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Methylation, MTHFR and Associated Diseases by Les Cole, MD

Do you deal with debilitating Fatigue? Fibromyalgia? Depression?

Do you deal with debilitating Fatigue? Fibromyalgia? Depression?

 

Do you deal with Chronic Fatigue, Fibromyalgia, Depression?

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 likelyhood 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 Relavence

  • 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.

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