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Session: Novel Biomarkers of Micronutrient Intake, Status, and Metabolism (Oral 18)

(OR18-01-23) Plasma Metabolite Signature for Assessing Choline Intake Adequacy

Monday, July 24, 2023
10:00 AM – 10:12 AM ET
Location:  Commonwealth

    Presenting Author(s)

  • Martin Kohlmeier, MD PhD

    Professor
    UNC Nutrition Research Institute
    Chapel Hill, North Carolina, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • EB

    Emmanuel Baah, MD MPH

    Postdoctoral Research Associate
    UNC Nutrition Research Institute
    Kannapolis, North Carolina, United States

  • JS

    Julie Stegall

    UNC Nutrition Research Institute

  • IT

    Isis Trujillo

    UNC Nutrition Research Institute

  • Steven H. Zeisel, MD, PhD

    Professor and Director, Nutrition Research Institute
    UNC Nutrition Research Institute
    Kannapolis, North Carolina, United States

Disclosure(s):
Martin Kohlmeier, MD PhD: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Inadequate choline intake contributes to numerous adverse health conditions such as hepatosteatosis, increased muscle fragility, heightened risk of having a child with a birth defect, and DM2 risk.

We aimed to develop and validate a biomarker for identifying low choline intake by combining suitable metabolite concentrations with defined cut-offs.

Methods: Plasma concentrations of choline-related metabolites (choline, betaine, sarcosine, dimethylglycine, phosphorylcholine, glycerophosphocholine, sphingomyelin, total choline) were measured in 26 adults who had no signs of deficiency during an initial feeding period with adequate choline intake and who showed newly emerging liver signs of depletion (elevated AST or ALT activities or high fat content in the liver) while getting only 50 mg choline per day for at least 4 weeks.

A later validation study fed 83 adults for two weeks each in randomized order a diet providing 138 mg choline per day and the same foods fortified for adequate choline intake (550 mg choline per day).

Results: Based on combinatorial modeling of the data from the initial feeding study, the best-performing plasma metabolite signature distinguishing between adequate and demonstrably insufficient choline intake was found to be a choline concentration in fasting plasma under 7.93 µM/L. This metabolite combination predicted insufficient choline intake with high sensitivity (1.00) and good specificity (0.88). None of the other metabolite combinations performed better than this two-metabolite signature.

The validation study comparing restricted choline and presumably adequate choline intake for two weeks each induced the low-choline signature in most (37 of 42) of the participating premenopausal women, but only in 9 of them while getting the higher choline amount. Ten of the 16 menopausal women showed the signature with the low choline intake compared to only one of them while getting the higher amount. Sixteen of the 25 men showed the signature with low choline and only three of them on the higher choline intake.

Conclusions: This choline-betaine signature appears to be the first one that can effectively distinguish between adequate and inadequate choline intake of healthy, free-living individuals.

Funding Sources: Supported by NIDDK 1R01DK115380-01