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

Abstract

(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.

Keywords: cardiometabolic health; fatty liver index; hyperlipidemia; hypertension; insulin resistance; prolonged fasting; water-only fasting; whole-plant-food diet.

Figure 1

Enrollment and participation flow diagram. EOF, End of fast; EOR, end of refeed; FU, follow up; AE, adverse event. See results section for details of specific AEs.

Figure 2

Boxplots of Body Weight, BMI, and AC at Baseline, EOF, EOR, and FU. Box-plot distribution of (A) body weight (kg), (B) BMI (kg/m²), and (C) AC. BMI above 30 kg/m² (red line) is obese, BMI between 25 (green line) and 29 kg/m² is overweight, and BMI between 18 and 24 kg/m² is normal. AC above102 cm (blue) denotes upper threshold for males and above 88 cm (pink line) denotes upper threshold for females [22]. Boxplots include the minimum value, first (lower) and third (upper) quartiles, the median, and the maximum value. On all plots, blue dots represent male participants and pink dots represent female participants. EOF, end of fast; EOR, end of refeed, FU, follow up; BMI, body mass index; AC, abdominal circumference; kg, kilogram; m, meter; cm, centimeter.

Figure 3

Boxplots of Metabolic Health Indicis at Baseline, EOF, EOR, and FU. Box-plot distribution of (A) ln(HOMA-IR) where values below 0.64 (red line) is optimal insulin sensitivity [12]. ln indicates that HOMA-IR values and reference values were natural log transformed and (B) FLI where values between 0–30 (red line) are desirable and values equal to or above 60 (red line) denote presence of fatty liver disease [13]. Boxplots include the minimum value, first (lower) and third (upper) quartiles, the median, and the maximum value. On all plots, blue dots represent male participants, and pink dots represent female participants. EOF, end of fast; EOR, end of refeed; FU, follow up; HOMA-IR, homeostatic model assessment for insulin resistance; FLI, fatty liver index.