More than 50% of the population are affected by genetic mutations in the methylation pathway.1 The Methyl Detox profile provides greater insight into genetic variations of the following MTHFR, MTR, MTRR, COMT and AHCY pathways.Standard MTHFR genotyping only evaluates folic acid metabolism. The MethylDetox Profile makes it easy to understand the complicated methylation process by giving comprehensive insights into the functional status of the methylation pathway.
Methylation can play an important role in many chronic diseases. By understanding your genetics you can prevent and address these conditions with the right nutrition.
The MethylDetox Profile tests critical genes in the methylation pathway. By understanding your genes and how they impact methylation, you may prevent and address existing health problems with the right nutrition.
This profile provides greater insight into genetic variations of the following MTHFR, MTR, MTRR, COMT and AHCY pathways.
The MethylDetox Profile includes genetic markers involved in methylation and homocysteine metabolism provided in a detailed lab report with personalized commentary. Additionally, continued homocysteine testing enables easy monitoring of patient progress.
Genetic variations in this pathway are associated with elevated homocysteine levels, impaired methylation processes and limited detoxification capacity. 1, 3
As a result, these SNPs (single nucleotide polymorphisms) may contribute to accelerated aging, certain chronic diseases like cardiovascular disease and neurodegenerative disorders, impaired gene-regulation, poor drug clearance, and impaired neurotransmitter metabolism. 1, 3-21
Comprehensive testing for methylation and detoxification
The MethylDetox Profile gives more actionable information than MTHFR testing alone, giving you a more complete picture of your body’s methylation and detoxification. The MethylDetox profile includes suggestions for specific nutrient needs to address with practitioner guidance.
Standard MTHFR genotyping only evaluates folic acid metabolism. Scientific research reveals that a variety of genes are involved in maintaining methionine/homocysteine balance. Genetic variations (SNPs) in these important genes influence your methylation potential. Individual methylation is monitored using homocysteine levels. Important SNPs are included to evaluate your ability to methylate neurotransmitters, DNA, and toxins.
Who May Benefit from This Test?
Individuals with any of the following diagnoses or symptoms:
- Cardiovascular Diseases e.g. hypertension, coronary artery disease, stroke 4-10
- Neurological Disorders e.g. depression, dementia, Alzheimer’s disease, ADD/ADHD, ASD, chronic fatigue syndrome, migraine, insomnia 7, 10-17
- Metabolic Conditions e.g. metabolic syndrome, diabetes mellitus, kidney diseases, reduced ability to metabolize medications, multiple chemical sensitivity 10, 18-21
- Musculoskeletal Disorders e.g. osteoporosis 10, 22
- Eye Diseases e.g. macular degeneration 23, 24
- Cancer e.g. colorectal, breast, and others 1, 10, 25
What kind of Patient Is Methyl Detox Profile Order for?
Individuals with a manifestation and/or family history of:
- Cardiovascular disease
- Hypertension, coronary artery disease, stroke
- Neurodegenerative disorders
- Poor drug clearance
- Multiple chemical sensitivity (MCS)
- Chronic fatigue syndrome (CFS)
- Chronic metabolic disorders
- Metabolic syndrome
- Kidney or liver disease
- Musculoskeletal disorders
- Autism spectrum disorder
- Alzheimer’s Disease
What’s Being Tested in the Methyl Detox Profile
Homocysteine can also be done but is the only test requires a blood draw. This is an add on with extra cost.
Understanding Methionine and Homocysteine Balance
The primary purpose of methionine/ homocysteine balance is to ensure proper methylation by donating methyl groups for:
- DNA methylation (gene regulation)
- Regulation of neurotransmitters (e.g. epinephrine, norepinephrine, and serotonin)
- Detoxification of catecholamines from the environment
- Drug clearance (phase II liver detoxification)
- Homocysteine is also a precursor in the biosynthesis of L-cysteine for glutathione; glutathione is important for the detoxification of electrophilic compounds (metals).
- Elevated serum homocysteine is a widely accepted marker for methionine/homocysteine imbalance, which is a genetically controlled process. 28
Elevated homocysteine levels can lead to accelerated aging, cardiovascular disease and neurodegenerative disorders among others. 20, 21, 29
The Methyl Detox Profile includes
- 30 minute consult with Dr Hagmeyer.
The MTHFR gene’s purpose is to produce the important MTHFR enzyme in the body. This enzyme is an important part of maintaining optimal health. If the MTHFR gene has a variant, folate metabolism can be negatively impacted. Improper folate metabolism is implicated in many different diseases. 5, 6, 10, 26-29
MTR codes for the enzyme, methionine synthase (MS). MS converts homocysteine to methionine using methylated vitamin B12. variants in this gene significantly impact homocysteine metabolism, which can increase the risk for a number of chronic conditions such as cardiovascular diseases, metabolic and neurological conditions and certain cancers. 30
The MTRR gene codes for the important enzyme, methionine synthase reductase (MSR). Methionine synthase reductase is required for the proper function of methionine synthase (see MTR). Both genes act together to convert homocysteine to methionine. variants can be involved with the development of cancers, Parkinson’s disease, depression, hypertension and many others. 31-36
COMT is the major gene involved in methylation. It plays an important role in a variety of disorders, including estrogen-induced cancers, Parkinson’s disease, depression, hypertension and many others. COMT is also necessary for maintaining the proper balance of neurotransmitters with SAMe obtained from methionine. Genetic variants in COMT can result in various neurological problems and has also been associated with Autism. 31-36
AHCY is the only enzyme known to convert S-Adenosylhomocysteine (AdoHcy) to homocysteine. It is crucial that AHCY immediately converts AdoHcy to homocysteine and adenine in order to maintain optimal methylation potential. Studies show a link between variants in this gene with poor methylation potential and severe myopathies, developmental delays and hypermethioninemia.
Homocysteine is an amino acid that is involved in maintaining the methionine cycle. Elevated homocysteine levels are well known risk factors for chronic disease, particularly cardiovascular, diabetes and neurodegenerative disorders 7, 10, 37
1 Sharp L, Little J. Polymorphisms in Genes Involved in Folate Metabolism and Colorectal Neoplasia: A HuGE Review. Am. J. Epidemiol. (2004) 159(5):423–443.
2 Figueiredo JC, Grau MV, Wallace K, Levine AJ, Shen L, Hamdan R, Chen X, Bresalier RS,McKeown-Eyssen G, Haile RW, Baron JA, Issa JP. Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics, Dietary and Genetic Factors. Cancer Epidemiol Biomarkers Prev. 2009 April ; 18(4):1041- 1049
3 Watkins D, Rosenblatt DS. Update and new concepts in vitamin responsive disorders of folate transport and metabolism J Inherit Metab Dis. 2012 Jul;35(4):665-70.
4 Seshadri, N., Robinson, K. Homocysteine and coronary risk, Curr Cardiol Rep 1999; 1, 91-98.
5 Bautista LE, Arenas IA, Peñuela A, Martínez LX. Total plasma homocysteine level and risk of cardiovascular disease: a meta-analysis of prospective cohort studies. J Clin Epidemiol. 2002 Sep;55(9):8827.
6 Meleady R, Ueland PM, Bloom H et al.: Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: The European Concerted Action Project. Am J Clin Nutr 2003; 77:63–70.
7 Brosnan JT, Jacobs RL, et al. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol. 2004;51:405-413.
8 Papatheodorou L, Weiss N. Vascular oxidant stress and inflammation in hyperhomocysteinemia. Antioxid Redox Signal. 2007;9:1941-1958.
9 Osanai T, Fujiwara N, et al. Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: a possible linkage to homocysteine. Ann Med. 2010;42:79-86.
10 Brustolin S, Giuglian R, et al. Genetics of homocysteine metabolism and associated disorders. Braz J Med. Biol Res. 2010 January ; 43(1): 1–7.
11 Seshadri S, Beiser A, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002 Feb 14;346(7):476-83.
12 Plassman BL, Langa KM, et al. Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med. 2008;148:427-434
13 Oterino A, Toriello M, et al. The relationship between homocysteine and genes of folate-related enzymes in migraine patients. Headache. 2010;50:99-168.
14 Gokcen C1, Kocak N, Pekgor A. Methylenetetrahydrofolate reductase gene polymorphisms in children with attention deficit hyperactivity disorder. Int J Med Sci. 2011;8(7):523-8.
15 Sener EF, Oztop DB, Ozkul Y. MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders. Genet Res Int. 2014;2014:698574.
16 Beydoun MA, Gamaldo AA, Canas JA, Beydoun HA, Shah MT, McNeely JM, Zonderman AB. Serum nutritional biomarkers and their associations with sleep among US adults in recent national surveys. PLoS One. 2014 Aug 19;9(8):e103490.
17 Regland B, Forsmark S, Halaouate L, Matousek M, Peilot B, Zachrisson O, Gottfries CG. Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia. PLoS One. 2015 Apr 22;10(4):e0124648.
18 Haagsma CJ, Blom HJ, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis. 1999;58:79-84.
19 Desouza C, Keepler M, et al. Drugs affecting homocysteine metabolism: impact on cardiovascular risk. Drugs. 2002;62:605-616.
20 Foucher C, Brugère L, et al. Fenofibrate, homocysteine, and renal function. Curr Vasc Pharmacol. 2010;8:589-603.
21 Di Renzo L, Marsella LT, Sarlo F, Soldati L, Gratteri S, Abenavoli L, De Lorenzo A. C677T gene polymorphism of MTHFR and metabolic syndrome: response to dietary intervention. J Transl Med. 2014 Nov 29;12(1):329.
22 Lee SH, Kim MJ, et al. Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis in patients with Parkinson’s disease. Calcif Tissue Int. 2010;86:132-141.
23 Rochtchina E, Wang JJ, et al. Elevated serum homocysteine, low serum vitamin B12, folate, and age- related macular degeneration: the Blue Mountains Eye Study. Am J Ophthalmol. 2007;143:344-346.
24 Christen WG, Glynn RJ, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med. 2009;169:335-341.
25 Yager JD. Catechol-O-methyltransferase: characteristics, polymorphisms and role in breast cancer. Drug Discov Today Dis Mech. 2012 June 1; 9(1-2).
26 Ocal IT, Sadeghi A, Press RD. Risk of venous thrombosis in carriers of a common mutation in the homocysteine regulatory enzyme methylenetetrahydrofolate reductase. Mol Diagn 1997; 2: 61–68.
27 Nelen WL, Blom HJ, Thomas CM, Steegers EA, Boers GH, Eskes TK. Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr. 1998 Aug;128(8):1336-41.
28 Kelly PJ, Rosand J, Kistler JP, Shih VE, Silveira S, Plomaritoglou A, Furie KL. Homocysteine, MTHFR 677CT polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology. 2002 Aug 27;59(4):529-36.
29 Ulvik A, Ueland PM, Fredriksen A, Meyer K, Vollset SE, Hoff G, Schneede J. Functional inference of the methylenetetrahydrofolate reductase 677C > T and 1298A > C polymorphisms from a large-scale epidemiological study. Hum Genet. 2007 Mar;121(1):57-64.
30 Watkins D, Ru M, Hwang HY, Kim CD, Murray A, Philip NS, Kim W, Legakis H, Wai T, Hilton JF, Ge B, Doré C, Hosack A, Wilson A, Gravel RA, Shane B,Hudson TJ, Rosenblatt DS. Hyperhomocysteinemia due to Methionine Synthase Deficiency, cblG: Structure of the MTR Gene, Genotype Diversity, and Recognition of a Common Mutation, P1173L. Am J Hum Genet. 2002 Jul;71(1):143-53.
31 Dawling S, Roodi N, Mernaugh RL, Wang X, Parl FF. Catechol-O-Methyltransferase (COMT)-mediated Metabolism of Catechol Estrogens Comparison of Wild-Type and Variant COMT Isoforms. Cancer Res September 15, 2001 61; 6716.
32 Shield AJ, Thomae BA, Eckloff BW, Wieben ED, Weinshilboum RM. Human catechol O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes. Molecular Psychiatry (2004) 9, 151–160
33 Åberg E, Fandiño-Losada A, Sjöholm LK, Forsell Y, Lavebratt C. The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population-based study. J Affect Disord. 2011 Mar;129(1-3):158-66.
34 Htun NC, Miyaki K, Song Y, Ikeda S, Shimbo T, Muramatsu M. Association of the catechol-O-methyl transferase gene Val158Met polymorphism with blood pressure and prevalence of hypertension: interaction with dietary energy intake. Am J Hypertens. 2011 Sep;24(9):1022-6.
35 Schalinske KL, Smazal AL. Homocysteine Imbalance: a Pathological Metabolic Marker. Adv Nutr Nov 2012 Adv Nutr vol. 3:755-762, 2012.
36 Ziegler DA, Ashourian P, Wonderlick JS, Sarokhan AK, Prelec D, Scherzer CR, Corkin S. Motor impulsivity in Parkinson disease: associations with COMT and DRD2 polymorphisms. Scand J Psychol. 2014 Jun;55(3):278-86.
37 Jacques PF, Rosenberg IH, et al. Serum total homocysteine concentrations in adolescent and adult Americans:results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 1999;69:482-489.