CFS, The Condition

CFS/FM/ME can be a debilitating condition affecting around 3% of the population
The condition is generally misunderstood, however, symptoms are very similar to those seen with an absolute deficiency of vitamin B12
The condition is characterized by Paradoxical B12 deficiency
Studies on over 700 individuals have shown all have functional B2 deficiency
Functional B2 deficiency results in functional B12 deficiency.
Functional B2 deficiency leads to poor energy conversion from fat, sugar and protein, contributing to Constant Fatigue
The defining characteristic of the condition is reduced cycling of Methyl B12 and hence the under-production of creatine.
Over 40% of S-Adenosyl-Methionine (SAM) produced in the body is involved in the production of Creatine.
Lack of Creatine production results in prolonged lack of energy, with prolonged over-usage or underproduction eventually leading to the subject being chronically fatigued (CFS)
Reduced production of Creatine has been associated with many conditions including dementia, Parkinson's disease, Autism, Chronic Fatigue Syndrome.
Reduced methylation due to functional B12 deficiency results in depression, anxiety and poor sleep - common symptoms in CFS
Reduced methylation due to functional B12 deficiency, results in lower production of melatonin and poor maturation of the gut

Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME)

Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyalitis (ME) is an ill defined disease that is characterized by a post exercise tiredness or malaise. The condition usually lasts for more than six months and in affected individuals is very disabling. Symptoms include muscle soreness, inability to concentrate (brain fog), headaches and severe mental and physical fatigue. In addition these symptoms may be accompanied by sensitivity to light, sounds and smells, digestive disturbances, depression, painful and often slightly swollen lymph nodes, and it may also be accompanied by cardiac and respiratory problems.

Most would be familiar with the fatigue that one feels after over-exercising, when stores of muscle glycogen and creatine-phosphate are used up. Fatigue can also occur in vitamin B12 deficiency, due to the lack of production of the electron-transport vehicle CoQ10 (a methylation product) and due to lack of production of the ATP shuttle vector creatine. Fatigue is also common in hypothyroidism, in which lack of Iodine and/or Selenium results in lack of activation of vitamin B2, and that then affects the activation of vitamin B12, with functional vitamin B12 deficiency resulting. A feature of Chronic Fatigue is lack of functional B2 and functional B12, which can occur to prolonged infection, and/or constant over-training or over-work, the two most common causes of CFS/ME.

Contributing to lower energy in CFS can be lower levels of iron, as this will reduce the amount of oxygen that can be used in oxidative phosphorylation, further it reduces the efficiency of the Electron Transport Chain (ETC). Of greater significance, though, is the uncoupling of the enzyme aconitase, the major enzyme involved in the metabolism of citrate in the citric acid. As ferritin levels drop below 70 ug/L, aconitase starts to reduce it ability to metabolize citric acid with the result that energy (as unmetabolized citrate) appears in urine. As ferritn drops to around 20 ug/L as much as 80-90% of citrate can be lost into urine. Optimal levels of iron, therefore should be with ferritin >70 ug/L, Haemoglobin >14.5 and Haematocrit >0.45.

Genetic Linkage

Recently it has been found that CFS may be related to defects in either folate metabolism and/or the methylation cycle, with a high incidence of sufferers have genetic mutations in the MTHFR, MTR, MTRR, MTS and/or SHMT genes. In addition many CFS individuals have genetically similar vitamin D receptor genes. It is possible that CFS sufferers have had these "inborn errors of metabolism" for much of their life, without experiencing any significant problem until some precipitating event such as stress or a chronic infection has triggered chemical changes inside the body thereby resulting in CFS.

Treatment of CFS

Many, many different treatments have been tried in an attempt to cure CFS, with little success. However, there is some independent published clinical evidence that suggests potential benefits from repeated dose treatment with high levels of injected vitamin D3, adenosylcobalamin and methylcobalamin (both forms of Vitamin B12). It is believed that this repeated high dose supplementation is required to stock both the body’s methylcobalamin levels but also the adenosylcobalamin. Over time, and with the addition of high dose vitamin D supplementation the majority of subjects appear to return to their pre-fatigue status.

The RnB protocol has been found to be highly effective in reversing the symptoms of CFS (RnB protocol)

Creatine supplementation has also proven to have some success in some individuals (Allen, 2012).

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Russell-Jones, GJ 2022 Functional vitamin B12 deficiency in CFS. Int J. Psychiatry 27 Jul 2022 PDF

Russell-Jones, GJ 2022 Paradoxical vitamin B12 deficiency PDF