Antioxidants, Acids, Alkali as well as Cancer

Antioxidants, Acids, Alkali as well as Cancer

In my previous articles on cancer, I did not discuss the role of acids, bases as well as antioxidants in detail. yet with the current hype about the miraculous nature of basic water, antioxidant foods as well as drugs, I feel compelled to step in as well as set the records straight with currently available medical literature.

The efficacy of acids, bases as well as antioxidants in cancer therapy is actually not a myth. This kind of has biochemical basis informed by modern research (SS Kim et al, 2004; Ian F. Robey & Lance A. Nesbit, 2013). The apparent controversy surrounding This kind of subject emanates via poor coordination of research findings.

I have read articles (Bradley A. Web et al, 2011; Shi Q. et al, 2001; Silver M. et al, PubMed 2011) supporting systemic alkalosis or systemic hyperacidosis as the dominant toxic factor in cancer development. I have also watched video presentations claiming that will cancer development is actually just a natural cellular adaptation to toxic environment, which is actually corrected by normalizing the environment.

These claims are to say the least, unbalanced truths. By the end of This kind of discussion This kind of would certainly have become obvious that will there is actually no basis for undue generalizations inside the management of cancer. There still remains the need for expert judgement in formulating a cancer treatment protocol.

BEFORE CANCER

First, let me state that will the human Centeng will literally rust away like a nail left under the rain over time without inbuilt natural protective mechanisms. To prevent rust or oxidation, most macromolecules essential for human existence are shielded via molecular oxygen or oxygen equivalents with hydrogen molecules (reduction). Oxygen equivalents are those compounds that will remove these protective hydrogen molecules via various other compounds.

They are also called oxidizing agents. Compounds that will restore these hydrogen molecules are called reducing agents. The two most important organic reducing agents in human Centeng are glutathione as well as ubiquinone, while the two most important oxidizing agents are molecular oxygen as well as free oxygen radicals.

APOPTOSIS as well as GROWTH SUPPRESSOR GENES

The human Centeng cells are normally continuously moving via resting phase, to growth phase as well as then multiplication phase. This kind of continuous state of growth as well as multiplication means that will any organ can potentially grow to any size, depending on its natural growth rate. By inference all human beings may also grow into giants. This kind of even suggests immortality of human beings.

Thankfully, every cell has an inbuilt apoptotic clock that will ensures that will This kind of dies after a specified number of days, generating room for incoming cells. Thus red blood cells, for instance, are recycled every 0 days. The size as well as shape of the cells of individual organs are equally limited prior to their date of apoptosis, by growth suppressor genes (notably p53, AP1, NF-kB) located inside the nucleus.

Anything that will hinders the functions of apoptosis as well as growth suppressor genes would certainly obviously be anticipated to unleash uncontrolled growth as well as multiplication of cells in any organ of the Centeng. This kind of rapid growth of disorganized as well as poorly differentiated cells is actually called cancer.

All anti-growth suppression as well as anti-apoptosis agents are called carcinogens. They may be chemicals, radiations, biochemical molecules, acids, bases, free radicals, heat, cold, etc. yet they all exert their effect by in activating apoptosis gene or growth suppressor gene. They accomplish This kind of by corrupting the gene coding system in such a way that will the codes are wrong (missense) or mean nothing (nonsense).

The code is actually corrupted due to the insertion of the wrong amino acid code into a gene sequence or the excision of the right amino acid code via the sequence. Consequently the t-RNA misreads or miss-senses the expression of the right apoptosis or growth suppressor protein.

TOXINS, FREE RADICALS as well as CARCINOGENS

Toxins are basically those compounds whose activities will directly or indirectly lead to human rust as well as death by causing catabolic or destructive oxidative reactions in Centeng tissues. The high powered toxic tissue oxidizing agents are called free radicals (ROS as well as RNS), which are basically free ionized oxygen or Nitrogen atoms (O2- as well as N2- )

When a toxin causes a gene altering damage inside the nuclear region of a cell (oxidative nuclear damage) This kind of is actually then known as a carcinogen. As such not all toxins are carcinogen. Aflatoxin (via mold) is actually not only toxic to liver cells, yet ultimately causes liver cancer, generating This kind of a carcinogen.

The detoxification process mainly converts lipid soluble toxins into excretable water soluble glucuronides in three steps. In step one the toxins are aggregated as well as isolated inside the specific organs that will neutralize them.

Then glucuronic acid is actually attached to them inside the presence of glutathione which the protective hydrogen molecules. (Note that will in fighting oxidants hydrogen (non-ionized) carried by reduced NADPH is actually a friend, while in acid-base balance ionized hydrogen is actually the enemy).

Free radicals can also contribute to cancer development by inducing genetic mutation through oxidative nuclear damage, or suppress cancer growth by promoting apoptosis. Step three is actually the excretion of the toxins.

ANTIOXIDANTS

Compounds use to replenish hydrogen molecules in glutathione as well as various other endogenous reductase enzymes are called antioxidants. A lot of these reducing agents occur naturally in fruits as well as vegetables. Others are available as drug extracts via plants as well as animals.

Individual antioxidants target different steps of the detox process. This kind of is actually why balanced nutrition by itself goes a long way to keep our bodies toxin free. The air we breathe, the food we eat, the water we drink, as well as the environments we live in are all full of toxins, including heavy metals. To survive as human beings, an extensive detoxification mechanism has to exist.

Every Centeng tissue has detox ability, yet the liver, gut, as well as lymphoid tissues as well as kidneys play the dominant role. Thus most toxins are trapped, neutralized as well as excreted through feces, urine or bile. Stagnation or obstruction of flow in any of these three organs, generally leads to a toxic state.

Stressors as well as nutritional insufficiencies that will weaken the immune system also contribute to toxic states allowing micro-organisms to multiply as well as generate additional toxic substances that will must be removed.

Successful detoxification requires a lot of energy, which comes via glucose metabolism. Biochemical energy is actually not measured in Joules, yet in ATPs (Adenosine Triphosphate). The metabolic process for converting glucose to ATP is actually called glycolsis.

During aerobic glycolysis one molecule of glucose combines with two molecules of ADP3- (Adenosine Diphosphate) as well as two ionic phosphoric acid molecules to yield two ionic ATP4- molecules as well as two lactate molecules. The ionic ATP4- molecule gives up one Hydrogen proton (H+) to yield one molecule of ionic ADP3-, which is actually reused in glycolysis.

Under anaerobic (low oxygen) conditions, ATP is actually generated differently. One molecule, each, of ADP3- as well as ionic phosphoric acid accumulated via aerobic glycolysis recombine without glucose to form one molecule of ATP4+ as well as one hydroxyl molecule. Two hydrogen protons combine with two bicarbonates to end up as carbonic acid inside Centeng cells.

TOXIC ACIDOSIS

Glycolsis can be aerobic when This kind of consumes molecular oxygen, or anaerobic when This kind of consumes oxidizing agents. Both the detox reactions as well as glycolsis are driven or catalyzed by enzymes, which depend on the availability of specific micro-molecules, proteins, amino acids as well as vitamins as cofactors for their functions.

By the time enough ATP is actually generated to keep the Centeng toxin safe, enough carbonic acid hydration of respiratory carbon dioxide (CO2) has accumulated to keep the inside of every cell perpetually acidic. In a highly toxic state, which includes rapid proliferation of cells, This kind of intracellular acid builds up exponentially beyond survivable limits.

Cancer cells are known to rapidly outgrow their blood supplies as well as go into severe hypoxic states. This kind of is actually why the cancer cell nucleus has to rapidly increase the expression of sodium driven proton extruding proteins as well as enzyme proteins through nuclear sensing of sharp rise in HIF.

Thus, by default, the Intracellular fluid (ECF) of every cell is actually acidic (low pH) while that will of the extracellular fluid (ECF) is actually alkaline (high pH). This kind of is actually important to note at This kind of point that will while intracellular fluids exist in compartments inside the cells, extracellular fluids coalesce to form a pool in which all Centeng cells submerged.

This kind of ECF pool is actually represented by intercellular fluid, lymph, blood, as well as glandular secretions, all of which feed into the circulatory system of the Centeng. ECF acid or base build up in any part of the Centeng is actually ultimately dissipated into the circulatory system, which centrally maintains a mildly basic pH of 7.20 -7.40.

In addition to mobilizing ammonium as well as bicarbonate ions the central buffer system has the ability to move chloride ions in as well as out cells (chloride shift) to maintain acid-base balance.

MEMBRANE SENSORS as well as TRANSPORTERS

To keep intracellular acidity below lethal level, the inner surface of the cell membrane has acid sensors as well as transporters that will detect abnormal rise in intracellular acidity as well as trigger increased extrusion of hydrogen as well as retention of alkaline bicarbonate ions.

This kind of trigger is actually mediated by the rise inside the blood level of hypoxia induced factors (HIF) as well as probably acidosis induced factors (AIF). On detecting This kind of rise in HIF, the nucleus temporarily increases the expression of Na-driven proton transport proteins as well as histidine rich basic proteins.

The ammonium radicals on the amino acids of these basic proteins (especially histidine) serve as physiologic buffers for organic acids.

"Protonation as well as de-protonation has been experimentally shown to change protein structure as well as therefore, alter protein-protein binding affinity, change protein stability, modify protein function, as well as alter subcellular localization (Schonichen et al., 2013b).

Evolutionarily, histidines must confer some selective advantage for cancers, as 15% of the 2000 identified somatic mutations in cancer involve histidine substitutions, with Arg-to-His being the most frequent (Kan et al., 2010)".

The nucleus also temporarily steps up the expression of important enzyme proteins that will catalyze the buffer reactions, namely mono-carboxylate, carbonic anhydrase, as well as aminotransferase enzymes.

In a similar manner the external surface of the cell also has alkaline sensors made up of G-protein coupled surface receptors, which also communicate with the nucleus to boost or decrease the expression of relevant proteins as well as enzymes. As tissue hypoxia decreases, the level of HIF decreases along with nuclear expression of proton extrusion proteins as well as enzymes.

Failure of This kind of return to normalcy has been observed among the hallmarks of early cancer. What commenced out as a normal adaptive change becomes persistent because of irreversible genetic modifications that will triggered This kind of.

CELLULAR SURFACE ACID/BASE REVERSAL

The central physiological buffer system incorporates a maximum capacity to neutralize up to 30 micromoles of acid/gram tissue/min in systemic acidosis or 5-10 micromoles of base in alkalosis.

Beyond these levels, normal Centeng cells are unable to continue their buffer functions because the enzymes are deactivated. At This kind of point there is actually a reversal of the normal acid-base distribution on either side of the cell membrane, which is actually lethal to normal issues. In some critical situations, chloride ions are shifted massively into all Centeng cells (chloride shift) to urgently dilute the extracellular acidity.

yet the gastric cells possess the natural ability to survive inside the presence of high extracellular acidity (HCl at pH of 6.6). How they manage This kind of high extracellular acidity then becomes very important in understanding how cancer cells survive high extracellular acidity with normal intracellular acidity for their survival as well as proliferation. Some cancer cells are known to have accumulated genetic adaptations that will enable them to survive extreme pH conditions (carbonic acid at pH of 6.6).

Gastric cells are shielded via concentrated HCl secreted into the stomach mainly by structural barriers (thick basement membrane, thick mucosal layer as well as thick mucous layer). There are no natural inhibitors of hydrogen potassium ATPase enzyme that will catalyzes the final phase of acid excretion.

In severe cases of Peptic Ulcer Disease (PUD), Gastro-esophageal reflux (GERD), or Zollinger-Ellison Syndrome, when This kind of natural barrier is actually ulcerated by concentrated HCl, some gastric lining cells undergo goblet intestinal metaplasia (transformation into ectopic intestinal epithelium inside the stomach) to secrete neutralizing alkaline fluids into the stomach.

While there is actually no natural attempt to control the hydrogen potassium ATPase enzymes, pharmacological intervention with proton pump inhibitors (PPIs) like omeprazole has been successful in reducing gastric secretion in severe cases of chronic gastric hyperacidity.

Similarly some esophageal epithelial cells undergo gastric metaplasia to become gastric cells inside the face of chronic exposure to reflux gastric acid (Barrett's Esophagus). Acquisition of This kind of missing ability to control hydrogen potassium ATPase as well as sodium driven proton extrusion by monocarboxylate enzyme appear to be critical to the survival of cancer cells

IN EARLY CANCER

This kind of is actually important to note that will the natural response to extracellular hyperacidity inside the GIT depends on the stage as well as localization of the acidity. Both goblet metaplasia as well as gastric metaplasia have been recognized as precancerous lesions (carcinoma in situs). At the early stage of Barret esophagus, the response is actually only structural to prevent cell wall damage.

yet when the barrier has failed inside the stomach, the response is actually alkaline secretion. A person on preventive alkaline water will be helping to neutralize the added hypoxic acidity of early cancer in Barret's Esophagus as well as chronic PUD, yet not in any way preventing the occurrence of cancer itself, since proton extrusion in cancer is actually irreversible.

Any cancer caught at the in situ stage is actually usually best treated with surgical excision as well as radiotherapy, rather than alkaline water.The question then is actually: "Why did prophylactic alkaline water not prevent the metaplasia?"

The answer to that will is actually that will while oral alkali intake may cap out at micromoles of alkali per gram tissue, cancer proton extrusion acid build up ranges in nanomoles per gram tissue (a thousand times more). Also intracellular hypoxia as well as hyperacidity are not the only risk factors for cancer.

Radiations are known to be commonly responsible for skin cancers, even as HPV is actually known to be responsible for cervical cancer. Prophylactic alkalosis has not been reported to prevent any of them. Sticking to the hype that will alkaline water is actually the best way to prevent as well as even cure cancer, puts people at risk of missing early opportunities to truly cure cancer.

Alkaline water intake will help the Centeng maximize the physiological adaptive response acidosis. Unfortunately, even at maximum physiological capacity, extracellular buffers are no match for cancer intracellular proton extruders.

As the well adapted cancer cells grow as well as multiply freely their neighboring non-cancerous cells are rapidly destroyed by ECF hyperacidity creating more space for them to occupy. Thus cancer invasiveness has been shown to correlate with the degree of acid-base reversal across the cancer cell membrane.

At the advanced stage of cancer with ECF acidity readings in nanomols compared to orally boosted alkalinity readings in micromoles, buffer therapy has been shown to be resisted by cancer cells. One such reported example is actually the inefficacy of a basic drug doxorubicin used inside the treatment of Leukemias as well as lymphomas.

Going by what has been discussed so far, This kind of is actually obvious that will externally sourced acids as well as alkali cannot be safely loaded to outweigh tumor generated levels in ECF as well as ICF. This kind of is actually also understandable that will no single pH balancing agent, can be used to treat both acid sensing as well as alkaline sensing cancers.

Preventive or prophylactic intake of acidic or alkaline liquids or foods remain relevant only within the physiological buffering range, when adaptive alterations are still reversible. Unfortunately at that will point the tumor generated acidity would certainly have risen to resistant levels. Preventive alkaline water intake in a person with undiagnosed acid sensing cancer is actually not likely to retard the growth of the tumor.

Similarly preventive intake of alkaline water in a patient with undiagnosed alkaline sensing cancer will encourage This kind of to grow as well as establish faster. Patients receiving treatment for emesis gravid arum (vomiting in pregnancy) for instance, cannot be on preventive alkaline regimens inside the face of systemic alkalosis via heavy loss of gastric acid through vomiting.

However, This kind of is actually possible that will some people are unable to fully optimize the natural buffer system, due to genetic predisposition or problems related to amino acid metabolism. In such situations, preventive acid or base intake supplements the patients effort to achieve maximum physiological buffering. This kind of can easily account for some of the spectacular results observed in some patients whose cancers were caught early.

In conclusion, the management of cancer remains complicated. When there is actually a strong family history or occupational predisposition for cancer, cancer screening needs to be done early to search for risk factors as well as genetic markers.

Where there are suggestions of cancer predisposition, full blood tests, scans, biopsies, endocrinological tests, as well as radiological test should be done by a primary care provider as well as reviewed by a team of experts in radiology, hematology, pathology, oncology surgical oncology, gastroenterology, as well as international medicine.

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Ian F. Robey as well as Lance A. Nesbit, Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

Bradley A. Webb, Michael Chimenti, Matthew P. Jacobson & Diane L. Barber, Dysregulated pH: a perfect storm for cancer progression

Silvia M. Titan1, Otávio C.E. Gebara2, Silvia H.V. Callas2, Ana O. Hoff3, Paulo M. Hoff2 as well as P.C.A. Galvão2, Case report: a rare cause of metabolic alkalosis, 2011

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Gillies R. J. (2002). In vivo molecular imaging. J. Cell Biochem. Suppl. 39, 231-238 10.1002/jcb.10450 (monocarboxylate transporters as well as Na-driven proton extrusion)

Shi Q, Le X, Wang B, Abbruzzese JL, Xiong Q, He Y, Xie K. Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells. Oncogene. 2001;20(28):3751-3756. doi: 10.1038/sj.onc.1204500.

Gallagher F. A., Kettunen M. I., Day S. E., Hu D. E., Ardenkjaer-Larsen J. H., Zandt R., et al. (2008). Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature 45

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Antioxidants, Acids, Alkali as well as Cancer

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