At the 16th Invest in ME Research conference, Professor Ron Davis discussed a hypothesis that a molecule known as BH4 could be involved in the pathogenesis of ME/CFS.
BH4 – a molecule that is “tightly regulated” in healthy individuals, is thought to be involved in many processes in the body; including the generation of energy molecules in mitochondria – often referred to as the “powerhouses of the cell”, and chemical messengers that facilitate communication between nerve cells (neurotransmitters).
Research has shown that uncontrolled upregulation of BH4 is associated with:
- Mitochondrial dysfunction.
- Cognitive impairment.
- Immune dysregulation.
- Progression of inflammatory and autoimmune diseases.
Interestingly, biological abnormalities that research has also linked with ME/CFS.
A pilot study by Dr Avik Roy and colleagues found that participants with ME/CFS who also had orthostatic intolerance (OI) had increased levels of BH4 – indicating upregulation. Since the pilot study was published, Dr Roy and colleagues have published another paper considering why BH4 might be upregulated in people with ME/CFS and OI.
The study was complex, but findings indicate that an alternative pathway for energy production in the body – the pentose phosphate pathway, could play an important role in BH4 upregulation in people with ME/CFS and OI, particularly when this pathway produces energy in the absence of oxygen – under anaerobic conditions.
It is important to note that as the study was carried out “in vitro” – by analysing samples from people with ME/CFS and OI using laboratory equipment such as test tubes, the results may not fully reflect the dynamic environment within the human body.
More research is needed to consider whether BH4 upregulation can be observed across all individuals with ME/CFS, or whether it can only be found in certain subgroups of people with the disease – such as those with OI, this research would also need to take into consideration the diverse nature of ME/CFS. It could also be useful to consider whether the level of BH4 dysregulation may be associated with ME/CFS severity.
