NutriStack
Hydrochlorothiazide and Magnesium Glycinate, a synergy.
HCTZ increases renal magnesium excretion, and chronic use can lead to hypomagnesemia. Magnesium depletion can worsen potassium depletion (refractory hypokalemia) and increase the risk of cardiac arrhythmias, especially in patients also taking digoxin.
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At a glance
- Substances
- Hydrochlorothiazide and Magnesium Glycinate
- Pair type
- Synergy
- Evidence (highest tier)
- Moderate
- Source citations
- 4 sources
- Stack Score effect
- +2 to your Stack Score (per scored synergy row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Synergy · Moderate evidence
Synergy
What is happening. HCTZ increases renal magnesium excretion, and chronic use can lead to hypomagnesemia. Magnesium depletion can worsen potassium depletion (refractory hypokalemia) and increase the risk of cardiac arrhythmias, especially in patients also taking digoxin.
Mechanism. HCTZ increases magnesium excretion by reducing its reabsorption in the distal convoluted tubule. Magnesium depletion impairs the Na+/K+-ATPase and ROMK channel function, making hypokalemia refractory to potassium supplementation alone.
Recommendation. Monitor magnesium levels during chronic HCTZ therapy. Consider magnesium supplementation (200-400mg/day), especially if potassium levels are difficult to correct. Magnesium repletion often helps resolve resistant hypokalemia.
Sources (4)
- Dai LJ et al. Magnesium transport in the renal distal convoluted tubule. Physiol Rev. 2001;81(1):51-84. PMID 11152754
- Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis.. BMC Complementary Medicine and Therapies. 2021. PMID 33865376
- Veronese N, Dominguez LJ, Pizzol D et al.. Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.. Nutrients. 2021. PMID 34836329
- Veronese N, Pizzol D, Smith L et al.. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials.. Nutrients. 2022. PMID 35277037
Stack Score
How this pair moves the number.
Effect on the composite score
If both Hydrochlorothiazide and Magnesium Glycinate are in the same stack, this pair applies +2 to your Stack Score (per scored synergy row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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