Fasting Mimicking Diets

Intermittent Fasting is not going away any time soon. My latest PubMed search for human research in intermittent fasting revealed over 110 research studies published in 2020.

In addition to Intermittent Fasting, Fasting Mimicking Diets are also being researched but by a smaller group of researchers. I will share the most current human research on Fasting Mimicking Diets in humans including during cancer treatment.

This blog post does not replace medical advice and you should speak to your health care professional before undertaking fasting or fasting mimicking diet or any changes to your prescribed medications.

You can read this blog post top to bottom, or you can navigate using this Table of Contents

What are Fasting Mimicking Diets?

These are diets that allow you to eat, but trick your body into thinking that it’s fasting. They are low to moderate carbohydrate, low protein, moderate to high fat and limited calories. They are designed to allow you to consume some food, while still receiving the metabolic benefits of fasting.

Benefits of Fasting

When you fast, your body switches from using glucose and stored glycogen in the liver as the main source of fuel and uses fat, producing ketones as a bi-product. This is called metabolic switching or “the switch”.

Some of the metabolic benefits include; a reduction in blood sugar, insulin and insulin-like growth factor 1 (IGF-1). The breakdown of stored fat to be used as fuel for the body in the form of fatty acids and ketones. Leptin is reduced, this is a hormone made by the fat cells that inhibits hunger and adiponectin is increased, which drives more fat breakdown. Based on work in cells and animal research, these changes have been shown to extend both lifespan and healthspan (Nencioni, 2018).

What’s the Difference Between Ketogenic Diet, Fasting and Fasting Mimicking Diets?

With intermittent fasting and fasting mimicking diets, the body is going into starvation mode and then switching out again. It’s that “switch” that promotes a major breakdown of intracellular components and beneficial regeneration which  provide the benefits to the body. With a ketogenic diet, there is not ongoing switching as you enter ketosis and stay there (Nencioni, 2018).

Fasting Mimicking Diets in Healthy Adults

Fasting Mimicking Diets in Healthy Adults Study No. 1

In this pilot study, 19 people (7 women and 12 men)  were given a fasting mimicking diet for five consecutive days once a month for three months and a further 19 served as controls as they continued with their usual diet.

The Fasting Mimicking Diet (FMD) was described this way:

• Plant based diet with a proprietary recipes of:
  • vegetable-based soups,
  • energy bar,
  • energy drinks,
  • chip snacks,
  • chamomile flower tea,
  • vegetable supplement formula tablet

The calorie and macro distribution were as follows:

• Day 1: 1090 kcal, 34% carbohydrate, 10% protein, 56% fat
• Days 2-5: 725 kcal: 47% carbohydrate, 9% protein, 44% fat

Results

Those that received the fasting mimicking diet for five days consecutively for three months had a lower blood sugar level after returning to their normal diet, and lower IGF-1 (Insulin-like growth factor-1).

There was a 3% reduction in body weight, there was a trend towards reduction in trunk fat while lean body mass was increased. Pelvic bone mineral density did not change.

Eight people in the fasting mimicking diet group had elevated C-reactive protein (CRP) levels before the study began. By the end of the three month trial, 7 out of the 8 had reduced their CRP into the normal range.

These results coupled with the safety and high compliance to the diet, left the researchers optimistic for further and larger trials of fasting mimicking diets (Brandhorst, 2015).

Fasting Mimicking Diets in Healthy Adults Study No. 2

Researchers from the University of Southern California enrolled 100 people into a study to examine the metabolic effects of a fasting mimicking diet for five days consecutively once a month (Wei, 2017).

The fasting mimicking diet used in this protocol was described as; low in calories, sugars, and protein but high in unsaturated fats and had 700-1,100 kcal per day. The calorie and macro breakdown were as follows:

• Day 1: 1099 kcal with 43% carb, 11% protein and 46% fat
• Days 2-5: 717 kcal, 47% carb, 9% protein and 44% fat

After three months and they had completed three cycles of fasting mimicking diet, the results showed that the people that fasted had;

• lost weight
• lost body fat
• lowered their blood pressure 
• decreased their blood levels of insulin-like growth factor 1 (IGF-1)

all without any serious side-effects.

While these people, aged 20-70 were generally healthy, some did have disease risk factors such as high cholesterol, high triglycerides, low HDL cholesterol, high blood sugar, excess fat around the waist, elevated C-reactive protein (CRP) (a measure of inflammation) or elevated IGF-1 (Insulin-like growth factor 1). This group of people were called the “at-risk subgroup”.

In the at-risk subgroup, the improvement in body weight, blood pressure, fasting, IGF-1, blood lipids and CRP were improved more than in the participants who were not “at risk”. The improvements were still present three months after finishing the final cycle of fasting mimicking diet.

There were some side-effects reported, namely fatigue, weakness and headache, but overall, the fast mimicking diet was found to be safe and effective, but it’s important to note that 25% of the fasters (82% female) dropped out. It’s thought that the drop out was related to the difficulty in following a fasting mimicking diet for five consecutive days (Wei, 2017).

Bottom Line on Fasting Mimicking Diets in Healthy Adults:

If you are relatively healthy but have some at-risk issues, like excess body weight, high cholesterol etc. you could talk to your doctor about trying a fasting mimicking diet (see below for the types of diets).

When you are in this position, you have several options in using diet to help you, for example, you could follow a DASH diet, a Mediterranean diet, intermittent fasting or fasting mimicking diet. You will find yourself drawn to one of these protocols based on your food preferences as well as your personality. Working with a registered dietitian can help you to safely implement the strategy that is the best fit for you.

Fasting Mimicking Diets and Cancer

In my blog post called How to Starve Cancer, I provided a chart that summarized research on cancer patients who fasted before receiving chemotherapy. While the studies done to date, include a small number of subjects, they do show that the outcomes are mostly positive with fewer negative side effects of the chemotherapy.

Why is intermittent fasting used during cancer treatment? It turns out the metabolic changes that happen in your body when you are fasting can help to protect your healthy cells from damage while leaving the cancer cells more vulnerable. The metabolic changes are   twofold;

Differential Stress Resistance

Firstly, our healthy cells are able to protect themselves during starvation by switching from a growing/proliferative state to a maintenance/repair state. Cancer cells, are not able to do this. This phenomenon is called Differential Stress Resistance (DSR) (de Groot, 2020).

Differential Stress Sensitization

The second reason for fasting before chemo is that cancer cells are unable to adapt to starvation conditions and are deprived of nutrients which makes them more sensitive to the chemotherapy. This is called Differential Stress Sensitization (DSS).

Fasting Before Chemotherapy

In these studies, participants were asked to fast for 1-3 days before receiving their chemotherapy. Their cancer cells, which were unable to switch into the maintenance state, became deprived of nutrients and were more vulnerable to the chemotherapy.  Meanwhile, the healthy cells which had switched into maintenance/repair had some protection from the chemo.

The results of the four fasting during chemo studies I reviewed were very promising. Read more about fasting during chemo in my blog post How to Starve Cancer.

But many people who are receiving chemotherapy might have lost weight and might be at risk for further weight loss, compromising their health even further. For this reason, they might be reluctant to fast and their health care may be reticent to recommend fasting too, which is completely understandable.

To minimize the risk of further weight loss in this situation, researchers are trying fasting mimicking diets. The fasting mimicking diet allows you to continue to eat, but tricks the body into thinking its fasting, thereby ‘mimicking fasting’. Do they work?  That’s what the following three studies that I will describe set out to investigate.

Studies of Fasting Mimicking Diets During Cancer Treatment

Study No. 1 HER2- Breast Cancer and Xentigen

In a study by researchers in the Netherlands along with Longevity Institute in Southern California, researchers used a prolon fasting mimicking diet during treatment for breast cancer (de Groot, 2020).

In this study, 129 women with HER2- stage II and III breast cancer, 65 received a fasting mimicking diet without dexamethasone and 64 ate their regular diet plus dexamethasone (only for AC-T chemo) for three days before their chemotherapy. Dexamethasone (see below) is a corticosteroid that is given during cancer treatment to help control nausea and vomiting caused by the AC-T treatment.

4 Cycles of Chemotherapy

Of the 65 women who received the fasting mimicking diet (FMD), they received either;

• 6 cycles of FEC-T chemotherapy (5-fluorouracil, epirubicin, cyclophosphamide and docetaaxel) or
• 8 cycles of AC-T chemotherapy (doxorubicin and cyclophosphamide and docetaxel)

depending on which chemo regimen they needed for their particular situation. Here are the numbers of women that were able to use the fasting mimicking diet per cycle:

• 53 women completed 1 chemo cycle with FMD
• 32 women completed 2 chemo cycles with FMD
• 22 women completed 4 chemo cycles with FMD
• 13 women completed all of their chemo cycles with FMD

The reason stated for not completing the fasting mimicking diet was a dislike of the diet. It’s hard to say if the diet itself was the issue or the fact that these women were getting chemo which is known to change your tastes and create food aversions and of course it is likely a combination of both of these factors.

Results

There was no significant difference between the fasting mimicking diet group and the regular diet group+dexamethasone for;

• Toxicity symptoms to the chemotherapy
• The percentage of patients who discontinued chemotherapy (24-27%)
• The pCR rate (see below)
• Quality of life

The researchers examined and compared ultrasound or MRI pre and post-treatment and categorized the results as either;

1. Complete or partial response (good)
2. Stable/progressing disease (bad)

The women who ate the fasting mimicking diet had three times more ‘complete or partial response’ to treatment compared to the control group and fewer ‘stable or progressing’ responses. The more fasting mimicking cycles that a patient completed, the more the patient had this positive response to treatment. These women also had less DNA damage to healthy T-lymphocyte cells.

In addition, they didn’t need the dexamethasone to control the nausea and vomiting associated with AC-T chemotherapy. This is good as dexamethasone has its own set of side-effects (Verineri, 2020).

In a comment paper published about this study, author Claudio Verineri and co-authors report that the radiological response to the chemotherapy is not a good a measure of pre-operative response to chemotherapy. A better measure would be pCR – the Pathological Complete Response, which is the absence of residual invasive cancer within the breast and lymph nodes, excluding isolated tumor cells, in other words “lack of all signs of cancer” (Verineri, 2020).

But this study was not able to demonstrate an increase in the pCR in the fasting mimicking diet group – possibly because only 13 out of 65 women (20%) were able to consume the Xentigen (see below for a description) for all of their chemo cycles. Why didn’t the women complete all their chemo cycles with Xentigen? They complained that they didn’t like it.

The authors of this study concluded that fasting mimicking diet is safe and effective as an adjunct to chemotherapy, in patients with early stage breast cancer and a normal BMI (body mass index). The topic of fasting mimicking diets should be further explored in patients receiving cancer therapy.

It should be noted that one of the 23 authors on this study Valter Longo has equity interest in L-Nutra and that Hein Putter has shares in a biological sciences company that invested in L-Nutra, the makers of Xentigen longevity diet.

Fasting Mimicking Diets and Dexamethasone

As mentioned above, dexamethasone is a corticosteroid that is often used during chemotherapy treatment to stimulate the appetite, manage nausea, and vomiting, to reduce inflammation and fluid retention and manage other side-effects.

But one of the effects of dexamethasone is to increase the blood sugar and insulin levels (de Groot, 2015). This may negate some of the metabolic benefits of fasting or a fasting mimicking diet. If fasting or a fasting mimicking diet is something you want to try before your chemotherapy, then you should discuss with your oncologist and included in that discussion should be whether dexamethasone can be skipped or not.

Study No. 2 Real Food Fasting Mimicking Diet and Breast and Ovarian Cancer

In a study from German researchers, 34 women with breast or ovarian cancer used a real food fasting mimicking diet or their normal diet to assess quality of life, fatigue and wellbeing. This real food fasting mimicking diet consisted of;

Unrestricted amounts of;

• Water
• Herbal tea

Restricted amounts of;

• Vegetable juice (2L)
• Light vegetable broth (small quantities)

for a total of 350 kcal for the day. The compliance to this protocol of fasting for 36 hours before and 24 hours after chemo was good. In fact, 5 of the women continued with the fasting mimicking diet when the study protocol dictated that they should switch to the normal diet, but they didn’t want to (Bauersfeld, 2018).

For this study 18 women used a FMD for the first three of six chemotherapies, then a normal diet for the second three. Another 16 women ate a normal diet for their first three chemo cycles, then FMD for the final three. In this way, the women served as their own controls.

There were some side-effects of the FMD, including headache, hunger and nausea. Body weight did not change significantly, either up or down.

The conclusions from these researchers was that short term fasting with a real food fasting mimicking diet led to better tolerance to chemotherapy with less compromised quality of life and reduced fatigue. When questioned, 31 out of 34 women said they would fast again during chemotherapy (Bauersfeld, 2018).

Study No. 3 Short term Ketogenic diet with Breast and Gynaecological Cancer

In this study, they refer to the ketogenic diet as a ‘modified fast’ rather than a ‘fasting mimicking diet’, but I am including it in my summary as a further example nonetheless because it was used intermittently and would therefore have repeated metabolic switching (see above).

In this study, 30 women received 4 or 6 cycles of chemotherapy as prescribed by their oncologist (Zorn, 2020). This study placed women with gynaecological cancer into one of four study arms  as follows;

1. Modified short term fasting for 2-3 chemo cycles then normal diet for 2-3 cycles
2. Normal diet for 2-3 chemo cycles then modified short term fasting for 2-3 cycles
3. Ketogenic diet of 100% of calories for 6 days, then modified short term fasting for 2-3 chemo cycles, then normal diet for 2-3 cycles
4. Normal diet for 2-3 chemo cycles, then Ketogenic diet for 6 days followed by modified short term fasting for 2-3 cycles

Here is what the diets looked like;

Modified short term fasting:  25% of your daily estimated calorie requirement. For the women in this study, that worked out to between 400-600 calories per day. The calories were distributed as per a ketogenic diet; 75% fat, 15% protein and 10% carbohydrate. In addition, the women were advised to drink 2.5L of fluid including; water, herbal tea, diet drinks, but no alcohol or caffeine.

Ketogenic diet: No calorie restriction but a keto distribution of energy as 75% fat, 15% protein and 10% carbohydrate. This diet was followed for 6 days prior to the modified fast. The patients received advice and recipes and could choose their own keto meals and were allowed a maximum of 40 grams of carbohydrate per day but needed to consume at least 75% of calories from fat.

Normal diet: No calorie, protein, fat or carbohydrate restrictions.

Modified Fasting Protocol

In this protocol, clients would begin their fast at 6:00 pm, three days before their chemo. The fast would end at 6:00 pm, 1 day after chemo. This adds up to a total of 96 hours of fasting. This was done to ensure that the patients were in ketosis when they received their chemotherapy. According to the hypothesis of Differential Stress Resistance (see above) the greatest protection benefit comes when an individual is in ketosis (Zorn, 2020).

Results

When the women had done the modified short term three day fasting with chemotherapy they experienced significantly less frequent mouth sores (stomatitis). They also reported fewer headaches and weakness in the week after chemotherapy compared to when they ate their normal diet before chemotherapy.

The 6 days of ketogenic diet prior to fasting did not provide any additional benefit. In fact, the women found this harder, and not easier, as was the intention.

The IGF-1 (insulin-like growth factor-1) and insulin levels both reduced with short term fasting. This is seen to be a positive result as it is hypothesized that a reduction in IGF-1 promotes differential stress resistance (see above).

But the fasting itself, came with its own set of side-effects, including complaints of hunger, dizziness, weakness and headaches. But there were significantly fewer post chemo side-effects when the women fasted.

While they did lose weight during the fasting cycles which was not regained, when analysed by bioelectrical impedance, this was found to be fat loss and not muscle.

The high drop-0ut rate prior to the study makes it suspect if people who are already burdened with a cancer diagnosis and looming treatment, are capable of adding fasting to their regime. This would have to be assessed on an individual basis.

Who Should NOT Fast Before Chemotherapy?

It is common in research to exclude certain participants due to potential risks. Because individuals with these conditions are not tested, it is not possible to say if it would be safe to use a fasting mimicking diet during chemotherapy. Here is an example from one study of the exclusion list (Zorn, 2020) and therefore, if you have one of these conditions, there is no safety data available for you;

• Malnutrition or high risk for malnutrition (lost more than 5% weight in the past 3 months, or BMI <18)
• Eating disorder
• Diabetes controlled by medication or insulin
• Gout
• Severe cardiovascular disease
• Pregnant or breastfeeding
• Using parental nutrition
• Using steroids or IGF-1 receptor blockers

Current Trials Underway on Fasting Mimicking Diets and Cancer

According  www.clinicaltrials.gov there are currently 9 studies of fasting mimicking diets and cancer. Of those, four are actively recruiting participants. These studies include lung, breast, colorectal, and prostate cancers. These trials are taking place in the U.S., Italy, Ireland, the Netherlands and Germany (ClinicalTrials.gov, 2020).

What Can I Eat on a Fasting Mimicking Diet?

There appears to be two options used in research with  fasting mimicking diets. Either a diet of permitted fresh foods or a pre-prepared FMD formula. Here are some examples for the current research studies, along with the reference clinicaltrials.gov trial number.

• Fresh Food Protocol Milan:
  • 600 kcal on day 1, and about 300 kcals on days 2-5.
  • Patients choose from a list of permitted fresh foods and beverages that are low carbohydrate and low protein (NCT03340935)
• Fresh Food Protocol California:
  • 10kcal/kg/day made up of 50% fat, 40% carb and 10% protein.
  • The diet includes nuts, olives, vegetable broth, broccoli/cauliflower, white rice/puffed rice, onion, tea/coffee and almond milk. (NCT04027478)
• Fresh Food Protocol Germany (Bauersfeld, 2018)
  • Unlimited water and herbal tea
  • 2 L of Vegetable juice and small quantities of light vegetable broth
  • Total 350 kcal per day
• Xentigen by L-Nutra:
  • a plant-based, low amin0-acid substitution diet, consisting of soups, broths, liquids and tea.
  • The company L-Nutra that makes Xentigen is  currently seeking a US patent for their formulation (USOTO, 2020).
• Chemolieve by L-Nutra:
  • a 4-day plant based low amino-acid formula including soups, broths, liquids and tea
  • designed for cancer patients undergoing chemotherapy
• Prolon by L-Nutra:
  • a 5-day diet providing 43% carb, 46% fat and 11% protein and days 2-5; 700 kcal with 47% carb, 44% fat and 9% protein
  • designed for weight loss and ‘healthy metabolic balance’

Should I Do a Fasting Mimicking Diet During My Chemo?

Like every decision in life, this one must be considered through a risk-benefit lens. What are the benefits or potential benefits of a fasting mimicking diet and what are the risks or potential risks?

While the research is extremely limited, the potential benefits so far are:

• Reduction in body weight, blood pressure, fasting, IGF-1, blood lipids and CRP if in the “at-risk” level
• Potential improved response to treatment
• Less reliance on dexamethasone
• Fewer mouth sores
• Less weakness and headaches following chemo

These need to be weighed with the potential risks of the fasting mimicking diet itself, including;

• Headache
• Hunger
• Nausea
• Dizziness
• Weakness
• Unwanted weight loss

Chemotherapy is powerful medicine designed to destroy cells in your body. For many people, surviviring cancer is about surviving the toxic side-effects of the treatment. To date, many of the toxic side-effects of treatment have required new drug development and/or hospitalization and aggressive treatment (Nencioni, 2018). Using fasting to protect your healthy cells from damage is an affordable and accessible approach (de Groot, 2019).

Ultimately, this question should be answered in a discussion with your oncologist, when you weigh the benefits and risks for your individual situation. If I can be of help, then I am happy to schedule a virtual nutrition assessment with you.

Final Thoughts on Fasting Mimicking Diets

I notice that while there are several studies on fasting mimicking diets, it’s the same researchers conducting this research and this makes me wonder why the topic doesn’t have broader appeal. Many of these same researchers have financial interest in one of the prepared fasting mimicking diet products, which makes we wonder about potential bias in the research.

All and all, it’s a fascinating topic. As a registered dietitian, I definitely believe in the power or food, eating (and not eating) to help heal the body. I’ll be watching this topic and writing more as more research becomes available.

To read more about intermittent fasting, diet for cancer therapy, check out the other Cancer Bites blogs:

Intermittent Fasting for Women over 40

How to Starve Cancer

Special Diet for Triple Negative Breast Cancer

To read more about Intermittent Fasting and enjoy 50 delicious recipes, you can purchase my book Complete Intermittent Fasting

References for Fasting Mimicking Diets

Bauersfeld SP, Kessler CS, Wischnewsky M, et al. The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. BMC Cancer. 2018;18(1):476. Published 2018 Apr 27. doi:10.1186/s12885-018-4353-2

Brandhorst S, Choi IY, Wei M, et al. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015;22(1):86-99. doi:10.1016/j.cmet.2015.05.012

Clinical Trials dot Gov. search results for “Fasting Mimicking Diets and Cancer“. Accessed Nov 28, 2020.

de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, Smit VTHBM, de Graaf H, Heijns JB, Portielje JEA, van de Wouw AJ, Imholz ALT, Kessels LW, Vrijaldenhoven S, Baars A, Kranenbarg EM, Carpentier MD, Putter H, van der Hoeven JJM, Nortier JWR, Longo VD, Pijl H, Kroep JR; Dutch Breast Cancer Research Group (BOOG). Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nat Commun. 2020;11(1):3083. Published 2020 Jun 23. doi:10.1038/s41467-020-16138-3

de Groot S, Pijl H, van der Hoeven JJM, Kroep JR. Effects of short-term fasting on cancer treatment. J Exp Clin  Cancer Res. 2019;38(1):209. Published 2019 May 22. doi:10.1186/s13046-019-1189-9

de Groot S, Vreeswijk MP, Welters MJ, et al. The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. BMC Cancer. 2015;15:652. Published 2015 Oct 5. doi:10.1186/s12885-015-1663-5

Nencioni A, Caffa I, Cortellino S, Longo VD. Fasting and cancer: molecular mechanisms and clinical application. Nat Rev Cancer. 2018;18(11):707-719. doi:10.1038/s41568-018-0061-0

Vernieri C, Ligorio F, Zattarin E, Rivoltini L, de Braud F. Fasting-mimicking diet plus chemotherapy in breast cancer treatment. Nat Commun. 2020 Aug 26;11(1):4274. doi: 10.1038/s41467-020-18194-1. PMID: 32848145; PMCID: PMC7450058.

Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377):eaai8700. doi:10.1126/scitranslmed.aai8700

Zorn S, Ehret J, Schäuble R, Rautenberg B, Ihorst G, Bertz H, Urbain P, Raynor A. Impact of modified short-term fasting and its combination with a fasting supportive diet during chemotherapy on the incidence and severity of chemotherapy-induced toxicities in cancer patients – a controlled cross-over pilot study. BMC Cancer. 2020 Jun 22;20(1):578. doi: 10.1186/s12885-020-07041-7. PMID: 32571329; PMCID: PMC7310229.