Abstract and Introduction
Abstract
BACKGROUND: Previous studies have evaluated the impact of oral magnesium on blood pressure; however, they used magnesium salts with low bioavailability, had methodological issues, and showed differing results.
OBJECTIVE: To evaluate the long-term blood pressure-lowering ability of oral magnesium L-lactate versus placebo in patients with implanted cardioverter defibrillators (ICDs).
METHODS: In this double-blind, 24-week trial, 50 patients with ICDs were randomized to receive magnesium L-lactate (6 tablets daily, supplying a total of 504 mg of elemental magnesium daily) or matching placebo for at least 12 weeks. Baseline intracellular and serum magnesium concentrations were determined. The primary efficacy endpoint was the mean sitting systolic blood pressure at 24 weeks.
RESULTS: In 50 patients who completed at least 12 weeks of follow-up, 86% of patients, regardless of randomization, had a baseline intracellular magnesium deficiency, but no patients had a serum magnesium deficiency. At 12 weeks, magnesium L-lactate significantly reduced systolic blood pressure compared with placebo (117.7 ± 11.8 vs 126.3 ± 16.7 mm Hg, respectively; p = 0.04). In the 45 patients who continued in the study through the 24-week time period, the systolic blood pressure reduction was maintained, but statistical significance was lost (118.1 ± 14.1 vs 125.5 ± 17.2 mm Hg, respectively; p = 0.13). Magnesium L-lactate did not impact diastolic blood pressure at either time period (p ≥ 0.75 for both). Patients with a documented history of hypertension at baseline showed similar qualitative results to the primary analysis.
CONCLUSIONS: A large number of subjects with ICDs have an intracellular magnesium deficiency not captured through serum magnesium determination. The use of magnesium L-lactate in patients with an ICD results in significant improvement in systolic blood pressure at 12 weeks, which may be maintained through 24 weeks.
Introduction
Magnesium is the second most abundant intracellular cation, with less than 1% in the body found extracellularly. It has been demonstrated that intracellular magnesium levels are not related to serum concentrations, with intracellular repletion lagging behind serum levels in response to an intravenous infusion of magnesium.[1] Magnesium deficiency is common among patients with coronary heart disease but often goes untreated (or undertreated). Oral magnesium is available in many formulations, the majority of which are not significantly absorbed, ranging from 2% with magnesium oxide to 20% with magnesium chloride.[2] Magnesium L-lactate is a sustained-release oral formulation of magnesium with a higher bioavailability (41%) than that of other commonly used magnesium salts.[3]
Epidemiologic studies support the role that hypomagnesemia plays in the pathogenesis of hypertension.[4,5,6,7] However, clinical trials evaluating the effect of magnesium supplementation on blood pressure have shown inconsistent results, making its practical application as an antihypertensive controversial.[8,9,10,11,12,13] Motoyama et al.[8] provided 21 male patients with uncomplicated essential hypertension magnesium oxide (600 mg/day) for 4 weeks, followed by placebo for 4 weeks. They found that magnesium supplementation reduced patients' mean systolic blood pressure from 111 ± 6 mm Hg at baseline to 102 ± 6 mm Hg after 4 weeks (p < 0.001), which then increased to 108 ± 5 mm Hg (p < 0.001) after 4 weeks of subsequent placebo treatment. In an 8-week crossover study, 62 Japanese men and women with mild-to-moderate essential hypertension were randomized to receive either magnesium oxide 480 mg/day or placebo.[9] During the follow-up period, average blood pressures (both systolic and diastolic) were significantly lower in patients receiving magnesium compared with those receiving placebo (-3.7 ± 1.3 and -1.7 ± 0.7 mm Hg, respectively; p < 0.05). Alternatively, a randomized, double-blind, placebo-controlled trial of 76 patients with type 2 diabetes and borderline hypertension at baseline trial found no beneficial impact of a magnesium oxide/zinc sulfate combination on either systolic or diastolic blood pressure.[10] Likewise, Doyle et al.[11] failed to identify a significant effect of a magnesium oxide-supplemented diet (21.6 mmol/day) on either systolic or diastolic blood pressure among 26 healthy normotensive individuals over a 28-day period in a placebo-controlled crossover trial.
To date, only 2 clinical trials have evaluated the impact of magnesium lactate on blood pressure.[12,13] In a prospective, double-blind trial, patients with mild-to-moderate hypertension were randomized to receive 30 mEq/day of magnesium (27.48 mEq /day magnesium lactate and 2.52 mEq/day magnesium citrate) or placebo for 6 months.[12] In patients with an average blood pressure of 159 ± 13 and 95 ± 4.8 mm Hg (systolic and diastolic, respectively), magnesium supplementation did not induce significant changes in either systolic or diastolic blood pressure compared with placebo.
There is also evidence that low body stores of magnesium increase the risk of abnormal heart rhythms, which may increase the risk of complications following a myocardial infarction.[14] In a pilot study completed in 20 patients with a history of arrhythmias requiring drug therapy, we found that 63.2% of patients had baseline intracellular magnesium concentrations below the normal reference range.[15] No deficiencies in other intracellular ions (phosphorus, chloride, calcium, potassium, or sodium) were seen. Following supplementation with magnesium L-lactate (504 mg of elemental magnesium daily) for 48 hours, the intracellular magnesium concentrations rose significantly (p = 0.002), with all patients achieving a concentration within the reference range. Treatment with placebo did not alter intracellular magnesium concentrations (p = 0.32).
Given the inconsistent efficacy data currently available with magnesium supplements in hypertensive patients, as well as the lack of trials in patients with arrhythmias, we designed the current study to evaluate the blood pressure-lowering ability of oral magnesium L-lactate versus placebo in patients with an implantable cardioverter defibrillator (ICD). The current investigation was a piggyback study of the Adjuvant Magnesium Trial (AdMag). The AdMag trial was planned to be a 12-month follow-up trial in 240 subjects with ICDs evaluating ICD shocks. That study could not be completed due to the problems with patient recruitment and patient tolerability due to the pill burden.
The Annals of Pharmacotherapy. 2009;43(4):569-576. © 2009 Harvey Whitney Books Company
Cite this: Effect of Magnesium L-Lactate on Blood Pressure in Patients with an Implantable Cardioverter Defibrillator - Medscape - Apr 01, 2009.
