1) Undermethylation
Screened with Whole Blood Histamine (WBHistamine) and clarified by the Doctor’s Data Methylation Panel — not by SNP testing.
Undermethylators don’t generate enough methyl groups to keep certain genes properly “quiet.” In plain English, methyl groups are tiny chemical tags that help regulate which genes speak up and which stay muted — including those that govern the serotonin and dopamine transporters (SERT/DAT). Low methylation can destabilize this balance.
Rather than blocking reuptake with SSRIs, nutrient therapy supports the methylation cycle itself so the brain can re‑establish its own regulation. In clinical practice, Dr. Epstein also evaluates creatine demand and systemic alkalinity, which can materially affect methylation efficiency. The methylation panel helps identify where support is most needed.
2) Overmethylation
Here, methyl tagging is excessive. The goal is not to “add more methyl,” but to gently down‑regulate serotonin and dopamine activity at the gene‑expression level.
Folates are used for their capacity to slow expression on serotonin/dopamine pathways, and Niacin helps metabolize excess methionine — reducing methyl load.
Mechanistically, clinicians discuss both DNA methylation and histone acetylation as the epigenetic switches we are modulating.
3) Copper Overload
When copper is high relative to zinc — or insufficiently bound to ceruloplasmin — the brain tends to convert dopamine → norepinephrine, driving agitation and anxiety. Copper is also a pro‑oxidant.
- Key ratios: Copper/Zinc, Copper/Ceruloplasmin, and total copper.
- Zinc up‑regulates metallothionein and ceruloplasmin, binds free copper, and improves antioxidant defense.
Correcting copper excess supports cognition and can help protect against neurodegeneration over time.
4) Pyrrole Disorder (Pyroluria)
Due to a heme‑synthesis error, excess kryptopyrroles bind and deplete zinc and vitamin B6. The result is stress intolerance, mood lability, inflammation, poor dream recall — and often school performance issues in youth.
Treatment is typically lifelong yet highly responsive with consistent zinc, B6/P5P, and appropriate antioxidants.
5) Toxic Overload
Detox capacity is impaired when methylation falters. Labs often show elevated SAH, high homocysteine, low SAM, and decreased glutathione.
Walsh’s protocol emphasizes optimizing the conversion SAH → HCY (supported by zinc and co‑factors). Dr. Epstein extends this with targeted methylation support (guided by the methylation panel) and attention to areas most depleted, including detox and glutathione regeneration.
Dr. William J. Walsh is the founder of the Walsh Research Institute and a leading figure in nutrient‑based mental health. Across more than 40 years of clinical research and physician education, he has helped establish a practical, lab‑guided approach for addressing mood and behavior through biochemistry. His work emphasizes objective markers, patient education, and targeted nutrient plans that complement or, when appropriate, provide alternatives to medication‑only approaches.