Calorie restriction without malnutrition has been found to extend the healthy lifespans of cancer-prone laboratory animals. Multiple periods of intermittent caloric restriction are even more effective in inhibiting mammary tumors in mice than continuous low calorie diets. Recent studies suggest that fasting around chemotherapy treatments and during radiation treatment could protect normal cells from the toxic effects of treatment while sensitizing cancer cells to the therapy. Is fasting a good idea for breast cancer patients undergoing chemotherapy?
Calorie restriction reduces factors associated with cancer
Elevated blood sugar, insulin, insulin-like growth factor 1 (IGF-I) and inflammation levels are known risk factors for breast cancer and also increase the risk of recurrence. Long-term calorie restriction results in consistent improvement in these and other markers associated with cancer.
However, such calorie restriction requires weeks or months to be effective and causes modest changes in glucose and IGF-I levels, while promoting chronic weight loss (which would only be desirable in overweight patients). On the other hand, fasting—no calorie intake at all—induces a much more dramatic reduction in glucose and IGF-I levels.
Reducing energy availability with exercise is not equivalent
While exercise can also be used to limit calorie availability, calorie restriction and exercise exert their effects on breast cancer development through distinct pathways. Although regular exercise in the years before a diagnosis of breast cancer has been shown to improve prognosis, heavy exercise during chemotherapy would not have the same effects as fasting. In fact, there is some evidence that heavy exercise could reduce the effectiveness of chemotherapy.
Effects of calorie restriction on breast cancer development
Calorie restriction has been shown to be broadly effective in preventing cancer in laboratory animals. Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. Chronic calorie restriction inhibits mammary tumor development in mice. However, multiple periods of intermittent caloric restriction are even more effective in inhibiting mammary tumors. One study found that periods of severe calorie restriction accompanied by weight loss had a protective effect on mammary tumor development even if the weight was regained.
Effects of fasting on breast cancer during chemotherapy
Chemotherapy can expose patients to toxic side effects such as heart damage and a reduction in the production of blood cells. Fasting protects normal cells from the toxic effects of chemotherapy while sensitizing cancer cells to the treatment. Normal cells deprived of nutrients during fasting enter a dormant state, whereas cancer cells attempt to keep growing and dividing, exposing them to treatment.
It has been suggested that a schedule of fasting for a few days before, during, and day after the date of chemotherapy would enhance its treatment effects while providing protection against toxic side effects. However, fasting during chemotherapy should only be undertaken with the guidance and supervision of your oncology team.
Several studies have provided evidence concerning fasting during chemotherapy:
- A 2020 study reported that fasting three days before and on the day of neoadjuvant chemotherapy resulted in a higher rate of radiologically complete response and tumor cell loss than a regular diet.
- Another study found that a 30% reduction in calorie intake was linked to longer survial and fewer metastases in a mouse model of triple negative (ER-/PR-/HER2-) breast cancer treated with chemotherapy.
- A small human trial found that women who fasted 24 hours before and after TAC (Taxotere, Adriamycin, cyclophosphamide) chemotherapy cycles experienced less hematological toxicity than women assigned to eat a healthy diet.
- Cycles of starvation (fasting) were as effective as chemotherapy drugs in delaying progression of mammary tumors in mice in one study. In addition, starvation plus chemotherapy increased the effectiveness of the treatment.
- A study in which rats were deprived of protein during anthracycline chemotherapy found that protein malnutrition reduced the elimination of both Adriamycin (doxorubicin) and epirubicin, prolonging the exposure of the heart to the drugs and increasing the anthracycline-associated heart damage.
- Another study reported that fasting for up to five days, followed by a normal diet, might protect patients against chemotherapy without causing unwanted weight loss.
- In another study, fasting for 48-hours was found to be sufficient to markedly suppress tumor progression in a mice model of breast cancer. Fasting alone (without chemotherapy) caused more than a 50% decrease in tumor growth. When fasting was combined with chemotherapy, fasting was found to sensitize cancer cells to chemotherapy and further reduce tumor growth up to 90% compared to untreated mice. The protection against drug toxicity was due to reduced DNA damage to normal cells.
- A 72-hour fast in mice reduced circulating IGF-I by 70% in still another study. Sixty percent of melanoma-bearing mice treated with Adriamycin (doxorubicin) achieved long-term survival whereas all non-fasting mice died either of metastases or chemotherapy-related toxicity.
Metformin has effects on breast cancer similar to fasting
Metformin, a drug used to treat type 2 diabetes, has been shown to reduce breast cancer risk and recurrence. Metformin appears to mimics some aspects of caloric restriction in the body. In fact, metformin has been shown to enhance the effectiveness of Adriamycin chemotherapy.
Is fasting during chemotherapy a good idea?
More studies and human trials are required before it can be determined whether fasting during chemotherapy is a safe and effective way to reduce the toxic side effects of chemotherapy while enhancing its treatment effects. The finding that rats deprived of protein increases Adriamycin-induced cardiomyopathy is troubling and suggests that patients should not attempt fasting. Fasting might also cause health problems in some women.
Rodents are different from human beings in many ways and are not a good model for assessing the long-term effects of a proposed treatment strategy. Fasting during chemotherapy could have unintended long-term consequences. For example, it is not implausible that fasting could trigger cancer cell adaptive systems (to cope with the stress of a lack of nutrients). This in turn could result in a rebound effect in any cancer cells not killed by chemotherapy, an effect that could heighten their aggressiveness.
Having said this, the evidence to date points to some possible strategies that are less extreme than fasting but could enhance the treatment effects of chemotherapy. These include avoiding large meals and weight gain during chemotherapy, and treating metabolic syndrome and type 2 diabetes with metformin:
- Large meals that cause spikes in circulating insulin cause effects in the body that are essentially the opposite of fasting and are to be avoided. This includes meals heavy in refined carbohydrates and any meal that causes a feeling of extra fullness (over approximately 500 to 800 calories). It is better to eat whole fruits and vegetables (with all their fiber) than to consume juice or smoothies. Allow yourself to become hungry between meals.
- Gaining weight during chemotherapy is not uncommon and should be avoided. Weight gain during treatment is associated with increased risk of breast cancer recurrence and metastasis.
- Metformin is used to treat metabolic syndrome, pre-diabetes, and polycystic ovary syndrome in addition to type 2 diabetes. Women with these conditions can check with their physicians as to whether metformin is appropriate for them.
- Women with type 2 diabetes should keep their blood sugar under tight control, preferably through diet and metformin rather than insulin if at all possible. Lantus long-acting insulin in particular has been associated with increased risk of breast cancer and might increase risk of recurrence.
Below are links to recent studies on fasting or calorie restriction and chemotherapy. For a more complete list of studies, please click on the tag calorie restriction.