Cranks who recommend deferring or replacing standard oncological care with the ketogenic diet are grossly irresponsible, writes MedicalBrief columnist Alastair McAlpine. Desperate and impressionable cancer patients should not be fodder for book sales or click-bait for websites.
“Cancer. Truthfully, is there a more frightening word in the English language? Everybody knows someone who has had cancer, whether a close friend, family member, or colleague. And despite its ubiquity, it is still so poorly understood by the general public. Furthermore, the treatment seems terrifying: harsh chemotherapeutic drugs that make you go bald, invasive surgery to slice out the offending tumour, machines that emit radiation to burn the offending cells away.
“And yet, despite the best that modern medicine has to offer, people still die, often well before their time, which leads to a general sense of frustration. What is going on? Why can’t we cure it?
“The truth is, despite great strides in the past few decades, there is still so much about cancer that we simply don’t understand yet. But there is another field which is equally poorly understood, and which has been gaining a lot of attention, particularly for its ability to treat or prevent cancer. That field is nutrition, specifically the role of the ketogenic diet.
“But when you combine two such murky fields, confusion is bound to ensue. And into that confusion step the quacks, with easy explanations and solutions (available at cost, of course). It’s time to untangle the lies and get to the bottom of the debacle.
“Before we even begin looking at what does and doesn’t work for people with cancer, we have to immediately acknowledge a giant hurdle: that despite the fact that all cancers share an underlying abnormality (the uncontrolled proliferation of cells in the body), there are hundreds of them, and they are all different. They have different causes, different manifestations, different treatments and different outcomes. Some are more likely in the young, others in the old. Some more common in men, others in women.
“So, what works for cancer ‘A’ may have absolutely no effect on cancer ‘B’. What this means is that making generalisations that apply to ALL cancers is essentially impossible; each one is unique, which means the treatment will be as well.
“The cause of cancer is the subject of intense research and is mind-bendingly complex. To summarise it in a few short sentences is almost impossible. Speaking generally, however, the genesis of many cancers is damage to the DNA of a cell, and a loss of the ability of that cell to repair itself. This damage may be from exogenous factors (cigarette smoke, viruses) or endogenous ones (macrophage activation from inflammation, bile salts). When the cell can no longer repair the DNA adequately, due to the DNA repair mechanism being overwhelmed, or because it has been lost (which may be due to spontaneous mutations, epigenetic mutations, or congenital), the cell essentially ‘goes rogue’ and proliferates uncontrollably.
“The above is known as the ‘somatic theory’ of cancer, and is the most widely-accepted one in scientific circles. It’s important to note that it is far from complete, with heavy research ongoing. Many other factors, such as metabolism, and epigenetics, play a role, and these are the subject of hundreds of ongoing studies. But… as you can see… it’s complicated.
“So, you can see how frustrating it is for legitimate cancer researchers when people like serial Digital Clubbing offender Tim Noakes tweet simplistic things like, ‘Cancer is a carbohydrate-driven disease’, or others who say, ‘Sugar causes cancer!’. Making simplistic generalisations about an exceedingly complex disease does no one – including cancer sufferers – any favours.
“So where does it come from? Why are some people so convinced that carbohydrates and sugar cause cancer? And that a ketogenic diet can help?
“There is well-established link between obesity and cancer, but this is unrelated to carbohydrate ingestion, and is thought to be as a result of the fact that adipose cells in the body cause a chronic level of low-grade inflammation which can damage cells (see above). (1) Adipose cells also release hormones and adipokines, which can be carcinogenic. (2)
“Much of the real interest, however, stems from a phenomenon called the ‘Warburg Effect’. Otto Warburg was a Nobel Prize-winning scientist who noted that some cancerous cells seemed unable to efficiently metabolise glucose, preferring the fermentation to lactic acid even in the presence of oxygen, which would usually allow the more effective oxidation of pyruvate. He hypothesised that this shift was the cause of the malignant transformation of cells. It was a clever idea. Except we now know he was wrong. The effect he noted is the consequence of malignant transformation, not the cause. To put it another way: cells don’t become malignant because they metabolise glucose weirdly, they metabolise glucose weirdly because they are malignant.
“Despite this well-established fact, many have jumped up and down and said, ‘Look! The Warburg effect shows that glucose causes cancer!’ This is false, but what if we ignore the Warburg effect as a cause of cancer, and say, ‘Ok, sure, but those cells still need glucose to work. More so than healthy cells because they’re so metabolically active. What if we simply stopped eating sugar? Wouldn’t that “starve” the cancer?’
“The answer, sadly, is no. Firstly, there is no ‘magical’ property of sugar that separates it from other forms of glucose. Table sugar as we know it is simply a disaccharide called sucrose (one unit of fructose combined with one unit of glucose). In the intestine, the enzyme sucrase cleaves this into fructose and glucose which are then absorbed. Any other starch is similarly broken down to glucose. In other words, there’s nothing about sugar that makes it particularly ‘attractive’ for cancer cells. Like every other form of starch, it is simply a source of glucose.
“Also, unless you happen to be diabetic, the body regulates your glucose levels very tightly, regardless of what you eat. Even if you avoid carbohydrates altogether, your blood glucose levels remain remarkably constant, because without glucose in your bloodstream, you would die very quickly. So, it is impossible to ‘starve’ cancer cells of glucose, regardless of what you eat.
“There are other reasons, however, why ketosis may be beneficial in the fight against cancer. For the nerds out there, there is some evidence that ketosis may have an effect on mammalian target of rapamycin (mTOR) and glutaminergic pathways in the brain, which are related to the inhibition of cell signaling, which is possibly why it is efficacious in those with intractable epilepsy, and why it may have potential in cancerous cells.
“There is also the hypothesis that tumour cells have increased levels of reactive oxygen species (ROS) and that forcing them to use the mitochondrial oxidative metabolism via a ketogenic diet could sensitise them to chemotherapy and radiation. These mechanisms remain theoretical, however, and have not been adequately demonstrated in human subjects.
“The lack of concrete evidence hasn’t stopped the cranks from coming to the fore. A regularly cited expert is Thomas Seyfried, professor of biology at Boston College, and author of the book ‘Cancer as a Metabolic disease’. He claims that the cure for cancer is the ketogenic diet, which works better than chemotherapy. Nephrologist Dr Jason Fung has written an entire blog series rubbishing the somatic theory of cancer, agreeing with Seyfried that metabolism is the culprit, and advising intermittent fasting as a treatment, despite a complete lack of evidence to support his claims. (3) They both claim ‘the establishment’ and ‘Big Pharma’ are suppressing research into the idea of cancer as a metabolic disorder because there’s simply too much money to be made from chemotherapy. We’re overlooking a simple truth, they claim, and those silly cancer researchers and their high falutin’ ideas about ‘receptors’ and ‘cell division’ are simply barking up the wrong scientific tree.
“But as always, the truth is a little more complicated than that. Firstly, to claim that science is ‘ignoring’ the metabolic side of cancer is simply incorrect. A quick Pubmed search of research into the metabolism of cancer cells yields over 40,000 papers: hardly the sign of a field being maliciously ignored by scientists at large. Indeed, a brief perusal of these papers indicates that looking at cancer as ‘either’ somatic or metabolic is to create a false dichotomy; quite simply, it is likely both.
“In addition, the beloved Warburg effect only applies to 60-90% of cancerous cells, (4) with good evidence that certain tumours (specifically breast cancers) may actually be exacerbated by ketones in the blood. (5) When we look at the actual evidence of the effect of ketosis on cancer cells, two things immediately stand out. First, the vast majority of the existing research is on animals, specifically rodents. And second, most of the research is on brain tumours. Now there is nothing wrong with animal research per se (unless you believe it is unethical, but that is a discussion for another day), and it provides an important platform for human studies. But assuming that because something works on rats it can be successfully applied to humans is a mistake, because there are major physiological differences between the species. Furthermore, as noted, even if the ketogenic diet were shown to be beneficial for brain tumours (where its effect is likely the greatest), it cannot be extrapolated that it works for, say, thyroid cancer.
“Because as stated above, all cancers are unique. And yet Seyfried and company blithely march on banging the ‘Science shows the ketogenic diet works for cancer!’ drum.
“To add insult to injury, many of them use the so-called ‘2% Gambit’ – that is, that in recent years, chemotherapy has only improved mortality for cancer sufferers by 2% (the implication is clear: don’t use it! It will make you sick but won’t really help you live). It is based on a single analysis (6) that, bizarrely, included both palliative and curative patients, ignored leukaemias and some lymphomas (both of which respond well to chemotherapy), and cherry-picked odd studies while omitting others. A subsequent letter to the editor highlighted the many, many problems with the study, but it continues to be shared with gleeful abandon by professors and journalists who should know better. (7)
“Some might be wondering right about now: what’s the harm? I mean, if someone is doing the whole chemo/radiation thing, and they want to try the ketogenic diet as well, what’s the big deal? Maybe it can be used as an adjunct to existing treatment modalities?
“A big problem with most cancers is cachexia (weight loss). This is due to both a suppression of appetite, and an increase in the metabolic rate of those affected. Regardless of the mechanism, the presence of cachexia is well established as a negative prognostic sign for cancer sufferers (8), which is why caloric intake is so important.
“Concerns have been raised that the ketogenic diet may exacerbate cachexia, both because it may inhibit appetite, and because of its severely restrictive nature. There are some small studies that seem to indicate that it is, in fact, safe, (9) but doubts persist, and it would be foolhardy to blithely assume that advising a ketogenic diet to cancer sufferers is without risk. In addition, many find the extreme nature of the diet simply too difficult to adhere to.
“This has not stopped cranks from relentlessly promoting it, however. ‘The Keto Kitchen’ – the brainchild of Irish Chefs Domini Kemp and Patricia Daly – regularly advises its readers to use the ketogenic diet if they have cancer. Despite being sanctioned by the Advertising Standards Authority of Ireland (ASAI) and told to stop, they blithely continue, and are given endless space in the apparently reputable Irish Times to peddle their unproven ideas.
“South Africa’s own Marika Sboros advised her 10,000 twitter followers to consider ‘deferring’ chemotherapy and try the ketogenic diet instead. Internet uber quack, Joseph Mercola, is on record as stating that the ketogenic diet should be used instead of standard oncological care. These are all grossly irresponsible claims and have the potential to harm very vulnerable people.
“So, where does that leave us? Firstly, there is simply no evidence whatsoever that eating carbohydrates or sugar either increases your chances of developing cancer or exacerbates an existing cancer. The ketogenic diet shows early promise for some cancers but not others(10), but this evidence is limited to animal and tiny human studies, and in addition to being difficult to adhere to, may have dangerous side effects.
“This makes it very difficult for evidence-based oncologists to recommend it to their patients at this time. Given the serious and emotive subject of cancer, we should be treading carefully with such knowledge, and avoiding generalisations and hype. We should not be casting aspersions on hard-working cancer researchers, telling people to dismiss their oncologists, or advising them to embark upon restrictive diets against medical advice.
“Desperate and impressionable cancer patients are not fodder for book sales or click-bait for websites. Promoters of the ketogenic diet would do well to remember that and be more responsible in their claims moving forward.”
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