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Synbiotics emerge as promising tool for managing extreme fatigue and post-exercise malaise, clinical trial suggests

New clinical evidence highlights potential of three-month synbiotic supplementation in attenuating post-exercise malaise and increasing brain metabolites in adults with post-COVID-19 chronic fatigue syndrome (CFS).

Kaiseraugst (Switzerland), Heerlen (Netherlands), [April 29, 2025]

A new randomized, placebo-controlled clinical trial published in the European Journal of Nutritioni has shown that daily supplementation with a synbiotic blend may help to manage key clinical features of post-COVID-19 chronic fatigue syndrome (CFS), such as exercise tolerance metabolism in the brain.

The findings mark a potential breakthrough in nutritional support for consumers looking for a non-medical solution to manage the symptoms of CFS.

Post-COVID-19 CFS is a neurological condition affecting as many as 45% of those previously infected with COVID-19 and has been identified as the most common symptom of ‘long COVID’.ii The syndrome is characterized by extreme fatigue, post-exercise malaise and unrefreshing sleep, and is often associated with disruptions in the gut microbiome and brain energy metabolism. Although COVID-19 dramatically increases the risk of developing CFS, it can also manifest after other viral or bacterial infections and periods of high stress.

Synbiotics to manage CFS via the gut-brain-energy axis

This latest clinical trial involved 26 adults with diagnosed post-COVID-19 CFS. One group received a synbiotic blend for three months daily, while the other received a placebo.

Synbiotics were selected for the study due to the gastrointestinal disturbances that are commonly associated with post-COVID-19 CFS, and the possibility that restoration of gut microbiota through dietary supplementation could help to manage chronic fatigue symptoms.

The synbiotic mixture included four strains from dsm-firmenich’s Humiome® portfolio – Lacticaseibacillus rhamnosus DSM 32550, Humiome® Lactiplantibacillus plantarum DSM 34532, Bifdobacterium lactis DSM 32269, Bifdobacterium longum DSM 32946, in combination with fructooligosaccharides (2.5 g) and zinc (5 mg).

Establishing synbiotic success: key results

The primary objective of the trial was to measure the change in general fatigue from baseline to the three-month follow-up, assessed using the Multidimensional Fatigue Inventory (MFI-20) test, which evaluates key dimensions of fatigue including physical and mental fatigue, reduced motivation, and reduced activity.

The results showed a significant reduction in post-exercise malaise – where the body is not able to recover, a hallmark symptom of CFS – in the synbiotic group compared to placebo. There was also a marked improvement in brain metabolites, determined using proton magnetic resonance spectroscopy. Higher creatine levels were found, particularly in regions of the brain such as the left frontal white and gray matter, as well as higher choline levels in the thalamus, suggesting enhanced neuronal energy metabolism in the synbiotic group.

Notably, while general fatigue scores decreased in both groups, there was a strong trend within the synbiotic group of reduced concentration difficulties when compared with the placebo group – supporting the idea of a gut-brain-energy axis modifiable by nutritional intervention.

Opportunity for innovation in fatigue support

“This study offers compelling new evidence that targeted synbiotic supplementation to restore gut microbiota can positively influence brain energy metabolism and can reduce hallmark symptoms of post-viral fatigue syndromes like CFS,” said Robert E. Steinert, HNC Principal Scientist at dsm-firmenich. “Chronic fatigue is a debilitating condition that can severely impact quality of life for those affected by it, with this research marking an important step forward in demonstrating the potential of synbiotics in managing CFS symptoms. It opens the door for greater innovation in development of nutritional supplements and solutions that can provide both a physical and metaphorical boost for CFS patients.”

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