Our growing understanding of tumour metabolism provides new opportunities to conquer this dread disease. But it also brings a new threat: people are confused between what their tumour ‘eats’ and what their body needs to eat. Do you know the difference?
There is a new wave of cancer cognoscenti – empowered patients who are fearlessly getting to grips with the swings and roundabouts of Krebs cycle to improve their chances of survival. The metabolic approach to cancer allows us to take an active role in our own cancer care. There are many routes into this new territory but Jane McLelland’s ground-breaking ‘metro map’ is leading the way, providing new inspiration for patients with advanced cancer.
It’s good to see people looking beyond what the NHS currently offers but metabolic pathways are complex, and they don’t always work according to the text book. Controlling nutrient delivery to tumour cells is complex, and there is a risk that in trying to starve your cancer you may accidentally disable some of the ways your body is trying to heal you.
On the other hand, those of us who have had cancer know we would try anything to get rid of it. That includes enduring a level of suffering and a lower level of health for a time. This is the theory behind chemo- and radiotherapy: they’re not healthy or restorative, they offer the hope of killing dangerous cells and they come with a whole load of unpleasant side effects and carry risk of death. So if avoiding some key nutrients can do a similar job, or make treatment work better, we’d be mad not to try.
Let’s be clear, cancer cells have been shown to thrive on many different fuel types (glucose, ketones, amino acids, fructose, to name a few) and there is evidence that if you restrict certain fuel lines they will swiftly adapt to use another. Thus, the best anti-cancer diets provide have an underlying philosophy of nutrient sparing – providing the bare minimum for survival of the organism without providing excess fuel of any sort for tumours to use. Since cancer cells feed and grow and divide much more than healthy cells they have a much higher nutrient requirement, so any anti-cancer diet should, at the very least, act as a ‘speed bump’. Which is as good a reason as any to resist the pressure of some oncology departments to ‘feed you up’ and help you put a bit of weight on.
If ‘you are what you eat’, your tumour certainly isn’t. Your body can readily manufacture glucose, fatty acids and some amino acids even if you don’t provide them in your diet, and tumour cells are capable of commandeering metabolic processes to get the nutrients they prefer. Extreme avoidance of nutrients in your diet may lead to undesirable tissue breakdown which doesn’t help you but does feed your tumour. So we are walking a fine line with diet, trying to support healthy cells and thwart cancerous ones.
For prevention and early stage disease where surgery has been able to remove all detectable cells, it’s possible to talk about a more generalised anti-cancer diet. For these cancer patients personalisation is an oppprtunity to mitigate environmental and genetic risk factors without the need to starve cancer cells.
For patients with advanced stage disease, those with lymphatic spread and/or metastatic development, a further level of personalisation is possible if we can ascertain what the tumour is using to fuel growth and division and we can attempt to reduce supply of key nutrients. This is a brave new world where research is scarce and human studies are unlikely to exist. If they do, there’s no guarantee that your breast tumour is behaving in the same way as someone else’s, even if they have an identical diagnosis. We simply don’t have that level of knowledge. Yet.
For example, triple negative breast cancer is the most difficult breast cancer diagnosis because there are not so many conventional treatments available. Unlike hormonally responsive cancers we can’t stop the oestrogen supply to arrest growth so in this area nutritional solutions are even more appealing. There is early and confusing evidence that triple negative breast cancer is responsive to a ketogenic diet, and also to methionine deprivation and also driven by fatty acids: limiting sugars, fats and proteins have all been shown to produce inhibition in these tumours. The six-million-dollar question is which one of these is fuelling yours? And how can you find out?
One thing is certain – you can’t make an assumption that your body is behaving in the same way as a bunch of cells in a Petri dish – there’s too much at stake. At this stage of our knowledge, trial and error is the only way, using different dietary approaches between scans and blood tests to see what works for you.
In my view, a diet that encourages ketosis is the best starting point for all forms of breast cancer because a low sugar environment is linked to reduced risk gap for all of the receptor types. But what does that mean?
There is widespread confusion about the ketogenic diet and some clarification is needed. There are various ways of being ‘in ketosis’ and various diets can raise blood ketones. New born babies are in ketosis for their first 48 hours, body builders eating only steak and eggs may also be in ketosis, vegans on coconut oil and avocado, and starvation also induces ketosis, so any talk of the ketogenic diet needs to acknowledge that it is not a single diet style. In fact ketosis is simply what happens when your body runs out of sugar and turns to fats for energy. It’s nothing new or radical: healthy bodies do it every day, several times, overnight and between meals.
Being in full throttle ketosis with high blood ketones has been shown to work well for some brain tumours but evidence for other cancers is mixed. So, we need to make a distinction between full ketosis and being “keto-adapted”. If you don’t occasionally switch between carbs and fats for fuels you are likely to be sugar dependent and insulin resistant, both of which are clearly linked to increased rates of cancer and worse cancer outcomes. Becoming keto adapted by reducing your carbohydrate intake (again a very personal equation) is the only way to reverse these issues. And they must be reversed if you want to create a health and cancer-hostile tissue microenvironment.
All healthy humans are keto-adapted, producing some ketones every day. The inherent metabolic flexibility provides many anti-cancer benefits beyond the question of tumour fuelling and may still be adapted to limit key amino acids and reduce fatty acid availability in the longer term.
To explain that a little more I need to return to the key message behind my work: your body has far more powerful healing mechanisms than we understand. More than the NHS and beyond the ken of current research. My view is that supporting innate healing is still the best route to health. If you treat or eat in a way that disables those powers you are risking more than we know in order to follow unproven theories.
This rest of this post provides more detail about how the ketogenic diet works as an integrated choice. It’s a long read, cramming several years of study and clinical experience into a few paragraphs, so please “bear with”. And if I’m teaching you to suck eggs, forgive me.
1. The fate of macronutrients
The inconvenient truth that inspired this article is this: the nutrients you put into your mouth don’t determine the nutrient supply to your tumour: they rarely reach your cells in the same format. So, for example, if you want to starve your tumour of fats, a low fat diet might not be the way to do it. Likewise, if you want to limit key amino acids (the building blocks of protein) a vegan diet might not be the best or only way.
The macronutrients we eat are, by and large, broken down into smaller particles for absorption and frequently rebuilt in an entirely different way when they hit the bloodstream.
- Proteins, for example, are eaten whole as ‘beef’ or ‘tofu’ and then broken down by digestion to their component amino acids (eg glutamine, methionine, asparagine) and rebuilt on the other side into the ‘you’ shaped molecules that your body needs. Rarely are they used for energy though both healthy and cancerous cells can do so.
- As far as carbohydrates are concerned, the digestible ones are broken down into sugars before crossing into the blood to be burned for immediate energy or stored as glycogen or fats if we eat too much. Again both healthy and damaged cells can easily use a range of sugars to make energy.
- Fats are eaten mainly as triglycerides and broken down during digestion into free fatty acids and monoglycerides for absorption. They are either used immediately for energy or reassembled into triglycerides and stored if we have consumed more energy than we need. During weight loss triglycerides are broken down into free fatty acids and released into the blood stream whether you eat them or not. There is some evidence that cancer cells find it more difficult to use fats and ketones for energy but we know that some can: more on this later in the article.
More importantly, these raw materials can be transformed into other energy forms: we can manufacture fats from sugar, and make sugar from both proteins and fats if metabolic conditions dictate. So the food you put in your mouth can and will be made into something else to meet your metabolic needs – depending on your metabolic state. And if our diets are inadequate the nutrients we need, or our tumour needs, may be released them tissue stores.
2. The metabolic impact of macronutrients
Your metabolic state is the most important driver of nutrient utilisation – more important than the composition of your diet. Nutritionists recognise two contrasting metabolic states, normally referred to as ‘fed state’ and ‘fasting state’ (or absorptive and post-absorptive). Your prevailing metabolic state is controlled by hormones triggered by food, but also by exercise, stress and environment.
Insulin, triggered by eating glucose and to a lesser extent by protein, controls fed state metabolism and is associated with growth and reproduction (not something to encourage in tumour cells). Glucagon, secreted when glucose levels are low, when we’re hungry and during vigorous exercise, predominates during fasting state and is associated with a lack of available nutrients, or ‘nutrient sparing’ – an important goal where cancer is concerned.
Fasting state is currently considered to be the optimal metabolic background to help your body deal with cancer, not only because it can minimise fuel supply but also because it reverses many other risk factors associated with cancer – like insulin resistance, hormonal imbalances, inflammation, oxidative stress and growth signals – and triggers nutrient-sensing mechanisms to switch on innate survival programmes. It has also been shown to augment the effects of various cancer treatments because it appears to weaken and sensitise the cells to drugs and toxins.
3. What does your tumour eat?
Following on from the general discussion above we know that choosing the ‘right diet’ for cancer is about more than fuel supply. Not only because we cannot ignore the influences of the wider metabolic environment but also because we don’t fully understand what fuels tumour cells at any given moment. We simply don’t know enough about the behaviour of individual tumours in individual bodies. The Human Genome Project told us that, if nothing else.
We know the individual cells within a tumour are not identical: they don’t necessarily share the same gene mutations and they may not share the same fuel supply. Studies have shown that when tumour cells migrate they can change their fuel supply according to what’s available, and we know the same is true for cancers at different stages. In terms of dietary restriction it follows that nutrient restriction may, at best, provide a window of opportunity rather than a safe long term strategy. Despite some promising studies, it’s sensible to assume that any given tumour may be able to use, or adapt to use, a wide range of fuels, so when we focus in on fuel for tumours, it makes sense to stick to a diet that limits overall fuel supply across a range of energy substrates, rather than one particular macro. (Though of course you may also wish to restrict certain foods in an attempt to inhibit cell division.)
4. About the ketogenic diet
Which brings us neatly to a discussion of the ketogenic diet, or the ‘fasting mimicking diet’ as it is also known. Ketosis is a metabolic pathway favoured by the body when glucose is in short supply, and it activates many of the same pathways as fasting state metabolism. The only thing we know that may be better for cancer than keto is fasting, which obviously has its limitations as a nutritional strategy. Thus, the ketogenic diet creates the best healthy tissue microenvironment for cancer patients who also want to eat.
Like many popular diets, the ketogenic diet is much misunderstood. The biochemistry of ketosis (what Atkins called the metabolic advantage) allows people to overeat fats and still lose weight, which has led to a glut of ‘unhealthy’ keto recipes (fat bombs, bulletproof coffee, and steak with cream and cheese), and created a widespread belief that the ketogenic diet is an unbridled fat fest. Of course, you can do keto that way but you don’t have to. It also has a reputation of being a high protein duet which is simply not true: it’s perfectly possible to be a keto vegetarian, or vegan.
Done well, the ketogenic diet is a way of training your body to use fuel efficiently and to switch seamlessly between the two metabolic states, promoting healing and repair while ensuring optimal nutritional status. This way of doing Keto is more properly called Keto-adaptation. It’s a brilliant way of matching your energy intake to your energy requirement to ensure that you’re not overeating anything and, more importantly, not overfeeding your tumour. Which makes it the ideal anti-cancer diet and the best way to accompany integrated cancer protocols, including Jane’s McLelland’s metro map.
Keto experts tend to recommend blood testing for ketone levels but for this aspect of the diet I particularly like using urinary ketone testing because it gives you a visual guide to when you are overeating. It works like this:
- carbohydrates – if you’re “in ketosis” we know your blood glucose and insulin are way down low so your tumour is not being overfed with glucose.
- fats – measuring urinary ketone output shows you if you are overeating fatty acids (and potentially oversupplying your tumour) and allows you to adjust accordingly.
This means that whether your tumour is fuelled by sugars or fats (and to be honest, most tumours are not that fussy when they are pushed) the keto-adapted diet is the best way to restrict both sources of energy and monitor what’s happening.
5. The ketogenic diet and glutamine
But what if your tumour is glutamine driven? Does the keto-adapted diet still work for that?
This is the main problem that Dr Thomas Seyfried struggled with in his anti-cancer mouse studies. When starved of glucose, glutamine can be used as an alternative source of energy by tumour cells. Since glutamine is the most abundant amino acid in the human body, and forms a major component of nearly all proteins, it is difficult to restrict. Quite simply, if you try to restrict glucose and glutamine by reducing your dietary intake, your body will start to eat you instead – to get at your stored glutamine supply. This inconvenient truth has led many people to abandon the ketogenic diet as a false dawn. But are they right?
It’s correct that studies have shown that glutamine is readily broken down to make glucose in fasting state human metabolism when glucose is scarce. On the other hand, a meta-analysis of studies suggests that the ketogenic diet tends to protect muscle mass because ketone bodies can be used by brain and muscle tissue in place of glucose. Therefore, since ketogenic diets preserve muscle mass better than fasting it follows that they are more likely to limit glutamine supply to tumours, and may be a better choice than other diets (and better than fasting) for restricting glutamine.
6. Nutrition and repurposed drugs
If the aim of your anti-cancer diet is to reduce tumour uptake of any of the major macronutrients (or their component molecules) then the keto-adapted diet, or nutrient sparing diet, is the best way to achieve that nutritionally, based on current research. Intermittent fasting or time-restricted feeding can combine well with this approach to provide synergistic support for medical protocols including chemotherapy, radiotherapy AND repurposed drugs.
Jane McLelland’s zeroes in on the individual metabolic pathways that cancer cells use and healthy cells don’t. But the metro map doesn’t scale up to provide a nutrition blueprint for the whole body. Any anti-cancer diet needs to focus primarily on rebooting and rebalancing the body’s systems to awaken the healing response of the whole body, and the ketogenic diet is the best way we know of creating a cancer-hostile tissue environment.
It must be said that no one has all the answers for cancer at this point in time, and the information shared here may be confounded by future research – but I think any future understanding is likely to build on what we are learning rather than turn it on its head. Thank you for staying with me through such a long and convoluted post. I hope it has helped you make up your mind about the diet you want to follow and I wish you well in your quest for health.
My specialist area is breast cancer and if you are struggling to improve your health after diagnosis I’d be happy to help. Please book a free exploratory chat.