Glioblastoma (GBM) is a highly aggressive form of brain cancer, and while there is no single food or diet that can cure it, nutrition plays a crucial role in supporting the patient's immune system, energy levels, and overall healing process. This article provides an overview of nutrition guidelines for individuals with glioblastoma, incorporating the latest research and expert recommendations.
The Importance of Nutrition in Glioblastoma Treatment
Brain tumors and their treatments, including surgery, chemotherapy, radiation, and medications, can significantly impact a patient's body. These treatments can affect appetite, energy levels, digestion, and even the ability to swallow. Getting good nutrition throughout treatment is essential to promote healing and recovery while preventing unintentional weight loss. It's important to recognize that nutrition recommendations for patients with cancer are not one size fits all. Dietary recommendations found on social media, in online articles, and from well-meaning friends and family who may have had cancer might not be appropriate for you and could even be harmful.
Individualized Nutrition Plans
Because every patient is different, your nutrition plan should be tailored to your individual needs. Some factors that can influence the specific recommendations you receive from a registered dietician may include your type of cancer, type of treatment, expected side effects, other health or medical issues, and prognosis. A registered dietitian (RD) can help by providing strategies to combat common side effects of treatment. Every patient at Fred Hutch has access to nutrition planning throughout their cancer care that matches their specific needs.
Addressing Treatment-Related Challenges
Surgery, radiation, and chemotherapy can make it difficult to eat normally. Surgery to the digestive tract might result in changes in the absorption of food and the need to follow a lower fiber diet. If you have surgery to the head or neck area, it might be difficult to chew or swallow, making it necessary to eat only soft foods. With radiation, the part of the body being treated might influence what you can eat. For example, radiation to the chest might cause inflammation to your esophagus, which makes swallowing difficult.
Key Nutritional Strategies for Glioblastoma Patients
During your treatment, you might need to change your diet to help with healing, minimize unintentional weight loss, and build strength. Often, your treatment may require more protein in your diet. Protein helps keep our bodies strong. When we don’t get enough protein, our bodies can break down muscle to get fuel. Some examples of protein-rich foods are fish, chicken, eggs, yogurt, nut butters, and legumes.
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The Balanced Plate Method
A simple way to build healthy meals is by using the Balanced Plate Method. Before starting treatment, your goal is to build strength and nourish your body.
Emphasizing Protein Intake
Often, cancer treatment may require more protein in the diet. Protein helps keep our bodies strong. When we don’t get enough protein, our bodies can break down muscle to get fuel. Some examples of protein-rich foods are fish, chicken, eggs, yogurt, nut butters, and legumes.
The Role of Fiber
A diet that is rich in high-fiber plant foods (fruits, vegetables, whole grains, nuts, seeds, and legumes) is recommended to provide essential nutrients for healing. These foods contain phytonutrients, which are chemicals that have health-promoting compounds. Depending on your cancer type or treatment, you may not be able to eat high-fiber foods because your body might process nutrients differently, and you may not tolerate them well.
Carbohydrates as an Energy Source
Carbohydrates are your body’s main source of energy. Examples of nutrient-dense carbohydrates include fruits, vegetables, whole grains, and legumes. If you’re able to eat a well-balanced diet, you can get all the nutrients you need from food. Of course, certain treatments might impact your ability to eat a well-balanced diet. Your dietitian can help to ensure that your diet is rich in these essential nutrients, even if your diet is limited.
Antioxidants and Supplements
Antioxidants are popular among cancer patients, but antioxidants in supplement form could interfere with treatment.
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The Ketogenic Diet: A Potential Metabolic Treatment
In the last 10 years, there has been a growing interest in alternative, metabolic treatments of GBM. GBM cancer cells utilize aerobic fermentation of glucose in the cytosol for energy supply instead of mitochondrial oxidative phosphorylation (the “Warburg effect”). 18 F-fluoro-2-deoxyglucose positron emission tomography (PET) shows that human GBMs have much higher glucose utilization than normal cortex. In states of prolonged glucose deprivation, such as fasting or starvation, normal brain cells metabolize ketone bodies derived from fatty acids for energy instead of glucose. Tumor cells are poorly able to do so. They depend on glucose and glycolysis for survival. This makes tumor cells vulnerable to therapies of glucose restriction.
How the Ketogenic Diet Works
Glucose reduction and ketone exposure reduce proliferation and growth rate of human GBM cells and of rodent astrocytoma lines. The effect occurs independently with both glucose reduction and with ketone body exposure, with a synergistic effect between the two. Glucose deprivation results in apoptotic death in human GBM cells but not in normal cells. Similarly, ketone bodies inhibit the viability of cultured human GBM cells, but not of normal cells. In mice, high circulating glucose levels accelerate tumor growth and angiogenesis and prevent apoptosis. Reduction in circulating glucose and increase in ketone levels through ketogenic diet (KD) with caloric restriction have pro-apoptotic, anti-angiogenic, and anti-inflammatory effects, reduce expression of mTOR effector in mice with experimental malignant gliomas, reduce rodent tumor growth and tumor size, and increase survival of animals.
Evidence from Animal Studies
In a mouse model of malignant glioma treatment with 4:1 KD, KD increased median survival by 22% from 23 to 28 days. Remarkably, treatment with KD given together with radiation resulted in complete tumor remission in 9/11 animals. KD treatment lasted for 101 days. Animals remained tumor-free until they were sacrificed at 299 days. Calorically restricted KD combined with the glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), appears similarly effective in 2 mouse models of orthoptic implanted GBM.
Human Studies and Challenges
In patients with GBM, hyperglycemia is associated with shorter survival. There have been seven reports of KD treatment of patients with GBM: 3 of 1-2 patients and 4 with 9-20 patients. Outcomes in the anecdotal cases were better than expected. However, in the larger studies, no positive findings were reported. These studies have varied widely. They have ranged in treatment duration from 6-14 weeks, in disease stage from adjunctive treatment with standard initial care to recurrent GBM, in diet CH content from 60 g CH/day or 25% of calories derived from CH to 4:1 KD, in fat content, and in presence, absence, and degree of caloric restriction.
Studies with > 2 patients reported difficulty with doing the diet and, in 3/4 studies, continuing it beyond 3 months. In these 3 studies, the diet duration was limited to 6 weeks-3 months because the investigators thought that patients could not tolerate longer periods. In one study, treatment continued for 14 weeks, but increased CH content after 8 weeks and required “intense counseling”. There are three main problems with the “classic” 3:1 or 4:1 ketogenic diet: (1) it is complicated to do; (2) it is not palatable; and (3) it is done individually by each patient, and thus differs between patients in a study, and between studies.
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Total Meal Replacement (TMR) Program
To address these challenges, a novel program of total meal replacement (TMR) of ready-made 4:1 and 3:1 KD meals was developed to simplify and standardize the diet in order to make it easier to do and adhere to, and to make it uniform across a study and comparable between studies. The program delivers patients ready-made meals using a large palette of our own recipes in a TMR program with 4:1 KD with 10 g CH and 1600 kcal/day, with no other food consumed. The goal of this pilot study was to evaluate feasibility, safety, and tolerability of GBM treatment with this program and to obtain pilot data on efficacy.
Study Results of TMR Program
Eight subjects were enrolled between June 2014 and April 2019 (2 women, mean age 49.8 years (range 40-64). Recruitment was slow resulting in early study termination. Six subjects were self-referred via the web (clinicaltrials.gov); 1 each was referred by a neurosurgeon and by an oncologist. Additional 27 eligible subjects declined participation after screening. Ratio of eligible screened: enrolled patients was 3.37. Reasons for non-participation after screening included discouragement by treating oncologists (n = 11), unwillingness to undergo food restriction (n = 8) or alcohol abstinence.
Five (62.5%) subjects completed the 6 months of treatment, 4/4 subjects in group 1 and 1/4 in group 2. Three subjects stopped KD early: 2 (25%) because of GBM progression and one (12.5%) because of diet restrictiveness. Four subjects, all group 1, continued KD on their own, three until shortly before death, for total of 26, 19.3, and 7 months, one ongoing. The diet was well tolerated. TEAEs, all mild and transient, included weight loss and hunger (n = 6) which resolved with caloric increase, nausea (n = 2), dizziness (n = 2), fatigue, and constipation (n = 1 each). No one discontinued KD because of TEAEs. Seven patients died. For these, mean (range) survival time from diet initiation was 20 months for group 1 (9.5-27) and 12.8 months for group 2 (6.3-19.9). Mean survival time from diagnosis was 21.8 months for group 1 (11-29.2) and 25.4 months for group 2 ( 13.9-38.7). One patient with recurrent GBM and progression on bevacizumab experienced a remarkable symptom reversal, tumor shrinkage, and edema resolution 6-8 weeks after KD initiation and survival for 20 months after starting KD.
Conclusion on Ketogenic Diet
Treatment of GBM patients with 4:1 KD using total meal replacement program with standardized recipes was well tolerated.
The Role of Healthy Dietary Patterns
Glioma is the most common type of brain cancer, associated with a high mortality rate. Diet is one of the most modifiable factors that can influence the risk of various cancers, including glioma. While the relationship between diet and glioma has been explored in recent years, the number of studies in this area remains limited, and the findings are often controversial. Moreover, all existing studies are observational, which means they may be influenced by a range of confounding variables.
Healthy vs. Unhealthy Dietary Patterns
Research suggests that adherence to healthy dietary patterns-such as the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, Paleolithic diet, high-protein dietary patterns, and vegetarian dietary patterns-may be associated with a reduced risk of glioma. These diets are rich in phytochemicals and antioxidants. Additionally, certain food groups, including fruits, vegetables, legumes, nuts, eggs, fresh fish, tea, and coffee, are emphasized for their protective effects against glioma. Conversely, adherence to unhealthy dietary patterns, such as the Western diet, or diets with high inflammatory potential, glycemic and insulinemic loads, and high consumption of grains (especially refined grains), processed meats, and processed fish, has been linked to an increased risk of glioma. Current studies suggest that following a healthy diet may reduce the odds of developing glioma.
Meta-Analysis Findings
Findings from a systematic review and meta-analysis indicate that higher intakes of healthy dietary patterns, vegetables, and fruits are significantly associated with the lower risk of glioma. There was a reduced risk of glioma in the highest compared with the lowest categories of healthy dietary patterns (RR = 0.58; 95% CI: 0.44-0.77; P < 0.0001). Moreover, compared with the lowest intakes, the highest intakes of vegetables (RR = 0.84; 95% CI: 0.73-0.96; P = 0.012) and fruits (RR = 0.85; 95% CI: 0.72-1.00; P = 0.045) significantly reduce the risk of glioma.
Components of Healthy Dietary Patterns
The healthy dietary patterns are characterized by higher intakes of vegetables, fruits, fish, nuts, legume, olive oil, whole grains, and lower intakes of refined grains, red meat, high-fat dairy products.
Specific Food Groups and Glioma Risk
Pooled results from 13 articles (including 15 original studies) showed an inverse association between vegetables intake and risk of glioma (RR = 0.84; 95% CI: 0.73-0.96; P = 0.012). Sixteen articles reporting eighteen original studies were included, and Figure 4 showed that there was evidence of a reduced risk of glioma in the highest intake of fruits compared with the lowest intake (RR = 0.85; 95% CI: 0.72-1.00; P = 0.014). However, in pooled analyses of five studies, high intake of fresh fish was not associated with the risk of gioma (RR = 0.82; 95% CI: 0.60-1.11; P = 0.197).
Addressing Malnutrition in Cancer Patients
The nutrition status of patients with cancer can vary at presentation and through the continuum of cancer care. Many patients experience unintentional weight loss leading to a diagnosis of cancer. Studies have reported malnutrition in 30% to 85% of patients with cancer. In addition, malnutrition increases treatment toxicities, diminishes quality of life, and accounts for 10% to 20% of mortality in patients with cancer.
Etiology-Based Definitions of Malnutrition
Etiology-based definitions of malnutrition include the following:
- Starvation-related malnutrition: pure chronic starvation (e.g., anorexia nervosa).
- Chronic disease-related malnutrition (e.g., organ failure, pancreatic cancer, rheumatoid arthritis, and sarcopenic obesity, resulting in mild to moderate inflammation).
- Acute disease-related or injury-related malnutrition (e.g., major infection, burns, trauma, and closed head injury, resulting in moderate to severe inflammation).
Identifying Malnutrition
In 2012, ASPEN and the Academy released a joint statement regarding assessment of malnutrition. The statement serves as a guide for nutrition assessment, including nutrition-focused physical assessment, to determine nutrition status. The assessment takes into consideration that obesity may mask malnutrition and that weight and BMI alone are not good surrogates for nutrition status. The consensus statement provides the criteria for evaluating each of the following six potential indicators of malnutrition, with the recommendation that if two or more characteristics are present, the diagnosis of malnutrition is warranted.
- Insufficient energy intake.
- Weight loss.
- Loss of muscle mass.
- Loss of subcutaneous fat.
- Localized or generalized fluid accumulation that may sometimes mask weight loss.
- Diminished functional status as measured by hand grip strength.
Significant Weight Loss as an Indicator
Weight loss is often used as a surrogate for malnutrition. It has been correlated with adverse outcomes, including increased incidence and severity of treatment side effects and increased risk of infection, thereby reducing chances for survival. Weight loss has been used as an indicator of poor prognosis in cancer patients. One limitation of using weight loss as a surrogate for malnutrition is that it does not take into account the time course of the weight loss or the type of tissue loss. In addition, weight may be affected by fluid shifts and may represent changes in hydration status, edema, or ascites rather than actual changes in fat and lean body mass.
Anorexia and Cachexia
Anorexia, the loss of appetite or desire to eat, is typically present in 15% to 25% of all patients with cancer at diagnosis and may also occur as a side effect of treatments or related to the tumor itself. Anorexia can be exacerbated by chemotherapy and radiation therapy side effects such as taste and smell changes, nausea, and vomiting. Surgical procedures, including esophagectomy and gastrectomy, may produce early satiety, a premature feeling of fullness. Depression, loss of personal interests or hope, and anxious thoughts may be enough to bring about anorexia and result in malnutrition. Anorexia is an almost-universal symptom in individuals with widely metastatic disease because of physiologic alterations in metabolism during carcinogenesis.
Anorexia can hasten the course of cachexia, a progressive wasting syndrome evidenced by weakness and a marked and progressive loss of body weight, fat, and muscle. It can develop in individuals who have adequate protein and calorie intake but have primary cachexia whereby tumor-related factors prevent maintenance of fat and muscle. Patients with diseases of the gastrointestinal tract are particularly at risk of developing anorexia.
Sarcopenia and Sarcopenic Obesity
Sarcopenia is the condition of severe muscle depletion. The importance of lean body mass is shown in studies of sarcopenia in cancer. A meta-analysis of 38 studies found that a low skeletal muscle index at cancer diagnosis was associated with worse survival in patients with solid tumors. Other studies have also reported poorer overall survival and increased chemotherapy toxicity in patients with sarcopenia. Sarcopenic obesity may represent a chronic low-level inflammatory state that, as with disease-related malnutrition, often limits the effectiveness of nutrition interventions and requires successful treatment of the underlying disease or condition. Sarcopenia is associated with increased toxicity of treatment and therefore treatment interruptions and dose reductions. It is reported to occur in 50% of patients with advanced cancer.
Sarcopenic obesity is the presence of sarcopenia in individuals with a high BMI (≥25 kg/m2), often precipitated by the loss of skeletal muscle and gain of adipose tissue. Sarcopenic obesity is an independent risk factor for poor prognosis.
The Importance of Early Identification and Intervention
It is important to identify and anticipate malnutrition and other nutrition impact symptoms early. (Nutrition impact symptoms are a range of side effects of cancer and cancer treatment that impede oral intake, e.g., alterations in taste and smell, mucositis, dysphagia, stomatitis, nausea, vomiting, diarrhea, constipation, malabsorption, pain, depression, and anxiety.) Nutrition intervention improves outcomes by helping a patient do the following:
- Maintain weight.
- Maintain the ability to stay on the intended treatment regimen with fewer changes.
- Improve quality of life.
- Produce better surgical outcomes.
It is suggested that the treating clinician assess baseline nutrition status and be aware of the possible implications of the various therapies. Patients receiving aggressive cancer therapies typically need aggressive nutrition management.
Tumor-Induced Effects on Nutrition Status
Tumors may have systemic or local effects that affect nutrition status, including hypermetabolism, malabsorption, dysmotility, and obstructions. Nutrition complications are usually most notable and severe with tumors involving the digestive tract or head and neck, owing to mechanical obstruction or dysfunction.
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