There have been two recent papers on mitochondrial dysfunction and chronic fatigue syndrome.

• Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit, Sarah Myhill, Norman E. Booth , John McLaren-Howard, Int J Clin Exp Med 2013;6(1):1-15
• Chronic fatigue syndrome and mitochondrial dysfunction, Sarah Myhill, Norman E. Booth , John McLaren-Howard, Int J Clin Exp Med (2009) 2, 1-16

As a mathematical modeler, I tend to automatically ask the question – which is simpler (Osler’s Principle) with better evidence

• mitochondrial dysfunction causes microflora dysfunction
• microflora dysfunction causes mitochondrial dysfunction

My conclusion is that microflora dysfunction causes mitochondrial dysfunction.

Looking at the 2013 paper, the treatment (pp.4,5) from Dr. Myhill  is:

• Stone Age Diet – known to alter microflora
• Standard pack of nutritional supplements (substituting what the microflora should have been producing)
• Plus balance of sleep, rest and work.

So, the exact same outcome would be expected from correcting microflora.

For example, B12 is classically low in CFS patients. Gut flora appears to be the source per this PubMed article Vitamin B12 synthesis by human small intestinal bacteria. One species has been identified, Lactobacillus reuteri CRL1098, which ” The cell extract of L. reuteri corrected the coenzyme B12 requirement of Lactobacillus delbrueckii subsp. lactis ATCC 7830 and allowed the growth of Salmonella enterica serovar Typhimurium (metE cbiB) and Escherichia coli (metE) in minimal medium.” Several other articles reported other species of Lactobacillus reuteri producing B12.

Below are what the best buys’s for a probiotic consisting only of L.Reuteri…

• US Orders (single strain) [ 90 capsules $16]
• UK Orders (single strain) [ 90 capsules £22]

There are several supplements that have been demonstrated to be neuroprotective according to PubMed. These items in general protects the brain and decrease brain fog. Theses items can be divided into to classes. Items that could cause a herx (worsening symptoms initially) and low risk of herx.

• Low Herx Risk
  • Ashwagandha
  • Boswellia
  • D-Ribose – already covered
  • Piracetam – already covered
  • Ginger – slight
• Probable Herx
  • Olive Leaf Extract
  • Most tetracycline antibiotic)
  • Some Beta-lactam antibiotics
  • Citicoline – not effective for CFS, per studies

This is the start of a series of posts dealing with remission from CFS/IBS/FM and related autoimmune diseases. There are many approaches that have reported a 70-80% remission rate. The last 20-30% is a concern for me. My model of CFS is simple to describe but not so simple to treat 😦

Onset is the establishment of a dysfunctional gut bacteria that is stable. This shifts the production of amino acids, minerals, etc into a state that results in re-activation of one or more pathogens (Lyme, EBV, CMV, Q-fever and about 30 other known infections). The re-activated pathogens contribute to keeping the dysfunctional gut-bacteria stable. Until both the pathogens and the gut bacteria are normalized, the CFS condition continues.

Consequences of this model are

• Often a substance will result in one set of symptoms disappearing or improving. For example, I experienced Sjorgen’s syndrome disappearing after 3 days of Mutaflor
• Often a substance will work for only 2-4 months (as studies found for NADH), this may be because it impacts one species of one family which then disappears and the space it occupied was populated with a different species

For pathogens, the following are known mechanism that they use to defend themselves from eradication:

• Resistors — about 0.01-0.5% become long term sleepers. Most antivirals and antibiotics disrupt the reproduction process. A resistor sleeps through this!
• Biofilms — often produce by bacteria but exploited by viruses. This can view as a “space dome” that acts as a barrier to anitvirals and antibiotics
• Fibrin Walls — Instead of forming a biofilm to form a space dome, it uses the body clotting mechanism to create walled off valleys inside of tissues. Overtime some of the walls will be naturally dissolved, releasing the pathogen. Antivirals and antibiotics cannot get to these safe valleys
• Mutations — Studies suggests that some pathogens increase their mutation rate when they sense members of their own species dying. In other cases there may be several mutations already in the body. All it takes is a mutation that resists or ignores the antiviral or antibiotics to keep the infection alive

The easiest way to method to determine if biofilms are being exploited by pathogens causing CFS symptoms is to do a 5 day course of EDTA or NAC (or both together). This should be done only after under medical review. The expected result would be a worsening of symptoms (herx) for those days, followed by some improvement of symptoms.

• EDTA (Check with CFS friends in case they have extra — you only need 10-15 capsules to test)
  • US [750mg @ 120 capsules $10]
  • UK [500mg @ 120 capsules £16]
• NAC
  • US [60 capsules $6]
  • UK [60 capsules £7]

Note Some people will claim that the herx is because you are full of toxins. I have been unable to find a single study where NAC or EDTA treatment for known surplus toxins (outside of autoimmune illnesses) produced a herx. It is more probable that the herx is due to pathogens then the typical toxins.

Preamble

When I came down with CFS about 1999, Licorice was one of the items that assisted me to full remission by 2001.

Licorice comes in several forms, we are NOT talking about a confectionery candy. There is a pure Licorice candy called Spezzata which Cap’n Dave introduced me to in 1999 and which I continues to use. The active ingredient is Glycyrrhiza.

What does it do?

It does almost everything that you really want from a supplement: PubMed studies report that it alters microfloras, is anti-bacterial, Inhibits viruses(including EBV via a unique mechanism, and rota-virus). It reduces inflammation, depression and crosses the blood-brain-barrier.

In terms of the thyroid, it increases the biological half-life of cortisol and potentiates the action of hydrocortisone.

It has been documented in patient studies to reduce symptoms — in fact, there are published reports of remission. This report is very creditable if EBV is the primary pathogen.

Three ways of taking

The report of remission was by dissolving taking 2.5 grams of extract dissolved in a pint of milk. Taking 40 grams/day as capsules did not result in remission.

The last  approach is using Spezzata and dissolving it in the mouth (possibly with warm milk, hot chocolate or a latte). This is my usual method.

Licorice may cause adverse interactions with some drugs so you should review any use of it with your medical resources.

• Spezzata – this can sometime be purchased in bulk (1 kg), but until you see that it is helping, just buy 40 grams
  • [US Order: 40g for $6]
  • [EU Order: 40g for £6]
• Licorice Capsules – if no impact from the capsules: open them up and dissolve in milk (5 capsules = 2.5 grams)
  • [US Order: 100 capsules for $4]
  • [EU Order: 100 capsules for £4]
• Licorice Powder (about 1/2 the price per oz as capsules)
  • [US Order: 1 pound (Organic) for $13]
  • [EU Order: 1 pound (Organic) for £22]