Keto And Fasting: Cancer's Unlikely Foes?

The ketogenic diet, or keto, is a high-fat, low-carbohydrate diet that has been studied as a potential supportive treatment for cancer. The rationale behind this is based on the established differences in glucose metabolism between cancer cells and normal cells. Cancer cells have a higher glucose metabolism compared to normal cells, and they convert glucose to lactic acid even in the presence of oxygen – this mechanism is known as the Warburg effect. Fasting and calorie restriction have been shown to slow and even stop the progression of cancer, kill cancer cells, and improve the effectiveness of chemotherapy and radiation therapy.

Intermittent fasting may improve the effectiveness of chemotherapy

Fasting induces changes associated with cellular protection, which can help to protect against weight loss and increase protection from oxidative stress. It results in a significant drop in insulin levels and an increase in insulin sensitivity in a shorter amount of time compared to calorie restriction. Given that insulin levels play a role in cancer risk, these differences are potentially clinically important.

Furthermore, it is theorised that cancer cells do not respond to the protective signals generated by fasting, thus leaving them vulnerable to both the immune system and cancer treatment. This process is known as differential stress resistance (DSR). Short-term starvation (STS), or fasting for 48 hours, causes a rapid switch of cells to a protected mode, which is capable of protecting mammalian cells and mice from various toxins, including chemotherapy.

Research studies have shown that fasting cycles combined with chemotherapy were more effective than chemotherapy alone in all cancers studied. A 2007 study showed that alternate-day fasting reduced blood levels of glucose, insulin, and IGF-1, with a long-term risk reduction of chronic diseases, including cancer.

The ketogenic diet is now being studied as a potential supportive treatment approach in cancer. The rationale is based on the established differences in glucose metabolism between cancer cells and normal cells. Cancer cells demonstrate increased glucose metabolism compared to normal cells, with a shift toward lactic acid production despite the presence of oxygen, a mechanism also referred to as the Warburg effect.

By consuming a ketogenic diet, blood glucose levels are reduced through a drastic reduction in the amount of carbohydrates consumed. As a result, less insulin is secreted, which downregulates signalling pathways that are frequently constitutively active in tumour cells. Because glucose metabolism is inhibited, energy must be derived primarily from fats.

The ketogenic diet is proposed as a potential adjuvant therapy by exploiting these differences between cancer and normal cells.

Fasting may reduce chemotherapy-related side effects

Fasting has been used as a therapy for many different conditions as well as a part of spiritual and religious practices throughout history. It is thought that these practices can divert energy into multiple protective systems to minimize damage that would reduce fitness. This can prolong life and decrease cancer risk.

Fasting for up to five days, followed by a normal diet prior to treatment, may reduce side effects from chemotherapy or radiation therapy without causing chronic weight loss or interfering with the therapeutic effect of treatment.

The benefits of fasting

Fasting induces changes associated with cellular protection to actually protect against weight loss initially and increases protection from oxidative stress. Fasting results in a more significant drop in insulin levels, as well as an increase in insulin sensitivity in a shorter amount of time compared to calorie restriction. Given that insulin levels play a role in cancer risk, these differences are potentially clinically important.

Furthermore, it is theorised that cancer cells do not respond to the protective signals generated by fasting, thus leaving them vulnerable to both the immune system and cancer treatment. This process is known as differential stress resistance. Short-term starvation (STS), fasting for 48 hours, causes a rapid switch of cells to a protected mode, which is capable of protecting mammalian cells and mice from various toxins, including chemotherapy.

The evidence for fasting

The first scientific paper reporting that calorie restriction inhibited the growth of tumours transplanted into mice was published by Carlo Moreschi in 1909. Since then, a large body of work has established that calorie restriction reduces the progression of tumours in various animal models. Additional research in both rodents and monkeys have shown that when calorie restriction was started by 12 months of age, lifespan was increased and incidence of spontaneous cancers was reduced by 50%.

Human studies have to date been limited; however, there are some interesting outcomes related to cancer risk reduction and reducing treatment-related side effects.

Risk reduction and tumour regression

In 2014, Longo and colleagues demonstrated that fasting caused "old" immune cells to die in mice, which were replaced by stem cells as soon as the subjects recommenced eating. They concluded that a 3-day fast could help regenerate a strong immune system. They also demonstrated that a 48-hour fast in mice slowed the growth and spread of five out of the eight cancers studied. They showed that the combination of fasting cycles with chemotherapy was more effective than chemotherapy alone in all cancers studied.

A 2007 study (n=16) showed that alternate-day fasting, in which one day calories stayed at 400 for women and 600 for men, and the other day was unregulated, reduced blood levels of glucose, insulin and IGF-1 with a long-term risk reduction of chronic diseases including cancer, diabetes, and cardiovascular disease. Two calorie restriction studies, one that included women at moderately increased risk of breast cancer (n = 19) and the other that included newly diagnosed pancreatic cancer patients (n = 19) showed a decrease in serum markers (IGF, stearoyl-CoA desaturase, fatty acid desaturase, and aldolase C), possibly related to cancer risk and prognosis.

A recent study analysed data from the Women’s Healthy Eating and Living study and found that breast cancer survivors who didn’t eat for at least 13 hours overnight had a 36% reduction in the risk of recurrence and were 21% less likely to experience breast cancer-related mortality. The proposed mechanism for this finding is thought to be related to better glycemic control resulting in protection against carcinogenesis. Each 2-hour increase in nightly fasting was linked to progressively lower hemoglobin A1C levels.

Protection from treatment-related side effects

Fasting may also protect patients against the harmful side effects of chemotherapy or radiation therapy. Older cancer patients (n=10), who voluntarily underwent short-term fasting before and/or after chemotherapy reported fewer side effects. A small study (n=6) reported a reduction in fatigue, weakness, and gastrointestinal side effects, compared to receiving chemotherapy without fasting. As shown in the figure below, the trend for a reduction of many additional side effects was also reported by the group of patients who always fasted before chemotherapy.

! [Average self-reported severity of symptoms in patients that received chemotherapy with or without fasting](https://i.imgur.com/v0v5y7k.png)

Ketogenic diets may protect healthy cells from damage caused by chemotherapy

A ketogenic diet is a very high-fat, low-carbohydrate way of eating. It can help with weight loss by forcing the body to burn fat instead of carbs as its main source of energy.

There is interest in how a ketogenic diet may help treat some types of cancer. One theory is that cancer feeds on the sugar you eat, but a high-fat diet starves the tumors.

Ketogenic diets mimic the fasting state, wherein the body responds to the lack of glucose by producing ketones for energy. The resulting tumor dependence on glucose can be exploited with KD use. Ketogenic diets selectively starve tumors by providing the fat and protein that otherwise could not be used by glucose-dependent tumor cells.

In a study by Zuccoli et al., two female pediatric patients with advanced-stage malignant astrocytoma demonstrated a 21.8% decrease in tumor SUV when fed a ketogenic diet. Another case report showed improvement in a 65-year-old female patient with glioblastoma multiforme treated with a calorie-restricted ketogenic diet and standard treatment.

In summary, ketogenic diets may protect healthy cells from damage caused by chemotherapy by providing an alternative source of energy in the form of ketones and fatty acids. This can help starve tumors and slow cancer growth while preserving healthy cells.

Fasting may help fight cancer by lowering insulin resistance

Fasting has been used as a medical therapy for thousands of years. It is thought to have a positive impact on cancer treatment and prevention by lowering insulin resistance and levels of inflammation.

Insulin is a hormone that allows cells to extract glucose from the blood to use as energy. When more food is available, the cells in the body become less sensitive to insulin, leading to higher levels of glucose in the blood and higher fat storage. This is known as insulin resistance.

When food is scarce, the human body tries to conserve as much energy as possible. It does this by making cell membranes more sensitive to insulin, allowing cells to metabolize insulin more efficiently and removing glucose from the blood. This process is known as improving insulin sensitivity.

Fasting may help improve the effectiveness of chemotherapy by making it harder for cancer cells to grow or develop. It may also reverse the effects of chronic conditions such as obesity and type 2 diabetes, which are both risk factors for cancer.

Research suggests that fasting may make cancer cells more responsive to chemotherapy while protecting other cells. Fasting may also boost the immune system to help fight cancer that is already present.

Fasting has been shown to have significant restorative benefits through molecular mechanisms, such as enhanced autophagy and sirtuin activity. Autophagy is a process that breaks down superfluous or malfunctioning cellular components, allowing for orderly breakdown and recycling. It is critical for maintaining proper cell function and defending the body against disease.

In summary, fasting may help fight cancer by lowering insulin resistance and levels of inflammation, improving the effectiveness of chemotherapy, reversing the effects of chronic conditions, boosting the immune system, and providing significant restorative benefits.

Ketogenic diets may help anti-cancer drugs work faster or better

The ketogenic diet is being studied as a potential supportive treatment for cancer. The rationale is based on the established differences in glucose metabolism between cancer cells and normal cells. Cancer cells demonstrate increased glucose metabolism compared to normal cells, with a shift toward lactic acid production despite the presence of oxygen, known as the Warburg effect.

The ketogenic diet is proposed as a potential adjuvant therapy by exploiting these differences between cancer and normal cells. Consuming a ketogenic diet reduces blood glucose levels through a drastic reduction in the amount of carbohydrates consumed. As a result of decreased blood glucose levels, less insulin is secreted, which downregulates signaling pathways that are frequently constitutively active in tumor cells. Because glucose metabolism is inhibited, energy must be derived primarily from fats.

Fat metabolism results in the production of ketone bodies and β-hydroxybutyrate by the liver, which are used to fuel energy production. Cancer cells have difficulty using these pathways because they rely on glucose; the metabolism of fat increases oxidative stress.

Combining a ketogenic diet with standard chemotherapeutic and radiotherapeutic options may help improve tumor response, although more research is needed.

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