Some Plasma Metabolites can Forecast Insomnia Severity

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Higher levels of hydrocinnamate and indolepropionate were associated with lower WHIIRS, with stronger associations found in female participants.

Certain metabolites are associated with insomnia severity, specifically hydrocinnamate and indolepropionate, in Hispanic/Latino individuals.1

A team, led by Jose Santos Cabrera, Harvard University, examined metabolites in patients with insomnia in new data presented during Sleep 2023 in Indianapolis.

Insomnia and Metabolites

Insomnia is linked to neurodegenerative diseases, while concentration levels of some metabolites are associated with pathophysiologic changes, potentially in a sex-specific manner. This means that serum metabolite levels are crucial in understanding insomnia-related pathophysiological changes and how they potentially relate to neurodegenerative disease.

In the longitudinal cohortstudy called the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the investigators followed self-reported Hispanic/Latino individuals in the US.

The investigators captured insomnia symptoms at baseline using the Women Health Initiative Insomnia Rating Scale (WHIIRS). Insomnia was defined as a WHIIR of at least 9.

The team also measured metabolites using blood serum from the baseline exam in independent discovery and replication datasets.


Metabolic associations with WHIIRS and insomnia were estimated using linear regression.

They also tested significant associations in the replication dataset and the direction of association matched with the discovery analysis.

The investigators further studied associations for gender interaction and all analyses were adjusted for age, self-reported gender, study center, and Hispanic/Latino background.

The study included 3895 participants in the discovery analysis and 2121 participants in the replication analysis. The mean age of females in the study was 46.5 years and the mean age of males was 44.8 years.

In addition, 35% of female participants had insomnia and 24% of male participants had insomnia. Following quality control, the investigators tested 767 metabolites for association and found 6 metabolites were associated with WHIIRS (FDR <0.05) in the gender-combined analysis.

The investigators also found 3 metabolites were xenobiotics, which were on the benzoate or salicylic acid metabolism-pathway and of the 6 metabolite associations, 2 replicated (P <0.05) in hydrocinnamate and indolepropionate.

The 2 metabolites had a spearman correlation of 0.44.

The results also show that higher levels of both metabolites were associated with lower WHIIRS, with stronger associations found in female participants (interaction P = 0.04 for hydrocinnamate and P = 0.13 for indolepropionate).

These associations remained basically unchanged in a model further adjusting for hypertension and diabetes.

The investigators then removed 534 participants who self-reported using sleeping pills at least once a week and found the associations attenuated slightly, going from an effect estimate of -0.0075 to -0.0069 for hydrocinnamate and from -0082 to -0068 for indolepropionate.

“Among the HCHS/SOL target population, insomnia symptom severity is associated with a lower concentrations of some plasma metabolite levels which are important antioxidant needed in preventing oxidative stress and neurodegeneration,” the authors wrote.


Jose Santos Cabrera and others, 0030 Insomnia is associated with lower serum antioxidants in the Hispanic Community Health Study/Study of Latinos, Sleep, Volume 46, Issue Supplement_1, May 2023, Page A14,