Mediterranean Diet, Energy Restriction, Physical Activity, and Atherogenicity of Very-Low Density Lipoproteins: Findings from Two Randomized Controlled Trials

Mol Nutr Food Res. 2023 Jan;67(1):e2200338. doi: 10.1002/mnfr.202200338. Epub 2022 Nov 18.


Scope: Some very-low density lipoprotein (VLDL) properties may render them more pro-atherogenic. We aimed to assess whether a Mediterranean diet (MedDiet) or an energy-reduced MedDiet with increased physical activity improves them.

Methods and results: In a sample of the PREvención con DIeta MEDiterránea (PREDIMED) study, a 1-year intervention with MedDiet with extra-virgin olive oil (n = 89) or nuts (MedDiet-Nuts; n = 79) is compared with a low-fat diet (n = 90). In the PREDIMED-Plus study, a 1-year intervention with energy-reduced MedDiet and physical activity (n = 103) is compared with an ad libitum MedDiet (n = 101). VLDL levels of apolipoprotein C-I, C-III, triglycerides, and cholesterol; the apolipoprotein E-/C-I ratio; and VLDL ex-vivo triglyceride transfer are measured. In PREDIMED participants in both MedDiet groups combined, VLDL apolipoprotein C-III levels are nominally reduced (-0.023 SD units, 95% CI -0.44 to -0.014, p = 0.037). VLDL triglyceride transfer is nominally increased in the MedDiet-Nuts group (+0.39 SD units, 95% CI 0.012-0.78, p = 0.045). In PREDIMED-Plus, no inter-group differences are detected.

Conclusions: In older adults at high cardiovascular risk, MedDiet is associated with lower VLDL atherogenicity versus a low-fat diet. No differences are seen after an energy-reduced MedDiet with physical activity.

Keywords: Mediterranean diet; energy-reduced diet; randomized controlled trial; triglycerides; very low-density lipoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diet, Mediterranean*
  • Exercise
  • Humans
  • Lipoproteins, LDL
  • Nuts
  • Olive Oil
  • Randomized Controlled Trials as Topic
  • Risk Factors


  • Lipoproteins, LDL
  • Olive Oil