Methyl Folate and Schizophrenia
http://www.schizophreniaoptions.com/methyl-folate-and-b12/"Many individuals with schizophrenia have deficits in metabolism related to methylation, a metabolic process involving carbon donation. This issues stem from multiple interrelated risk factors involving Cobalamine (B12), Folic Acid (Folate) and Pyridoxine (B6) and the enzymes that interact with these vitamins.
Specifically, low folate levels, high homocysteine levels, and poor folate activation genetics are common in schizophrenia, and these issues appear to confer significant increased risk for development and maintenance of the disorder. While these deficits occur for a variety of reasons, research has shown that supplementation can correct some aspects of this problem and directly improve symptoms in many individuals."
"Homocysteine is a specific marker for methylation deficits that involve Folate, B12 and/or B6. Homocysteine is a toxic metabolic step in the methylation cycle (and folate cycle) and high levels of homocysteine have been implicated in many diseases including Depression, Heart Disease, Stroke, Dementia, and Bone Loss.
High plasma homocysteine levels are also common in schizophrenia. One case-control study reported mean plasma homocysteine levels that were almost 50% higher in schizophrenia compared to controls (16.1 versus 10.9 µmol/L; p=0.028). Hyperhomocysteinemia with levels greater than 15 µmol/L was seen in 34.4% of subjects with schizophrenia compared to 15.2% of controls (Mabrouk et al. 2011)."
"High homocysteine levels imply that myriad complex metabolic processes essential to physical and mental health are impaired.
One example is Glutathione, an endogenous antioxidant that is often dangerously low in schizophrenia. In building glutathione homocysteine is first converted to cysteine, the sulfur containing amino acid that acts as its limiting reagent. Impairment in the complex methylation cycles illustrated in Figure 1 below (from Bradley and Lascalzo 2009) can help explain why glutathione levels are often so low in schizophrenia. Regardless of whether this is due to genetic abnormalities (e.g., clutamate-cysteine ligase enzyme) or low levels of folate, B6 or B12, intervention is warranted."
"Two problems related to folate have been clearly identified in schizophrenia. The first issue is clear. Low plasma folate levels are quite common in this disorder.
One small double-blind study found that 37% of inpatients admitted for schizophrenia had folate levels below 200 µg/l (Godfrey et al. 1990). A case-control study found high homocysteine levels in schizophrenia in conjunction with folate levels that were half that of controls (8.2 versus 4.2 µmol/L; p<0.001) (Mabrouk et al. 2011).
And these low folate levels appear to matter regarding symptom severity. Goff et al. (2004) reported plasma folate levels in schizophrenia that are reduced by 43% compared to controls, and they correlated these lower levels to negative symptoms severity as measured by the Schedule for Assessment of Negative Symptoms (SANS) (r=–0.31, N=91, p<0.01). In other words, there is a correlation between low folate levels and a worsening negative symptoms."
"Kale et al. (2010) reported 36% reductions in plasma folate and 53% reductions in red blood cell folate in individuals with a first episode of psychosis compared to healthy controls. This study clearly demonstrates that low levels are not the result of antipsychotic medication use."
"In their study of 123 Han Chinese, Feng et al. (2009) reported that subjects with schizophrenia were more than twice as likely to have two copies of the C677T allele of MTHFR compared with controls (31.7% versus 14.6% in controls with p<0.001). The presence of two copies was associated with significantly increased homocysteine levels in controls and in schizophrenia. Particularly notable however was that this adverse effect on homocysteine was especially pronounced in schizophrenia, perhaps due to other overlapping genetic risk factors."
"Folate Trials in Schizophrenia
The studies are clear. Individuals with schizophrenia are at risk for low plasma folate levels and these low levels are likely to impact symptom severity. At the same time, there is also risk for carrying folate-related genetics that reduce folate activity by over 50%. In fact, both issues can exist within the same individual because both are common.
Studies using inactive folate in schizophrenia are likely to increase chances of false negative outcomes. The use of methyfolate is likely to be a more effective treatment approach in general."
