The Genova Methylation Panel provides a functional, non-genetic look at methylation, transsulfuration, glutathione production, and related metabolic pathways. Rather than identifying genetic tendencies, it measures metabolites that show what these pathways are actually doing at the time of testing.
What Does the Genova Methylation Panel Evaluate?
Methylation Capacity
SAM SAH SAM:SAH MethionineThese markers help determine whether methyl groups are adequately available and whether methylation reactions may be restricted by accumulation of SAH, a potent inhibitor of methyltransferase reactions.
Homocysteine & Pathway Flow
Homocysteine Methionine RemethylationHomocysteine sits at an important metabolic junction. It may be recycled toward methionine or directed toward transsulfuration and ultimately antioxidant production.
Transsulfuration
Cystathionine Cysteine TaurineThese markers provide information about sulfur metabolism and movement of homocysteine toward pathways involved in antioxidant defense and cellular protection.
Glutathione & Oxidative Stress
Glutathione Glycine CysteineGlutathione is a major intracellular antioxidant. These findings can help identify inadequate antioxidant capacity or increased metabolic demand that may need attention before aggressively stimulating methylation.
Methylation Is a Connected Pathway
SAH: An Important Functional Methylation Marker
One of the most useful features of direct methylation testing is measurement of S-adenosylhomocysteine (SAH).
SAM donates a methyl group during methylation reactions and becomes SAH. SAH must then be efficiently cleared because accumulation of SAH inhibits methyltransferase enzymes and can suppress methylation even when SAM is adequate.
If SAH is also elevated, methylation reactions may remain inhibited. This is why SAM and SAH should be interpreted together rather than looking at SAM alone.
Why Can SAH Become Elevated?
SAH is converted through the SAH hydrolase (SAHH) reaction toward homocysteine and adenosine. Importantly, this reaction is reversible.
For the pathway to continue efficiently in the direction of SAH clearance, its downstream products must also be adequately removed.
Homocysteine Clearance
Homocysteine can be remethylated toward methionine or directed through transsulfuration. Problems in either direction may influence pathway flow.
Adenosine Clearance
Adenosine metabolism is another important part of SAH clearance. When downstream clearance is impaired, the reversible SAHH reaction may be less favorable for removal of SAH.
How Does This Fit With the Walsh Approach?
The traditional Walsh assessment of methylation relies heavily on whole-blood histamine interpreted together with symptoms and clinical history.
That remains useful because histamine metabolism in blood cells involves a methyl-dependent methyltransferase pathway and because decades of Walsh clinical data associate characteristic histamine patterns with undermethylation and overmethylation.
The Genova panel answers a somewhat different question: What is happening within the methylation and transsulfuration pathways themselves?
Walsh Methylation Screen
Whole-Blood Histamine HomocysteineHelps identify the traditional clinical patterns associated with Walsh undermethylation and overmethylation.
View Methylation ScreenFunctional Methylation Panel
SAM SAH Homocysteine Transsulfuration GlutathioneExamines active pathway metabolites and can identify methylation bottlenecks that may not be apparent from histamine alone.
Methylation, Mood & Neurotransmitter Regulation
Methylation is particularly relevant to psychiatric and behavioral health because methylation can influence expression of proteins involved in neurotransmitter regulation, including the serotonin transporter (SERT) and dopamine transporters.
Within the Walsh model, this provides an important biochemical distinction between undermethylation and overmethylation and helps explain why people with apparently similar psychiatric symptoms may respond very differently to nutrients and medications.
Creatine and Methylation Demand
Methylation depends not only on how many methyl groups the body can produce, but also on how rapidly they are being consumed.
Endogenous creatine synthesis represents one of the body's major uses of methyl groups. During creatine synthesis, SAM is consumed and SAH is produced.
This can be particularly relevant when methylation abnormalities coexist with fatigue, poor exercise tolerance, cognitive symptoms, or evidence of impaired cellular energy metabolism.
Transsulfuration, Glutathione & Detoxification
Methylation does not operate independently. Homocysteine also provides the connection to the transsulfuration pathway, ultimately contributing to production of cysteine and glutathione.
Cysteine
An important sulfur-containing amino acid and precursor required for glutathione production.
Glycine
Another required component of glutathione and an important amino acid in cellular metabolism.
Glutathione
A major intracellular antioxidant involved in redox balance, cellular protection, and detoxification.
When antioxidant capacity or transsulfuration is impaired, simply supplying additional methyl donors may not address the underlying metabolic problem.
Genetic Testing vs. Functional Methylation Testing
Genetic Testing
Shows inherited variants that may influence enzymes involved in folate and methylation metabolism.
It shows potential.
Functional Testing
Measures metabolites produced by the pathways and therefore provides information about current biochemical function.
It shows what is happening now.
Genes can influence methylation, but so can diet, nutrient status, oxidative stress, inflammation, medications, metabolic health, environmental exposures, kidney function, and other acquired factors.
What Does the Genova Methylation Panel Measure?
| Pathway | Markers |
|---|---|
| Methylation | SAM, SAH, SAM/SAH relationship, Methionine |
| Homocysteine Metabolism | Homocysteine and related pathway markers |
| Methyl Donor Metabolism | Choline, Betaine, Serine and related metabolites |
| Downstream Methylation Metabolites | DMG, Sarcosine, Glycine and related markers |
| Transsulfuration | Cystathionine, Cysteine, Taurine |
| Antioxidant Capacity | Glutathione and related precursors |
Who May Benefit From This Testing?
Functional methylation testing may be particularly useful when evaluating patients with:
Mood & Behavior
Depression, anxiety, OCD, mood instability, irritability, attention problems, or unusual responses to psychiatric medications or nutrients.
Cognitive Concerns
Memory problems, cognitive decline, brain fog, impaired concentration, or other neurological concerns.
Fatigue & Poor Resilience
Chronic fatigue, reduced stress tolerance, poor recovery, or symptoms suggesting increased metabolic demand.
Toxic & Oxidative Stress
Chemical sensitivity, suspected toxic exposure, oxidative stress, or evidence that impaired detoxification may be affecting methylation.
Explore Methylation & the Walsh Approach
These educational sections explain how methylation abnormalities can influence neurotransmitter function, nutrient requirements, cellular energy, and treatment strategy.
Undermethylation Overmethylation Five Epigenetic BiotypesHow the Results Can Guide Nutrient Strategy
The purpose of testing is not simply to label someone as a “poor methylator.” The results can help determine where the pathway appears to be impaired and what should be addressed first.
Low Methyl Availability
Findings may support consideration of methylation substrates or other nutrients needed to restore adequate pathway function.
Elevated SAH
Rather than simply adding methyl donors, attention may need to shift toward the factors interfering with SAH clearance.
High Methyl Demand
Reducing unnecessary methyl-group consumption—for example through the creatine pathway—may sometimes be more useful than simply increasing methyl supply.
Oxidative / Transsulfuration Stress
Glutathione precursors, antioxidant status, sulfur metabolism, and sources of metabolic stress may deserve priority.
Interpret the Pathway — Not Just the Numbers
SAM, SAH, homocysteine, methionine, transsulfuration markers, and glutathione are interconnected. Their clinical value comes from understanding the pattern they create together and how that pattern relates to symptoms, Walsh biotype findings, nutrient status, and other laboratory results.
For patients undergoing a Walsh-based or comprehensive functional assessment, these findings can be incorporated into the physician consultation and individualized biochemical report.
Consultation + Biochemical Report 20-Minute ConsultationSample Type
Follow the collection and preparation instructions supplied with the laboratory kit. Proper specimen handling is important for accurate measurement of methylation and antioxidant metabolites.



