Methylation and Nutrition

We’ve been on a long series about Methylation and how an individual’s nutrition can affect the outcome of their health. Here’s a quick review of MTHFR:

MTHFR-baucom-institute

Once the MTHFR tests shows (+) variants exist, what else can the health provider do to effectively treat the patient?

MTHFR-solutions-baucom-institute

So, what are you doing as a patient to take control of your health in relation to genome testing and restorative care with a physician that understands the impact of these aspects?

As a medical practitioner, are you having your patients tested for this all important genome so that they can be more proactive with their health and prevent disease?

Autism and Impaired Methylation: PMhx Case – Chris

From the last blog we presented impaired methylation and the connection to autism. This week, we look at a specific case where a subject, named Chris, was given treatment through nutrition and supplements.

  • Treatment: Elimination diet 6 weeks followed by no gluten or cow dairy.autism-baucom-institute

  • EPA/DHA liquid

  • chewable muti-vitamins (organic)

  • Probiotics c FOS

  • B12/5mthf, B6, mg glycinate, Nac

  • Phospho serine at  Hs

The symptoms resolved! Although a few minor issues with dyslexia continued, Chris integrated back into school after his mom took him out of school and home schooled him for a year until she could control his diet.  Methyl-folate and methyl-B12 were added this past year which helps energy and support detoxification in Phase II of the liver function.

nutrition-autism-baucom-instituteINTERVENTION 1: Supplementation with folinic acid and betaine

Although supplementation was effective in normalizing the methionine cycle metabolites to the concentrations in the control subjects, the intervention significantly improved but did not normalize tGSH or GSSG concentrations or tGSH:GSSG

INTERVENTION 2: Supplementation with folinic acid and betaine and Methyl vitamin B12

The addition of injectible methylcobalamin (intervention 2) did not alter the mean concentrations of methionine, SAM, SAH, or homocysteine beyond the alterations induced by the intervention with folinic acid and betaine. However, relative to intervention 1, the addition of injectible methylcobalamin further decreased the concentrations of adenosine and GSSG and further increased the concentrations of methionine, cysteine, and tGSH and SAM:SAH and tGSH:GSSG.

Autism and Impaired Methylation

  • epigenetics-autism-methylation-baucom-instituteAn increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.

  • Children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione.

  • Consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione).

Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with Autism 1 From the Department of Pediatrics, University of Arkansas for Medical Sciences, and the Arkansas Children‘s Hospital Research Institute, Little Rock, AR (SJJ, SM, and SJ); Niagara Falls, NY (PC); Colden, NY (LJ); Gaylor and Associates, LLC, Eureka Springs, AR (DWG); and Edison, NJ (JAN)2 Rep

PMhx – case:autism-methylation-baucom-institute

  • 6 years old
  • HM hx of severe anxiety,
  • unable to perform in class,
  • crying,
  • restless,
  • insomnia,
  • ADD,
  • dyslexia
  • small bumps on cheeks and upper arms mom describes as acne..

The mother of the child took him to the doctor to medicate him for anxiety and for a referral to a special education program. The mother was considering home schooling due to the severity of the child’s anxiety. This testing was done in addition:

  • Labs:  HLA Dq2/ Hla Dq8 negative

  • Food allergy test + gluten, wheat, dairy, honey, yeast, and some other minor antibodies (leaky gut).

  • MTHFR: c677T+/A1298C+

Stay tuned for the results on our next blog.

Case Study: Susan

  • 49 yo CF recent dx of Stage II Breast Ca hormone Rec +,s/p partial mastectomy, body-case-study-baucom-instituteradiation, irregular periods, shingles, intolerant of Fereston due to Headaches, constipated.  Hx of fibroids, heavy periods, fibrocystic breast. G2P2

  • nl vitals,   Estradiol 26.8pg/ml (0-32.2 menopause range)

  • Sed rate 22 (0-20)

  • Cbc, chem, thyroid panel cholesterol wnl

  • Vit D 153 (30-100)

  • GGT 15   Uric Acid 3.2

  • Glutathione 992

  • MTHFR C677+/A1298C+

  • Cytokine: base Il-6++, IL-17+, IL-12–,IFN gamma ++, TNF-a ++, IL-4++, IL-5–, IL-10++, IL-8++, G-CSF++

How would you approach treatment of this patient?

Spectracell-Methylation-Susan-Baucom-Institute

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