Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans

Pharmacopsychiatry. 2002 Jul;35(4):135-43. doi: 10.1055/s-2002-33195.

Abstract

The process of normal aging is accompanied by changes in sleep-related endocrine activity. During aging, an increase in cortisol at its nadir and a decrease in renin and aldosterone concentration occur. In aged subjects, more time is spent awake and slow-wave sleep is reduced: there is a loss of sleep spindles and accordingly a loss of power in the sigma frequency range. Previous studies could show a close association between sleep architecture, especially slow-wave sleep, and activity in the glutamatergic and GABAergic system. Furthermore, recent studies could show that the natural N-methyl-D-aspartate (NMDA) antagonist and GABA(A) agonist Mg(2+) seems to play a key role in the regulation of sleep and endocrine systems such as the HPA system and renin-angiotensin-aldosterone system (RAAS). Therefore, we examined the effect of Mg(2+) in 12 elderly subjects (age range 60-80 years) on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. A placebo-controlled, randomised cross-over design with two treatment intervals of 20 days duration separated by 2 weeks washout was used. Mg(2+) was administered as effervescent tablets in a creeping dose of 10 mmol and 20 mmol each for 3 days followed by 30 mmol for 14 days. At the end of each interval, a sleep EEG was recorded from 11 p.m. to 7 a.m. after one accommodation night. Blood samples were taken every 30 min between 8 p.m. and 10 p.m. and every 20 min between 10 p.m. and 7 a.m. to estimate ACTH, cortisol, renin and aldosterone plasma concentrations, and every hour for arginine-vasopressin (AVP) and angiotensin 11 (ATII) plasma concentrations. Mg(2+) led to a significant increase in slow wave sleep (16.5 +/- 20.4 min vs. 10.1 +/- 15.4 min, < or =0.05), delta power (47128.7 microV(2) +21417.7 microV(2) vs. 37862.1 microV(2) +/- 23241.7 microV(2), p < or =0.05) and sigma power (1923.0 microV(2) + 1111.3 microV(2) vs. 1541.0 microV(2) + 1134.5 microV(2), p< or =0.05 ). Renin increased (3.7 +/- 2.3 ng/ml x min vs. 2.3 +/- 1.0 ng/ml x min, p < 0.05) during the total night and aldosterone (3.6 +/- 4.7 ng/ml x min vs. 1.1 +/- 0.9 ng/ml x min, p < 0.05) in the second half of the night, whereas cortisol (8.3 +/- 2.4 pg/ml x min vs. 11.8 +/- 3.8 pg/ml x min, p < 0.01) decreased significantly and AVP by trend in the first part of the night. ACTH and ATII were not altered. Our results suggest that Mg(2+) partially reverses sleep EEG and nocturnal neuroendocrine changes occurring during aging. The similarities of the effect of Mg(2+) and that of the related electrolyte Li+ furthermore supports the possible efficacy of Mg(2+) as a mood stabilizer.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenocorticotropic Hormone / blood
  • Aged
  • Aging / blood*
  • Aging / drug effects
  • Aldosterone / blood
  • Angiotensin II / blood
  • Arginine Vasopressin / blood
  • Cross-Over Studies
  • Dietary Supplements
  • Drug Administration Schedule
  • Electroencephalography / drug effects*
  • Female
  • Hormones / blood*
  • Humans
  • Hydrocortisone / blood
  • Magnesium Compounds / administration & dosage
  • Magnesium Compounds / pharmacology*
  • Male
  • Middle Aged
  • Renin / blood
  • Sleep / drug effects*
  • Sleep Stages / drug effects
  • Sleep Wake Disorders / drug therapy
  • Sleep Wake Disorders / etiology
  • Treatment Outcome

Substances

  • Hormones
  • Magnesium Compounds
  • Angiotensin II
  • Arginine Vasopressin
  • Aldosterone
  • Adrenocorticotropic Hormone
  • Renin
  • Hydrocortisone