(1) Background: Chronic inflammation and insulin resistance are associated with cardiometabolic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Therapeutic water-only fasting and whole-plant-food refeeding was previously shown to improve markers of cardiometabolic risk and may be an effective preventative treatment but sustained outcomes are unknown. We conducted a single-arm, open-label, observational study with a six-week post-treatment follow-up visit to assess the effects of water-only fasting and refeeding on markers of cardiometabolic risk. (2) Methods: Patients who had voluntarily elected and were approved to complete a water-only fast were recruited from a single-center residential medical facility. The primary endpoint was to describe changes to Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores between the end-of-refeed visit and the six-week follow-up visit. Additionally, we report on changes in anthropometric measures, blood lipids, high-sensitivity C-reactive protein (hsCRP), and fatty liver index (FLI). Observations were made at baseline, end-of-fast (EOF), end-of-refeed (EOR), and six-week follow-up (FU). (3) Results: The study enrolled 40 overweight/obese non-diabetic participants, of which 33 completed the full study protocol. Median fasting, refeeding, and follow-up lengths were 14, 6, and 45 days, respectively. At the FU visit, body weight (BW), body mass index (BMI), abdominal circumference (AC), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein (LDL), hsCRP, and FLI were significantly decreased from baseline. Triglycerides (TG) and HOMA-IR scores, which had increased at EOR, returned to baseline values at the FU visit. (4) Conclusion: Water-only fasting and whole-plant-food refeeding demonstrate potential for long-term improvements in markers of cardiovascular risk including BW, BMI, AC, SBP, DBP, blood lipids, FLI, and hsCRP.

The overconsumption of calorie-dense foods high in added salt, sugar, and fat is a major contributor to current rates of obesity, and methods to reduce consumption are needed. Prolonged water-only fasting followed by an exclusively whole-plant-food diet free of added salt, oil, and sugar may reduce the consumption of these hyper-palatable foods, but such effects have not been quantified. Therefore, we conducted a preliminary study to estimate the effects of this intervention on salty and sweet taste detection and recognition thresholds and perceived taste intensity after at least five days of fasting and at refeed day three. We also assessed the effects on sweet, salty, and fatty food preference and overall dietary consumption 30 days after the day three refeed visit. Based on this data, we estimated that 10 days after the start of the fasting, salty taste recognition, sweet taste detection, and sweet taste recognition thresholds decreased significantly, salty taste intensity ratings increased significantly, and sweet taste intensity ratings decreased significantly. We also have preliminary data that prolonged water-only fasting followed by refeeding on an exclusively whole-food-plant diet may reduce salty/fatty and sweet/fatty food liking, reduce sugar intake, and increase vegetable intake. These results support further research into the effects of fasting and diet on taste function and food likability and consumption.