Magnesium L-threonate: Effects in Alzheimer's disease and Oral Application

General Description

Magnesium L-threonate shows promise as a therapeutic agent for Alzheimer's disease by modulating the microbiota-gut-brain axis, enhancing cognitive function, reducing oxidative stress and inflammation, and restoring intestinal barrier function. It influences gut microbiota composition, systemic metabolism, and the serum metabolome, highlighting its multifaceted approach to neuroprotection. Additionally, oral application of Magnesium L-threonate has been shown to enhance opioid analgesia, reduce opioid dosage requirements, and alleviate opioid-induced constipation in patients with advanced cancer. These findings suggest potential for Magnesium L-threonate in alleviating Alzheimer's symptoms and improving cancer pain management.

Figure 1. Magnesium L-threonate

Effects in Alzheimer's disease

Cognitive Function

Magnesium L-threonate has emerged as a promising therapeutic agent for Alzheimer's disease, particularly through its modulation of the microbiota-gut-brain axis. Alzheimer's disease is increasingly recognized to involve disruptions in gut microbiota composition and function, which can exacerbate cognitive decline and neuroinflammation. Studies on animal models, such as those expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1), have shown that Magnesium L-threonate treatment enhances cognitive function and reduces oxidative stress and inflammation. 

Gut Microbiota

Notably, it influences the gut microbiota by altering the abundance of specific genera. In particular, Magnesium L-threonate decreases levels of Allobaculum while increasing populations of beneficial bacteria like Bifidobacterium and Turicibacter. These changes in gut microbiota composition are crucial as they can influence systemic inflammation and metabolic pathways linked to neurodegenerative diseases. Furthermore, Magnesium L-threonate treatment affects the serum metabolome, enriching metabolites associated with pathways critical for neuroprotection. This suggests a systemic effect whereby Magnesium L-threonate not only targets cognitive function directly but also modulates biochemical pathways that support neuronal health.

Systemic Impact

An additional significant finding is the restoration of intestinal barrier function in APP/PS1 mice treated with Magnesium L-threonate. This is evidenced by improvements in the expression of intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5), which play a crucial role in maintaining gut barrier integrity. Restoring intestinal barrier function is important as it prevents the translocation of harmful substances from the gut into systemic circulation, thereby mitigating neuroinflammation and cognitive decline associated with Alzheimer's disease. In summary, Magnesium L-threonate shows promise in alleviating Alzheimer's disease symptoms by targeting the microbiota-gut-brain axis. Its ability to modulate gut microbiota composition, influence systemic metabolism, and restore intestinal barrier function highlights its multifaceted approach to neuroprotection. These preclinical findings provide a strong rationale for further investigating Magnesium L-threonate as a potential therapeutic strategy for Alzheimer's disease in clinical settings. ¹

Oral Application

Cancer Pain Management

The oral application of Magnesium L-threonate has shown significant potential in enhancing opioid analgesia and reducing opioid dosage requirements in patients with advanced cancer. This was observed in a randomized, double-blind, placebo-controlled trial conducted at a tertiary hospital in Shanghai, China, which aimed to assess the effects of Magnesium L-threonate on opioid analgesia. In this study, Magnesium L-threonate was administered in the form of L-TAMS capsules, at dosages of either 1.5 g or 2.0 g based on the patient's weight. Patients were monitored over a 90-day period, with evaluations at 7, 14, 21, 30, 60, and 90 days. The results showed that Magnesium L-threonate significantly enhanced the analgesic effects of opioids. Patients in the Magnesium L-threonate group required less incremental increases in their daily morphine doses compared to those receiving a placebo. For example, by day 30, the Magnesium L-threonate group showed a 9.85 mg/d increase in morphine dose versus 20.49 mg/d in the placebo group, and this trend continued through days 60 and 90.

Enhancing Opioid Analgesia

Moreover, Magnesium L-threonate was effective in mitigating opioid-induced constipation, a common side effect that can significantly affect quality of life. The ability of Magnesium L-threonate to reduce opioid dosages and alleviate associated side effects offers a dual benefit for patients with advanced cancer, potentially improving pain management and overall patient comfort. This trial highlights the value of Magnesium L-threonate as a supplementary treatment in cancer pain management, suggesting broader applications for this compound in clinical practice. ²

Reference

1. Liao W, Wei J, Liu C, et al. Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis. Neural Regen Res. 2024; 19(10): 2281-2289.

2. Wu S, Jin T, Ma B, et al. Oral application of magnesium-L-threonate enhances analgesia and reduces the dosage of opioids needed in advanced cancer patients-A randomized, double-blind, placebo-controlled trial. Cancer Med. 2023; 12(4): 4343-4351.