SAM-e

SAM-e (S-adenosyl-L-methionine) is not a direct agonist of any neurotransmitter receptor. Instead, it is a universal methyl donor involved in the synthesis and regulation of several neurotransmitters, hormones, and phospholipids. Its neurological effects come from upstream biochemical support, not direct receptor binding.

🧠 Neurotransmitter Activity of SAM-e

❌ Direct Agonism?

• SAM-e does not bind to or activate neurotransmitter receptors.

• It is not an agonist of:

  • Dopamine

  • Serotonin (5-HT)

  • GABA

  • Norepinephrine

  • Acetylcholine

⚙️ Pharmacological Actions of SAM-e

🔹 1. Methyl Donor in Neurotransmitter Synthesis

• SAM-e donates methyl groups in the synthesis and metabolism of:

  • Dopamine

  • Serotonin

  • Norepinephrine

  • Melatonin

• It supports enzymes like COMT (catechol-O-methyltransferase) and PNMT, involved in neurotransmitter conversion and clearance.

✅ Indirectly increases levels of key mood-related neurotransmitters

🔹 2. Epigenetic Modulation

• SAM-e affects DNA and histone methylation, influencing the expression of genes tied to:

  • Brain plasticity

  • Mood regulation

  • Inflammation

🔹 3. Liver Function & Detoxification

• Critical for glutathione production and phase II detox pathways in the liver.

• Often used in research and clinical settings for fatty liver, hepatitis, or drug-induced liver damage.

🔹 4. Joint & Connective Tissue Support

• Promotes cartilage repair and anti-inflammatory effects by enhancing sulfur metabolism and methylation in connective tissue.

🧬 Summary Table

⚠️ Important Notes

• Works best with adequate levels of folate, B12, and B6, which are needed to recycle SAM-e via the methylation cycle.

📏 Typical Daily Dosing Ranges

✅ Start low (e.g., 200–400 mg/day), then gradually increase based on tolerance and goals.

⏱️ How to Take SAM-e

• Timing: Best taken on an empty stomach, at least 30 minutes before food.

• Frequency: Split larger daily doses into 2–3 smaller doses to reduce GI upset and maintain stable plasma levels.

• Form: Use enteric-coated tablets or capsules to protect against stomach acid degradation.

⚠️ Important Considerations

• Methylation support: If taken long-term or in high doses, pair with:

  • Methylated B12 (methylcobalamin)

  • Folate (5-MTHF)

  • Vitamin B6

• This helps prevent homocysteine buildup and supports the methylation cycle.

⚠️ Individuals with bipolar disorder should avoid SAM-e without supervision — it may trigger mania or agitation.

🧊 Storage

• SAM-e is sensitive to heat and moisture

• Store in a cool, dry place

🔁 Cycle Length

• Often used daily for 4–12 weeks, then re-evaluated.

• Some protocols use 5 days on, 2 days off to prevent tolerance or overstimulation.