# Modulation of inflammasome components in patients with heart failure using oral nutritional supplements: investigating the molecular mechanisms beyond the clinical benefit

## TL;DR

This study shows that adding high-protein supplements with EPA and DHA to a Mediterranean diet can reduce inflammation in heart failure patients by altering inflammasome pathways.

## Contribution

The study reveals novel molecular mechanisms by which specific nutritional supplements modulate inflammasome components in heart failure.

## Key findings

- Supplements reduced expression of inflammasome components like NLRP12, NLRP6, CASP5, TLR2, and TLR9.
- Cytokines and inflammation-related molecules such as CXCR1, CXCR2, and CCL2 were downregulated.
- Cell cycle regulators like CDKN2D decreased, suggesting effects on cellular senescence and DNA repair.

## Abstract

Inflammation is a key contributor to the pathogenesis and progression of heart failure (HF), correlating with increased morbidity and mortality. This study aimed to evaluate the molecular impact of a 24-week nutritional intervention on inflammasome-related components in HF patients, comparing a Mediterranean diet alone versus the same diet supplemented with hypercaloric, high-protein oral nutritional supplements (ONS) enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In a cohort of 38 patients, expression levels of inflammasome markers were assessed via microfluidic quantitative polymerase chain reaction (PCR) in peripheral blood mononuclear cells at baseline and post-intervention.

Some components, especially cytokines and apoptosis regulation components are overexpressed in patients with sarcopenia (NLRP1, NLRC4, CASP1, CASP5, CTSL, IFI16, TLR8, PSXR7, CCR1, CHUCK, MAPK14, CDKN1B). We observed a significant downregulation of Nod-like receptors NLRP12 and NLRP6, along with decreased expression of inflammasome activation components CASP5, TLR2, and TLR9 in the intervention group (p < 0.05). Additionally, cytokines and inflammation-related molecules such as CXCR1, CXCR2, TGFB, CCL2, and NF-κB showed reduced expression, while the inhibitor CHUCK increased (p < 0.05). Cell cycle regulators also shifted, with decreased CDKN2D expression (p < 0.05), suggesting potential effects on cellular senescence and DNA repair pathways. Notably, these molecular changes were absent in patients adhering solely to the Mediterranean diet.

these findings suggest that supplementing a Mediterranean diet with hypercaloric, high-protein, EPA and DHA-enriched ONS induces molecular modifications in inflammasome pathways associated with cardiac remodeling. Therefore, targeted nutritional strategies may offer a promising adjunct to improve cardiac function and disease progression in HF patients.

The online version contains supplementary material available at 10.1007/s00394-025-03878-5.