Cancer: causes and cures

[jsf]

Anyway Criss Kresser's article is contradictory to Patrick Vickers :

About acidity :

One of the more popular claims of the alkaline diet is that it can cure cancer. Proponents say that because cancer can only grow in an acidic environment, a net-alkaline diet can prevent cancer cells from growing, and can eliminate existing cancer cells. This theory is incorrect for a few reasons. First of all, the hypothesis depends on the ability of food to substantially change the pH of the blood and extracellular fluid, which I've already shown is not the case. (8, 9, 10) Second, cancer is perfectly capable of growing in an alkaline environment. The pH of normal body tissue is 7.4, which is slightly alkaline, and in almost every experiment done with cancer cells, they are grown in an environment at that pH. (11)

Now, cancer cells do tend to grow better in an acidic environment, but the causality is reversed. Once a tumor develops, it creates its own acidic environment through up-regulated glycolysis and reduced circulation, so the pH of the patient's blood no longer determines the pH of the cancer. (12)

And as explains James Sloane in his interview with Markus Rothkranz, a tumor is alcaline.

So if the pH of the blood and extracellular fluid cannot substantially change, why would it be the case inside the cells, as Patrick Vickers says ?

And the more buildup of high hydrogen protons that you have in the body, the greater your level of acidity in the body. Well here is something that you will very rarely hear because very few people truly understand this; that when you have the buildup of hydrogen ions in the body in the form of acidity, and that what happens, acidity, hydrogen ions, accumulate inside the cells.

And about salt :
_http://chriskresser.com/shaking-up-the-salt-myth-the-human-need-for-salt

An abrupt increase in dietary salt can cause a redistribution of fluid from the intra- to the extracellular space. But after a few days, the kidney is able to compensate with extra sodium excretion to match the dietary intake. Therefore, healthy people are generally able to adapt to a wide range of salt intakes without a significant change in blood pressure. (11)

 

[nicklebleu]

Salt requirements are vastly different on a high carb vs ketogenic diet. Eating lots of carbs leads to water retention in your body, which in turn will also limit salt excretion by the kidney to maintain electrolyte balance. On a ketogenic diet however, low on carbs, the salt excretion by the kidney is much higher, which has to be supplemented.

I live in a tropical climate and sweat a lot. If I don't supplement myself with a lot of salt (salted water in the morning, extra salt on all the dishes) I will get muscle cramps. Lots of people complain of muscle spasm and the common medical wisdom is, that this is a symptom of magnesium deficiency, which very often is certainly part of the picture. But because mainstream medicine has been hammering the low-salt paradigm into everyone's head the low-salt connection often gets overlooked. And as jsf mentioned, low potassium is often part of the picture too.

 

[jsf]

Thanks nicklebleu, very interesting.

Another thing (I thought cancer cells couldn't use ketones ?) :

_http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117136/

Ketones and lactate increase cancer cell “stemness”, driving recurrence, metastasis and poor clinical outcome in breast cancer

Achieving personalized medicine via metabolo-genomics
Ubaldo E Martinez-Outschoorn,#1,2,3 Marco Prisco,#1,3 Adam Ertel,#1,3 Aristotelis Tsirigos,4 Zhao Lin,1,3 Stephanos Pavlides,1,3,5 Chengwang Wang,1,3 Neal Flomenberg,1,2 Erik S Knudsen,1,2 Anthony Howell,6 Richard G Pestell,1,2,3 Federica Sotgia,corresponding author1,2,3,6 and Michael P Lisanticorresponding author1,2,3,5,6

Go to:
Abstract
Previously, we showed that high-energy metabolites (lactate and ketones) “fuel” tumor growth and experimental metastasis in an in vivo xenograft model, most likely by driving oxidative mitochondrial metabolism in breast cancer cells. To mechanistically understand how these metabolites affect tumor cell behavior, here we used genome-wide transcriptional profiling. Human breast cancer cells (MCF7) were cultured with lactate or ketones, and then subjected to transcriptional analysis (exon-array). Interestingly, our results show that treatment with these high-energy metabolites increases the transcriptional expression of gene profiles normally associated with “stemness”, including genes upregulated in embryonic stem (ES) cells. Similarly, we observe that lactate and ketones promote the growth of bonafide ES cells, providing functional validation. The lactate- and ketone-induced “gene signatures” were able to predict poor clinical outcome (including recurrence and metastasis) in human breast cancer patients. Taken together, our results are consistent with the idea that lactate and ketone utilization in cancer cells promotes the “cancer stem cell” phenotype, resulting in significant decreases in patient survival. One possible mechanism by which high-energy metabolites might induce stemness is by increasing the pool of Acetyl-CoA, leading to increased histone acetylation and elevated gene expression. Thus, our results mechanistically imply that clinical outcome in breast cancer could simply be determined by epigenetics and energy metabolism, rather than by the accumulation of specific “classical” gene mutations. We also suggest that high-risk cancer patients (identified by the lactate/ketone gene signatures) could be treated with new therapeutics that target oxidative mitochondrial metabolism, such as the anti-oxidant and “mitochondrial poison” metformin. Finally, we propose that this new approach to personalized cancer medicine be termed “metabolo-genomics,” which incorporates features of both (1) cell metabolism and (2) gene transcriptional profiling. This powerful new approach directly links cancer cell metabolism with clinical outcome, and suggests new therapeutic strategies for inhibiting the TCA cycle and mitochondrial oxidative phosphorylation in cancer cells.

Key words: ketones, lactate, cancer stem cells, clinical outcome, recurrence, metastasis, personalized medicine, breast cancer, metformin, oxidative mitochondrial metabolism, metabologenomics

 

[Joe]

There's also a possible link between insulin and cancer.

_http://www.hindawi.com/journals/jdr/2012/789174/

(1)Chronic hyperinsulinemia, in affected individuals, may promote cancer, as insulin can exert its oncogenic potential via abnormal stimulation of multiple cellular signaling cascades, enhancing growth factor-dependent cell proliferation and/or by directly affecting cell metabolism.

(2)Insulin increases the bioactivity of IGF-I by enhancing hepatic IGF-I synthesis and by reducing hepatic protein production of the insulin-like growth factor binding proteins 1 (IGFBP-1) and 2 (IGFBP-2) [10, 11]. Therefore, although insulin can directly induce tumour growth, many of its mitogenic and antiapoptotic effects are operating through the IGF-I system, as reported in individuals with high levels of circulating IGF-I, in which an increased risk of developing certain types of tumours, in particular breast and prostate cancers, has been documented [12, 13].

(3)Insulin, by reducing SHBG levels, exerts a positive effect on estrogen bioavailability, therefore increasing breast cancer risk.

 

[jsf]

And oxidative stress :

_http://www.sciencedaily.com/releases/2011/02/110215102836.htm

Genetic evidence that antioxidants can help treat cancer
Date:
February 15, 2011
Source:
Thomas Jefferson University
Summary:
Researchers have genetic evidence suggesting the antioxidant drugs currently used to treat lung disease, malaria and even the common cold can also help prevent and treat cancers because they fight against mitochondrial oxidative stress -- a culprit in driving tumor growth.

For the first time, the researchers show that loss of the tumor suppressor protein Caveolin-1 (Cav-1) induces mitochondrial oxidative stress in the stromal micro-environment, a process that fuels cancer cells in most common types of breast cancer.
"Now we have genetic proof that mitochondrial oxidative stress is important for driving tumor growth," said lead researcher Michael P. Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University and member of the Kimmel Cancer Center at Jefferson. "This means we need to make anti-cancer drugs that specially target this type of oxidative stress. And there are already antioxidant drugs out there on the market as dietary supplements, like N-acetyl cysteine."
These findings were published in the online Feb. 15 issue of Cancer Biology & Therapy.
Lisanti's lab previously discovered Cav-1 as a biomarker that functions as a tumor suppressor and is the single strongest predictor of breast cancer patient outcome. For example, if a woman has triple negative breast cancer and is Cav-1 positive in the stroma, her survival is greater than 75 percent at 12 years, versus less than 10 percent at 5 years if she doesn't have the Cav-1 protein, according to Dr. Lisanti.
The researchers also established Cav-1's role in oxidative stress and tumor growth; however, where that stress originates and its mechanism(s) were unclear.
To determine this, Jefferson researchers applied a genetically tractable model for human cancer associated fibroblasts in this study using a targeted sh-RNA knock-down approach. Without the Cav-1 protein, researchers found that oxidative stress in cancer associated fibroblasts leads to mitochondrial dysfunction in stromal fibroblasts. In this context, oxidative stress and the resulting autophagy (producton of recycled nutrients) in the tumor-microenvironment function as metabolic energy or "food" to "fuel" tumor growth.
The researchers report that the loss of Cav-1 increases mitochondrial oxidative stress in the tumor stroma, increasing both tumor mass and tumor volume by four-fold, without any increase in tumor angiogenesis.
"Antioxidants have been associated with cancer reducing effects -- beta carotene, for example -- but the mechanisms, the genetic evidence, has been lacking," Dr. Lisanti said. "This study provides the necessary genetic evidence that reducing oxidative stress in the body will decrease tumor growth."
Currently, anti-cancer drugs targeting oxidative stress are not used because is it commonly thought they will reduce the effectiveness of certain chemotherapies, which increase oxidative stress.
"We are not taking advantage of the available drugs that reduce oxidative stress and autophagy, including metformin, chloroquine and N-acetyl cysteine," Dr. Lisanti said. "Now that we have genetic proof that oxidative stress and resulting autophagy are important for driving tumor growth, we should re-consider using antioxidants and autophagy inhibitors as anti-cancer agents."
The diabetic drug metformin and chloroquine, which is used for the prevention and treatment of malaria, prevent a loss of Cav-1 in cancer associated fibroblasts (which is due to oxidative stress), functionally cutting off the fuel supply to cancer cells.
This research also has important implications for understanding the pathogenesis of triple negative and tamoxifen-resistance in ER-positive breast caner patients, as well as other epithelial cancers, such as prostate cancers.
"Undoubtedly, this new genetically tractable system for cancer associated fibroblasts will help identify other key genetic 'factors' that can block tumor growth," Dr. Lisanti said.

And :
_http://www.sciencedaily.com/releases/2012/06/120626131854.htm

Glucose deprivation activates feedback loop that kills cancer cells, study shows
Date:
June 26, 2012
Source:
University of California - Los Angeles
Summary:
Researchers demonstrate the power of systems biology to uncover relationships between metabolism and signaling at the network level. The findings add to the emerging concept of systems integration between oncogenic signaling networks and metabolism of malignant tumors. The work lays a foundation for future studies delineating how signaling and metabolism are linked, with the ultimate goal of refining therapeutic strategies targeting cancer metabolism.

In research published June 26 in the journal Molecular Systems Biology, Graeber and his colleagues demonstrate that glucose starvation -- that is, depriving cancer cells of glucose -- activates a metabolic and signaling amplification loop that leads to cancer cell death as a result of the toxic accumulation of reactive oxygen species, the cell-damaging molecules and ions targeted by antioxidants like vitamin C.

(...)
Assessing the "crosstalk" between metabolism and signaling, they discovered that the glucose deprivation activates a positive feedback loop whereby the withdrawal of glucose induces increased levels of reactive oxygen species, which in turn inhibit negative regulators of tyrosine signaling. The resulting supra-physiological levels of tyrosine phosphorylation then generate additional reactive oxygen species.
"Because cancer cells live on the edge of what is metabolically feasible, this amplifying cycle of oxidative stress ultimately overwhelms and kills the cancer cell," Graeber explained. "These findings illustrate the delicate balance that exists between metabolism and signaling in the maintenance of cancer cell homeostasis."
(...)

And also :

Dietary downregulation of mutant p53 levels via glucose restriction: Mechanisms and implications for tumor therapy
Olga Catalina Rodriguez, Sujatra Choudhury, Vamsi K. Kolukula, Eveline E. Vietsch, Jason Catania, Anju Preet, Katherine Reynoso, Jill Bargonetti, Anton Wellstein, Chris Albanese, Maria Laura Avantaggiati*

Abstract
The majority of human tumors express mutant forms of p53 at high levels, promoting gain of oncogenic functions and correlating with disease progression, resistance to therapy and unfavorable prognosis. p53 mutant accumulation in tumors is attributed to the ability to evade degradation by the proteasome, the only currently recognized machinery for p53 disruption. We report here that glucose restriction (GR) induces p53 mutant deacetylation, routing it for degradation via autophagy. Depletion of p53 leads, in turn, to robust autophagic activation and to cell death, while expression of degradation-defective mutant p53 blocks autophagy and enables survival to GR. Furthermore, we found that a carbohydrate-free dietetic regimen that lowers the fasting glucose levels blunts p53 mutant expression and oncogenic activity relative to a normal diet in several animal model systems. These findings indicate that the stability of mutant forms of p53 is influenced by the levels of glucose and by dietetic habits. They also unravel the existence of an inhibitory loop between autophagy and mutant p53 that can be exploited therapeutically.

So we have cancer cells using glucose fermentation.
And glucose fermentation produces lactic acid, acidifying cancerous tissues.
And yes, also the Insulin-like growth factor-1 (IGF) increases the growth of cancer.
So I still don't understand why lactate and ketones are involved in the process :

we showed that high-energy metabolites (lactate and ketones) “fuel” tumor growth

 

[nicklebleu]

Another thing (I thought cancer cells couldn't use ketones ?) :

That's what I thought too - and from what I have read it is true for most cancer cells. There might be some for which this is incorrect, maybe these particular cancer cells were relatively close to stem cells, so that they could maintain the metabolic pathways to utilize ketones for energy needs.

Having said that in case I developed cancer I would still put my hat on a ketogenic diet.

Intriguing it is ...

 

[nicklebleu]

Just happened to read the following article - coincidences ...

Is there a way to exploit the metabolic quirk of cancer?

by Peter Attia, MD/ The Eating Academy

One night, as I alluded to in this post, Tim and I were having dinner and the topic of cancer came up. Personally and professionally I have a great interest in cancer, so when Tim asked if I could write something about cancer that was: (i) interesting to a broad audience, (ii) not technically over the top, (iii) not my typical 5,000 word dissertation, (iv) yet nuanced enough for his readers, I agreed to give it a shot, in about 1,000 words. (The content of this blog went up on Tim’s blog last week, but I’ve reproduced it here, less Tim’s commentary.)

Semantics and basics

Before jumping into this topic I want to be sure all readers — regardless of background — have a pretty good understanding of the ‘basics’ about cancer and metabolism. In an effort to do this efficiently, I’ll list concepts here, such that folks can skip them if they want to, or refer back as necessary. This way, I don’t need to disrupt the ‘story’ with constant definitions. (Yes, I realize this is sort of cheating on my 1,000 word promise.)

Cancer – a collection of cells in our bodies that grow at roughly normal speeds, but that do not respond appropriately to cell signaling. In other words, while a collection of ‘normal’ cells will grow and stop growing in response to appropriate messages from hormones and signals, cancer cells have lost this property. Contrary to popular misconception, cancers cells do not grow especially fast relative to non-cancer cells. The problem is they don’t ‘know’ when to stop growing.

Metabolism – the process of converting the stored energy in food (chemical energy contained mostly within the bonds of carbon and hydrogen atoms) into usable energy for the body to carry out essential and non-essential work (e.g., ion transport, muscle contraction).

ATP – adenosine triphosphate, the ‘currency’ of energy used by the body. As its name suggests, this molecule has three (tri) phosphates. Energy is liberated for use when the body converts ATP to ADP (adenosine diphosphate), by cutting off one of the phosphate ions in exchange for energy.

Glucose – a very simple sugar which many carbohydrates ultimately get broken down into via digestion; glucose is a ring of 6-carbon molecules and has the potential to deliver a lot, or a little, ATP, depending on how it is metabolized.

Fatty acid – the breakdown product of fats (either those stored in the body or those ingested directly) which can be of various lengths (number of joined carbon atoms) and structures (doubled bonds between the carbon atoms or single bonds).

Aerobic metabolism – the process of extracting ATP from glucose or fatty acids when the demand for ATP is not too great, which permits the process to take place with sufficient oxygen in the cell. This process is highly efficient and generates a lot of ATP (about 36 units, for example, from one molecule of glucose) and easy to manage waste products (oxygen and carbon dioxide).

The process of turning glucose and fatty acid into lots of ATP using oxygen is called ‘oxidative phosphorylation.’

Anaerobic metabolism – the process of extracting ATP from glucose (but not fatty acids) when the demand for ATP is so great that the body cannot deliver oxygen to cells quickly enough to accommodate the more efficient aerobic pathway. The good news is that we can do this (otherwise a brief sprint, or very difficult exertion would be impossible). The bad news is this process generates much less ATP per carbon molecule (about 4 units of ATP per molecule of glucose), and it generates lactate, which is accompanied by hydrogen ions. (Contrary to popular belief, it’s the latter that causes the burning in your muscles when you ask your body to do something very demanding, not the former).

Mitochondria – the part of the cell where aerobic metabolism takes place. Think of a cell as a town and the mitochondria as the factory that converts the stored energy into usable energy. If food is natural gas, and usable energy is electricity, the mitochondria are the power plants. But remember, mitochondria can only work when they have enough oxygen to process glucose or fatty acids. If they don’t, the folks outside of the factory have to make due with suboptimally broken down glucose and suboptimal byproducts.

DNA – deoxyribonucleic acid, to be exact, is the so-called “building block” of life. DNA is a collection of 4 subunits (called nucleotides) that, when strung together, create a code. Think of nucleotides like letters of the alphabet. The letters can be rearranged to form words, and words can be strung together to make sentences.

Gene – if nucleotides are the letters of the alphabet, and DNA is the words and sentences, genes are the books – a collection of words strung together to tell a story. Genes tell our body what to build and how to build it, among other things. In recent years, scientists have come to identify all human genes, though we still have very little idea what most genes ‘code’ for. It’s sort of like saying we’ve read all of War and Peace, but we don’t yet understand most of it.

FDG-PET – a type of ‘functional’ radiographic study, often called a ‘pet scan’ for short, used to detect cancer in patients with a suspected tumor burden (this test can’t effectively detect small amounts of cancer and only works for ‘established’ cancers). F18 is substituted for -OH on glucose molecules, making something called 2-fluoro-2-deoxy-D-glucose (FDG), an analog of glucose. This molecule is detectable by PET scanners (because of the F18) and shows which parts of the body are most preferentially using glucose.

Phosphoinositide 3-kinase – commonly called PI3K (pronounced “pee-eye-three-kay”), is an enzyme (technically, a family of enzymes) involved in cell growth and proliferation. Not surprisingly, these enzymes play an important role in cancer growth and survival, and cancer cells often have mutations in the gene encoding PI3K, which render PI3K even more active. PI3Ks are very important in insulin signaling, which may in part explain their role in cancer growth, as you’ll see below.

The story (in about 1,000 words, as promised)

In 1924 a scientist named Otto Warburg happened upon a counterintuitive finding. Cancer cells, even in the presence of sufficient oxygen, underwent a type of metabolism cells reserved for rapid energy demand – anaerobic metabolism. In fact, even when cancer cells were given additional oxygen, they still almost uniformly defaulted into using only glucose to make ATP via the anaerobic pathway. This is counterintuitive because this way of making ATP is typically a last resort for cells, not a default, due to the very poor yield of ATP.

This observation begs a logical question? Do cancer cells do this because it’s all they can do? Or do they deliberately ‘choose’ to do this? I’m not sure the answer is entirely clear or even required to answer the macro question I’ve posed in this post. However, being curious people we like answers, right?

The first place to look is at the mitochondria of the cancer cells. Though not uniformly the case, most cancers do indeed appear to have defects in their mitochondria that prevent them from carrying out oxidative phosphorylation.

Explanation 1

Cancer cells, like any cells undergoing constant proliferation (recall: cancer cells don’t stop proliferating when told to do so), may be optimizing for something other than energy generation. They may be optimizing for abundant access to cellular building blocks necessary to support near-endless growth. In this scenario, a cancer would prefer to rapidly shuttle glucose through itself. In the process, it generates the energy it needs, but more importantly, it gains access to lots of carbon, hydrogen, and oxygen atoms (from the breakdown of glucose). The atoms serve as the necessary input to the rate-limiting step of their survival — growth. The selection of cancer cells is based on this ability to preferentially grow by accessing as much cellular substrate as possible.

Explanation 2

Cells become cancerous because they undergo some form of genetic insult. This insult – damage to their DNA – has been shown to result in the turning off of some genes (those that suppress tumor growth) and/or the activation of other genes (those that promote cell growth unresponsive to normal cell-signaling). Among other things, this damage to their DNA also damages their mitochondria, rendering cancer cells unable to carry out oxidative phosphorylation. So, to survive they must undergo anaerobic metabolism to make ATP.

Whichever of these is more accurate, the end result appears the same – cancer cells almost exclusively utilize glucose to make ATP without the use of their mitochondria. A detailed discussion of which explanation is better is beyond the scope of my word allotment, and it’s not really the point I want to make. The point is, cancer cells have a metabolic quirk. Regardless of how much oxygen and fatty acid they have access to, they preferentially use glucose to make ATP, and they do it without their mitochondria and oxygen.

So, can this be exploited to treat or even prevent cancer?

One way this quirk has been exploited for many years is in medical imaging. FDG-PET scans are a useful tool for non-invasively detecting cancer in people. By exploiting the obligate glucose consumption of cancer cells, the FDG-PET scan is a powerful way to locate cancer (see figure).

FDG-PET

You can probably tell where I’m leading you. What happens if we reduce the amount of glucose in the body? Could such an intervention ‘starve’ cancer cells? An insight into this came relatively recently from an unlikely place – the study of patients with type 2 diabetes.

In the past few years, three retrospective studies of patients taking a drug called metformin have shown that diabetic patients who take metformin, even when adjusted for other factors such as body weight and other medications, appear to get less cancer. And when they do get cancer, they appear to survive longer. Why? The answer may lie in what metformin does. Metformin does many things, to be clear, but chief among them is activating an enzyme called AMP kinase, which is important in suppressing the production of glucose in the liver (the liver manufactures glucose from protein and glycerol and releases it to the rest of the body). This drug is used in patients with diabetes to reduce glucose levels and thereby reduce insulin requirement.

So, the patients taking metformin may have better cancer outcomes because their glucose levels were lower, or because such patients needed less insulin. Insulin and insulin-like growth factor (IGF-1) also appear to play an integral role in cancer growth as recently demonstrated by the observation that people with defective IGF-1 receptors appear immune to cancer. Or, it may be that activation of AMP kinase in cancer cells harms them in some other way. We don’t actually know why, but we do know that where there is smoke there is often fire. And the ‘smoke’ in this case is that a relatively innocuous drug that alters glucose levels in the body appears to interfere with cancer.

This may also explain why most animal models show that caloric restriction improves cancer outcomes. Though historically, this observation has been interpreted through the lens of less ‘food’ for cancer. A more likely explanation is that caloric restriction is often synonymous with glucose reduction, and it may be the glucose restriction per se that is keeping the cancer at bay.

Fortunately this paradigm shift in oncology – exploiting the metabolic abnormality of cancer cells – is gaining traction, and doing so with many leaders in the field.

Over a dozen clinical trials are underway right now investigating this strategy in the cancers that appear most sensitive to this metabolic effect – breast, endometrial, cervical, prostate, pancreatic, colon, and others. Some of these trials are simply trying to reproduce the metformin effect in a prospective, blinded fashion. Other trials are looking at sophisticated ways to target cancer by exploiting this metabolic abnormality, such as targeting PI3K directly.

To date, no studies in humans are evaluating the therapeutic efficacy of glucose and/or insulin reduction via diet, though I suspect that will change in the coming year or two, pending outcomes of the metformin trials.

Last point (beyond my 1,000 word allotment)

Check out this blast from the past! Gary Taubes, who is currently working hard on his next book, came across the article the other day from 1887.

1887, NYT, sugar and cancer - see picture in original article.

Influences

I’ve been absurdly blessed to study this topic at the feet of legends, and to be crystal clear, not one thought represented here is original work emanating from my brain. I’m simply trying to reconstruct the story and make it more accessible to a broader audience. Though I trained in oncology, my research at NIH/NCI focused on the role of the immune system in combating cancer. My education in the metabolism of cancer has been formed by the writings of those below, and from frequent discussions with a subset of them who have been more than generous with their time, especially Lewis Cantley (who led the team that discovered PI3K) and Dominic D’Agostino.

Otto Warburg
Lewis Cantley
Dominic D’Agostino
Craig Thompson
Thomas Seyfried
Eugene Fine
Richard Feinman (not to be confused with Richard Feynman)
Rainer Klement
Reuben Shaw
Matthew Vander Heiden
Valter Longo
Further reading

I do plan to continue exploring this topic, but for those of you who want to know more right now and/or for those of you with an appetite for depth, I recommend the following articles, some technical, some not, but all worth the time to read. This is the short list:

Relatively non-technical review article on the Warburg Effect written by Vander Heiden, Thompson, and Cantley
Science piece written about cancer (for non-technical audience) by Gary Taubes
Non-technical talk by Craig Thompson
Detailed review article by Tom Seyfried
Review article on the role of carb restriction in the treatment and prevention of cancer
Talk given by author of above paper for those who prefer video
Moderately technical review article by Shaw and Cantley
Clinical paper on the role of metformin in breast cancer by Ana Gonzalez-Angulo
Mouse study by Dom D’Agostino’s group examining role of ketogenic diet and hyperbaric oxygen on a very aggressive tumor model
Mechanistic study by Feinman and Fine assessing means by which acetoacetate (a ketone body) suppresses tumor growth in human cancer cell lines

 

[trendsetter37]

Hmm...Be careful here jsf. That article is riddled with areas where they choose their words carefully to imply a conclusion that is not there. Wow.

Some definitions to start with:

Metastasis: the development of secondary malignant growths at a distance from a primary site of cancer.

Angiogenesis: the development of new blood vessels.

From Wikepedia about Lactate being converted to glucose

Lactate is transported back to the liver where it is converted into pyruvate by the Cori cycle using the enzyme lactate dehydrogenase. Pyruvate, the first designated substrate of the gluconeogenic pathway, can then be used to generate glucose.

More context.

Wikipedia

In the brain ketone bodies are also used to make Acetyl CoA into long chain fatty acids because long chain fatty acids cannot pass through the blood brain barrier. The liver breaks down protein to produce glucose during starvation for the very few glucose obligate cells that cannot use ketone bodies.[1][2] In the brain, ketone bodies are a vital source of energy during fasting or strenuous exercise.[3] Although termed "bodies", they are molecules, not particles.

From Journal article:

Interestingly, 3-hydroxy-butyrate (a ketone body) significantly increased tumor growth (∼2.5-fold), without any increases in tumor angiogenesis.8 In contrast, L-lactate increased experimental lung metastasis (by ∼10-fold), but did not affect primary tumor growth.8

This quote is what I find interesting. So the ketone increased tumor growth by 2.5 fold. However, without any increase in angiogenesis. Which as seen above is the developement of new blood vessels. I may be wrong about this but developement of new blood vessels would signify building infrastructure because it is spreading or planning to.

Now let's look at the lactate. Apparently, it increased lung metastasis by 10-fold. Yet they did not deem that as significant like the ketone performance. I guess because they are trying to make a distinction between angiogenesis and metastasis. BUT both are probably signs that a tumor is spreading. Oh and they made sure to mention that the primary tumor did not get bigger with lactate. But if it's busy spreading to newer areas of the organism it would make sense that most of it's resources are being used to spread.

Even if you looked at the raw numbers. 10 is bigger than 2.5. Literally. But i'm not sure which mechanism yields more malignant/pathological mass so that point could be irrelevant.

I think it's also be important to note that this was in vitro ( a petridish) and not within a human body where there would be immune responses as well as dietary input to aid in either mechanism. Still though it appears that the ketone is inhibiting the spread compared to the lactate.

Interestingly, we show that ketones and lactate both increase the transcriptional profiles of genes that are associated with “stemness” (neural, embryonic, and hematopoietic stem cells). Thus, the metabolic use of ketones and lactate could “fuel” the cancer stem cell phenotype, which may be responsible for promoting tumor growth and metastasis.[/b ] In accordance with this notion, we show that the ketone- and lactate-induced “gene signatures” (generated using the luminal A-like MCF7 cell line) predict recurrence, metastasis, and reduced overall survival in the most common form of human breast cancer [the ER(+) luminal A subtype]. Thus, this new “metabolo-genomics” approach to personalized cancer medicine links biomarker stratification with novel energy-based therapeutic strategies, such as metformin.

This entire notion is predicated on them knowing exactly what cancer is. And that certain genes profiles can directly predict qualities in a cancer cell's ability to proliferate and become self-renewing ("stemness"). This is where I realized or thought to myself that they really are building their entire argument on a supposition that contains way too many variables and overlapping conditions to be seen as the smoking gun.

This especially with what we now know about fungi in relation to cancer and all of its seemingly identical qualities.

Similarly, the liver (a major site of ketogenesis) would provide a ketone-rich microenvironment for cancer cells, that could then use ketones as a metabolic fuel for oxidative mitochondrial metabolism. This may explain why cancer cells often metastasize to the liver, and the outcome of breast cancer patients with liver metastases is so poor.

Here is yet another example where they suppose that maybe this is why liver cancer is so deadly. Because the liver is a production center for ketone. Well actually when they induce liver cancer in those mice studies they apparently use the mycotoxin aflotoxin b1. Which is ofcourse a toxin produced by fungi and their infection. This points in an entirely different direction than what they are using to build their argument.

Further, the liver does produce ketones but they do not stay their in a concentrated manner. They are supposedly transported immediately to other organs that use them. As the liver does not. So it would make more sense for a cancer tumor to set up shop where there would be a higher concentration of ketones. Not an area that had a negative flux of them such as the liver.

This logic may be on shaky ground though because I didn't go down that road to far.

I would also think that they would be privy to that kind of information (fungal toxins being the standard in producing liver cancer in mice) since it is in their same field. But I could be wrong.

In accordance with our assertion that cancer cells use mitochondrial oxidative phosphorylation for energy production, metformin treatment prevents and/or inhibits tumor formation both in diabetic patients and in mouse animal models.40,41 Moreover, metformin also kills “cancer stem cells”.42–45 These findings are all consistent with our proposal that the treatment of cancer cells with high-energy metabolites (lactate and ketones) drives mitochondrial oxidative phosphorylation, and increases the “stemness” of cancer cells. Moreover, we see that these high-energy metabolites induce a “stem-like” transcriptional profile that is specifically associated with tumor recurrence, metastasis and poor clinical outcome.

Metformin, is a anti-glycaemic drug. So basically it rids you of available glucose, lowers your blood glucose levels, and therefore would starve cancer and/or fungal growth. This is a big contradiction to their theory. But it's their nonetheless. Greater intake of saturated fats or ketogenic inducing foods lowers your blood sugar levels and has been shown to starve and inhibit tumor growths. This is slap in the face of their theoretic trajectory at this point. osit. But they still power through with their hypothesis through obfuscation. Which helps no one...well besides themselves because if you can't understand their logic then some people default to the rationale that it is over their own head and therefore the authors must be right or at least on to something.

But really i think it's a defense mechanism. Those were my observations but what do you guys think?



Edit: link to the full paper _http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117136/

 

[nicklebleu]

In accordance with our assertion that cancer cells use mitochondrial oxidative phosphorylation for energy production, metformin treatment prevents and/or inhibits tumor formation both in diabetic patients and in mouse animal models.40,41

The assertion that "cancer cells use mitochondrial oxidative phosphorylation for energy production" flies in the face of everything I have ever read about cancer cell metabolism. The usual stance on this is that cancer cells cannot use oxidative phosphorylation and thus need to go down the "anaerobic metabolic pathway" (producing lactate). I haven't read the full article yet, but I do wonder where they take this assertion from.

And as trendsetter37 correctly points out, metformin reduces blood sugar, but also insulin, which is also known to be a factor driving cancer development (as noted in my last post, the absence of IGF-1 receptors seem to convey immunity to cancer development in the affected organism). So how this ties in with the notion that ketones drive cancer development is unclear to me, too.

 

[Michal]

Re: Hemochromatosis and Autoimmune Conditions

Hi,
I think that this article from SOTT is really inspiring:
http://www.sott.net/article/273789-Has-Cancer-Been-Completely-Misunderstood

If that is reality for cells to live in 2 modes: one normal state - healthy, and the other - survival mode = cancer. Survival mode is triggered by extremely toxic and hostile environment.

So maybe all that stuff we say that kills cancer actually just switches the mode of living for the cell?

And one more link from Jack Kruse - related:
http://jackkruse.com/cold-thermogenesis-three/

 

[shijing]

Thanks for the links, Mikel -- I've moved your post to this thread since they deal specifically with cancer. They tie together well with this article posted recently by LQB:

http://www.westonaprice.org/cancer/cancer-to-the-rescue

 

[Bosphorus1982]

There may be many causes of cancer however as far as i know there are 4 things to stop its growing. These are cutting out 1) sugar, 2) alcohol 3) red meat 4) protein. As these help cancer cells to grow leaving them might help a great deal.

 

[Nienna]

There may be many causes of cancer however as far as i know there are 4 things to stop its growing. These are cutting out 1) sugar, 2) alcohol 3) red meat 4) protein. As these help cancer cells to grow leaving them might help a great deal.

Number 1 - yes, number 2 - yes, number 3 - NO, number 4 - NO.

You have been making a lot of statements in your most recent posts that seem to be nothing more than your opinions. You have not had any reliable data to back up your claims. It would be good if you could read the posts here on the forum to get up to speed with what we discuss here to keep the noise ratio down.

 

[Nancy2feathers]

Hi Everyone. I was looking for the right thread to post in, so I hope this one will do. I found out today that someone dear to me has pancreatic cancer. My youngest daughter called and told me the news today. My daughter and I have been friends with this person for years. My daughter would call P over the years when we were going through rough times and I know P would give my daughter sound advice. I want to call P to see if she`s up to having a visit with me. I want to give her a hug and let her know how much our friendship means. I also want to be externally considerate, but I`m thinking "Keto Diet". I don`t know any details of how far the cancer has progressed. How would I approach someone in her situation to give her Keto diet advice. It breaks my heart and I know if I don`t share with her about the Keto diet, well there`s always that question of "what if?". What if the Keto diet would work for her? How do I even bring it up in conversation in an externally considerate way? I would appreciate advice on this, please!

Thank you, N2F

 

[LQB]

Hi Everyone. I was looking for the right thread to post in, so I hope this one will do. I found out today that someone dear to me has pancreatic cancer. My youngest daughter called and told me the news today. My daughter and I have been friends with this person for years. My daughter would call P over the years when we were going through rough times and I know P would give my daughter sound advice. I want to call P to see if she`s up to having a visit with me. I want to give her a hug and let her know how much our friendship means. I also want to be externally considerate, but I`m thinking "Keto Diet". I don`t know any details of how far the cancer has progressed. How would I approach someone in her situation to give her Keto diet advice. It breaks my heart and I know if I don`t share with her about the Keto diet, well there`s always that question of "what if?". What if the Keto diet would work for her? How do I even bring it up in conversation in an externally considerate way? I would appreciate advice on this, please!

Thank you, N2F

That's a tough one N2F - I'm very sorry to hear that. From what I know, pancreatic cancer is very serious and usually quick. Options for her now may depend on what treatments she has done or planned to do. If it were me right now, I might go for a low carb juice fast to support detox and take strain off the digestive system. My own idea would be to enter ketosis on the juice fast and transition to the keto diet as things improved - but there are so many unknowns including what she wants to do.