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The important role of Methylation Cycle (one-carbon metabolism) in the CNS: Implications on Mood and Cognition.
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Diễn Đàn Cựu Sinh Viên Quân Y
© 2010
© 2010
Earlier in this decade, data released from the famed Framingham Longitudinal Study revealed a shocking finding: People with elevated level of homocysteine have higher risk of developing dementia, particularly Alzheimer’s disease. To be exact, 100% of subjects with homocyteine level above 14 came down with dementia.
Confusion ensued with knee-jerk reactions. Many academic centers concentrated their research on the toxicities of homocysteine, a byproduct in the methylation of methionine. Only in recent years, did researchers realize that this methylation cycle carries huge impact on the function and plasticity of neuron synapses in the Central Nervous System (CNS) and elevated homocysteine is just a marker of the cycle’s malfunction.
This paper deals only with the CNS aspects of the Methylation Cycle although effects of elevated homocysteine via oxidative stress to endothelial cells have been implicated in cardio-vascular diseases, venous thrombosis, peripheral nervous system damage, malignant tumors, osteoporosis and of course, the classic megaloblastic anemia.
This paper deals only with the CNS aspects of the Methylation Cycle although effects of elevated homocysteine via oxidative stress to endothelial cells have been implicated in cardio-vascular diseases, venous thrombosis, peripheral nervous system damage, malignant tumors, osteoporosis and of course, the classic megaloblastic anemia.
In the methylation cycle (1-carbon metabolism), methylene is returned to homocysteine to restore methionine so that SAM (SAMe, S-Adenosyl-Methionine) will continue to be available for various cellular functions; in the CNS, it has to do with synaptic plasticity and neuro-transmitters exchanges. This process requires the methylation of vitamin B12 (cobalamine) which requires the availability of methyl-tetrahydrofolate (5-methyl-THF). Without adequate B12 or methyl-THF, there will be an accumulation of homocysteine and a deficiency of SAMe.
Low SAMe in the CNS is associated with depression, dysthymia, psychosis and dementia. Homocysteine is a marker of this methylation cycle dysfunction but not the culprit as previously thought.
Taking SAMe supplement therefore can improve the symptoms of depression as demonstrated in a recent report; however if the deficiency of B12 or folate is not addressed, it will lead to a rapid development of hyper-homocysteinemia which raises the risk of thrombotic blood clots.
Most Americans are not deficient of folic acid due to the law requires fortification of baking flower with folic acid to prevent neural tube defect in newborn. However, 6% of Caucasians and 16 to 20% of Hispanics, a total 10% of across the board American population has genetic polymorphism , particularly as homozygote of the C677T variant (TT of the C to T) and therefore can’t convert folate into methyl-THF. These unfortunate subjects experience depression, low academic achievement with high homocysteine. They only respond to methyl-folate supplement on top of the usual anti-depressant.
7% of older Americans have B12 deficiency but 20-24% of Americans with dementia have low B12 level and elevated homocysteine. Vitamin B12 supplement is helpful for those subjects. In fact, a recent study using neuro-psychological tests and MRI scan of the brain demonstrated that subjects with MCI (Mild Cognitive Impairment), a precursor to dementia, who were given a mixture of B12, B6 and folic acid can delay dementia onset and preserve the gray matter in their brains longer than those who took placebo.
Implications for Vietnamese-Americans:
The prevalence of C677T polymorphism in Vietnamese-Americans is unknown (10% is a good estimate) but many of us have B12 deficiency from strict vegetarianism, atrophic gastritis from chronic Helicobacteria Pylori infection, chronic alcoholism (which can cause deficiency of both B12 and folate)so periodic (every 2 years) checking of B12, Folate, Methyl Malonic Acid and Homocysteine levels is recommended (desirable values: Homocysteine < 12, B12 > 430, Folate >6) so proper treatment can be given in time to prevent damage from methylation cycle dysfunction.
Pham H. Liem QYHD20
Low SAMe in the CNS is associated with depression, dysthymia, psychosis and dementia. Homocysteine is a marker of this methylation cycle dysfunction but not the culprit as previously thought.
Taking SAMe supplement therefore can improve the symptoms of depression as demonstrated in a recent report; however if the deficiency of B12 or folate is not addressed, it will lead to a rapid development of hyper-homocysteinemia which raises the risk of thrombotic blood clots.
Most Americans are not deficient of folic acid due to the law requires fortification of baking flower with folic acid to prevent neural tube defect in newborn. However, 6% of Caucasians and 16 to 20% of Hispanics, a total 10% of across the board American population has genetic polymorphism , particularly as homozygote of the C677T variant (TT of the C to T) and therefore can’t convert folate into methyl-THF. These unfortunate subjects experience depression, low academic achievement with high homocysteine. They only respond to methyl-folate supplement on top of the usual anti-depressant.
7% of older Americans have B12 deficiency but 20-24% of Americans with dementia have low B12 level and elevated homocysteine. Vitamin B12 supplement is helpful for those subjects. In fact, a recent study using neuro-psychological tests and MRI scan of the brain demonstrated that subjects with MCI (Mild Cognitive Impairment), a precursor to dementia, who were given a mixture of B12, B6 and folic acid can delay dementia onset and preserve the gray matter in their brains longer than those who took placebo.
Implications for Vietnamese-Americans:
The prevalence of C677T polymorphism in Vietnamese-Americans is unknown (10% is a good estimate) but many of us have B12 deficiency from strict vegetarianism, atrophic gastritis from chronic Helicobacteria Pylori infection, chronic alcoholism (which can cause deficiency of both B12 and folate)so periodic (every 2 years) checking of B12, Folate, Methyl Malonic Acid and Homocysteine levels is recommended (desirable values: Homocysteine < 12, B12 > 430, Folate >6) so proper treatment can be given in time to prevent damage from methylation cycle dysfunction.
Pham H. Liem QYHD20
