Do you deal with Chronic Fatigue, Fibromyalgia, Depression?

by Les Cole, MD & Delene Cole, LMFT

Methylation is the most common biochemical reaction in your cells.

This is because methyl groups contain a single carbon atom (1 carbon & 3 hydrogens = a methyl group). Carbon is the essential building block of all organic molecules, of which 99% of your body is composed. So lengthening and shortening the molecules that make up your body by 1 carbon at a time is critically important to your health and life.

The methyl groups come from vitamin B-12 (which is what makes it so important) and are transferred to folate (vitamin B-9, which is what makes it so important) to then contribute the methyl group to all those important biochemical reactions in your cells that keep them and you healthy and alive.

A critical enzyme in this methylation pathway is called Methylenetetrahydrofolate reductase (MTHFR) and the Gene that codes for this enzyme has a high frequency of mutation that significantly reduces your ability to methylate if you have this genetic mutation. And you will see below that you have a high likelihood of having this mutation.

The Importance of MTHFR and It’s Mutations

Functions of Methylation:

Production of Neurotransmitters:

• Dopamine (motivation, pleasure)
• Norepinephrine (excitement)
• Epinephrine (Hormone)
• Serotonin (feeling at home, comfort)
• Melatonin (sleep, circadian rhythm)
• Acetylcholine (memory, concentration, clarity)

DNA Synthesis

• Repair DNA
  • Prevent Cancer
  • Prevent cells from dying
• Produce DNA
  • Generate Stem Cells to replace dying cells

Cellular Command Central & Epigenetics – turns on & off all genes allowing your body the ability to respond to its internal & external environment and is stimulated by

• Hormones
• Food
• Toxins
• Other

• Detoxification – Methylation is a big part of Phase 2
• Amino Acid Metabolism
• Lipid Metabolism
• Choline production for Acetylcholine and important lipids like Myelin
• Clotting
• And More

 MTHFR Mutations & Their Relevance

• There are over 6500 articles in PubMed about MTHFR
• MTHFR genes code for enzymes that take a methyl group (carbon & 3 hydrogens) from B12 (Major reason B12 so important – methyl donor) and sticks it on folate (reason folate so important), which then carries it on to do so many things in the body (see above list)
• There are 2 sets of genes and each gene has 2 copies – one from Mom & one from Dad
  • C677T gene has 2 copies
    • The normal gene has a C (cytosine) at the 677 position
    • The abnormal (mutated, SNP) gene has a T (thymidine) at the 677 position
    • The MTHFR Enzyme produced from the abnormal T gene has a decreased function (ability to “Methylate”) of about 40%
    • Therefore, your ability to methylate is:
      • 60% if you have C/T
      • 20% if you have T/T
    • A1298C gene has 2 copies
      • The normal gene has a A (adenine) at the 1298 position
      • The abnormal (mutated, SNP) gene has a C (cytosine) at the 1298 position
      • The MTHFR Enzyme produced from the abnormal C gene has a decreased function (ability to “Methylate”) of about 10%
      • Therefore, your ability to methylate is:
        • 90% if you have A/C
        • 80% if you have C/C
      • If you have a combination of C/T (from the C677T) and A/C (from the A1298C) your ability to methylate is about 50%
      • These percentages vary according to different researchers and this is a very simplified explanation
    • Approximately 50% of people have 1 MTHFR genetic mutation

 Conditions Caused by MTHFR Mutations

• ADD/ADHD
• Addictive Behaviors
• Alcoholism
• Allergies
• Alzheimer’s
• Anxiety
• Atherosclerosis
• Autism
• Bipolar
• Cancer
• Chemical Sensitivity – diminished detox
• Chronic Fatigue Syndrome
• Chronic Viral Infection
• Cleft Palette
• Congenital Heart Defects
• Dementia
• Depression
• Diabetes
• Down’s Syndrome
• Endothelial Dysfunction
• Erectile Dysfunction
• Fibromyalgia
• Heart Disease
• Immune Deficiency – White blood cell function
• Infertility
• Insomnia
• Multiple Sclerosis – production of Choline for Myelin sheath
• Neural Tube Defects
• Neuropathy
• Parkinson’s
• Pulmonary Embolism
• Recurrent Miscarriage
• Schizophrenia
• Spina Bifida
• Thyroid Dysfunction

 Drugs to avoid with MTHFR Mutation

• Antacids (depletes B12)
• Proton Pump Inhibitors (depletes B12)
• Cholestyramine (depletes B12 & folate)
• Cholestipol (depletes B12 & folate)
• Methotrexate (inhibits DHFR: Folate->THF)
• Nitrous Oxide (Inhibits MTR – Methionine Synthase)
• High Dose Niacin (depletes SAMe & inhibits pyridoxyl Kinase
• Theophylline (inhibits pyridoxyl Kinase = active B6)
• Cyclosporin (decreases renal function & increases Homocysteine)
• Metformin (depletes B12)
• Phenytoin (folate antagonist)
• Carbamazepine (folate antagonist)
• Oral Contraceptives (deplete B12 & folate)
• Antimalarials (inhibits DHFR)
• Trimethoprim (inhibits DHFR)
• Ethanol
• Bactrim (inhibits DHFR)
• Sulfasalazine (inhibits DHFR)
• Triamterine (inhibits DHFR)

 To make an appointment to be evaluated for your MTHFR status or to determine the best course of treatment for you MTHFR status, call 727-202-6807.