Water Structure, Osmolytes And Cancer

[LLight]

Hello,

Please find below the summary of a theory about cancer which I find quite interesting

Unmasking the secrets of cancer: water type A non-structured promotes carcinogenesis and water type B structured restores the physiology and cellular bioenergetics transforming cancerous cells into normal cells. Hypothesis of carcinogenesis (http://www.medicinacomplementar.com.br/biblioteca/pdfs/Cancer/ca-0417.pdf)

"It is important to note that clusters of water are created by the interaction of tiny quantities of organic or inorganic substances with water, the osmolytes (Lo-2000, Wiggins-1971-2001, Chaplin MF-1999) and being classic in literature the existence of osmolytes that build (kaotropos) and osmolytes that destroy (caotropos) the hydrogen bonds of intracellular water. The first ones increases amount of type B water in intracellular and the latter increases type water A."

"Water A: high density, osmotically active and fluid to have weak hydrogen bonds. It is a water without structure (non-structured), with small clusters; in other words, with the "n" in (H2O)n too low. Density: 1.18 g / ml

Water B: low density, osmotically inactive and viscous to have strong hydrogen bonds. It is a structured water, with larger clusters; that is, with the "n" in (H2O)n high and of great duration. Density: 0.91 g / ml"

"In the evolution of the human species, during the transition of the primitive organisms of the aqueous way for the terrestrial the genes suffered mutations and parallelly they provoked the necessary decrease of the cellular proliferation with increase of the differentiation and still provided protection against drying cell, without which the organisms would not survive in no-aqueous atmosphere. The protection against desiccation was provided by the accumulation of organic and inorganic cytoplasmatic osmolytes (Ferraris1999-2001, Dmitrieva-2006). In carcinogenesis occurs the opposite of what happened in evolution, that is, we observed increase in cell proliferation with decrease of the differentiation and following this reasoning we can infer that the mechanism against cell desiccation also been reversed, therefore we hope to find in the cancerous cells a decrease of the organic and inorganic osmolytes. In fact, in the medical literature of good level, we found several scientific works that show that tissue cancer has drastic decrease of osmolytes in relation to the corresponding normal tissue.

Interstitial hypertonicity actives transcription factors (TonEBP / OREBP - "tonicity-responsive enhancer / osmotic response element binding protein) that results in increase of the genes expression involved in the accumulation of osmoprotectors organic osmolytes (Burg-1995-2007, Zhou-2006). Interstitial hyperosmolality causes an increase in cytoplasmic osmolytes as a mechanism of defense to avoid drying / dehydration of the cell. This is one of the oldest mechanisms that allowed the passage of life from water to land. The primitive organisms that managed to avoid desiccation were those who managed to live outside the water. From the opposite side, we believe that the interstitial hypotonicity promoted by persistent chronic inflammation edema, inhibits the transcription factors TonEBP / OREBP which causes a decrease of cytoplasmatics osmolytes."

"Many evidences indicate the prevalence of high density and osmotically active non-structured water type A in proliferating cells."

"One of the characteristics of cancer cells is their water content similar to embryonic tissue of the same origin that is high. In fact, the cancer cells have consistently water content higher than the normal cells of the same origin (Winzler-1959)."

"The strategy of reducing the amount of type A water and increase type B water of malignant cells interfering in osmolytes reaches the target, reaches the fundamental and initial point of carcinogenic process and inhibit cell proliferation, promotes apoptosis, decreases the formation of new vessels and increases the cellular differentiation."

"PEG increases the osmotic pressure in a dose-dependent manner and removes water from the intracellular. The removed water is the type A water, which is osmotically active and thus in the cell increases the relative concentration of type B water, standard of the bioenergetic function. [...] In fact the withdrawal of non-structured type A water from cytoplasm allows that the cell acquires its normal initial characteristics which restores the negative entropy, increases the degree of order, the metabolism becomes oxidative phosphorylation and cell proliferation no more is required."

"The researcher Waheed Roomi and his staff at the Division of Cancer Institute Matthias Rath of California, through 13 works very ingenious brilliantly showed that the employment of a mixture of nutritional substances that structures intracellular water has anti tumor effect in several types of cancer both in vitro and in-vivo: lung, prostate, breast, pancreas, urinary bladder, glioma, testicles, melanoma and fibrosarcoma"​

TL;DR: loss of osmolytes in a cell (due to stress/inflammation) decreases the structure of its intracellular water which disturbs its metabolism. In reaction, the cell adopts a cancerous metabolism. Flushing unstructured water from the cell and providing it with osmolyte could restore the proper metabolism.

I just found a paper that seems to state a similar hypothesis: Cell hydration as the primary factor in carcinogenesis: A unifying concept. - PubMed - NCBI

 

[Inaut]

Urea came to mind after reading this

 

[somuch4food]

Flushing unstructured water from the cell and providing it with osmolyte could restore the proper metabolism.

Does anyone have a theory on how to achieve this?

 

[LLight]

Urea came to mind after reading this

Could you expand your idea a bit please ?

I'm not nowledgeable about urea, but I read yesterday that it has a antibacterial effect.

 

[LLight]

Does anyone have a theory on how to achieve this?

If you ask me (but it's quite taboo here), I'd say that dry fasting could be helpful because dehydration and amino acids deprivation could activates TonEBP (also called NFAT5 in the literature) that promotes osmolytes uptake/synthesis by cells. The osmotic pressure could also flush some water out of the cell.

I also think that the activation of TonEBP has also the advantage of stimulating the immune system.

I can provide some details about that in this thread if you are interested

 

[GAF]

HD: So what water do you recommend people drink Dr Peat? Do you have one?

RP: No actually. You have to go to or be near a glacier.

Deuterium. Search the forum. This may be the water needed.

 

[GAF]

Defeating Cancer!: The Biological Effect of Deuterium Depletion https://www.amazon.com/dp/0759692602/ref=cm_sw_r_cp_apa_i_ZbtyDbJ4YQB2B

 

[GAF]

Description
Product description
This book is an account of experiments carried out using deuterium-depleted water (Dd-water) and of the human clinical trials underway in Hungary. The most astonishing discovery was that healthy cells quickly adapt to the lower deuterium concentration, whereas tumour cells are unable to do so. This, in the majority of cases, resulted in the destruction of cells, a decrease in tumour mass, or its total regression. The discovery detailed in the book reflects an inherent possibility for mankind to start the 21st century in the hope of finding the cure for cancer.

About the Author
Gbor Somlyai is a molecular biologist. Having finished his studies in 1982, he worked in the field of genetic engineering and gene mapping in Germany (1988 - Georg-August University, Gttingen) and in the USA (University of Missouri Columbia, Columbia). He was first inspired by Hungarian Nobel-prize winner Albert Szent-Gyrgyi, who believed that the true cause of cancer might be found at sub-molecular level. Somlyai began his investigations in 1990 with the examination of whether the naturally occurring deuterium - the heavy isotope of hydrogen - plays any role in the regulation of biological, i.e. intracellular molecular processes. His investigation was quite unique. The existence of deuterium has been known for nearly seventy years, and it is also known that it behaves differently from hydrogen and that in our body deuterium is present in 12-14 mmol/L concentration. Yet, nobody before had ever investigated the possible role of naturally occurring deuterium in living organism.

 

[LLight]

Deuterium. Search the forum. This may be the water needed.

Hi GAF,

I did know about deuterium depleted water via this publication: Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle. - PubMed - NCBI
It's well above my knowledge about biology! But I'm not sure it's totally the same topic than the one talked about in these articles

 

[LLight]

Interestingly, abscisic acid, which has been praised by Virginia Livingstone, seems to regulate osmolyte accumulation in plants: Phytohormones Regulate Accumulation of Osmolytes Under Abiotic Stress. - PubMed - NCBI

"The accumulation of osmolytes is further modulated by phytohormones like abscisic acid, brassinosteroids, cytokinins, ethylene, jasmonates, and salicylic acid."
​

 

[GAF]

"Plants face a variety of abiotic stresses, which generate reactive oxygen species (ROS), and ultimately obstruct normal growth and development of plants. To prevent cellular damage caused by oxidative stress, plants accumulate certain compatible solutes known as osmolytes to safeguard the cellular machinery. The most common osmolytes that play crucial role in osmoregulation are proline, glycine-betaine, polyamines, and sugars. These compounds stabilize the osmotic differences between surroundings of cell and the cytosol. Besides, they also protect the plant cells from oxidative stress by inhibiting the production of harmful ROS like hydroxyl ions, superoxide ions, hydrogen peroxide, and other free radicals." (from the above link)

Polyamines in aging and disease.

Abstract
Polyamines are polycations that interact with negatively charged molecules such as DNA, RNA and proteins. They play multiple roles in cell growth, survival and proliferation. Changes in polyamine levels have been associated with aging and diseases. Their levels decline continuously with age and polyamine (spermidine or high-polyamine diet) supplementation increases life span in model organisms. Polyamines have also been involved in stress resistance. On the other hand, polyamines are increased in cancer cells and are a target for potential chemotherapeutic agents. In this review, we bring together these various results and draw a picture of the state of our knowledge on the roles of polyamines in aging, stress and diseases.

INTRODUCTION
Polyamines have been known for a long-time as the first one, spermine, was discovered over 330 years ago by microscopic observation of human semen [reviewed in 1]. They have since been found in all eukaryotes and most prokaryotes. Polyamines are polycations (Figure (Figure1)1) and thus one of their main features is to interact with negatively charged molecules, such as DNA, RNA or proteins. Given their promiscuity in binding other molecules, they are involved in many functions, mostly linked with cell growth, survival and proliferation. Three polyamines, putrescine, spermidine and spermine, are part of the very tightly regulated polyamine metabolic pathway. Polyamines are the subject of intensive research in order to elucidate their functions and involvement in physiology. Polyamines are important players in plant growth, stress and disease resistance [2], but they are also involved in diseases [3], for example Alzheimer's or infectious diseases. The main research area for the involvement of polyamines in diseases is cancer, as high levels of polyamines are observed in cancer cells [3]. More recently, we have shown a causative role for polyamines in longevity [4].

[these science nerds love their wordplay...]

 

[GAF]

So, I read the book mentioned above. The bottom line is to drink low deuterium water to dilute your body's total body deuterium content, if you have cancer.

If you don't have cancer, drink some of the water for a month or two every year or two, in case it is preventative.

The water is very expensive on Ebay. However, it is a whole lot cheaper than one month of ultra crappy "Health" Insurance in the USA.

I compromised and bought some Icelandic Water on Amazon. I plan to just drink that and coffee made with that and Red Bull for a few months and see what happens. I will limit intake of other water by not eating foods with high water content.

I don't have cancer at the moment that I know of.

 

[Inaut]

Can it be as simple as this ?

 

[LLight]

"Plants face a variety of abiotic stresses, which generate reactive oxygen species (ROS), and ultimately obstruct normal growth and development of plants. To prevent cellular damage caused by oxidative stress, plants accumulate certain compatible solutes known as osmolytes to safeguard the cellular machinery. The most common osmolytes that play crucial role in osmoregulation are proline, glycine-betaine, polyamines, and sugars. These compounds stabilize the osmotic differences between surroundings of cell and the cytosol. Besides, they also protect the plant cells from oxidative stress by inhibiting the production of harmful ROS like hydroxyl ions, superoxide ions, hydrogen peroxide, and other free radicals." (from the above link)

Polyamines in aging and disease.

Abstract
Polyamines are polycations that interact with negatively charged molecules such as DNA, RNA and proteins. They play multiple roles in cell growth, survival and proliferation. Changes in polyamine levels have been associated with aging and diseases. Their levels decline continuously with age and polyamine (spermidine or high-polyamine diet) supplementation increases life span in model organisms. Polyamines have also been involved in stress resistance. On the other hand, polyamines are increased in cancer cells and are a target for potential chemotherapeutic agents. In this review, we bring together these various results and draw a picture of the state of our knowledge on the roles of polyamines in aging, stress and diseases.

INTRODUCTION
Polyamines have been known for a long-time as the first one, spermine, was discovered over 330 years ago by microscopic observation of human semen [reviewed in 1]. They have since been found in all eukaryotes and most prokaryotes. Polyamines are polycations (Figure (Figure1)1) and thus one of their main features is to interact with negatively charged molecules, such as DNA, RNA or proteins. Given their promiscuity in binding other molecules, they are involved in many functions, mostly linked with cell growth, survival and proliferation. Three polyamines, putrescine, spermidine and spermine, are part of the very tightly regulated polyamine metabolic pathway. Polyamines are the subject of intensive research in order to elucidate their functions and involvement in physiology. Polyamines are important players in plant growth, stress and disease resistance [2], but they are also involved in diseases [3], for example Alzheimer's or infectious diseases. The main research area for the involvement of polyamines in diseases is cancer, as high levels of polyamines are observed in cancer cells [3]. More recently, we have shown a causative role for polyamines in longevity [4].

[these science nerds love their wordplay...]

Interesting, Travis was also criticizing polyamines if I'm not mistaken. From the article of the first post, there are "good" and "bad" osmolytes. Or maybe it is observed in cancer cells but it's not a cause, just a consequence

 

[LLight]

Can it be as simple as this ?

I'm a bit skeptic, I don't know if this is easy to test but we should to see if this is functionning.

And if we have to repeat the procedure a few times to reach high purity, it could be tedious!

 

[LLight]

I am not sure but I also think that boron could be related to dehydration/water homeostasis somehow.

Indeed, boron could have a role in plants' response to drought (Boron delays dehydration and stimulates root growth in Eucalyptus urophylla (Blake, S.T.) under osmotic stress).

Moreover, boron seems to stimulate the immune system similarly to dehydration in mammals:

Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages. - PubMed - NCBI

"Boron further stimulated the
secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. [...] The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases"​

Regulation of Inflammatory Functions of Macrophages and T Lymphocytes by NFAT5

"NFAT5 is quite unique among Rel-family factors as it can be activated by hyperosmotic stress caused by elevated concentrations of extracellular sodium ions."​

"In parallel to its enhancing pro-inflammatory macrophage functions, high salt opposes M2 macrophage polarization, as shown by the decrease in M2 markers"​

"Macrophages lacking NFAT5 exhibited a more severe impairment in the expression of diverse TLR-induced gene products such as iNOS, TNFα, IL-6, and IL-12 when they were stimulated with low doses of TLR ligands, which suggests a relevant role in early stages of infection when pathogen burden may be relatively moderate. Correspondingly, NFAT5-null mice showed reduced ability to clear Leishmania majorinfections in vivo, and their skin macrophages exhibited poor induction of iNOS, which is needed to control parasite burden".​

Also, NFAT5 seems to be implicated in rheumatoid arthritis:

Regulation of Inflammatory Functions of Macrophages and T Lymphocytes by NFAT5

"The role of NFAT5 as promoter of proinflammatory macrophage function has been further documented in mouse models (21) as well as in studies in human rheumatoid arthritis (RA) patients [...] Another work using the same NFAT5-haploinsufficient mouse model showed that these animals developed less severe arthritis than wild-type ones in an experimental model of collagen-induced arthritis".​

While boron seems to be able to help treat RA:

The adjuvant use of calcium fructoborate and borax with etanercept in patients with rheumatoid arthritis: Pilot study

"The use of boron, as adjuvant with etanercept, has potentiated therapeutic outcomes in RA patients, and may be a new strategy to improve treatment, and avoid the problems associated with biologics utilized in RA treatment."​

 

[Inaut]

 

[LLight]

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter:

Here, we identified a novel function of TonEBP as a potent suppressor of HO-1 expression both in human and murine macrophages.

--------------------

https://www.sciencedirect.com/science/article/pii/S0092867414006710:

Here, we show that HO-1 drives insulin resistance in mouse and man. In the absence of macrophage HO-1 animals fail to develop metaflammation and key hallmarks of metabolic disease. The findings redefine the current view of HO-1, have substantial implications for the stratification of healthy and unhealthy obesity, and open the door for HO-1 inhibitors as a new therapeutic strategy for obesity and diabetes.

So NFAT5/TonEBP (theoretically activated by dehydration) reduces HO-1 in macrophages, which could stop metabolic diseases development.

 

[LLight]

Osmolality controls the expression of cathelicidin antimicrobial peptide in human macrophages:

An imbalance between extracellular and intracellular fluid osmolality causes osmotic stress and affects cellular homeostasis. Recent research suggests that osmotic stress is also associated with various innate and adaptive immune responses. Here we present the surprising finding that osmolality tightly controls the expression of cathelicidin antimicrobial peptide (CAMP) in human macrophages. CAMP expression is strongly upregulated under hyperosmotic conditions and downregulated under hypoosmotic conditions. We also provide evidence that this osmolality-mediated antimicrobial response is dependent on nuclear factor of activated T-cells 5 (NFAT5) and mitogen-activated protein kinase (MAPK) p38. Finally, Toll-like receptor (TLR) activation inhibits osmolality-mediated expression of CAMP in human macrophages, suggesting that this osmolality-dependent regulation of CAMP is more relevant under homeostatic conditions, rather than during acute infections. This study expands our knowledge of the regulation of human antimicrobial peptides and highlights osmolality as an important and independent factor shaping host innate immune homeostasis.

NFAT5/TonEBP makes the immune system produce antimicrobial substance, CAMP or also called LL-37.

LL-37 is able to bind to LPS: Evaluation of the ability of LL-37 to neutralise LPS in vitro and ex vivo. - PubMed - NCBI

Human cathelicidin LL-37 is a cationic antimicrobial peptide (AMP) which possesses a variety of activities including the ability to neutralise endotoxin.

 

[LLight]

HIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting(https://www.tandfonline.com/doi/full/10.1080/15548627.2019.1596483)

In this work, we demonstrate that HS (High salt) induces autophagy, favors autolysosomal formation and targeting of E. coli to acidic lysosomal compartments which, ultimately, results in enhanced intracellular bacterial degradation.

[...]

Several bacteria, viruses and parasites developed strategies to evade autophagy-mediated immune surveillance. It is conceivable that local increases in extracellular Na+ might help overcome pathogen-triggered strategies to circumvent autophagy-mediated degradation. Moreover, Na+-increased autophagy might facilitate clearing infected and inflamed tissues from dead cells and thereby curtail inflammatory responses upon sterile tissue damage as well.

[...]

However, in contrast to HS-treated cells, AKT and MTOR inhibition under NS conditions was not linked with enhanced targeting to autolysosomes. This strongly suggests that increases in autophagy and autolysosome formation are not sufficient but that in addition HS-triggered subcellular targeting of intracellular E. coli to autolysosomes is critically required for HS-enhanced antimicrobial MΦ activity.

In this study, we provide evidence that NFAT5 coordinates targeting of E. coli to autolysosomes under HS-conditions. In contrast to a recent study, but in line with findings demonstrating that NFAT5 does not affect expression of genes involved in autophagy such as Becn1 under normal salt conditions, our findings suggest that the osmoprotective transcription factor NFAT5 is not directly involved in autophagy induction. Our data demonstrate that NFAT5 is rather involved in regulation of subcellular trafficking, including formation of autolysosomes, and targeting of E. coli to these acidic compartments.