How energy production is affected in ME/CFS and Long Covid

Fatigue is a hallmark symptom in ME/CFS and is a major symptom in Long Covid. Here we describe how energy is usually produced by the body, and then describe energy production is affected in ME/CFS and Long Covid.

1.   How energy is made in the human body

Energy production in humans is a complex process that involves converting the foods we eat, such as glucose, fats and proteins, into a form of energy, which is produced in all of the cells in the human body, which is called adenosine triphosphate, or ATP.

The conversion of food into energy involves several biochemical pathways, leading to the production of ATP, which stores and supplies energy for all cellular functions.

ATP provides the energy for the work of all of our cells, for growth, repair and functioning. Every living cell needs a constant supply of ATP in order to survive.

2.   Foods used by the body to produce energy

The human body can use carbohydrates, (which converts to glucose after eating), fats or protein to produce energy.  The body uses different biochemical processes to convert food into energy, dependent on the type of food eaten. However, different foods produce different amounts of energy. Whilst one molecule of glucose will be converted into 38 molecules of ATP,  one molecule of fat produces 129 molecules of energy!

How the body uses different macronutrients

3.   The nutrients needed to help convert food into energy

The body also needs a range of vitamins and minerals in order to convert foods into energy.

Essential nutrients for energy production include:

•       Vitamins B1, B2, B3, B5, B6 and Vitamin C,

•       Key minerals include iron, magnesium, copper

•       Co-enzyme Q10 (CoQ10), which is a fat-soluble molecule

•       Carnitine, which is essential to support the use of fat in the production of energy

4.   Types of energy production

There are two main types of energy production, a process which is also called cellular respiration:

5.   The role of mitochondria

Most energy production occurs within the mitochondria, which are organelles found within all cells of every complex organism, often called the powerhouses of the cell. Every adult has 10 million, billion mitochondria, which make up about 10% of our bodyweight!

When mitochondria are not working properly, it can lead to a decrease in energy production. It can also lead to an increased production of reactive oxygen species (ROS), and the initiation of inflammatory pathways, all of which can contribute to the development of a number of  diseases.

Mitochondria are dynamic and are constantly changing:

• Mitochondria continuously combine & divide through fusion and fission

• They exist for a few days or several weeks depending on where they are in the body

• Mitophagy is a process of  ‘self-eating’ – which is important for the efficiency and quality  of mitochondria

• Biogenesis – is the generation of new mitochondria

  
  

Mitochondria are essential for energy production as they transform oxygen and food into energy, producing 90% of the energy (ATP) that cells need to survive. They also have other important functions such as cell signaling, cell death (apoptosis), maintaining calcium levels, releasing neurotransmitters, and regulating the release of insulin. Some very important functions!

Diagram showing mitochondria within a human cell

This diagram is produced by the Science Learning Hub – Pokapū Akoranga Pūtaiao, The University of Waikato Te Whare Wānanga o Waikato, www.sciencelearn.org.nz

Energy production may be affected if mitochondria are damaged, which can arise in a number of ways as shown in the diagram below:

6.   Factors which can affect mitochondrial health

There are many factors which may affect mitochondrial health including:

• Viral/bacterial infections – can lead to non-mitochondrial respiration, as the cell uses oxygen to kill the pathogen rather than for energy

• Biotoxins/mycotoxins e.g from Aspergillus

• Some parasites

• Heavy metals – mercury, arsenic, increase ROS

• Pesticides and herbicides

• Chemical contaminants

• Household chemicals

• Gastro-intestinal/gut issues

• Medications – e.g. most anti-depressants and mood stabilisers inhibit ATP production

• Electromagnetic fields

7.   How energy production affected in ME/CFS

Research has found a number of differences in energy production in people with ME/CFS compared to others:

• Evidence of oxidative stress – research shows significantly increased levels of ROS (Reactive Oxygen Species) and RNS (Reactive Nitrogen Species) indicative of oxidative stress. Significantly decreased levels of antioxidants e.g Glutathione, have also been found in ME/CFS

• Lower ATP levels

• Defective oxidative phosphorylation (Electron Transport Chain),  a part of the biochemical process which produces the most ATP in  aerobic respiration

• Elevated lactate after exercise and resting – evidence of a greater dependence on anaerobic respiration

• Significantly decreased levels of Coenzyme Q10, a nutrient which is essential for ATP production in the electron transport chain in aerobic respiration

• Deficits in pathways which generate energy from amino acids, fatty acids and simple sugars

• Carnitine - mixed evidence on levels of Carnitine in ME/CFS compared to controls, but higher Carnitine in ME/CFS was associated with lower levels of fatigue

  
  

8.   Energy production and mitochondria in Long covid

Research suggests that the SARS-CoV-2 virus may disrupt the homeostasis of mitochondria as part of its method of replication in the body. This may lead to mitochondrial dysfunction in those affected.

Diagram showing how the SARS-CoV-2 virus may initially disrupt the function of mitochondria (Shang, 2022)

Shang 2022

Whilst the SARS-CoV 2 virus may impact on the functioning of the mitochondria during acute infection, it is unclear how this initial impact may affect mitochondrial function in those with Long Covid thereafter. However, research points to similar issues with energy production in Long Covid as found in ME/CFS:

• Mitochondrial dysfunction including loss of mitochondrial membrane potential and possible dysfunctional mitochondrial metabolism

• Altered fatty acid metabolism in particular has been identified in research in Long Covid

• Redox imbalance – accumulation of excess ROS (Reactive Oxygen Species) and oxidative stress

• Exercise intolerance and impaired oxygen extraction

Diagram showing Interplay of mitochondrial dysfunction and Long COVID: pathophysiological mechanisms and therapeutic approaches (Molnar et al, 2024)

Molnar, 2024

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