Xenobiotic Effects on COMT

A xenobiotic is a foreign chemical substance found within an organism that is not normally, naturally produced by or expected to be present within that organism. It can also cover substances which are present in much higher concentrations than are usual.41_SchemaRTS_Eng

  • In humans, 2-Oh and 4-Ohestradiol (catechol estrogens) are rapidly O-methylated to form monomethyl ethers catalyzed by COMT and S-adenosyl-L-methionine.

  • Xenobiotics may strongly inhibit COMT-mediated
    O-methylation of catechol estrogens by xenobiotics and may facilitate the development of estrogen-induced tumors.

  • Xenobiotics may therefore deplete intermediates in the Folate cycle.  Environmental burden of Xenobiotics may create a higher need for methylation support.

Catechol-O-methyl_transferase_baucom-instituteAbstract: COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk - Goodman JE, Lavigne JA, Wu K, Helzlsouer KJ, Strickland PT, Selhub J, Yager JD; Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.

  • Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor.

  • Several studies have indicated that the val108met COMT polymorphism, which results in a 3-4-fold decrease in activity, is associated with increased breast cancer risk.

  • Folate, whose intake levels have also been associated with breast cancer risk, and other micronutrients in the folate metabolic pathway influence levels of SAM and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation of SAM.

  • Because these micronutrients have been shown to alter SAM and SAH levels, we hypothesized that they could also affect COMT-catalyzed CE methylation.

  • Although measurements of SAM and SAH were not initially collected, a secondary analysis of data from two nested case-control studies was performed to examine whether serum levels of folate, vitamin B12 (B12), pyridoxal 5′-phosphate (PLP), cysteine and homocysteine, in conjunction with COMT genotype, were associated with breast cancer risk. COMT(HH) (high activity COMT homozygote) breast cancer cases had statistically significantly lower levels of homocysteine (P = 0.05) and cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMT(HH) controls. In contrast, COMT(LL) (low activity COMT homozygote) cases had higher levels of homocysteine than COMT(LL) controls (P = 0.05).

  • No associations were seen between B12, COMT genotype, and breast cancer risk. An increasing number of COMT(L) alleles was significantly associated with increased breast cancer risk in women with below median levels of folate (P(trend) = 0.05) or above median levels of homocysteine (P(trend) = 0.02). These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.

These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk.

Case Study: Susan – Treatment

Methylation-xenoestrogens-baucom-institute

Methylation-nutrition-estrogen-metabolism-baucom-institute

 

  • Treatment: 28 day   detox, gluten, diary, soy free, with  protein smoothie (rice) due to low body weight.
  • Di-indole methane and 3 indole-carbinol for estrogen balance, NAC,(glutathione)
  • Trimethyglycine/Methyl -folate & B12 for methylation support
  • L-theanne/Gaba, 5-HTP to improve sleep and pain control
  •  Co-Q10 support
  • Selenium/Lipoic acid,vit E for anti-oxidant support
  • High concentrate EPA/DHA  Magnesium Glycinate 200mg qhs for alkaline, mineral, and bowel support
  • Probiotics, 50 bill/ FOS
  • Exercise daily, check urine ph goal> 6.6.  Sauna at the gym, alkaline diet, Xenoestrogen awareness!

Susan’s response: “I feel the best that I have felt in years. This is miraculous! I sleep deeper than ever, there are no hot flashes, I’m exercising because I have ENERGY, and my husband says I’m back again because I’m SASSY again!”

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)

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)

 

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

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)

There’s a “Pause” for Men Too!

Male-Andropause-BaucomInstitute

Male Andropause. You may have never heard of it, especially if you are a woman under 30. However, it is a very real and prevalent issue for men, especially after age 40. Let’s start with what it is and then what to do about it.

To put it simply, andropause is the steady decline in the hormone testosterone. It usually effects men around the age of 40 and continues for a longer period of time, possibly lasting for decades, than menopause with women which can have more extremeandropause_graph effects but over a shorter period of time. Most men think these symptoms are just a part of aging and that they should just accept their fate. They couldn’t be more wrong. In fact, by age 45-55 men can experience the same types of effects similar to menopause.

The effects can include changes in attitude and mood, mild depression, fatigue, lower sex drive, reduced erections, weight gain in the middle, loss of energy, and reduction in physical agility because of the loss of muscle mass.

So what’s the answer? It seems inevitable. It stands to reason that if the loss of testosterone is the cause then the replacing of testosterone would be the answer. True, but how do you replace an organic chemical that the body itself reproduces? This is where the answer and the problem both lie, as if two sides to the same coin.

Hormone therapy has become more common in treating the effects of menopause in women. However, the side-effects have become too dangerous, like when men take Viagra to enhance their sexual performance. It is not a natural component; therefore the body cannot assimilate it without side effects.

Bio-identical hormones have become preferable due to their natural effects on the body. These same types of bio-identical, natural hormones are now available to men as well. The bio-available testosterone not only increases muscle mass and improves a guy’s general well-being, it also lowers cholesterol, enhances libido and sexual energy, and helps prevent pre-mature heart disease.

If you have these symptoms from aging, even if you are just in your 40’s, don’t wait until they are worse. Contact us today at The Baucom Institute to learn from your own “Age Management Plan” what you need at your age.

What are some symptoms you have noticed in yourself or someone else you care about? We would love to hear from you.

Am I Losing It or Does Anybody Feel This Way?

Portrait of a middle aged woman sitting in a chair and looking sad

Hormones are vital in protecting and telling the body what to do. An important part of age management medicine is measuring and, where necessary, supplementing important hormones that decline, but contribute to longevity. Often patients come to the Baucom Institute with complaints of fatigue, decreased libido, poor concentration, and weight gain despite proper exercise and nutrition. The missing piece to their puzzle is often hormonal restoration and balance. When we restore and balance hormones to their youthful level, we use bio-available hormones. These bio-available hormonal messengers are the same as our bodies produce and can be utilized as natural restorative factors to qualify aging. Hormone restoration and balancing requires precise testing and monitoring. It should only be performed under the medical management of a qualified physician.

COMPARING HERBS AND BIO-AVAILABLE HORMONES

Bio-available hormones require a prescription by a physician. Often people confuse the difference between bio-available hormones and herbs that stimulate hormones. Herbs, or holistic naturopathic medicine, can be a contributor to the wholeness of a being, but instead of using naturopathic herbs to simulate what these hormones can do, as physicians we can have these hormones compounded by a pharmacy. In today’s world of medicine, many pharmaceutical companies are also now beginning to produce bio-available hormones.

A PERSONALIZED HORMONE BALANCING AND RESTORATION PLAN

Hormones work in concert with one another. The vital glands that send these important messengers throughout our brain and the rest of our body do so in a synchronized balanced manner. It’s our job, at the Baucom Institute, to identify if hormone balancing and restoration is appropriate and, if so, format for that patient a hormonal balancing and restoration plan designed to achieve increased vitality and youthful exuberance.

Learn More about Bio-Available Hormones

What symptoms do you struggle with?

One Patient Among Many

familyMRGrad2013Hi. My name is Beth Rose. I am one patient among many.

I’m one patient among many others who see Dr. Karan Baucom and who has seen significant changes from diagnosis and prescribing changes for me in my daily life.

I began to see “Dr. B.” a few months ago because I was having several symptoms that began to worry me about my health. I have been a fairly healthy person throughout my 52 years.

I was very active when I was younger up until I had my children. Like a lot of moms, our kids take precedence, and we forget about taking care of ourselves! Over the last 20 years I have begun to have aches and pains in my joints, fasciitis in my feet, increasing back pain, terrible heartburn especially at night, increasing fatigue, no energy for running around with my kids, and the last few months terrible pain after eating in my upper torso. I have felt a mess and, with working our business that my husband and I own, I know the stress of that has contributed to the issues.

I had talked to Dr. B. about my family’s health a lot but Dr. B. asked how I was doing. She knew I was under a great deal of stress and could see the fatigue and lack of energy. I made an appointment and soon was undergoing several tests, including a full blood workup, sonograms, and mammogram. When Dr. B. got the test results back, she sat me down and gave me the most thorough report I’ve ever heard about my health! I was amazed with all the information and how it all linked together. My hormone levels were out of whack, I had gallstones, there are nodules on my thyroid, and I have several food allergies among other issues. I was totally shocked.

With advice and direction as well as prescribing a vitamin and bioidentical hormone supplement regimen, I am beginning to feel good again. I have increasing energy and less fatigue each day. Even better, my outlook on life is much more positive, which I think that has everything to do with the hormonal balance.

I appreciate my family physician, who we have been going to since our children were babies, but Dr. Baucom, as my specialist in Restorative Medicine, has been a life changer for me personally. I’ve never seen anyone take so much time with their patients, not only to diagnose and treat but to also educate.

I’ve been through the “School of Longevity” at The Baucom Institute. I hope to graduate with flying colors in the few next the months to come!