Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia.

Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders.To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years.38 patients were included in a cross-sectional survey. Based on a validated observer's rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects.Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as "very much" or "much" improved, while Mild responders rated "much" or "minimally" improved.Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. It's important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed

Comparison of Good and Mild responders.

<p>Mean ± SD or frequency/percentage for a number of variables in Good (n = 15) or Mild responders (n = 23). P-value is calculated by Student’s t-test, or by Fischer’s exact two-tailed test in the categorical data. (n.s. = no significance)</p><p>Comparison of Good and Mild responders.</p

Prescribed Analgesics.

<p>Number of Good and Mild responders on daily use of prescribed analgesics. Tramadol, Codeine and Buprenorphine are opioids, while Duloxetine and Pregabalin are approved for the management of neuropathic pain. One patient was using Tramadol and Duloxetine at the same time.</p><p>Prescribed Analgesics.</p

Genotypes of MTHFR.

<p>Overview of prevalence (ref 6) and specific enzyme activity <i>in vitro</i> (ref 7) for various genotypes of MTHFR in healthy individuals, based on combinations of the polymorphisms C677T and A1298C.</p><p>Genotypes of MTHFR.</p

Vitamin B12 and folate in monocarbon metabolism.

<p>Schematic view of where enzyme MTHFR is contributing to synthesis of methyl-folate, and the subsequent methyl group transition from folate to B12 to homocysteine, which transforms into methionine. Activated methionine (S-Adenosyl Methionine; SAM) is the most important methyl donor in cell metabolism.</p