Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats.
Level 5 - mechanism / opinion, no new human data
Animal research
PubMed 20026095 · doi:10.1016/j.taap.2009.11.025
What was done
Male Fischer-344 rats were administered 2-deoxy-D-glucose (2DG) long-term to evaluate survival, tumor incidence, and toxicity. A subsequent 6-week follow-up study tested synthetic 2DG and a natural form of 2DG across male Brown Norway and Fischer-344 rats to assess food intake, weight gain, cardiac histopathology (lipid and glycogen staining of vacuoles), and cardiac autophagy markers (cathepsin D and LC3).
What was found
The abstract reports no numerical data. Long-term 2DG ingestion increased mortality and the incidence of adrenal medulla pheochromocytoma in male Fischer-344 rats. In the 6-week study, high levels of both synthetic and natural 2DG reduced food intake and secondary weight gain across both rat strains. Cardiac histopathology revealed dose-dependent myocyte vacuolization free of lipid and glycogen, alongside increased expression of cathepsin D and LC3.
Why it matters
Although 2DG replicates metabolic hallmarks of calorie restriction, its cardiotoxicity, increased tumor incidence, and lethality argue against its viability as a safe calorie restriction mimetic in mammals.
Limits
This is an animal study conducted exclusively in male rats of two inbred strains. The abstract does not report sample sizes, specific dosages, survival numbers, or statistical significance metrics. In vivo cardiac functional parameters were not measured.
Cited by
- supports The glycolytic inhibitor 2-deoxyglucose exerts anti-seizure effects at approximately 25 mg/kg, but becomes cardiotoxic at higher doses.