How Fasting Before Chemotherapy May Reduce Side Effects & Improve Efficacy

This post looks at research in which fasting prior to chemotherapy has been shown to be beneficial. Specifically how it has been shown to protect healthy cells from the toxic effects of chemotherapy, demonstrated in human cells in vitro, mice models¹Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008) and breast cancer patients²The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015).

Reducing chemotherapy side-effects³Fasting and cancer treatment in humans: A case series report – Valter Longo et al. (2009) and DNA damage⁴The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015).

In addition to protecting healthy cells, fasting has been shown to sensitize cancer cells to chemotherapy, demonstrated in vitro in breast and skin cancer cells⁵Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity – Di Biase et al. (2016).

It’s important to note that fasting for chemotherapy has not been approved by the FDA, and it is not possible to recommend it as a therapy until further human studies have been carried out. Thus this post is structured as a review of the existing research, and not a recommendation or medical advice.

The motivation for writing this post arose after two people close to me got cancer, and needed chemotherapy.

At the time I was “aware” that fasting had benefits, but didn’t feel comfortable discussing it with them, based on the information I had. So I started digging deep into the literature, and this is what I’ve come up with so far.

I’ll be honest, the literature is out there, but it’s dense, and does require some effort with the science.

To kick off the introduction, the below video is a great primer to the subject.

It covers the genesis of Valter Longo’s research (a key figure in the field), including the pivotal mice study which first showed fasting conveying protection to mice who had been treated with chemo drugs, and it continues to research in human patients.

^ The above screenshot is from an 11 minute video showing Valter’s early research in mice that first demonstrated how fasting may aid with chemotherapy.

Above we’ve touched on the benefits of fasting for chemotherapy. These benefits can be broken down into 2 categories; Differential Stress Resistance and Differential Stress Sensitivity – for which we will dig more into the details below.

Differential Stress Resistance (DSR)

The first benefit is that fasting causes your body’s healthy cells to enter what can be thought of as a “stress resistance” mode. Due to the nature of cancer cells, and their ability to grow despite normal cell signals telling them to cease, they are not protected to the same extent as normal cells by fasting⁶Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008). Although the fasting does still confer some protection to them. The primary upshot of this is:

• When chemotherapy is embarked upon in a fasted state, the toxic chemo drug(s) are less damaging to healthy, non-cancerous cells.

This is known as differential stress resistance – because the stress resistance differs between healthy and cancerous cell types.

Differential Stress Sensitivity (DSS)

Whilst toxicity resistance was the first benefit of fasting (in conjunction with chemotherapy) to be discovered (see the video above where it mentions their initial mouse study). It has later been found that fasting + chemo may also support improved immune system response.

In a study which looked at tackling breast tumors, they measured an increase in tumor infiltrating lymphocytes within the tumor cells. These lymphocytes are implicated in killing tumor cells, and their presence in tumors is often associated with better clinical outcomes⁷Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity – Di Biase et al. 2016.

Implications for Chemotherapy Patients

The upshot of harnessing DSR and DSS has a number of positive implications for patients undergoing chemotherapy:

1. Chemotherapy is openly known as toxic to healthy cells – and chemotherapy itself increases the risk of cancers. Thus, if fasting can reduce the toxicity to healthy cells, it reduces the risk of further cancer creation (wohoo!).
2. Chemotherapy has a number of side effects, many of which affect quality of life for patients (for example, low energy). Fasting around chemotherapy appears to reduce many of the common side effects⁸The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015).
3. Chemotherapy dose has to be calibrated to damage the cancerous cells, but at the same time, not do too much damage to the healthy cells. Fasting could open up the possibility of using higher than normal doses of chemo, if the situation warranted it.

It’s important to note that fasting only is not identified in any of the literature as being optimal. The treatment method with the greatest efficacy was chemotherapy drugs in combination with fasting beforehand⁹Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008). I’m sure we’d all love it if the cure to cancer was to fast – but unfortunately this is not the case. Now, this is not to say that fasting doesn’t have an impact on pre-cancerous cells – that’s something that is still being investigated. But once a cancer has progressed to being a diagnosable tumor, fasting alone is not enough.

Water-Only Fast vs Fast Mimicking?

A next, crucial stage of the research, has been the discovery that most benefits of a water-only fast can be acheived through what has been termed a “fast-mimicking diet”. Whilst the research had started well before, the key paper (as far as I can tell) that announced this finding to the world was released in 2015¹⁰A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan – Brandhorst et al. 2016. The study concludes by saying:

“Fast mimicking diet (FMD) cycles induce long-lasting beneficial and/or rejuvenating effects on many tissues, including those of the endocrine, immune, and nervous systems in mice and in markers for diseases and regeneration in humans”.

This study was not focused on cancer and chemotherapy, rather, just the outcomes of a fast mimicking diet on specific biomarkers. What it does note, is that two of the key markers associated with “differential stress resistance”, insulin like growth factor-1 (IGF-1) and blood glucose, dropped to levels similar to a water-only fast. So in a way that ticks 1 of the 2 boxes for positive benefits – box 1 being differential stress resistance.

However, a year later, a study ¹¹Fasting-Mimicking Diet Reduces HO-1 to PromoteT Cell-Mediated Tumor Cytotoxicity – Di Biase et al. 2016 was done on mice with grafted breast cancer, using a fast mimicking diet (rather than water-only), and the results were positive.

That being said, we do now need the large-scale clinical studies on a fast-mimicking diet and cancer.

Even so, this is really big stuff. Why? Well, water-only fasting for the approximately 4 days minimum needed before chemotherapy is really hard. Many people have never fasted 24 hours in their lives, so asking them to fast for 4 days straight is a big challenge. Thus the idea that it’s possible for these people to eat (low calorie, low protein) meals daily, and still yield much of the benefits that a water-only fast would achieve is fantastic. It puts this therapy within the reach of “regular people” – not just the small minority of outliers who regularly practice fasting.

Where does this research come from?

As we will look at later in this post, the initial seeds for this research were sown 11 years ago, in a 2008 study that found fasting protected mice from the toxicity of chemotherapy drugs. The results were remarkable, and kickstarted the whole research initiative. The clip below is less than 1 minute (cut from the above video), and illustrates the genesis of the research.

This original work was done by Valter Longo and his colleagues at University of Southern California in Los Angeles. Since then their group have been spearheading the research initiative, winning research grants to fund it.

ChemoLieve

As the research into fasting by Valter Longo and his team progressed, a private company was spun out of it, called L-Nutra. Stemming from the 2015 publication of the positive effects of the fast mimicking diet, they patented a formulation for a low calorie, low protein diet, with the goal to turn this into a product people can buy. Their first product, called ProLon, is designed to help people achieve improved health. ProLon is not designed for use with chemotherapy. L-Nutra are currently working on a new product called ChemoLieve which is designed specifically to help with chemotherapy.

At present, more human studies are needed before it can be brought to market. Valter and his colleagues are working to make this happen, with clinical trials being conducted at USC, Mayo Clinic, Leiden University, and the University of Genoa currently. The L-Nutra website has a list of Clinical Trials in progress, or that are due to start. If the progress in human studies continues at a fast enough pace, we may see ChemoLieve being brought to market at some point in 2020.

How ChemoLieve may work?

If you’re familiar with L-Nutra’s ProLon diet then you’ll already have a good idea. Essentially, it’s:

• Plant based, calorie restricted, macronutrient customized meals
• All food is pre-prepared and packaged for quick access. The only cooking involved is heating soups.

Where ChemoLieve will likely diverge from ProLon:

• It will be 4 days instead of the 5 that ProLon uses.
• It may have lower calorie counts for each day.
• They have had to design it so that you can buy multiple boxes with a variety different meals. This is because patients develop aversions to the food they eat during their chemotherapy process. The brain associates the chemo toxins with the food ingredients.

What further research needs doing?

Does fasting help with radiotherapy?

I’ve so far only seen research into fasting being beneficial to chemotherapy, but haven’t seen research done in radiotherapy. It would be interesting to know if and how it could help with radiotherapy. It’s worth noting that the ChemoLieve related patent specifically discusses using radiotherapy in combination with a fast mimicking diet, for example one line says:

“d) administering to the patient radiation therapy during or after the patient consumes the second diet for at least 48 hours” (note that radiotherapy and “radiation therapy” are the same thing)

This suggests there must be some indications that radiotherapy treatment can benefit from fasting.

Whilst chemotherapy is typically done in cycles (such as once every 2 weeks), radiotherapy tends to be done on back to back days. Due to radiotherapies’ required frequency of treatment, it may be difficult to fast for the whole therapy, without losing too much weight and energy. I’d be interested to see how that gets tackled for multi-week radiotherapy treatments. Perhaps the radiotherapy treatment itself could be modified to allow for refeeding periods. This will need a lot more research.

How Viable is Metabolically Supported Chemothearpy (MSCT)?

In a study in Turkey, they found they could increase mean survival times for an aggressive cancer type by administering insulin such that they induce mild (but controlled) hypoglycemia (50-60mg/dl)¹²Long-Term Outcomes of the Treatment of Unresectable (Stage III – IV)Ductal Pancreatic Adenocarcinoma Using Metabolically Supported Chemotherapy (MSCT): A Retrospective Study – Iyikesici et al (2015). With patients having stopped eating the night before the treatment. This is essentially a pharmacologically induced version of lowering blood glucose via fasting, and it may carry some of the Differential Stress Resistance benefits discussed above. It would be interesting to study this method further to see if it’s a viable alternative for those who can’t / don’t want to fast. Also worth noting that the study wasn’t a randomized controlled trial.

Do we need to be more careful of drugs approved for cancer treatment that induce hyperglycemia?

A 2017 study found that elevated glucose (from dexamethasone and rapamycin) increased chemo toxicity in mice (jump to section titled “Hyperglycemia induced by Rapa and Dexa increases cardiotoxicity”).

If we couple this research, with the above study in Turkey, it clarifies the importance of moderate to low blood glucose during chemotherapy. Therefore it makes sense that drugs like corticosteroids (which can increase blood glucose), should be treated with caution for patients on chemotherapy.

Water-only vs Fast Mimicking Diet

Whilst we have evidence that a fast mimicking diet is effective in conjunction with chemotherapy, it would still be interesting to see a comparison of efficacy between the two, in order to grasp any differences. If the difference is significant enough, given that with cancer ones life is quite literally in the balance, a minority may be willing to do the water-only.

Important Related Research Papers

In this section I’ll discuss a number of the key research papers in this field. I’d suggest skipping this section unless you really want to dig into the science further.

Paper #1 – 2008 – Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy

This paper¹³Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008) kickstarted Valter Longo and his colleagues experiments with fasting + chemotherapy.

Here the researchers began by testing in yeast & rat cells (before they moved on to mice). They would run 2 groups – fasted & non-fasted, then administer high levels of common chemotherapy drugs, and measure the survival rates.

Their results showed that fasting before the chemo resulted in greater survival rates for the fasted group. Additionally, it showed that the fasting didn’t prevent the chemo drugs from killing cancer cells – although there was a small amount of protection conferred.

The papers initial tests were performed on yeast & rat cells, which showed promise:

The above graphs show the survival rate of healthy nervous system cells (glia), when subjected to H2O2 (hydrogen peroxide) and cyclophosphamide (a common chemotherapy drug). The different color lines represent the concentration of glucose they provided the cells with. The less glucose (closer to starving) the greater the concentration of toxicity they could survive.

After the studies in cells, the paper moves on to studies in mice:

• 28 mice from three genetic backgrounds that were starved for 48–60 h before undergoing an exaggerated chemotherapy treatment, only one mouse in the cohort died from the chemotherapy. By contrast, of the 37 mice treated without starvation, 20 died of toxicity. In this study the chemotherapy drug used was etoposide, at 3x the “high dose” concentration used in humans.
• Additionally, the non-starved (fed) mice showed signs of toxicity, such as reduced mobility, ruffled hair & hunched back posture. Whereas the starved mice showed no visible signs of stress or pain after treatment.
• This initial set of results showed that fasting (or as they less eloquently put it; “starving”), can provide protection to healthy cells. What this didn’t show however, was if “differential stress resistance” was occurring, as they saw in their initial tests on cells. Differential stress resistance means (in this context) that the healthy cells are protected, but the cancerous cells are not protected to the same extent. Thus you are able to damage the cancer cells, but reduce the damage to healthy cells.
• To test differential stress resistance, they injected mice with cancer cells (a particularly aggressive tumor line called NXS2) and then setup cohorts. Some with just the cancer, some with the cancer + fasting, some with cancer + fasting + etoposide. Their results (below) showed that fasted mice lived marginally longer than non-fasted mice, and those with fasting + etoposide lived longer than just fasted. The cohort that lived the longest (allbeit only a few of them) were the cohort given etoposide without fasting. What happened with them was that 50% died almost straight after chemo administration, due to toxicity. There was only 1 dose of etopside, so the mice that survived then later died of the cancer itself. What this tells us, is that fasting does provide some degree of protection to the cancer cells, as well as the healthy cells. If it didn’t, then we’d have expected to see the cohort using fasting + chemo have the same life expectancy as the chemo only cohort. In practice, the chemo only cohort (those mice that survived) had more of their cancer cells killed by the initial chemo – and thus lived longer, eventually succumbing at a later date.
• What would have been interesting to see, is those two aforementioned cohorts compared against each other, with chemo being administered weekly. That way we could see if the lifetime of the fasting + chemo group could be extended beyond the chemo only group. Apparently for the paper they had issues administering regular injections because it was damaging the tails, thus they’d need to redesign the study to be able to test this.

Paper #2 – 2009 – Fasting and cancer treatment in humans: A case series report

This paper¹⁴Fasting and cancer treatment in humans: A case series report – Valter Longo et al. (2009) follows on from Valter’s work in the previous paper, this time analyzing the experience of 10 volunteers who combined fasting with their chemotherapy. It does not present the findings as a silver bullet to cancer. Instead it focuses on exploring two areas:

1. What effect did fasting have on the patients quality of life post-chemo? This was self-assessed.
2. Did the fasting reduce the chemotherapy’s efficacy?

The bulk of the paper is dedicated to detailing the 10 participants experience with chemotherapy. For many of them it contrasts how they got on with regular chemo, and then how they got on with the fasting + chemo.

It’s quite inspiring actually to read how much their quality of life was improved. Here’s an extract from patient #1:

“After the fasting-chemotherapy cycle, the patient experienced mild fatigue, dry mouth and hiccups; nevertheless she was able to carry out her daily activities (working up to 12 hours a day). By contrast, in the subsequent second and third treatment, she received chemotherapy accompanied by a regular
diet and complained of moderate to severe fatigue, weakness, nausea, abdominal cramps and diarrhea. This time the side effects forced her to withdraw from her regular work schedule. For the forth cycle, she opted to fast again, although with a different regimen which consisted of fasting 120 hours prior to and 24 hours post chemotherapy. Notably, her self- reported side effects were lower despite the expected cumulative toxicity from previous cycles.”

Overall the results suggested:

1. Fasting with chemotherapy improved quality of life for all patients without exception.
2. There was no evidence that fasting reduced the chemotherapy’s efficacy.

That being said, the paper says “only a clinical trial […] can establish whether fasting protects normal cells and increases the therapeutic index of chemotherapies.“. Which is fine, because this study was only ever envisioned to be a stepping stone.

The part I would take issue with in the paper is where it says (referring to the research in the 1st paper):

“In the neuroblastoma xenograft model, mice were allowed to consume only water for 48 hours prior to etoposide treatment. Whereas high dose etoposide led to 50% lethality in ad libitum fed mice, fasting protected against the chemotoxicity without compromising the killing of neuroblastoma cells“

However we see from looking at the previous paper that this doesn’t appear 100% true, because (if I’ve understood correctly) the fasting did convey some resistance to the cancer cells. Here’s a direct quote from the 1st paper:

“In summary, these results suggest that STS (short term starvation) greatly improves early survival by ameliorating chemotherapy toxicity but reduces the effect of a highly toxic dose of etoposide on metastases and cancer-dependent death by partially protecting NXS2 cells.” – NXS2 being the neuroblastoma tumor line they injected into the mice.

However in practice, a small amount of conferred protection to the cancer cells doesn’t invalidate the treatment modality. The key is that the human cells have greater confered protection, and the tumor cell protection is minor.

Paper #3 – The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study

This paper¹⁵The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015) studies 14 breast cancer patients, split into 2 groups, who then either fasted for 24 hours before and after chemotherapy, or didn’t fast at all. It’s almost more interesting for its “failures” (term used loosely) than its successes. For example, it showed:

• Zero measurable benefits to patients perceived side effects with their 24-hour fast prior to chemotherapy. This is useful to know – that fasting needs to be longer than 24 hours before chemotherapy.
• It also raised an interesting question around the compatibility of certain drugs with fasting. For example in this study they singled out dexamethasone as problematic. Dexamethasone is a corticosteroid, which are often used in chemotherapy treatment to mitigate side effects (at least I think that’s why they use it? A lot of this subject area is new to me). However, it also effects insulin and glucose regulation, which then interfers with the differential stress resistance benefits obtained (in part) by lowering blood glucose. Ideally coming into the chemotherapy blood glucose levels have dropped lower than normal, and so we don’t want drugs that modify this – or we risk reducing the benefits of the fast. The good thing is, that not only I noted this in the paper, so did Valter and his colleagues at USC, and we’ll see how in a later paper they did further research into this.

This “success” was also interesting:

• The study showed that short-term fasting reduced DNA damage (even with just 24-hours fasting), which is exciting to see. Specifically the study showed that y-H2AX phosphorylation was lower 7 days post chemo – suggesting short-term fasting improves cellular recovery. y-H2AX is a histone protein used as a marker of DNA damage. Because it is expressed when there is DNA damage, higher levels means more DNA damage, and lower levels means less.

Paper #4 – Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity

This paper ¹⁶Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity – Di Biase et al. (2016) focuses on “differential stress sensitivity” (DSS), which complements the differential stress resistance (DSR) discussed in paper #1 above. Whereas differential stress resistance appears to center around reduction of IGF-1 & blood glucose in protecting the healthy cells, differential stress sensitivity is more focused on immune system changes.

This paper broaches a number of new areas of research into fasting, chemo and the effect on cancer. Because of that it’s possible to get bogged down in the weeds with details (which is exactly how it felt working through the paper, probably not helped by my lack of basic immune system knowledge).

I think the main takeaways to understand from the paper are:

1) Goes into detail on Differential Stress Sensitivity (most research prior had been focused on Differential Stress Resistance)
It goes beyond the idea of Differential Stress Resistance (DSR), which was the original finding for why fasting before chemotherapy may be useful. And it starts to dig into Differential Stress Sensitivity (DSS), which is the ability for fasting to sensitive cancer cells to cell death. It specifically notes that the two things are mechanistically different – the reason why fasting helps DSR, is different from why it helps DSS. This is important from a therapeutic standpoint, because we “kind of” know what helps differential stress resistance, which is the lowering of blood glucose and IGF-1 (primarily). The latter could potentially be the target of drugs. However, what this paper shows, is even if you drop blood glucose and IGF-1, you only get (at best) the DSR effects, and you won’t get the DSS benefits. I think that’s pretty amazing, that fasting is able to provide benefits two very different, but synergistic effects.

2) Diging into Mechanisms for Differential Stress Sensitivity
So that’s the core thing – we have DSR, but we also have DSS (wohoo! the augmentation of cancer cell death), and DSS is a separate thing with separate mechanisms. So the next thing the paper digs into are mechanisms of action for DSS. The main thing that seems to be happening with fasting + chemo from a DSS perspective, is the infiltration of T lymphocytes that are “cytoxic”, meaning that they can kill cancer. In the paper see reference to CD3+/CD8+ T lymphocytes. How exactly these T lymphocytes end up in the tumor cell appears to be a combination of things. Firstly, there is a immune system regeneration after fasting (see Cheng et al. 2014), which reverses some of the immunosuppresion that we typically see with chemotherapy. One thing this increases what are called lymphoid progenitor cells, which originate in the bone marrow, they travel to the thymus and then mature into functional T lymphocytes – which are crucial to immune system function in the context of cancer. Secondly, we see a reduction of Heme Oxygenase 1 in the cancer cell tissue, which appears to reduce the number of T regulatory cells. And then that allows for tumor infiltrating lymphocytes to get into the tumor. The latter mechnism with the heme oxygenase 1 is noted in this particular mouse model with grafted breast cancer – it would be interesting to know if this is cross-applicable to many other cancers.

Paper #5 – Rapamycin decelerates cellular senescence

Whilst this study¹⁷Rapamycin decelerates cellular senescence – Demidenko et al. (2020) is not directly about fasting, I will explain why it has relevance. First though, let’s look at what it shows. They looked at what happens when you arrest the cell cycle in the presence of cell growth, or without cell growth. If the cell is growing, they found that this can induce cell senescence. If it’s not growing however, then senescence doesn’t occur. How does this relate to fasting? Well, in the paper they’re slowing growth through the use of a drug called rapamycin which inhibits a central regulator of cells called mtor. Fasting also inhibits mtor, it just takes a bit longer! Therefore, we can imagine that when people are fasted, and their cells growth is slowed, the chemo agent which may arrest the cell cycle, does not induce senescence in the cell. However, if people are eating normally going into their chemotherapy, then their cells are growing normally, and it’s possible to imagine that some of their cells may turn senescent as a result.

In practice I’d imagine that whatever you do going into chemotherapy, you will take “damage”, and may increase the number of senescent cells that you have. So this would be about reducing that number, not removing it completely.

Paper #6 – Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

In this study¹⁸Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial – de Groot et al (2020) from 2020 they tested out a “fasting mimicking diet’ in 131 patients with breast cancer. They were split into 2 groups, fasting mimicking diet and normal diet, with their results measured.

The main outcomes of note were:

• A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039)
• 90–100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016)
• FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes

Which is all very promising.

For their fasting mimicking diet they did 100% plant based, no animal proteins. Approximately 1200 calories on day 1, and ~200 calories on days 2, 3 and 4. With a ratio of 3.5/1/2 carbohydrates/proteins/fats on day 1. Then 80% of the ~200 calories on days 2, 3 & 4 were from complex carbohydrates. No rules on what time they ate.

Success Stories?

The only “famous” success story I’m aware of – but there may be more – is Mike Maser, CEO of the fasting app Zero.

On Mike’s blog post, he explains his story:

• Back in 2014 when he was running an app called “Fitstar” (which later got bought by Fitbit and became part of their Fitbit Premium service) he got diagnosed with advanced stage Non-Hodgkin’s Lymphoma.
• He came across research by Valter Longo, such as how fasting cycles could slow the growth of tumors. After speaking with Valter he learnt that fasting in combination with chemotherapy could lead to better results with fewer side effects than chemotherapy on its own.
• He put the theory to practice, and did his chemotherapy during 5-day water fasts.
• After just 2 of 5 scheduled chemotherapy sessions, he was declared cancer-free.

That’s a pretty miraculous story, and it’s unlikely everyone would be so fortunate. But nonetheless, it’s nice to hear. It’s perhaps then unsurprising that Mike went on to work in the area of fasting.

Would I personally use fasting if I needed chemotherapy?

Based on current medical practices, to my knowledge, this therapy can’t be used by health care practitioners because it hasn’t been through large-scale clinical trials in humans for each cancer. Currently, there are some large-scale clinical trials under way for a couple of types of cancer; breast and prostate specifically.

Once those results are in, and assuming they’re positive, we then become a step closer to being able to openly advocate for the therapies’ use. Which would be backed by robust human clinical data, in this small (but not inconsequential if you have it) subset of cancers.

On a longer time horizon, we will need large-scale human studies for all cancer types, to be able to advocate it for all. This is unfortunate for those with cancer in the interim, because they may not have time to wait.

The 1830 saying from Thomas Inman, “First, do no harm” – is a good basis for medicine in general. However in practice the idea must yield to nuance. As Daniel Sokol points out¹⁹First do no harm, revisited – Daniel Sokol, doctors inflict harm all the time. Whether it’s inserting a canula, performing a tracheotomy, opening an abdomen, or administering chemotherapy. Clinicians are constantly balancing their obligations to benefit the patient against their obligation to not cause harm.

Does fasting for chemotherapy cause more harm than chemotherapy on its own already creates? So far, we’ve no evidence of this, but it needs more research. In that interim, it will be down to individual patients to make the judgement call on whether or not they want to take a risk.

Personally, based on my research so far, I would be willing to consider using fasting if I needed chemotherapy. Knowing that chemotherapy itself is already going to cause significant systemic damage, the chance to reduce some of that damage appeals. A crucial piece of the puzzle we are missing is if there’s an outlier type of cancer that is actually worsened by fasting. Given the vast range of cancer types (>100) it’s not impossible, we just haven’t found it yet. Hopefully with continued research we can answer that question – but for sure that will take a long time answer.

Post Change Log

In the interests of tracking changes on this post, I’ve started a post change log as of August 3rd 2020.

References

• 1
  Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008)
• 2
  The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015)
• 3
  Fasting and cancer treatment in humans: A case series report – Valter Longo et al. (2009)
• 4
  The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015)
• 5
  Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity – Di Biase et al. (2016)
• 6
  Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008)
• 7
  Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity – Di Biase et al. 2016
• 8
  The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015)
• 9
  Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008)
• 10
  A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan – Brandhorst et al. 2016
• 11
  Fasting-Mimicking Diet Reduces HO-1 to PromoteT Cell-Mediated Tumor Cytotoxicity – Di Biase et al. 2016
• 12
  Long-Term Outcomes of the Treatment of Unresectable (Stage III – IV)Ductal Pancreatic Adenocarcinoma Using Metabolically Supported Chemotherapy (MSCT): A Retrospective Study – Iyikesici et al (2015)
• 13
  Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy – Lizzia Raffaghello, Valter Longo et al. (2008)
• 14
  Fasting and cancer treatment in humans: A case series report – Valter Longo et al. (2009)
• 15
  The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study – Stefanie de Groot et al. (2015)
• 16
  Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity – Di Biase et al. (2016)
• 17
  Rapamycin decelerates cellular senescence – Demidenko et al. (2020)
• 18
  Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial – de Groot et al (2020)
• 19
  First do no harm, revisited – Daniel Sokol