FASTING and CALORIE RESTRICTION can slow, and even stop, cancer progression, tumour growth and metastases, kill cancer cells and significantly improve chemotherapy and lessen radiotherapy damage; fasting has also been shown to boost the immune system, de-fat both the liver and pancreas, and significantly reduce chemotherapy side-effects.
It has long been established that fasting can improve longevity through the generation of Sirtuin 1. In Intermittent fasting - where you fast for three or more days, Sirtuin 1 is an important hormone in its actions to protect healthy cells. It is not a factor in Time Restricted fasting. In this article, we will explain the differences and the benefits of both.
Two new meta-analyses show that a fast is something to seriously consider when having conventional cancer treatments.
In a meta-analysis of women with breast cancer (16), intermittent fasting (IF) for 3 days across IV chemotherapy was found to be feasible, safe and able to reduce chemotherapy-induced adverse effects and cytotoxicity. It also seemed to improve quality of life during chemotherapy, through the reduction of fatigue, nausea and headaches. Intermittent fasting was found to reduce chemotherapy-induced DNA damage of healthy cells and improved serum glucose, insulin, and IGF-1 concentrations.
In a second meta-analysis, fasting and calorie restriction before and after radiation treatment also seem to reduce damage to healthy tissue and improve survival but benefits were not as clear cut as for those with chemotherapy (17).
The History of Fasting
Fasting has been a part of the treatment of illness since Hippocrates, and Plutarch was quoted as asserting, ‘Instead of using medicine, rather fast a day’.
Ayurvedic Medicine has long held that fasting was a way to regenerate the fire in the digestive system and to ‘burn’ away all the toxins accumulated in the body and mind.
Ayurvedic fasting can involve consuming nothing; or consuming only water; or water and herbal teas; or water and light food.
The results apparently give you a lightness of body, improved digestion, a reduction in bloating, increased energy and improved clarity of mind.
During the second World War, the people of countries such as Norway and Belgium had insufficient food. Apart from weight loss, it was noted that the populations seemed to be healthier with increased longevity.
In 1946 a study from Florida Medical School was published on rats (9). This showed that littermate females lived longer than males and that the benefits of fasting were more significant for males. The rats fasted either 1 in 2, 3 or 4 days. Best for males was 1 in 2, and they lived 20% longer; best for females was 1 in 3 and they lived 15% longer. There was no retardation of growth as a result of the fasting, but the researchers observed that the fasting female rats had less mammary tumours.
In 2000, research from Kyushu University (10) on female rats subject to fasting for 4 consecutive days every 2 weeks showed that the adult females were actually heavier, had less illness and lived to a mean age of 64 days, while the control group lived a mean of 47 days.
Longevity is clearly not the only benefit. Two UK Professors Roy Taylor and Mike Lean have used a non-starchy vegetable juice fast to reduce fats in the blood stream and from around the liver and reverse Type-2 diabetes in patients who had had the disease for up to 15 years (11).
The current ‘expert’ in the fasting field is probably Dr. Valter Longo, Professor of Biochemistry at the University of Southern California. He is a bio-gerontologist and has studied the effects of diet, particularly on cellular protections. He runs the Longo Foundation and has written a book called The Longevity Diet. His group at USC has shown that fasting retards the growth of tumours, strips the guard protecting cancer cells from the immune system, and that fasting can help chemotherapy work better.
Types of Fasting
Let's be absolutely clear what we are talking about!
1. Time-Restricted Fasting (TRF)
This is the big American fad where health 'experts' have decided you should not eat after 6 pm, and only start again after 10.00 or 11.00 or 12.00 the next morning. So you are limiting the eating period to 6-8 hours a day. It is correctly called Time Restricted Eating (TRE). As you will see, TRF is all about calorie consumption.
The research on the benefits is rather mixed (4). Human studies show that people tend to eat less calories and most usually lose weight (although not in all the studies). Of course, it depends on what types of food you actually eat during the eating period. This same 2014 study did find that there were benefits in lower concentrations of glucose, triglycerides and LDL, with higher HDL levels. One study (5), which looked at 'Ramadan fasting' over a 10-year period, saw subjects with a previous history of cardiovascular disease show benefits in systolic blood pressure, lipid profile, weight and BMI. However, an earlier study (6) showed no significant changes in serum cholesterol, LDL and triglycerides, although some benefit in inflammatory markers. One theory is that if Time Restricted Fasting does cause you to lose weight, your blood statistics improve. If it doesn't, they don't! Another theory is that you only see real health benefits if you adopt it for a long time period, for example, for longer than 5 years.
Not every research study on Tume Restricted Fasting has gone well nor been conclusive.
Go to: Time Restricted Fasting is a waste of time
However, importantly there is a 2016 study (12) following 2413 women from the Women’s Healthy Eating and Living Study showing that across an 11.3 year period, women with breast cancer who ‘fasted completely for at least 13 hours overnight had 36% less recurrence and were 21% less likely to die from breast cancer.
A major problem is that many people (including 'health experts') confuse 'Time Restricted Fasting' with ...
2. Intermittent Fasting (IF)
People who do this properly, understand this involves whole days in the week, not hours in the day. Intermittent fasting is significantly more beneficial. It's when, for example, you eat for five days, but fast for two (5:2). A few people practice Alternate Day Fasting.
As we said above, Time Restricted Fasting is about how many calories you consume in an 8 hour period rather than how many you would have eaten in a 24 hour period. This leads to weight loss and its potential benefits.
But Intermittent Fasting is longer and is about activating the body's self-defence mechanisms. It is far more about your hormones.
When you have fasted for 24 hours, the body produces sirtuins, particularly SIRT1 and SIRT3. According to a meta-analysis (7), these alter your insulin levels and reduce insulin resistance, they alter your anti-oxidant response and they alter glycolysis. They make the body less prone to oxidative stress, alter metabolic homeostasis and can restrict cell division. In cancer, sirtuins can slow or stop cancer growth and enhance the effects of certain cancer drugs.
Sirtuins, and particularly SIRT2, also have a significant effect on longevity and aging. In war-time Belgium and Norway, a lack of food often meant people went without eating for several days and this prompted a major hormone change in the body. A University of Florida team has shown (8) that the effect of sirtuins on insulin and other hormones protects the health of cells and encourages longevity.
If you fast for 5 days what happens? First your poor quality white cells die off after 24-36 hours. After 24 hours you produce Sirtuins which shut down your healthy cells to avoid damage. After 36-48 hours your body naturally goes into ketosis - providing fuel as ketone bodies for healthy cells. When you start eating again on day 6, your immune system starts to produce new 'healthy' cells. Your immune system is strong. Your cancer will not have progressed as there was vastly reduced levels of blood sugar (which the cancer NEEDS to feed), Levels of inflammation in the body will have declined.
If you want to use a fast with chemotherapy - When having IV Chemotherapy on a Wednesday for example, , we advocate that patients start a water fast at 6 pm on the Monday, two days before - at 6 pm on Tuesday, your body will produce Sirtuins and over Tuesday night your healthy cells will be shut down. When you have your IV chemo on Wednesday, your healthy cells will not pick up the chemotherapy (less toxicity, side-effects and damage) and more drug is available for the cancer cells. Win-Win. You come out of the fast at noon on the Thursday. Total time in the fast - less than 3 days.
(The only thing that might get in the way is an increase in blood sugar - the Doctors/Nurses might give you large amounts of sugar with the drugs and/or Dexamethasone (which is known to spike blood sugar).
Is there any evidence to support this? In 2019 a human study using 'Short-term fasting' involving at least 36 hours before chemotherapy, the day of chemotherapy and half a day after, showed beneficial effects on quality of life, well-being, fatigue and improved drug tolerence.
Go to: Benefits of Short-term fasting with chemotherapy
So much for the NHS booklets telling you to pour dairy, sugar and sticky buns down your throat when having chemotherapy!
The theory was simple. Fasting causes hormone messages to be sent to your healthy cells telling them to shut down – to go on standby. Their metabolic rate declines and so they don’t take on board the chemotherapy or free radicals, leaving more for the cancer cells which are metabolising vigorously. Result - more dead cancer cells, less damage to health cells.
It is now widely accepted among advocates of fasting that you should fast for 2-3 days before your chemo, the day of chemo and half a day afterwards. Patients report far less sickness; and studies report less neutropenia and other damaging side-effects. Obviously, you need to have all your chemotherapy on just one day to do this. With daily pills the plan doesn't apply.
So what is a fast?
People who want to fast want to know how to do it. Water only? Can I have green tea, or herbal teas? Can I eat juices or smoothies?
In Time Restricted Fasting you do not eat at all from 6 pm to 10 am.
In Intermittent fasting, whether this involves one day in two, two days per week (5:2), or 4 days per fortnight, although it is best to just drink water, so people can merely go down to 25% of normal calorie intake, particularly avoiding all carbs.
This is called …
Calorie Restriction
Calorie restriction (a reduction in energy intake without malnutrition - usually involving a reduction by 15% of carbohydrate calories consumed) is an interesting concept in the health field. It is linked to increased lifespan, better metabolism and reduced risk of chronic illness (1). Calorie restriction is good for you!
Research studies with animals have shown longevity improvements of up to 40 per cent by reducing the intake of daily calories consumed to just 10 to 15 per cent below normal levels.
A 2007 research study by Krista A Vardy and Marc K Hellerstein showed that Alternate Day Fasting (where every other day, there is a fast consisting only of a 400 calorie meal for women and a 600 calorie meal for men) was associated with reduced blood levels of glucose, insulin, IGF-1 and ‘bad’ fats, with a long-term reduced risk of chronic diseases including diabetes, cardiovascular disease and cancer.
In early 2013, The Oncologist magazine commented in the Editorial on research from Chicago Medical School that showed restricting calories by cutting carbs 15% in patients having radiotherapy produced better results. It suggested the same might be true of chemotherapy and calorie restriction (15).
This confirmed 2010 research (13) that water fasting protected normal mammalian cells but not cancer cells during chemotherapy and so greatly reduced side-effects. The researchers called this ‘differential stress resistance’.
Further studies at UCS and Leiden Medical Schools showed a 2 day fast prior to chemotherapy or radiotherapy reduced side-effects and improved survival times with GBM. Fasting made brain tumours more vulnerable (14).
Dr. Dominic D’Agostino of Florida University Medical School has also done a considerable amount of work on Calorie Restriction and fasting. He confirmed that carbohydrate restriction on its own is enough to reduce levels of blood glucose, insulin and IGF-1, all implicated in the cancer development process. But a complete fast forces the body after 2-3 days, into a state of Ketosis, where without carbohydrate, the healthy cells burn fats or Ketones. Cancer cells cannot do this and so starve.
However, while this is healthy in itself, he believes that when you have your next meal containing carbohydrates, the glucose and hormone levels will spike. He argues for a continuous ketogenic diet as a healthy diet – where carbohydrates are kept low and fat consumption is the norm. It should however be noted that saturated fats are proven to spread various cancers. Choose your fats wisely.
So, do you need to fast completely, or can you just restrict your calories?
Longo now adds to the confusion – he has launched his Fasting Mimicking Diet; it’s called ProLon. It is an Intermittent Fast – you do it for 5 days a month. And you eat foods that are chosen so the body doesn’t recognise it is eating. Yes, seriously. The diet – which looks remarkably like the Rainbow Diet – is eaten for the 5 ‘fasting’ days and manages your C-reactive protein, IGF-1, insulin, glucose etc. levels. Profits go to the Foundation that has been set up.
So what else can Fasting achieve?
* Fasting increases cancer survival – The National Cancer Institute in America is interested in fasting because they recognize that the foods you eat can affect the way your body absorbs and reacts to drugs.
For them, fasting may well be a way of helping chemotherapy deliver better results, with less side-effects and more cost-effectively.
They quote the work of Dr. Valter Longo, and his various studies since 2008; not just his work with rats but a study of 10 elderly cancer patients who voluntarily underwent short-term fasting before and/or after chemotherapy. The patients reported far fewer side-effects.
In 2012 in response to spurious arguments that fasting might promote cancer growth, the same team produced further research (Science Translational Medicine; 7 March 2012) showing that fasting makes cancer cells more sensitive to chemotherapy. Fasting actually stopped cancer cells producing ‘protection proteins’ from their mutated genes, while healthy cells made more protective proteins. As a result the healthy cells stop dividing and are less attacked by the chemotherapy resulting in lowered side-effects. In some combinations of fasting and chemotherapy the tumours actually disappeared. So fasting can improve effectiveness. And reduce the side-effects of chemotherapy.
Longo’s team identified a second factor working against the cancer cells: Fasting, of course, deprives a cancer cell of glucose. Dr. Longo describes these as two stressors acting simultaneously.
Indeed, in animal studies (mice with implanted breast cancer, melanoma or glioma cells) short-term fasting alone delayed tumour growth to the same extent as treatment with the drug cyclophosphamide!
* Fasting improves the immune system - In 2014 Longo and his UCS team showed that fasting caused ’old’ white immune cells to die. These were replaced from stem cells as soon as the subject recommenced eating. Thus a three day fast could regenerate a strong immune system.
* Fasting can improve cancer survival - The theory that calorie restriction or fasting could improve cancer outcomes was tested by Longo in 2008-2012. He found two additions. Fasting alone caused cancer cells to self-destruct; they didn’t understand the ’shut down’ message and so kept metabolising but with no nutrients, resulting in cell death. Secondly, not only was there reduced tumour activity but spread was also simultaneously reduced. It was shown that fasting alone (rather than by having simultaneous Chemotherapy or radiotherapy) could achieve these results in 5 out of eight cancer types. But repeated 2-3 day bursts of fasting with chemotherapy bursts was far more successful(3).
In tests with mice, 20% of those with metastases that fasted and had chemo were cured; 40% of those without spread. Human studies are covered below.
* Weight control increases survival - Northwestern Medical School in 2012 showed overweight women with breast cancer survived less that women of optimum weight. However, it was never too late to start cutting calories, and women who cut their weight to correct levels also survive longer.
All this fits with the American Cancer Society’s 2012 Research Report that stated there was overwhelming evidence that diet, exercise and weight control could improve survival times and even prevent a cancer returning.
* Sugar and insulin drive cancer – there is now overwhelming research that high blood sugar levels directly, or indirectly via insulin, drive cancer.
Go to: 20 links between sugar and cancer
How to fast
This is actually really important; but simple to understand.
Whether you are an advocate of Ayurvedic Medicine, a disciple of Longo, or having chemo, on a real fast you should drink water only for 3 to 5 days. No more, no less.
To summarise: this type of fast
· Brings plasma glucose, IGF-1 and insulin levels down to zero,
· Restricts free glutamine levels, reducing glutamate,
· Reduces Triglyceride and cholesterol levels
· Stops cancer progression, stops metastases,
· Makes chemotherapy and radiotherapy work better (and you need less chemo to achieve the same results)
· Reduces the side-effects of chemo and radiotherapy and can increase survival times, and,
· Helps reboot the immune system.
BUT
An organic non-starchy vegetable juice fast incorporating whole plants (to a maximum of 800 calories a day), can have similar effects and was shown to reduce cholesterol and triglyceride levels and reverse Type-2 diabetes. If you want to fast for health, or plan regular fasting, real intermittent fasting or fasting for more than 5 days, you could employ this fast.
Several mechanisms involved in fasting
Clearly then, many factors are at work during intermittent (24 hour plus) fasting. Importantly, it has a significant effect on key hormones - Sirtuins are produced, thyroid function alters, insulin levels fall.
Growth hormone levels actually increase – one effect is to keep your lean mass effective. Noradrenaline keeps our energy levels high so we have the strength to go hunting for food.
Meanwhile we eat our own fat.
Fasting as a cancer treatment
It was interesting to read the story of a lady who wrote into CANCERactive after we ran a story on Calorie Restriction in our e-magazine, telling us how her Doctor father who specialized in cancer achieved remarkable results by putting his patients on a water-only fast before treating them.
The next correspondence came a Doctor from India who puts everybody he receives on a fasting regime at the outset after diagnosis and does not start treatment for a couple of months. He claims that results are impressive and that fasting starves the cancer more than the patient. Research would suggest that is correct.
Of course, many cancer experts will point to the severe weight loss involved in cachexia and its dangers. But this is a very different issue – it is an uncontrolled weight loss caused by the side-effects of the chemotherapy drugs and side-effects such as nausea reducing the desire to eat. This is not a controlled weight loss but a drug-induced illness.
Research with lung cancer patients on chemotherapy showed that omega-3 from fish oils could help people regain their appetite and weight, avoiding cachexia. It may be true for other cancers.
So, should fasting be part of your integrative cancer programme? And is that a total, water-only fast? Should you maintain some intake of anti-cancer natural compounds? Let’s amplify what we have said above.
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Fasting, metabolic theory and cancer
An overwhelming aspect of fasting with chronic illness is the increasing understanding that the vast majority of chronic illness is the result of poor metabolism, of poor diet, of high blood fats, blood glucose, blood insulin. And the National Cancer Institute is clear on this. If the problem lies with metabolism, why cannot the solution. It’s called the metabolic theory of cancer.
Their Head of nutrition is Dr. Young S. Kim – she is an epigeneticist. The way forward is understanding how to correct what is happening in the body, not simply to blast a sequence change (a mutation) that may or may not have occurred inside the DNA with chemo or radiation.
1. Fasting and chemotherapy
Three clinical trials are now planned helped by Dr. Longo and his work. Furthermore, a group of 12 cancer centres across the world is planning two clinical trials – one at whether fasting can reduce chemo side-effects; the other at whether fasting can improve chemotherapy effectiveness.
According to USC research, 70 per cent of cancer patients would refuse a water-only fasting regime if offered. So, to mask this problem, a product called Chemolieve has been developed which provides no nutrients to cancer cells!
However, pharmaceutical companies might not be so happy if fasting (or what is now being called ‘The Food Effect’) means less drugs are needed. Elsewhere on this website we have already covered how some foods negatively react with some drugs. But some foods aid the action of other drugs. And now some pharmaceutical companies are even suggesting that fasting would allow the use of greater volumes of their drugs!
2. Preventing dormant cancers becoming active
In a March 2013 paper by the Max-Planck Institute in Germany, they argue that tumour cells often lie dormant in the body with as many dying off as replicating. When an event to change this occurs, it usually sees messenger compounds being produced which stimulate blood supply development and therefore tumour growth. The Institute argue that the obvious step is to stop nutrients feeding this change, leaving the dormant cells in a harmless state. Their work, entitled ‘Fasting time for cancer cells’ looks at lung cancer.
3. Inducing Ketosis through fasting
Professor Thomas Seyfried of Boston College is one of the main champions of the Ketogenic Diet. He outlines the following science:
“Reduced glucose availability will target aerobic glycolysis and the pentose phosphate shunt; pathways required for the survival and proliferation of many types of tumor cells. Dietary energy restriction specifically targets the IGF-1/PI3K/Akt/HIF-1α signaling pathway, which underlies several cancer hallmarks to include cell proliferation, evasion of apoptosis, and angiogenesis
Besides lowering circulating glucose levels, dietary energy restriction elevates circulating levels of fatty acids and ketone bodies (β-hydroxybutyrate and acetoacetate). Fats and especially ketone bodies can replace glucose as a primary metabolic fuel under calorie restriction.
The shift from the metabolism of glucose to the metabolism of ketone bodies for energy is due largely to the shift in circulating levels of insulin and glucagon, key hormones that mediate energy metabolism. Insulin, which stimulates glycolysis, is reduced under dietary restriction, while glucagon, which inhibits glycolysis and mobilizes fats, is increased. Glucose reduction not only reduces insulin, but also reduces circulating levels of IGF-1, which is necessary for driving tumour cell metabolism and growth. Glucocorticoids, which enhance glucagon action and the stress response, are also elevated under dietary energy restriction. The shift in levels of these metabolic hormones would place greater physiological stress on the tumor cells than on normal cells since the tumor cells lack metabolic flexibility due to accumulated genetic mutations.
Proof of concept for cancer metabolic therapy was illustrated for the management of malignant astrocytoma in mice, and malignant glioma in children. Prostate and gastric cancer also appears manageable using low carbohydrate ketogenic diets. Recent studies show that dietary energy restriction enhances phosphorylation of adenosine monophosphate kinase (AMPK), which induces apoptosis in glycolytic-dependent astrocytoma cells, but protects normal brain cells from death. This further illustrates the differential response of normal cells and tumor cells to energy stress.
His final views may overcome the ‘What about cachexia?’ critics. ‘It is important to recognize that pro-cachexia molecules such as proteolysis-inducing factor are released from the tumor cells into the circulation and contribute to the cachexia phenotype. By targeting the glycolytically active tumor cells that produce pro-cachexia molecules, restricted diet therapies can potentially reduce tumor cachexia. These therapies could be supplemented with omega-3 fatty acids, which can also reduce the cachexia phenotype. Omega-3 fatty acids from fish oil also have the benefit of maintaining low glucose while elevating ketone levels. Once the tumor becomes managed, individuals can increase caloric consumption to achieve weight gain’.
Go To: The KETOGENIC DIET
In 2012 Cancer Watch covered research studies showing that fish oils did indeed reduce cachexia levels in lung cancer patients.
The benefits of fasting with cancer; a summary
Generally, it would seem that Time Restricted Fasting is only useful where people do not consume the same number of calories in 8 hours as they would have in 24. And where it is used consistently for, say, 2 years or more.
Intermittent fasting seems to have more benefit in males than females and lasts typically for at least 2 days, in seven.
Fasting – and calorie restriction - before and during a one day chemotherapy, or across a radiotherapy programme seems to increase effectiveness, survival and reduce side effects.
Fasting alone, where patients have not had any orthodox therapies, may increase survival. Fasting alone can cause cancer cell death.
The fear of cachexia amongst hospital workers often causes them to provide totally misleading advice on diet during orthodox treatment.
Interestingly, when this article first appeared, I received several letters of praise from oncologists in America, where it seems to be quite a ’hot topic’. Thank you.
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Ref:
1. Mattison JA, Lane MA, Roth GS, Ingram DK. Calorie restriction in rhesus monkeys. Exp. Gerontol 2003;38:35–46).
2. https://www.ncbi.nlm.nih.gov/pubmed/28539118
3. Longo, V. 2012. Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy. Science Translational Medicine.
4. Nutr. Rev: Rothschild J; Hoddy et al: 2014 May;72(5):308-18. doi: 10.1111/nure.12104. Epub 2014 Apr 16.; https://www.ncbi.nlm.nih.gov/pubmed/24739093
5. Ramadan fasting: https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-11-69
6. Ramadan Fasting: https://www.ncbi.nlm.nih.gov/pubmed/17374948
7. Intermittent fasting, sirtuins and cancer - https://www.ncbi.nlm.nih.gov/pubmed/24048020
8. University of Florida - Intermittent fasting and Longevity - https://www.liebertpub.com/doi/abs/10.1089/rej.2014.1624
9. https://academic.oup.com/jn/article-abstract/31/3/363/4725632
10.https://www.sciencedirect.com/science/article/pii/S0047637400001093#!
11. https://chriswoollamshealthwatch.com/featured/now-you-can-reverse-type-2-diabetes/
12. https://www.ncbi.nlm.nih.gov/pubmed/27032109
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048045/
14. https://news.usc.edu/41212/fasting-makes-brain-tumors-more-vulnerable-to-radiation-therapy/
15. http://theoncologist.alphamedpress.org/content/18/1/97.full
16. Intermittent Fasting in Breast Cancer: A Systematic Review and Critical Update of Available Studies - Marios Anemoulis et al; Nutrients. 2023 Feb; 15(3): 532.
17. The Potential of Fasting and Caloric Restriction to Mitigate Radiation Damage-A Systematic Review - Simon Valayer et al; Front Nutr. 2020 Sep 18:7:584543.
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