Great idea @daniel. Methionine inhibition could be useful in more than just very aggressive cancers, so this is very actionable and useful info.

Also good to hear your product will be used in one or more clinical trials, Boswellia has great potential in many cancer and brain cancers in particular, and is a good combination with curcumin.

That is a great find, Thanks for posting!

Interestingly, AKBA decreases the SAM/SAH ratio, So compounds that decrease this ratio may also suppress methionine metabolism! 

Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism

The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM/SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.

Why did it get such a prominent place as a repurposed cancer drug because it has quite a few cancer-promoting effects e.g. it increases blood plasma lactate. On my blog, I mostly warn about the use of it in cancer and its dangers. It's being promoted heavily on social media as an anti-aging drug, I really believe this drug is going to harm a lot of people.

Here's another concern,  metformin causes an increase in UCP2 levels ("UCP2 was barely detected in control adipocytes, the treatment with metformin caused a marked increase in its expression that peaked on day 9").

In this study they "over-expressed UCP2 in the stem cells and showed that metabolism patterns changed before markers of pluripotency or cell maturation changed, indicating that changes in metabolism affect changes in differentiation and not the other way around, at least for UCP2. This was important, to show causation for metabolic changes in driving the process of cell differentiation. However, it still leaves open the key question of exactly how manipulating cell metabolism controls cell differentiation, a question we are working hard to address."

"Since metabolism in pluripotent stem cells and cancer cells appear quite similar, Teitell said the finding could potentially be used to target UCP2 in malignant tumors that express it, of which there are many. Silencing UCP2 could force cancer cells to respire, which might impair their ability to grow quickly."

Posted by: @j

Why did it get such a prominent place as a repurposed cancer drug because it has quite a few cancer-promoting effects e.g. it increases blood plasma lactate. On my blog, I mostly warn about the use of it in cancer and its dangers. It's being promoted heavily on social media as an anti-aging drug, I really believe this drug is going to harm a lot of people.

I need to nuance what I said here. It's a very useful drug for diabetics, there's no doubt about that. And there are studies that point to a possible benefit in cancer patients. But reading about young healthy people taking metformin for supposed anti-aging benefits is scary considering some of this drug's effects. Berberine can protect against the risk of increased lactic acid (ref). And B12 malabsorption is reversed with calcium supplementation (ref).

Good points, johan;

Metformin is actually a mitochondrial toxin (inhibitor of complex 1) whose main mechanism is to mimic starvation (mimetic of caloric restriction), which is why it is attractive for anti-aging research. Metformin is a hydrophilic compound charged positively at physiological pH. Its hydrophilicity limits its permeability through lipid membranes. Considering that cancer cells prefer lipophilic anions, I guess that metformin does not have a direct effect on cancer cells in the internal environment of the body!

Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis

Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine/glycine-dependent creatine biosynthesis.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388453/

In the past, the combination of urea and creatine has been used to treat cancer, can this combination have a synergistic effect with a methionine-deprived diet?

by Prof. Evangelos D. Danopoulos, M.D.

In 1987 in the Cancer Victors Journal, Vol. 21 No. 3 and in the Townsend Letter for Doctors (Feb./Mar. 1988) was published my article "The Possibility of Treating Malignancies with Urea."

Since this article was published, experience has led me to change my concept somewhat and to greatly improve my method of treating malignancies.

In the previous article I said that urea taken per os, once it has entered the blood circulation, is quickly excreted by the kidneys in urine. It is for this reason that urea, when administered intravenously, cannot reach organs with a high enough concentration to have anti-cancer effect. Taken per os, urea reaches the liver via the portal vein in a high enough concentration to have a most helpful effect on a primary liver malignancy or on a liver metastasis. After passing through the liver, urea comes to other organs in too low a concentration to have anti-cancer effect, so that concentration of urea in organs other than the liver has to be enriched by other means.

During the winter of 1987-1988, in treating a patient with pancreatic cancer with metastases to the para-aortic lymph nodes, I was astonished to observe that his blood urea (BU) was in the range of 70 to 90 mg. % even though he was receiving the small daily dose of 20 to 30 grams a day of urea. This high blood urea was unexpected. The patient had no sign of renal insufficiency, which meant that contrary to my previous thinking, he was excreting urea via the kidneys slowly. To my thinking this meant that the malignancy was making his kidneys excrete urea more slowly. It was further noted that BU increased or decreased over a period of a few days, depending probably on the quantity of proteins and fluids of the food the patient takes. It was found that to maintain the constant high level of blood urea of 75 to 85 mg. %, it was needed to test for BU every 5 to 8 days and to change the dosage of urea to maintain a constant level of BU in the range of 75-85 mg. %. When the patient was main tained in the level of BU of 75 to 85 mg. %, he showed vast improvement. This patient had unbearable abdominal pain as the enlarged lymph nodes pressed the nerves near the vertebral column. Before being treated with urea, he required morphia three times a day, however after taking urea and when his BU was maintained in the range of 75 to 85 mg. % his pain decreased to where he could get by with only 2 to 4 tablets of paracetamol a day. If however his BU dropped to under the range of 75 to 85 mg. %, or got up over this, then he again suffered intense abdominal pain. This is the second very significant and surprising observation made during the treatment of this patient. There is namely an active level (AL) of BU, which must be kept constant during treatment, in order to achieve good results.

This same observation was confirmed with two other cancer patients suffering severe pain. It was found that patients reacted in different ways, that some excreted urea at a more rapid rate than others and that the same patient would excrete urea at different rates as days went by. However, while the dosage of urea needed to maintain BU in the range of 75 to 85 mg. % varied from patient to patient and with one patient from time to time, when the active level of 75 to 85 mg. % was maintained, the patient had relief from pain. Note in the USA, BUN (blood urea nitrogen) is measured rather than BU and the proper range of BUN is 35 to 40 mg. %.

The story of my use of urea in the treatment of cancer began in 1954 when I discovered that urine has anti-cancer effect. After long research I discovered that the anti-cancer agent in urine is urea. In 1969, I began to treat cancer patients with oral urea with notable success in primary liver cancer or more often with liver metastases. Also it was soon found that injections of 15% to 50% urea in normal saline into and around skin cancers and malignant breast tumors were most effective.

In the meantime I had tried many other substances without effect. In 1980 I used for the first time creatine hydrate instead of creatinine which is very quickly excreted by the kidneys. Creatine is, on the contrary, very slowly excreted and then as creatinine to which it has been changed.

My first use of creatine hydrate as a monotherapy was with a patient with five small lung metastases from a sarcoma in his left thigh. After one month of treatment of this patient with 25 grams a day of creatine hydrate taken per os, all these small metastases vanished. They had been from 6 to 15 mm. in diameter. This confirmed in my mind that creatine hydrate, like urea, has a marked anticancer effect. Notation: Urea is water soluble. Creatine hydrate is not so. If 25 grams of creatine hydrate are put in a quart of water and quart is placed in a half gallon container, then the half gallon container can be shaken with vigor and a portion poured out and drunk. In this manner the creatine will act the same as if it were water soluble.

Next I treated two far advanced cancer patients with 25 grams a day of creatine hydrate per os. One had extensive adenocarcinoma metastases in both lungs. The other had extensive lung metastases from a primary sarcoma in a thigh. Neither of these patients were benefited by creatine hydrate as a monotherapy.

Then, with the knowledge that both urea and creatine hydrate have anti-cancer effect, I used the combination of urea and creatine hydrate in treating the aforementioned pancreatic cancer patient. I gave this patient sufficient urea to maintain BU in the range of 75 to 85 mg. %. Then I added oral creatine hydrate to the treatment starting with 10 grams a day. Again keeping BU at 75 to 85 mg. % with oral urea, I increased the daily dosage of creatine hydrate to 25 grams a day. With this treatment the patient showed many signs of regression of his cancer. His appetite improved, his pain decreased, and his erythrocytes sedimentation rate fell from 110/1 hr. to 47/1 hr.

Then to test how effective was this combination treatment, I discontinued the use of urea for four days. His BU decreased to 45 mg. % and his condition deteriorated. On adding urea to his treatment to achieve BU of 75 to 85 mg. % again....his condition once again improved. Then I withdrew creatine hydrate from treatment for nine days. Again the patient showed a deteriorated condition. When I resumed treatment with creatine hydrate, I used a dosage of 40 grams a day, then slowly decreased it back to 25 grams a day.

Thereafter, on enough urea to maintain BU at 75 to 85 mg. % and 25 grams of creatine hydrate a day, this patient showed progressive and gratifying improvement. It is to be regretted that five months and 11 days after the beginning of combined urea and creatine hydrate treatment, this patient suffered a fatal episode of myocardial infarction.
I then obtained the same good results with this combined treatment of urea and creatine hydrate with 10 more patients with cancers of various locations in the body. These cases will be published in a medical journal. I will note here that unlike the two above mentioned patients where creatine hydrate was used as a monotherapy, the patients treated with the combination of urea and creatine hydrate all showed improvement. If the patient suffers severe pain, then the patient can understand the benefit of this treatment as the pain decreases.

In cancer patients where only the liver is involved with malignancy, the test for BU or BUN is not needed because the liver always gets a proper concentration of urea as urea taken per os goes via the portal vein to the liver. However, where there is concern that there may be metastases in other parts of the body, then it would be well to do BU or BUN testing every 10 days and to maintain BU to 75 to 85 mg. %. In treating liver cancer only, 14 grams a day of urea are needed, along with 21 grams of creatine hydrate. This combination need be taken every hour and a half throughout the waking day. One suggestion is this. If urea alone is to be taken, put the urea, 14 grams or how many is to be used in a quart of water. If treating liver cancer also with creatine hydrate, then 21 grams of creatine hydrate is also added to this quart of water. With the quart in a half gallon container, one can shake the container with vigor, then 1/7th of a quart is poured out and drunk every hour and a hal f.

The same is true when 25 grams of creatine hydrate are being used.

In cases of severe liver cancer with great enlargement of this organ, we can increase the dose of urea only a little, from 14 grams to 18 grams a day and the dose of creatine hydrate to 25 to 30 grams a day. In case of liver metastases when the primary cancer (of the pancreas i.e.) is not removed, we cannot increase the dose of urea to obtain the AL because the liver cannot tolerate large doses of urea. Therefore we give 14 to 18 grams of urea and 25 to 30 grams of creatine hydrate. Creatine hydrate is more slowly excreted than urea, hence there is no need to measure the blood level of creatine as in the case of the need to measure BU or BUN in order to keep a constant AL.

The question arises, will the combination of urea and creatine hydrate be beneficial in the treatment of bone metastases? If the cancer is in the bone marrow which has a good supply of blood (myeloma), then good results are possible. Bone metastases are irrigated poorly by blood and the results of treatment with the combination of urea and creatine hydrate may be poor.

A vast majority of deaths from solid malignant tumors results from distant metastases. In any form of cancer therapy, it is of utmost importance that metastases are not permitted to form. I am certain that, after surgery, to excise a primary malignant tumor, the taking of the combination of urea and creatine hydrate for six months or more, while maintaining BUN in the range of 35 to 40 mg. %, will abolish the very small undetectable metastases that so often later grow into the large metastases that kill so many patients. The same is true with the possible remnant cancer cells from the primary tumor after it has been excised.

In conclusion, both urea and creatine hydrate have been demonstrated as having anti-cancer effect. Both are remarkably non-toxic. Both are non-drugs that require no prescriptions. I have used urea in water per os in treating liver cancer or liver metastases since 1969 and it has been ever so effective. Also urea in normal saline injected into skin cancers has been just as effective. By the use of the combination of urea and creatine hydrate it has been possible to obtain remarkable regressions of cancer in organs of the body other than the liver. Furthermore, one can with this treatment, prevent the growth of any metastases after surgical removal of the primary and prevent recurrences.

http://www.encognitive.com/node/2698

Relationships among biomarkers of one-carbon metabolism

One-carbon metabolism is a network of metabolic pathways, disruption of which has been associated with cancer and other pathological conditions. Biomarkers of these pathways include homocysteine (HCY), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). A better understanding of the relationships between these biomarkers is needed for their utilization in research. This study investigated the relationships between fasting concentrations of plasma HCY, SAM, SAH and the ratio of SAM:SAH, and serum folate, vitamin B₁₂ and creatinine in a healthy adult population. A cross-sectional study recruited 678 volunteers; only subjects with complete data (n = 581) were included in this analysis. Correlations were used to examine bivariate relationships among the biomarkers and multivariate linear regression determined independent relationships with HCY, SAM and SAH treated as dependent variables in separate models. Multivariate logistic regression examined determinants of a low SAM:SAH ratio (defined as having a SAM:SAH ratio in the bottom quartile and SAH value in the top quartile). HCY correlated inversely with folate and vitamin B₁₂ and weakly correlated with SAH and creatinine. Both SAM and SAH correlated with creatinine but were independent of serum folate and vitamin B₁₂. In multivariate analyses, folate, vitamin B₁₂, creatinine, sex and age were associated with HCY; age and creatinine were determinants of SAM, and sex and creatinine determinants of SAH. Finally, male sex and increasing creatinine (a breakdown product of creatine) levels were associated with having a low SAM:SAH ratio. Findings suggest that HCY, SAM and SAH are relatively independent parameters and reflect distinct aspects of one-carbon metabolism.

 

https://link.springer.com/article/10.1007/s11033-012-1623-y

Posted by: @aliml2

Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis

Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine/glycine-dependent creatine biosynthesis.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388453/

In the past, the combination of urea and creatine has been used to treat cancer, can this combination have a synergistic effect with a methionine-deprived diet?

by Prof. Evangelos D. Danopoulos, M.D.

In 1987 in the Cancer Victors Journal, Vol. 21 No. 3 and in the Townsend Letter for Doctors (Feb./Mar. 1988) was published my article "The Possibility of Treating Malignancies with Urea."

Since this article was published, experience has led me to change my concept somewhat and to greatly improve my method of treating malignancies.

In the previous article I said that urea taken per os, once it has entered the blood circulation, is quickly excreted by the kidneys in urine. It is for this reason that urea, when administered intravenously, cannot reach organs with a high enough concentration to have anti-cancer effect. Taken per os, urea reaches the liver via the portal vein in a high enough concentration to have a most helpful effect on a primary liver malignancy or on a liver metastasis. After passing through the liver, urea comes to other organs in too low a concentration to have anti-cancer effect, so that concentration of urea in organs other than the liver has to be enriched by other means.

During the winter of 1987-1988, in treating a patient with pancreatic cancer with metastases to the para-aortic lymph nodes, I was astonished to observe that his blood urea (BU) was in the range of 70 to 90 mg. % even though he was receiving the small daily dose of 20 to 30 grams a day of urea. This high blood urea was unexpected. The patient had no sign of renal insufficiency, which meant that contrary to my previous thinking, he was excreting urea via the kidneys slowly. To my thinking this meant that the malignancy was making his kidneys excrete urea more slowly. It was further noted that BU increased or decreased over a period of a few days, depending probably on the quantity of proteins and fluids of the food the patient takes. It was found that to maintain the constant high level of blood urea of 75 to 85 mg. %, it was needed to test for BU every 5 to 8 days and to change the dosage of urea to maintain a constant level of BU in the range of 75-85 mg. %. When the patient was main tained in the level of BU of 75 to 85 mg. %, he showed vast improvement. This patient had unbearable abdominal pain as the enlarged lymph nodes pressed the nerves near the vertebral column. Before being treated with urea, he required morphia three times a day, however after taking urea and when his BU was maintained in the range of 75 to 85 mg. % his pain decreased to where he could get by with only 2 to 4 tablets of paracetamol a day. If however his BU dropped to under the range of 75 to 85 mg. %, or got up over this, then he again suffered intense abdominal pain. This is the second very significant and surprising observation made during the treatment of this patient. There is namely an active level (AL) of BU, which must be kept constant during treatment, in order to achieve good results.

This same observation was confirmed with two other cancer patients suffering severe pain. It was found that patients reacted in different ways, that some excreted urea at a more rapid rate than others and that the same patient would excrete urea at different rates as days went by. However, while the dosage of urea needed to maintain BU in the range of 75 to 85 mg. % varied from patient to patient and with one patient from time to time, when the active level of 75 to 85 mg. % was maintained, the patient had relief from pain. Note in the USA, BUN (blood urea nitrogen) is measured rather than BU and the proper range of BUN is 35 to 40 mg. %.

The story of my use of urea in the treatment of cancer began in 1954 when I discovered that urine has anti-cancer effect. After long research I discovered that the anti-cancer agent in urine is urea. In 1969, I began to treat cancer patients with oral urea with notable success in primary liver cancer or more often with liver metastases. Also it was soon found that injections of 15% to 50% urea in normal saline into and around skin cancers and malignant breast tumors were most effective.

In the meantime I had tried many other substances without effect. In 1980 I used for the first time creatine hydrate instead of creatinine which is very quickly excreted by the kidneys. Creatine is, on the contrary, very slowly excreted and then as creatinine to which it has been changed.

My first use of creatine hydrate as a monotherapy was with a patient with five small lung metastases from a sarcoma in his left thigh. After one month of treatment of this patient with 25 grams a day of creatine hydrate taken per os, all these small metastases vanished. They had been from 6 to 15 mm. in diameter. This confirmed in my mind that creatine hydrate, like urea, has a marked anticancer effect. Notation: Urea is water soluble. Creatine hydrate is not so. If 25 grams of creatine hydrate are put in a quart of water and quart is placed in a half gallon container, then the half gallon container can be shaken with vigor and a portion poured out and drunk. In this manner the creatine will act the same as if it were water soluble.

Next I treated two far advanced cancer patients with 25 grams a day of creatine hydrate per os. One had extensive adenocarcinoma metastases in both lungs. The other had extensive lung metastases from a primary sarcoma in a thigh. Neither of these patients were benefited by creatine hydrate as a monotherapy.

Then, with the knowledge that both urea and creatine hydrate have anti-cancer effect, I used the combination of urea and creatine hydrate in treating the aforementioned pancreatic cancer patient. I gave this patient sufficient urea to maintain BU in the range of 75 to 85 mg. %. Then I added oral creatine hydrate to the treatment starting with 10 grams a day. Again keeping BU at 75 to 85 mg. % with oral urea, I increased the daily dosage of creatine hydrate to 25 grams a day. With this treatment the patient showed many signs of regression of his cancer. His appetite improved, his pain decreased, and his erythrocytes sedimentation rate fell from 110/1 hr. to 47/1 hr.

Then to test how effective was this combination treatment, I discontinued the use of urea for four days. His BU decreased to 45 mg. % and his condition deteriorated. On adding urea to his treatment to achieve BU of 75 to 85 mg. % again....his condition once again improved. Then I withdrew creatine hydrate from treatment for nine days. Again the patient showed a deteriorated condition. When I resumed treatment with creatine hydrate, I used a dosage of 40 grams a day, then slowly decreased it back to 25 grams a day.

Thereafter, on enough urea to maintain BU at 75 to 85 mg. % and 25 grams of creatine hydrate a day, this patient showed progressive and gratifying improvement. It is to be regretted that five months and 11 days after the beginning of combined urea and creatine hydrate treatment, this patient suffered a fatal episode of myocardial infarction.
I then obtained the same good results with this combined treatment of urea and creatine hydrate with 10 more patients with cancers of various locations in the body. These cases will be published in a medical journal. I will note here that unlike the two above mentioned patients where creatine hydrate was used as a monotherapy, the patients treated with the combination of urea and creatine hydrate all showed improvement. If the patient suffers severe pain, then the patient can understand the benefit of this treatment as the pain decreases.

In cancer patients where only the liver is involved with malignancy, the test for BU or BUN is not needed because the liver always gets a proper concentration of urea as urea taken per os goes via the portal vein to the liver. However, where there is concern that there may be metastases in other parts of the body, then it would be well to do BU or BUN testing every 10 days and to maintain BU to 75 to 85 mg. %. In treating liver cancer only, 14 grams a day of urea are needed, along with 21 grams of creatine hydrate. This combination need be taken every hour and a half throughout the waking day. One suggestion is this. If urea alone is to be taken, put the urea, 14 grams or how many is to be used in a quart of water. If treating liver cancer also with creatine hydrate, then 21 grams of creatine hydrate is also added to this quart of water. With the quart in a half gallon container, one can shake the container with vigor, then 1/7th of a quart is poured out and drunk every hour and a hal f.

The same is true when 25 grams of creatine hydrate are being used.

In cases of severe liver cancer with great enlargement of this organ, we can increase the dose of urea only a little, from 14 grams to 18 grams a day and the dose of creatine hydrate to 25 to 30 grams a day. In case of liver metastases when the primary cancer (of the pancreas i.e.) is not removed, we cannot increase the dose of urea to obtain the AL because the liver cannot tolerate large doses of urea. Therefore we give 14 to 18 grams of urea and 25 to 30 grams of creatine hydrate. Creatine hydrate is more slowly excreted than urea, hence there is no need to measure the blood level of creatine as in the case of the need to measure BU or BUN in order to keep a constant AL.

The question arises, will the combination of urea and creatine hydrate be beneficial in the treatment of bone metastases? If the cancer is in the bone marrow which has a good supply of blood (myeloma), then good results are possible. Bone metastases are irrigated poorly by blood and the results of treatment with the combination of urea and creatine hydrate may be poor.

A vast majority of deaths from solid malignant tumors results from distant metastases. In any form of cancer therapy, it is of utmost importance that metastases are not permitted to form. I am certain that, after surgery, to excise a primary malignant tumor, the taking of the combination of urea and creatine hydrate for six months or more, while maintaining BUN in the range of 35 to 40 mg. %, will abolish the very small undetectable metastases that so often later grow into the large metastases that kill so many patients. The same is true with the possible remnant cancer cells from the primary tumor after it has been excised.

In conclusion, both urea and creatine hydrate have been demonstrated as having anti-cancer effect. Both are remarkably non-toxic. Both are non-drugs that require no prescriptions. I have used urea in water per os in treating liver cancer or liver metastases since 1969 and it has been ever so effective. Also urea in normal saline injected into skin cancers has been just as effective. By the use of the combination of urea and creatine hydrate it has been possible to obtain remarkable regressions of cancer in organs of the body other than the liver. Furthermore, one can with this treatment, prevent the growth of any metastases after surgical removal of the primary and prevent recurrences.

http://www.encognitive.com/node/2698

 

Thanks for sharing, these extraordinary findings. So much promising cancer research from the '50s that was apparently buried. 

Regulating the urea cycle in cancer patients seems to be potentially curative e. g. the benefit in cancer treatment of phenylbutyrate, a prodrug for phenylacetylglutamine and phenylacetate.

Vitamin c and Ammonia increased - a phase IV clinical study of FDA data

https://www.ehealthme.com/ds/vitamin-c/ammonia-increased/

Posted by: @j

Vitamin c and Ammonia increased - a phase IV clinical study of FDA data

https://www.ehealthme.com/ds/vitamin-c/ammonia-increased/

I think that's part of the problem with high dose (IV) vitamin C.