by Sasha Nimmo

Melbourne scientists are testing a combination of mitochondrial supplements on 8 or 9 patients with chronic fatigue syndrome (Fukuda criteria).

The 20-week study for patients with Fukuda chronic fatigue syndrome is open-label, so patients are aware they are receiving the treatment and there is no placebo group.  Participants take the capsules daily, as well as medical treatment ‘as usual’, with assessment visits at the start then every four weeks.
The trial will assess the efficacy and tolerability of twice daily dosing of purpose-designed combination capsules providing a daily amount of:
  • N-acetylcysteine (NAC) 2000 mg
  • Acetyl L-carnitine (ALC) 1000mg
  • ubiquinone (Co Q10) 200 mg
  • magnesium (as orotate 500mg) 64mg
  • calcium ascorbate dehydrate (equiv ascorbic acid 200mg) 242mg
  • cholecalciferol (equiv vitamin D3 250IU) 12.5micrograms
  • a-tocopherol (equiv natural vitamin E 50IU) 60IU
  • alpha lipoic acid 150mg
  • Retinyl palmitate (equiv vitamin A 3000IU) 900ugREIU
  • vitamin B co-factors: biotin (vitamin H) (600micrograms), thiamin hydrochloride (100mg), riboflavin (100mg), nicotinamide (200mg), calcium pantothenate (100mg), pyridoxine hydrocholoride (100mg), folic acid (800micrograms), cyanocobalamin (vitamin B12) (800micrograms).

The study is run by the Melbourne Clinic Professorial Unit (described on their website as ‘Australia’s largest private psychiatric hospital’) & the University of Melbourne.

“Current treatments for CFS include pharmacological (e.g. fluoxetine, rintatolimod, galantamine), psychological (e.g. cognitive behaviour therapy (CBT), adaptive pacing therapy), and lifestyle interventions. For many who remain in treatment, they continue to experience significant social, occupational, and functional impairment. Thus new treatment approaches are urgently needed.”

from Trial registration application

According to the trial application, the study intends to have 30 patients. It will use the Chalder Fatigue Scale as the primary measure, plus a number of questionnaire scales throughout the trial as secondary measures.

(The Chalder Fatigue Scale was used in the PACE trial, of which there’s been significant criticism, and Sense about Statistics  explains why the Chalder Fatigue Scale’s ceiling effect casts doubt on data.)

The Melbourne scientists are hoping this new study will show the benefit of antioxidants and nutrients in helping restore energy production:

“…it is posited that CFS is related to metabolic dysfunction, mitochondrial dysfunction and impaired biogenesis, in turn related to oxidative stress and systemic inflammation. Mitochondria are structures within cells primarily responsible for energy generation, and are particularly active in oxygen-rich and highly energy dependent tissues, such as the brain. Recent research suggests that patients suffering from CFS may improve with the supplementation of mitochondrial nutrients and antioxidants. This supplementation may be associated with the reduction to mitochondrial membranes, restoring mitochondrial energy production, protecting cellular structures and enzymes from oxidative damage, and decreasing fatigue.”

Meet the Scientists: Dr Menon
Dr Ranjit Menon, consultant psychiatrist, is the principal investigator. Dr Menon says that new research, ‘Metabolic features of chronic fatigue syndrome’ by Robert Nauviaux et al, supports the metabolic dysfunction hypothesis and adds further credence to mitochondrial promoters.

I asked Dr Menon about the trial and his experience.

How were the supplements selected?
These supplements are a cohort that has been previously studied as mitochondrial promoters and have a good safety profile. Other experts in the field of neutraceuticals were also consulted prior to settling on these.

How did this study come about?
There are no effective treatments for CFS at this stage and this was an idea to try a pilot study to see if this combination had any effect.

Who is funding the trial?
There is no external funding for this study. The medications have been donated by the nutraceutical companies.

How long have you been working on chronic fatigue syndrome?
I have a few patients with CFS and associated mood difficulties over the last 5 years.

Do you think your studies will change the current treatments that many GPs recommend for CFS patients in Australia?
This is a pilot study and if this shows an improvement in the core symptoms, a larger study will need to be done. If successful this could lead to a change in the current management of CFS.

Now that the US Agency for Healthcare Research and Quality has downgraded the conclusions for graded exercise and cognitive behavioural therapy (and the PACE trial methodology has been found wanting by scientists in the field), do you think more attention will be paid to your work?
In my opinion the likely management will not be a single modality and rather a combination of medications, psychotherapy as well as some graded exercise. CFS is a syndrome with multiple variables in its presentation as well as management and reductionism will not serve it well.

Is Melbourne, and Australia, a good place to be a researcher?
Yes. It has a significant volume of highly specialised experts which generates more research and inquisitiveness into science and knowledge

Do you collaborate with any colleagues from the University or Melbourne or follow others’ work on CFS and ME? 
Yes. As an honorary faculty member at University of Melbourne, I follow research from colleagues as well as international sources.

Why is this study in the Professorial Unit when the USA’s National Institute of Medicine’s 2015 report Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome “stresses that SEID is a medical — not a psychiatric or psychological — illness”, rather than the university’s School of Biosciences for example?
As a psychiatrist my interest is largely related to the neuropsychiatric aspects of CFS. Whilst CFS is not a psychiatric illness over two thirds of patients with CFS have associated mood or anxiety disorders. The primary outcome measure of this study is alleviation of fatigue rather than psychiatric symptoms.

The idea about using nutraceuticals has been driven by psychiatry rather than ‘biosciences’, as such this study is being conducted through the Department of Psychiatry.

In addition to the above, the separation of body and mind as in Cartesian Dualism has long been discarded in favour of monism or holistic management. As such this approach can and should be conducted through all avenues of medicine rather than separating ‘biosciences’ from psychiatry since psychiatry is a bioscience!

For more information about the study, you can see their website and contact them here.

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