Quick Comparison

B-ComplexSAMe
Half-LifeWater-soluble; excreted daily (except B12 which is stored)1.5-2 hours
Typical DosageStandard: A quality B-complex providing 25-100 mg of B1, B2, B3, B5, B6, plus 400-800 mcg folate (as methylfolate) and 500-1000 mcg B12 (as methylcobalamin). Methylated forms preferred for B9 and B12 (folate → methylfolate, B12 → methylcobalamin). Take in the morning — B vitamins can be mildly energizing.Standard: 400-1600 mg daily on an empty stomach. Start at 200-400 mg and increase gradually. Take in the morning — can be activating. Enteric-coated tablets preferred for stability. Often combined with B vitamins (B12, folate) which are needed for SAMe recycling.
AdministrationOral (capsules, tablets, sublingual). Methylated forms preferred for B9 and B12. Take with breakfast.Oral (enteric-coated tablets). Take on empty stomach 30 minutes before food. Enteric coating protects from stomach acid degradation.
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Mechanism of Action

B-Complex

Each B vitamin serves specific neurological functions: B1 (thiamine) — cofactor for transketolase (pentose phosphate pathway), pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase; essential for glucose metabolism and ATP production in neurons. B2 (riboflavin) — precursor to FAD/FMN, cofactors for Complex I and II of the electron transport chain, and glutathione reductase. B3 (niacin/niacinamide) — precursor to NAD+/NADPH via the salvage pathway; NAD+ is substrate for sirtuins, PARP, and 400+ dehydrogenases. B5 (pantothenic acid) — component of coenzyme A, required for acetylcholine synthesis via choline acetyltransferase and for fatty acid oxidation. B6 (pyridoxine) — cofactor for AADC (5-HTP to serotonin, L-DOPA to dopamine), GABA synthesis (GAD), and homocysteine metabolism. B9 (folate) — tetrahydrofolate donates methyl groups for dTMP and purine synthesis, and for homocysteine remethylation. B12 (cobalamin) — cofactor for methionine synthase (myelin maintenance) and methylmalonyl-CoA mutase.

SAMe

SAMe serves as the principal methyl donor in over 100 transmethylation reactions catalyzed by SAM-dependent methyltransferases. In the brain, it donates methyl groups to phosphatidylethanolamine N-methyltransferase (PEMT), converting PE to phosphatidylcholine and maintaining neuronal membrane fluidity critical for receptor function. It methylates DNA via DNMT enzymes, modulating gene expression epigenetically. SAMe is essential for catechol-O-methyltransferase (COMT) activity, which metabolizes dopamine and norepinephrine, and for phenylethanolamine N-methyltransferase (PNMT), which converts norepinephrine to epinephrine. It feeds the transsulfuration pathway, producing cysteine via cystathionine beta-synthase (CBS) and cystathionine gamma-lyase, ultimately supporting glutathione synthesis for antioxidant defense. SAMe also donates methyl groups for myelin basic protein methylation, essential for myelin sheath integrity and nerve conduction velocity.

Risks & Safety

B-Complex

Common

Bright yellow urine (harmless — riboflavin excretion), mild nausea.

Serious

Very safe at standard doses. B6 can cause peripheral neuropathy at >200 mg daily for extended periods.

Rare

Flushing from niacin (B3) if non-flush form is not used.

SAMe

Common

Nausea, diarrhea, anxiety, insomnia.

Serious

Can trigger manic episodes in bipolar disorder. Serotonin syndrome risk when combined with SSRIs or MAOIs.

Rare

Skin rash, increased homocysteine without B vitamin co-supplementation.

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