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Methylation, MTHFR and Associated Diseases
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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.

Article History

Published: April 13, 2017

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