Slightly Elevated Serum Ionic Fluoride Levels Inhibit Insulin Secretion and Increase Glucose Levels in a General Japanese Population: a Cross-sectional Study

Biol Trace Elem Res. 2021 Aug;199(8):2819-2825. doi: 10.1007/s12011-020-02415-1. Epub 2020 Oct 8.


A cross-sectional study was performed to investigate the relationships between serum fluoride levels, glucose levels, and insulin secretion in a general population. A total of 330 healthy subjects (167 men; 163 women) aged between 40 and 69 years were examined. Lifestyle information was obtained using questionnaires. Blood samples were collected in the early morning, and biochemical parameters and glucose indices were measured. Serum ionic fluoride (SIF) levels were assessed using a highly sensitive method. Relationships between glucose indices and SIF levels were investigated using a multiple linear regression analysis. SIF levels positively correlated with fasting plasma glucose (FPG) and glycohemoglobin (HbA1c) levels in both sexes. In women, SIF levels negatively correlated with homeostasis model assessment insulin secretion (HOMA-β) levels. In men, the proportion of regular drinkers negatively correlated with HOMA-β, but not SIF levels. Although SIF levels < 1 μmol/L were associated with reduced insulin secretion and increased FPG levels, the risk of diabetes was not elevated. These results suggest that increased SIF levels caused by a large fluoride intake and compromised renal function combined with poor lifestyle choices elevate the risk of diabetes. Further studies are warranted to elucidate the effects of fluoride on glucose metabolism.

Keywords: Fluoride; Glucose; Glucose metabolism; Insulin secretion; Serum; Serum ionic fluoride.

MeSH terms

  • Adult
  • Aged
  • Blood Glucose
  • Cross-Sectional Studies
  • Female
  • Fluorides*
  • Glucose
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion
  • Japan
  • Male
  • Middle Aged


  • Blood Glucose
  • Insulin
  • Glucose
  • Fluorides