Magnesium Glycinate vs Zinc Picolinate

Mechanism

Magnesium is a cofactor for >600 enzymatic reactions including all ATP-dependent reactions (Mg-ATP is the true substrate), DNA/RNA polymerases, and ion channel regulation. Magnesium glycinate chelate provides highly bioavailable elemental magnesium bound to glycine. The glycine moiety itself is an inhibitory neurotransmitter (glycine receptors) and NMDA receptor co-agonist at the glycine binding site. The chelated form minimizes the osmotic laxative effect of ionic magnesium salts. Magnesium regulates NMDA receptor gating (voltage-dependent Mg2+ block), GABA-A receptor potentiation, HPA axis modulation, and parathyroid hormone secretion.

Standard Dosing

200-400mg elemental magnesium daily

Timing

Evening/bedtime (promotes relaxation and sleep quality). Can split AM/PM.

Cycle Duration

ongoing

Side Effects

• Drowsiness
• Mild GI discomfort
• Loose stools (less than other Mg forms)
• Hypotension at very high doses

Contraindications

• Severe renal insufficiency (impaired Mg excretion — risk of hypermagnesemia)
• Myasthenia gravis (Mg can worsen neuromuscular junction blockade)
• Heart block (Mg slows AV conduction)

Best Stacking Partners

Mechanism

Zinc is a cofactor for >300 enzymes and is a structural component of >2000 transcription factors (zinc finger proteins). It is essential for: immune function (T-cell maturation, NK cell activity, neutrophil function), DNA synthesis and repair, protein synthesis, wound healing, taste/smell perception, insulin storage and secretion (zinc-insulin hexamer in beta cells), testosterone synthesis (cofactor for 17-beta-hydroxysteroid dehydrogenase), and antioxidant defense (Cu/Zn-SOD, metallothionein induction). Picolinate chelation via picolinic acid (a tryptophan metabolite) enhances intestinal absorption via DMT1 transporters.

Standard Dosing

15-30mg elemental zinc (as zinc picolinate) daily

Timing

With food to minimize nausea. Separate from iron, calcium, and copper supplements by 2 hours. NOT with high-phytate meals.

Cycle Duration

ongoing (with copper balance — see notes)

Side Effects

• Nausea (especially on empty stomach)
• Metallic taste
• Copper depletion (chronic high-dose without copper)
• Headache
• GI upset
• Reduced HDL at very high doses

Contraindications

• Copper deficiency (zinc will worsen it)
• Concurrent penicillamine therapy without separation

Best Stacking Partners