December 2016 Issue

Unconventional Diets in Cancer Care
By Suzanne Dixon, MPH, MS, RDN
Today's Dietitian
Vol. 18, No. 12, P. 42

Research is inconclusive, but there are several dietary approaches that may improve symptom management and outcomes in cancer patients.

For many individuals, a cancer diagnosis brings with it a complete loss of control. As part of treatment, a person may undergo surgery, radiation therapy, chemotherapy, immunotherapy, or some combination of these modalities. There are scans, tests, biopsies, X-rays, and more. The person is thrust into the world of cancer, dealing with complicated names, medical jargon, and statistics concerning which treatment yields what possible benefit and at what cost. Confronting issues surrounding possible side effects and possible long-term damage to the body can overwhelm even the most informed patient.

For some individuals, regaining some control over a scary situation is of primary importance, and nutrition is a natural place to seek that control. The health care team tells the patient where to be and when and will administer treatments on its schedule; for patients, having some choice in their nutrition care plan can represent a much-needed reprieve from being told what they "have to do" to treat their cancer. With nutrition, patients can decide what and how they want to eat.

There are numerous unconventional dietary and nutrition approaches people with cancer may want to try, and there's no single approach that fits all patients. But it's important for dietitians to keep in mind that the efficacy of these approaches hasn't yet been proven beyond small trials and animal studies. As discussed in the first article of this two-part series ("Combating Cancer Malnutrition," November 2016), some patients will face serious malnutrition issues. For these individuals, nutrition impact symptoms, including nausea, vomiting, lack of appetite, taste and smell changes, mucositis, fatigue, constipation, diarrhea, and malabsorption, can contribute to declining nutritional status, which in turn may affect survival after a cancer diagnosis.1,2 Even patients who are overweight or obese when beginning treatment may be at high risk of malnutrition during cancer treatment.2-5

In these situations, stabilizing weight and providing adequate calories and protein can mean the difference between finishing treatment and becoming so sick that treatment no longer can be administered.6 Addressing malnutrition must take precedence over experimenting with new and trailblazing nutritional approaches.

Other individuals in active treatment, however, may have no trouble eating their usual diet, and some may even struggle to avoid excessive weight gain.7-13 In these cases, dietitians can work with patients to maximize health, help individuals avoid unhealthful weight gain, and address interest in nontraditional dietary approaches to cancer management. When patients remain active and engaged participants in their own care, it can foster a sense of control that patients want to regain.

Well Nourished Cancer Patient
Individuals who are generally well nourished at diagnosis and who don't experience symptoms and side effects that prevent adequate calorie and protein intake may be interested in unconventional dietary approaches. These approaches may have some promise of improving treatment outcomes and long-term, healthy cancer survivorship, but most aren't yet proven to do so. For RDs working in oncology, addressing expectations in a compassionate and realistic manner is critical. A treatment showing "some promise" doesn't mean it will definitely improve outcomes. At the same time, patient interest in these newer ideas about diet and cancer are normal and should be supported whenever possible, imparting to patients that these dietary manipulations don't yet have enough evidence to support their efficacy, and ensuring the diets aren't contraindicated for other medical reasons.

The Ketogenic Diet
One experimental diet approach for cancer is the ketogenic diet. Many people mistakenly believe this is a low-carbohydrate diet, but it goes far beyond simply reducing carbohydrate intake. The classic ketogenic diet comprises an eating pattern with 3 to 4 g fat for every 1 g carbohydrate plus protein.14 This is a very high-fat diet with little carbohydrate and protein. For example, on a 2,000-kcal diet, the classic ketogenic diet allows for just 16 g carbohydrate and 16 g protein daily.14 This results in a diet with greater than 90% kcal from fat. This is quite extreme and shouldn't be attempted without medical supervision and the help of a dietitian. If patients attempt to implement a ketogenic diet without the help of a dietitian, they may end up eating a poor-quality diet that's high in saturated fat, contains more protein than is allowable if they want to achieve ketosis, and is devoid of healthful foods such as fruits and vegetables. In addition, patients may subject themselves to all of the diet's potential downsides and yet never achieve ketosis. In other words, there's no such thing as "close enough" when seeking to reap the potential benefits of ketosis. Only a true ketogenic diet with appropriate monitoring of laboratory values to ensure ketosis is achieved is appropriate for patients interested in this approach.

Modified ketogenic diets also are being investigated for use in cancer care and may provide potential benefits of ketosis with a less extreme restriction of carbohydrate and protein. As with classic ketogenic diets, patients should consult with a dietitian and have their laboratory values monitored to ensure they meet dietary goals. These modified diets allow for a ratio of fat to nonfat kcal of 2:1 and 1:1, depending on the dietary pattern patients follow.14 On a 2:1 diet, 60 g protein and carbohydrate are allowed per 2,000 kcal daily. On a 1:1 modified ketogenic diet, the patient can eat 80 to 120 g carbohydrate plus protein per day. These diets can result in different levels or "depth" of ketosis, and for them to work as intended, patients must measure, weigh, and consume all the food. Again, working with a knowledgeable dietitian to ensure metabolic goals are met is critical. This includes regular laboratory monitoring to ensure the patient reaches target blood concentrations for insulin, glucose, and ketones.

Why Ketones?
Cancer cells use large amounts of energy, and much of that energy comes from glucose.15 This has led to the theory that severely restricting dietary carbohydrate to the point where the body is forced to use fat and ketones for energy may improve outcomes in the context of existing cancer.16 Ketones are a metabolite of fatty acid breakdown under conditions of depleted glycogen stores and intentionally restricted carbohydrate and protein intake.14,17 In a metabolically normal individual, ketone production is a normal adaptation to restriction of nonfat calories. Ketosis also can be produced in disease states, such as in uncontrolled, insulin-dependent diabetes, which is referred to as diabetic ketoacidosis. This isn't a healthful metabolic adaptation to restriction of carbohydrate and protein calories. Diabetic ketoacidosis results from a complete lack of insulin production, as in type 1 diabetes, or due to the body's failure to respond to insulin being produced. This is a medical emergency.

The metabolically healthy body can use ketones as an additional energy source. There's considerable interest in using the ketogenic diet for people receiving treatment for brain tumors. Most body cells readily adapt to using carbohydrate, protein, fat, or ketones for energy. Brain cells in particular, however, function well using glucose, and less well when using fat and ketones for energy. This has led to the theory that brain cancer cells also won't function as well using fat and ketones for energy. By drastically reducing the supply of glucose to brain cancer cells, it's hoped that ketosis may slow or halt tumor growth. This, in turn, may make brain cancer cells more sensitive to chemotherapy and radiation therapy.

Downsides of the ketogenic diet may include feeling foggy, fatigued, or lightheaded. However, RDs who counsel clients on the ketogenic diet say these side effects tend to dissipate fairly quickly. Leonora Renda, RD, is implementing the diet intervention in an ongoing clinical trial investigating the ketogenic diet as an adjunct to conventional treatment for glioblastoma multiforme (GBM) at the Barrow Neurological Institute in Phoenix. In her 2014 Food & Nutrition Conference & Expo™ presentation, Renda shared early observations from the study, and said her patients have adapted well to the diet and don't struggle with fogginess and fatigue for long.

The ketogenic diet provides little carbohydrate, and that means it offers little to no fiber. This can lead to constipation and other gastrointestinal discomforts. For people with an incurable brain cancer, these side effects may be a small price to pay for a chance at controlling the brain tumor. Medical interventions, including regular laxative use, can address this problem, but must be supervised by the medical staff, not the dietitian. Multivitamin/multimineral supplements can ensure the nutritional adequacy of the diet.

The main drawback of the ketogenic approach is that we don't yet know whether the diet works in people with cancer. The good news is many clinical trials of the ketogenic diet are ongoing, and we should know within the next few years whether this extreme dietary approach improves outcomes in hard-to-treat cancers. Based on available preclinical cell and animal studies, and what we know about how different cells in the body use glucose, one of the most promising areas for this approach seems to be brain tumors, particularly GBM.18 Also encouraging are early clinical trial results affirming the safety of a nutritionally adequate ketogenic diet in cancer patients.19 However, some preclinical studies suggest certain tumor cells use ketones efficiently when deprived of sufficient glucose, and the presence of ketones may spur development of metastatic clones in the tumor.20,21 Whether this would happen in humans in active treatment who are following a ketogenic diet is unknown.

High-Carbohydrate and Plant-Based Diets
At the opposite end of the spectrum are low-fat and vegan diets, which are very high in carbohydrate and lower in protein and fat. The goal of these diets is to improve health and hopefully reduce risk of recurrence in cancer survivors. The Women's Intervention Nutrition Study (WINS) is an excellent example of the very low-fat diet approach and one of the largest randomized controlled trials of long-term diet effects in cancer survivors.22 For WINS, researchers enrolled nearly 2,500 female breast cancer survivors and randomized these women to follow a very low-fat diet (15% kcal from fat), or a standard, healthful "typical American" diet in terms of fat intake (around 30% to 35% kcal from fat).

The intervention group didn't quite reach this fat intake goal of 15% kcal from fat, but did significantly reduce fat intake to around 22% to 24% kcal, maintained over several years. This was far less fat than they were previously consuming and significantly lower than the 35% kcal from fat consumed by the control group. On a low-fat diet, the majority of calories are replaced by carbohydrates, which means the women in the WINS study intervention group were eating plenty of carbohydrates. Despite this high carbohydrate intake—which is about as far as one can get from a ketogenic diet—the intervention group in WINS fared much better in terms of cancer recurrence compared with the control group.

After following the women in the study for several years, the researchers saw a 24% nonsignificant reduction in recurrence risk in the women in the intervention group. Nonsignificant means that statistically this risk reduction could have been due to chance, so the researchers couldn't be absolutely certain the diet provided any survival benefit. However, when the researchers looked at the results by tumor type—estrogen receptor-positive (ER+) vs estrogen receptor-negative (ER-) breast cancers—they found a 42% reduced recurrence risk in women with a history of ER- breast cancer who were on the very low-fat diet, compared with women with a history of ER- cancer following the control diet. ER- breast cancers tend to be more aggressive and harder to treat than ER+ cancers, so this was an important finding. A very low-fat diet might be one way to give women with an aggressive type of breast cancer an advantage for remaining cancer-free.

The very low-fat diet group in WINS did lose about 7 lbs on average, so it's possible the weight loss also helped reduce the risk of recurrence. But the bottom line is that in this study, a very low-fat diet seemed to offer these women some protection against recurrence of ER- breast cancer.23

Dean Ornish, MD, has been investigating a very low-fat vegan diet in men who have what is considered less aggressive forms of prostate cancer.24 This plant-based diet provided less than 10% kcal from fat and comprised mainly fruits, vegetables, whole grains, legumes, and soyfoods. The men in this study had been diagnosed with prostate cancer but hadn't yet undergone treatment. Instead, the men are followed closely by their doctors, a time period called watchful waiting or active surveillance. If the prostate cancer appears to start growing or spreading, patients can begin to receive treatment. In this population, a very low-fat vegan diet along with stress management (eg, yoga, meditation) was estimated to help these men with early stage prostate cancer avoid or delay conventional treatment for at least two years simply by making the dietary and lifestyle changes.25 Furthermore, this very low-fat, vegan diet-based intervention improved markers in the blood, suggesting improvements in health and potential benefits for delaying cancer progression.26 Compared with men following a typical American diet, the men in the very low-fat vegan diet group experienced increases in relative telomere length after five years of follow-up compared with men in the control group. Longer telomeres are considered a marker of younger, healthier cells.

No Fuel at All?
Another "extreme" nutrition intervention, which has shown promise in animal studies and small pilot clinical trials, is fasting before, during, or around the time a patient is undergoing chemotherapy.27 Fasting can refer to several different ways in which calorie intake is intentionally restricted.

When dietitians hear the term "fasting," many think of zero caloric intake over a period of as little as one day and up to five days. Intermittent fasting, however, refers to periodic fasting, and may or may not include a small amount of caloric intake on the fasting days. This small amount of caloric intake on some of the fasting days may be referred to as a fasting mimicking diet. The diet is meant to mimic a fast in terms of its effects on the body. Some research has shown that the body perceives a calorie intake of approximately 20% to 40% of normal intake—for example eating only 400 kcal if normal intake is 2,000 kcal per day—in a similar way as a complete fast (zero calorie intake). For many people, a fasting mimicking diet may be easier to follow than a complete fast.

The theory behind the potential benefits of fasting is that it may sensitize cancer cells to treatment while simultaneously protecting healthy cells from treatment-related damage. Cancer is caused by uncontrolled growth and replication of cells. Even when energy availability is severely restricted, cancer cells continue their destructive, uncontrolled growth. On the other hand, normal cells respond very quickly to an energy deficit. When the body is placed into a calorie-deficient state, healthy cells become quiescent and go into "housekeeping mode." The healthy cells perform only basic functions and the minimum number of activities required for growth or replication. This may protect healthy cells from the effects of chemotherapy or other systemic treatments because they aren't metabolically active. The idea is that this may help patients experience fewer or reduced side effects. The effect on the cancer cells is to sensitize them to chemotherapy, radiation therapy, or other treatments, so they're more susceptible and easily destroyed.28,29

There aren't enough data yet to determine with certainty that fasting works. Furthermore, it's unknown whether fasting is safe for all cancer patients. In treatments for certain tumor types in which it's unlikely the patient will lose much weight, and in many cases may be at risk of excessive weight gain, short-term fasting may prove safe and effective.7-13 For tumor types more strongly associated with severe weight loss and wasting, fasting may not be a safe or effective option.1-6 And even if fasting is safe, it's important for patients to work with their health care providers to design an effective way to engage in fasting. For example, patients will need to load up on noncaloric fluids to keep kidneys functioning well, particularly because some chemotherapy regimens are nephrotoxic; declining kidney function can delay treatments and result in dose reductions, neither of which is optimal for meeting treatment goals.30 As with the ketogenic diet, ongoing clinical trials will fill the gaps on fasting within the next few years.

Cancer Cell Metabolic Flexibility and Nutrition-Related Goals
Despite the need for further research, there are many potential ways to use diet that may improve outcomes in people with cancer. At this point, there aren't enough data to know with certainty which diets are best for individual patients and tumor types to improve outcomes. As outlined previously, it may turn out that a ketogenic diet is an excellent dietary approach for managing certain tumors, such as brain tumors, while a low-fat vegan or very low-fat diet, or fasting, is optimal for breast or prostate cancer.

The most important thing to keep in mind is that there's no one-size-fits-all diet approach for people diagnosed with cancer. Studies to date highlight one thing with certainty: Cancer cells are metabolically flexible.31-33 This means they alter their behavior and use of different fuels to adapt to the changing environment within the tumor itself and within the body. Whether this metabolic flexibility can be overcome with extreme dietary manipulations remains to be seen. The lack of consistency among diet and nutrition advice provided in cancer treatment facilities also points to the unresolved issues surrounding these complex matters.34

For dietitians, this means working with imperfect information and guiding patients who are willing to try anything and everything to help themselves beat cancer. Even if a given dietary approach isn't proven, patients may want to try it. As a result, dietitians need to work with each patient to make sure whatever dietary approach is tried is done so as safely as possible. Telling patients not to try a particular nutritional approach isn't a viable option; many patients will try these extreme dietary manipulations with or without their health care providers' consent and guidance. All patients must be encouraged to work with their doctors and dietitians to ensure they're meeting critical nutrition needs before, during, and after cancer treatment.

— Suzanne Dixon, MPH, MS, RDN, is a dietitian and epidemiologist best known as the creator of an award-winning cancer nutrition website. She has received numerous awards from the Academy of Nutrition and Dietetics and has authored journal articles, textbook chapters, and consumer health publications. She runs her own consulting business in Portland, Oregon.


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