Sugar intake and cardiovascular disease risk: With an emphasis on genetic and metabolomic biomarkers of sugar intake

Abstract

Introduction: Contrary to popular belief, there is limited research on sugar intake as a risk factor for cardiovascular disease. While the links between sugar-sweetened beverage intake and cardiovascular disease risk are well-established, little is known about the associations for overall added or free sugar intake and other dietary sources of added sugar. Objective markers of habitual sugar intake could help elucidate these links. 

Aim: The aim of this thesis was to investigate the associations between added and free sugar intake, as well as intake of various sugar-sweetened foods and beverages, and cardiovascular disease risk. Further, this thesis aimed to identify genetic and plasma metabolite markers of sugar intake to be used as objective markers of sugar intake.

Method: Prospective associations between added and free sugar intake, sugar sweetened foods and beverages, and cardiovascular disease incidence were studied in the Malmö Diet and Cancer study (n=25,877), and the Swedish mammography cohort combined with the cohort of Swedish men (n=69,705). Genetic markers of sugar intake were studied in the Malmö Diet and Cancer study (n=25,660) and the UK biobank (n=141,837), including both a replication study and genome-wide association studies. Finally, plasma metabolite profiles of sugar intake were identified in the Malmö Diet and Cancer study (n=830).

Results: High sugar intake was linked to higher ischemic stroke risk, but the highest risk for most studied outcomes was found in the lowest sugar intake group. Sugar sweetened beverage intake consistently showed increased cardiovascular disease risk, while treats showed a negative association. Genetic variants in the FTO gene, an intergenic region on chromosome 18, and near the FGF21 gene on chromosome 19 are linked to sugar intake, with only the FGF21 associations being independent of education, smoking, and BMI. Previously identified genetic variants in sweet-taste receptor and glucose transporter genes were not replicated. Finally, distinct metabolite profiles for various categories of habitual consumption of sugar and sugar-sweetened foods and beverages were characterized.

Conclusion: Based on the findings of this thesis, it is still difficult to conclude a clear increased risk of cardiovascular disease incidence associated with added or free sugar intake as the shape and directions of the associations vary between different cardiovascular diseases. The results did however consistently show positive linear associations between sugar-sweetened beverage intake and cardiovascular disease risk, while conversely, showing negative linear associations for intake of treats and cardiovascular disease risk. Future evaluation of these associations can be aided using the genetic and metabolomic markers of sugar intake identified in this thesis, but they should be validated in other populations first.

• author: Janzi, Suzanne
• supervisor: Emily Sonestedt; Yan Borné
• opponent: Associate Professor in Genomics and Precision Medicine Merino, Jordi, Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen
• organization: Nutrition Epidemiology (research group)
• publishing date: 2025
• type: Thesis
• publication status: published
• subject: Nutrition and Dietetics
• keywords: Added sugar intake, dietary sugar intake, cardiovascular disease, metabolomics, genomics, sugar biomarkers
• in: Lund University, Faculty of Medicine Doctoral Dissertation Series
• issue: 2025:66
• pages: 99 pages
• defense location: Agardh föreläsningssal, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
• defense date: 2025-05-30 13:00:00
• ISSN: 1652-8220
• ISBN: 978-91-8021-719-4
• language: English
• LU publication?: yes
• id: 10898ead-a297-4e11-ae3a-6fb741c7d67e
• date added to LUP: 2025-05-10 11:01:23
• date last changed: 2025-05-12 09:45:08