Targeting Bioenergetic, Redox and Prostaglandin Pathways in Long COVID Using Nutraceuticals
Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 14, 2026 50 minutes ago
Long COVID remains a major medical challenge, particularly for patients affected by post-exertional malaise (PEM) and persistent cognitive problems commonly described as “brain fog.” These symptoms can interfere with employment, household activities, exercise and even relatively minor physical or mental tasks.
A new scientific review proposes investigating eight nutraceuticals targeting interconnected mitochondrial
energy, redox and prostaglandin-related inflammatory pathways involved in Long COVID-associated
post-exertional malaise and brain fog.
A newly published scientific review now proposes a detailed research framework for targeting bioenergetic, redox and prostaglandin pathways in Long COVID using nutraceuticals. Rather than viewing nutritional compounds simply as general antioxidants, the researcher proposes investigating carefully selected compounds according to the specific biological pathways they may influence.
Importantly, the paper is a hypothesis-generating narrative review. It does not show that the proposed nutraceutical combination treats or cures Long COVID.
Researcher and Institutions Behind the Review
The review was authored by Stephan F. E. Praet, who is affiliated with the University of Canberra Research Institute for Sport and Exercise (UCRISE), University of Canberra, Canberra, Australia, and the Ochre Health Medical Centre Bruce, University of Canberra, Canberra, Australia.
The researcher examined evidence from Long COVID studies together with findings from acute COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), mitochondrial diseases, inflammatory biology and pharmacological research.
The central proposal involves three potentially interconnected biological problems: impaired mitochondrial bioenergetics, disturbed redox regulation and neurovascular inflammation that could include prostaglandin-related mechanisms.
Bioenergetic Failure Could Help Explain Post-Exertional Malaise
Bioenergetics simply refers to the way cells produce and use energy. At the center of this process are mitochondria, microscopic structures inside cells that convert nutrients into usable cellular energy called ATP.
The review describes evidence suggesting that mitochondrial energy production can be disturbed in Long COVID. Reported abnormalities include impaired fatty-acid oxidation, changes involving the tricarboxylic-acid cycle, reduced Complex I activity and other persistent mitochondrial abnormalities.
Another proposed problem involves pyruvate dehydrogenase, or PDH, which acts as an important gateway connecting glucose metabolism with mitochondrial energy production. Restriction of this pathway could push cells toward greater reliance on glycolysis, a substantially less efficient way of extracting energy from glucose.
This becomes particularly relevant during exertion. When muscles and other tissues suddenly require substantially more energy, a person with limited bioenergetic reserve could potentially reach that limit much faster.
Studies reviewed in the paper have also found impaired systemic oxygen extraction
during invasive cardiopulmonary exercise testing, while muscle-biopsy research has demonstrated mitochondrial and structural muscle abnormalities following exercise in people experiencing Long COVID-associated PEM.
The researcher therefore proposes that an energy system already operating with reduced reserves could be pushed into greater dysfunction following exertion, potentially contributing to the delayed “crash” experienced by patients with PEM.
Oxidative Stress May Create a Damaging Feedback Loop
The second major area involves redox regulation, which describes the biological balance between oxidizing molecules and the protective systems cells use to control them.
Mitochondrial dysfunction can increase production of reactive oxygen species. When these highly reactive molecules exceed the body's ability to control them, oxidative stress develops.
Long COVID research has reported markers associated with oxidative damage and redox imbalance, particularly among individuals experiencing fatigue and cognitive symptoms.
The review focuses partly on the Nrf2-thioredoxin antioxidant system. Nrf2 normally helps switch on numerous protective genes when cells encounter oxidative stress. Thioredoxin reductase and related antioxidant systems then contribute to maintaining normal cellular redox conditions and controlling damaging peroxides.
However, an important distinction is made in the paper: persistent suppression of the Nrf2-thioredoxin pathway has not been directly demonstrated in established Long COVID. It remains a biologically plausible mechanism requiring experimental confirmation.
Neurovascular Inflammation and the Prostaglandin Question
The third component of the proposed framework concerns persistent inflammation affecting blood vessels and potentially the brain.
Endothelial injury and continuing immune activation could stimulate inflammatory signaling pathways such as NF-kappa-B. This can increase inflammatory molecules and enzymes involved in producing prostaglandins.
Particular attention is given to microsomal prostaglandin E2 synthase-1, or mPGES-1, an inducible enzyme involved in producing prostaglandin E2, commonly abbreviated PGE2.
PGE2 is complicated because its biological effects depend on the tissue, timing and receptors involved. It can participate in pain, fever, blood-vessel regulation, immune responses and inflammation, while certain prostaglandin signaling can also have regulatory or resolution-associated effects.
Consequently, the review does not claim that PGE2 is simply “bad” or that blocking it would automatically improve Long COVID.
In fact, there is currently no direct evidence demonstrating an mPGES-1/PGE2-specific abnormality responsible for PEM or brain fog in Long COVID. This part of the model is among the most speculative elements of the hypothesis and would need direct biomarker studies.
Eight Nutraceuticals Proposed Across Three Modules
Rather than proposing one supplement, this Thailand
Medical News report highlights an eight-agent framework divided into three functional modules.
The bioenergetic/redox module consists of coenzyme Q10 (CoQ10) and alpha-lipoic acid (ALA).
CoQ10 participates directly in the mitochondrial electron transport chain and therefore has a plausible role in supporting cellular energy metabolism. Alpha-lipoic acid has redox and metabolic effects, although the researcher specifically warns against assuming that orally consumed ALA directly restores the lipoylation of mitochondrial PDH.
The second, redox-response module, includes selenium, sulforaphane and resveratrol.
Selenium is required by important antioxidant enzymes, including thioredoxin reductase and glutathione peroxidases. Sulforaphane, a compound associated particularly with cruciferous vegetables, can activate the Nrf2 pathway.
Resveratrol may influence Nrf2, NF-kappa-B and SIRT1-associated signaling, although its low systemic bioavailability creates challenges.
The third proposed prostaglandin/resolution module consists of Boswellia serrata, luteolin and eicosapentaenoic acid (EPA).
Boswellic acids from Boswellia have demonstrated effects on mPGES-1 and inflammatory signaling in laboratory research. Luteolin has shown effects involving COX-2, mPGES-1 and broader inflammatory pathways in experimental models. EPA can alter the substrates available for eicosanoid production and also serves as a precursor for specialized pro-resolving mediators.
What Does the Human Evidence Actually Show?
This is where considerable caution is required.
The complete eight-agent combination has never been tested in Long COVID patients.
Among the more relevant existing findings is a prospective, non-randomized comparison involving 174 patients. Those receiving CoQ10 together with alpha-lipoic acid reportedly experienced greater improvement in fatigue than an untreated comparison group.
However, because the investigation was not randomized and used untreated controls, factors including expectation effects, natural recovery, differences between patients and other forms of bias could have influenced the findings.
Furthermore, a placebo-controlled trial examining high-dose CoQ10 alone for six weeks produced negative results.
The author therefore argues that these contrasting results create a reason for further investigation, rather than evidence that combining multiple compounds necessarily works better.
Evidence surrounding omega-3 supplementation in Long COVID is similarly preliminary. Existing research provides more information about feasibility and tolerability than convincing evidence of effectiveness for an EPA-dominant strategy against PEM or cognitive dysfunction.
Why Combining the Pathways Could Be Interesting
The proposed model becomes especially interesting because the three biological pathways may potentially reinforce one another.
Mitochondrial dysfunction could increase reactive oxygen species. Inadequate antioxidant defenses could then allow oxidative stress to continue. Oxidative stress and inflammation could further activate inflammatory signaling, while neurovascular inflammation might impair oxygen delivery and worsen mitochondrial performance.
Under this hypothesis, exertion dramatically increases energy requirements in a biological system already operating with reduced reserves. The resulting metabolic stress could trigger an oxidative and inflammatory flare, potentially contributing to PEM.
Brain fog could represent related processes occurring within the nervous system, possibly involving neuroinflammation, vascular dysfunction or disruption of the blood-brain barrier.
This creates the rationale for studying multiple pathways simultaneously rather than assuming that one antioxidant or supplement will correct the entire problem.
Other Long COVID Mechanisms Cannot Be Ignored
The researcher makes another important point: this three-pathway model does not replace other leading explanations for Long COVID.
Viral persistence, autoimmunity, autonomic dysfunction and broader immune dysregulation all have important supporting evidence. These mechanisms could potentially operate upstream and produce downstream mitochondrial, oxidative and inflammatory abnormalities.
This distinction matters because correcting downstream metabolic problems would not necessarily eliminate persistent SARS-CoV-2 reservoirs or remove disease-related autoantibodies.
Consequently, even if the nutraceutical strategy eventually proves beneficial, the proposed framework predicts that it may provide symptomatic or functional improvements rather than eliminate the underlying cause of Long COVID in every patient.
Safety Is a Major Issue with an Eight-Agent Combination
Nutraceutical does not automatically mean harmless. EPA at the proposed research levels is pharmacologically different from ordinary low-dose fish oil and can raise concerns involving bleeding and atrial fibrillation or flutter. EPA, resveratrol and Boswellia may also have antiplatelet effects.
Alpha-lipoic acid can lower blood glucose and therefore requires particular caution among individuals taking glucose-lowering medications or those susceptible to hypoglycemia.
Selenium presents another problem because excessive long-term intake can become toxic. The researcher therefore recommends checking selenium status rather than indiscriminately giving supplementation.
CoQ10 can potentially interfere with warfarin anticoagulation, while botanical products can vary substantially in purity, concentration and absorption.
These concerns are why the doses discussed in the paper are research proposals rather than recommendations for patients to self-administer the eight compounds.
Researchers Propose a Three-Stage Testing Strategy
Instead of immediately launching a large clinical trial using all eight substances, the paper proposes a cautious staged program.
The first stage would examine formulation quality, absorption, tolerability, pill burden, adherence, pharmacokinetics, biological target engagement and interactions.
Researchers could measure markers such as plasma CoQ10, selenium status, sulforaphane metabolites and the omega-3 index to establish whether the compounds actually reach biologically meaningful levels.
A second stage could independently test the bioenergetic, redox and prostaglandin modules against placebo, potentially using factorial or multi-arm clinical trial designs.
Only after demonstrating acceptable safety, exposure and promising biological effects would researchers progress toward a confirmatory trial comparing the complete combination against placebo.
Importantly, trials would need meaningful measurements of PEM, fatigue and cognitive function rather than relying only on general symptom questionnaires.
Conclusions
The review provides a detailed new framework for targeting bioenergetic, redox and prostaglandin pathways in Long COVID using nutraceuticals, particularly in patients suffering from PEM and brain fog. Its main strength is the attempt to connect specific compounds with specific biological targets instead of treating all supplements as generic antioxidants. However, the evidence varies substantially between pathways, several mechanisms remain speculative, and the complete eight-agent combination has never been clinically tested. Carefully designed studies must first establish product quality, absorption, target engagement, safety and interactions before researchers can determine whether this multi-pathway approach genuinely improves Long COVID symptoms.
The study findings were published in the peer reviewed journal: Nutrients.
https://www.mdpi.com/2072-6643/18/16/2650
Read Also:
https://www.thailandmedical.news/articles/long-covid 
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