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ME/Chronic Fatigue Syndrome – Under or Misdiagnosed?

by Dr Rajendra Sharma(more info)

listed in cfs me long covid, originally published in issue 247 - July 2018


ME is not a very useful term. It has evolved from a diagnosis used in the 1950s, Benign Myalgic Encephalomyelitis, stemming from the Ancient Greek meaning painful and ‘inflammation of the muscles, brain and spinal cord’,[1] those labelled with ME rarely had, or have, actual evidence of brain or nerve inflammation. Not only is ME simply a label, it is not a very descriptive one at that.


Proposed Diagnostic Criteria for ME/CFS


Furthermore, ME is not a specific disease and is generally a ‘diagnosis of exclusion’ – one given when no definitive disease can be found. Nowadays, the condition associated with the group of symptoms is more commonly entitled Chronic Fatigue Syndrome (CFS). The initial criteria as defined by the US Centers for Disease Control and Prevention (CDC) in 1994 stated that for an individual to be given a diagnosis of CFS they must exhibit symptoms of fatigue or lethargy that must have been causing a 50 per cent loss of physical and social function, for at least six months.[2] An Australian website, CFS Health’ correctly highlights that in addition to the fatigue four of the following symptoms must be present:


  • Sore throat
  • Bad memory
  • Difficulty concentrating
  • Sore lymph nodes in the neck or under the arms
  • Muscle aches and pain (medically called myalgia)
  • Joint pain (medically called arthralgia)
  • Inability to get refreshing sleep
  • Headaches
  • Feeling of bodily discomfort (medically called malaise) after exertion. Also known as post exertion malaise.

Psychological depression:

  • Brain fog
  • Irritability
  • Dizziness
  • Disrupted sleep patterns
  • Sore eyes
  • Muscle spasms
  • Muscular pain and aches
  • Sore throat
  • Tender lymph nodes
  • Flu like symptoms
  • Insomnia
  • Anxiety
  • Depression
  • De-conditioned muscle
  • Nausea
  • Diarrhoea
  • Constipation
  • Lack of appetite
  • Weight loss
  • Weight gain
  • Inability to adapt to weather/temperature changes
  • Sensitivity around food, smell, light, sound and medication.
  • And many more

This long list of symptoms doesn’t help those with CFS, who can all too easily be blamed for hypochondriasis, which has led to the condition being considered one of a mental causation.


Could It Be B12 + Diagnosis

Could It Be B12     Diagnosis and Treatment of CFS 

A View of the Evidence

Most doctors haven’t yet caught up with some of the emerging science behind what causes CFS. There are very few studies which look at why some people develop the profound fatigue and various symptoms that can last months or years. Drug companies, which fund many large clinical trials, have little interest in CFS because there is no simple drug to be made that will ‘cure’ CFS due to their being so many possible contributory factors.

Chronic Fatigue Syndrome (CFS), has only been recognized by the medical profession world-wide since the mid-1990s. In fact, it was only in 2002 that it received official status as a condition here in the UK.[3]

Unfortunately, a considerable percentage of doctors continue to doubt CFS has a physiological cause and consider it a psychological issue.

Without doubt stressful events, be they physical or psychological (such as professional, personal or social issues), certainly have causative associations with CFS.  Also, CFS is more common in those who over exercise (especially athletes), lack sleep or have poor diets – all body-stressing events. Stress/adrenaline causes certain blood vessels to constrict, leading to diminished blood flow and long term poor perfusion of oxygen and nutrients to parts of the central nervous system, has been shown to lead to fatigue and other symptoms.[4]

One of the problems surrounding the continued knee-jerk response that CFS is a psychological issue is perhaps, that the conventional medical world seemingly, is as yet failing to embrace scientific papers published since 2009 concerning the involvement of mitochondria dysfunction in CFS.[5,6,7]

Mitochondria are the small parts of cells, numbering in their thousands in busy cells (heart muscle and nerve cells especially), that produce energy from sugar and oxygen.  It has been shown that ‘packets’ of energy, known as ATP, made by mitochondria, are associated in nerve pathways that transmit feelings of fatigue to the brain.[8]

Faulty mitochondria lead to a lack of available ATP denying energy for the cells to work optimally - so potentially any area in the body can end up functioning below its optimum level.

Other emerging evidence of physical, not psychological, causation indicates CFS as an inflammatory condition - although that is not identifying what is causing the excessive inflammation.[9] That said, people suffering from mental health problems, such as anxiety and depression, are apparently more at risk from developing CFS but that may be because the nervous system is so dependent on mitochondria that individuals cannot keep up the production of their happy and calming neurotransmitters.[10]

Overall, there is a chicken and egg situation here. Might psychology influence systemic health through the nervous system or does the physical illness underlying CFS lead to emotional disruption?  There is potential that both or either may be a root cause. 

Whilst we await the results of these avenues of research, there remains no NHS or commonly used conventional testing to ‘prove’ that someone has ME/CFS. Conventional treatment continues to be based on advice to take antidepressants, get plenty of rest and do graded exercise (as much as you can handle but no more, with gradual increase).

Too often patients are sent away with platitudes as GPs are unsure of what they can offer.  Medical School lacks education and clear guidelines.  A survey from 2005 (the last one I could find) suggested low knowledge and poor attitude towards patients with CFS.[11] More encouragement to teach the principles behind the science is, fortunately, coming to the fore as we overcome the barriers to diagnosis and management.[12]

As touched on above, evidence exists that between one in 5-10 elite athletes[13] or people who enjoy frequent and very active exercise,[14] will develop CFS at some point. This is much higher than the general population which is generally, although probably underestimated, as 1 in 500. 

CFS patients are often found to have been exposed to environmental pollution. Environmental oestrogens and other ‘endocrine disruptors’ that attach to cell receptors block information and nutrition to the cells and mitochondria.[15]

We are exposed to innumerate amounts of different toxic metals, pesticides and chemicals from industry - all of which are polluting our air, water supply and food chain - all and any of which may affect the mitochondria.[16,17] Then there are the many untested compounds in cosmetic that we apply to ourselves daily.[18]

There is an abundance of evidence linking infection and CFS. Particularly incriminated are those organisms that lie intracellularly directing the cell do its bidding – usually instructing the cell to make more of the germ. Viruses in particular link with the DNA in our nucleus, and the DNA belonging to each mitochondria, and may be passed to successive generations of daughter cells when the cell multiplies or replaces itself.  It is not clear that we know all the different pathogens that cause CFS[19] but many are suspected including Epstein-Barr virus, CMV, HHV-6 and other herpes infections as well as Borrelia (Lyme) and its co-infections. Of course, we must better define if a chronic infection is in its own right a diagnosis or if it is acceptable to define a chronic infection as Chronic Fatigue. My consideration is that any infection effecting the mitochondria allows an overlap in diagnostic labelling.

These chronic infections often supress the immune system, influencing immune cells or regulatory cytokines, such as CD57 cell counts, IL-10 or T-Reg cells, leading to other infections getting a hold more easily and more often.

There is also evidence of a direct link between CFS and the microbiome (healthy bowel flora) in the gut, which we know plays a huge role in keeping our nervous and immune systems healthy. There is direct communication between the bowel bacteria and mitochondria.[20,21,22]

As to the discussion of whether CFS can be applied to illnesses that have an established and defined cause, we must also be wary of a ‘wolf in sheep’s clothing’. Many diagnoses are missed and a label of CFS provided too often. As an example, in my experience and those in integrated medicine, we are underestimating the prevalence of hypothyroidism. There is little published research to bear that out, but it has certainly led to the formation of associations and created innumerable public ‘blogs’.  I also think we miss widespread Vitamin B12 deficiency and there is evidence that may be the case.[23]

Tests and Investigations

Testing mitochondrial function through ATP or Pyruvate/lactate ratio assessment, a simple blood test, is in the face of the emerging evidence, of great importance in diagnosing CFS. The majority of those patients that I test with symptoms that fit into the conventional guidelines, have low ATP or other mitochondrial markers.

One also needs to assess chronic infection, suppressed immunity, toxicity and the frequently overlooked health of the bowel flora. 

If a patient falls into the category of CFS, regardless of what diagnosis may have been given (often one of a psychological nature), it is best to approach doctors or health practitioners with established qualifications in functional medicine. As there may be many underlying causes to CFS, working with a health practitioner, and undergoing tests, can clarify the best treatments.

My approach as an Integrated Doctor, one who uses conventional methods as well as alternative therapies, is to look at the individual and assess all aspects of his or her emotional and physical health. This includes their psycho-spiritual state, lifestyle, exposure to environmental toxins and detoxification ability, infections, stress levels, diet and underlying disease.

book cover Live Longer Live Younger

Available from Amazon

Integrated Treatment and Therapeutic Options

I often feel I can advise and decide on how best to treat a patient on the back of history and examination. Initiating physiological and emotional changes generally impacts on the symptoms, but without investigations I do not always see the problem resolve as it is so important to know which area of causation needs the most therapy.

Nutritional advice, establishing a healthy exercise program and dealing with lifestyle choices must come first. If chronic (long term) stress is an issue, then natural remedies known as adaptogens can upregulate the nervous system’s ability to make calming and de-stressing neurotransmitter hormones. This is best used alongside meditation, yoga and various types of counselling. There is published evidence of non-drug programs, such as Yoga, dealing with mitochondrial dysfunction and chronic fatigue syndrome.[24]

Using natural supplements is well established as being of benefit to mitochondria. Carnitine and CoQ10,[25] alpha-lipoic acid, reduced nicotinamide adenine dinucleotide (NADH) & membrane phospholipids,[26] D-ribose (27), antioxidants in general (28) and magnesium[29] are just a few of the nutrients researched that show effect.

Plant and herbal extracts have various effects on cellular and mitochondrial function,[30] Rebalancing bowel bacteria, killing off chronic infections caused by bacterial, viral and yeasts/fungal or mould organisms, including a common culprit Candida[31] may all be important. Natural therapies can ‘up-regulate’ detoxification at a cellular level and increase liver activity.

Specialists and clinics world-wide all have specific and preferred protocols that are generally individualised and adapted for each case. There are anecdotal benefits from the use of intravenous (IV) therapies such as Myers’ cocktails, Protocol Inject N (PIN) infusions associated with Cell Symbiosis Therapy and Phospholipid Exchange all of which can be considered.

I am reading with interest the science behind mitochondria and their relationship to photons, small packets of "quantum" electromagnetic energy. Mitochondria may well emit as well as absorb this energy. This might be the underlying mechanism of mitochondrial activity in the cell and be associated with self-repair. Such science may explain early observation of LASER therapeutic benefits. This can now be administered trans-dermally as well as intravenously. An exciting potential for those troubled with non-refractory and long-term CFS.[32,33]


1.         Wojcik, W (2011). "Chronic fatigue syndrome: Labels, meanings and consequences". Journal of Psychosomatic Research. 70 (6): 500–504. doi:10.1016/j.jpsychores.2011.02.002. PMID 21624573. April 2011.

2.         CFS Health Centre Pty Ltd,  2014.

3.         Alan Hutchinson, A Report of the CFS/ME Working Group. 2002

4.         I Bou-Holaigah et al The relationship between neurally mediated hypotension and the chronic fatigue syndrome Jama, 1995.

5.         Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. International Journal of Clinical and Experimental Medicine. 2(1):1-16. 2009.

6.         Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). International Journal of Clinical and Experimental Medicine; 5(3):208-220. 2012.

7.         Myhill S, Booth NE, McLaren-Howard J. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. International Journal of Clinical and Experimental Medicine. 6(1):1-15. 2013.

8.         Staud, Roland. Peripheral and Central Mechanisms of Fatigue in Inflammatory and Non-Inflammatory Rheumatic Diseases. 2012.

9.         Jose G. Montoya, et al, Cytokine signature associated with ME/CFS severity

Proceedings of the National Academy of Sciences Jul 2017.

10.       JAMA and Archives Journals. "Stress, Childhood Trauma Linked To Chronic Fatigue Syndrome In Adults." ScienceDaily. ScienceDaily. . 7 November 2006.

11.       Jo Bowena et al,. Chronic Fatigue Syndrome: a survey of GPs’ attitudes and knowledge. Family Practice 2005; 22: 389–393. 2005.

12.       Bayliss K, Goodall M, Chisholm A, et al. Overcoming the barriers to the diagnosis and management of chronic fatigue syndrome/ME in primary care: a meta synthesis of qualitative studies. BMC Family Practice. 15:44. doi:10.1186/1471-2296-15-44. 2014.

13.       Budgett R, Newsholme E, Lehmann M, et al  Redefining the overtraining syndrome as the unexplained underperformance syndrome British Journal of Sports Medicine 34:67-68. 2000.

14.       Budgett R Fatigue and underperformance in athletes: the overtraining syndrome. British Journal of Sports Medicine: 32:107-110. 1998.

15.       Gore AC, Chappell VA, Fenton SE, et al. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocrine Reviews: 36(6):E1-E150. doi:10.1210/er.2015-1010.  2015.

16.       Li N, Sioutas C, Cho A, et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environmental Health Perspectives: 111(4):455-460. 2003.

17.       Stanislav A. Pshenichnyuk*a  and  Alberto Modellibc Can mitochondrial dysfunction be initiated by dissociative electron attachment to xenobiotics? Phys. Chem. Chem. Phys: 15, 9125-9135. 2013.


19.       Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease

Underhill, RA. Medical Hypotheses , Volume 85 (6) 765-773. Dec 2015. E-pub Oct 19 2016.

20.       Clark A, Mach N. The Crosstalk between the Gut Microbiota and Mitochondria during Exercise. Frontiers in Physiology:8:319. doi:10.3389/fphys.2017.00319. 2017.

21.       Franco-Obregón A, Gilbert JA. The Microbiome-Mitochondrion Connection: Common Ancestries, Common Mechanisms, Common Goals. McFall-Ngai MJ, ed. mSystems: 2(3):e00018-17. . 2017.

22.       Microbiome and Longevity: Gut Microbes Send Signals to Host Mitochondria Gruber, Jan et al. Cell , Volume 169 , Issue 7 , 1168 – 1169. Jun 15 2017.

23.       Could It Be B12?: An Epidemic of Misdiagnoses by Sally M. Pacholok (Author), Jeffrey J. Stuart (Author)  Published on Kindle. 2011.

24.       Takakazu Oka  et al., Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial. BioPsychoSocial Medicine The official journal of the Japanese Society of Psychosomatic Medicine 20148:27. . 2014.

25.       Filler K, Lyon D, Bennett J, et al. Association of mitochondrial dysfunction and fatigue: A review of the literature. BBA Clinical.;1:12-23.  2014.

26.       Nicolson GL. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Integrative Medicine: A Clinician’s Journal.13(4):35-43. 2014.

27.       Jacob E. Teitelbaum, Clarence Johnson, and John St. Cyr. The Journal of Alternative and Complementary Medicine Vol 12(9).  Nov 2006.

28.       Victor, Victor M.; et al  Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders), Volume 9, Number 4: 376-389(14). August 2009.

29.       Nils-Erik LSaris et al Magnesium: An update on physiological, clinical and analytical aspects. Clinica Chimica Acta Volume 294, Issues 1–2: 1-26. April 2000.

30.       Binu Tharakan  Bala V. Manyam Botanical therapies in chronic fatigue, Phytotherapy Research, Volume20, Issue2: 91-95. February 2006.

31.       Renfro, Lisa et al. Yeast connection among 100 patients with chronic fatigue

The American Journal of Medicine , Volume 86 (2): 165-168. 1989.

32.       Rahnama M, et al Emission of mitochondrial biophotons and their effect on electrical activity of membrane via microtubules. J Integr Neurosci. 10(1):65-88. March 2011.

33.       Ann D.Liebert, Brian T.Bicknell, Roger D.Adams. Protein conformational modulation by photons: A mechanism for laser treatment effects. Medical Hypotheses Volume 82(3): 275-281. March 2014.


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About Dr Rajendra Sharma

Dr Rajendra Sharma MB BCh BAO LRCP&S(Ire) MFHom is a fully qualified doctor with a specialist interest in Integrated Medicine. He is a fully qualified doctor trained in conventional medicine with post-graduate qualification in Homeopathy and training and practice in Functional & Complementary medicine. His special interest is working with patients with chronic disease and illustrating it’s underlying causes particularly CFS/ME, cancer and other difficult conditions that respond poorly to conventional medicine. Treatment of conditions focuses on encouraging the body’s innate healing ability using life-style, exercise, nutritional and non-pharmaceutical medicines whenever possible. Until recently he was the Secretary to the British Society for Ecological Medicine (the largest body of conventionally trained doctors working in Integrated Medicine) and was the Education Moderator – in charge of continual professional development and training doctors wishing to enter the field. This involved teaching about diagnostic investigations into environmental causes of disease such as metal toxicity, food allergy, pollution, chronic infection and mitochondrial dysfunction – all very relevant to CFS – and non-conventional therapeutic approaches.

He is the author of The Family Encyclopedia of Health and in 2014 published the ‘all you need to know’ healthy ageing book, Live Longer Live Younger. It won “The Janey Loves 2016 Platinum Book Award” (Radio 2’s Steve Wright in the Afternoon’s Health Advisor – Janey Lee Grace). He was the Medical Director at The Hale Clinic in the 1990s and, until 2012, Medical Director of the pioneering The Diagnostic Clinic where new care initiatives in health screening were forged. These included the broader introduction of investigating underlying causes of epigenetics in genomics, cancer and mitochondrial testing. Please visit

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