The methylation cycle
Methylation Panel.
A direct read on the chemistry behind DNA repair, neurotransmitter synthesis, detoxification, and a meaningful slice of cardiovascular risk.
By Genova Diagnostics · At-home finger-stick bloodspot
Why it matters
Methylation runs detoxification, neurotransmitter synthesis, DNA repair, energy metabolism, and a meaningful slice of your cardiovascular risk. When the cycle slows, all five slow with it. This panel reads the cycle directly: methionine, SAM, SAH, homocysteine, the folate metabolites, and the cystathionine handoff, so the interpretation can point to the specific lever that moves it for you. Collection is an at-home bloodspot kit shipped to you. This is a Genova specialty test; it is not a draw at LabCorp or Quest.
Methylated B-vitamins are everywhere now. Methylfolate, methyl-B12, P-5-P, and TMG appear in supplement stacks built off MTHFR results and Reddit guesses. The problem is that most patients have no idea whether they need them, and a meaningful subset feel worse on them than off. This panel removes the guessing. If your methylation cycle is genuinely backed up, the markers say so and we dose precisely. If it is not, we save you the supplement bill and the side effects.
What I read for
Homocysteine alone is not enough. I read it with the SAM/SAH ratio, the folate metabolites, and the cystathionine handoff to see where the cycle is bottlenecked. The point is to find the specific lever that moves it for you, not to chase a single number.
I read the methylation panel as five separate questions, each with its own answer and its own intervention:
- Is methionine adequate? (the cycle's starting substrate)
- Is SAM being made and used efficiently? (the SAM/SAH ratio is the methylation index)
- Are the folate metabolites moving cleanly through 5-MTHF? (the folate side of the cycle)
- Is the cystathionine handoff working? (the trans-sulfuration exit toward glutathione)
- Is homocysteine accumulating, and if so, where in the cycle is it stuck?
What it measures
The methylation cycle has three functional segments. This panel reads all three, and the report's interpretation depends on how they fit together rather than any single marker in isolation.
The methylation index (SAM, SAH, and the ratio). S-adenosylmethionine (SAM) is the universal methyl donor; every methylation reaction in the body draws from it. S-adenosylhomocysteine (SAH) is what's left after SAM gives up its methyl group, and high SAH actively inhibits further methylation. The SAM/SAH ratio is the single most useful number on the panel because it tells me whether the cell is methylating effectively or whether the brake is on.
The folate side (5-MTHF, folic acid, folinic acid). Methylfolate (5-MTHF) is the active folate that drives the cycle. Synthetic folic acid that has not been converted, particularly in MTHFR variants, can pile up unmetabolized and create downstream noise. Folinic acid sits between the two as a usable intermediate. Reading all three together tells me which form of folate this patient actually needs.
The trans-sulfuration handoff (homocysteine, cystathionine, cysteine). When the cycle is working, homocysteine either recycles back to methionine or exits via cystathionine toward glutathione and the antioxidant pathway. Elevated homocysteine with low cystathionine points at a B6 bottleneck. Elevated homocysteine with adequate cystathionine usually points at B12 or folate. These differences change the prescription.
See all 10 biomarkers
Methylation Cycle
- Methionine
- Homocysteine
- Cystathionine
- Cysteine
- S-adenosylmethionine (SAM)
- S-adenosylhomocysteine (SAH)
- SAM/SAH ratio
- 5-methyltetrahydrofolate (5-MTHF)
- Folic acid
- Folinic acid
Who this is for
The Methylation Panel earns its place when methylation is implicated by symptoms, by a routine lab number that does not add up, or by a known genetic variant that the patient wants to verify is actually causing functional trouble.
Common reasons I order it
- Mood, anxiety, brain fog, or sleep symptoms suggesting a neurotransmitter imbalance
- Elevated homocysteine on a standard cardiovascular panel
- A confirmed MTHFR or COMT variant, with uncertainty about whether the variant is actually impacting the cycle
- Considering high-dose methylated B-vitamins and wanting a baseline before starting
- Detoxification planning, especially before chelation or a glutathione protocol
- Family history of cardiovascular disease with the homocysteine question on the table
- Pre-conception planning, where methylation drives folate metabolism and fetal development
It is also one of the few advanced panels I offer as a standalone purchase outside the Precision Partnership. If you want a direct read on the cycle without committing to membership first, this is the entry point.
How collection works
- 1
We decide it is the right test.
A short conversation to confirm the Methylation Panel answers your question. If MTHFR or COMT genetics are part of the picture, we discuss whether to add a SNP panel to the same workup.
- 2
The kit ships to your home.
Genova mails the collection pack with everything you need: a finger-stick lancet, the bloodspot card, written instructions, a collection video, and prepaid return shipping.
- 3
You collect at home.
A single finger-stick produces enough bloodspot for the panel. Clean the finger, lance, fill the marked circles on the card, let it dry. Most people complete the whole collection in under 10 minutes.
- 4
You ship it back.
Use the prepaid FedEx materials in the kit. Genova receives the sample and runs the assays.
- 5
We read it together.
Results come back to me in about 7 to 10 business days. We sit down with them and translate the patterns into a specific intervention plan: which form of B-vitamins, at what doses, and what to recheck.
How to prepare
Methylation supplements directly raise the markers we are measuring, so the prep window matters more for this panel than for most. Never stop a prescription medication you need without clearing it with me first.
Methylated B-vitamins (methylfolate, methyl-B12, P-5-P, TMG): hold 48 to 72 hours before collection. These supplements directly load the cycle and will mask whatever functional state you are actually in.
SAMe: hold 7 days before collection. SAMe takes longer than the B-vitamins to wash out.
Folic acid and standard B-complex supplements: hold 48 hours.
Methionine-containing protein powders or single amino-acid supplements: hold 48 hours.
Fasting: not required. Eat normally before collection.
Caffeine and alcohol: not strictly required to hold, but moderate use the day before reads more cleanly.
If you are on prescription folate (Deplin, L-methylfolate) or B12 injections for a documented deficiency, we discuss timing on the call. We do not stop those without a plan.
What you get
A full Genova report with all measurements and contextual interpretation. A debrief with me where we walk through where the cycle is stuck, what form of B-vitamins your body can actually use, the right dose to start at, and the rechecks that confirm it worked.
Methylation is one of the most responsive systems you can measure. The right form of folate at the right dose moves these numbers in 6 to 12 weeks. We measure, we compare to optimal, and we recheck.
Questions
No. MTHFR is a genetic test; it tells you what variant you carry, which is fixed for life. The Methylation Panel is a functional test; it tells you what your methylation chemistry is actually doing right now. Many MTHFR carriers methylate fine. Some non-carriers methylate poorly. The functional read is what changes the treatment.
Yes. The Methylation Panel is offered standalone, which is unusual for the specialty testing in my practice. It includes the test kit, lab processing, a written interpretation, and a 30-minute review visit.
[NEEDS YOUR INPUT: published standalone price for the Methylation Panel package. Confirm and update product.price in the data file.]
No. Eat normally before collection. The panel runs on a finger-stick bloodspot, not a fasting venous draw.
[NEEDS YOUR INPUT: This is typically cash-pay through the practice. Genova provides CPT codes for possible reimbursement; coverage varies. Confirm and adjust.]
About 7 to 10 business days from when Genova receives the sample.
Available standalone
Kit ships within 2 business days. Your written interpretation arrives within 7 business days of the lab releasing results.
From the writing