Catechol-O-Methyltransferase

Spectracell Methylation Presentation.pptx

 

  • Involved in phase II metabolism of hydroxy-estradiols
  • Involved in metabolism of xenobiotics
  • Involved in metabolism of chocolate
  • Involved in metabolism of caffeine by-products (catechins)
  • Involved in metabolism of excitatory neurotransmitters

Spectracell Methylation Presentation.pptx (1)

  • S-adenosylmethionine and magnesium dependent
  • Linked to estrogen
  • imbalance disorders
  • Is involved in hyperhomocystinemia in Parkinson patients on L-dopa
  • Is linked to psychiatric disorders

Spectracell Methylation Presentation.pptx (2)

Methionine Synthase Mutations

  • 250px-PBB_Protein_MTR_image_Baucom_InstituteMutations in the MTR gene have been identified as the underlying cause of methylcobalamine deficiency.

  • This may lead to megaloblastic anemia as seen in elevated MCV in the patients CBC.

  • Patients may actually have high levels of B12 in the serum as the Cobalamine is not converting to Methylcobalamine.

  • May compound mutations in MTHFR

Mega Dosages of Me-B12B12_b-s

  • Supplementation with megadoses of MeB12 has been advocated to protect the cognitive function of patients suffering from:

  • Chronic Fatigue

  • Stroke

  • Depression

  • Alzheimer’s disease Neurological diseases

Folate Cycle Nutrients, Homocysteine, and Transsulfuration

  • Transsulfuration is the conversion of Homocysteine with the co-factors B6 and Serine to Cystathionine.

Homocysteine-Damage-Ladd-McNamara

  • Cystathionine is then converted to Cysteine which is one of the three amino acids that compose Glutathione.
  • Polymorphisms in Cysta beta-synthase may affect the rate of conversion of Cystathionine to Cysteine.
  • Cysteine is thought to be the rate limiting step in the formation of Glutathione.

glutathione-structure-baucom-institute (2)

 

What are the Effects of MTHFR?

MTHFR mutational effects include:MTHFR-DNA-Effects-Baucom-Institute

  • chronic low glutathione
  • leaky gut and food allergies
  • chronic viruses
  • high serum B12 levels
  • low serotonin and melatonin
  • high serum ferritin and HFE mutation
  • Thalassemia and hepatorenal failure
  • FSG and renal failure
  • autoimmunity frequency in women
  • chronic dysbiosis/chronic yeast infections
  • estrogen dominant cancers
  • subtype and elevated homocysteine
  • ADD/bipolar/PMS/Chronic Fatigue/Fibromylagia
  • tongue/fingernails/thin hair
  • vericose veins/spider veins
  • hypercoagulopathy/infertility
  • elevated testosterone in men/PCOS in women
  • acne, fibroids, Endometriosis, Menometorrhagia
  • depression when on OCPs
  • exacerbation of menopausal symptoms on BHRT
  • elevated uric acid and elevated ammonia levels
  • gut barrier and dysbiosis
  • CANCER
  • estrogen dominance and obesity (estrogens effects on insulin and the insulin receptor and adiponectin)

 

A1298C Variant

A1298C – a mutation from adenine to cytosine at position 1298 within the gene. These variants lead to amino acid differences in the protein that reduces its ability to function.

1298:genes_MTHFR_baucom_institute

  • AA-normal homozygous
  • AC or CC – one or two variant copies
  • about 30% of the population
  • not associated with increased risk
  • associated with increased risk if found together with a 677 variant

Severe MTHFR deficiency:

  • Severe MTHFR deficiency is rare (about 50 cases worldwide) and caused by mutations resulting in 0-20% residual enzyme activity.
  • Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 15 (3): 280-7
  • These patients exhibit:
  1. developmental delay,
  2. motor and gait dysfunction,
  3. seizures,
  4. neurological impairment and
  5. have extremely high levels of homocysteine in their plasma and urine as well as low to normal plasma methionine levels.

Epigenetic_mechanisms_MTHFR_methylationBottom line:  If one leads a lifestyle which is unhealthy (smoking, high stress, toxic exposures) and consumes an unhealthy diet (refined carbs, processed meats, saturated fats), having a heterozygous A1298C mutation may contribute to cardiovascular disease, depression, fibromyalgia and others.

Possible symptoms associated with A1298C MTHFR mutations:

  • hypertension
  • delayed speech
  • muscle pain
  • insomnia
  • irritable bowel syndrome
  • fibromyalgia
  • chronic fatigue syndrome
  • hand tremor
  • memory loss
  • headaches
  • brain fog

Possible signs associated with A1298C MTHFR Mutations:

  • elevated ammonia levels
  • decreased dopamine
  • decrease serotonin
  • decreased epinephrine and norepinephrine
  • decreased nitric oxide
  • elevated blood pressure
  • muscle tenderness
  • ulcers
  • pre-eclampsia

Possible conditions associated with A1298C MTHFR mutations:

  • fibromyalgia
  • chronic fatigue syndrome
  • autism
  • depression
  • insomnia
  • ADD/ADHD
  • irritable bowel syndrome
  • inflammatory bowel syndrome
  • erectile dysfunction
  • migraine
  • Raynaud’s
  • cancer
  • Alzheimer’s
  • Parkinson’s
  • recurrent miscarriages

Frequency of MTHFR Polymorphisms

30-40% of Americans are found to have either a single or double polymorphism of either C677T or A1298C.

  • There is ethnic variability in the frequency of the T allel-frequency in Mediterranean/Hispanics>Caucasians>Africans/African-Americans (Worldwide distribution of a common methylenetetrahydrofolate reductase mutation. Am J Hum Genet 62 (5): 1258-60)
  • Higher frequency in chronic disease: Autoimmune diseases, diseases of the gut, Fibromyalgia, Chronic Fatigue, Chronic Retroviruses, Cancer, Hormone dysregulation, Mood issues, Cardiometabolic patients.

C667Tpolymorphtandem-baucom-institute

  • There is a mutation from cytosine to adenine at position 677 within the gene.
  • Possible genotypes?
  • 677-CC, CT, or TT
  • CC-homozygous normal
  • About 45% of the population
  • No increased risk associate
  • CT-on variant copy
  • About 45% of the population
  • Some reduced enzymatic activity, alone not associated with increased risk
  • TT-two variant copies
  • About 10% of the population
  • Increased risk for elevated homocysteine level and associated complications

Homocysteine & Vascular Disease

Pathophysiology of Homocysteine:

1. Interference with normal thrombolysisHomocysteine-Damage-Ladd-McNamara

  • decreased antithrombin III activity
  • Activation of factor V or XII
  • Inactivation of protein C
  • Promote binding of Lp(a) to fibrin
  • Platelet inhibition (interaction with nitric oxide)

2. Promote SMC proliferation

3. Promote LDL oxidation

4. Direct toxicity to endothelium

Genetic and Dietary Determinants of Serum Homocysteine Concentrations:

Genetic -

  • Cystathionine-beta-synthase deficiency
  • Methionine synthase deficiency
  • MTHFR deficiency
  • Defective absorption of B12 or folate
  • Prevalence – 30% Female V. 25% Male

lowering-homocysteine-levels-naturally-baucom-instituteNutritional -

  • Vitamin B6
  • Vitamin B12
  • Folate

Risks Associated with MTHFR Variants/High Homocysteine:

  • Cardiovascular Disease
  • Cerebral Vascular Disease (stroke)
  • Venous and Arterial Thrombosis
  • Methotrexate Toxicity for Cancer Therapy

 

Methylation

Methylation can turn genes on or off.

Some nutrients affect the methylation process quite dramatically. Methylating factors like B12, B6, MD, Zinc monitor specific methylation reactions.

Methylation_DNA_Baucom_InstituteMTHFR

What is MTHFR?

  • Methylenehydrofolatereductase is an enzyme responsible for converting 5, 10- methylenetetrahydrofolate to the product: 5-methytetrahydrofolate (5-MTHF)
  • Certain mutations in the gene coding for MTHFR produce an enzyme that has reduced activity
  • Reduced activity can lead to elevated levels of homocysteine especially when folate levels are low
  • MTHRF genotyping can provide information about potential causes of elevated homocysteine and how to address it
  • 5-methyltetrahydrofolate is involved in the metabolism of folate and homocysteine
  • The product of the reaction catalyzed by MTHFR converts homocysteine (a potentially toxic amino acid) to methionine (a useful and necessary amino acid)

Testosterone and Heart Disease

low_testosterone_heart_disease_baucom_instituteFor years, we’ve known that low testosterone for men has created many issues but now there is evidence that it is linked to heart disease. Here are a few of the findings (JAMA, Aging Male, Geriatrics, European Heart Journal,Circulation, JACC, JCEM, Endocrinology):

Low Testosterone and Heart Disease

  • Men with coronary heart disease had significantly lower total testosterone.
  • A study showed a correlation between lower testosterone levels and conditions associated with cardiovascular disease.
  • Another study showed that men with coronary heart disease had significantly lower levels than the control group.
  • Low testosterone levels have been shown to be associated with atherosclerosis in men.

High Estrogens and Heart DiseaseHEART-DISEASE-low testosterone-baucom-institute

  • A study showed that elevated circulating estradiol is a predictor of progression of carotid artery issues.
  • High estradiol levels in men were associated with acute myocardial infarctions.
  • Elevated levels of estrogen in men are associated with an increased risk of heart disease.

Testosterone Replacement and Heart Disease

  • A study showed that with an increase of testosterone there was a 14% drop in risk of death.
  • A study revealed that testosterone replacement was associated with a decrease in HDL-C and lipoprotein a.
  • Introduction of testosterone increases coronary artery blood flow in men with coronary heart disease.
  • Testosterone replacement has shown to decrease inflammation and lower total cholesterol.

Do you know a male in his 40′s or older with a history of heart disease in his family? Share these studies and encourage him to seek medical attention, particularly a doctor educated on the connection of hormones and disease prevention.

If you are a medical professional, what are your findings on the connection of low testosterone and heart disease?

What Does Gluten Do?

Rose Family Fall 2013 074Maddy’s story begins like so many others – born into a middle class family in the midwest, she has had the privileges of most teenagers her age and is now a freshman Criminal Justice major at Olivet Nazarene University in Bourbonnais, Illinois.

Maddy has found that eating is a rather difficult thing, especially at college, even though they have a gluten-free menu, because of all the temptations on the regular menu. She has a gluten intolerance, on the extreme end. It makes it hard to take care of herself away from home, yet she’s working hard to do it, realizing that eating gluten is just not worth the pain.

Maddy says, “First off, you can tell as you are eating it you start to feel full but you aren’t sure if you are bloated or if you are actually getting full. After you’ve eaten, about only 30 minutes later, you start to get indigestion. You get really bad issues that come with extreme gastrointestinal stress, extreme nausea, heavy fatigue, you become moody and irritable and it can even result in vomiting. You also have energy depletion and headaches that include throbbing, making it hard to focus. Speaking of focus, your attention span is decreased, making it hard to work, study, pay attention in class, and go through daily activities that would normally not be an issue for you. You also feel heavy, muggy, miserable, and all around sickly. I also get hot and cold flashes sometimes – that’s when I know it’s really severe. It wasn’t until I talked to Dr. Baucom about my symptoms that I realized why I was having trouble every time I ate. She had me read various articles on gluten, making me realize I was on the extreme end of this issue.”

What is gluten? It is a protein that has been engineered as a component of wheat that provides the elastic qualities for baked goods. But the protein is also difficult to digest. And even a healthy intestine does not completely break gluten down. For those with celiac disease, the undigested gluten essentially causes the body’s immune system to lash out at itself, leading to malabsorption, bloating and diarrhea — the classic gastrointestinal symptoms — but also, at times, joint pain, skin rashes, etc.

Joseph A. Murray, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota says of gluten-intolerance, “It truly has become more common.” Comparing blood samples from the 1950s to the 1990s, Murray found that young people today are nearly five times as likely to have celiac disease, for reasons he and others researchers cannot explain. And it’s on the rise not only in the U.S. but also in other places where the disease was once considered rare, like Mexico and India. “We don’t know where it’s going to end,” Murray says.

Mark Hyman, M.D. practicing physician and founder of The UltraWellness Center is a pioneer in functional medicine. He’s done some extensive study on the effects of gluten. He says that a review paper in The New England Journal of Medicine listed 55 “diseases” that can be caused by eating gluten. (iv) These include osteoporosis, irritable bowel disease, inflammatory bowel disease, anemia, cancer, fatigue, canker sores, (v) and rheumatoid arthritis, lupus, multiple sclerosis, and almost all other autoimmune diseases. Gluten is also linked to many psychiatric (vi) and neurological diseases, including anxiety, depression, (vii) schizophrenia, (viii) dementia, (ix) migraines, epilepsy, and neuropathy (nerve damage). (x) It has also been linked to autism.(ix)

Gluten sensitivity is actually an autoimmune disease that creates inflammation throughoutgluten-warning-baucom-institute the body, with wide-ranging effects across all organ systems including your brain, heart, joints, digestive tract, and more. It can be the single cause behind many different “diseases.” To correct these diseases, you need to treat the cause–which is often gluten sensitivity–not just the symptoms.

How can you know if you are gluten-intolerant? Try going off food that causes the symptoms – breads, pastas, sauces made with flour, chips, french fries, chocolate, anything with wheat or barley in it, etc. Even body and hair care products can have gluten and can be absorbed through the skin. See how you feel. If you have less symptoms like intestinal distress, bloating, etc. you know that gluten was at least a culprit. Most importantly seek a medical professional educated in restorative medicine or naturopathic education. Unfortunately, most MD’s are not aware nor educated on the effects of gluten, although society’s awareness is pushing the medical community to become more aware.

How do you relate to Maddy’s story? What symptoms cause you to think you may be gluten intolerant?