Letter to the Editor Open Access
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World J Psychiatry. Sep 19, 2022; 12(9): 1261-1263
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1261
Magnesium may be an effective therapy for Alzheimer’s disease
Dao-Yun Lei, Jie Sun
Dao-Yun Lei, Jie Sun, Department of Anesthesiology, Zhongda Hospital Southeast University, Nanjing 210009, Jiangsu Province, China
ORCID number: Dao-Yun Lei (0000-0001-9105-9021); Jie Sun (0000-0002-8647-7867).
Author contributions: Lei DY and Sun J contributed to the conception of the research; Lei DY and Sun J wrote the letter and contributed to the revision of the letter; all authors approved the final manuscript for submission.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jie Sun, PhD, Doctor, Professor, Research Scientist, Department of Anesthesiology, Zhongda Hospital Southeast University, No. 87 Dingjiaqiao, Nanjing 210009, Jiangsu Province, China. dgsunjie@hotmail.com
Received: May 10, 2022
Peer-review started: May 10, 2022
First decision: June 11, 2022
Revised: June 13, 2022
Accepted: September 1, 2022
Article in press: September 1, 2022
Published online: September 19, 2022


Magnesium deficiency in serum or the brain of Alzheimer’s disease (AD) patients has been shown to be associated with AD. Current research suggests that supplementing or restoring magnesium may be a novel approach to AD treatment. However, the physiological properties of magnesium make such treatment difficult. It is undeniable that magnesium may be an effective therapy for AD.

Key Words: Alzheimer’s disease, Magnesium, Therapy, Deficiency

Core Tip: Magnesium deficiency in serum or the brain of Alzheimer’s disease (AD) patients has been shown to be associated with AD. However, the physiological properties of magnesium make such treatment difficult. Undeniably, magnesium may be an effective therapy for AD.


Alzheimer’s disease (AD) is the most common dementia characterized by the decline of cognitive function in the elderly. The accumulation of β-amyloid plaques and the existence of neurofibrillary tangles are the pathological bases for the dysfunction of various signaling pathways in the nervous system[1]. Since the pathogenic mechanism of AD is still not clear, its treatment approaches are unlikely to be meaningfully effective. Several approved drugs ameliorate some of the symptoms of AD, but no current interventions can modify the underlying disease mechanisms[2,3]. We read the interesting article by Xiong et al[4], which was published in World Journal of Psychiatry. Their study found that magnesium L-threonate alleviated neuronal apoptosis by inhibiting oxidative stress, especially in the hippocampus. Although the research work revealed a potential scheme for the treatment of AD, we still believe that some views deserve further consideration and look forward to receiving the reply from the authors.

Admittedly, magnesium is one of the most abundant cations in the intracellular environment after potassium. Mg2+ is tightly regulated and kept at basal levels by normal Mg2+ intake, absorption, and metabolism under physiological conditions. Total magnesium levels in the hippocampus of AD patients decreased by 18% compared with that of normal subjects[5]. Although the presence of magnesium deficiency in patients with AD is notable, its severity may be underestimated. The concentration of serum Mg2+ in healthy people ranges from 0.70 mM to 1.05 mM[6]. Mg2+ deficiency is generally determined by measuring the total serum Mg2+ concentration, but it cannot accurately reflect the concentration of magnesium in the human body. Most Mg2+ is stored in bone, muscle, and soft tissue, and the proportion of serum Mg2+ is very low. Even if the human body is in a serious state of Mg2+ depletion, serum magnesium may also be in the normal range. Although the magnesium concentration in AD patients is reduced, the degree of deficiency cannot be accurately evaluated. It is not only difficult to evaluate magnesium deficiency, but also a reasonable supplement of magnesium. Slutsky et al found that following long-term magnesium supplementation, Mg2+ concentration in cerebrospinal fluid only increases by 15%[7]. On one hand, systemic magnesium is closely regulated by renal function. On the other hand, the blood-brain barrier separates the brain from the daily fluctuations of blood magnesium. Hippocampal synapses are very sensitive to small changes in extracellular Mg2+ concentration (increasing the concentration of magnesium by 15% can increase the synaptic density by 50%)[8]. Encouragingly, compared with other Mg2+ compounds (such as magnesium chloride, magnesium citrate, and magnesium gluconate), dietary intake of magnesium L-threonate could significantly increase Mg2+ levels in the brain[4]. Therefore, restoring brain magnesium may be a potential way to treat cognitive impairment in patients with AD.


In summary, magnesium may be a novel therapeutic strategy for AD-induced cognitive impairment. However, numerous clinical studies are still needed to confirm the clinical application of magnesium.


Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Medicine, research and experimental

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Chakrabarti S, India; Van Den Bossche MJA, Belgium S-Editor: Chen YL L-Editor: Wang TQ P-Editor: Chen YL

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