A new study published at the end of June 2023 in Nutrients has investigated the link between prolonged fatigue and new pomegranate extract Improve (trademarked) from Esserre Pharma, and established the efficacy of it as a treatment.
Titled "Combination of Chemically Characterized Pomegranate Extract and Hydrophilic Vitamins against Prolonged Fatigue: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial", the study used UHPLC-HRMS analysis of Improve to establish the presence of 59 compounds. Of these 59, gallotannins and ellagitannins were shown to be the most abundant phytochemicals.
[The mechanism of action[ considering the high content of ellagitannins in this pomegranate extract that are able to reshape the gut microbiota by increasing eubiotic bacteria (Lactobacillaceae), [is] likely through urolithins
The study by Ullah et al. builds on the growing interest in pomegranate extract as an ingredient of interest in the nutraceutical industry.
A fair trial
To establish the greatest level of control possible, the clinical trial was created to be monocentric, randomised, double-blind, placebo-controlled clinical trial.
Monocentric - means only one research site will recruit study participants, so there is only one Principal Investigator. The opposition to this is a Multicentric study, which would have more than one research site recruit study participants, and therefore, more than one Principal Investigator.
Randomised - means there will be a random selection of which participants receive the treatment and, in this case, the placebo.
Double-blind - means neither the patient nor the researchers know who is receiving the treatment vs the placebo.
Placebo-controlled - means there is an undistinguishable treatment regimen being given to the patient to measure the actual subject compound against.
What is "prolonged fatigue"
There is a defined difference between acute, prolonged, and chronic fatigue. Building in side effects as you build through the levels, with chronic being designated as a disability.
Prolonged fatigue tends to be designated anywhere from 30 days to 6 months and "is associated with non-pathological causes and lacks an established therapeutic approach", the study states in its premise.
There is a defined difference between acute, prolonged, and chronic fatigue
Estimated levels in the general population have been proposed to be anywhere from 1% to 20%. As such, many ingredients are being studied to try and help solve this issue in society.
How to measure fatigue
The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2.
This fatigue severity scale (FSS) was used primarily but a measure of quality of life score was also taken by researchers, as well as a blood sample to look at biomarkers of stress and fatigue.
What did they find?
The FSS questionnaire scores significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on quality of life was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stress conditions.
This study shows that the food supplement based on the combination of a chemically characterised pomegranate extract, B vitamins, and vitamin C tested reduces prolonged fatigue following two months of supplementation in healthy subjects with mild prolonged fatigue.
The lack of biomarker change left the mechanism of action still in question. The researchers from this study proposed that "considering the high content of ellagitannins in this pomegranate extract that are able to reshape the gut microbiota by increasing eubiotic bacteria (Lactobacillaceae), [it is] likely through urolithins generated from the metabolism of polyphenolic components of pomegranate, and due to the suggested role of gut microbiota in prolonged and chronic fatigue."
The researchers finished by adding that an in vitro study on this proposed mechanism of action, evaluating the effect on the composition and functionality of gut microbiota, is currently in progress.