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Session: Nutritional Proteomics and Metabolomics (Oral 2)

(OR02-01-23) Plasma Proteomic Profiles of Sugar- and Artificially Sweetened Beverage Intake in Men and Women

Saturday, July 22, 2023
2:30 PM – 2:42 PM ET
Location:  Constitution B

    Presenting Author(s)

  • Shilpa N. Bhupathiraju, PhD

    Assistant Professor
    Harvard Medical School and Brigham and Women's Hospital
    Boston, Massachusetts, United States

    Disclosure information not submitted.

    • Co-Author(s)

  • Danielle E. Haslam, PhD

    Postdoctoral Research Fellow
    Brigham and Women's Hospital and Harvard Medical School
    Canton, Massachusetts, United States

    • Co-Author(s)

  • JL

    Jun Li

    Brigham and Women's Hospital and Harvard Medical School

  • ZC

    Zsu-Zsu Chen

    Beth Israel Deaconess Medical Center, Harvard Medical School

  • JL

    Jessica Lasky-Su

    Brigham and Women's Hospital and Harvard Medical School

  • DT

    Deirdre K. Tobias, ScD (she/her/hers)

    Assistant Professor
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

  • ER

    Eric B. Rimm, ScD

    Professor
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

  • RG

    Robert E. Gerszten

    Beth Israel Deaconess Medical Center, Harvard Medical School

  • AC

    Andrew T. Chan, MD, MPH

    Professor of Medicine
    Massachusetts General Hospital and Harvard Medical School
    Boston, Massachusetts, United States

  • Sylvia H. Ley, PhD, RD (she/her/hers)

    Assistant Professor
    Tulane University School of Public Health and Tropical Medicine
    New Orleans, Louisiana, United States

  • WW

    Walter c. Willett, DrPH, MPH, MD

    Professor
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

  • MS

    Meir J. Stampfer, MD, PhD

    Professor
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
    Boston, Massachusetts, United States

  • MH

    Mark A. Herman

    Baylor College of Medicine

  • NM

    Nicola M. McKeown, Ph.D

    Boston University

  • JM

    James B. Meigs, MD

    Massachusetts General Hospital and Harvard Medical School
    Boston, Massachusetts, United States

  • Frank B. Hu, MD, MPH, PhD

    Chair, Department of Nutrition Harvard T.H. Chan School of Public Health Fredrick J. Stare Professor of Nutrition and Epidemiology at Harvard T.H. Chan School of Public Health Professor of Medicine, Harvard Medical School and Brigham and Women’s Hospital
    Harvard T.H. Chan School of Public Health
    Boston, Massachusetts, United States

Disclosure(s):
Danielle E. Haslam, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Deirdre K. Tobias, ScD: No relevant financial relationship(s) with ineligible companies to disclose.
Sylvia H. Ley, PhD, RD: No relevant financial relationship(s) with ineligible companies to disclose.
Frank B. Hu, MD, MPH, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Shilpa N. Bhupathiraju, PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: We sought to identify plasma proteins reflecting habitual sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intake.

Methods: We quantified 754 proteins using Olink aptamer-based high-throughput proteomics profiling in stored plasma from 570 men in the Health Professionals Follow-up Study and 118 women in the Nurses’ Health Study II US cohorts. SSB and ASB intake were estimated from food frequency questionnaires closest to the time of blood draw. In a protein-wide association study, we used linear regression models to examine associations of SSBs and ASBs with individual proteins, adjusting for potential confounders and correcting for multiple testing with a false discovery rate (FDR). Among proteins with a nominal p< 0.05, elastic net regression with 10-fold-cross-validation in a random training set (n=482) was used to derive weighted proteomic profiles separately associated with higher SSB and ASB intake. We examined Pearson correlation coefficients [r] between proteomic scores and self-reported intake in the training and internal testing (n=206) sets.

Results: In models adjusted for blood draw, demographic, lifestyle, and dietary factors, 39 and 79 proteins were nominally associated (p < 0.05) with SSB and ASB intake, respectively, and 48 and 14 with additional adjustment for BMI. No proteins were significantly associated with SSB intake after correcting for multiple testing. Participants with higher ASB intake had higher plasma leptin (FDR=0.002), fatty acid-binding protein (FDR=0.01), small heat shock protein (FDR=0.02), and reticulon-4 receptor (FDR=0.04) concentrations, and these were attenuated after adjustment for BMI and recent change in body weight (FDR >0.05). The SSB-derived (29 proteins; r=0.43 [95% CI: 0.35, 0.50; p < 0.0001] and r=0.24 [95% CI: 0.11, 0.37; p=0.0005]) and ASB-derived (14 proteins; r=0.33 [95% CI: 0.24, 0.40; p < 0.0001] and r=0.16 [95% CI: 0.03, 0.29; p=0.02]) proteomic profiles were positively correlated with self-reported intake in the training and testing sets, respectively.

Conclusions: We identified novel proteomic signatures that may reflect habitual SSB and ASB intake. These biomarker targets may be leveraged in subsequent longitudinal studies that minimize reverse causation and investigate mechanisms linking SSBs and ASBs to various health outcomes.

Funding Sources: NIH