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Pharmacopsychiatry 2002; 35(4): 135-143
DOI: 10.1055/s-2002-33195
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Oral Mg2+ Supplementation Reverses Age-Related Neuroendocrine and Sleep EEG Changes in Humans

K. Held1 , I. A. Antonijevic1 , H. Künzel1 , M. Uhr1 , T. C. Wetter1 , I. C. Golly2 , A. Steiger1 , H. Murck1
  • 1Max Planck Institute of Psychiatry, Munich, Germany
  • 2Institute of Pharmacology and Toxicology, LMU, Munich, Germany
The study was supported by Hermes Arzneimittel GmbH, Großhesselohe/Munich
Further Information

Publication History

Manuscript received: 2. 5. 2001 Revised: 13. 7. 2001

Accepted: 30. 10. 2001

Publication Date:
06 August 2002 (online)

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Introduction

The process of normal ageing is characterised by changes of CNS function leading to alteration of the sleep electroencephalogram (EEG) and hormone secretion. In the elderly, a decline in sleep continuity, a shortening of rapid eye movement (REM) latency, a decrease in slow wave sleep (SWS) and an increase in nocturnal wakefulness are detectable [9] [28] [65]. Beside these changes, a loss of the sleep dependent increase in spindle incidence and duration has been demonstrated in elderly [51].

In addition, ageing is accompanied by a disinhibition of HPA system activity in both experimental animals [35] and humans [38] [84]. Another altered endocrine system in the course of ageing is the renin-angiotensin-aldosterone system (RAAS). An age-related decrease in plasma renin activity has been demonstrated in normotensive human subjects [22] [60] [71] [83] [86] accompanied by a tendency for a reduced aldosterone concentration [32]. Similarly, a reduced activity of the RAAS in experimental animals has been shown in aged compared to young animals [21] [36].

There is a close association between sleep architecture, especially SWS, and the activity of the glutamatergic and GABAergic system. An increase in SWS in rats was observed after intrathalamic administration of the NMDA antagonist DL-2-amino-5-phosphono-pentanoic acid (APV) [46] and after the intraperitoneal injection of NMDA antagonist MK-801 [16]. Also, the GABAA agonists THIP (gaboxadol) increased delta activity in rats [49] [50] and SWS in young healthy controls [27] and in elderly humans [55]. An earlier study from our group on the effects of i. v. Mg2+ on the sleep EEG and nocturnal hormone secretion pointed to an NMDA-antagonistic and a GABA-agonistic efficacy of Mg2+ [59], an assumption well in line with preclinical studies [40] [61] [72] [73] [78].

Direct evidence for a disturbance of the glutamatergic neurotransmission in ageing was given by preclinical studies in mice demonstrating a reduced reuptake of glutamate in aged compared to younger animals [70]. The resulting glutamatergic overactivity might secondarily result in the age-related declines of NMDA receptors, as has been reported in rodents [20] [80]. This is of interest since a decrease in NMDA binding sites has been correlated with a declining performance of memory-associated tasks [63].

Also, the changes in the sleep EEG occurring during ageing bear some similarities to those in Mg2+ deficiency. Mg2+ deficits lead to sleep disturbances with increased wakefulness at the expense of SWS [23] or a predominance of active waking and a decrease in total sleep time [64] in rats. On the other hand, there have also been reports on a sleep-stabilising effect of Mg2+. Intravenous (i. v.) administration of Mg2+ before surgery led to a significantly better quality of sleep in a double blind trial on surgical patients [81].

Besides its modulatory influence on glutamatergic and GABAergic neurotransmission, Mg2+ also has an angiotensin II (ATII)-antagonistic effect [4] [43], and is able to influence the HPA system [59]. The combination of these properties of Mg2+ influencing systems involved in the process of ageing and reports on its sleep stabilising effect led us to perform a study on the effect of oral Mg2+ supplementation on the sleep EEG and the nocturnal hormone secretion.

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Katja Held, M.D. 

Max Planck Institute of Psychiatry

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