Methyl Detox Profile Plus 30 Minute Consult

1. MTHFR

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}

2. MTR

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

3. MTRR

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

4. COMT

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

5. AHCY

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.

6. Homocysteine

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}

Literature

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.