Methylation Panel - Genova Diagnostics

Methylation is a biochemical process in which methyl groups (CH3) are transferred or donated between molecules, thereby changing their structure and function. This happens billions of times per second in every cell throughout the body. The methylation cycle is dependent on amino acids, vitamin cofactors, and minerals obtained from the diet to ensure adequate function of this biochemical pathway.

The incredibly vast processes in the body that depend upon methylation are what ultimately make functional testing for methylation impairment a valuable clinical tool. Some of these processes include, but are not limited to:

- creatine production for skeletal muscle contraction

- DNA and RNA synthesis

- gene regulation (epigenetics)

- hormone regulation and detoxification

- energy production

- cell membrane repair

- fat metabolism

- myelination

- immune function

- neurotransmitter production and metabolism

- vascular endothelial function and nitric oxide production

To keep these processes functioning optimally, there is a necessary balance between many different biochemical pathways. What is termed the “methylation cycle” involves an interplay between folate metabolism, methionine metabolism, and homocysteine transsulfuration.

The body continually adapts these interconnected pathways in order to maintain homeostasis.

However, key amino acid deficiencies, a lack of vitamin and mineral cofactors, genetic enzymatic predispositions, and a wide array
of oxidative stressors can impact multiple enzymes leading to a disruption in a patient’s overall methylation status.


Optimal range: 21 - 71 micromol/L

- Betaine (trimethylglycine) can be used to turn homocysteine back into methionine

- Betaine is derived from dietary choline (Meats, eggs, and beets)

- Betaine is used for: Methylation / Osmolyte, under cell stress (mainly in kidneys)


Betaine/Choline Ratio

Optimal range: 2.6 - 7.7 Ratio

Betaine and choline can be obtained from the diet or synthesized de novo.

Betaine is derived from dietary cholinenuts, cauliflower and broccoli, beets, meats, and eggs.

Choline is a lipotrope, in that it helps to mobilize fat from the liver. Phosphatidylcholine, a derivative, is required for the production of hepatic very-low-density lipoprotein and the mobilization of fat from the liver. Therefore, choline deficiency can result in fatty liver and liver abnormalities.



Optimal range: 5.2 - 13 micromol/L

Choline is a nutrient that supports various bodily functions, including cellular growth and metabolism. The body makes some choline, but the majority comes from dietary sources.



Optimal range: 271 - 392 micromol/L


Optimal range: 74 - 369 nanomol/L

Dimethylglycine (DMG)

Optimal range: 1.6 - 5 micromol/L


Optimal range: 669 - 5000 micromol/L


Optimal range: 181 - 440 micromol/L


Optimal range: 3.7 - 10.4 micromol/L

Met/Sulf Balance Ratio

Optimal range: 0.55 - 0.64 Ratio

This calculated ratio is called the ‘Met/Sulf Balance’ and it compares analytes between the methylation pathway and transsulfuration pathways.

Biomarker levels are compared proportionately allowing potential insight into which of the pathways is being favored.

The four analytes from the main methylation pathway that are used in the Met/Sulf Balance are SAM, SAH, methionine, and homocysteine. The four analytes from the transsulfuration pathway are cystathionine, cysteine, taurine, and glutathione.



Optimal range: 23 - 38 micromol/L

Methionine is an essential amino acid that plays an important role in the methylation cycle.


Methylation Balance Ratio

Optimal range: 1.03 - 1.2 Ratio

Compares 8 different biomarkers
– 4 biomarkers with a methyl group to give
– 4 biomarkers that have had a methyl group removed

The clinical utility of the Methylation Balance Ratio is that it represents a potential way to detect subtle methylation imbalance prior to alterations in the SAM/SAH ratio.

Methylated Metabolites are:
- SAM 
- Methionine 
- Betaine 
- Serine

Un-Methylated Metabolites are:
- SAH 
- Homocysteine 
- DMG 
- Sarcosine


Methylation Index (SAM/SAH Ratio)

Optimal range: 2.2 - 6.4 micromol/L

S-adenosylhomocysteine (SAH)

Optimal range: 16 - 41 nanomol/L

S-adenosylmethionine (SAM)

Optimal range: 65 - 150 nanomol/L

- The methylation cycle is all about making sure there is adequate SAM (S-adenosylmethionine)

- SAM is overwhelmingly the body’s main methyl donor

- Think of SAM as the body’s methylation currency

- SAM can donate a methyl group wherever it is needed



Optimal range: 3670 - 6743 nanomol/L


Optimal range: 91 - 161 micromol/L


Optimal range: 50 - 139 micromol/L