• Onset: Sleep effects often within 2-3 nights for glycinate. Calm/anxiolytic effect over 1-2 weeks. BP and metabolic effects over 4-12 weeks.
• Acute experience: Most forms produce no acute "feel." Glycinate at 300-400 mg pre-bed often produces mild relaxation within 30-60 min.
• Chronic experience: Users replete from baseline deficiency report subjectively better sleep, fewer muscle cramps, less anxiety, and more steady energy. Users already replete report little subjective change — Mg is a structural baseline tool, not a state-change tool.
• Dreams: Vivid dreams in 10-30% of users at >300 mg pre-bed.
• GI: Loose stool at high doses, especially with citrate or oxide. Glycinate well-tolerated to 600 mg. Switch form before reducing dose if GI intolerance is the limit.
• Off-cycle: Mg leaves the body slowly (whole-body turnover is weeks). No withdrawal pattern; deficiency symptoms creep back over weeks if supplementation stops in a low-intake context.

• Tolerance buildup: None. Mg is a structural mineral, not a receptor-acting drug.
• Recommended cycle: None. Daily-safe indefinitely.
• Reset protocol: N/A.

Synergistic with

• magnesium-l-threonate — Brain-penetrant Mg; covers CNS targets that systemic Mg does not. The user's V4 default: glycinate for systemic, Magtein for CNS. Complementary, not redundant.
• taurine — Both Ca²⁺-modulating, both calming, both CV-protective. Taurine independently lowers BP and HR (Guan 2024 meta-analysis). Mg taurate combines both in one molecule for users prioritizing CV.
• glycine — Mg glycinate IS the chelate. Free glycine (3 g pre-bed) layers cleanly with Mg for sleep — different mechanisms (glycine: thermoregulation + GlyR; Mg: NMDA block + GABA-A). Common pre-bed pair.
• l-theanine — Both calming pre-bed adjuncts via different mechanisms (theanine: GABA + glutamate + alpha-wave; Mg: NMDA + GABA-A). Stacks well for anxiety + sleep.
• Vitamin D3 — Mg is the obligate cofactor for vitamin D activation (both 25-hydroxylation and 1α-hydroxylation). Mg deficiency blunts D3 response. Always co-supplement when running D3.
• Vitamin B6 (P5P) — Facilitates intracellular Mg transport. Combined Mg + B6 has slight additional anxiolytic and PMS benefit.
• Zinc — Common co-supplementation. Mild competition for absorption only at very high simultaneous doses (>40 mg zinc + >400 mg Mg); typical doses fine.

Avoid stacking with

• High-dose calcium (>1 g) at the same dose — Compete for absorption; separate by 2 h. Standard dietary calcium is non-issue.
• Quinolone (cipro, levo) and tetracycline (doxy) antibiotics — Mg chelates and reduces absorption. Separate by 2-4 h.
• Bisphosphonates — Reduced absorption. Separate by 2 h.
• Levothyroxine — Reduced absorption. Separate by 4 h.

Neutral / safe co-administration

All other V4/V5 stack components — DHA, NAC, citicoline, curcumin, rhodiola, modafinil, bromantane, ALCAR, apigenin, astaxanthin, creatine, beta-alanine, vitamin C, K2, ashwagandha, etc.

• Absorption-reducing chelation: Quinolones, tetracyclines, bisphosphonates, levothyroxine — separate by 2-4 h.
• Increased urinary Mg loss: Loop diuretics (furosemide, bumetanide), thiazide diuretics (HCTZ), aminoglycosides, cisplatin, foscarnet, amphotericin B, cyclosporine.
• Reduced intestinal Mg absorption: Chronic PPIs (omeprazole, esomeprazole etc.) — FDA black-box warning for hypomagnesemia with chronic PPI use >1 year.
• Additive hypotension: With other antihypertensives — clinical concern at very high Mg doses, not at supplemental doses.
• CYP enzymes: None — Mg is not CYP-metabolized.
• Lithium: Mg can increase lithium levels modestly; coordinate with prescribing physician if on lithium therapy.
• Digoxin: Mg deficiency potentiates digoxin toxicity; repletion is part of digoxin toxicity management.

• TRPM6 / TRPM7 variants affect intestinal Mg absorption efficiency. Loss-of-function TRPM6 mutations cause hypomagnesemia with secondary hypocalcemia; common variants may affect supplemental dose required for repletion. Not actionable without genotyping.
• CNNM2 variants affect renal Mg reabsorption.
• SLC41A1 / SLC41A3 variants affect Mg transport.
• For the user (23andMe pending June 2026): If raw data shows TRPM6 reduced-function variants, may benefit from higher total Mg dose or split dosing across more meals. Otherwise, current V4 doses (~544 mg total) are appropriate.

For the user: V4 stack uses Doctor's Best Albion TRAACS glycinate (4 tabs = 400 mg elemental, ~$0.28/day) + Source Naturals Magtein (3 caps = 144 mg elemental as L-threonate). This dual-form approach is correct and locked.

General buying rules:

1. Look for licensed chelate names (Albion TRAACS, Magtein, Magnesium Bisglycinate Buffered) — these guarantee true chelation.
2. Read elemental Mg content per serving carefully — many "1000 mg magnesium" products are 1000 mg of the salt (e.g., glycinate molecule) of which only ~140 mg is elemental Mg.
3. Avoid generic "magnesium complex" blends that hide cheap oxide as the bulk. Look for single-form labels.

• Baseline (before optimizing):

  • RBC Mg (better than serum) — normal range 4.2-6.8 mg/dL; aim for mid-to-upper range. Most accurate widely-available test. Quest, LabCorp run it.
  • Serum Mg — included on standard CMP. Normal 1.7-2.2 mg/dL but <1% of body Mg is in serum, so this is a low-sensitivity test. Use as screening only.
  • Ionized Mg (where available) — most physiologically relevant fraction; not widely available outside specialty labs.
  • Urinary Mg loading test — gold standard but rarely done outside research. 24-h urine Mg after IV Mg load — % excretion <80% suggests deficiency. Practical only in clinical research settings.
  • Sleep quality (PSQI) — subjective sleep quality questionnaire; useful for tracking Mg-supplementation response.
  • Blood pressure — track for hypertensives on Mg.
  • Fasting glucose, HbA1c — for insulin sensitivity tracking.
  • hsCRP — Mg-deficient state is mildly inflammatory; CRP may drop with repletion.

• During use (3-6 months): RBC Mg to confirm repletion. Sleep quality, BP, glucose for outcome tracking.

• For the user: Bloodwork window is June 5-15, 2026 (post-23andMe). RBC Mg is a useful add to the panel — confirms 400 mg glycinate + Magtein dosing is producing repletion. Should be in mid-to-upper normal.