National Nutrition Month: Intermittent Fasting and Cancer

Continuing with our nutrition theme this month, in celebration of National Nutrition Month, I wanted to delve a little deeper into fasting and the fasting-mimicking diet (FMD) in cancer prevention and treatment.

This has been partly fuelled by my interest in - or some might say, obsession with (!) - stem cells. I have a number of Masters students beginning their research projects with me at the moment, and one of them is looking at whether there is any synergy between diet and exercise in mobilizing stem cells.

But before I go into any detail about fasting, FMD, exercise and stem cells, I feel like I want to back up a little and explain a bit about stem cells first.

Not all stem cells are created equal

I think a lot of people hear the term “stem cells” and make an assumption that the reference is to embryonic stem cells, and certainly there has been a lot of controversy around the use of embryonic stem cells in research. But I’m not talking about embryonic stem cells here. No, I’m referring to a few different classes of stem cells.

The term “stem cell” refers to a naive cell that has the potential to change and become a different type of cell. We call these cells progenitor cells, and the process of change is called differentiation.

There are many different types of stem cells. For example, there are those that form different types of blood cell - we call these hematopoietic stem cells. Or, there are those that form new muscle tissue after exercise - we call these satellite cells or myogenic stem cells. And then there are those that are derived from such places as adipose tissue (fat cells), bone marrow and dental pulp - these are called mesenchymal stem cells.

Something I’m particularly interested in is cancer stem cells, which have acquired different mutations in their DNA that gives them the ability to change dramatically. This high degree of plasticity makes them particularly dangerous because not only can they change their characteristics to become more mobile and invasive, but they also have the potential to seed a new tumor and then alter their characteristics again at the secondary site so they can “fade” into the background, like a chameleon. They fit in with the local environment and fool the body’s immune system into leaving them alone.

So what have stem cells got to do with fasting and FMD?

Well, in short, fasting or fasting-mimicking causes a rise in stem cells in the body after food is reintroduced. And it’s our stem cells - these naive, baby, ‘you-can-be-anything-you-want-to-be-when-you-grow-up’ cells that repopulate our areas of tissue damage to help repair and renew the body. In essence, they keep us young.

Early studies in mice and yeast revealed a role for caloric restriction in prolonging lifespan. You may also have heard about the Biosphere 2 experiment conducted in the 1990s where eight researchers lived self-sufficiently for two years in a completely enclosed ecological system.

As part of the experiment, they were also calorie-restricted to evaluate the impact of nutrition on delaying the onset of various age-related diseases.

And it worked!

But it was gruelling.

According to Dr Valter Longo in his book “The Longevity Diet”*, who went to see the scientists emerge from the Biosphere at the end of the study, when they came out, “they were extremely thin and looked angry.”

Driven by the curiosity to find out how nutrition and caloric restriction delays the aging process, but with a desire to find a more palatable way to implement it than living the rest of his days “hangry”, Longo followed the crumbs of his curiosity and has built an incredibly successful academic career in the field of longevity and nutrition. His findings led to some fascinating insights into the role of fasting and fasting-mimicking in stimulating stem cell growth and tissue regeneration.

The evidence base

Whilst studies show that a complete water-only fast for three days can improve the effectiveness of chemotherapy in patients, and reduce the severity of side effects, it is hard to stick to.

In a bid to try and mimic the effects of short-term fasting, Longo and his group developed a dietary protocol that was low in proteins and sugars and high in healthy fats, in order to recreate the four major changes in blood observed in mice that were needed to show that the mouse had entered a protected state as a result of the fast:

  1. Lower levels of the growth factor, insulin-like growth factor-1 (IGF-1) - which has been implicated in promoting tumor growth;
  2. Lower blood glucose levels - which, of course, can lead to type II diabetes (T2D) and there’s a causal link between T2D and cancer;
  3. Higher levels of ketone bodies - the by-product of fat metabolism (see ketogenic diet);
  4. Higher levels of the IGF-1 growth factor inhibitor, insulin-like growth factor binding protein-1 (IGFBP1).

They called this dietary regimen “the fasting-mimicking diet” (FMD), and when tested in mice, they found those that were on this diet lived longer than mice on a normal diet, they ate the same amount of food as mice on a normal diet but the FMD-fed mice had lost weight, particularly abdominal fat, yet without losing any muscle mass. In addition, tumors in mice on the FMD reduced by nearly half, and the onset of cancer was pushed back by 6 months (which is the equivalent to 10 human years). Other benefits included fewer inflammatory skin disorders, improved cognition and increased stem cell-dependent tissue regeneration of the immune system, the liver, muscle and brain.

In a follow up study, a randomized controlled trial (RCT) in 100 human participants, those who adopted the FMD for 5 days a month over three months lost weight (again, majority abdominal fat), increased their lean muscle mass, had lower levels of blood glucose, cholesterol, IGF-1 and C-reactive protein (CRP - an inflammatory marker), as well as lower levels of triglycerides and lowered blood pressure. These are all risk factors for diabetes, cardiovascular disease, and of course, cancer.

The science behind the “magic shield”

What’s important to note is that it’s the fasting that destroys the damaged cells, but then it’s the reintroduction of food that stimulates the growth of new stem cells which serve to regenerate the depleted, damaged tissue.  

Rather than pursuing a “magic bullet” that will target and destroy cancer cells, Longo pursued this idea of fasting and FMD being a “magic shield” that protects the healthy tissues from the harsh realities of chemotherapy.

In his studies in yeast, he made a remarkable discovery: the very same genes that accelerate aging and makes cells more vulnerable were those central to cancer - the oncogenes.

Oncogenes are simply mutated versions of proto-oncogenes, which are the normal genes in our healthy cells that drive cell growth and proliferation. We want our proto-oncogenes to be switched on and off as and when we need them to be: to repopulate our damaged tissue when we have a wound or injury that needs repairing; to line the interior of the womb each month in preparation for embedding a potentially fertilized egg; and so that our children will grow taller and stronger. Without proto-oncogenes, none of these things would happen, and so proto-oncogenes, in themselves, are not a bad thing.

Where the danger lies is when they develop or acquire mutations in their DNA, which leads to their inappropriate activation, like a faulty light switch that is always stuck “on”. Even if they receive signals to stop growing and dividing, cancer cells expressing these oncogenes just ignore these messages and carry on growing, regardless. This also makes them weaker and more vulnerable to damage caused by toxins.

The reason why fasting and FMD works as a magic shield is down to a phenomenon called “differential stress resistance”. If you starve the body, it’ll go into a self-preservation mode - it stops growing, and shuts down all unnecessary processes. This is “the shield”. But with cancer cells, because they’ve acquired these mutations that makes them ignorant to these anti-growth signals, they carry on growing and dividing, even when the body is in starvation mode. They don’t have this same protective “shield” that their healthier counterparts do. And so, if you starve a cancer patient before injecting chemotherapy, the normal cells will respond by putting up this defensive shield, but the cancer cells, ignoring all commands, remain vulnerable to the cytotoxic (cell killing) effects of the chemotherapy.

This is potentially very exciting because it provides us with a method to get rid of all cancer cells with minimal damage to normal, healthy tissues - something that is currently the biggest cause of chemo-related side effects.

Animal studies have shown this approach to be effective in making chemotherapy much more toxic to melanoma, breast cancer, prostate cancer, lung cancer, colorectal cancer, neuroblastoma, and many other cancers. Not all mice were cured, but Longo and his group regularly obtained a 20-60% cure rate! I’d take those odds any day of the week. Studies are still ongoing in humans.

Proceed with caution

There are a number of safety considerations I want to point out here. First, please do NOT, for the love of all that is good in this world, try and implement the FMD for yourself or anyone you’re working with, on the basis of this blog post! I am NOT a medical doctor, or a trained nutritional therapist, and I am NOT in the business of giving out medical advice. I’m just a science geek with a passion for learning everything I can about how cancer works, and critically, how we can overcome it.

That said, if you’re interested in finding out more, then I’d start with his book* and I’d book yourself in to speak to a trained nutritional specialist.

I was very interested to see Longo mention the following in his book (p101):

“A label that is now widely used by the media is ‘Intermittent Fasting.’ I believe this represents a problematic direction because, like the ‘Mediterranean Diet’ or ‘eating in moderation’ it allows people to improvise and pick and choose periods of fasting that range from 12 hours to weeks, giving the impression that just because they all involve some period of ‘abstention from food’ they are similar or equivalent and all provide health benefits. In fact, they have very different effects.”

I’m certainly guilty of this “pick ‘n’ mix” approach to my diet and lifestyle choices. We all love a good compilation, don’t we?! But where patient health is concerned, it is extremely important to follow guidelines that are grounded in scientific evidence.

Some other cautionary notes from his book:

  • Don’t do this diet if you’re pregnant, underweight, over 70 years old, fragile, have liver or kidney diseases, or other pathologies
  • Don’t do this diet if you’re on medication - unless, of course, you have prior approval of your specialized doctor
  • Don’t do this diet if you have low blood pressure or are on medication for hypertension
  • Don’t do this diet if you have any rare genetic mutations that block the ability to make glucose from glycerol or amino acids - the process of gluconeogenesis
  • NEVER do FMD in association with insulin or other medication that lowers blood sugar levels - this could be fatal

Nutrition and FMD for cancer prevention

The Longevity Diet outline in Dr Longo’s book* can be generally applied for cancer prevention, but it can be particularly useful for people with genetic predispositions to cancer, such as those with the BRCA gene mutations that lead to increased risk of breast and ovarian cancer. The Longevity Diet can also help reduce the risk of secondary recurrence in patients whose cancer is in remission. Please note, it is not recommended to replace prophylactic surgeries (e.g. mastectomies) with nutritional interventions, but rather to accompany them.

If this is something you’re interested in following, then please do refer to the book. In brief, the 10 dietary tips for those at high risk for cancer are:

  1. Follow the Longevity Diet (described in chapter 4) with a protein intake on the lower range of the scale
  2. Limit fish intake to 1-2 times a week; otherwise stick to plant-based foods
  3. Reduce sugars to very low levels. Also minimize the consumption of pasta and breads. It is important to keep blood sugar levels as low as possible within the safe range
  4. Maintain a healthy weight and BMI
  5. Exercise regularly
  6. Undergo a five-day FMD every one to three months, depending on your weight and health status
  7. Nourish yourself with essential fatty acids (omega-3 and omega-3), vitamins and  minerals from a variety of vegetables and fish. Your immune system is one of the major defenses against cancer. The diet must be balanced to kill cancerous or precancerous cells without causing deficiencies in your immune system or hormonal changes that can make you frail.
  8. Discuss with your oncologist the option of taking 6 grams of vitamin C daily for a few weeks every 6 months. Multiple studies have demonstrated vitamin C to possess cancer-fighting properties, although its effectiveness in preventing cancer is controversial.
  9. Consume plenty of good fats from olive oil, nuts and fish, but minimize saturated fats, even those that are vegetable-derived
  10. Consume as little alcohol as possible

But where’s the fun in that?!

Invariably, when people hear these recommendations they may think (or say!) something along the lines of:

“I would rather die young than have to eat like that!”

There is an old joke about a man who asks his doctor how he can live longer. The doctor recommends he eat very little, give up alcohol, and stop having sex.

“Are you sure it will work?” the man asks.

“I don’t really know,” the doctor replies, “but no matter how long you live, it will seem an eternity!”

For me, life is about balance, but if it was a choice between cancer and “eating like that”, I know which I’d choose.

One more thing!

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