Time-Restricted Eating and Mindfulness-Based Stress Reduction to Reduce the Risk of Early-Onset Colorectal Cancer

Early onset colorectal cancer (EOCRC) is defined as a diagnosis of colorectal cancer (CRC) in patients younger than 50 years old. The American Cancer Society reported that 12% of all CRC diagnoses as occurring in individuals younger than 50 years old. Worldwide, a steady increase in EOCRC cases is observed among Westernized countries, which suggests that similar risk factors and exposures within these developed countries are contributors to EOCRC. In particular, increased adiposity from an early age that persists through adulthood and chronic psychosocial stress are under investigation as drivers of the recent uptick in EOCRC in the United States (US) and other Westernized countries. Obesity in early adulthood is strongly associated with increased risk of EOCRC; in the US, obesity affects 42% of adults. In addition, obesity is associated with metabolic, hormonal, and immune perturbations that can promote gene mutations that drive EOCRC tumorigenesis. Chronic stress can negatively impact several different systems of the human body including the sympathetic nervous system (SNS)-related catecholamines, epinephrine and norepinephrine, and hypothalamic-pituitary-adrenal (HPA)-axis related hormones including adrenocorticotropic hormone and the glucocorticoid, cortisol. Due to the broad impact that exposure to chronic stress has in the human body, chronic stress has been linked to several diseases, including cancer. The gut and the brain are connected through a bidirectional system coined the gut-microbiota-brain axis (GMBA). Chronic stress can disrupt the SNS, HPA-axis and immune system, leading to a shift in gut microbial ecology and metabolic function that tips the balance to a more pro-inflammatory colonic state conducive to the formation of EOCRC. This study will examine if mitigating chronic stress and weight loss can modify EOCRC risk in young adults at risk of EOCRC. Accumulating evidence suggests that time-restricted eating (TRE), a type of intermittent fasting, produces a ~300-500 kcal/d energy deficit by limiting an individual's daily eating window to 4-8 hours each day. Mindfulness meditation is the practice of cultivating a moment-to-moment awareness of internal and external experience in an accepting and open manner. In 1990, Kabat-Zinn developed Mindfulness Based Stress Reduction (MBSR): an intervention with a goal of reducing stress, pain, and suffering. MBSR is associated with lower perceived stress and decreased circulating cortisol concentrations. Existing evidence suggests that MBSR also yields EOCRC preventive effects specific to body weight reduction, increase of insulin sensitivity and reduction of inflammation. We propose to conduct an 8-week 4-arm randomized-controlled study of 1. TRE alone; 2. MBSR alone; 3. TRE + MBSR; and 4. Control among 40 young adults with obesity (BMI ≥ 30 kg/m2) and moderate to severe perceived stress (Perceived Stress Score ≥14) to evaluate the feasibility of the interventions and preliminary effect on EOCRC-related markers. Data generated from this preliminary trial would serve in developing a fully powered efficacy trial testing TRE+MBSR for EOCRC prevention among young adults in the Chicagoland area.

Inclusion criteria

• 18-39 years old.
• BMI 30-49.99 kg/m2.
• Own and use a smartphone, computer, or tablet with access to the Internet.
• Score ≥ 14 on the Perceived Stress Score (PSS) at screening.

Exclusion criteria

• Have a personal or family history of EOCRC.
• Have taken antibiotics in the previous 2 months.
• Have an inflammatory bowel disease or genetic predisposition to EOCRC or CRC (e.g., Lynch syndrome);.
• Any cancer diagnosis or cancer treatment in the past 12 months.
• Consume >50 grams ethanol daily (approximately 4-5, 12 ounces beers).
• Use combustible tobacco.
• Have history of bariatric surgery or bowel resection.
• Have an active infection.
• Have type 1 or type 2 diabetes, immunodeficiency/autoimmune disorder, or inflammatory bowel disease.
• Use fiber or pre-/probiotic supplements >3 days per week.
• Currently taking corticosteroids medication - inhaled, topical, or oral in the past 2 months (affects cortisol measures).
• Are on a weight-loss diet or involved in a formal weight-loss program or are not weight stable for 3 months (+/- 4.5 kg) prior to the study.
• Females who are pregnant/trying to become pregnant.
• Have schizophrenia (medication can affect study outcomes).
• Have an eating window of <10 hours/day or are currently following an intermittent fasting pattern.
• Night shift workers (shift passes midnight).
• Present a history of eating disorder.
• Currently taking weight loss medication.
• Illegal drug use in the past month (not marijuana).