A comprehensive genetic analysis of one-carbon metabolism, folate cycling, homocysteine clearance, and neurotransmitter methylation โ personalised to your DNA.
Methylation is a fundamental biochemical process โ it switches genes on and off, clears toxins and hormones, produces energy, repairs DNA, and regulates mood. Hanees carries several genetic variants that reduce his methylation capacity, with specific bottlenecks at MTHFR, COMT, and B12 transport.
This diagram shows the complete one-carbon metabolism pathway with Hanees's specific gene status overlaid. Red = bottleneck, Amber = caution, Green = strength.
Each gene in the methylation pathway has been analysed against Hanees's actual genotype. Cards are sorted by clinical priority.
Catechol-O-methyltransferase โ breaks down dopamine, noradrenaline, and adrenaline. Also deactivates oestrogen metabolites.
๐ด Significantly reduced COMT activity. Stress hormones linger 3โ4x longer than normal. Directly amplifies allergy symptoms โ elevated adrenaline triggers mast cell histamine release. His sneezing gets worse on stressful days through this exact mechanism. Mood dysregulation, anxiety sensitivity, and pain sensitivity also elevated.
Transcobalamin โ the carrier protein that transports vitamin B12 into cells. Without adequate TCN2 activity, B12 circulates but cannot enter cells.
๐ด Reduced B12 cellular transport. Even if blood B12 looks normal on tests, cellular B12 may be functionally deficient. This impairs the MTR enzyme (homocysteine โ methionine), raises homocysteine risk, and reduces SAMe production. Sublingual methylcobalamin bypasses this transport issue.
Methylenetetrahydrofolate reductase โ the rate-limiting enzyme of the entire methylation cycle. Converts folate into its active form (5-MTHF / methylfolate).
๐ก ~30% reduced MTHFR enzyme activity. Less methylfolate is produced, meaning less homocysteine is cleared via the folate pathway. Plain folic acid from supplements or fortified foods cannot be converted efficiently. Must use L-methylfolate (active form) directly. Compensated partially by his strong MTHFD1.
Fucosyltransferase 2 โ controls secretor status in the gut. FUT2 variants allow H. pylori attachment sites in gut mucosa, which reduces stomach acid and impairs B12 absorption.
๐ก Increased FUT2 activity โ lower B12 gut absorption. This compounds his TCN2 and CUBN B12 issues, creating a triple-layer B12 deficit โ poor gut absorption, poor gut uptake, and poor cellular transport. Active B12 (Holotranscobalamin) blood test is the correct marker to use, not total B12.
Methionine synthase โ the enzyme that converts homocysteine back into methionine using methylcobalamin (active B12) and methylfolate.
๐ก Slightly increased but altered MTR activity. While the enzyme is active, the G/A variant creates an altered activity pattern that affects homocysteine clearance efficiency. Since MTR requires both B12 and methylfolate, his TCN2 and MTHFR issues compound here โ all three must be addressed together.
Cubilin โ an intestinal protein that physically captures the B12-intrinsic factor complex and enables its absorption into the bloodstream.
๐ก Slightly reduced cubilin activity. Third layer of his B12 absorption deficit. Even when dietary B12 is available and bound to intrinsic factor, CUBN's reduced uptake efficiency means less actually enters circulation. Sublingual methylcobalamin completely bypasses this โ it absorbs directly through the oral mucosa.
DNA Methyltransferase 3B โ performs direct DNA methylation using SAMe as the methyl donor. This is the epigenetic switch that turns genes on and off.
๐ก Altered DNMT3B activity. DNA methylation patterns may be suboptimal, affecting gene expression regulation. This can have downstream effects on immune regulation, inflammation control, and cell repair. Optimising SAMe production (via methylfolate + B12) is the primary support mechanism.
Methionine Adenosyltransferase โ converts methionine into SAMe (S-adenosylmethionine), the universal methyl donor for hundreds of reactions in the body.
๐ก One MAT1A variant reduces activity. Partially offset by his other MAT1A variant (rs7087728, which increases activity). Net effect: slightly suboptimal SAMe production. SAMe supplementation directly compensates. Important for mood, liver health, and COMT enzyme function.
Methenyltetrahydrofolate synthetase โ converts 5-formylTHF to active folate forms, regulating how folate is distributed between the methylation and DNA synthesis cycles.
๐ก Increased MTHFS activity. May redirect folate away from methylation toward DNA synthesis, effectively competing for the same folate pool as his already-reduced MTHFR. Adequate folate intake becomes even more critical to ensure both pathways have sufficient supply.
Cystathionine beta-synthase โ the gateway enzyme of the transsulfuration pathway. Converts homocysteine into cystathionine, then cysteine, and ultimately glutathione.
๐ข Excellent CBS activity. His transsulfuration pathway is a significant strength โ glutathione (the master antioxidant) production is robust. This provides strong cellular defence against oxidative stress caused by his methylation bottlenecks. Also means he can clear excess homocysteine through this backup route.
Methylenetetrahydrofolate dehydrogenase โ produces active folate (methyl-THF) and supports the one-carbon cycle. A key compensatory enzyme for MTHFR.
๐ข Strong MTHFD1 activity partially compensates for MTHFR weakness. This is a meaningful compensatory strength โ it means his folate activation capacity is not entirely compromised despite the MTHFR reduction. Maintaining magnesium levels (MTHFD1 cofactor) is important to preserve this advantage.
Betaine-homocysteine methyltransferase โ clears homocysteine using betaine (derived from choline) as the methyl donor. An alternative to the folate/B12 pathway.
๐ข Healthy BHMT pathway. This is a critical compensatory route for Hanees โ since his MTR/MTHFR pathway is impaired, his BHMT can pick up the slack using betaine (TMG). Supplementing TMG/betaine directly feeds this working pathway and helps maintain healthy homocysteine levels even when the folate cycle is underperforming.
These insights connect Hanees's methylation genetics to his lived symptoms and coaching priorities โ including the allergy-methylation connection.
All supplements are prioritised by clinical urgency and targeted to Hanees's specific gene variants. Dosing follows SelfDecode evidence-based guidelines.
| Supplement | Form & Dose | Timing | Targets | Why it matters for Hanees |
|---|---|---|---|---|
| ๐ Methylcobalamin B12 | 1000mcg/day sublingual | Morning, dissolve under tongue | TCN2 ยท FUT2 ยท CUBN ยท MTR | Bypasses his triple B12 absorption deficit. Active methyl form required โ not cyanocobalamin. |
| ๐ฟ L-Methylfolate | 400โ800mcg/day | Morning with food | MTHFR ยท MTR ยท DNMT3B | Active folate bypasses MTHFR bottleneck. Never use folic acid โ he cannot convert it. |
| ๐ชจ Magnesium Glycinate | 350mg/day | Evening before bed | MTHFR ยท MAT1A ยท COMT | Cofactor for MTHFR and MAT1A. Directly calms COMT pathway by reducing sympathetic nervous system activation. |
| ๐พ Betaine (TMG) | 500โ1000mg/day | With meals | BHMT ยท Homocysteine | Feeds his strong BHMT pathway โ the most reliable compensatory route for homocysteine clearance given his MTHFR. |
| ๐ก Riboflavin (Vitamin B2) | 25โ50mg/day | With breakfast | MTHFR ยท MTHFD1 | B2 is a direct cofactor for MTHFR enzyme. Improves MTHFR efficiency โ especially important for C677T variant carriers. |
| โ๏ธ SAMe | 400mg/day | Empty stomach, morning | MAT1A ยท COMT ยท DNMT3B | Provides methyl groups directly. Supports COMT function (dopamine clearance) and DNA methylation via DNMT3B. |
| ๐ต EGCG (Green Tea Extract) | 400mg/day | With lunch | COMT support | Modulates COMT activity โ helps balance dopamine and noradrenaline clearance. Reduces stress hormone accumulation. |
| ๐ถ Vitamin B6 (P5P form) | 50mg/day | With breakfast | CBS ยท DAO enzyme | Active P5P form. Dual benefit: CBS cofactor (glutathione via transsulfuration) AND DAO enzyme cofactor (histamine clearance). |
| ๐ฉ Zinc | 15mg/day | With dinner | BHMT ยท Folate absorption | Required for gut enzymes that absorb folate. Also supports BHMT enzyme activity. Take away from copper supplement. |
| ๐ Omega-3 (EPA+DHA) | 2g/day | With meals | COMT ยท DNMT3B | Reduces neuroinflammation. Supports COMT gene expression. Anti-inflammatory benefit compounds with his allergy protocol. |
These tests will reveal Hanees's actual methylation status beyond genetics. Run baseline before starting the protocol, then repeat at 8โ12 weeks.