The association between dietary intakes of methionine, choline and betaine and breast cancer risk: A systematic review and meta-analysis

Cancer Epidemiol. 2023 Apr:83:102322. doi: 10.1016/j.canep.2023.102322. Epub 2023 Jan 24.


Background and aim: This study evaluates the associations between dietary intakes and circulating blood levels of methionine, choline or betaine and breast cancer risk, which remains currently unclear.

Methods: Systematic searches for observational epidemiological studies were performed of the MEDLINE, Embase, and Web of Science databases through July, 2022. Two review authors independently screened titles and abstracts against the eligibility criteria at a first stage, and screened full texts of potentially eligible records at a second stage, followed by data extraction from qualified studies. Quality of evidence was assessed using the Newcastle-Ottawa scale quality assessment tool. Risk estimates were calculated using random-effects meta-analysis.

Results: In total, 21 studies were selected for qualitative analyses and 18 studies were included in the meta-analyses. Random-effects analysis combining prospective cohort (N = 8) or case-control studies (N = 10) showed little evidence of an association between dietary intake of methionine or betaine and the risk of breast cancer. However, inconclusive evidence for a significant inverse association between choline intake and breast cancer risk was found in case-control studies (odds ratio [OR] estimates for highest vs. lowest intakes = 0.38; 95 % CI: 0.16-0.86) but not in prospective cohort studies (hazard ratio [HR] estimates for highest vs. lowest intakes = 1.01; 95 % CI: 0.92-1.12).

Conclusion: This study did not suggest an effect of dietary intake of methionine, choline, nor betaine on breast cancer risk, mainly due to the lack of precision of the combined risk estimates as few studies are available. To overcome this uncertainty, more well-designed studies with relevant individual-level covariates are needed.

Keywords: Betaine; Breast cancer; Choline; Meta-analysis; Methionine.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betaine*
  • Breast Neoplasms*
  • Choline
  • Eating
  • Female
  • Humans
  • Methionine
  • Prospective Studies
  • Racemethionine


  • Betaine
  • Choline
  • Methionine
  • Racemethionine