Whole-body Omega-3 and Omega-6 fatty-acid reserves in healthy controls and fatal COVID-19: Evidence of systemic long-chain n-3 depletion.

Authors

Pavel Skořepa, Zdeněk Zadák, Marek Vecka, Michal Burda, Dalibor Kovařík, Petr Hejna, Iva Selke Krulichová, Radomír Hyšpler, Alena Tichá, Miroslav Fajfr, Pavel Boštík, Aleš Žák

Published in

Clinical nutrition (Edinburgh, Scotland). Volume 66. Pages 106777. Sep 02, 2026. Epub Sep 02, 2026.

Abstract

While circulating lipid biomarkers are widely used, little is known about the absolute tissue reserves of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) in humans or their availability during severe systemic illness. We therefore mapped absolute PUFA concentrations across major human tissues and examined whether fatal COVID-19 is associated with depletion of long-chain n-3 substrate pools.
Absolute fatty acid concentrations (mg/g wet tissue) were quantified across nine tissues (adipose tissue, brain, heart, lungs, liver, spleen, skeletal muscle, small intestine, and kidney) using gas chromatography with flame-ionization detection (GC-FID). Whole-body fatty-acid reserves were then estimated from tissue concentrations and organ weights. The cohort included sudden-death controls and patients with fatal COVID-19 pneumonia.
Controls exhibited distinct organ-specific lipid signatures with high n-3 concentrations in adipose tissue and brain. In fatal COVID-19, we observed a coherent cross-organ reduction in long-chain n-3 substrate pools driven primarily by depletion of EPA and DPA. DHA showed tissue-specific preservation or relative elevation, most notably in brain, adipose tissue, and spleen. Adipose tissue, the primary reservoir, showed a severe imbalance characterized by an approximately 3.3-fold increase in the n-6/n-3 ratio (median 50.66 vs. 15.56; p = 0.004) and lower total n-3 content (0.93 vs. 2.76 mg/g; p = 0.004). Brain tissue displayed species-specific remodeling: EPA and DPA were lower in COVID-19, whereas DHA was relatively higher (EPA, 0.018 vs. 0.16 mg/g; p = 0.004). In the lungs, EPA was similarly depleted (0.015 vs. 0.34 mg/g; p = 0.004), and the myocardium shifted toward a pro-inflammatory profile with an elevated n-6/n-3 ratio (16.87 vs. 4.01; p = 0.004). Estimated whole-body n-3 reserves were lower in the COVID-19 group (41.7 g vs. 86.6 g).
This study establishes a comprehensive quantitative human tissue map of absolute PUFA reserves and suggests that severe systemic illness, exemplified here by fatal COVID-19, is associated with coherent depletion of long-chain n-3 substrates across organs. These findings support the concept that tissue substrate availability may be a clinically relevant constraint on resolution signalling during acute metabolic stress.

PMID:
42753341
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

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