimer: I’m not an expert, I’m merely sharing. If you prefer, just read it directly from the source.

I think the elephant in the room is the unsaturated Fats quote. To me at least, swank's treatment of MS involved high amounts of unsaturated fats.
And I know myself and others are confused by that.

People With The Lowest Overall Mortality Are Overweight

 

[Mjhl85]

Yeah, it’s a disclaimer: I’m not an expert, I’m merely sharing. If you prefer, just read it directly from the source.


People With The Lowest Overall Mortality Are Overweight

What is it about that post that you wanted to emphasis exactly Amazoniac?

 

[CarbAppreciator]

Wow, awesome post!
So maybe too many carbs can work against you over time.

 

[Amazoniac]

What is it about that post that you wanted to emphasis exactly Amazoniac?

The part that he mentioned Denise Minger and Roy Swank.
This one is also relevant (and excellent): Fructose Alters Brain Genes Negatively. How To Counter This From Peat Perspective?

Wow, awesome post!
So maybe too many carbs can work against you over time.

The main concern here is going too low protein and chronically..

 

[Mjhl85]

The part that he mentioned Denise Minger and Roy Swank.
This one is also relevant (and excellent): Fructose Alters Brain Genes Negatively. How To Counter This From Peat Perspective?

The main concern here is going too low protein and chronically..

Ah yes, ok that's what I figured. Yea I did see that before but I'm still confused that PUFA can still maintain insulin signaling
as well as it helping MS. I thought pufa was the main bad guy in blood sugar diseases and also how is it that it helped a
disease like MS.

 

[NathanK]

Excellent post on the importance of adequate protein.

 

[tca300]

@Amazoniac Good post! Thanks!

 

[superhuman]

They dont talk about any amount, frequency etc etc ?

 

[Amazoniac]

They dont talk about any amount, frequency etc etc ?

Using nitrogen balance is a rough way to estimate how much on average people ingest and excrete (usually about 55g seems the amount that keeps most people at neutral balance). However, it's one of those cases that Ray mentions in which there's not much value to aim for deficiency prevention rather than the amount for thriving. And also, depending on your state, ingesting the average won't be enough keep a neutral balance; as the authors commented: the type of protein, physical activity, age, pregnancy, micronutrient deficiencies, infections, malabsorption, and so on; all affect that value.
Since he also mentioned that 1/3 can be gelatin, that would give you something close to what he considers a decent protein intake of 80g per day..

 

[Parsifal]

What about people having weak kidneys (high creatinine).

 

[Amazoniac]

Protein - Adelle Davis

 

[Makrosky]

@Amazoniac,

What do you think about Adelle's statements like these :
"Gelatin, for example, lacks two essential amino acids and is almost entirely lacking in three others; hence its protein value approaches nil."

And then... She places these on top of the list :
soybean flour, low fat 1 cup com. 60
cottonseed flour 1 cup com. 60

 

[Amazoniac]

@Amazoniac,

What do you think about Adelle's statements like these :
"Gelatin, for example, lacks two essential amino acids and is almost entirely lacking in three others; hence its protein value approaches nil."

And then... She places these on top of the list :
soybean flour, low fat 1 cup com. 60
cottonseed flour 1 cup com. 60

I think the same as you do.
Perhaps she's looking at the amino acid content and disregarding the context, but again, that doesn't make the entire text invalid..

 

[Makrosky]

I think the same as you do.
Perhaps she's looking at the amino acid content and disregarding the context, but again, that doesn't make the entire text invalid..

No, I liked the text in fact... It reminded me to up protein intake. I think I'm gonna try the brewers yeast...

 

[Amazoniac]

http://www.sciencedirect.com/science/article/pii/S2341454515001015

“Deficiency of water-soluble vitamins, especially group B vitamins, is common in cirrhosis, particularly in alcoholic disease.32 and 33 Deficiency of fat-soluble vitamins has been reported in alcoholic disease, in the presence of steatorrhea associated with cholestasis and in the bile salt deficiency.34 and 35”

“Thiamine deficiency is quite common, and is not exclusive of alcoholic disease. Decreased intake, absorption and hepatic reserves may contribute to it. Alcohol intake also reduces intestinal absorption of thiamine and prevents metabolization in its active substrate. Thiamine deficiency may lead to Wernicke encephalopathy and Korsakoff dementia.36

Vitamin B12 deficiency is mainly related to the decrease of its liver reserves. Serum levels may be increased, but tissue levels are decreased.26 This deficiency is associated with anemia, glossitis and neurological symptoms. Folic acid deficiency develops faster in cirrhotic patients due to decreased hepatic storage levels.29

Retinol deficiency is related with decreased absorption and impaired hepatic mobilization.37 It can cause dermatitis, night blindness or photophobia and increased risk of neoplastic disorders, including hepatocellular carcinoma. A retrospective study reported that the majority of liver disease patients being considered for liver transplantation present with vitamin A and D deficiencies.38 Because high doses of vitamin A are potentially hepatotoxic, care must be taken to avoid excessive supplementation.11

Vitamin K deficiency is caused by decreased liver storage levels and is associated with increased risk of bleeding.4

Vitamin D deficiency results from ingest reduction, decreased absorption (due to cholestatic disease or portal hypertension enteropathy) and reduction of exposure to UV light. Since vitamin D is hydroxylated in the liver to produce calcidiol, patients with severe parenchymal or obstructive hepatic disease may have reduced production of this metabolite.39 and 40 The majority of the liver must be dysfunctional before calcidiol synthesis is reduced. Thus, these patients rarely manifest biochemical or histological evidence of osteomalacia, unless concomitant nutritional deficiency or interruption of the enterohepatic circulation occurs.39 and 40 Extremely low serum levels of vitamin D are associated with increased mortality in patients with chronic liver disease.41

Zinc and selenium deficiency have been described in patients with alcoholic and non-alcoholic liver disease.42, 43 and 44 Zinc deficiency is caused by intake reduction (to which contributes a diet with restriction of animal origin protein), impaired intestinal absorption and treatment with diuretics.45, 46 and 47 This deficiency may increase ammonia levels in circulation, increasing the risk of HE [hepatic encephalopathy] and may also induce anorexia, dysfunction of the immune system and dysgeusia, which further decreases its intake.48, 49, 50, 51 and 52

Alcohol consumption may also cause folate and magnesium deficiency.53 It has been demonstrated that alcohol impairs magnesium transport and homeostasis in brain, skeletal muscle, heart and liver.11”

“Food should be well cooked, given the patient's increased susceptibility to infections, and should be distributed in 5–7 small daily meals in order to prevent protein overload and nausea/vomiting.4 and 26 Meal schedule may be more important than the amount of food ingested, because during the postprandial period there is a suppression of protein degradation in favor of synthesis stimulation. Increasing postprandial period can improve the patient's condition.73, 74, 75 and 76

A late evening snack has a positive effect on the nitrogen balance, increases muscle mass by reversing sarcopenia, can improve quality of life, reduce the severity and frequency of HE and increase survival.4, 73, 76 and 77 Thus, it is recommended to minimize overnight fasting period, in order to avoid fasting periods longer than 6 h and reduce the catabolism rate.4 and 68 Although data on this topic is scarce, patient's compliance may be difficult because this late meal can worsen reflux complains, impair sleep quality and cause glucose intolerance.78

A late snack of at least 710 kcal or 110 g of carbohydrates increases lean mass, which was not demonstrated with a meal or 200 kcal or 40 g of carbohydrates.4 and 73 Although there is no consensus on the meal composition, foods with high caloric content (at least 50 g of carbohydrates) and enriched with BCAA (leucine, isoleucine and valine) are preferred.4 If administered during the night, BCAA are preferably used in protein synthesis, while during daytime they are preferably used as energy.74 The normalization of serum BCAA levels promotes protein synthesis, reduces the concentration of nitrogenous products and prevents the formation of false neurotransmitters which may have a role in the development of HE.26

The use of BCAA-enriched formulae can improve the prognosis of patients with advanced cirrhosis.68 These supplements may reduce the progression of liver failure, improve quality of life, reduce the severity and frequency of HE and increase survival.4, 68, 79, 80, 81 and 82 However, some studies have failed to demonstrate these benefits and further data are lacking to clarify their long-term effects. In this context, ESPEN does not recommend its regular use, given the higher cost and oral intolerance, recommending, in general, a diet rich in whole protein formulae.68 The oral/digestive intolerance has been bypassed by the new formulations with new supplement flavors, but the high cost still prevents a broader use.4 and 83

In patients with compensated cirrhosis without malnutrition, the ingestion of 1.2–1.5 g/kg(weight) daily protein is recommended.63 In malnourished patients, 1.0–1.8 g/kg(weight) is recommended, depending on the severity of malnutrition and liver disease.11 Protein needs are higher in malnourished patients and in stress situations (such as bleeding, infection or surgery), provided that there is no renal dysfunction (in which may be necessary a protein restriction).

In patients with ascites, more concentrated high-energy formulae should be preferred.68 Sodium restriction may be required in patients with ascites/edema. In patients unresponsive to diuretic therapy, the amount of sodium should be restricted to 2 g/day.44 Fluid restriction should only be recommended in severe hyponatremia (Na+ <120 mEq/mL) and is not indicated in compensated liver disease.4

Carbohydrates are the base of the diet of cirrhotic patients and should cover 50–60% of non-proteic daily needs.44 and 67 An infusion of glucose (2–3 g/kg(weight)/day) should be initiated when patients have to abstain from food for more than 12 h.67 Diet should tend to be hypercaloric and foods rich in complex carbohydrates should be preferred.26 and 84 Lipids should cover the remaining non-proteic daily needs.67 Adjustments should be performed in the presence of steatorrhea.11

An energy content of 35–40 kcal/kg(weight)/day is usually sufficient to restore/maintain nutritional status and enhance liver regeneration.11 and 68 Whenever possible, they should be provided an energy content to cover 1.3 × REE.67 However, caloric excess must be avoided due to harmful effects of lipogenesis, which can cause liver dysfunction.6”

“Whichever approach is chosen, there are some considerations to be kept in mind. Thiamine supplementation may be considered in all patients, especially in those who have alcoholic disease.22 In cholestatic disease, fat-soluble vitamins supplementation should be considered.22 Vitamin K supplementation should be considered only in situations of high hemorrhagic risk.85 The supplementation of zinc and magnesium can indirectly enhance food intake and nutritional status improving dysgeusia.86 and 87 Some authors propose supplementation with calcium (1–1.2 g/day) and vitamin D (400–800 UI/day), especially in cholestatic disease and in patients with osteopenia.67 and 85”

“In patients with steatorrhea, the diet content of long chain fatty acids must be reduced at the expense of medium and short chain fatty acids.20 and 26 Some patients, such as those with alcoholic disease, may require supplemental pancreatic enzymes due to the presence of pancreatic insufficiency.20”

“In cirrhotic patients with HE, contrary to what has been advocated in the past, protein restriction is not recommended, since most patients present with an advanced protein-calorie deficit.12 and 44 A maintained negative nitrogen balance through protein restriction leads to an increase in PCM [protein-calorie malnutrition] and cachexia.6, 92 and 93”

“Protein restriction can aggravate malnutrition leading to an increased muscle breakdown, and release of amino acids with a consequent increase of ammonia levels, worsening the prognosis of HE.10 and 94 Even transient protein restriction does not have any proven benefit during an episode of HE.68 In cases of severe protein intolerance in HE unresponsive to optimized therapy (control of precipitating factors, lactulose, rifaximin),20 and 44 a transitional restriction (0.8 g/kg/d) can be attempted for the shortest time possible (less than 48 h); and normal protein intake should be resumed as soon as possible.6 Other possible exceptions are the patients with gastrointestinal bleeding, in whom a protein restriction, for very short periods, may be necessary while they are being stabilized.69 An alternative approach for initial intolerance would be a gradually increase of the protein dosage.4 and 6 Paradoxically, the protein excess can induce HE, for so, the treatment must always be individualized.”

“Studies showed that dairy protein is better tolerated than protein from mixed sources and that vegetable protein is better tolerated than meat protein.69 The proteins of vegetable and dairy origin may improve the nitrogen balance and, if well tolerated by the patients, they may be provided without constraints.44, 95 and 96 The vegetable proteins are better tolerated than those of animal origin, and they may influence intestinal transit, have a higher content of fiber and BCAA and a lower content of AAA.95 and 96”
*I read on another review that giving isolated amino acids yielded a poorer outcome compared to casein.

“Some studies have shown that patients with grade III/IV HE benefit from a diet rich in BCAAs and low in AAA.67 and 97 The use of oral BCAA supplements, in daily divided doses, may facilitate the provision of an adequate nitrogen intake in the occasional patient who is truly protein intolerant.98 The greatest consensus for use of BCAA-enriched supplements is in patients with HE unresponsive to standard treatment and in the presence of protein intolerance.68 These supplements improve HE, particularly if administered in chronic cases.99 There is evidence that BCAA-enriched supplements may improve clinical outcome when prescribed to patients with an established nutritional deficit68, 80 and 100 and there are no studies suggesting that their use is harmful to HE.26”

“The zinc and selenium deficiency is very common in the advanced stages of cirrhosis. Its supplementation was associated with an improvement of the metabolism of amino acids and HE.48, 101 and 102 Although ASPEN recommends its empirical supplementation, studies on the HE improvement with zinc supplements are controversial and there is no consensus on the optimal dosage.20, 26, 44, 48, 49, 103 and 104”


--
http://www.sciencedirect.com/science/article/pii/S1089326113000652

“The use of branch-chain amino acids (BCAA) as directed therapy to improve outcomes in advanced cirrhosis warrants special discussion. Deficiency of the BCAAs (valine, leucine, isoleucine) relative to ammonia and aromatic amino acids (AAAs) has been well established in the setting of cirrhosis and there have been several studies suggesting positive effects on HE, protein levels, and overall liver function.39–41 Theoretically this makes sense because BCAAs are essential for protein synthesis and turnover and may provide an alternate pathway of ammonia detoxification. AAAs are normally metabolized and detoxified by the liver; however, in chronic liver disease, AAAs accumulate as a result of dysfunctional hepatocytes with impaired capacity for deamination42 as well as portal shunting and BCAA levels decrease because they are taken up by skeletal muscle cells as substrate for energy or ammonia degradation.43 In theory, replacement of BCAAs stimulates the synthesis of glutamine from glutamate and ammonia in skeletal muscle.44,45 A relative deficiency of BCAAs is also believed to lead to increased tryptophan uptake in the brain, which may also contribute to HE. BCAA supplementation would theoretically limit tryptophan uptake because the BCAAs compete for the same blood-brain barrier transporters.46

The ESPEN 2006 consensus guidelines support the use of BCAA supplements to improve clinical outcomes, largely based on the results of 3 studies investigating BCAAs in HE. Marchesini and colleagues47 conducted a 1-year double-blinded RCT of 174 patients with advanced cirrhosis provided with BCAA (14 g/d) supplementation or 2 control groups with equicaloric amounts of lactoalbumin or maltodextrin. The primary end point was a combination of death and liver decompensation, defined by worsening HE, refractory ascites, or a Child-Pugh score of 12 or more. The BCAA arm had significantly lower rates of reaching this composite primary end point compared with the control group on lactoalbumin. Significant limitations of this study included a high dropout rate in the treatment arm because of inability to tolerate the taste of the BCAA formulation bringing into question whether or not this trial could truly be blinded. In terms of the overall conclusions from this study, it would suggest a modest albeit not striking benefit to BCAAs.”

“Bacterial overgrowth is common in patients with cirrhosis and can result in increased bacterial translocation leading to infection and fat malabsorption. In 1 study, 33% of 24 patients with portal hypertension versus none in a control group of 33 patients demonstrated small bowel bacterial overgrowth.49 This may be secondary to slower transit times in patients with more advanced liver disease. A recent study demonstrated 6.17-hour transit time versus 3.56 hours in patients with decompensated versus compensated cirrhosis.50”

Extremely improbable life form that might be interested: @haidut

 

[PeatThemAll]

I had been waiting for a while for a meta-styled thread like this one.

 

[Amazoniac]

"Serum levels increased, tissue levels decreased"

I had been waiting for a while for a meta-styled thread like this one.

What happened to the fist?