Thomas Seyfried, Ph.D., professor of biology at Boston School, is a number one skilled and researcher in the area of most cancers metabolism and dietary ketosis. His e-book, “Cancer as a Metabolic Disease: On the Origin, Management and Prevention of Cancer” is a foundational textbook on this matter, and in August 2016, he acquired the Mercola.com Recreation Changer Award for his work.
Right here, we talk about the mechanisms of most cancers and the affect of mitochondrial perform, which plays an important position in the improvement and remedy of this disease. His landmark most cancers concept is obtainable as a free PDF
Many of his views at the moment are encapsulated in his most recent paper,1 “Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis,” revealed on-line December 27, 2018. He’s also revealed a quantity of different papers2,3,4 on the metabolic underpinnings of cancer.
“The paper … is a review and hypothesis paper identifying the missing link in Otto Warburg’s central theory,” Seyfried explains. “[Warburg] outlined the origin of cancer very precisely back in the 1920s, ’30s, ’40s, and ’50s in his work in Germany. Principally, he argued and offered knowledge displaying that each one cancer cells, regardless of tissue origin, have been fermenters. They fermented lactic acid from glucose as a substrate.
Even in the presence of oxygen, these cells have been fermenting. This is clearly a defect in oxidative phosphorylation. The issue is that for many years, individuals stated Warburg was improper — mainly because we see rather a lot of most cancers cells take up oxygen and make adenosine triphosphate (ATP) from inside the mitochondria … Individuals began to query, ‘If most cancers cells have regular respiration, why would they need to use glucose as a fermentable gasoline?’
The entire concept turned distorted … The cancer cells merely select to ferment fairly than respire. Now, of course, in the event you look beneath the electron microscope at the majority of cancers, you’ll see that the mitochondria are defective in a quantity of alternative ways. Their buildings are irregular. The numbers are abnormal. There are various abnormalities of mitochondria seen immediately underneath electron microscopy. Clearly, Warburg was not fallacious.”
Before we go delve into the meat of how cancer truly occurs it will be good to evaluate a diagnostic technique that almost all of us are provided when confronted with a cancer analysis. It is important to know that this will not be your greatest technique and that for a lot of it will be clever to keep away from the biopsy.
Seyfried warns towards doing biopsies, as this process may actually trigger most cancers to unfold. A tumor is principally a gaggle of proliferating cells in a specific half of your physique. For functions of analysis, a small biopsy sample will typically be taken to determine whether the tumor is benign or malignant.
The issue is that whenever you stab into the cancer microenvironment to remove an element of the tissue, it creates a wound in that microenvironment that in flip elicits the invasion by macrophages and other immune cells.
If you have already got an acidic microenvironment, you run the danger of inflicting a fusion hybridization event in that microenvironment between your macrophages and most cancers stem cells (as mentioned under). This could flip a probably benign state of affairs into a malignant one, and if the tumor is malignant, stabbing into it might make a nasty state of affairs worse.
“The question is, what is the worth of doing a biopsy in the first place? We take biopsies of breast tissue to get a genomic readout of the totally different sorts of mutations that could be in the cells. Now, if most cancers is just not a genetic disease and the mutations are largely irrelevant, then it is senseless to try this in the first place. If the tumor is benign, why would you need to stab it? If the tumor is malignant, why would you ever need to stab it?
I got here to this view by reading so many articles in the literature based mostly on brain cancer, breast most cancers, colon most cancers, liver cancer displaying how needle biopsies have led to the dissemination of these tumor cells, placing these individuals at risk for metastatic cancer and dying,” Seyfried says.
In metabolic remedy, you wouldn’t touch the tumor; you wouldn’t disturb the microenvironment. By leaving it alone, you permit the tumor to shrink and go away.
“Once you begin to take a look at this as a biological drawback, many of the issues that we do in most cancers make no sense. We’ve, in mind most cancers, individuals say, ‘You’ve a really low-grade tumor. Let’s go in and get it out.’ What happens is you go in and get it out, and then the following yr it turns right into a glioblastoma.
How did that happen? Nicely, you disturbed the microenvironment. You allowed these cells which might be marginally aggressive to turn out to be extremely aggressive. Then you definitely lead to the demise of the affected person,” Seyfried says.
“That occurs considerably as a result of it’s referred to as secondary glioblastoma arising from a therapeutic try and handle a low-grade tumor. The same thing can happen with all these totally different organs. You stab breast tumors, you stab colon tumors, you run the danger of spreading the cells …
My argument is the following: If the affected person has a lump, whether it’s in the breast, in the colon, lung or wherever or a lesion of some type, that ought to be the cue to do metabolic remedy.
Do metabolic remedy first. In all probability, it should shrink down and turn into less aggressive. Then the choice becomes, ‘Should we debulk utterly somewhat than performing some type of a biopsy?’ We need to scale back the danger, as a result of if we will catch the entire tumor utterly, then we don’t run the danger of spreading it …
In our procedure, you deliver the body back into a very excessive state of metabolic stability, and you then strategically go and degrade the tumors slowly without harming the relaxation of the body.
Radiation, chemo and the methods that we’re utilizing right now don’t do this. They’re based mostly on the gene principle of cancer that genetic mutations are inflicting the cell cycle to grow out of management. Properly, this isn’t the case. Once more, so much of these toxic procedures must be rethought, reanalyzed in my thoughts.”
- 1 Fixing the Warburg Concept’s Dilemma
- 2 Warburg’s Cancer Concept Proves Right
- 3 Genetic Mutations Are Not the Trigger of Cancer
- 4 Why and How Cancer Spreads
- 5 Metastatic Cancer Is a Hybrid Cell Combination
- 6 Typical Cancer Remedies Are Unnecessarily Deadly
- 7 A Strategic Strategy to Killing Cancer Cells
- 8 The Press-Pulse Strategy
Fixing the Warburg Concept’s Dilemma
In biology, construction determines perform. This is an evolutionarily conserved idea. So, how can mitochondria be structurally irregular in tissue, yet have regular respiration? As Seyfried notes, this doesn’t make sense. Confusion has arisen in half because many research cancer in culture, and “make profound statements and comments regarding what happens in culture,” Seyfried says.
“For those who take a look at most cancers cells in culture, many of them to take in oxygen and make ATP, but at the similar time, they’re fermenting. This was the conundrum. They referred to as it the Warburg Impact. They’re fermenting, however many individuals at the similar time thought their respiration was normal.
This was the major drawback with Warburg’s principle. But Warburg clearly stated in his papers [that] it’s not the proven fact that they take in oxygen; it’s how a lot ATP they will generate from oxidative phosphorylation, which is the regular respiratory capability of the mitochondria.”
As defined by Seyfried, should you measure ATP and take a look at oxygen consumption in tumor cells, it appears they’re making ATP and taking in oxygen, subsequently, their respiration is assumed to be normal. Nevertheless, whenever you take a look at the tissues in cancer patients, the mitochondria are abnormal.
“What I and Dr. Christos Chinopoulos from Semmelweis University in Budapest, Hungary, who is the world-leading expert on mitochondrial physiology and biochemistry … realized [was] that the mitochondria of tumor cells are actually fermenting amino acids, glutamine in particular. They’re not respiring. They’re fermenting an alternative fuel, which is glutamine,” Seyfried says.
Warburg’s Cancer Concept Proves Right
With this understanding, Warburg’s concept might be confirmed right — most cancers arises from injury to the mitochondria’s capability to supply power by means of respiration in their electron transport chain.
The compensatory fermentation includes not only lactic acid fermentation but in addition succinic acid fermentation utilizing glutamine as a fermentable gasoline. It’s been recognized for decades that glutamine is the foremost gasoline for a lot of totally different sorts of cancers, but most individuals thought it was being respired, not fermented.
Seyfried and Chinopoulos’ discovery confirms that cancer cells, in reality, have damaged respiration, and to survive, the most cancers cells should use fermentation. The 2 most out there fermentable fuels in most cancers microenvironment are glucose and glutamine. Therefore, concentrating on glucose and glutamine is an important element of most cancers remedy.
With out glucose and glutamine, the cancer cells will starve, as they can’t use ketones. The only strategy to most cancers then is to convey sufferers into therapeutic ketosis and then strategically goal the availability of glucose and glutamine.
“Basically, what we’re saying [is] that mitochondrial substrate-level phosphorylation is a non-oxidative metabolism mechanism inside the mitochondria that would generate significant amounts of energy without oxidative phosphorylation,” Seyfried says.
Genetic Mutations Are Not the Trigger of Cancer
Based on Seyfried, mitochondrial dysfunction is at the heart of almost every sort of most cancers. Unfortunately, few oncologists have this understanding and many nonetheless consider most cancers is the end result of genetic defects. Nevertheless, nuclear switch experiments clearly present most cancers can’t be a genetic illness.
“There’s been no rational scientific argument that I have seen, to discredit the multitude of evidence showing that the [genetic] mutations are not the drivers but the effects [of mitochondrial dysfunction],” Seyfried says.
“As a matter of reality, there’s new info now where individuals are finding so-called genetic drivers of most cancers expressed and current in normal cells, regular pores and skin and additionally esophagus … That is one other [issue] — the way you get these so-called driver mutations in normal tissues. We’re additionally discovering some cancers that haven’t any mutations, but, they’re fermenting and growing out of management.
There are a selection of new observations coming out that problem the concept that most cancers is a genetic illness. And once you understand that it’s not a genetic disease, then you need to significantly query the majority of therapies getting used to handle the illness. This [helps] clarify [why] we’ve got 1,600 individuals a day dying from most cancers in the United States.
Why do we’ve got such an epidemic of struggling and dying when we have now been learning this disease for decades? Nicely, should you take a look at the large quantities of scientific papers being written on cancer, you’ll typically discover that they’re structured around gene defects.
What I’m saying is that if most cancers shouldn’t be a genetic disease and the mutations are downstream epiphenomena, why would the area continue to give attention to things which might be principally irrelevant to the nature of the disease? What I’m saying could be very devastating, as a result of I’m telling the majority of the individuals in the area that they’re principally wasting their time …
I feel we will drop the dying fee of this disease by about 50% in 10 years if cancer is handled as a mitochondrial metabolic illness, concentrating on fermentable fuels relatively than utilizing toxic therapies which might be targeted on downstream results.
Radiation is designed to stop DNA replication. DNA replication requires power. When you pull the plug on their fermentable fuels, they’re not going to be able to replicate anyway … All of the issues that we’re doing to deal with most cancers is principally approaching the illness from a misunderstanding of the biology …
We know viruses may cause most cancers. We all know radiation causes most cancers. We know carcinogens cause cancer. We all know intermittent hypoxia causes cancer. We know systemic inflammation causes cancer. We know simply getting older places you at risk for extra cancer.
We all know there are inherited mutations in the genome that can cause cancer. But how are all this stuff linked by way of a standard pathophysiological mechanism? The widespread pathophysiological mechanism is broken by means of the construction and perform of the mitochondria.”
Each one of the issues … including inherited mutations, injury the respiration of a specific population of cells in a tissue. You take a look at the breast most cancers gene (BRCA 1), for instance. Individuals will say, ‘Cancer have to be a genetic illness since you inherit a mutation that causes the illness.’
You solely get the disease if that mutation disrupts the perform of the mitochondria. Fifty % of ladies who carry the mutation never get cancer or breast cancer because the mutation, for some purpose, did not injury the mitochondria in that individual.”
So, to summarize, the true origin of most cancers is injury to the respiratory perform of the mitochondria, triggering compensatory fermentation, which is run by oncogenes. Oncogenes play a task by facilitating the entry of glucose and glutamine into the cell to exchange oxidative phosphorylation.
Why and How Cancer Spreads
Seyfried also has a really totally different view on the biology of metastasis (the unfold of most cancers). He explains:
“We’ve looked at most cancers stem cells in a quantity of our preclinical fashions … These guys develop like crazy in place. The tumor just keeps expanding, nevertheless it doesn’t spread. It doesn’t unfold into the bloodstream or metastasize to varied organs.
We found a very uncommon most cancers 20 years ago. It took us 10 to 15 years to determine what it was. You’ll be able to put a couple of of these cells anyplace in the mouse’s body and inside three to four weeks, this mouse is full of metastatic most cancers. It made the cover of the International Journal of Cancer, once we revealed this again in 2008, but we had worked on the drawback for years.
We couldn’t work out what it was that made these cells so incredibly metastatic. We came upon that when we recognized the biology of the cell, it turned out [it has] many traits in widespread with the macrophage, which is one of the strongest immune cells in our physique.
We stated, ‘Wow. Is that this distinctive only to this type of cell or do metastatic cancers in humans also categorical characteristics of macrophages?’ We appeared and we found that nearly each main cancer that metastasizes has traits of macrophages. Then we stated, ‘Properly, how might this probably happen? Is it coming from the macrophage?’
A quantity of scientists … have all clearly proven that there is some fusion hybridization character happening. In different phrases, macrophages, our wound-healing cells, they arrive right into a microenvironment the place you may discover many proliferating neoplastic stem cells, but they don’t have the capacity to metastasize.
It’s only when the macrophages fuse with these stem cells that you’ve a dysregulated power metabolism coming in this hybrid cell. This hybrid cell now has traits of each stem cells and macrophages.
The stem cell isn’t genetically outfitted to enter and exit tissue. The macrophage, as a traditional cell of your physique, is genetically outfitted to enter and exit tissue and reside in the bloodstream. They’re very strongly immunosuppressive. These are all traits of metastatic most cancers.”
Metastatic Cancer Is a Hybrid Cell Combination
In line with Seyfried, metastatic cancer cells are primarily a hybrid, a mixture of an immune system cell and a dysregulated stem cell, the latter of which might originate from a disorganized epithelial cell or something comparable. Briefly, it’s a hybrid cell with macrophage traits.
Macrophages are essential for wound healing and half of our main defense system towards bacterial infections. They reside both in the bloodstream and in tissues and can go anyplace in the body. When an damage or infection happens, they immediately transfer in to protect the tissue.
“The metastatic cancer cell has many of those same properties,” Seyfried explains, “But the energy and the function of the cell is completely dysregulated, so it proliferates like crazy but has the capacity to move and spread through the body, so it’s a corrupted macrophage. We call it a rogue macrophage.”
Like macrophages, metastatic cancer cells also can survive in hypoxic environments, which is why most angiogenic therapies are ineffective towards metastatic most cancers.
So, what do these metastatic hybrid cells have to survive? Both macrophages and immune cells are major glutamine shoppers, and in line with Seyfried, you possibly can successfully kill metastatic cells by concentrating on glutamine.
Typical Cancer Remedies Are Unnecessarily Deadly
Nevertheless, it have to be achieved in such a method so as to not harm the regular macrophages and the regular immune cells. In other words, it have to be strategic. Because of this, Seyfried developed a “press-pulse therapy” for cancer, which allows the patient to take care of regular immune system perform, whereas at the similar time concentrating on the corrupted immune cells — the macrophage fusion hybrid metastatic cells — as well as irritation.
“The therapies we are utilizing to aim to kill these [metastatic] cells put us in danger for having the cells survive and kill us. You’ll be able to control these cells for a short period of time, but they will hunker down and enter into some type of a slightly dormant state, but they reappear.
Individuals say, ‘Oh, these tumor cells are so nifty and sensible they will come back at you.” The problem is you’ve never actually challenged them on their very existence, which is they rely upon fermentation to outlive. In case you don’t target their fermentation, they’re going to continue to outlive and come again at you.
Many of the therapies that we use — radiation, chemo and some of these other procedures — will not be really going after the coronary heart of the drawback. That oftentimes put you at risk for the recurrence of the disease. Your physique is already significantly weakened by the toxic remedies. And in the battle, you lose. In case you are lucky enough to outlive … your body continues to be beat up.
You have got now put your [body] in danger for other kinds of maladies … Why are we utilizing such poisonous therapies to kill a cell once we know what its weaknesses are? These are the paradigm modifications that should occur as we transfer into the new period of managing most cancers in a logical means.”
A Strategic Strategy to Killing Cancer Cells
To correctly handle cancer, then, you want to clean up the microenvironment, because the microenvironment will strategically kill cells which are dependent on fermentation while enhancing cells that aren’t. At the similar time, the microenvironment may also scale back inflammation.
“You also have to be very careful not to kill your normal and healthy immune cells, because they need glutamine too,” Seyfried says. “What we discover is that once we strategically attack the tumor this manner, it turns out that our immune cells are paralyzed.
The cancer cells are killed, but the normal immune cells are paralyzed. They’re not dying, they’re just not doing their job. What we do is we again off the remedy somewhat; permit the normal immune cells to regain their biological capacity, decide up lifeless corpses, heal the microenvironment, and then we go after the cancer cells once more.
It’s a graded response, understanding the biology of the regular cells and the abnormal biology of the tumor cells. This can be a lovely strategy. Once individuals know how one can play one group of cells off another, and how you can strategically kill one group of cells without harming the other cells, it really turns into a precision mechanism for eliminating tumor cells with out harming the rest of the physique.
You don’t have to be poisoned and irradiated. You simply need to know the way to use these procedures to strategically kill the cells. Defending normal macrophages is a component of the strategic course of. Killing the corrupted ones is a component of the strategic course of. Once more, you must put all of these together in a very logical path. Otherwise, you’re not going to get the degree of success that we must be getting.”
The Press-Pulse Strategy
This technique is what Seyfried calls “press-pulse treatment,” and primarily includes proscribing the fermentable fuels — glucose and glutamine — in a cyclical trend to keep away from causing injury to regular cells and tissues. Glucose is successfully restricted via a ketogenic eating regimen. Proscribing glutamine is barely trickier.
The press-pulse technique was developed from the idea of press-pulse in the subject of paleobiology. A “press” was some continual stress on populations, killing off giant numbers, but not every little thing, as a result of some organisms can adapt to stress. The “pulse” refers to some catastrophic occasion.
The simultaneous prevalence of these two unlikely occasions led to the mass extinction of virtually all organisms that existed on the planet. This was a cyclic occasion over many a whole lot of hundreds of thousands of years. The geological data show proof for this press-pulse extinction phenomenon.
“What we merely did was take that concept and say, ‘Let’s chronically stress the tumor cells.’ They want glucose. You possibly can in all probability kill a big quantity of tumor cells by just stressing their glucose. That’s the press. The press is alternative ways to lower blood sugar. You set that continual stress on prime of the inhabitants both by restricted ketogenic diets [or] therapeutic fasting. There are lots of ways that you can do this.
Additionally, emotional stress reduction. Individuals are freaked out because they have most cancers, subsequently their corticoid steroids are elevated, which elevates blood sugar. Using numerous varieties of stress administration, average exercise — all of these will decrease blood sugar and contribute to a persistent press and stress on the cancer cells.
Nevertheless, you’re not going to kill all cancer cells for those who simply take away glucose. As a result of the different gasoline that’s maintaining the beast alive is the glutamine. We’ve got to pulse because we will’t use a press for glutamine concentrating on, because then you definitely’re going to kill your regular immune cells or impair them, and they are wanted for the eventual resolution of the illness.
What we’re going to do is we’re going to pulse numerous medicine. We don’t have a weight loss plan system that may target glutamine. Glutamine is in all places. It’s the most plentiful amino acid in your body … But you need to use [the drugs] very strategically; otherwise, they will harm our normal immune system and then be counterproductive …
I feel that when we perceive how we will goal effectively glutamine without harming our regular immune cells … this is the technique that may make most of these different therapies obsolete … It’s cost-effective and non-toxic and it’s going to work very properly.
However we’re still at the very beginning of this. We have to continue to develop the doses, timing, and scheduling of these medicine which might be only in concentrating on glutamine that can be accomplished with out harming the relaxation of the cells in our body.”
If you need to help Dr. Seyfried’s analysis, please think about making a donation to the “Foundation For Metabolic Cancer Therapies.” The donation tag is on the prime row of the basis website (http://www.foundationformetaboliccancertherapies.com/). This Foundation is dedicated to supporting Dr. Seyfried’s studies utilizing metabolic remedy for cancer administration with 100% of the donated funds going directly to analysis on metabolic therapy for most cancers.
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