Intermittent fasting and changes in Galectin-3: A secondary analysis of a randomized controlled trial of disease-free subjects

Nutr Metab Cardiovasc Dis. 2022 Jun;32(6):1538-1548. doi: 10.1016/j.numecd.2022.03.001. Epub 2022 Mar 7.


Background and aims: Intermittent fasting reduces risk of interrelated cardiometabolic diseases, including type 2 diabetes and heart failure (HF). Previously, we reported that intermittent fasting reduced homeostasis model assessment of insulin resistance (HOMA-IR) and Metabolic Syndrome Score (MSS) in the WONDERFUL Trial. Galectin-3 may act to reduce insulin resistance. This post hoc evaluation assessed whether intermittent fasting increased galectin-3.

Methods and results: The WONDERFUL Trial enrolled adults ages 21-70 years with ≥1 metabolic syndrome features or type 2 diabetes who were not taking anti-diabetic medication, were free of statins, and had elevated LDL-C. Subjects were randomized to water-only 24-h intermittent fasting conducted twice-per-week for 4 weeks and once-per-week for 22 weeks or to a parallel control arm with ad libitum energy intake. The study evaluated 26-week change scores of galectin-3 and other biomarkers. Overall, n = 67 subjects (intermittent fasting: n = 36; control: n = 31) completed the trial and had galectin-3 results. At 26-weeks, the galectin-3 change score was increased by intermittent fasting (median: 0.793 ng/mL, IQR: -0.538, 2.245) versus control (median: -0.332 ng/mL, IQR: -0.992, 0.776; p = 0.021). Galectin-3 changes correlated inversely with 26-week change scores of HOMA-IR (r = -0.288, p = 0.018) and MSS (r = -0.238, p = 0.052). Other HF biomarkers were unchanged by fasting.

Conclusion: A 24-h water-only intermittent fasting regimen increased galectin-3. The fasting-triggered galectin-3 elevation was inversely correlated with declines in HOMA-IR and MSS. This may be an evolutionary adaptive survival response that protects human health by modifying disease risks, including by reducing inflammation and insulin resistance.

Trial registration:, NCT02770313 (registered on May 12, 2016; first subject enrolled: November 30, 2016; final subject's 26-week study visit: February 19, 2020).

Keywords: Insulin resistance; Metabolic syndrome; Periodic fasting; Therapeutic fasting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Diabetes Mellitus, Type 2* / diet therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Fasting*
  • Galectin 3* / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Metabolic Syndrome* / diet therapy
  • Metabolic Syndrome* / metabolism
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Water / administration & dosage
  • Young Adult


  • Biomarkers
  • Galectin 3
  • Insulin
  • Water

Associated data