The effect of the apolipoprotein E genotype on response to personalized dietary advice intervention: Findings from the Food4Me randomized controlled trial

Rosalind Fallaize, Carlos Celis-Morales, Anna L. MacReady, Cyril F.M. Marsaux, Hannah Forster, Clare O'Donovan, Clara Woolhead, Rodrigo San-Cristobal, Silvia Kolossa, Jacqueline Hallmann, Christina Mavrogianni, Agnieszka Surwillo, Katherine M. Livingstone, George Moschonis, Santiago Navas-Carretero, Marianne C. Walsh, Eileen R. Gibney, Lorraine Brennan, Jildau Bouwman, Keith GrimaldiYannis Manios, Iwona Traczyk, Christian A. Drevon, J. Alfredo Martinez, Hannelore Daniel, Wim H.M. Saris, Michael J. Gibney, John C. Mathers, Julie A. Lovegrove

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Background: The apolipoprotein E (APOE) risk allele (e4) is associated with higher total cholesterol (TC), amplified response to saturated fatty acid (SFA) reduction, and increased cardiovascular disease. Although knowledge of gene risk may enhance dietary change, it is unclear whether e4 carriers would benefit from gene-based personalized nutrition (PN). Objectives: The aims of this study were to 1) investigate interactions between APOE genotype and habitual dietary fat intake and modulations of fat intake on metabolic outcomes; 2) determine whether gene-based PN results in greater dietary change than do standard dietary advice (level 0) and nongene-based PN (levels 1-2); and 3) assess the impact of knowledge of APOE risk (risk: E4+, nonrisk: E42) on dietary change after gene-based PN (level 3). Design: Individuals (n = 1466) recruited into the Food4Me pan- European PN dietary intervention study were randomly assigned to 4 treatment arms and genotyped for APOE (rs429358 and rs7412). Diet and dried blood spot TC and v-3 (n-3) index were determined at baseline and after a 6-mo intervention. Data were analyzed with the use of adjusted general linear models. Results: Significantly higher TC concentrations were observed in E4+ participants than in E42 (P , 0.05). Although there were no significant differences in APOE response to gene-based PN (E4+ compared with E42), both groups had a greater reduction in SFA (percentage of total energy) intake than at level 0 (mean 6 SD: E4+, 20.72% 6 0.35% compared with 21.95% 6 0.45%, P = 0.035; E42, 20.31% 6 0.20% compared with 21.68% 6 0.35%, P = 0.029). Gene-based PN was associated with a smaller reduction in SFA intake than in nongene-based PN (level 2) for E42 participants (21.68% 6 0.35% compared with 22.56% 6 0.27%, P = 0.025). Conclusions: The APOE e4 allele was associated with higher TC. Although gene-based PN targeted to APOE was more effective in reducing SFA intake than standard dietary advice, there was no difference between APOE "risk" and "nonrisk" groups. Furthermore, disclosure of APOE nonrisk may have weakened dietary response to PN. This trial was registered at as NCT01530139. Am J Clin Nutr 2016;104:827-36.

Original languageEnglish
Pages (from-to)827-836
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Issue number3
StatePublished - 1 Sep 2016


  • APOE
  • Dietary fat
  • Food4me
  • Nutrigenomics
  • Personalized nutrition


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