Studies regarding the correlation between coronary artery disease incidence and abnormally high blood levels of the amino acid homocysteine have been appearing with increasing regularity. Relatively overlooked among the research articles is a recently published Swedish study, the results of which demonstrate consistently high homocysteine levels and low concentrations of vitamin B12 in the cerebrospinal fluid (CSF) of patients meeting established clinical criteria for Chronic Fatigue Syndrome and Fibromyalgia
Chronic Fatigue Syndrome and Fibromyalgia are two disorders only recently widely recognized clinically, and though not identical, share in common many features which include fatigue, reduced pain thresholds and depression. Criteria for Chronic Fatigue Syndrome and Fibromyalgia diagnosis have been established by the Centers for Disease Control and the American College of Rheumatology, respectively.
In the Swedish study by Regland M.D., Ph.D., et al., published in the Scandinavian Journal of Rheumatology, twelve female patients that met criteria for both Fibromyalgia and Chronic Fatigue Syndrome were studied along with a control group of eighteen healthy women. Subjects were also evaluated using a subset of items from the Comprehensive Psychopathological Rating Scale. The aim of the study was to determine factors present in cerebrospinal fluid related to homocysteine metabolism that correlate with Chronic Fatigue Syndrome and Fibromyalgia.
The mean value of cerebrospinal fluid homocysteine in the patient group was over three times the mean level in the control group, a highly significant difference. Cerebrospinal fluid vitamin B12 levels measured below normal in the majority (7/12) of Fibromyalgia and Chronic Fatigue Patients.
On the other hand, Serum levels of homocysteine, folate, and vitamin B12 did not significantly deviate from normal ranges in the Fibromyalgia / Chronic Fatigue Syndrome patients. The authors interpret their findings to mean that biochemical events leading to high homocysteine levels in their patient group occur predominantly, if not exclusively, within the brain itself. Low vitamin B12 levels in the cerebrospinal fluid may reflect disruption of the mechanism of transport across the blood brain barrier. Incidentally, according to health practitioners who have used vitamin B12 therapeutically, high doses are often required to achieve measurable effects.
Homocysteine is a sulfur-containing amino acid involved in several important methyl and sulfur transfer reactions. Excessive accumulation of homocysteine in the body fluid compartments is normally prevented by degradation through two enzymatic reactions called transsulfuration and remethylation. Importantly, these enzyme reactions depend on folate, vitamin B 6 (pyridoxal 5- phosphate), and vitamin B12 (cobalamin) as cofactors.
When functioning properly, the enzymatic break-down of homocysteine forms methionine, which can then be converted to S-adenosyl-methionine (SAM). SAM is an important cofactor in the metabolism of central nervous system monoamine neurotransmitters, including dopamine, norepinephrine and serotonin. It has also been used successfully to treat both Fibromyalgia and depression. Unfortunately, SAM was not measured in the Swedish study.
Another explanation for high cerebrospinal fluid homocysteine levels was considered by the Swedish authors. Nitric oxide, which is an inhibitor of the enzyme that converts homocysteine to methionine, is produced as a result of inflammatory reactions. Most of the patients in the study, in addition to their neurological condition, had accompanying symptoms of viral or bacterial infections. Theoretically, the inflammation caused by these infections increased nitric oxide levels, which in turn increased homocysteine levels.
In conclusion, this study provides convincing preliminary evidence that high homocysteine levels in cerebrospinal fluid homocysteine is an underlying factor in patients suffering from Fibromyalgia and Chronic Fatigue Syndrome. Low vitamin B12 levels in cerebrospinal fluid and possibly low SAM levels are implicated as contributing factors. Additional evidence from other studies further support the idea that deficiencies in enzymatic pathways in the brain involving vitamin B12 , homocysteine, and folic acid underlie a range of neurological disorders. Deficiencies in these essential biochemical pathways in the brain should be considered by health practitioners in the evaluation of successful interventions for reversing symptoms of Fibromyalgia, Chronic Fatigue Syndrome, and other neurological conditions.