Evidence browser

Energy MetabolismPost-Exertional Malaise

Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach.

Wirth, Klaus J, Scheibenbogen, Carmen·Medicina (Kaunas, Lithuania)·2022

Many people with post-COVID syndrome experience shortness of breath and chest pain, even though their lungs and heart are typically healthy. This study proposes that the problem may stem from overbreathing (hyperventilation) during exercise, combined with problems in how the body regulates breathing and uses energy in muscles. The authors suggest that overbreathing creates a harmful cascade inside cells—disrupting sodium and calcium balance—which worsens fatigue and breathing difficulties. Preventing overbreathing might be a way to help these patients recover.

E3 PreliminaryMechanismPEM unclearObservational

Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Castro-Marrero, Jesús, Domingo, Joan Carles, Cordobilla, Begoña et al.·Antioxidants & redox signaling·2022

This study tested whether taking Coenzyme Q10 and selenium supplements together could help ME/CFS patients feel better. Twenty-seven patients took these supplements daily for 8 weeks, and researchers measured their fatigue, quality of life, sleep, and blood markers related to stress and inflammation. The supplements improved overall fatigue and quality of life, and blood tests showed reduced oxidative stress and inflammation, though sleep did not improve.

Red ginseng extract improves skeletal muscle energy metabolism and mitochondrial function in chronic fatigue mice.

Zhang, Haijing, Zhao, Chunhui, Hou, Jinli et al.·Frontiers in pharmacology·2022

This study tested whether red ginseng extract could help mice with chronic fatigue by improving how their muscles produce energy. Researchers found that medium and high doses of red ginseng reduced markers of fatigue and improved the function of mitochondria (the "power plants" inside muscle cells), helping restore the muscle's ability to generate energy.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla.

Godlewska, Beata R, Williams, Stephen, Emir, Uzay E et al.·Psychopharmacology·2022

Researchers used a powerful brain scanning technique to measure chemicals in the brains of people with ME/CFS and compared them to healthy people. They found that people with ME/CFS had lower levels of three important brain chemicals: glutathione (which helps protect against cell damage), creatine (which helps produce energy), and myo-inositol (which is important for brain cell function). These findings suggest that ME/CFS may involve problems with energy production and cell damage in the brain.

Commonalities in the Features of Cancer and Chronic Fatigue Syndrome (CFS): Evidence for Stress-Induced Phenotype Instability?

Rusin, Andrej, Seymour, Colin, Cocchetto, Alan et al.·International journal of molecular sciences·2022

This review compares ME/CFS with cancer-related fatigue, two conditions that share similar exhaustion symptoms. The authors examined research showing that both conditions may involve problems with stress hormones, immune system inflammation, energy production in cells, and genetic factors. They suggest these two different diseases might actually represent different points on a spectrum of how the body responds to stress, rather than being completely separate conditions.

[Effect of herbal cake-separated moxibustion on behavioral stress reactions and blood lactic acid level and muscular AMPK/PGC-1α signaling in rats with chronic fatigue syndrome].

Xu, Xiao-Shan, Ma, Wei, Xiong, Luo-Jie et al.·Zhen ci yan jiu = Acupuncture research·2022

Researchers tested a traditional Chinese medicine treatment called herbal cake-separated moxibustion on rats with chronic fatigue syndrome to see if it could improve fatigue and stress responses. The treatment appeared to reduce physical exhaustion markers in the blood (lactic acid) and activate cellular energy-producing pathways in muscles, similar to effects seen with oral herbal medicine.

Mitochondria as the Essence of Yang Qi in the Human Body.

Luo, Junjie, Shen, Shiwei, Xia, Jingjing et al.·Phenomics (Cham, Switzerland)·2022

This article explores whether the ancient Chinese medicine concept of 'Yang Qi' (vital energy) maps onto modern understanding of mitochondria—the energy-producing structures in our cells. The authors argue that both concepts describe something essential to human health and that weakness in either leads to illness, including chronic fatigue syndrome, poor sleep, cognitive decline, and metabolic problems.

Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review.

Marshall, Robert Percy, Droste, Jan-Niklas, Giessing, Jürgen et al.·Nutrients·2022

This review examines whether creatine supplements—commonly used by athletes to boost performance—might also help people with diseases involving mitochondrial problems (the energy-producing parts of cells). Creatine appears to have several beneficial effects, including improving energy production, reducing harmful oxidative stress, and protecting nerve cells. While early evidence suggests creatine could be helpful for conditions where mitochondria aren't working well, more rigorous clinical trials are needed before doctors can recommend it as a standard treatment.

Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review.

Hirano, Shin-Ichi, Ichikawa, Yusuke, Sato, Bunpei et al.·Frontiers in neurology·2022

This review examines whether molecular hydrogen (H₂) gas might help treat ME/CFS by fixing problems in the energy-producing parts of cells. The researchers looked at existing studies showing that H₂ can reduce harmful molecules called free radicals and improve fatigue in animals and healthy people. While the idea is promising, the authors emphasize that more human studies are needed before H₂ can be recommended as a treatment.

Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats.

Hara, Yurie, Kume, Satoshi, Kataoka, Yosky et al.·Heliyon·2021

This study tested whether citric acid (a compound found in citrus fruits) changes the levels of energy-related chemicals in the blood of rats. Researchers found that giving citric acid increased levels of several metabolites involved in energy production—the opposite pattern seen in ME/CFS patients. This suggests citric acid might help restore normal energy metabolism, which could explain why some people report feeling less fatigued after consuming it.

E3 PreliminaryMechanismPEM unclearMechanistic

Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts.

Missailidis, Daniel, Sanislav, Oana, Allan, Claire Y et al.·International journal of molecular sciences·2021

This study looked at how cells from ME/CFS patients use energy differently than healthy cells. Researchers found that ME/CFS cells are overproducing enzymes that break down fats, amino acids, and other nutrients to fuel their mitochondria (the cell's power plants), while their glycolysis (the main way cells normally produce energy) stays normal. This suggests ME/CFS cells may be forced to use alternative, less efficient pathways to generate the energy they need.

Dysregulation of cellular energetics in Gulf War Illness.

Raju, Raghavan Pillai, Terry, Alvin V·Toxicology·2021

Gulf War Illness affects about one-third of veterans from the 1991 Persian Gulf War and causes chronic fatigue, brain fog, pain, and immune problems similar to ME/CFS. This review examines evidence that the problem may stem from mitochondria (the energy-producing parts of cells) not working properly. The authors suggest that treatments targeting mitochondrial function could potentially help restore energy production and relieve symptoms.

Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 'long-haulers'?

Wood, Emily, Hall, Katherine H, Tate, Warren·Chronic diseases and translational medicine·2021

This study reviews research on how mitochondria (the energy-producing centers in our cells) and oxidative stress (cellular damage from harmful molecules) may contribute to ME/CFS and long COVID symptoms. The authors examine whether antioxidant treatments could help restore energy production and reduce fatigue in these conditions. They highlight that many COVID-19 long-haulers develop symptoms that look very similar to ME/CFS, suggesting they may share underlying biological causes.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing.

Maggini, Silvia, Óvári, Veronika, Ferreres Giménez, Inmaculada et al.·Nutricion hospitalaria·2021

Your body needs several vitamins and minerals—like vitamins A, D, E, folate, iron, zinc, and selenium—to make energy in your cells. Many people, even in wealthy countries, don't get enough of these nutrients. Studies show that taking a combination of these micronutrients, sometimes with coenzyme Q10, may help reduce fatigue, improve thinking, and make people feel better overall.

E3 PreliminaryCommentaryPEM unclear

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome.

Komaroff, Anthony L, Lipkin, W Ian·Trends in molecular medicine·2021

This article compares myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with long COVID to see if they might share similar causes. The authors suggest that some people who develop long COVID symptoms—like persistent fatigue, cognitive problems, and pain—may experience similar biological problems to those seen in ME/CFS. Understanding these shared mechanisms could help doctors better treat both conditions.

Energy MetabolismLong COVID Overlap

Substrate utilisation of cultured skeletal muscle cells in patients with CFS.

Tomas, Cara, Elson, Joanna L, Newton, Julia L et al.·Scientific reports·2020

This study examined how muscle cells from ME/CFS patients use different fuels for energy compared to healthy people. Researchers found that ME/CFS muscle cells have trouble using glucose (a key fuel source) for energy, but can still use other fuels normally. This suggests the energy-producing problem in ME/CFS starts very early in the energy-making process, and may be caused by something genetic or chemical that persists even when cells are grown in a laboratory.