Feature

Ketogenic diet superior to standard for women with ovarian, endometrial cancers

The ketogenic diet yielded greater reductions in fat mass and serum insulin levels than the diet recommended by the American Cancer Society among women with ovarian and endometrial cancers, according to results of a randomized, controlled trial.

Kevin Fontaine, PhD, Antoine Lavoisier endowed professor of energetics and healthy lifestyles in the School of Public Health at The University of Alabama at Birmingham, and colleagues suggested that the high-fat, low-carbohydrate ketogenic diet may potentially “starve” cancer cells by reducing their supply of glucose.

The researchers assigned women with ovarian or endometrial cancer and a BMI of 18.5 or greater to either the ketogenic or American Cancer Society diet. The ketogenic diet was comprised of 70% fat, 25% protein and 5% carbohydrate, whereas the American Cancer Society diet — in accordance with federal nutrition guidelines — was defined as moderate-to-high carbohydrate, high-fiber and low-fat.

Findings at 12 weeks indicated that patients on the ketogenic diet had greater reductions of total fat mass, android — or upper body — fat mass and visceral — or abdominal — fat than those on the cancer society diet (P < .05 for all). The ketogenic group also had a lower adjusted fasting serum insulin level (7.6 µU/mL vs. 11.2 µU/mL; P < .01).

Changes in serum beta-hydroxybutyrate, a marker of adherence to the ketogenic diet, were significantly associated with insulin-like growth factor I concentrations (r = –0.57; P < .0001), suggesting that the ketogenic diet may have anti-inflammatory effects.

HemOnc Today spoke with Fontaine about the impact of diet on cancer therapy, the potential concerns with the ketogenic diet, and whether targeted dietary advice may be the future of cancer treatment.

Question. What was the rationale for conducting this study?

Answer : The standard American diet, based on the federal nutrition guidelines, is roughly 40% to 60% carbohydrates. This high consumption of carbs likely provides the fuel for cancer cells. The ketogenic diet — which is 5% carbohydrates — might reduce glucose, thereby compromising the ability of cancer cells to thrive. The diet also reduces insulin and inflammation, two factors that appear to be related to cancer development and growth. We chose to study the ketogenic diet’s effects on ovarian and endometrial cancer because they are among the deadliest cancers among U.S. women and are strongly linked to obesity and higher levels of insulin and inflammation.

Q : Could you talk about some of the key primary and secondary results?

A : We found that, compared with the high-fiber, low-fat diet recommended by the American Cancer Society, 12 weeks on a low-carbohydrate, high-fat ketogenic diet produced significantly lower levels of fat mass and fasting insulin and greater levels of circulating ketones, a marker of ketosis, which we associated with lower levels of systemic inflammation.

Q : Given the shift toward individualized treatment s , will clinicians begin to make decisions about the diets of their patients based on the malignancy?

A : In practice, I don’t think clinicians routinely make dietary recommendations unless asked by the patient. Because what constitutes a healthy diet is such a controversial issue, most shy away from making recommendations. However, if the ketogenic diet continues to confer benefits, hopefully, American Cancer Society dietary recommendations for patients with cancer will be modified accordingly.

Q : Could you talk specifically about how this diet interacts with cancer treatment?

A : We cannot answer that question yet because the women in the study were at different stages of treatment. However, we speculate that, because the ketogenic diet greatly reduced glucose and insulin, it may enhance the effectiveness of therapy, such as chemotherapy and/or radiation, while reducing the toxic side effects of treatment.

Q : Are there any potential drawbacks to the ketogenic diet in this patient population?

A : The biggest challenge is getting patients to radically change their diet, especially in light of the fact that we are prescribing a diet that is the exact opposite of the federal guidelines. We recently published another paper that suggests the diet improves physical functioning and quality of life and diminishes specific food cravings.

Q : Should s omething be done to change the diet recommended in the f ederal g uidelines ?

A : The guidelines are about to be revisited again. My hope is that the new guidelines will be informed by the recent work suggesting that lower carbohydrate consumption appears to be beneficial for weight management and perhaps the treatment of chronic metabolic-related illnesses, such as cancer and type 2 diabetes.

Q : C ould you talk a bit more about how to get patients to change their diet s ?

A : The biggest challenge in a study is to provide the rationale for the dietary change and the education and support to help the person make the change. A study is artificial in that the participants get a great deal of individualized attention and are provided with the resources to make the change. In the clinic, it’s pretty rare to have the expertise or resources to help a patient change their diet. Also, insurance generally doesn’t cover dietary counseling.

Q : What are the clinical implications of these findings?

A : The ketogenic diet may offer an adjunctive treatment for these cancers. However, it requires a more rigorous randomized-controlled trial to better understand its effects — as well as how it might interact with therapies — before we can definitively recommend it.

Q : W ith that in mind, where does the research need to go from here?

A : We hope to acquire additional grant funding so that we can conduct a larger study in which women are randomized to the American Cancer Society diet or the ketogenic diet right at the time of diagnosis so we can better estimate its effects on subsequent treatment, prognosis and survival. Such a trial would require over 100 women and, to enhance rigor, we would like to provide all of the food to help ensure they are eating the prescribed diets.

Q : Do you have any thoughts on using the keto genic diet as a clinical strategy in other cancer populations?

A : There is anecdotal evidence that the ketogenic diet might be an effective treatment for glioblastoma and prostate cancer. —by Rob Volansky

Reference:

Cohen CW, et al. J Nutr. 2018;doi:10.1093/jn/nxy119.

For more information:

Kevin Fontaine, PhD, can be reached at The University of Alabama at Birmingham, 1665 University Blvd., Birmingham, AL 35294-0022; kfontai1@uab.edu.

Disclosure: Fontaine reports advisory committee roles with Atkins Nutritionals and Virta Health Inc.

The ketogenic diet yielded greater reductions in fat mass and serum insulin levels than the diet recommended by the American Cancer Society among women with ovarian and endometrial cancers, according to results of a randomized, controlled trial.

Kevin Fontaine, PhD, Antoine Lavoisier endowed professor of energetics and healthy lifestyles in the School of Public Health at The University of Alabama at Birmingham, and colleagues suggested that the high-fat, low-carbohydrate ketogenic diet may potentially “starve” cancer cells by reducing their supply of glucose.

The researchers assigned women with ovarian or endometrial cancer and a BMI of 18.5 or greater to either the ketogenic or American Cancer Society diet. The ketogenic diet was comprised of 70% fat, 25% protein and 5% carbohydrate, whereas the American Cancer Society diet — in accordance with federal nutrition guidelines — was defined as moderate-to-high carbohydrate, high-fiber and low-fat.

Findings at 12 weeks indicated that patients on the ketogenic diet had greater reductions of total fat mass, android — or upper body — fat mass and visceral — or abdominal — fat than those on the cancer society diet (P < .05 for all). The ketogenic group also had a lower adjusted fasting serum insulin level (7.6 µU/mL vs. 11.2 µU/mL; P < .01).

Changes in serum beta-hydroxybutyrate, a marker of adherence to the ketogenic diet, were significantly associated with insulin-like growth factor I concentrations (r = –0.57; P < .0001), suggesting that the ketogenic diet may have anti-inflammatory effects.

HemOnc Today spoke with Fontaine about the impact of diet on cancer therapy, the potential concerns with the ketogenic diet, and whether targeted dietary advice may be the future of cancer treatment.

Question. What was the rationale for conducting this study?

Answer : The standard American diet, based on the federal nutrition guidelines, is roughly 40% to 60% carbohydrates. This high consumption of carbs likely provides the fuel for cancer cells. The ketogenic diet — which is 5% carbohydrates — might reduce glucose, thereby compromising the ability of cancer cells to thrive. The diet also reduces insulin and inflammation, two factors that appear to be related to cancer development and growth. We chose to study the ketogenic diet’s effects on ovarian and endometrial cancer because they are among the deadliest cancers among U.S. women and are strongly linked to obesity and higher levels of insulin and inflammation.

PAGE BREAK

Q : Could you talk about some of the key primary and secondary results?

A : We found that, compared with the high-fiber, low-fat diet recommended by the American Cancer Society, 12 weeks on a low-carbohydrate, high-fat ketogenic diet produced significantly lower levels of fat mass and fasting insulin and greater levels of circulating ketones, a marker of ketosis, which we associated with lower levels of systemic inflammation.

Q : Given the shift toward individualized treatment s , will clinicians begin to make decisions about the diets of their patients based on the malignancy?

A : In practice, I don’t think clinicians routinely make dietary recommendations unless asked by the patient. Because what constitutes a healthy diet is such a controversial issue, most shy away from making recommendations. However, if the ketogenic diet continues to confer benefits, hopefully, American Cancer Society dietary recommendations for patients with cancer will be modified accordingly.

Q : Could you talk specifically about how this diet interacts with cancer treatment?

A : We cannot answer that question yet because the women in the study were at different stages of treatment. However, we speculate that, because the ketogenic diet greatly reduced glucose and insulin, it may enhance the effectiveness of therapy, such as chemotherapy and/or radiation, while reducing the toxic side effects of treatment.

Q : Are there any potential drawbacks to the ketogenic diet in this patient population?

A : The biggest challenge is getting patients to radically change their diet, especially in light of the fact that we are prescribing a diet that is the exact opposite of the federal guidelines. We recently published another paper that suggests the diet improves physical functioning and quality of life and diminishes specific food cravings.

Q : Should s omething be done to change the diet recommended in the f ederal g uidelines ?

A : The guidelines are about to be revisited again. My hope is that the new guidelines will be informed by the recent work suggesting that lower carbohydrate consumption appears to be beneficial for weight management and perhaps the treatment of chronic metabolic-related illnesses, such as cancer and type 2 diabetes.

PAGE BREAK

Q : C ould you talk a bit more about how to get patients to change their diet s ?

A : The biggest challenge in a study is to provide the rationale for the dietary change and the education and support to help the person make the change. A study is artificial in that the participants get a great deal of individualized attention and are provided with the resources to make the change. In the clinic, it’s pretty rare to have the expertise or resources to help a patient change their diet. Also, insurance generally doesn’t cover dietary counseling.

Q : What are the clinical implications of these findings?

A : The ketogenic diet may offer an adjunctive treatment for these cancers. However, it requires a more rigorous randomized-controlled trial to better understand its effects — as well as how it might interact with therapies — before we can definitively recommend it.

Q : W ith that in mind, where does the research need to go from here?

A : We hope to acquire additional grant funding so that we can conduct a larger study in which women are randomized to the American Cancer Society diet or the ketogenic diet right at the time of diagnosis so we can better estimate its effects on subsequent treatment, prognosis and survival. Such a trial would require over 100 women and, to enhance rigor, we would like to provide all of the food to help ensure they are eating the prescribed diets.

Q : Do you have any thoughts on using the keto genic diet as a clinical strategy in other cancer populations?

A : There is anecdotal evidence that the ketogenic diet might be an effective treatment for glioblastoma and prostate cancer. —by Rob Volansky

Reference:

Cohen CW, et al. J Nutr. 2018;doi:10.1093/jn/nxy119.

For more information:

Kevin Fontaine, PhD, can be reached at The University of Alabama at Birmingham, 1665 University Blvd., Birmingham, AL 35294-0022; kfontai1@uab.edu.

Disclosure: Fontaine reports advisory committee roles with Atkins Nutritionals and Virta Health Inc.

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