Strongest support is in liver disease, where trials show consistent improvement in bile and liver-injury markers. Mood and joint evidence is split. Most tolerate it; stomach upset is common and mild. Main concerns are mood elevation in susceptible people and adding to medicines that raise serotonin. Evidence for treating a deficit beats topping up a healthy system. (Full Review)
| Marker | Target | Why |
|---|---|---|
| Alanine transaminase | 10–26 U/L men, 10–19 U/L women | Primary liver-injury marker and the endpoint SAMe is most credibly claimed to move |
| Aspartate transaminase | 10–26 U/L | The enzyme that fell significantly in pooled liver trials, making it the most responsive marker |
| Gamma-glutamyl transferase | Under 20 U/L | Sensitive marker of bile-flow obstruction and oxidative stress, the pathway SAMe acts on |
| Total bilirubin | 0.3–1.0 mg/dL | The other marker that fell significantly in pooled trials; tracks bile flow directly |
| Homocysteine | Under 8 µmol/L | Tracks the disposal route for the homocysteine that SAMe metabolism generates |
| Vitamin B12 (serum) | 500–1,000 pg/mL | Determines whether methionine can be regenerated, capping what supplementation can achieve |
| Folate (red-cell) | Above 400 ng/mL | Reflects tissue folate over months rather than the last meal, unlike serum folate |
| Plasma SAMe-to-S-adenosylhomocysteine ratio | No established target; track change from the individual's own baseline | The only direct read on methylation capacity rather than on substrate supply |
Cadence: Baseline, 4 weeks, 12 weeks, then every 6–12 months on continued use. Homocysteine again at 8 weeks where baseline B-vitamin status was marginal; liver enzymes at 4 and 8 weeks where SAMe is taken for a liver indication.