The Effects of Prolonged Water-Only Fasting and Refeeding on Markers of Cardiometabolic Risk

Abstract

(1) Background: Cardiometabolic disease, including insulin resistance, hyperlipidemia, and hypertension, are major contributors to adverse health outcomes. Fasting has gained interest as a nonpharmacological therapeutic adjunct for these disorders. (2) Methods: We conducted a prospective, single-center study on the effects of prolonged water-only fasting followed by an exclusively whole-plant-food refeeding diet on accepted measures of cardiovascular risk and metabolic health. Participants were recruited from patients who had voluntarily elected to complete a water-only fast in order to improve their overall health according to an established protocol at an independent, residential medical center. Median fasting and refeed lengths were 17 and 8 days, respectively. The primary endpoint was to describe the mean glucose tolerance as indicated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores at baseline, end-of-fast (EOF), and end-of-refeed (EOR) visits. Secondary endpoints were to describe the mean weight, body mass index (BMI), abdominal circumference (AC), systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid panel, and high-sensitivity C-reactive protein (hsCRP) at the same time points. (3) Results: The study enrolled 48 overweight/obese non-diabetic participants, of which 26 completed the full study protocol. At the EOF visit, the median SBP, AC, low-density lipoprotein (LDL), and hsCRP were decreased and triglycerides (TG) and HOMA-IR scores were increased. Conclusion: Prolonged water-only fasting and whole-plant-food refeeding holds potential as a clinical therapy for cardiometabolic disease but increased TG and HOMA-IR values after refeeding necessitate further inquiry.

A Six-Week Follow-Up Study on the Sustained Effects of Prolonged Water-Only Fasting and Refeeding on Markers of Cardiometabolic Risk

“…Red top tubes were incubated for 30 min at room temperature before being centrifuged at 1500× g , 10 min, 4 °C. The serum was separated, refrigerated at 4 °C, and samples were sent to a commercial lab (Labcorp, Burlington, NC, USA) for analysis [ 6 ]. LabCorp reports the following: Glucose was determined by enzymatic reference method with hexokinase and UV test; Insulin was determined by electrochemiluminescence immunoassay; hsCRP was determined via particle enhanced immunoturbidimetric assay, where human CRP agglutinates with latex particles were coated with monoclonal anti-CRP antibodies and precipitate was determined turbidimetrically; TC, TG, high-density lipoprotein (HDL), and GGT were determined via enzymatic, colorimetric method.…”

“…In this report, a regression coefficient is considered significant when the CI does not include zero. The Bayesian framework was used for the statistical analysis due to the small sample size and the availability of baseline, EOF, and EOR data from a different population in a previous study [ 6 ]. This prior information was incorporated into the model by incorporating the current data and the prior data to the model all at once [ 17 ] using Bayesian Regression Models in Stan (brms) default priors and extending the model to include an indicator variable to distinguish current and prior data.…”

“…Research into intermittent fasting, the fasting mimicking diet, and prolonged fasting methods have demonstrated the potential of these therapies to improve overall health and promote immunity and longevity [ 4 ]. Prolonged fasting protocols have been shown to improve cardiometabolic markers associated with obesity such as insulin sensitivity, blood lipids, body weight, and abdominal circumference [ 5 , 6 , 7 ]. Prolonged fasting is typically conducted as a very-low-calorie or zero-calorie (e.g., water-only fasting) intervention for a period of 2 or more days [ 8 ].…”

“…We recently reported that at least 10 days of water-only fasting and five days of refeeding on an exclusively whole-plant-food diet free of added salt, oil, and sugar (SOS-Free Diet) had mixed effects on markers of cardiovascular and metabolic health at the end of refeed in a non-diabetic, overweight/obese population [ 6 ]. We observed clinically meaningful reductions in body weight (BW), abdominal circumference (AC), blood pressure (BP), total cholesterol (TC), low-density lipoprotein (LDL), and high-sensitivity C-reactive protein (hsCRP).…”

“…Calculated homeostatic model of insulin resistance (HOMA-IR) scores, which reduced after fasting, had increased significantly after the refeeding period, indicating increased insulin resistance. We hypothesized that these effects may be a transient rebound phenomena observed during the refeeding period as fatty acid metabolism, activated during fasting, switches back to glucose metabolism during refeeding [ 6 , 11 ]. To further elucidate these findings, we conducted a follow-up, single-arm, open-label, observational study on the effects of water-only fasting and refeeding with an additional six-week post-treatment in a non-diabetic, overweight/obese population.…”