Treatment Of Cirrhosis Of The Liver By A Nutritious Diet And Supplements Rich In Vitamin B Complex

[Amazoniac]

@Dan Wich - Consider a dedicated section for natural B-vitamins extracts on your website, with a place of the holders for @Zeus' future product in attempt to pressure him to hurry up. Especially because now it's no longer optional: Sheila requested.

 

[Wagner83]

But there's no information on the doses of each vitamin. I only know of this product which is extracted from quinoa (so, no yeast I suppose) : https://www.nutrixeal.fr/Mobile/qui...-b-naturelles-60-gelules-vegetales-c2x7950018
Garden for life and Enzymedica (interesting enzyme products) carry decent multi vitamins from whole foods I think (unless they use both fruits and synthetic vitamins).

 

[lollipop]

Another excellent find Monsieur,

As an alternative here, I have found that the somewhat expensive Swiss product A. Vogel BioStrath tablets well tolerated and efficacious in the past as a natural b vitamin-with-minerals yeast-based supplement. They grow their yeast for this on herbs and root vegetables then hydrolyse it. Some quite nice scientific data to support its use in those children with 'failure to thrive' which appears missing now from their websites, shame. I found it similarly useful, if dear. There is also a tonic which was designed to be palatable for children. 100% children I knew 'who expressed a preference' pronounced it: vile. Tabs were fine.

Although it is suggested that some react to natural yeast products, another cohort of course think nothing of reacting to even low dose synthetic b-vitamins - orally or topically. An organic liver extract (calves, not lambs! - worm burden eek!) from a trusted source might be the best of both worlds if Mr Haidut is feeling bored with his current range.

Thank you Amazoniac, you never fail to amaze with your finds.

Sheila

Hi @Sheila! I also appreciate this recommendation of BioStrath. Thank you! This is excellent for my family that simply will not look after their health like I do.

 

[Sheila]

Dear Nighteyes, and greetings dear Lisaferraro,

Please find the attached for your delectation, I knew it was hiding somewhere in my electronic deep litter filing system.
Note, you may wish to do some maths to get the per dose equivalences; some might call the amounts thus obtained equivalent to a sparrow's fart* but I found it worked nicely. (It also does not contain iodine, so some might consider my efficacious experiences illusionary. I wave Germanium in their general direction as a peace offering instead.)

I have a new appreciation of your braveness Nighteyes, and 32% v/v alcohol is about what I would expect to keep the solution preserved. I wish I had thought to tell children that 'hey - this has stuff like your parents' vodka in it!' that might have made it instantly more palatable.

Best regards to you both,
Sheila

(*old naval term for not exactly vast amounts)

 

[lollipop]

Dear Nighteyes, and greetings dear Lisaferraro,

Please find the attached for your delectation, I knew it was hiding somewhere in my electronic deep litter filing system.
Note, you may wish to do some maths to get the per dose equivalences; some might call the amounts thus obtained equivalent to a sparrow's fart* but I found it worked nicely. (It also does not contain iodine, so some might consider my efficacious experiences illusionary. I wave Germanium in their general direction as a peace offering instead.)

I have a new appreciation of your braveness Nighteyes, and 32% v/v alcohol is about what I would expect to keep the solution preserved. I wish I had thought to tell children that 'hey - this has stuff like your parents' vodka in it!' that might have made it instantly more palatable.

Best regards to you both,
Sheila

(*old naval term for not exactly vast amounts)

You are so awesome @Sheila . I used to live in France long ago and discovered this company - they have been around for a long time. I found, like you mentioned, that their low doses are highly effective. Must be the quality and combinations.

 

[Sheila]

Indeed precious Lisaferraro, the whole is more than the sum of the parts x

 

[Nighteyes]

I have a new appreciation of your braveness Nighteyes, and 32% v/v alcohol is about what I would expect to keep the solution preserved. I wish I had thought to tell children that 'hey - this has stuff like your parents' vodka in it!' that might have made it instantly more palatable.

Thank you for the nutrient analysis Sheila! I did feel a little rebellious and some might say giddy? after taking the full dose yesterday. It felt good to be a little placebo-drunk for a while. Today's dose brought only a slightly interesting flavor to my morning juice. It actually smells and tastes kind of nice. I think the elixir might taste much worse (often what happens when an attempt is made to make something vile taste great by masking). You often end up with a double no rather than improve anything really.

 

[Amazoniac]

There are a lot of articles from those decades. Some more:

- Choline as an adjuvant to the dietary therapy of cirrhosis of the liver

"samples of yeast vary considerably in choline content and sometimes may have only very small amounts."

"There can now be little doubt that diets rich in protein of high biological value are indicated in the presence of liver damage."

"In recording the efficacy of choline as an adjuvant to the already recommended high caloric, high protein, high carbohydrate, low fat, high vitamin diet on the basis of treating only seven cases with beneficial results, we do so to call attention to what may well be a helpful therapeutic agent; and our experience in the close observation of several patients, who failed to respond to the diet until choline was administered, lends strong support to this view."

"In the treatment of our cases, we prescribed a diet normal or high in calories, high in protein of good biological value (and rich in methionine), high in carbohydrate, and as low in fat as could be prepared easily by the dietitians and tolerated by the patients (C 250-300, P 125-200, F not more than 60). Lean meats, as well as skimmed milk and cottage cheese, were used freely as sources of protein. In several instances after a preliminary period on diet alone, choline was started. At first, due to timidity, small doses were prescribed; later, as much as six grams of choline chloride was administered daily in divided doses. We chose peppermint water as a solvent, for flavoring and for the specific purpose of denying our patients even the small amounts of alcohol present in an elixir."

"Vitamin K was given parenterally to all jaundiced patients without regard to the prothrombin time. Non-icteric patients with increased prothrombin time received vitamin K by mouth. One patient received as much as 10 mg. of a vitamin K preparation intravenously several times daily to control bleeding (case 1). We prescribed 15,000 to 20,000 U.S.P. units of vitamin A and 1,500 to 2,000 U.S.P. units of vitamin D daily. No bile salt therapy was used in this group of cases."

"Of the nine patients treated adequately with this regimen, seven improved. Three of these patients manifested little or no change when treated first for several weeks with the high protein diet alone, but showed distinct improvement within a week after the beginning of choline therapy."

Could find this anywhere:
Broun, G.O. and Muenther, R.D. Treatment of hepatic cirrhosis with choline chloride and diet low in fat and cholesterol. J.A.M.A. 1942; 118: 1403​

- THE TREATMENT OF CIRRHOSIS OF THE LIVER WITH CHOLINE AND CYSTINE

"In the experimental studies1 by the various groups of investigators there is complete agreement that an inadequate amount of casein in the diet is the determining factor which causes hepatic injury consisting of fatty infiltration and degeneration, necrosis and cirrhosis. This effect of casein is explained on the basis of a lipotropic action.2 It is generally believed 2 that this is in direct proportion to its content of methionine, which has been found to prevent experimental dietary hepatic injury when given in adequate amounts."

"In addition to methionine there are other substances, choline and cystine, which are concerned in the problem of experimental hepatic injury. There is good evidence3 that cystine administered in sufficient amounts may aggravate or cause hepatic injury, whereas choline1 protects the liver from injury, especially from fibrosis, but has no effect on necrosis. There is some difference of opinion as to the mechanism of this action. György and Goldblatt found that choline was more effective when administered with cystine, and they pointed out that in the experimental studies in which choline alone prevents hepatic injury the diets contain a certain amount of cystine."

"In this study only patients with cirrhosis of the liver who had ascites were selected. A group of 20 patients received from 1.5 to 3 Gm. of choline and the same amount of cystine daily divided into three doses for periods of one to five months. They were given a high protein and low fat diet which consisted of approximately 110 Gm. of protein (derived from meat, vegetables and dairy products), 50 to 70 Gm. of fat and 250 Gm. of carbohydrates supplemented with 30 to 45 Gm. of brewers' yeast daily."

"[..]This [patient] represents an instance in which choline and cystine appeared to supply the factors necessary to reverse the process in the liver. They could not be supplied by diet alone because the patient was not able to tolerate large amounts of food. In instances of this kind the choline and cystine are comparable to vitamin concentrates, which are often necessary in addition to diet in the treatment of certain deficiency diseases."

"It is generally agreed that, as the fibrosis increases, the liver becomes smaller and the possibility of obtaining a reversal of the process becomes less. On the other hand, the large cirrhotic liver in most instances contains more fat and less fibrosis. Fleming and Snell5 found in their study that favorable results occurred in patients with large livers, and they expressed the opinion that the "cures" probably are to be expected among the patients who possess various degrees of fatty metamorphosis and degeneration without extensive periportal fibrosis. There seems to be general agreement that treatment is more effectual when there are fatty changes in the liver. However, other changes such as cloudy swelling and necrosis, which are characteristic microscopic findings in cirrhotic livers, may be altered by treatment.
Since the combined administration of choline and cystine was effective only in the patients with large livers where fatty changes were suspected, a lipotropic action of choline and cystine is the logical explanation for the results which were obtained. These results are what might be expected in view of the experimental studies1 in which choline, the combination of choline and cystine, or methionine has been found to prevent the deposition of fat in the liver.
The only reference which can be found in medical literature as to the clinical use of choline and cystine in the treatment of human cirrhosis is that of Russakoff and Blumberg who report a personal communication from Gordon. He observed striking improvement in 5 cases of alcoholic cirrhosis treated with a combination of choline and cystine. There are several clinical reports8 in which choline in conjunction with a high protein, low fat diet and vitamin supplements appeared to exert a favorable influence in the treatment of cirrhosis.
The favorable results in the treatment of cirrhosis of the liver reported by Patek and Post9 and by Fleming and Snell5 with high protein diets and vitamin supplements must be attributed to certain factors in the proteins which arrest or reverse the process in the liver. On the basis of the present experimental studies choline, a combination of choline and cystine, and methionine are the only substances which are known to exert this action. There is a close analogy between cirrhosis of the liver and certain vitamin deficiency diseases in which diet alone may correct the condition when it can provide a sufficient amount of the deficient factors. However, when diet does not do this vitamin concentrates must be supplemented."

Various opinions:

"The importance of certain nutritional factors in the treatment of hepatitis appears to rest on good laboratory and clinical evidence. The sulfur containing amino acid methionine or cystine plus choline is apparently the essential factor. That either methionine or cystine plus choline has any advantage over the other is doubtful unless it is the simplicity of using one drug in place of two. My experience has been entirely with methionine, but results obtained with methionine could be expected to occur with cystine plus choline."

"Patek obtained very encouraging results in a group of patients with cirrhosis who were placed on a high protein, carbohydrate and low fat diet supplemented by large quantities of yeast. But he points out that in order to obtain such improvement it is necessary for the patient to receive a high caloric intake daily. In a small series of cases treated with a high protein, carbohydrate, low fat diet and with supplements of choline-cystine mixture of methionine, improvement (disappearance of symptoms, return of the electrophoretic pattern to normal and normal liver function) was observed provided the patients took an adequate caloric intake and reduced their alcoholic consumption."

"These experiences with supplements of yeast powder, choline-cystine mixture and/or methionine, in addition to a high caloric diet and abstinence from alcohol suggest a very favorable prognosis for persons suffering from cirrhosis of the liver, especially those in the early stages of the disease before the pathologic process becomes irreversible."

"There are differences between the syndrome of chronic hepatic insufficiency accompanied by clinical signs of enlargement of the liver and the cirrhotic syndrome in which the liver is not palpable and therefore probably decreased in size. The prognosis is far better in the former type of cirrhosis, and it is in the group of patients who present signs of enlargement of the liver that by far the largest number of spontaneous remissions occur. It is in this group also that the best therapeutic results have been achieved with an adequate diet, rest, transfusions of blood, plasma and homologous albumin, and the administration of crude liver extract and vitamins."

"Any measure which may be expected to relieve one or more of the metabolic defects arising in this complex syndrome should be included in the therapy of chronic hepatic insufficiency. Measures such as an adequate caloric intake, transfusion of blood, plasma and homologous serum albumin, and the administration of choline, the sulfur-amino acids, crude liver extract and the vitamins may be expected to contribute to some degree in raising the total metabolic efficiency of the liver and to play an important role in helping to check the processes at work in early cirrhosis of the liver, which, if uninfluenced, lead ultimately to a state of irreversible hepatic insufficiency and death."

"Failure to inactivate estrone is one of the manifestations of experimental dietary hepatic injury. It can be studied on living castrated female rats with pellets of estrone implanted in their spleen. Estrus appearing in such animals when kept for varying lengths of time on a cirrhosis producing ration can be suppressed by adding methionine or methionine-containing protein to the diet. This therapeutic effect of methionine and protein can also be demonstrated histologically by comparing sections of the liver taken by biopsy from animals that have been kept for a period of about one hundred and fifty days on a cirrhosis producing basal diet, with sections taken at autopsy of the same animals killed one hundred and fifty days after treatment. In addition to diet, endocrine factors appear to play an important role in experimental hepatic injury. It has been recently shown that estrone exerts a definite, although limited, protective effect on the liver on female rats fed a cirrhosis producing diet. Testosterone or methyltestosterone were without similar beneficial influence. In male rats exposed to carbon tetrachloride the survival time was shorter and parenchymatous changes, especially in the kidneys as part of the hepatorenal syndrome, were more evident than in identically treated female controls. Methionine has shown definite protective effect in both groups, relatively more pronounced in males. The protective effect of thiouracil in experimental hepatic injury might conceivably be regulated through the thyroid gland. It remains to be shown whether management of human cirrhosis of the liver will improve by combination of dietary and endocrine therapy."

"[..]I agree with Dr. Eddy that choline and cystine have no advantage over methionine in the treatment of cirrhosis. In the past year I have employed methionine in the treatment of a group of patients with cirrhosis and hepatitis, and the results are similar to those obtained with choline and cystine."

"I agree that there are evidences for multiple metabolic deficiencies in chronic liver insufficiency, and every measure which may relieve the metabolic defects should be employed. However, in cirrhosis, just as in many of the other deficiency diseases, there is good evidence of one factor being the essential cause of the disease, and the other metabolic defects are the result of the disturbed metabolism. This is especially true in the liver, where many metabolic processes occur. It is quite true that additional experimental and clinical evidence is necessary before it can be established that choline plus cystine or methionine is the essential nutritional factor that is required in the successful treatment of cirrhosis of the liver."​

- USE OF CHOLINE SUPPLEMENTS IN FATTY METAMORPHOSIS OF THE LIVER

"During the investigations on 149 alcoholic and tuberculous patients, it was observed that in a certain number diet or diet with multivitamin supplements failed to produce any appreciable change in fatty metamorphosis of the liver. Among this group eight patients remained under observation a sufficient length of time to enable a study to be carried out on the effect of choline supplements as a lipotropic agent. These cases form the basis of this communication. The methods of study have been previously reported.13 Five patients were placed on a 2,800 calory diet alone, and three were on a 3,400 calory diet with multivitamin supplements. After an initial control period, choline chloride in daily doses of 3 to 9 Gm. was administered orally."

"The results presented indicate that, in persons with fatty change of the liver due to the malnutrition associated with alcoholism or tuberculosis, choline supplements offer no particular value over proper diet alone in clearing fat from the liver."

"Clearance of fat from the liver of 66 alcoholic patients on the house diet alone varied in degree. The majority, however, showed an appreciable reduction in fat, and in many the rate of reduction was exceedingly rapid. These changes were noted in two weeks after the withdrawal of alcohol and the resumption of normal diet. Among these patients were 25 whose biopsies showed early cirrhosis. In 20 of them a significant reduction in fat was seen after one or two weeks."

Summary:
"The rate of fat clearance in a number of patients with fatty metamorphosis while on routine house diets is discussed. The effect of choline supplements on the rate of fat clearance in eight patients with fatty metamorphosis is presented. The majority of patients showed rapid reduction in fat content on diet alone. The administration of choline supplements did not accelerate the rate of fat clearance."​

- THE PREVENTION OF LIVER DAMAGE

"Although it is generally believed that attempts to improve the resistance of the liver to injury from hepatotoxic agents is a contribution of the present century, elaborate studies in this field were undertaken during the nineteenth century.1 It was, however, the experiments of Opie and Alford2 which led clinicians, at least in this country, to believe that a diet high in carbohydrate offered direct protection of the liver from the necrotizing effects of chloroform. Their work received confirmation in the later experiments of Davis, Hall and Whipple 3 and Graham.4"

"To perpetuate the statement that "cellular repair of the liver is best facilitated by a carbohydrate diet"6 violates the fundamental knowledge available to us on cellular repair, for such repair in the main is dependent on protein components available to the regenerating tissue, and on a strictly carbohydrate diet repair would have to depend entirely on the breakdown of endogenous protein. Sanders and Garrison7 have shown that the products of endogenous protein breakdown do not take the place of the protein in an adequate diet during wound repair."

"Carbohydrate protected the liver from injury if, during the deposition of glycogen in the liver, fat was displaced, according to the hypothesis of Rosenfeld,1 and if the ingested carbohydrate spared the body stores of protein. Protein, on the other hand, was found to be a much more active lipotropic agent than carbohydrate (Johnson, Ravdin, Vars and Zintel) and, in addition, certain components of the protein molecule directly protected the liver from the harmful effects of certain hepatotoxic agents. Messinger and Hawkins12 found that a similar diet protected the liver from arsphenamine necrosis. Schultz13 found it to protect against selenium injury, while M. I. Smith reported that it protects against experimental sulfonamide hepatitis."

"A few years ago we found that approximately 29 per cent of patients with long standing gallstone disease had abnormally high amounts of lipid present in the liver. We have now studied the composition of the liver in 127 patients operated on for biliary tract disease. The operations were all done under local or spinal anesthesia. Some of the patients were not on a special diet prior to operation, while others were on a diet which we considered adequate in composition and amount for from five days to one month prior to operation.
The diet consisted of approximately 74 per cent of carbohydrate, 20 per cent of protein and not more than 6 per cent of fat. The carbohydrate was in large part obtained from the banana, for this foodstuff was found to be well tolerated by the patients. [: idi] The protein in large part consisted of casein in the form of cottage cheese, skimmed milk and Casec." "The diet must be varied in order to encourage the patient to eat a sufficient amount of food."

"In any consideration of diet it is important to select a diet which is adequate in the various constituents and which, at the same time, is sufficiently variable so that it will not become monotonous. It is important not only that the patients be offered a satisfactory diet but that they eat it. It cannot be too strongly pointed out that a high caloric intake is just as important as the composition of the food."

"In addition to the diet the patients received yeast, thiamine hydrochloride and one of the potent bile salt preparations. Such accessory therapy is, we believe, useful."

"The data demonstrate that one can by diet bring about a change in the liver so that the concentrations of glycogen and fatty acids are practically identical with those found in histologically normal livers. It is interesting to note that the mean concentration of glycogen in the last two groups was the same, while the mean fatty acid concentration varied by more than 300 per cent."

"It is generally agreed that hepatic regeneration takes place rapidly when circumstances favorable to regeneration are offered. For regeneration to proceed at a maximum rate it is necessary that the organism be offered foodstuffs which supply in maximum amount those components which must be utilized for cellular repair. @schultz [didn't know you were involved] and Vars15 have found in the rat that repair is associated with a change in the ratio between the total liver protein and the nucleoprotein, the latter fraction increasing in amount during the period of repair. Such repair can be facilitated greatly if foodstuffs containing nuclear material are present in the diet during this period. Regardless of any other factors which may be involved, it has been found by them that the food best suited for facilitating this repair is liver itself.
During the past year we have placed our convalescing bad risk biliary tract patients on a diet which while similar in caloric intake and distributon to that used prior to operation, contains a generous share of the protein as liver. While it is difficult to evaluate such a procedure in man without further chemical and histologie data, we have been impressed with the smoothness of the convalescence of these patients and with the rapidity with which abnormalities of function which existed prior to operation have returned to normal thereafter. While casein is an active lipotropic agent and provides in maximal amounts those components of protein which provide protection from hepatotoxic agents, liver protein is more useful during periods when repair is desirable. Thus specificity in the protein provided during different phases of care receives additional significance."

"SUMMARY
1. The ingestion of carbohydrate alone does not afford maximal protection to the liver against a variety of hepatotoxic agents.
2. Glycogen cannot be accumulated in the liver over a considerable number of hours unless the individual is receiving a caloric intake in excess of his basal requirements.
3. Dextrose injected intravenously frequently fails to raise the liver glycogen because the total caloric requirement of the patient is not being provided.
4. Chemical analyses of liver biopsies showed striking correlation between the obesity of the patient and the lipid content of the liver.
5. Chemical analyses of the liver tissue of 37 patients obtained at operation indicates that a dietary regimen based on animal experimental work previously reported is effective in restoring the liver glycogen and liver lipid concentration of patients with severe microscopic damage to the values found in patients with simple cholecystic disease.
6. The average lipid content of severely damaged livers from 10 patients who were not prepared by diet was 14.2 per cent. The average lipid content of 37 patients who were prepared five days or longer with diet was 4.2 per cent. The glycogen content in the latter group was 3.3 per cent as compared with 2.8 per cent in a control group composed of specimens from 16 patients not receiving diet but with microscopically normal livers.
The diet employed consisted of at least 20 per cent protein, not over 6 per cent fat and 74 per cent carbohydrate. An adequate caloric intake is most important and was insisted on."​

- NEW METHODS OF THERAPY IN CIRRHOSIS OF THE LIVER

"The treatment which I have adopted consists in the administration of methionine, 2 Gm. daily; choline chloride, 2 Gm. daily, a special liver extract prepared by the filtration and concentration of an aqueous liver solution containing vitamin B complex; a high protein (higher than heretofore advocated), low fat, moderate carbohydrate diet and frequent feedings of skimmed milk. To my knowledge this identical combination has not previously been reported for human cirrhosis of the liver, and its adoption is based on experimental and clinical evidence.2"

"This therapeutic regimen was adopted for two reasons: first, as is now well known, the experimental evidence obtained in animals indicates conclusively that choline and methionine are proven lipotropic agents in the prevention and alleviation of fatty cirrhosis of the liver in the experimental animal. The experimental evidence that has been amassed in cirrhosis of the liver and in cirrhosis due to alcoholism in human indicates that cirrhosis is subjects a form of nutritional deficiency disease, or, more specifically, a labile methyl-group deficiency disease.3 It is also possible that cirrhosis of the liver may be due to a specific vitamin deficiency, just as the macrocytic anemia of pernicious anemia and sprue appears now to respond specifically to folic of the acids therapy.4"

"Conflicting results were obtained with synthetic cystine, some investigators reporting lipotropic activity of cystine5 and others reporting its cirrhosis-producing effect.6 For this reason, synthetic cystine was not employed in this series of cases."

"It has been suggested that the lipotropic agent methionine could enhance in a synergistic way the lipotropic (or fatty-cirrhosis-preventing) activity of choline.7 Animal experiments revealed further that in hepatic damage choline would largely prevent the cirrhosis but not the necrosis and hemorrhage. Methionine was found to effectively prevent both types of damage to the liver. Experimental studies also showed that the cirrhotic symptoms due to choline deficiency result from lack of a methyl-containing essential other than choline and that methionine can directly supply this lack.8 It is now apparent that although diets may contain an adequate supply of choline, an imbalance or deficiency of other dietary constituents can nullify the lipotropic action of the choline.9"

"Experimental studies demonstrated that an inadequate level of methionine cannot be compensated for by excessive levels of choline and cystine.10 It was further demonstrated that when methionine was added to choline in experimental hepatic damage and growth, a 50 per cent improvement in therapeutic results occurred.10,15 The damaged liver thus appears to have lost its transmethylation ability and requires both synthetic methionine and choline until normal transmethylation can take place from the ingested food."

"Second, in a controlled series of 62 patients over an eight year period,11 therapeutic results suggested that the combination of methionine and choline resulted in a better therapeutic response than did various other combinations of amino acids, diet, liver and vitamin supplements in the treatment of hepatic cirrhosis. Methionine was taken orally in capsule form, the dosage being 2 Gm. daily. Similarly, choline chloride was administered orally in a daily dosage of 2 Gm.10d"

"A special liver extract was used by me because of experimental evidence that indicated its importance, when used with choline derivatives, as an aid in the prevention of hepatic damage.11 In addition, clinical evidence showed that a crude liver extract has definite therapeutic value in the treatment of human cirrhosis of the liver.1a,h I used a specially filtered liver extract11a fortified with vitamin B complex, the administration of which was relatively painless, thus allowing large quantities (3 to 5 cc.) to be injected intramuscularly daily, or every other day, for periods varying from several weeks to several months; injections were tapered off to twice or once a week depending on clinical and laboratory progress in each case. Total vitamin supplements in the diet were often used for the same reasons, which demonstrated their experimental and clinical value in cirrhosis.12 Each cubic centimeter of the vitamin B complex incorporated in the liver extract contained 10 mg. of thiamine chloride, 10 mg. of nicotinamide and 0.3 mg. of riboflavin. It is possible that the liver extract or the vitamin B complex contains a catalytic agent, which permits transmethylation and utilization by the liver of methionine and choline. In support of this suggestion is the experimental evidence that although the choline and methionine content in the cirrhotic liver may be normal or actually higher than normal,8a these factors are not available for utilization."

"The high protein diet which I prescribed consisted not only of a high casein source of proteins by the use of skimmed milk feedings and cottage cheese but also of servings of meat three times a day wherever possible. The importance of a high protein diet in cirrhosis of the liver is now thoroughly established13 and takes precedence over dietary carbohydrate in therapeutic importance. The maximum use of meat in this diet appeared to be advisable because of the necessity for providing the essential amino acids which contain the basic methyl groups, with and without the sulfur radical. These methyl groups are required by the liver for the transmethylation function which institutes regeneration and healing in cirrhosis. As has previously been stated, cirrhosis of the liver when produced experimentally is now regarded as a methyl-group deficiency disease."

"In all possible ways, in cases in which the patient could tolerate it, the patient's diet was stepped up to the limits of tolerance by forced feedings, or any other device, in the attempt to ingest the ideal maximum intake of 200 to 300 Gm. of protein, 300 Gm. of carbohydrate and 50 Gm. of fat."

"All 20 patients revealed characteristic physical signs of cirrhosis of the liver, such as palpable enlargement of the liver, increased venous circulation in the skin over the anterior part of the abdomen and upper portion of the chest, ascites, edema of the legs, glossitis and decided loss of weight. In addition characteristic symptoms were present, such as weakness, malaise, inability to engage in normal mental activities, or physical anorexia or nausea, abdominal distress, gas, belching and constipation."

"[A] patient was placed on a protein diet as high as could be tolerated (three servings of meat a day), low in fat, high in carbohydrate, high in fruit and vegetable content, with 2 quarts (2.3 liters) of skimmed milk and one serving of cottage cheese daily. Two multivitamin capsules15 were taken daily; 5 cc. of whole aqueous liver extract was injected intramuscularly daily for one week, then every other day for two weeks, then twice weekly for one month. Two grams each of methionine and choline chloride were taken daily for three months."
[15] "Capsules contained vitamin A 5,000 units, vitamin B1 3 mg., vitamin B2 2 mg., vitamin B6 1 mg., calcium pantothenate 1 mg., niacinamide 20 mg., ascorbic acid 30 mg. and vitamin D 500 international units."

"There is now ample experimental and clinical evidence, to indicate that a damaged liver will invariably be followed by some damage of the reproductive organs, particularly the testes and the sex accessories. This is probably due to the hepatic failure of steroid hormone inactivation, particularly the estrogens, so that abnormal concentrations of free, biologically active estrogens are available for the induction of gonadal damage, especially in the male. The damage to the sex organs is, in my experience, proportional to the severity and the duration of the hepatic disease. My associates and I reported in 1940 such hormonal observations in the striking syndrome of gynecomastia and testicular atrophy associated with advanced hepatic cirrhosis. Recently our group observed damage of sex organs in rats with experimental cirrhosis. Apropos of this liver-gonadal relationship, Snell and his associates reported in 1945 striking testicular damage in cases with acute hepatitis. Wood in 1946 likewise reported testicular damage in men with acute hepatitis. It is necessary to emphasize this liver-gonadal relationship so that a closer inspection of the patient be made at the bedside as well as at the postmortem table for evidences of pathologic conditions of the reproductive system particularly in the male testes, in the sex accessories and in the breast, in every case of disease of the liver. Where facilities are available, hormone assays for the estimation of urinary estrogens should be carried because the presence of free unconjugated estrogens in the urine is, in our experience, an accurate index of the failure of that particular function of the liver which has to do with the inactivation of the sex steroids. The clinical implications of this particular liver-gonadal relationship are truly legion."​

 

[Nighteyes]

Thank you for another very interesting write-up amazoniac. To me this sounds like 2-3 eggs Per Day might be very liver protective. Eggs provide choline, methionine, protein and fat solubles and I am surprised the authors above do not mention Them more (rather than cottage cheese for Example)

 

[Koveras]

There are a lot of articles from those decades. Some more:

- Choline as an adjuvant to the dietary therapy of cirrhosis of the liver

"samples of yeast vary considerably in choline content and sometimes may have only very small amounts."

"There can now be little doubt that diets rich in protein of high biological value are indicated in the presence of liver damage."

"In recording the efficacy of choline as an adjuvant to the already recommended high caloric, high protein, high carbohydrate, low fat, high vitamin diet on the basis of treating only seven cases with beneficial results, we do so to call attention to what may well be a helpful therapeutic agent; and our experience in the close observation of several patients, who failed to respond to the diet until choline was administered, lends strong support to this view."

"In the treatment of our cases, we prescribed a diet normal or high in calories, high in protein of good biological value (and rich in methionine), high in carbohydrate, and as low in fat as could be prepared easily by the dietitians and tolerated by the patients (C 250-300, P 125-200, F not more than 60). Lean meats, as well as skimmed milk and cottage cheese, were used freely as sources of protein. In several instances after a preliminary period on diet alone, choline was started. At first, due to timidity, small doses were prescribed; later, as much as six grams of choline chloride was administered daily in divided doses. We chose peppermint water as a solvent, for flavoring and for the specific purpose of denying our patients even the small amounts of alcohol present in an elixir."

"Vitamin K was given parenterally to all jaundiced patients without regard to the prothrombin time. Non-icteric patients with increased prothrombin time received vitamin K by mouth. One patient received as much as 10 mg. of a vitamin K preparation intravenously several times daily to control bleeding (case 1). We prescribed 15,000 to 20,000 U.S.P. units of vitamin A and 1,500 to 2,000 U.S.P. units of vitamin D daily. No bile salt therapy was used in this group of cases."

"Of the nine patients treated adequately with this regimen, seven improved. Three of these patients manifested little or no change when treated first for several weeks with the high protein diet alone, but showed distinct improvement within a week after the beginning of choline therapy."

Could find this anywhere:
Broun, G.O. and Muenther, R.D. Treatment of hepatic cirrhosis with choline chloride and diet low in fat and cholesterol. J.A.M.A. 1942; 118: 1403​

- THE TREATMENT OF CIRRHOSIS OF THE LIVER WITH CHOLINE AND CYSTINE

"In the experimental studies1 by the various groups of investigators there is complete agreement that an inadequate amount of casein in the diet is the determining factor which causes hepatic injury consisting of fatty infiltration and degeneration, necrosis and cirrhosis. This effect of casein is explained on the basis of a lipotropic action.2 It is generally believed 2 that this is in direct proportion to its content of methionine, which has been found to prevent experimental dietary hepatic injury when given in adequate amounts."

"In addition to methionine there are other substances, choline and cystine, which are concerned in the problem of experimental hepatic injury. There is good evidence3 that cystine administered in sufficient amounts may aggravate or cause hepatic injury, whereas choline1 protects the liver from injury, especially from fibrosis, but has no effect on necrosis. There is some difference of opinion as to the mechanism of this action. György and Goldblatt found that choline was more effective when administered with cystine, and they pointed out that in the experimental studies in which choline alone prevents hepatic injury the diets contain a certain amount of cystine."

"In this study only patients with cirrhosis of the liver who had ascites were selected. A group of 20 patients received from 1.5 to 3 Gm. of choline and the same amount of cystine daily divided into three doses for periods of one to five months. They were given a high protein and low fat diet which consisted of approximately 110 Gm. of protein (derived from meat, vegetables and dairy products), 50 to 70 Gm. of fat and 250 Gm. of carbohydrates supplemented with 30 to 45 Gm. of brewers' yeast daily."

"[..]This [patient] represents an instance in which choline and cystine appeared to supply the factors necessary to reverse the process in the liver. They could not be supplied by diet alone because the patient was not able to tolerate large amounts of food. In instances of this kind the choline and cystine are comparable to vitamin concentrates, which are often necessary in addition to diet in the treatment of certain deficiency diseases."

"It is generally agreed that, as the fibrosis increases, the liver becomes smaller and the possibility of obtaining a reversal of the process becomes less. On the other hand, the large cirrhotic liver in most instances contains more fat and less fibrosis. Fleming and Snell5 found in their study that favorable results occurred in patients with large livers, and they expressed the opinion that the "cures" probably are to be expected among the patients who possess various degrees of fatty metamorphosis and degeneration without extensive periportal fibrosis. There seems to be general agreement that treatment is more effectual when there are fatty changes in the liver. However, other changes such as cloudy swelling and necrosis, which are characteristic microscopic findings in cirrhotic livers, may be altered by treatment.
Since the combined administration of choline and cystine was effective only in the patients with large livers where fatty changes were suspected, a lipotropic action of choline and cystine is the logical explanation for the results which were obtained. These results are what might be expected in view of the experimental studies1 in which choline, the combination of choline and cystine, or methionine has been found to prevent the deposition of fat in the liver.
The only reference which can be found in medical literature as to the clinical use of choline and cystine in the treatment of human cirrhosis is that of Russakoff and Blumberg who report a personal communication from Gordon. He observed striking improvement in 5 cases of alcoholic cirrhosis treated with a combination of choline and cystine. There are several clinical reports8 in which choline in conjunction with a high protein, low fat diet and vitamin supplements appeared to exert a favorable influence in the treatment of cirrhosis.
The favorable results in the treatment of cirrhosis of the liver reported by Patek and Post9 and by Fleming and Snell5 with high protein diets and vitamin supplements must be attributed to certain factors in the proteins which arrest or reverse the process in the liver. On the basis of the present experimental studies choline, a combination of choline and cystine, and methionine are the only substances which are known to exert this action. There is a close analogy between cirrhosis of the liver and certain vitamin deficiency diseases in which diet alone may correct the condition when it can provide a sufficient amount of the deficient factors. However, when diet does not do this vitamin concentrates must be supplemented."

Various opinions:

"The importance of certain nutritional factors in the treatment of hepatitis appears to rest on good laboratory and clinical evidence. The sulfur containing amino acid methionine or cystine plus choline is apparently the essential factor. That either methionine or cystine plus choline has any advantage over the other is doubtful unless it is the simplicity of using one drug in place of two. My experience has been entirely with methionine, but results obtained with methionine could be expected to occur with cystine plus choline."

"Patek obtained very encouraging results in a group of patients with cirrhosis who were placed on a high protein, carbohydrate and low fat diet supplemented by large quantities of yeast. But he points out that in order to obtain such improvement it is necessary for the patient to receive a high caloric intake daily. In a small series of cases treated with a high protein, carbohydrate, low fat diet and with supplements of choline-cystine mixture of methionine, improvement (disappearance of symptoms, return of the electrophoretic pattern to normal and normal liver function) was observed provided the patients took an adequate caloric intake and reduced their alcoholic consumption."

"These experiences with supplements of yeast powder, choline-cystine mixture and/or methionine, in addition to a high caloric diet and abstinence from alcohol suggest a very favorable prognosis for persons suffering from cirrhosis of the liver, especially those in the early stages of the disease before the pathologic process becomes irreversible."

"There are differences between the syndrome of chronic hepatic insufficiency accompanied by clinical signs of enlargement of the liver and the cirrhotic syndrome in which the liver is not palpable and therefore probably decreased in size. The prognosis is far better in the former type of cirrhosis, and it is in the group of patients who present signs of enlargement of the liver that by far the largest number of spontaneous remissions occur. It is in this group also that the best therapeutic results have been achieved with an adequate diet, rest, transfusions of blood, plasma and homologous albumin, and the administration of crude liver extract and vitamins."

"Any measure which may be expected to relieve one or more of the metabolic defects arising in this complex syndrome should be included in the therapy of chronic hepatic insufficiency. Measures such as an adequate caloric intake, transfusion of blood, plasma and homologous serum albumin, and the administration of choline, the sulfur-amino acids, crude liver extract and the vitamins may be expected to contribute to some degree in raising the total metabolic efficiency of the liver and to play an important role in helping to check the processes at work in early cirrhosis of the liver, which, if uninfluenced, lead ultimately to a state of irreversible hepatic insufficiency and death."

"Failure to inactivate estrone is one of the manifestations of experimental dietary hepatic injury. It can be studied on living castrated female rats with pellets of estrone implanted in their spleen. Estrus appearing in such animals when kept for varying lengths of time on a cirrhosis producing ration can be suppressed by adding methionine or methionine-containing protein to the diet. This therapeutic effect of methionine and protein can also be demonstrated histologically by comparing sections of the liver taken by biopsy from animals that have been kept for a period of about one hundred and fifty days on a cirrhosis producing basal diet, with sections taken at autopsy of the same animals killed one hundred and fifty days after treatment. In addition to diet, endocrine factors appear to play an important role in experimental hepatic injury. It has been recently shown that estrone exerts a definite, although limited, protective effect on the liver on female rats fed a cirrhosis producing diet. Testosterone or methyltestosterone were without similar beneficial influence. In male rats exposed to carbon tetrachloride the survival time was shorter and parenchymatous changes, especially in the kidneys as part of the hepatorenal syndrome, were more evident than in identically treated female controls. Methionine has shown definite protective effect in both groups, relatively more pronounced in males. The protective effect of thiouracil in experimental hepatic injury might conceivably be regulated through the thyroid gland. It remains to be shown whether management of human cirrhosis of the liver will improve by combination of dietary and endocrine therapy."

"[..]I agree with Dr. Eddy that choline and cystine have no advantage over methionine in the treatment of cirrhosis. In the past year I have employed methionine in the treatment of a group of patients with cirrhosis and hepatitis, and the results are similar to those obtained with choline and cystine."

"I agree that there are evidences for multiple metabolic deficiencies in chronic liver insufficiency, and every measure which may relieve the metabolic defects should be employed. However, in cirrhosis, just as in many of the other deficiency diseases, there is good evidence of one factor being the essential cause of the disease, and the other metabolic defects are the result of the disturbed metabolism. This is especially true in the liver, where many metabolic processes occur. It is quite true that additional experimental and clinical evidence is necessary before it can be established that choline plus cystine or methionine is the essential nutritional factor that is required in the successful treatment of cirrhosis of the liver."​

- USE OF CHOLINE SUPPLEMENTS IN FATTY METAMORPHOSIS OF THE LIVER

"During the investigations on 149 alcoholic and tuberculous patients, it was observed that in a certain number diet or diet with multivitamin supplements failed to produce any appreciable change in fatty metamorphosis of the liver. Among this group eight patients remained under observation a sufficient length of time to enable a study to be carried out on the effect of choline supplements as a lipotropic agent. These cases form the basis of this communication. The methods of study have been previously reported.13 Five patients were placed on a 2,800 calory diet alone, and three were on a 3,400 calory diet with multivitamin supplements. After an initial control period, choline chloride in daily doses of 3 to 9 Gm. was administered orally."

"The results presented indicate that, in persons with fatty change of the liver due to the malnutrition associated with alcoholism or tuberculosis, choline supplements offer no particular value over proper diet alone in clearing fat from the liver."

"Clearance of fat from the liver of 66 alcoholic patients on the house diet alone varied in degree. The majority, however, showed an appreciable reduction in fat, and in many the rate of reduction was exceedingly rapid. These changes were noted in two weeks after the withdrawal of alcohol and the resumption of normal diet. Among these patients were 25 whose biopsies showed early cirrhosis. In 20 of them a significant reduction in fat was seen after one or two weeks."

Summary:
"The rate of fat clearance in a number of patients with fatty metamorphosis while on routine house diets is discussed. The effect of choline supplements on the rate of fat clearance in eight patients with fatty metamorphosis is presented. The majority of patients showed rapid reduction in fat content on diet alone. The administration of choline supplements did not accelerate the rate of fat clearance."​

- THE PREVENTION OF LIVER DAMAGE

"Although it is generally believed that attempts to improve the resistance of the liver to injury from hepatotoxic agents is a contribution of the present century, elaborate studies in this field were undertaken during the nineteenth century.1 It was, however, the experiments of Opie and Alford2 which led clinicians, at least in this country, to believe that a diet high in carbohydrate offered direct protection of the liver from the necrotizing effects of chloroform. Their work received confirmation in the later experiments of Davis, Hall and Whipple 3 and Graham.4"

"To perpetuate the statement that "cellular repair of the liver is best facilitated by a carbohydrate diet"6 violates the fundamental knowledge available to us on cellular repair, for such repair in the main is dependent on protein components available to the regenerating tissue, and on a strictly carbohydrate diet repair would have to depend entirely on the breakdown of endogenous protein. Sanders and Garrison7 have shown that the products of endogenous protein breakdown do not take the place of the protein in an adequate diet during wound repair."

"Carbohydrate protected the liver from injury if, during the deposition of glycogen in the liver, fat was displaced, according to the hypothesis of Rosenfeld,1 and if the ingested carbohydrate spared the body stores of protein. Protein, on the other hand, was found to be a much more active lipotropic agent than carbohydrate (Johnson, Ravdin, Vars and Zintel) and, in addition, certain components of the protein molecule directly protected the liver from the harmful effects of certain hepatotoxic agents. Messinger and Hawkins12 found that a similar diet protected the liver from arsphenamine necrosis. Schultz13 found it to protect against selenium injury, while M. I. Smith reported that it protects against experimental sulfonamide hepatitis."

"A few years ago we found that approximately 29 per cent of patients with long standing gallstone disease had abnormally high amounts of lipid present in the liver. We have now studied the composition of the liver in 127 patients operated on for biliary tract disease. The operations were all done under local or spinal anesthesia. Some of the patients were not on a special diet prior to operation, while others were on a diet which we considered adequate in composition and amount for from five days to one month prior to operation.
The diet consisted of approximately 74 per cent of carbohydrate, 20 per cent of protein and not more than 6 per cent of fat. The carbohydrate was in large part obtained from the banana, for this foodstuff was found to be well tolerated by the patients. [: idi] The protein in large part consisted of casein in the form of cottage cheese, skimmed milk and Casec." "The diet must be varied in order to encourage the patient to eat a sufficient amount of food."

"In any consideration of diet it is important to select a diet which is adequate in the various constituents and which, at the same time, is sufficiently variable so that it will not become monotonous. It is important not only that the patients be offered a satisfactory diet but that they eat it. It cannot be too strongly pointed out that a high caloric intake is just as important as the composition of the food."

"In addition to the diet the patients received yeast, thiamine hydrochloride and one of the potent bile salt preparations. Such accessory therapy is, we believe, useful."

"The data demonstrate that one can by diet bring about a change in the liver so that the concentrations of glycogen and fatty acids are practically identical with those found in histologically normal livers. It is interesting to note that the mean concentration of glycogen in the last two groups was the same, while the mean fatty acid concentration varied by more than 300 per cent."

"It is generally agreed that hepatic regeneration takes place rapidly when circumstances favorable to regeneration are offered. For regeneration to proceed at a maximum rate it is necessary that the organism be offered foodstuffs which supply in maximum amount those components which must be utilized for cellular repair. @schultz [didn't know you were involved] and Vars15 have found in the rat that repair is associated with a change in the ratio between the total liver protein and the nucleoprotein, the latter fraction increasing in amount during the period of repair. Such repair can be facilitated greatly if foodstuffs containing nuclear material are present in the diet during this period. Regardless of any other factors which may be involved, it has been found by them that the food best suited for facilitating this repair is liver itself.
During the past year we have placed our convalescing bad risk biliary tract patients on a diet which while similar in caloric intake and distributon to that used prior to operation, contains a generous share of the protein as liver. While it is difficult to evaluate such a procedure in man without further chemical and histologie data, we have been impressed with the smoothness of the convalescence of these patients and with the rapidity with which abnormalities of function which existed prior to operation have returned to normal thereafter. While casein is an active lipotropic agent and provides in maximal amounts those components of protein which provide protection from hepatotoxic agents, liver protein is more useful during periods when repair is desirable. Thus specificity in the protein provided during different phases of care receives additional significance."

"SUMMARY
1. The ingestion of carbohydrate alone does not afford maximal protection to the liver against a variety of hepatotoxic agents.
2. Glycogen cannot be accumulated in the liver over a considerable number of hours unless the individual is receiving a caloric intake in excess of his basal requirements.
3. Dextrose injected intravenously frequently fails to raise the liver glycogen because the total caloric requirement of the patient is not being provided.
4. Chemical analyses of liver biopsies showed striking correlation between the obesity of the patient and the lipid content of the liver.
5. Chemical analyses of the liver tissue of 37 patients obtained at operation indicates that a dietary regimen based on animal experimental work previously reported is effective in restoring the liver glycogen and liver lipid concentration of patients with severe microscopic damage to the values found in patients with simple cholecystic disease.
6. The average lipid content of severely damaged livers from 10 patients who were not prepared by diet was 14.2 per cent. The average lipid content of 37 patients who were prepared five days or longer with diet was 4.2 per cent. The glycogen content in the latter group was 3.3 per cent as compared with 2.8 per cent in a control group composed of specimens from 16 patients not receiving diet but with microscopically normal livers.
The diet employed consisted of at least 20 per cent protein, not over 6 per cent fat and 74 per cent carbohydrate. An adequate caloric intake is most important and was insisted on."​

- NEW METHODS OF THERAPY IN CIRRHOSIS OF THE LIVER

"The treatment which I have adopted consists in the administration of methionine, 2 Gm. daily; choline chloride, 2 Gm. daily, a special liver extract prepared by the filtration and concentration of an aqueous liver solution containing vitamin B complex; a high protein (higher than heretofore advocated), low fat, moderate carbohydrate diet and frequent feedings of skimmed milk. To my knowledge this identical combination has not previously been reported for human cirrhosis of the liver, and its adoption is based on experimental and clinical evidence.2"

"This therapeutic regimen was adopted for two reasons: first, as is now well known, the experimental evidence obtained in animals indicates conclusively that choline and methionine are proven lipotropic agents in the prevention and alleviation of fatty cirrhosis of the liver in the experimental animal. The experimental evidence that has been amassed in cirrhosis of the liver and in cirrhosis due to alcoholism in human indicates that cirrhosis is subjects a form of nutritional deficiency disease, or, more specifically, a labile methyl-group deficiency disease.3 It is also possible that cirrhosis of the liver may be due to a specific vitamin deficiency, just as the macrocytic anemia of pernicious anemia and sprue appears now to respond specifically to folic of the acids therapy.4"

"Conflicting results were obtained with synthetic cystine, some investigators reporting lipotropic activity of cystine5 and others reporting its cirrhosis-producing effect.6 For this reason, synthetic cystine was not employed in this series of cases."

"It has been suggested that the lipotropic agent methionine could enhance in a synergistic way the lipotropic (or fatty-cirrhosis-preventing) activity of choline.7 Animal experiments revealed further that in hepatic damage choline would largely prevent the cirrhosis but not the necrosis and hemorrhage. Methionine was found to effectively prevent both types of damage to the liver. Experimental studies also showed that the cirrhotic symptoms due to choline deficiency result from lack of a methyl-containing essential other than choline and that methionine can directly supply this lack.8 It is now apparent that although diets may contain an adequate supply of choline, an imbalance or deficiency of other dietary constituents can nullify the lipotropic action of the choline.9"

"Experimental studies demonstrated that an inadequate level of methionine cannot be compensated for by excessive levels of choline and cystine.10 It was further demonstrated that when methionine was added to choline in experimental hepatic damage and growth, a 50 per cent improvement in therapeutic results occurred.10,15 The damaged liver thus appears to have lost its transmethylation ability and requires both synthetic methionine and choline until normal transmethylation can take place from the ingested food."

"Second, in a controlled series of 62 patients over an eight year period,11 therapeutic results suggested that the combination of methionine and choline resulted in a better therapeutic response than did various other combinations of amino acids, diet, liver and vitamin supplements in the treatment of hepatic cirrhosis. Methionine was taken orally in capsule form, the dosage being 2 Gm. daily. Similarly, choline chloride was administered orally in a daily dosage of 2 Gm.10d"

"A special liver extract was used by me because of experimental evidence that indicated its importance, when used with choline derivatives, as an aid in the prevention of hepatic damage.11 In addition, clinical evidence showed that a crude liver extract has definite therapeutic value in the treatment of human cirrhosis of the liver.1a,h I used a specially filtered liver extract11a fortified with vitamin B complex, the administration of which was relatively painless, thus allowing large quantities (3 to 5 cc.) to be injected intramuscularly daily, or every other day, for periods varying from several weeks to several months; injections were tapered off to twice or once a week depending on clinical and laboratory progress in each case. Total vitamin supplements in the diet were often used for the same reasons, which demonstrated their experimental and clinical value in cirrhosis.12 Each cubic centimeter of the vitamin B complex incorporated in the liver extract contained 10 mg. of thiamine chloride, 10 mg. of nicotinamide and 0.3 mg. of riboflavin. It is possible that the liver extract or the vitamin B complex contains a catalytic agent, which permits transmethylation and utilization by the liver of methionine and choline. In support of this suggestion is the experimental evidence that although the choline and methionine content in the cirrhotic liver may be normal or actually higher than normal,8a these factors are not available for utilization."

"The high protein diet which I prescribed consisted not only of a high casein source of proteins by the use of skimmed milk feedings and cottage cheese but also of servings of meat three times a day wherever possible. The importance of a high protein diet in cirrhosis of the liver is now thoroughly established13 and takes precedence over dietary carbohydrate in therapeutic importance. The maximum use of meat in this diet appeared to be advisable because of the necessity for providing the essential amino acids which contain the basic methyl groups, with and without the sulfur radical. These methyl groups are required by the liver for the transmethylation function which institutes regeneration and healing in cirrhosis. As has previously been stated, cirrhosis of the liver when produced experimentally is now regarded as a methyl-group deficiency disease."

"In all possible ways, in cases in which the patient could tolerate it, the patient's diet was stepped up to the limits of tolerance by forced feedings, or any other device, in the attempt to ingest the ideal maximum intake of 200 to 300 Gm. of protein, 300 Gm. of carbohydrate and 50 Gm. of fat."

"All 20 patients revealed characteristic physical signs of cirrhosis of the liver, such as palpable enlargement of the liver, increased venous circulation in the skin over the anterior part of the abdomen and upper portion of the chest, ascites, edema of the legs, glossitis and decided loss of weight. In addition characteristic symptoms were present, such as weakness, malaise, inability to engage in normal mental activities, or physical anorexia or nausea, abdominal distress, gas, belching and constipation."

"[A] patient was placed on a protein diet as high as could be tolerated (three servings of meat a day), low in fat, high in carbohydrate, high in fruit and vegetable content, with 2 quarts (2.3 liters) of skimmed milk and one serving of cottage cheese daily. Two multivitamin capsules15 were taken daily; 5 cc. of whole aqueous liver extract was injected intramuscularly daily for one week, then every other day for two weeks, then twice weekly for one month. Two grams each of methionine and choline chloride were taken daily for three months."
[15] "Capsules contained vitamin A 5,000 units, vitamin B1 3 mg., vitamin B2 2 mg., vitamin B6 1 mg., calcium pantothenate 1 mg., niacinamide 20 mg., ascorbic acid 30 mg. and vitamin D 500 international units."

"There is now ample experimental and clinical evidence, to indicate that a damaged liver will invariably be followed by some damage of the reproductive organs, particularly the testes and the sex accessories. This is probably due to the hepatic failure of steroid hormone inactivation, particularly the estrogens, so that abnormal concentrations of free, biologically active estrogens are available for the induction of gonadal damage, especially in the male. The damage to the sex organs is, in my experience, proportional to the severity and the duration of the hepatic disease. My associates and I reported in 1940 such hormonal observations in the striking syndrome of gynecomastia and testicular atrophy associated with advanced hepatic cirrhosis. Recently our group observed damage of sex organs in rats with experimental cirrhosis. Apropos of this liver-gonadal relationship, Snell and his associates reported in 1945 striking testicular damage in cases with acute hepatitis. Wood in 1946 likewise reported testicular damage in men with acute hepatitis. It is necessary to emphasize this liver-gonadal relationship so that a closer inspection of the patient be made at the bedside as well as at the postmortem table for evidences of pathologic conditions of the reproductive system particularly in the male testes, in the sex accessories and in the breast, in every case of disease of the liver. Where facilities are available, hormone assays for the estimation of urinary estrogens should be carried because the presence of free unconjugated estrogens in the urine is, in our experience, an accurate index of the failure of that particular function of the liver which has to do with the inactivation of the sex steroids. The clinical implications of this particular liver-gonadal relationship are truly legion."​

Free L-Cysteine seems to cause oxidative stress which is why N-Acetyl-Cysteine is the preferred supplemental source (Chris Masterjohn reference?) - probably accounts for some of the negative comments regarding cysteine above.

I think the value of methionine and cysteine in liver health might primarily be from the synthesis of glutathione.

Interestingly, methionine restriction and glutathione depletion seem to have some longevity and metabolic benefits - at the same time that it can be stressful or compromise immune function.

J Biol Chem. 2010 Jun 11;285(24):18528-36. doi: 10.1074/jbc.M109.099333. Epub 2010 Apr 15.
Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: impact on mitochondrial S-adenosyl-L-methionine and glutathione.
Caballero F1, Fernández A, Matías N, Martínez L, Fucho R, Elena M, Caballeria J, Morales A, Fernández-Checa JC, García-Ruiz C.

The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis. However, the individual contribution of the lack of methionine and choline in liver steatosis, advanced pathology and impact on mitochondrial S-adenosyl-L-methionine (SAM) and glutathione (GSH), known regulators of disease progression, has not been specifically addressed. Here, we examined the regulation of mitochondrial SAM and GSH and signs of disease in mice fed a MCD, methionine-deficient (MD), or choline-deficient (CD) diet. The MD diet reproduced most of the deleterious effects of MCD feeding, including weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD feeding was mainly responsible for steatosis, characterized by triglycerides and free fatty acids accumulation. These findings were preceded by MCD- or MD-mediated SAM and GSH depletion in mitochondria due to decreased mitochondrial membrane fluidity associated with a lower phosphatidylcholine/phosphatidylethanolamine ratio. MCD and MD but not CD feeding resulted in increased ceramide levels by acid sphingomyelinase. Moreover, GSH ethyl ester or SAM therapy restored mitochondrial GSH and ameliorated hepatocellular injury in mice fed a MCD or MD diet. Thus, the depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine. Moreover, therapy using permeable GSH prodrugs may be of relevance in NASH.​

 

[Koveras]

@Amazoniac

Also of interest

Eur Rev Med Pharmacol Sci. 2012 Jun;16(6):728-36.
Glycine alleviates liver injury induced by deficiency in methionine and or choline in rats.
Barakat HA1, Hamza AH.

OBJECTIVES:
Nonalcoholic steatohepatitis (NASH) is an advanced stage of non-alcoholic fatty liver disease (NAFLD) from steatosis. Methionine and choline are important amino acids play a key role in many cellular functions. Glycine is a non-essential amino acid having multiple roles in many reactions. This study aimed to investigate liver damage induced by feeding male albino rats either methionine deficient (MD), choline deficient (CD), or MCD diets. And to clarify the alleviatory effect of dietary glycine supplementation (5%) on reduced complications caused by feeding each of the deficient diets.

MATERIAL AND METHODS:
Nutritional status, liver functions, lipids profile, hepatic oxidative stress, hepatic antioxidant enzymes, tumor markers and hepatic fatty acid transport protein gene were assessed.

RESULTS:
Rats fed with either MD or MCD diet had less body weight gain unlike rats fed the CD diet. Liver injury was detected in deficient groups by elevating plasma ALT, AST, ALP, total and direct bilirubin, albumin and protein levels. Lipid accumulation was more prominent in rats fed the MCD or CD diet than in those fed the MD diet. Fatty acid transport protein (FATP) was significantly elevated in the different glycine supplemented groups.

CONCLUSION:
Oral administration of glycine confers a significant protective effect by optimizing all the assessed parameters and gene expression.

 

[Amazoniac]

@Koveras, do you remember this thread?
I find it odd that they were aware of gelatin (some of those articles mentioned it) but decided to focus on methionine and choline despite the fact that some patients had the methyl donors accumulated. I can't keep up with your pace of good links, please post some kitten videos once in a while.

Here they report something similar: it was not until methionine was added that estrogen could be cleared.

This is from your first link:

"we observed a disproportionate depletion of mitochondrial SAM in relation to that of hepatic SAM content. This outcome was accompanied by increased levels of SAH and homocysteine resulting in a subsequent lower SAM/SAH ratio, which has been shown to control key cellular functions such as methylation reactions of different targets, including DNA, proteins, and lipids (14). Consistent with these findings, increased SAH has been shown to compete for SAM for transport into mitochondria, accounting for the mitochondrial SAM depletion induced by alcohol intake (22). Moreover, increased SAH and subsequent hyperhomocysteinemia may also participate in the ER stress and UPR [unfolded proteid response], which it is considered a critical mechanism leading to NASH."

"Thus, the lack of methionine leads to a low SAM/SAH ratio, resulting in mitochondrial SAM depletion in addition to ER stress and UPR. Although the latter may be responsible for certain aspects of the pathology, the former may account for the mitochondrial dysfunction and mitochondrial GSH depletion, which in turn determine the hepatocellular susceptibility to oxidative stress and inflammatory cytokines (6), characteristic of NASH."

"Although CysNAc [well, NAC], a GSH precursor, reverses the moderate depletion of hepatic GSH, it fails to restore the mitochondrial pool of GSH following MCD or MD feeding. The newly synthesized GSH from CysNAc in the cytosol is not effectively transported to mitochondria because of the block imposed by the loss of membrane fluidity associated with a decreased PC/PE ratio, consistent with previous observations in alcohol-fed rats (36)."

"Unlike CysNAc, GSH-EE [ethyl ester] is permeable to mitochondria and has been shown to boost GSH stores directly in conditions of impaired transport imposed by perturbed membrane fluidity (36). As expected and consistent with the effects observed with GSH-EE, SAM therapy exerted a protective effect against MCD-induced NASH similar to that observed with GSH-EE and in agreement with previous findings (40). In addition to serving as a GSH precursor in the transsulfuration pathway, SAM has been shown to regulate membrane dynamics by modulating the cholesterol/phospholipids and PC/PE ratios, thus overcoming the impaired transport of GSH into mitochondria in rats fed alcohol (41)."

Second link:

"MCD diet-fed animals accumulate fat in the central perivenous zone of the liver, whereas animals on CD diet first accumulate fat in the periportal zone before it spills over into the other areas. Deficiency of both methionine and choline impairs hepatocyte secretion of VLDL both in vivo and vitro (Raubenheimer et al., 2006)."

"The glycine receptor is a pentameric chloride channel, expressed in neurons, Kupffer cells, neutrophiles, pancreas, and other cells in the body. After glycine-receptor binding, ion chloride influx promotes membrane hyper-polarization, inhibiting calcium influx into the cell (Wheeler et al., 2000). Since cytokine production is dependent on influx of calcium into the cell, the same effect may occur in fibroblast and adipose cells. Hence, when type 2 diabetes patients treated with glycine, the pro-inflammatory cytokines diminished after 3 months of glycine treatment (Garcia-Macedo et al., 2008)."

Methyl groups are generated in the mammalian tissues during degradation of choline to glycine. Generally in adult rats around 40– 45% of the choline uptake is converted to glycine and this value can sometimes increases up to 70% when the choline uptake is very low.

Glycine is impressive. Consider a diet supplemented with it, taurine and creatine to spare the body of synthesizing its own.

 

[Koveras]

z

@Koveras, do you remember this thread?
I find it odd that they were aware of gelatin (some of those articles mentioned it) but decided to focus on methionine and choline despite the fact that some patients had the methyl donors accumulated. I can't keep up with your pace of good links, please post some kitten videos once in a while.

Here they report something similar: it was not until methionine was added that estrogen could be cleared.

This is from your first link:

"we observed a disproportionate depletion of mitochondrial SAM in relation to that of hepatic SAM content. This outcome was accompanied by increased levels of SAH and homocysteine resulting in a subsequent lower SAM/SAH ratio, which has been shown to control key cellular functions such as methylation reactions of different targets, including DNA, proteins, and lipids (14). Consistent with these findings, increased SAH has been shown to compete for SAM for transport into mitochondria, accounting for the mitochondrial SAM depletion induced by alcohol intake (22). Moreover, increased SAH and subsequent hyperhomocysteinemia may also participate in the ER stress and UPR [unfolded proteid response], which it is considered a critical mechanism leading to NASH."

"Thus, the lack of methionine leads to a low SAM/SAH ratio, resulting in mitochondrial SAM depletion in addition to ER stress and UPR. Although the latter may be responsible for certain aspects of the pathology, the former may account for the mitochondrial dysfunction and mitochondrial GSH depletion, which in turn determine the hepatocellular susceptibility to oxidative stress and inflammatory cytokines (6), characteristic of NASH."

"Although CysNAc [well, NAC], a GSH precursor, reverses the moderate depletion of hepatic GSH, it fails to restore the mitochondrial pool of GSH following MCD or MD feeding. The newly synthesized GSH from CysNAc in the cytosol is not effectively transported to mitochondria because of the block imposed by the loss of membrane fluidity associated with a decreased PC/PE ratio, consistent with previous observations in alcohol-fed rats (36)."

"Unlike CysNAc, GSH-EE [ethyl ester] is permeable to mitochondria and has been shown to boost GSH stores directly in conditions of impaired transport imposed by perturbed membrane fluidity (36). As expected and consistent with the effects observed with GSH-EE, SAM therapy exerted a protective effect against MCD-induced NASH similar to that observed with GSH-EE and in agreement with previous findings (40). In addition to serving as a GSH precursor in the transsulfuration pathway, SAM has been shown to regulate membrane dynamics by modulating the cholesterol/phospholipids and PC/PE ratios, thus overcoming the impaired transport of GSH into mitochondria in rats fed alcohol (41)."

Second link:

"MCD diet-fed animals accumulate fat in the central perivenous zone of the liver, whereas animals on CD diet first accumulate fat in the periportal zone before it spills over into the other areas. Deficiency of both methionine and choline impairs hepatocyte secretion of VLDL both in vivo and vitro (Raubenheimer et al., 2006)."

"The glycine receptor is a pentameric chloride channel, expressed in neurons, Kupffer cells, neutrophiles, pancreas, and other cells in the body. After glycine-receptor binding, ion chloride influx promotes membrane hyper-polarization, inhibiting calcium influx into the cell (Wheeler et al., 2000). Since cytokine production is dependent on influx of calcium into the cell, the same effect may occur in fibroblast and adipose cells. Hence, when type 2 diabetes patients treated with glycine, the pro-inflammatory cytokines diminished after 3 months of glycine treatment (Garcia-Macedo et al., 2008)."


Glycine is impressive. Consider a diet supplemented with it, taurine and creatine to spare the body of synthesizing its own.

Even though methionine & cysteine restriction induces ER stress and UPR (part of the ISR - integrated stress response?) - one of the consequences is increased secretion of FGF21 - which works to lower ER stress and seems to be responsible for most (but not all) of the metabolic benefits of methionine restriction.

Note: Glycine seems to upregulate FGF21 (possibly through glucagon?)

It also seems that at the same time that methionine restriction depletes GSH in the liver, it seems to upregulate glutathione synthesis and promote sparing elsewhere:

Tissue glutathione and cysteine levels in methionine-restricted rats.
Nutrition. 2004 Sep;20(9):800-5.
Richie JP Jr1, Komninou D, Leutzinger Y, Kleinman W, Orentreich N, Malloy V, Zimmerman JA.

OBJECTIVE:
Previously, we demonstrated that lifelong methionine (Met) restriction (MR) increases lifespan, decreases the incidence of aging-related diseases, increases blood glutathione (GSH) levels, and prevents loss of GSH during aging in rats. Our present objective was to elucidate the effects of MR on GSH metabolism and transport by determining the time course and nature of GSH and cysteine changes in blood and other tissues in young and mature rats.

METHODS:
Male F-344 rats were placed on control (0.86% Met) or MR (0.17% Met) defined amino acid diets at age 7 wk and killed at different times thereafter. MR was also initiated in adult (12-mo-old) rats.

RESULTS:
Throughout the first 2 mo of MR, blood GSH levels increased 84% and liver GSH decreased 66% in relation to controls. After this period, liver GSH levels remained constant through at least 6 mo. GSH levels also decreased in the pancreas (80%) and kidney (22%) but remained unchanged in other tissues examined after 11 wk of MR. The increase in blood GSH was evident as soon as 1 wk after initiating MR and reached a plateau by 6 wk. A similar increase in erythrocyte GSH levels was observed when MR was administered to mature adult rats. Fasting decreased liver GSH in controls but had no further effect in MR animals. By 1 mo, cysteine levels had decreased in all tissues except brain.

CONCLUSION:
These results suggest that adaptive changes occur in the metabolism of Met, cysteine, and/or GSH as a result of MR in young and adult rats. These early metabolic changes lead to conservation of GSH levels in most extrahepatic tissues and increased GSH in erythrocytes by depleting liver GSH to a critical level.​

...and this one claims increased protection from acetaminophen/tylenol (toxicity through hepatic GSH depletion) in methionine restricted mice

​

Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance.
Miller RA1, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M.

A diet deficient in the amino acid methionine has previously been shown to extend lifespan in several stocks of inbred rats. We report here that a methionine-deficient (Meth-R) diet also increases maximal lifespan in (BALB/cJ x C57BL/6 J)F1 mice. Compared with controls, Meth-R mice have significantly lower levels of serum IGF-I, insulin, glucose and thyroid hormone. Meth-R mice also have higher levels of liver mRNA for MIF (macrophage migration inhibition factor), known to be higher in several other mouse models of extended longevity. Meth-R mice are significantly slower to develop lens turbidity and to show age-related changes in T-cell subsets. They are also dramatically more resistant to oxidative liver cell injury induced by injection of toxic doses of acetaminophen. The spectrum of terminal illnesses in the Meth-R group is similar to that seen in control mice. Studies of the cellular and molecular biology of methionine-deprived mice may, in parallel to studies of calorie-restricted mice, provide insights into the way in which nutritional factors modulate longevity and late-life illnesses.
​

There was another showing reduced steatosis with methionine restriction in a leptin deficient obese mouse model

 

[Amazoniac]

So glutathione increases along with stress? Travisord would probably think in terms of polyamine, methylglyoxal and keeping those in check. But I difficulty thinking of a way to explain its elevation in bl00d. Maybe because it's not being required as much elsewhere?
I posted somewhere about vegans (but not freegans) having elevated levels of glycine in blood, I don't know what it means, but seems interesting.

They are also dramatically more resistant to oxidative liver cell injury induced by injection of toxic doses of acetaminophen.

 

[Koveras]

So glutathione increases along with stress? Travisord would probably think in terms of polyamine, methylglyoxal and keeping those in check. But I difficulty thinking of a way to explain its elevation in bl00d. Maybe because it's not being required as much elsewhere?
I posted somewhere about vegans (but not freegans) having elevated levels of glycine in blood, I don't know what it means, but seems interesting.

Oxidative stress induces NRF2 which increases the synthesis of glutathione

 

[Koveras]

So glutathione increases along with stress? Travisord would probably think in terms of polyamine, methylglyoxal and keeping those in check. But I difficulty thinking of a way to explain its elevation in bl00d. Maybe because it's not being required as much elsewhere?

Oxidative stress induces NRF2 which increases the synthesis of glutathione

Maybe the stress induced my methionine restriction...

"We recently showed that MR regulated the integrated stress response in liver by activation of NRF2 and ATF4 (13)."

FGF21 Mediates the Thermogenic and Insulin-Sensitizing Effects of Dietary Methionine Restriction but Not Its Effects on Hepatic Lipid Metabolism​

...increases NRF2 - increasing glutathione synthesis everywhere... but the methionine/cysteine is prioritized by other demands in the liver?

Whereas whatever methionine/cysteine/glutamine/glycine in the blood is more freely available for that?

 

[haidut]

There are a lot of articles from those decades. Some more:

- Choline as an adjuvant to the dietary therapy of cirrhosis of the liver

"samples of yeast vary considerably in choline content and sometimes may have only very small amounts."

"There can now be little doubt that diets rich in protein of high biological value are indicated in the presence of liver damage."

"In recording the efficacy of choline as an adjuvant to the already recommended high caloric, high protein, high carbohydrate, low fat, high vitamin diet on the basis of treating only seven cases with beneficial results, we do so to call attention to what may well be a helpful therapeutic agent; and our experience in the close observation of several patients, who failed to respond to the diet until choline was administered, lends strong support to this view."

"In the treatment of our cases, we prescribed a diet normal or high in calories, high in protein of good biological value (and rich in methionine), high in carbohydrate, and as low in fat as could be prepared easily by the dietitians and tolerated by the patients (C 250-300, P 125-200, F not more than 60). Lean meats, as well as skimmed milk and cottage cheese, were used freely as sources of protein. In several instances after a preliminary period on diet alone, choline was started. At first, due to timidity, small doses were prescribed; later, as much as six grams of choline chloride was administered daily in divided doses. We chose peppermint water as a solvent, for flavoring and for the specific purpose of denying our patients even the small amounts of alcohol present in an elixir."

"Vitamin K was given parenterally to all jaundiced patients without regard to the prothrombin time. Non-icteric patients with increased prothrombin time received vitamin K by mouth. One patient received as much as 10 mg. of a vitamin K preparation intravenously several times daily to control bleeding (case 1). We prescribed 15,000 to 20,000 U.S.P. units of vitamin A and 1,500 to 2,000 U.S.P. units of vitamin D daily. No bile salt therapy was used in this group of cases."

"Of the nine patients treated adequately with this regimen, seven improved. Three of these patients manifested little or no change when treated first for several weeks with the high protein diet alone, but showed distinct improvement within a week after the beginning of choline therapy."

Could find this anywhere:
Broun, G.O. and Muenther, R.D. Treatment of hepatic cirrhosis with choline chloride and diet low in fat and cholesterol. J.A.M.A. 1942; 118: 1403​

- THE TREATMENT OF CIRRHOSIS OF THE LIVER WITH CHOLINE AND CYSTINE

"In the experimental studies1 by the various groups of investigators there is complete agreement that an inadequate amount of casein in the diet is the determining factor which causes hepatic injury consisting of fatty infiltration and degeneration, necrosis and cirrhosis. This effect of casein is explained on the basis of a lipotropic action.2 It is generally believed 2 that this is in direct proportion to its content of methionine, which has been found to prevent experimental dietary hepatic injury when given in adequate amounts."

"In addition to methionine there are other substances, choline and cystine, which are concerned in the problem of experimental hepatic injury. There is good evidence3 that cystine administered in sufficient amounts may aggravate or cause hepatic injury, whereas choline1 protects the liver from injury, especially from fibrosis, but has no effect on necrosis. There is some difference of opinion as to the mechanism of this action. György and Goldblatt found that choline was more effective when administered with cystine, and they pointed out that in the experimental studies in which choline alone prevents hepatic injury the diets contain a certain amount of cystine."

"In this study only patients with cirrhosis of the liver who had ascites were selected. A group of 20 patients received from 1.5 to 3 Gm. of choline and the same amount of cystine daily divided into three doses for periods of one to five months. They were given a high protein and low fat diet which consisted of approximately 110 Gm. of protein (derived from meat, vegetables and dairy products), 50 to 70 Gm. of fat and 250 Gm. of carbohydrates supplemented with 30 to 45 Gm. of brewers' yeast daily."

"[..]This [patient] represents an instance in which choline and cystine appeared to supply the factors necessary to reverse the process in the liver. They could not be supplied by diet alone because the patient was not able to tolerate large amounts of food. In instances of this kind the choline and cystine are comparable to vitamin concentrates, which are often necessary in addition to diet in the treatment of certain deficiency diseases."

"It is generally agreed that, as the fibrosis increases, the liver becomes smaller and the possibility of obtaining a reversal of the process becomes less. On the other hand, the large cirrhotic liver in most instances contains more fat and less fibrosis. Fleming and Snell5 found in their study that favorable results occurred in patients with large livers, and they expressed the opinion that the "cures" probably are to be expected among the patients who possess various degrees of fatty metamorphosis and degeneration without extensive periportal fibrosis. There seems to be general agreement that treatment is more effectual when there are fatty changes in the liver. However, other changes such as cloudy swelling and necrosis, which are characteristic microscopic findings in cirrhotic livers, may be altered by treatment.
Since the combined administration of choline and cystine was effective only in the patients with large livers where fatty changes were suspected, a lipotropic action of choline and cystine is the logical explanation for the results which were obtained. These results are what might be expected in view of the experimental studies1 in which choline, the combination of choline and cystine, or methionine has been found to prevent the deposition of fat in the liver.
The only reference which can be found in medical literature as to the clinical use of choline and cystine in the treatment of human cirrhosis is that of Russakoff and Blumberg who report a personal communication from Gordon. He observed striking improvement in 5 cases of alcoholic cirrhosis treated with a combination of choline and cystine. There are several clinical reports8 in which choline in conjunction with a high protein, low fat diet and vitamin supplements appeared to exert a favorable influence in the treatment of cirrhosis.
The favorable results in the treatment of cirrhosis of the liver reported by Patek and Post9 and by Fleming and Snell5 with high protein diets and vitamin supplements must be attributed to certain factors in the proteins which arrest or reverse the process in the liver. On the basis of the present experimental studies choline, a combination of choline and cystine, and methionine are the only substances which are known to exert this action. There is a close analogy between cirrhosis of the liver and certain vitamin deficiency diseases in which diet alone may correct the condition when it can provide a sufficient amount of the deficient factors. However, when diet does not do this vitamin concentrates must be supplemented."

Various opinions:

"The importance of certain nutritional factors in the treatment of hepatitis appears to rest on good laboratory and clinical evidence. The sulfur containing amino acid methionine or cystine plus choline is apparently the essential factor. That either methionine or cystine plus choline has any advantage over the other is doubtful unless it is the simplicity of using one drug in place of two. My experience has been entirely with methionine, but results obtained with methionine could be expected to occur with cystine plus choline."

"Patek obtained very encouraging results in a group of patients with cirrhosis who were placed on a high protein, carbohydrate and low fat diet supplemented by large quantities of yeast. But he points out that in order to obtain such improvement it is necessary for the patient to receive a high caloric intake daily. In a small series of cases treated with a high protein, carbohydrate, low fat diet and with supplements of choline-cystine mixture of methionine, improvement (disappearance of symptoms, return of the electrophoretic pattern to normal and normal liver function) was observed provided the patients took an adequate caloric intake and reduced their alcoholic consumption."

"These experiences with supplements of yeast powder, choline-cystine mixture and/or methionine, in addition to a high caloric diet and abstinence from alcohol suggest a very favorable prognosis for persons suffering from cirrhosis of the liver, especially those in the early stages of the disease before the pathologic process becomes irreversible."

"There are differences between the syndrome of chronic hepatic insufficiency accompanied by clinical signs of enlargement of the liver and the cirrhotic syndrome in which the liver is not palpable and therefore probably decreased in size. The prognosis is far better in the former type of cirrhosis, and it is in the group of patients who present signs of enlargement of the liver that by far the largest number of spontaneous remissions occur. It is in this group also that the best therapeutic results have been achieved with an adequate diet, rest, transfusions of blood, plasma and homologous albumin, and the administration of crude liver extract and vitamins."

"Any measure which may be expected to relieve one or more of the metabolic defects arising in this complex syndrome should be included in the therapy of chronic hepatic insufficiency. Measures such as an adequate caloric intake, transfusion of blood, plasma and homologous serum albumin, and the administration of choline, the sulfur-amino acids, crude liver extract and the vitamins may be expected to contribute to some degree in raising the total metabolic efficiency of the liver and to play an important role in helping to check the processes at work in early cirrhosis of the liver, which, if uninfluenced, lead ultimately to a state of irreversible hepatic insufficiency and death."

"Failure to inactivate estrone is one of the manifestations of experimental dietary hepatic injury. It can be studied on living castrated female rats with pellets of estrone implanted in their spleen. Estrus appearing in such animals when kept for varying lengths of time on a cirrhosis producing ration can be suppressed by adding methionine or methionine-containing protein to the diet. This therapeutic effect of methionine and protein can also be demonstrated histologically by comparing sections of the liver taken by biopsy from animals that have been kept for a period of about one hundred and fifty days on a cirrhosis producing basal diet, with sections taken at autopsy of the same animals killed one hundred and fifty days after treatment. In addition to diet, endocrine factors appear to play an important role in experimental hepatic injury. It has been recently shown that estrone exerts a definite, although limited, protective effect on the liver on female rats fed a cirrhosis producing diet. Testosterone or methyltestosterone were without similar beneficial influence. In male rats exposed to carbon tetrachloride the survival time was shorter and parenchymatous changes, especially in the kidneys as part of the hepatorenal syndrome, were more evident than in identically treated female controls. Methionine has shown definite protective effect in both groups, relatively more pronounced in males. The protective effect of thiouracil in experimental hepatic injury might conceivably be regulated through the thyroid gland. It remains to be shown whether management of human cirrhosis of the liver will improve by combination of dietary and endocrine therapy."

"[..]I agree with Dr. Eddy that choline and cystine have no advantage over methionine in the treatment of cirrhosis. In the past year I have employed methionine in the treatment of a group of patients with cirrhosis and hepatitis, and the results are similar to those obtained with choline and cystine."

"I agree that there are evidences for multiple metabolic deficiencies in chronic liver insufficiency, and every measure which may relieve the metabolic defects should be employed. However, in cirrhosis, just as in many of the other deficiency diseases, there is good evidence of one factor being the essential cause of the disease, and the other metabolic defects are the result of the disturbed metabolism. This is especially true in the liver, where many metabolic processes occur. It is quite true that additional experimental and clinical evidence is necessary before it can be established that choline plus cystine or methionine is the essential nutritional factor that is required in the successful treatment of cirrhosis of the liver."​

- USE OF CHOLINE SUPPLEMENTS IN FATTY METAMORPHOSIS OF THE LIVER

"During the investigations on 149 alcoholic and tuberculous patients, it was observed that in a certain number diet or diet with multivitamin supplements failed to produce any appreciable change in fatty metamorphosis of the liver. Among this group eight patients remained under observation a sufficient length of time to enable a study to be carried out on the effect of choline supplements as a lipotropic agent. These cases form the basis of this communication. The methods of study have been previously reported.13 Five patients were placed on a 2,800 calory diet alone, and three were on a 3,400 calory diet with multivitamin supplements. After an initial control period, choline chloride in daily doses of 3 to 9 Gm. was administered orally."

"The results presented indicate that, in persons with fatty change of the liver due to the malnutrition associated with alcoholism or tuberculosis, choline supplements offer no particular value over proper diet alone in clearing fat from the liver."

"Clearance of fat from the liver of 66 alcoholic patients on the house diet alone varied in degree. The majority, however, showed an appreciable reduction in fat, and in many the rate of reduction was exceedingly rapid. These changes were noted in two weeks after the withdrawal of alcohol and the resumption of normal diet. Among these patients were 25 whose biopsies showed early cirrhosis. In 20 of them a significant reduction in fat was seen after one or two weeks."

Summary:
"The rate of fat clearance in a number of patients with fatty metamorphosis while on routine house diets is discussed. The effect of choline supplements on the rate of fat clearance in eight patients with fatty metamorphosis is presented. The majority of patients showed rapid reduction in fat content on diet alone. The administration of choline supplements did not accelerate the rate of fat clearance."​

- THE PREVENTION OF LIVER DAMAGE

"Although it is generally believed that attempts to improve the resistance of the liver to injury from hepatotoxic agents is a contribution of the present century, elaborate studies in this field were undertaken during the nineteenth century.1 It was, however, the experiments of Opie and Alford2 which led clinicians, at least in this country, to believe that a diet high in carbohydrate offered direct protection of the liver from the necrotizing effects of chloroform. Their work received confirmation in the later experiments of Davis, Hall and Whipple 3 and Graham.4"

"To perpetuate the statement that "cellular repair of the liver is best facilitated by a carbohydrate diet"6 violates the fundamental knowledge available to us on cellular repair, for such repair in the main is dependent on protein components available to the regenerating tissue, and on a strictly carbohydrate diet repair would have to depend entirely on the breakdown of endogenous protein. Sanders and Garrison7 have shown that the products of endogenous protein breakdown do not take the place of the protein in an adequate diet during wound repair."

"Carbohydrate protected the liver from injury if, during the deposition of glycogen in the liver, fat was displaced, according to the hypothesis of Rosenfeld,1 and if the ingested carbohydrate spared the body stores of protein. Protein, on the other hand, was found to be a much more active lipotropic agent than carbohydrate (Johnson, Ravdin, Vars and Zintel) and, in addition, certain components of the protein molecule directly protected the liver from the harmful effects of certain hepatotoxic agents. Messinger and Hawkins12 found that a similar diet protected the liver from arsphenamine necrosis. Schultz13 found it to protect against selenium injury, while M. I. Smith reported that it protects against experimental sulfonamide hepatitis."

"A few years ago we found that approximately 29 per cent of patients with long standing gallstone disease had abnormally high amounts of lipid present in the liver. We have now studied the composition of the liver in 127 patients operated on for biliary tract disease. The operations were all done under local or spinal anesthesia. Some of the patients were not on a special diet prior to operation, while others were on a diet which we considered adequate in composition and amount for from five days to one month prior to operation.
The diet consisted of approximately 74 per cent of carbohydrate, 20 per cent of protein and not more than 6 per cent of fat. The carbohydrate was in large part obtained from the banana, for this foodstuff was found to be well tolerated by the patients. [: idi] The protein in large part consisted of casein in the form of cottage cheese, skimmed milk and Casec." "The diet must be varied in order to encourage the patient to eat a sufficient amount of food."

"In any consideration of diet it is important to select a diet which is adequate in the various constituents and which, at the same time, is sufficiently variable so that it will not become monotonous. It is important not only that the patients be offered a satisfactory diet but that they eat it. It cannot be too strongly pointed out that a high caloric intake is just as important as the composition of the food."

"In addition to the diet the patients received yeast, thiamine hydrochloride and one of the potent bile salt preparations. Such accessory therapy is, we believe, useful."

"The data demonstrate that one can by diet bring about a change in the liver so that the concentrations of glycogen and fatty acids are practically identical with those found in histologically normal livers. It is interesting to note that the mean concentration of glycogen in the last two groups was the same, while the mean fatty acid concentration varied by more than 300 per cent."

"It is generally agreed that hepatic regeneration takes place rapidly when circumstances favorable to regeneration are offered. For regeneration to proceed at a maximum rate it is necessary that the organism be offered foodstuffs which supply in maximum amount those components which must be utilized for cellular repair. @schultz [didn't know you were involved] and Vars15 have found in the rat that repair is associated with a change in the ratio between the total liver protein and the nucleoprotein, the latter fraction increasing in amount during the period of repair. Such repair can be facilitated greatly if foodstuffs containing nuclear material are present in the diet during this period. Regardless of any other factors which may be involved, it has been found by them that the food best suited for facilitating this repair is liver itself.
During the past year we have placed our convalescing bad risk biliary tract patients on a diet which while similar in caloric intake and distributon to that used prior to operation, contains a generous share of the protein as liver. While it is difficult to evaluate such a procedure in man without further chemical and histologie data, we have been impressed with the smoothness of the convalescence of these patients and with the rapidity with which abnormalities of function which existed prior to operation have returned to normal thereafter. While casein is an active lipotropic agent and provides in maximal amounts those components of protein which provide protection from hepatotoxic agents, liver protein is more useful during periods when repair is desirable. Thus specificity in the protein provided during different phases of care receives additional significance."

"SUMMARY
1. The ingestion of carbohydrate alone does not afford maximal protection to the liver against a variety of hepatotoxic agents.
2. Glycogen cannot be accumulated in the liver over a considerable number of hours unless the individual is receiving a caloric intake in excess of his basal requirements.
3. Dextrose injected intravenously frequently fails to raise the liver glycogen because the total caloric requirement of the patient is not being provided.
4. Chemical analyses of liver biopsies showed striking correlation between the obesity of the patient and the lipid content of the liver.
5. Chemical analyses of the liver tissue of 37 patients obtained at operation indicates that a dietary regimen based on animal experimental work previously reported is effective in restoring the liver glycogen and liver lipid concentration of patients with severe microscopic damage to the values found in patients with simple cholecystic disease.
6. The average lipid content of severely damaged livers from 10 patients who were not prepared by diet was 14.2 per cent. The average lipid content of 37 patients who were prepared five days or longer with diet was 4.2 per cent. The glycogen content in the latter group was 3.3 per cent as compared with 2.8 per cent in a control group composed of specimens from 16 patients not receiving diet but with microscopically normal livers.
The diet employed consisted of at least 20 per cent protein, not over 6 per cent fat and 74 per cent carbohydrate. An adequate caloric intake is most important and was insisted on."​

- NEW METHODS OF THERAPY IN CIRRHOSIS OF THE LIVER

"The treatment which I have adopted consists in the administration of methionine, 2 Gm. daily; choline chloride, 2 Gm. daily, a special liver extract prepared by the filtration and concentration of an aqueous liver solution containing vitamin B complex; a high protein (higher than heretofore advocated), low fat, moderate carbohydrate diet and frequent feedings of skimmed milk. To my knowledge this identical combination has not previously been reported for human cirrhosis of the liver, and its adoption is based on experimental and clinical evidence.2"

"This therapeutic regimen was adopted for two reasons: first, as is now well known, the experimental evidence obtained in animals indicates conclusively that choline and methionine are proven lipotropic agents in the prevention and alleviation of fatty cirrhosis of the liver in the experimental animal. The experimental evidence that has been amassed in cirrhosis of the liver and in cirrhosis due to alcoholism in human indicates that cirrhosis is subjects a form of nutritional deficiency disease, or, more specifically, a labile methyl-group deficiency disease.3 It is also possible that cirrhosis of the liver may be due to a specific vitamin deficiency, just as the macrocytic anemia of pernicious anemia and sprue appears now to respond specifically to folic of the acids therapy.4"

"Conflicting results were obtained with synthetic cystine, some investigators reporting lipotropic activity of cystine5 and others reporting its cirrhosis-producing effect.6 For this reason, synthetic cystine was not employed in this series of cases."

"It has been suggested that the lipotropic agent methionine could enhance in a synergistic way the lipotropic (or fatty-cirrhosis-preventing) activity of choline.7 Animal experiments revealed further that in hepatic damage choline would largely prevent the cirrhosis but not the necrosis and hemorrhage. Methionine was found to effectively prevent both types of damage to the liver. Experimental studies also showed that the cirrhotic symptoms due to choline deficiency result from lack of a methyl-containing essential other than choline and that methionine can directly supply this lack.8 It is now apparent that although diets may contain an adequate supply of choline, an imbalance or deficiency of other dietary constituents can nullify the lipotropic action of the choline.9"

"Experimental studies demonstrated that an inadequate level of methionine cannot be compensated for by excessive levels of choline and cystine.10 It was further demonstrated that when methionine was added to choline in experimental hepatic damage and growth, a 50 per cent improvement in therapeutic results occurred.10,15 The damaged liver thus appears to have lost its transmethylation ability and requires both synthetic methionine and choline until normal transmethylation can take place from the ingested food."

"Second, in a controlled series of 62 patients over an eight year period,11 therapeutic results suggested that the combination of methionine and choline resulted in a better therapeutic response than did various other combinations of amino acids, diet, liver and vitamin supplements in the treatment of hepatic cirrhosis. Methionine was taken orally in capsule form, the dosage being 2 Gm. daily. Similarly, choline chloride was administered orally in a daily dosage of 2 Gm.10d"

"A special liver extract was used by me because of experimental evidence that indicated its importance, when used with choline derivatives, as an aid in the prevention of hepatic damage.11 In addition, clinical evidence showed that a crude liver extract has definite therapeutic value in the treatment of human cirrhosis of the liver.1a,h I used a specially filtered liver extract11a fortified with vitamin B complex, the administration of which was relatively painless, thus allowing large quantities (3 to 5 cc.) to be injected intramuscularly daily, or every other day, for periods varying from several weeks to several months; injections were tapered off to twice or once a week depending on clinical and laboratory progress in each case. Total vitamin supplements in the diet were often used for the same reasons, which demonstrated their experimental and clinical value in cirrhosis.12 Each cubic centimeter of the vitamin B complex incorporated in the liver extract contained 10 mg. of thiamine chloride, 10 mg. of nicotinamide and 0.3 mg. of riboflavin. It is possible that the liver extract or the vitamin B complex contains a catalytic agent, which permits transmethylation and utilization by the liver of methionine and choline. In support of this suggestion is the experimental evidence that although the choline and methionine content in the cirrhotic liver may be normal or actually higher than normal,8a these factors are not available for utilization."

"The high protein diet which I prescribed consisted not only of a high casein source of proteins by the use of skimmed milk feedings and cottage cheese but also of servings of meat three times a day wherever possible. The importance of a high protein diet in cirrhosis of the liver is now thoroughly established13 and takes precedence over dietary carbohydrate in therapeutic importance. The maximum use of meat in this diet appeared to be advisable because of the necessity for providing the essential amino acids which contain the basic methyl groups, with and without the sulfur radical. These methyl groups are required by the liver for the transmethylation function which institutes regeneration and healing in cirrhosis. As has previously been stated, cirrhosis of the liver when produced experimentally is now regarded as a methyl-group deficiency disease."

"In all possible ways, in cases in which the patient could tolerate it, the patient's diet was stepped up to the limits of tolerance by forced feedings, or any other device, in the attempt to ingest the ideal maximum intake of 200 to 300 Gm. of protein, 300 Gm. of carbohydrate and 50 Gm. of fat."

"All 20 patients revealed characteristic physical signs of cirrhosis of the liver, such as palpable enlargement of the liver, increased venous circulation in the skin over the anterior part of the abdomen and upper portion of the chest, ascites, edema of the legs, glossitis and decided loss of weight. In addition characteristic symptoms were present, such as weakness, malaise, inability to engage in normal mental activities, or physical anorexia or nausea, abdominal distress, gas, belching and constipation."

"[A] patient was placed on a protein diet as high as could be tolerated (three servings of meat a day), low in fat, high in carbohydrate, high in fruit and vegetable content, with 2 quarts (2.3 liters) of skimmed milk and one serving of cottage cheese daily. Two multivitamin capsules15 were taken daily; 5 cc. of whole aqueous liver extract was injected intramuscularly daily for one week, then every other day for two weeks, then twice weekly for one month. Two grams each of methionine and choline chloride were taken daily for three months."
[15] "Capsules contained vitamin A 5,000 units, vitamin B1 3 mg., vitamin B2 2 mg., vitamin B6 1 mg., calcium pantothenate 1 mg., niacinamide 20 mg., ascorbic acid 30 mg. and vitamin D 500 international units."

"There is now ample experimental and clinical evidence, to indicate that a damaged liver will invariably be followed by some damage of the reproductive organs, particularly the testes and the sex accessories. This is probably due to the hepatic failure of steroid hormone inactivation, particularly the estrogens, so that abnormal concentrations of free, biologically active estrogens are available for the induction of gonadal damage, especially in the male. The damage to the sex organs is, in my experience, proportional to the severity and the duration of the hepatic disease. My associates and I reported in 1940 such hormonal observations in the striking syndrome of gynecomastia and testicular atrophy associated with advanced hepatic cirrhosis. Recently our group observed damage of sex organs in rats with experimental cirrhosis. Apropos of this liver-gonadal relationship, Snell and his associates reported in 1945 striking testicular damage in cases with acute hepatitis. Wood in 1946 likewise reported testicular damage in men with acute hepatitis. It is necessary to emphasize this liver-gonadal relationship so that a closer inspection of the patient be made at the bedside as well as at the postmortem table for evidences of pathologic conditions of the reproductive system particularly in the male testes, in the sex accessories and in the breast, in every case of disease of the liver. Where facilities are available, hormone assays for the estimation of urinary estrogens should be carried because the presence of free unconjugated estrogens in the urine is, in our experience, an accurate index of the failure of that particular function of the liver which has to do with the inactivation of the sex steroids. The clinical implications of this particular liver-gonadal relationship are truly legion."​

There are Russian studies on Pubmed showing reversal of cirrhosis with saturated phosphatidylcholine (PC) but I don't think it was the choline that was beneficial - i.e. it is simply a great carrier of the saturated fat into the cells as Peat said (and hence MitoLipin). Your quote also shows high choline/methionine in the liver in cirrhosis.

 

[Wilfrid]

@Amazoniac , @haidut

What do you think about this product:
Liver Extract - BIOFAC A/S

 

[Wilfrid]

As for the yeast and rice bran extract used in the past for vitamins deficiencies, I found the following product ( the manufacturer have a patented process using only water and lemon juice as unique solvents ):
Équilibre Vitamines B bio

 

[Wagner83]

As for the yeast and rice bran extract used in the past for vitamins deficiencies, I found the following product ( the manufacturer have a patented process using only water and lemon juice as unique solvents ):
Équilibre Vitamines B bio

Thanks, I posted about this one before: Quinogerm B complex (vitamines B naturelles) - 60 gélules végétales