Nutrition, genes, and brain dysfunctions: Folate

Sometimes eating a healthy diet is not enough. In their search to answer why supplementing with folate helps some people with the brain symptoms of schizophrenia, NARSAD-funded research scientists are studying some people with schizophrenia who may have genetic defects that lower the amount of folate (vitamin B9) available in their bodies for their cells to use. This was found to be true in my daughter's case, as well (see book).

Folate, folic acid, and Pteroylglutamic acid, are names for a water-soluble vitamin (B9) critical for the normal functioning of our cells, and for the development of neurons. We use folate, working synergistically with vitamin B12 (cobalamin) and vitamin C to help break down, use, and create new proteins that are then used to form red blood cells and help produce DNA.

Since folate is water-soluble, it is not stored in our bodies. Any excess is excreted out, so we need a daily fresh supply. Green leafy vegetables are rich in folate.

Folate is best known as the vitamin critical in pregnancy to prevent birth defects such as the neural tube defect—spina bifida, and to promote proper brain development. It also lowers homocysteine levels. High levels of homocysteine during pregnancy may increase the risk of the child developing brain disorders that may be later diagnosed as schizophrenia.[1, 2]

Poor diet may explain why some people with symptoms of schizophrenia are helped with folate supplementation, but their genes may explain why some people even with a healthy diet may need supplementation.

From an article in Medical News Today[3]:

According to Dr. Goff, whose pioneering research identified a link between low blood levels of folate and negative schizophrenia symptoms, folate is involved in many different chemical pathways in the brain, including keeping levels of the amino acid homocysteine low. When homocysteine levels are too high, this interferes with the functioning of receptors located all over the brain -- called NMDA ( N-methyl-D-aspartate) receptors -- that are critical to learning, memory, brain development, and general neural processing.

Dr. Goff's team are looking at two genes: GCPII (glutamate carboxypeptidase II), which controls the absorption of folate and may be deficient in people with schizophrenia, and MTHFR (methylenetetrahydrofolate reductase), which activates folate for use in the brain. They are hoping to eventually be able to determine in advance, which people need the folate supplementation.

The article has yet more promising insight:

“Dr. Roffman's team is looking at the combination of MTHFR and another gene -- COMT (catechol-O-methyltransferase) -- that affects dopamine levels in the brain. Although the two genes have separately been associated with schizophrenia, Dr. Roffman's just completed study finds that when these genes interact, a specific subset of patients is at greater risk for cognitive impairment.

In individuals who carry the risk variants of both MTHFR and COMT, lower-than-normal levels of dopamine in the part of the brain called the prefrontal cortex may cause problems with information processing and working memory. Using functional neuroimaging, Dr. Roffman and his colleagues also found that the same combination of MTHFR and COMT variants were associated with abnormally low activity in the prefrontal cortex.

"We now have the techniques to determine how genes combine to produce schizophrenia symptoms," Dr. Roffman explained. "As we gain a better understanding of individual biogenetic pathways, we can identify high-risk groups and those most likely to benefit from specific treatments."

In one study of allele variants, it showed, as is often the case, some mutations are more severe and less correctable than others, and having multiple defective alleles cause a more severe condition: "These results suggested that multiple less-frequent alleles, in aggregate, might significantly contribute to metabolic dysfunction."[^]

Labs for MTHFR genetic testing:

• 23 and Me -- you can get a plethora of DNA information for just $99.
• There is even a methylation analysis site for the 23andMe results: Genetic Genie - Methylation and detox analysis from 23andMe results
• Also, see: Kimball Genetics - MTHFR DNA Test.
• For others, look for "Nutritional Genetics," "Nutritional Genomics", or "NUTRIGENOMICS."

But, you can also simply check for a deficiency in methylated folate (B9) and methylated cobalamin (B12) via labs such as SpectraCell or Genova Diagnostics - NutrEval.

Prescription bioavailable (methylated) B vitamins are available:

• Metanx - In addition to the methylated folate (B9), contains methylated cobalamin (B12) and pyridoxal-5'-phosphate (P5P - an activated form of B6).
• Deplin - Contains only the methylated folate (B9)

However, there are also brands of methylated folate and vitamin B12 available without a prescription, such as MetaFolin by Solgar and L-5-MTHF by Designs for Health and Methylcobalamin from Pure Encapsulations.

There are many other (at least 25 genetic errors already identified) that prevent methylation of folic acid--which is actually a complex process: Here is Folate Metabolism There are therefore other theories about enhancing the body's own ability to methylate, involving histamines and orthommolecular treatment, but that is too involved to go into here. You may want to investigate it yourself.

Drugs (medications) that deplete folate/folic acid (Vitamin B9) include (see link for specifics):

• Antacids (Sodium Bicarbonate) 
• Anti-inflammatory Medications (5-Aminosalicylic Acid Derivatives, Inhalant, Systemic, and Topical Corticosteroids, Nonsteroidal Anti-inflammatory Drugs (NSAIDs), Salicylates)
• Antibiotic Medications 
• Anticonvulsant Medications 
• Antidiabetic Medications 
• Birth Control Medications 
• Cholesterol-Lowering Medications (Bile Acid Sequestrants) 
• Diuretics 
• Ulcer Medications

Link: Drugs that Deplete: Vitamin B9 (Folic Acid)
 

The take home lessons from all this are:

• These B vitamins are critical to neurological health.
• Some people have a methylation problem, or other metabolic problem causing a "functional nutritional deficiency."
• Some people need extra vitamin supplementation due to medications they are taking.
• Many people need methylated and activated forms of B6, B12 and folate.

Read More (Off-site):

• Dr Lyle Rawlins on MTHFR

Additional Related Reading (On-Site):

• Brain Health: Nutrition and Epigenetics
• Brain Health: The Gluten (Dis)Connection
• Brain Health: Omega-3 Fatty Acids ("Fish Oil")
• Genetic Links to “Developmental”, “Mental”, “Auto-Immune” and other Medical Disorders
• Important Links to Help Our Children
• Inflammation of Body and Brain
• The Stress Connection: Meeting Hormonal, Nutritional, and Metabolic Needs
• Childhood-Onset Schizophrenia Has High Rates of Comorbid Diagnoses Including Autism and ADHD
• Some Known Medical Causes of “Mental” Symptoms?

References:

• [^]The prevalence of folate-remedial MTHFR enzyme variants in humans
• Elevated Prenatal Homocysteine Levels as a Risk Factor for Schizophrenia (Archives of General Psychiatry)
• Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia?Picker JD, Coyle JTHarv Rev Psychiatry. 2005 Jul-Aug ; 13(4): 197-205
• NARSAD Researchers Identify Specific Genes And Family Traits Linked To Schizophrenia, Bipolar Disorder And Depression

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Genetics and Epigenetics:

• Specific Genes Inherited from Both Parents May Lead to Type of "Schizophrenia" (How schizophrenia can skip a generation)
• What are some genetic causes of psychosis?
  
• What is Epigenetics
  
• Brain Health: Nutrition and Epigenetics
  
• Mitochondrial Dysfunction and Psychiatric Symptoms

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Last Updated:  11 May 2013