Today’s Dietitian
Vol. 28 No. 1 P. 38
Take this course and earn 2 CEUs on our Continuing Education Learning Library
Nutrition plays a vital role in both reducing the risk of cancer as well as during treatment. As RDs, it is important to stay abreast of the latest diet trends in oncology nutrition. One emerging dietary trend that has recently gained considerable attention is time-restricted eating (TRE), a type of intermittent fasting that limits food intake to a particular time window each day. Though there are different kinds of TRE making research on the topic more challenging, it is a diet pattern that has shown promising, yet inconclusive results in cancer risk reduction and management.
This continuing education course examines the latest research on the potential benefits of TRE related to cancer, and how RDs can apply this information to provide patients with appropriate and up-to-date recommendations.
Role of Nutrition in Cancer Risk Reduction
Cancer diagnoses continue to rise in the United States. The American Cancer Society estimates there will be 2 million new cancer diagnoses in the year 2024.1 Age is a contributing risk factor for cancer, with the average age of a cancer diagnosis being 66 years old.2 Nevertheless, there is emerging research on increased cancer diagnoses in the younger population, specifically those under 50 years of age.3,4 These trends were seen in specific types of cancers, such as colorectal, kidney, pancreatic, uterine, and breast cancer.4 The etiology of these trends remains unclear. However, studies suggest that increased cancer incidence in the younger population may be due to more advanced cancer screenings and earlier onset of chronic disease. Risk factor exposures early on in life and adolescence, such as diet and physical activity, may also play a role.3
The National Cancer Institute explains that cancer is a “disease where the orderly process of cell regeneration breaks down and abnormal cells generate and multiply when they shouldn’t.” These damaged cells can multiply and form cancerous tumors and then spread to different areas in the body.5 While the development of cancer is multifactorial, diet and nutrition can play a critical role in cancer risk reduction and management.
Weight and Cancer Risk Reduction
Obesity can cause metabolic disturbances in cellular and molecular processes that increase the development of cancer. Altered levels of insulin, steroid hormones, and proinflammatory cytokines can favor tumor development and growth.6,7 Thus, obesity is identified as a risk factor for several cancers, including breast, endometrial, prostate, pancreatic, and colon cancer.7 Many epidemiological studies demonstrate that weight loss in obese and/or overweight individuals may decrease cancer incidence. For example, a retrospective cohort study assessed whether bariatric surgery was associated with lower cancer risk and mortality rates in patients with obesity. The 30,318 study participants were divided into two groups: surgical intervention (Roux-en-Y gastric bypass or sleeve gastrectomy) vs nonsurgical intervention. The surgical intervention group experienced a 19.2% greater weight loss than the nonsurgical group. The incidence of cancer in the bariatric surgery group was 2.9% vs 4.9% in the nonsurgical control group (P=0.002). The authors concluded that greater weight loss among the bariatric surgery group was associated with a lower risk of obesity-associated cancer.8 Another large prospective study found an association between intentional weight loss (greater than 5%) among obese women and a significantly lower risk for endometrial cancer.9 These findings propose that weight loss may be an important tool in cancer risk reduction.
Diet and Cancer Risk Reduction
There is a growing number of studies that demonstrate a significant association between dietary patterns such as the Mediterranean diet and a reduced risk of cancer. In a meta-analysis of randomized controlled trials (RCTs), cohort, and case-controlled studies, a higher adherence to the Mediterranean diet was associated with a lower risk of cancer mortality, especially with colorectal cancer (CRC). It is believed the benefits were primarily driven by higher intakes of fruits, vegetables, and whole grains.10 A review of observational studies found a similar association with plant-based diets, specifically with colorectal and breast cancers.11 In addition, several studies have shown an association between the consumption of ultraprocessed foods and unhealthy dietary patterns (red/processed meats, sugar sweetened drinks, refined carbohydrates) and higher overall cancer risk, whereas diets rich in fruits, vegetables, legumes, and whole grains are linked to a reduced risk of cancer.12,13 These beneficial effects may be due to the high fiber content, antioxidants, and balanced ratio of fatty acids, which may play a role in inhibiting cancer-related biological pathways and protecting against cellular damage.13 This research suggests adopting a healthful and balanced diet may help reduce overall cancer risk.
Nutritional Implications for People With Cancer
While nutrition appears to play a role in reducing the risk of cancer, it may also play a critical role in managing it as well, once a person is diagnosed. A balanced and healthful diet can help support a patient’s immune system and maintain both their energy and strength levels. It can also help reduce the risk of complications and support recovery.14 Cancer patients are at an increased risk for malnutrition and loss of muscle mass due to metabolic and physical effects of cancer, therapy side effects, and inadequate nutritional intake, which may negatively impact clinical outcomes.14 During chemotherapy treatments, patients often experience dysgeusia, nausea, and vomiting. Per the European Society for Clinical Nutrition and Metabolism guidelines, MNT should be focused on maintaining or improving oral intake by recommending a nutritionally adequate diet. Each patient’s nutritional needs will vary depending on the type and stage of cancer, as well as their individual treatment plan.14,15
Time-Restricted Eating
In addition to a balanced and healthful diet, it has been postulated that the timing of intake may also have benefits for cancer risk reduction and management. TRE is a type of intermittent fasting that restricts food intake to a specific window of time. Typically, TRE limits food consumption to a four- to 12-hour window, while the remaining 12 to 20 hours of the day are dedicated to fasting.16
Time-Restricted Eating on Weight Loss and Metabolic Parameters
Studies have shown that TRE may have a positive impact on weight loss for those who are overweight or obesity. One of the main ways in which TRE aids with weight loss is by reducing the number of hours in a day that a person consumes calories. By limiting the eating window, TRE can naturally lead to a reduction in overall caloric intake, which can result in weight loss. A 14-week, parallel-arm RCT evaluated whether TRE was more effective in weight loss, fat loss, and improved cardiometabolic parameters compared with energy restriction alone. Ninety participants were randomized to either an early TRE (eTRE) group—an eight-hour eating window from 7:00 to 15:00—or a control group with a self-selected eating window of 12 hours or more, designed to mimic typical US eating patterns. All participants received matched dietary counseling involving a hypocaloric diet and exercise goals. The co-primary outcomes were weight and fat loss, and secondary outcomes included cardiometabolic markers. The eTRE group demonstrated significantly greater weight loss (P=0.002) and improvement in blood pressure (P=0.04) compared with the control group.17 However, some studies have shown similar benefits regarding weight loss with a non-TRE calorie restriction diet.18,19
Additionally, some forms of TRE has shown positive effects on insulin sensitivity and glucose regulation. These metabolic benefits, in turn, may help prevent weight gain and obesity. A 2020 systematic review and meta-analysis of 16 studies, of which 11 were RCTs, analyzed the effects of TRE (defined by these researchers as fasting for 12 to 20 hours because generally people eat three times a day over a 12-hour period) on body weight, body composition, and metabolic markers.20 Twelve of these studies reported weight changes with TRE. Five of those included participants with metabolic abnormalities such as overweight/obesity, prediabetes, metabolic syndrome, or nonalcoholic fatty liver disease and demonstrated significant weight loss. The other seven analyzed healthy participants, and while weight loss occurred, it was not statistically significant. Regarding body composition, 10 studies reported significantly lower fat percentages with TRE, defined in this review as a daily fasting period of 12 to 20 hours. In addition, TRE significantly lowered blood pressure, fasting blood glucose, and triglyceride levels. The review concluded that TRE reduced body weight and fat and improved metabolic parameters. However, limitations of the meta-analysis included small sample sizes, short study durations, and increased risk of bias. An additional review of clinical trials assessed the impact of TRE (defined in the study as a fasting time ≥ 12 hours/day) specifically on glucose and lipid metabolism.21 Several trials included in the review revealed that TRE (averaging an “eating window” between six and 12 hours/day) lowered glucose levels, lowered fasting insulin, and improved insulin sensitivity in mixed participants (people with overweight/obesity, “healthy” status, and even athletes); an improvement in triglyceride levels and cholesterol levels were also noted. Nevertheless, a few studies had adverse or no effects on glycemic and lipid markers. This may be attributed to the heterogeneity of studies included in the review. For example, the studies differed in fasting/eating durations, time of eating, differences in caloric intake, and duration of interventions. The subjects also differed in metabolic status, age, and gender.21 Thus, more studies are needed to evaluate the specific benefits of TRE on weight loss and metabolic parameters and better understand the use of TRE long-term, including any safety concerns. It is also important to consider that the effects of TRE may vary depending on the individual and their overall diet and lifestyle habits.
Time-Restricted Eating and Cancer
Animal Models
Several studies have suggested that TRE may have potential benefits in cancer risk reduction, specifically in animal models. Das et al conducted a study on the effects of TRE (a nine-hour eating window during the night, which aligns with the active phase of mice as they are nocturnal) on metabolic dysfunction and breast cancer in two animal models with postmenopausal obesity. The two groups were randomly assigned to either TRE or ad libitum feeding with normal chow for seven weeks. Both groups gained weight and food intake did not differ between groups. TRE resulted in improved glucose levels and insulin tolerance. In addition, the researchers found that TRE reduced tumor initiation, progression, and metastasis in obesity-driven postmenopausal breast cancer.22 Sundaram and Yan had similar findings in which TRE inhibited mammary tumor growth in spontaneous breast cancer in mice.23
Another animal research study evaluated how TRE impacts microbiota and potentially reduces the risk of CRC. Forty nine-week-old healthy mice were randomly assigned to one of four groups: TRE for two months, ad libitum feeding in the first month prior to TRE in the second month, TRE in the first month followed by ad libitum feeding in the second month, and continuous ad libitum feeding. TRE was defined in this study as allowed to eat one hour after lights off to three hours before lights on, an eight-hour feeding window during the dark/active phase. The results demonstrated that TRE caused changes in the gut microbiota, specifically Firmicutes phylum, Clostridia class, Ruminococcaceae family, and Roseburia genus. The findings suggest potential protective effects against CRC through these beneficial changes in the gut microbiome.24
However, these findings are not consistent with other types of cancer, such as renal cancer.25 Turbitt et al investigated whether TRE alone or combined with immunotherapy would delay renal tumor growth in mice. In the study, mice were randomized to TRE (eating window six hours, from 8:00 am to 2:00 pm, with no caloric intake outside this period.) with or without immunotherapy administration or ad libitum feeding. The outcomes assessed were body composition, tumor variability and growth, and immune responses. They concluded that TRE did not reduce tumor growth in mice with aggressive renal cancer.25
Human Studies
Although most studies have been conducted in animal models, there are a few studies that have investigated the relationship between TRE and cancer risk in humans. The research available is mainly epidemiological studies or small sample-size studies that have assessed cancer biomarkers.
The Multicase-Control (MCC) study, an epidemiological trial conducted in Spain, examined the association between TRE and prostate cancer risk in men. The participants, 607 men with prostate cancer and 848 men with no diagnosis of cancer, completed a questionnaire where information was collected on meal timing. Researchers found that men who fasted for more than 11 hours overnight, followed by an early breakfast, referred to as early TRE, had a lower risk of developing prostate cancer.26
The MCC study also assessed whether the timing of eating and sleep patterns were associated with an increased risk of breast and prostate cancer. They evaluated 1,321 breast and 621 prostate incident cancer cases against 3,402 control participants. Participants who had an earlier dinner meal (before 9 pm) and longer interval periods between dinner and sleep (greater than two hours), had an approximately 25% decreased combined cancer risk. The researchers suggested that changes in the timing of sleep or diet may have potential benefits in decreasing prostate and breast cancer risk.5,27
Another prospective study investigated the impact of nightly fasting on breast cancer risk and recurrence. Data from 24-hour dietary recalls were collected from 2,413 women with breast cancer. The results demonstrated that fasting less than 13 hours per night was associated with an increased breast cancer risk. The authors concluded that prolonging the number of hours of the nightly fasting interval may be an effective strategy to prevent breast cancer reoccurrence, although they acknowledged the need for RCTs to establish causation.28 These three studies suggest the mechanism by which TRE may reduce cancer risk is related to circadian rhythm and improvement in glycemic control.26-28
A pilot study conducted by Kleckner et al evaluated the effects of TRE in cancer survivors. Participants included in the study were four to 60 months postcancer treatment and were experiencing fatigue symptoms. Participants were instructed to adhere to a 10-hour self-selected fasting window for 14 days. The eating window occurred during the day and was chosen by each participant based on their usual meal patterns and preferences, with the expectation that it will remain consistent throughout the study. Water and medications were always allowed, but coffee, tea, chewing gum, and diet beverages were discouraged during the fasting window due to their potential impact on circadian rhythm. The researchers found that fatigue symptom scores improved with a moderate effect size. However, a larger, more diverse sample size would need to be studied, as there were only 39 participants and 89.7% were breast cancer survivors. The study did not have a control group to allow for comparison.29 Although the fasting window was standardized to 14 hours, outcomes may vary depending on the timing of the eating window; studies applying the same fasting duration at different times of day (eg, early vs late) have shown varying metabolic and behavioral effects.
While not directly aimed at cancer, several studies previously discussed may infer some cancer protection. The metanalysis by Moon et al revealed that TRE (defined as fasting for 12 to 20 hours because generally people eat three times a day over a 12-hour period) significantly lowered fasting glucose concentration in participants with metabolic dysregulation. In addition, the 2021 review by Schuppelius et al demonstrated that TRE lowered glucose levels and fasting insulin, and improved insulin sensitivity. Since obesity causes an increased risk for hyperinsulinemia, and in turn obesity-driven cancers, these findings may indirectly infer a reduced cancer risk.20,21
Clearly more research is needed in order to better understand the link between TRE and the potential for cancer risk reduction. High quality RCTs would be immensely helpful in not only knowing what eating patterns might work best and for which cancers but also addressing concerns around safety and duration.
Physiological Mechanisms of Action
The mechanisms by which TRE affects cancer are not fully understood; however, several potential mechanisms have been proposed. One mechanism is through inflammation modulation. Several studies on TRE and cancer treatment or risk reduction have shown TRE of various kinds ranging from a four- to 12-hour eating window to 5:2 (five days normal eating with two days restricted to 65% energy) suppresses inflammation and induce autophagy to remove or repair damaged organelles.16,30
Another potential mechanism is through improved alignment with circadian rhythms. Circadian rhythm is a predetermined, 24-hour cycle in which various physiological, including behavioral, pathways are regulated, including metabolic homeostasis.23 Disruptions in circadian rhythm may promote obesity, insulin resistance, abnormal cellular division, and tumorigenesis. The circadian clock supports normal metabolic regulation, and TRE (limiting food consumption to a four- to 12-hour window) has been shown to restore circadian rhythms in animal models.16
TRE is also linked to reductions in markers of oxidative stress. These reductions are likely related to improvements in insulin resistance, which may decrease cancer risk.20,21 Finally, TRE may also have a positive influence on the gut microbiome. TRE has been shown to improve the gut microbiota and prevent colon cancer in one animal study.24 In two human trials, however, TRE was shown to improve the diversity and overall composition of the gut microbiome in normal-weight individuals but had no effect in obese individuals.18
Safety of Time-Restricted Eating
Based on the literature, TRE is a safe and viable method for individuals trying to achieve weight loss and improve cardiometabolic health. In fact, one important finding is that TRE has been shown to preserve muscle mass in overweight and/or obese individuals losing weight.16 Weight loss interventions typically result in a decrease of both fat and lean body mass in overweight and/or obese individuals.31 However, in the review conducted by Moon et al, TRE reduced fat mass while preserving muscle mass.20 This may infer why TRE improves metabolic parameters in overweight and/or obese patients, specifically because of the crucial role muscle mass plays in weight management and metabolic health.
There are no current specific studies that evaluate the safety of TRE and cancer. Thus, there is lack of evidence to deduce whether TRE is safe for individuals who have cancer, especially for those who are in active cancer therapy.30 A recent review conducted by Das and Webster did discuss the general safety of TRE. The authors reported that four to 12 hours per day TRE is a more effective and safe way for individuals to lose weight compared with energy restriction, possibly due to its ability to preserve muscle mass. In addition, no major adverse events were reported among adults with obesity, metabolic syndrome, diabetes, or prediabetes. Nevertheless, the authors highlighted that TRE may not be appropriate for individuals with type 1 diabetes or impaired liver function.16 These authors cite evidence-based data about the link between obesity and certain cancers including colorectal, endometrial, kidney, liver, pancreatic, esophageal, and some types of breast cancer and TRE may be an effective strategy for patients at risk of or with these cancers. However, malnutrition is a major concern during cancer treatment, with up to 70% or more patients experiencing unintended weight loss combined with the inability to meet their nutrition needs. TRE may not be safe for all, and malnutrition screening tools should be used to assess the safety for each individual patient.32 More long-term studies that further assess the safety of TRE are needed, specifically related to patients undergoing cancer treatment.
Adherence of Time-Restricted Eating
Studies have demonstrated adherence to TRE, particularly when the eating window is consistent and falls during daytime hours, most commonly between a four- and 12-hour window, and typically involves overnight fasting to align with circadian rhythms may contribute to its sustainability. During the fasting window, water and zero-calorie beverages are generally permitted. While most TRE research focuses on daily eating windows of four to 12 hours, some studies have also explored intermittent patterns like the 5:2 model, which includes five unrestricted eating days and two days of total or partial caloric restriction. TRE may be an easier approach for individuals to follow, as it typically does not require decreasing caloric intake, tracking calories, or changing the diet composition. Since fasting periods are during the night, an individual may experience less feelings of hunger.16 Some studies have also suggested that TRE may positively impact hunger and satiety hormones.32 In the study conducted by Kleckner et al, adherence was high, with 86% of the participants adhering to the diet.29 Many of the participants also stated they would continue a TRE pattern after the completion of the study. As TRE can be perceived as more flexible and simpler to follow than a calorie-restricted diet, weight loss maintenance is often more sustainable.33
Study Limitations and Areas of Future Research
More research is needed to fully understand the relationship between TRE and cancer as well as the underlying mechanisms of action. While some studies suggest that TRE may have potential benefits in reducing cancer risk, other studies have not found significant effects.16,17 It is also important to note that individual factors, such as genetics and lifestyle habits, may influence cancer risk as well. Future research should also focus on identifying the optimal timing and duration of TRE as well as appreciating individual differences potentially influencing fasting outcomes, such as age, weight, and baseline adiposity.34
Moreover, many of the studies were conducted in mice and not humans.16,22-25,34 There are significant differences between rodents and humans concerning biological adaptations to fasting. Furthermore, mice in these studies were fed nutritionally balanced chow during nonfasting periods, whereas in humans, typically during nonfasting periods, the diet quality and food composition are not controlled.30 Although these studies provide some preliminary evidence supporting TRE in reducing cancer risk, further research is needed to determine whether TRE has similar effects in humans. Due to the lack of human studies, clinical trials of longer duration are needed to determine the safety, feasibility, and potential benefits of TRE in patients with active cancer who are undergoing treatment.
In addition, many of the human trials used self-reported dietary recalls, which may result in recall bias and measurement error.20-22 Several studies were epidemiological in nature and had small sample sizes, thus were not able to establish causation. Furthermore, the current research available is primarily on obesity-driven cancers, not making it generalizable to other types of cancers.
Importantly, the term “TRE” encompasses a wide range of fasting protocols that may have very different short- and long-term physiological effects. More restrictive forms of TRE may impact the body’s stress response system and could theoretically exert a dose-dependent effect, where shorter durations may result in beneficial metabolic changes, but prolonged adherence could trigger harmful outcomes.34 This variability underscores a key research gap, as long-term human data on the health impacts of different TRE regimens remains limited.
The current literature is variable and unable to establish a causal relationship between TRE and cancer. Two promising RCTs are currently in progress that plan to evaluate the links between TRE and cancer, specifically for breast and CRC.
IMPACT-Women Trial35
The IMPACT-Women (Impact of Metabolic health Patterns And breast Cancer over Time in Women) study is a RCT that is seeking to investigate the effect of TRE, healthful eating, and decreased sedentary behaviors during chemotherapy treatment for stages I-III breast cancer participants. TRE is defined in the study as a flexible 16:8 protocol, with the option to adjust the eating window to eight to 10 hours, start eating at a self-selected time (ending at least three hours before bedtime), and take up to one to two days off per week after five consecutive days of adherence. The trial will enroll 130 women with early-stage breast cancer who are in chemotherapy treatment. The intervention group will receive 30- to 60-minute telephonic counseling by an RD on TRE, healthy eating, and goal setting for reducing sedentary time. The control group will receive customary cancer and supportive care that includes a nutrition class on healthy eating and physical activity. The study will assess visceral fat accumulation and cardiometabolic dysfunction by MRI, laboratory markers, and blood pressure at baseline, after chemotherapy treatments, and at the two-year follow-up. The study will determine if TRE is successful in lessening the impact of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, thus potentially reducing the risk of cardiometabolic disease and mortality in individuals with breast cancer.35
TRE-CRC Trial36
Another promising RCT is the TRE-CRC trial. This is a parallel-arm, RCT that plans to evaluate the effect of TRE compared with calorie restriction on weight loss, weight-loss maintenance, and reducing the risk of CRC in obese adults. The researchers will recruit 255 adults with obesity and prediabetes who are at an increased risk for CRC. Participants will be randomized to either eight-hour TRE, calorie restriction, or a control group. This study uses a delayed TRE protocol with an eight-hour eating window from 12 pm to 8 pm during the weight-loss phase, later extended to a 10-hour window from 10 am to 8 pm for weight maintenance. No calorie tracking is required, and only calorie-free beverages are allowed during the fasting period. The calorie restriction protocol reduces energy intake by 25% of total energy expenditure during the weight-loss phase. Energy needs are calculated using indirect calorimetry and adjusted for activity level. In the weight-maintenance phase, participants consume 100% of energy needs to maintain weight. The study is proposed to last 12 months, separated into a six-month weight-loss phase and a six-month weight-maintenance phase. Outcome variables to be assessed include body weight and composition, diet adherence, metabolic, inflammatory, and oxidative stress biomarkers, and CRC risk markers, including colonic mucosal gene expression profiles and tissue microenvironment. Overall, the study hopes to determine whether TRE may be an effective, alternative method for weight loss and maintenance and in turn, may be effective in reducing the risk of CRC in adults with obesity.36
Putting It Into Practice
TRE may be a useful dietary tool for reducing the risk of and the management of cancer. The research is promising, with many new trials underway; however, currently we have insufficient evidence to fully understand its role in cancer and particularly in which types of cancer it may or may not be most helpful. While some data indicate a role for TRE in cancer risk reduction, TRE should not be recommended for patients undergoing active cancer treatment due to a lack of long-term studies on the efficacy and safety of TRE at this point in time. While more research emerges, RDNs should continue to take an individualized approach when providing MNT to patients for cancer risk reduction and management. This includes completing a comprehensive nutritional assessment and making recommendations based on the patients’ unique preferences and goals, with a focus on adequate caloric and protein intake.37
Based on recent literature, TRE may be recommended for adults interested in the diet for reducing the risk of cancer through weight management and improved metabolic markers. However, it is important to help the patient understand that TRE should not be a substitute for a balanced, healthful diet and physical activity. RDs should continue to emphasize the consumption of a variety of foods, including fruits, vegetables, whole grains, and legumes, and help identify ways to incorporate plant-based foods into the diet. Patients should be advised to consult with their medical provider prior to implementing any dietary changes, especially TRE, to ensure there are no contraindications with their current medical treatment and/or medications. If they do start TRE, beginning with a longer eating window of eight to 10 hours and reducing if needed based on their schedule and experience with the dietary changes could be a first step.
In conclusion, RDs can play a key role in providing personalized education and guidance to help patients reduce their risk of cancer through diet and lifestyle modifications. TRE, when appropriate, may be a useful tool RDs can suggest for additional risk mitigation. For patients undergoing cancer treatment, however, RDs should continue to provide evidence-based MNT to optimize nutritional status and improve quality of life.
— Damaris Cruz, MS, RDN, CSR, LDN, is a clinical registered dietitian based in Miami.
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