Exploring the Effects of Magnesium Ions on Peripheral Neuropathy, Serum Magnesium Ion Concentration,Sleep Quality, and Quality of Life in Patients With Colorectal Cancer Receiving Chemotherapy.

(I) Study Main Purpose This study aims to understand the relevant impact and changes of magnesium on peripheral neuropathy during chemotherapy in colorectal cancer patients. Since there is currently no absolutely effective method to prevent the occurrence of peripheral neuropathy, the expected results of this research can provide colorectal cancer patients with an evidence-based method for peripheral neuropathy prevention, thereby improving their quality of life.

(II) Background and Objectives l Overview of Colorectal Cancer (CRC) According to data from the Ministry of Health and Welfare in 2024, malignant tumors have remained the leading cause of death in Taiwan since 1982. Colorectal cancer (CRC) accounts for 13.2% of cancer deaths, ranking second among the top ten major cancer causes. CRC is one of the most common and fatal cancers globally. Its development is often gradual, involving multiple genetic mutations. Based on the adenoma-carcinoma sequence, normal colonic mucosal epithelial cells overproliferate due to the loss of the APC (adenomatous polyposis coli) gene, gradually forming early adenomas. This progresses to CRC due to K-RAS (Kirsten-ras gene) activation and DCC(deleted in colon cancer) gene deletion, subsequently metastasizing to other body parts. The wall of the large intestine consists of the mucosa, submucosa, muscularis propria, subserosa, and serosa. While polyps typically start as benign, prolonged development can lead to a portion becoming cancerous and transforming into CRC. CRC is classified by location: approximately 10% in the cecum, 2% in the ascending colon, 10% in the transverse colon, 3% in the descending colon, 25% in the sigmoid colon, and 50% in the rectum. Over 95% of CRC cases are primarily adenocarcinoma. The incidence of CRC in Taiwan is associated with diet, lifestyle, and heredity, and the incidence in men is approximately 20% to 30% higher than in women.

l Treatment-Related Side Effects and Neuropathy Individuals newly diagnosed with CRC are primarily treated with surgery, often supplemented by radiation therapy and chemotherapy, which may be administered alone or in combination. Side effects of combined chemo- and radiotherapy include oral mucositis, altered taste, dry mouth, nausea, vomiting, fatigue, diarrhea, and peripheral neuropathy, which consequently affect patients' physiological function and quality of life. Chemotherapy has a significant effect on improving the survival rate of CRC. However, patients often suffer long-term side effects from this treatment. Chemotherapy drugs commonly used to treat CRC are highly toxic to the peripheral nervous system. Therefore, patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN). The most common manifestation is sensory neuropathy, leading to severe impairment of dexterity, mobility, and balance. Symptoms include tingling, numbness, and burning pain in the hands or feet, collectively known as Hand-Foot Syndrome (HFS).

The occurrence of HFS causes discomfort in the daily lives of CRC patients, severely impairing their daily activities, including difficulties with fine motor skills, dexterity, mobility, and balance. This impacts patient routines, sleep, and reduces quality of life, potentially leading to dose reduction or even treatment discontinuation. HFS can take six months or more after treatment cessation to slowly improve and disappear, making prevention and continuous management of HFS highly important. Common tools for assessing HFS include the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-neurotoxicity (FACT/GOG-Ntx), the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), and the Patient Neurotoxicity Questionnaire (PNQ).

l Potential Mechanism of Magnesium in Improving CIPN Neurologist Erick Gamelin proposed that oxalate, a metabolite of oxaliplatin, acts on sodium ion channels or chelates with calcium ions, disrupting the voltage potential and increasing neuronal excitability, leading to nerve damage. Administering calcium and magnesium salt preparations can prevent ion depolarization, thereby preventing neuropathy. Magnesium is crucial for neuromuscular transmission and acts as a membrane stabilizer, influencing both the central and peripheral nervous systems. Its neuroprotective mechanisms include reducing abnormal dorsal root ganglion (DRG) and neuronal degeneration, decreasing oxidative stress, and preventing tissue hypoxia. Therefore, low concentrations of magnesium may be linked to neuropathic pain, especially diabetic neuropathy (DN). Magnesium also acts as an antagonist to the N-methyl-D-aspartate (NMDA) receptor channel, involved in abnormal sensation and pain signal processing. Magnesium is a charged, highly water-soluble ion that cannot directly cross the lipid stratum corneum. It can permeate through essential oils, which loosen the skin barrier, increasing the permeability of water and other molecules, and promoting local blood circulation, indirectly aiding the movement of solutes (like magnesium salts). Studies show that iontophoresis can enhance absorption. A weak direct current in an electric footbath with magnesium solution creates an "electrodriving" effect, pushing magnesium ions towards the skin, increasing the chance for charged particles to be absorbed through the skin in an aqueous medium.