# Effects of Cacao Flavonoids in Long COVID-19 Patients with Chronic Fatigue: FLALOC, a Placebo-Controlled Randomized Clinical Trial

## TL;DR

This study found that a cacao flavanol supplement improved inflammation, fatigue, and endothelial function in long COVID patients.

## Contribution

The study provides first clinical evidence that (−)-epicatechin supplementation benefits long COVID patients with chronic fatigue.

## Key findings

- ECES significantly reduced inflammatory markers like IL-1β, IL-6, and TNF-α compared to placebo.
- ECES improved endothelial dysfunction marker syndecan-1 and fatigue levels in participants.
- Participants reported better quality of life after 90 days of ECES treatment.

## Abstract

Background: In the context of long COVID, persistent fatigue is among the most prevalent symptoms that can develop after SARS-CoV-2 infection. Mitochondrial myopathy and endothelial dysfunction, which are triggers of inflammation, have emerged as prominent causes of long COVID-induced fatigue. Interestingly, the intake of flavanols, particularly (−)-epicatechin (EC), has been associated with the positive modulation of endothelial and mitochondrial structure and function. Methods: In this work, we conducted a randomized, double-blind, placebo-controlled clinical trial to determine whether an EC-enriched supplement (ECES) improves plasma markers of inflammation, endothelial structure, and fatigue-related endpoints in patients with long COVID-19. Results: The study included 46 subjects (mean age 52 years) who were instructed to consume two capsules/day for 90 days of either ECES (n = 23) or placebo (n = 23). Endpoints assessed included mean changes in plasma inflammatory markers (IL-1β, IL-6, and TNF-α) and endothelial dysfunction markers (syndecan-1), handgrip strength, fatigue scale, and quality of life (QoL). The results showed significant improvements in the ECES group for inflammatory markers, syndecan-1, and fatigue compared with the placebo group. Conclusions: The results yield intriguing positive findings for EC and open a new avenue for treating long COVID.