Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans.
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.
Held
Katja
K
Max Planck Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany. held@mpipsykl.mpg.de
Antonijevic
I A
IA
Künzel
H
H
Uhr
M
M
Wetter
T C
TC
Golly
I C
IC
Steiger
A
A
Murck
H
H
D000284:Administration, Oral; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000375:Aging / Q000097:blood* / Q000187:drug effects; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001127:Arginine Vasopressin / Q000097:blood; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D017616:Magnesium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
D006728:Hormones; D017616:Magnesium Compounds; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D006854:Hydrocortisone