Plasma carotenoids are inversely correlated with granulocyte counts and soluble inflammatory markers in a middle-aged population: a cross-sectional study with mediation analysis

TL;DR

This study finds that higher plasma carotenoids are linked to lower granulocyte counts and inflammation markers in middle-aged people.

Contribution

It is the largest study showing carotenoids' inverse relationship with inflammation, mediated by granulocyte counts.

Findings

Plasma carotenoids are inversely correlated with granulocyte counts and inflammatory markers like CRP and MMP-9.

Mediation analysis shows granulocyte counts mediate the link between carotenoids and inflammation markers.

Lutein and β-cryptoxanthin remain independently associated with MMP-9 after adjusting for granulocyte mediation.

Abstract

High intake of fruits and vegetables is generally associated with reduced levels of inflammation. In line with this, plasma levels of carotenoids have shown inverse associations with inflammatory markers, in particular C-reactive protein (CRP) and leukocyte counts. However, it remains unclear to what extent carotenoids are associated with specific leukocyte subsets or other inflammatory markers. This study systematically assessed the inter-relationships among total and individual carotenoids, circulating leukocyte subsets, and soluble inflammatory markers in a middle-aged population.

A subcohort of 1078 subjects, aged 50–64, was recruited from the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. Leukocyte subsets were determined by whole blood flow cytometry. Five major carotenoids, namely lutein, β-cryptoxanthin, lycopene, α-carotene and β-carotene, and inflammatory markers including CRP, interleukin (IL)-6 and interleukin-18, matrix metalloproteinase (MMP)-9, and myeloperoxidase (MPO), were measured in plasma. Nutrient intake was estimated by validated food frequency questionnaires.

Among leukocyte subsets, only granulocytes showed independent and inverse associations with all carotenoids after adjustment. CRP, IL-18, and MMP-9 exhibited similar inverse relationships with most carotenoids. Mediation analysis revealed that the associations of carotenoids with CRP and MMP-9 were mediated by granulocyte counts. Lutein and β-cryptoxanthin remained independently associated with MMP-9 after accounting for the mediation effects of granulocyte counts. No estimated nutrient intake showed comparable associations with leukocyte subsets or inflammatory markers.

To our knowledge, this is the largest population-based study investigating relationships between plasma carotenoids, leukocyte subsets, and soluble inflammatory markers. It provides evidence that low levels of carotenoids in plasma are linked to low-grade chronic inflammation and, furthermore, that this relationship is mediated by granulocyte numbers.

The online version contains supplementary material available at 10.1186/s12916-025-04266-w.

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