Key Advantages

  • Evaluates the plasma levels of Methionine, Cysteine, SAMe, SAH, Hcys and Cystathionine
  • Provides the important “methylation index,” a ratio of SAMe to SAH
  • Test results can appropriately guide nutritional support

Normal metabolism of methionine is critical for cellular methylation of DNA, proteins and neurotransmitters.

Aberrant methionine metabolism can occur in anyone at any age and can be associated with numerous health consequences.

More Information

Methionine is first enzymatically converted to S-adenosylmethionine (SAM), the principal methyl donor for methylation of DNA, RNA, protein, phospholipids, creatinine and neurotransmitters. S-adenosylhomocysteine (SAH) is generated as a product of transmethylation and is hydrolyzed to homocysteine (Hcy) and adenosine through a reversible reaction. SAH is a potent inhibitor of methylation reactions. Efficient removal of adenosine and Hcy is imperative to prevent accumulation of SAH. Hcy is normally removed or recycled by remethylation to methionine through a series of reactions that require 5-methyltetrahydrofolate and B12 or possibly betaine to complete the normal methylation cycle. A low ratio of SAM to SAH is a sensitive indicator of under-methylation. Elevated plasma Hcy is an independent risk factor for cardiovascular disease (CVD). Recent research suggests that elevated SAH may be an even better predictor of risk for CVD.

 Transsulfuration: Methionine > Homocysteine > Cysteine

The methionine transsulfuration pathway occurs primarily in the liver and diverts Hcys away from remethylation to methionine toward synthesis of the conditionally essential amino acid cysteine. Homocysteine in the presence of serine and B6 is enzymatically converted to cystathionine and ultimately cysteine. Cysteine is the rate-limiting amino acid in the biosynthesis of essential glutathione (GSH). GSH is pivotal in the regulation of intracellular redox homeostasis, oxidative stress, immune function, DNA synthesis and repair, apoptosis and detoxification of metals and chemicals.

Clinical Aspects of Methylation Dysfunction

Limited Oestrogen Detoxification

The 2-OH and 4-OH metabolites (catechol estrogens) are readily oxidized to quinones which are highly reactive.  2,4-hydroxy estrones can be significant mechanisms of estrogen quinone cell damage.  This harmful pathway can be minimised through detoxification and excretion of the catechol estrogens by methyl groups donated by S-adenosylmethionine (SAMe).  The inability to efficiently detoxify these estrogen metabolites has been linked to an increased susceptibility to postmenopausal estrogen sensitive cancers and overall prostate cancer risk.

Neurotransmitter Imbalance

Methylation defects are associated with altered neurotransmitter metabolism. SAMe is an essential cofactor both for synthesis and metabolism of neurotransmitters. Normal SAMe levels may also be required for the maintenance of myelin (the fatty layer of insulation that surrounds each nerve).

Mitochondrial Dysfunction

Coenzyme Q10 (CoQ10) and carnitine are two cellular nutrients required in order to produce sufficient mitochondrial energy.  CoQ10 is important for its role in ATP production in the mitochondrial respiratory chain while carnitine is involved in the transport of fatty acids into the mitochondrial matrix.  Synthesis of both nutrients relies heavily upon the methyl donating capacity of SAMe.  Compromised methionine metabolism may decrease levels of SAMe, thus resulting in impaired methylation and decreased cellular energy.

Cardiovascular Disease

Plasma homocysteine and S-adenosylhomocysteine (SAH) are positively associated with occlusive artery and cardiovascular disease and homocysteine has been historically considered to be an independent risk factor for cardiovascular disease.  SAH is the immediate precursor of homocysteine, and although present in blood at less than 1/500th the concentration of homocysteine, recent research has suggested that SAH may be an even stronger indicator of vascular disease.

Type 2 Diabetes

A recent study showed that increased plasma concentrations of homocysteine and other methylation pathway intermediates are related to disturbed renal function in patients with type 2 diabetes.  Additionally, patients with renal failure had a much lower methylation index SAMe/SAH ratio and elevated SAH.

Toxic Element Exposure

Epigenetics is the study of heritable changes in gene expression that occur without changes in DNA sequence. Epigenetic mechanisms are flexible genomic parameters that can change genome function under environmental influence. Toxic element exposure may contribute to epigenetic mechanisms which are known to affect enzymatic action required for proper methionine synthesis.

The Doctors Data Methylation profile evaluates the plasma levels of Methionine, Cysteine, SAMe, SAH, Hcys and Cystathionine, and provides the important “methylation index,” a ratio of SAMe to SAH. The test results can appropriately guide nutritional support to improve or normalise Methionine metabolism and ameliorate or prevent the potential adverse consequences associated with inadequate methylation and transsulfuration capacity.

Resources
Related Research

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MALDI-TOF vs DNA

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IJHNFM 2014 – DNA vs MALDI-TOF

Lagier et. al   Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect. 2012 Dec;18(12):1185-93.

Tan KE, Ellis BC, Lee R, Stamper PD, Zhang SX, Carroll KC. Prospective evaluation of a matrix-assisted laser desorption ionization-time of flight mass spectrometry system in a hospital clinical microbiology laboratory for identification of bacteria and yeasts: a bench-by-bench study for assessing the impact on time to identification and cost-effectiveness.  J Clin Microbiol. 2012 Oct;50(10):3301-8

Manz, Michael;  Burri, Emanuel;  Rothen, Claude;  Tchanguizi, Nuschin;  Niederberger, Christian et al. (2012)  Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study. BMC Gastroenterol. 2012 Jan 10;12:5.

Beilfuss HA, Quig D, Block MA, Schreckenberger PC. 2015. Definitive identification of Laribacter hongkongensis acquired in the United States. J Clin Microbiol 53:2385–2388.

Wall Chart
Related Research

Zhang CX, Ho SC, Chen YM, Lin FY, Fu JH, Cheng SZ.  Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by estrogen and progesterone receptor status.  BMC Medical Genomics 2014, 7:5.

Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH.  Homocysteine, folate, methylation, and monoamine metabolism in depression.  J Neurol Neurosurg Psychiatry. 2000 Aug;69(2):228-32

Phillipson OT.   Management of the aging risk factor for Parkinson’s disease.   Neurobiol Aging. 2014 Apr;35(4):847-57.

Baccarelli A and V. Bollati V.  Epigenetics and environmental chemicals.  Curr Opin Pediatr. 2009 Apr; 21(2): 243–251.

Baccarelli A and Ghosh S.  Environmental Exposures, Epigenetics and Cardiovascular Disease.  Curr Opin Clin Nutr Metab Care. 2012 Jul; 15(4): 323–329.

Herrmann W, Schorr H, Obeid R, Makowski J, Fowler B, Kuhlmann MK. Disturbed homocysteine and methionine cycle intermediates S-adenosylhomocysteine and S-adenosylmethionine are related to degree of renal insufficiency in type 2 diabetes. Clin Chem. 2005 May;51(5):891-

This Test May be Useful in…

  • Autism
  • Cancer Risk
  • Cardiovascular Disease
  • Detoxification Impairment
  • Down Syndrome
  • General Health and Longevity
    Genetic Disorders
  • Immune Dysfunction
  • Neuro-degenerative Diseases
  • Nutritional Deficiencies
  • Psychiatric Disorders
  • Stress (Oxidation/Inflammation)

IMPORTANT – Please Read Before Prescribing:

The collection for this test is very time sensitive and we request that practitioners reiterate to their patient the importance of following the instructions carefully. All instructions are inside the test, however due to the short time frame and freezing of the sample, lab rejections are common for this test.  Before prescribing this test to patients, please make sure they are able to comply with the following:

1)      Place the ice block in freezer as soon as kit is received

2)      Ensure test is performed on a Monday

3)       On Monday, patients should pre-book their courier to pick up kit on the Tuesday

4)      Take kit and all instructions to a Collection Centre for the blood draw

5)      After blood is drawn, patient will need to wait for it to be spun (approx. 1 hour)

6)      As soon as they receive their sample, put it straight on the ice in the esky and get it home and into the freezer within 45mins to be frozen overnight

7)      Courier will pick up the frozen sample on Tuesday

If the patient is unable to comply with this time-frame, this test is not suitable for them.