Weight Loss and Endocrine Disrupting Chemicals (EDCs): Lifestyle interventions to lose weight and reduce EDC exposure in individuals with overweight/obesity - ABSTRACT The rising rates of obesity and metabolic disorders are a major health concern1 with an medical cost of $260 billion annually in the US.2 While poor diet/lack of exercise contribute to this issue, it doesn’t explain it fully.1,3,4 Many harmful endocrine disrupting chemicals (EDCs) act as “obesogens,” environmental chemicals that alter metabolic endpoints and promote fat deposition.3 Increased BMI has been associated with increased EDC levels,5,6 and higher EDC levels at baseline have been associated with a greater increase in body weight over time7 and greater difficulty achieving and maintaining weight loss.8–10 It has been estimated that EDC-related obesity/ metabolic disease costs the US $5.4 billion annually.11 While there are several digital weight-loss tools and programs currently available to treat obesity, there are very few tools that allow individuals to track and reduce their daily EDC exposures. Million Marker (MM), a science-based health and wellness company,12 offers the first effective direct-to-consumer EDC testing and intervention program.13 It is known that behavioral interventions can both promote weight loss in adults with obesity14,15 and reduce their non-persistent EDC exposures in urine.16–18 However, it is unclear if 1) weight loss programs can reduce EDC exposures, or if 2) EDC reduction intervention can result in weight loss. Thus, we propose a two-armed, randomized clinical trial to examine these relationships in individuals with overweight/obesity. We will, 1) determine if MM’s 16-week EDC intervention program (EDC testing and report-back, EDC reduction curriculum, and group coaching) can reduce weight; 2) determine if a 16-week validated digital weight loss program (Noom)14 can reduce EDC exposures; and 3) compare the effectiveness of the two interventions at reducing weight and urinary EDC metabolites. All three aims will assess EDC metabolites and weight loss, as well as the effects of the interventions on improving EDC and weight related health literacy, readiness to change, adoption of healthy behaviors, and wellness (stress, sleep, general health, physical activity, social support, and financial well being), assessed via validated surveys before and after the interventions. Urinary EDC metabolites will be measured via MM mail-in EDC testing kits pre- and post-intervention.16 We hypothesize that post-intervention, participants in both arms will have reduced EDC exposures and weight, as well as improved health literacy, readiness to change, healthy behaviors and wellness. The results of this Phase I pilot will enable the larger Phase II study, in which we will examine the interaction of both interventions in order to determine whether the combination results in greater weight loss and greater EDC reduction than either intervention alone. Additional clinical endpoints (e.g. cholesterol, HbA1c, inflammatory markers) will also be investigated in the Phase II study. We will also be well situated to increase our study sample size as well as recruit more racially/ethnically diverse participants in the Phase II study, in preparation for commercialization of the EDC testing and intervention program among clinics, employee wellness programs, and large healthcare systems and insurers.