- Advanced Functional Testing
Methylation Profile Test
The SAM/SAH ratio — your body's most important biochemical measure you've never heard of.
Methylation controls gene expression, neurotransmitter production, detoxification, hormone clearance, and immune function. The Methylation Profile from Doctor’s Data directly measures SAM and SAH — the two molecules that determine whether your methylation cycle is running efficiently or breaking down. No genetic test, no guesswork. This is the actual biochemistry.
markers
Analysis
"I tested negative for the MTHFR gene variant. My doctor said my methylation is fine. But I still feel terrible."
This is a critically important distinction. Genetic testing like MTHFR is not an accurate assessment for true methylation disorders because it is only one enzyme in the backup pathway, not the primary one (see above diagram). Nor does it play a prominent role in mental health. Every cell in the body has a unique histone and methylation pattern, which gives cells their instructions. Methylation status is determined by a tug-of-war between enzymes that drive undermethylation versus enzymes that drive overmethylation. Whichever group wins determines methylation status, not a single enzyme like MTHFR.
When the backup pathway is fed instead of the primary one, it becomes depleted, resulting in neurotransmitter changes, including elevated glutamate and reduced serotonin production.
The Methylation Profile SAM/SAH test measures the biochemistry directly — not the genetics. It evaluates each pathway in the methylation cycle and shows the levels of your methyl donor (SAM) and its inhibitor (SAH) in your blood, along with the ratio between them. That ratio is the most accurate real-time measure of whether your methylation cycle is working — and it is information many doctors are unaware of.
Understanding the Test
What is the Methylation Profile SAM/SAH Test?
The Methylation Profile is a blood test run by Doctor’s Data — a specialty functional laboratory — that evaluates each pathway in the methylation cycle and measures two specific molecules central to your methylation cycle: SAM (S-Adenosylmethionine) and SAH (S-Adenosylhomocysteine), along with the ratio between them.
Methylation is a biochemical process that happens billions of times per second in every cell of your body. It controls how your genes are expressed, how your brain makes and breaks down neurotransmitters, how your liver detoxifies hormones and chemicals, and how your immune system functions. When methylation is disrupted — either too low (undermethylation) or too high (overmethylation) — the downstream effects are wide-reaching and often misdiagnosed.
Unlike genetic tests, which don’t show whether a SNP is actually causing issues, the Methylation Profile SAM/SAH test shows what is happening in your body in real time. And unlike homocysteine — a common but incomplete proxy for methylation — SAM and SAH together provide a fuller picture of methylation capacity and efficiency. I use this test because it directly guides nutrition and supplement protocols I build for each client.
| Lab Marker | Reference Range | The Role of This Marker | What Your Levels Indicate |
|---|---|---|---|
| SAM S-adenosylmethionine | 170–270 nmol/L | SAM is the body's primary methyl donor, produced from methionine and responsible for transferring methyl groups to DNA, neurotransmitters, hormones, and proteins. It is the driving force behind gene expression, detoxification, and nervous system regulation. |
Low Often signals undermethylation, low methionine intake, and critical nutrient deficiencies. Associated with fatigue, low mood, and impaired detoxification.
High May reflect overmethylation or impaired downstream conversion, sometimes presenting as anxiety or irritability in sensitive individuals.
|
| SAH S-adenosylhomocysteine | 12–35 nmol/L | SAH is produced each time SAM donates a methyl group. It is a potent inhibitor of methyltransferase enzymes, meaning accumulation actively suppresses methylation even when SAM levels appear adequate. |
Low Rarely a primary clinical concern. May reflect reduced methionine intake or a slowdown of the overall methylation cycle.
High Signals impaired SAH clearance, blocking methylation reactions throughout the body. Elevated SAH may also be a more sensitive cardiovascular risk marker than homocysteine alone.
|
| SAM/SAH Ratio Methylation Index | 4.0–9.0 | This ratio reflects the body's overall capacity to perform methylation reactions. Because SAH inhibits SAM-dependent enzymes, the balance between the two is a more meaningful clinical picture than either value in isolation. |
Low A sensitive early indicator of undermethylation, even when individual SAM and SAH values appear within range. Linked to impaired mood, cognition, and detoxification. A ratio below 4.0 warrants clinical attention.
High May reflect overmethylation or excess supplementation with inappropriate nutrients for biochemistry.
|
| Methionine Essential Amino Acid | 16–37 µmol/L | Methionine is the essential amino acid that initiates the methylation cycle and serves as the direct precursor to SAM. It must be obtained through dietary protein and cannot be produced by the body on its own. |
Low Often reflects inadequate dietary protein, poor digestion, or high demand on the methylation cycle. Directly limits SAM production and may contribute to fatigue and impaired detoxification.
High May indicate impaired conversion to SAM. Best interpreted alongside SAM and homocysteine levels.
|
| Homocysteine Metabolic Intermediate | 4.0–15.0 µmol/L | Homocysteine sits at a critical junction where it can be recycled back to methionine, or converted to cysteine and glutathione via the transsulfuration pathway using B6. It is one of the most studied markers for cardiovascular and neurological risk. |
Low Uncommon and generally not a clinical concern. Very low levels alongside low SAM may point to a slowdown of the overall cycle.
High A well-established risk factor for cardiovascular disease, stroke, and cognitive decline. Often points to nutrient insufficiency, or a block in the transsulfuration pathway.
|
| Cysteine Conditionally Essential Amino Acid | 160–350 µmol/L | Cysteine is produced at the end of the transsulfuration pathway and is the rate-limiting building block for glutathione, the body's primary antioxidant and detoxifier. It also contributes to taurine synthesis and overall sulfur metabolism. |
Low May indicate impaired transsulfuration, B6 insufficiency, or high demand for glutathione. Associated with reduced detoxification capacity, inflammation, and increased sensitivity to environmental toxins.
High May reflect a downstream block in cysteine metabolism. Should be evaluated alongside cystathionine and homocysteine to identify where accumulation is occurring.
|
| Cystathionine Transsulfuration Intermediate | 0.05–0.55 µmol/L | Cystathionine is the intermediate compound formed during the B6-dependent conversion of homocysteine to cysteine. Measuring it helps identify where a bottleneck exists within the transsulfuration pathway. |
Low May suggest reduced flux through the transsulfuration pathway, often related to B6 insufficiency or low enzyme activity. Low cystathionine alongside low cysteine can signal poor glutathione production.
High Typically reflects accumulation due to impaired conversion to cysteine, frequently associated with B6 deficiency, magnesium insufficiency, or genetic expression affecting downstream enzymes.
|
Reference ranges reflect Doctor's Data laboratory standards for plasma specimens. Results should always be interpreted by a qualified practitioner in the context of your full clinical picture.
SAM — METHYL DONOR
S-Adenosylmethionine (SAM) is the universal methyl donor — the molecule that donates a methyl group to hundreds of reactions throughout the body. Low SAM means the methylation cycle is underperforming. High SAM (relative to SAH) means the cycle is running efficiently.Tags: Neurotransmitter synthesis, DNA methylation, Hormone clearance, Immune regulation
SAH — METHYL INHIBITOR
S-Adenosylhomocysteine (SAH) is the byproduct produced when SAM donates its methyl group. SAH inhibits methylation reactions — so elevated SAH slows the entire cycle. The ratio of SAM to SAH is the most accurate indicator of functional methylation capacity.Tags: Methylation inhibitor, Converts to homocysteine, Cycle efficiency marker
SAM/SAH RATIO — KEY MARKER
Methylation Index: The ratio between SAM and SAH is called the methylation index. A high ratio indicates robust methylation capacity. A low ratio indicates impaired methylation. This single number tells us more about your functional methylation status than any genetic test.Tags: Real-time methylation status, More accurate than MTHFR, Guides treatment protocol
Why This Cycle Matters
Methylation touches everything
Cycle Diagram Steps
- INPUT: Methionine — Amino acid from protein — the raw material
- TESTED: SAM — S-Adenosylmethionine — Active methyl donor — powers hundreds of reactions
- TESTED: SAH — S-Adenosylhomocysteine — Inhibitory byproduct — elevated SAH stalls the cycle
- DOWNSTREAM: Homocysteine — Cardiovascular and cognitive risk marker — but not a complete methylation measure on its own
- RECYCLED: Methionine regenerated — The cycle continues — when nutrients are sufficient
Required Nutrients
- Folate (B9)
- B12
- B6
- Riboflavin (B2)
- Magnesium
- Zinc
- Methionine
- TMG
The methylation cycle is not a niche biochemical pathway. It is a central hub that connects to your mental health, detoxification, hormone balance, immune response, and even how your genes are turned on and off. When it runs well, everything downstream runs better. When it falters, the effects ripple outward in ways that are frequently misattributed to other conditions.
For the brain specifically: methylation controls the production and breakdown of serotonin, dopamine, norepinephrine, and histamine. This is why methylation disruption so consistently presents as depression, anxiety, OCD, and ADHD — the neurotransmitter systems that regulate mood and focus depend directly on a functioning methylation cycle.
Why nutrients matter: The methylation cycle is nutritionally driven. Deficiencies in B12, B6, methionine, zinc, and magnesium can all impair the cycle, which is why I pair the SAM/SAH test with additional lab work. Knowing the methylation index is step one. Understanding which nutrient deficiencies are driving it, along with any underlying infections, is step two.
The Two Methylation Biotypes
Under or Over— the treatment
is completely different
This is one of the most important things to understand about methylation: undermethylation and overmethylation look different, feel different, and require opposite interventions. Getting this wrong— for example, supplementing an undermethylator with demethylating agents, such as methylfolate—can significantly worsen symptoms. The SAM/SAH test tells us exactly which direction you’re in.
Undermethylation
In undermethylation, the body lacks the methyl groups needed to produce neurotransmitters efficiently, regulate gene expression, and clear hormones properly. Serotonin, dopamine, and norepinephrine production is low.
Common symptoms:
- Depression
- Anxiety
- OCD tendencies
- High achievement
- Perfectionism
- ADHD
- Seasonal allergies
- Competitive nature
- Addictive tendencies
- Responds well to SSRIs
Overmethylation
In overmethylation, too many methyl groups causes hyperexcitability in the brain, leading to excessive production of the neurotransmitters serotonin, dopamine, and norepinephrine.
Common symptoms:
- High anxiety
- Panic disorders
- Food and chemical sensitivities
- Inability to sit still
- Sleep difficulties
- Verbosity
- Adverse reaction to SSRIs
- Low motivation
What This Test Reveals
Six things the SAM/SAH ratio
tells us about your health
The methylation index touches every major system in the body.
Here is what a disrupted SAM/SAH ratio can explain that standard testing never will.
Neurotransmitter Status
Methylation directly controls the synthesis and breakdown of serotonin, dopamine, norepinephrine, and adrenaline. An impaired SAM/SAH ratio frequently underlies treatment-resistant depression, anxiety, OCD, and ADHD that medication alone cannot fully address.
Gene Expression (Epigenetics)
Methylation controls which genes are switched on or off through a process called DNA methylation. The SAM/SAH ratio directly reflects whether this epigenetic regulation is functioning — relevant to cancer risk, immune regulation, and developmental health.
Estrogen and Hormone Clearance
The liver uses methylation to detoxify and clear estrogen. Poor methylation leads to estrogen buildup, contributing to PMS, fibroids, PCOS, endometriosis, and estrogen-driven mood symptoms. This is why methylation testing often pairs with DUTCH hormone testing (internal link to DUTCH test page).Immune Function and Inflammation
Methylation regulates inflammatory gene expression and immune cell differentiation. Low SAM is associated with increased inflammatory signaling — which connects to autoimmune conditions, chronic infections, and histamine intolerance.Detoxification Capacity
Phase II liver detoxification relies on methylation to neutralize and excrete environmental toxins, heavy metals, and pharmaceutical byproducts. Poor methylation means these substances accumulate — contributing to copper toxicity (internal link to copper toxicity page), chemical sensitivity, and systemic burden.Mitochondrial Energy Production
SAM is required for the synthesis of coenzyme Q10 and carnitine — two molecules essential for mitochondrial energy production. Low SAM contributes to fatigue, exercise intolerance, and the kind of exhaustion that sleep does not fix.SAM/SAH vs. Inaccurate Methylation Testing
Why MTHFR and Homocysteine
don't tell the full story
Most people who come to me have already had homocysteine or MTHFR testing. Here is exactly why those tests are incomplete and what the SAM/SAH profile adds that they cannot.
MTHFR Gene Test + Homocysteine
- MTHFR testing shows only possible genetic variants — it does not measure your body’s real-time methylation activity
- Two people with identical MTHFR variants can have completely different real-world methylation status
- Homocysteine is a downstream marker — it can be normal even when SAM/SAH ratio is significantly impaired
- Neither test distinguishes between undermethylation and overmethylation — the protocols for each are opposite
- Does not guide nutrient selection — you cannot know whether methyl donors will help or harm without knowing SAM/SAH
The Methylation Profile SAM/SAH
- Measures actual SAM and SAH levels in the blood — your real-time functional methylation status, not genetic potential
- The SAM/SAH ratio is the most direct and clinically meaningful measure of methylation cycle efficiency available
- Identifies both undermethylation and overmethylation precisely — so the treatment protocol is appropriate for your biotype
- Directly guides which methyl-supporting nutrients are safe and appropriate for your specific biochemistry
- Results interpreted with full functional nutrition context — connected to your other labs, symptoms, and health history
How It Works
A simple blood draw.
Profound insight.
The Methylation Profile requires a blood draw from a local walk-in clinic or a mobile phlebotomist. Here is what the process looks like from discovery call to treatment plan.
01
Free Discovery Call
We spend 20 minutes talking through your symptoms, history, and health goals to determine whether the Methylation Profile is the right starting point for you.
02
Initial Consultation and Lab Order
After sign-up, we complete a full intake session. I order your Methylation Profile SAM/SAH test through Doctor's Data.
03
Blood Draw from a local walk-in clinic or a mobile phlebotomist
You visit your nearest walk-in clinic or have a mobile phlebotomist come to your home at your convenience. The blood draw takes a few minutes and the sample is sent directly to Doctor's Data.
04
Your Personalized Treatment Plan
Once all your results are in, I build your starting treatment plan. We review everything together — I explain your SAM/SAH ratio, what it means for your biotype, and build your targeted nutrition and supplement protocol. We then meet monthly with updates.
years in practice
Why Work With Samantha
Methylation is at the center
of everything I do
- I connect your methylation results to your full picture — including zinc and copper levels (internal link to copper/zinc page), pyrrole disorder status (internal link to pyrrole disorder page), gut health, hormones, and mental health symptoms, so nothing is treated in isolation.
- I never supplement without testing — giving methyl donors to an overmethylator can be harmful. The SAM/SAH ratio tells me exactly what your biochemistry needs.
- All sessions are virtual — I work with clients across the United States and internationally.
Common Questions
Everything you need to
know before you start
What is the Methylation Profile SAM/SAH test?
The Methylation Profile SAM/SAH is a blood test by Doctor’s Data that directly measures two molecules central to your methylation cycle: SAM (S-Adenosylmethionine), your body’s primary methyl donor, and SAH (S-Adenosylhomocysteine), its inhibitory byproduct. The ratio between them — the methylation index — is the most accurate real-time measure of whether your methylation cycle is running efficiently. This is biochemical testing, not genetic testing. It tells you what is actually happening in your body in real time.
How is this different from homocysteine testing?
Homocysteine is a downstream byproduct of the methylation cycle and is commonly used as a rough proxy for methylation status. But it is an incomplete marker. Homocysteine can be within normal range even when the SAM/SAH ratio is significantly impaired. SAM and SAH together tell you far more about what is happening earlier and more centrally in the cycle — and critically, they help distinguish between undermethylation and overmethylation, something homocysteine cannot do reliably on its own.
How is the test done? Does it require a clinic visit?
How long does it take to get results?
Once Doctor’s Data receives your blood sample results are typically available within 1 to 2 weeks. After that, we schedule a results review session where I walk you through your results, explain your methylation index and what it means for your biotype, and build your personalized starting treatment plan from the findings.
What other tests do you commonly run alongside the Methylation Profile?
Methylation does not work in isolation — it connects to zinc and copper status, Pyrrole disorder, gut health, and hormones. I frequently pair the Methylation Profile with zinc and copper bloodwork, the urine kryptopyrrole test for Pyrrole disorder (internal link to pyrrole page), the DUTCH hormone test (internal link to DUTCH page), and the GI Map with zonulin (internal link to GI Map page). Together these tests give a comprehensive picture of the biochemical factors driving your symptoms, and the treatment plan I build addresses all of them in the correct order and combination.
How is this different from the MTHFR gene test?
MTHFR is not an accurate assessment for true methylation disorders because it is only one enzyme in the backup pathway, not the primary one. It says nothing about how your methylation is actually functioning in real time and does not play a role in mental health. Two people with identical MTHFR variants can have completely different real-world methylation status depending on their diet, nutrient levels, stress, and environment. The SAM/SAH test measures the actual biochemistry — the live functional status of your methylation cycle — not one enzyme with a high rate of inaccuracy.
What is the difference between undermethylation and overmethylation?
Undermethylation means the methylation cycle is deficient — methyl donors are depleted, and neurotransmitter production, particularly serotonin and dopamine, is impaired. It is associated with depression, anxiety, OCD, perfectionism, seasonal allergies, and competitive personality traits. Overmethylation means the cycle is overactive — excess methyl groups create hyperexcitability in the brain, and disrupt the balance of dopamine, serotonin, and norepinephrine. It commonly presents as high anxiety, racing thoughts, verbosity, difficulty sitting still, and sleep problems. The treatment protocols for each are opposite, which is why testing before supplementing is essential.
Is it dangerous to take methyl donors without knowing my SAM/SAH ratio?
It certainly can be. This is one of the most important reasons I always test before recommending nutrients. Methyl donors are appropriate and beneficial for undermethylators. For overmethylators, however, those same nutrients can significantly worsen anxiety, racing thoughts, and mood instability. Many clients come to me after being prescribed high-dose methylfolate by a well-meaning practitioner who tested the MTHFR gene but never measured actual methylation status, with crippling effects such as elevated glutamate and shunted serotonin synthesis. The SAM/SAH ratio removes the guesswork entirely.
Is this test covered by insurance?
The Methylation Profile SAM/SAH through Doctor’s Data is a specialty functional lab test and is not typically covered by insurance. It is an out-of-pocket cost. During your free discovery call I can walk you through current pricing and help you decide whether this is the right starting test for your specific situation, or whether we should begin with other testing first based on your symptoms.
I live outside the United States. Can I still get this test?
Yes. I work with international clients regularly. For blood-based tests like the Methylation Profile, the draw must be done at a walk-in clinic in the United States. Canadian clients and others near the border can cross the border for the draw, or use a U.S. address through a UPS mailbox or a friend or family member’s home. If you live in a country where the test can be ordered through a local provider, we can often arrange that. Reach out during your discovery call, and we will find the best solution for your situation.
Ready to understand your
methylation — for real?
Schedule your free 20-minute discovery call with Samantha. We will talk through your symptoms, your history, and whether the Methylation Profile SAM/SAH is the right next step for you.