Hypomagnesemia, the medical term for low magnesium in the blood, is a common and concerning complication in cancer patients. Magnesium is a mineral that plays a fundamental role in over 300 enzyme systems, regulating processes like nerve signal transmission, muscle contraction, and energy production within cells. A deficiency can lead to serious symptoms, including muscle weakness, irregular heart rhythms, and seizures. Due to the nature of the disease and its treatments, patients with cancer frequently face multiple risks that can deplete the body’s magnesium reserves.
Magnesium Wasting Caused By Cancer Treatments
Many anti-cancer therapies can directly interfere with the body’s ability to maintain healthy magnesium levels, primarily by causing the kidneys to excrete too much of the mineral. The kidneys normally reabsorb 90% to 95% of filtered magnesium in structures like the loop of Henle and the distal convoluted tubule. Certain chemotherapy drugs damage the cells lining these tiny kidney structures, leading to excessive magnesium loss in the urine, known as renal wasting.
Platinum-based chemotherapies, especially cisplatin, are the most well-known culprits, causing hypomagnesemia in a large percentage of patients. Cisplatin is largely unbound in the bloodstream, allowing it to be freely filtered by the kidney and accumulate in the tubular cells, where it causes direct injury. This damage impairs magnesium reabsorption, resulting in inappropriate urinary excretion despite low serum levels. This magnesium wasting can be severe and may persist for several years after the treatment has been stopped.
Another class of drugs that causes significant magnesium loss is the monoclonal antibodies and tyrosine kinase inhibitors that target the Epidermal Growth Factor Receptor (EGFR). These agents, such as cetuximab, interfere with the function of a magnesium channel protein called TRPM6 located in the kidney tubules. The TRPM6 channel is required for the final reabsorption step of magnesium in the distal convoluted tubule. By blocking or disrupting this mechanism, the drugs cause a specific and persistent loss of magnesium into the urine.
Direct Effects of the Tumor and Disease
The cancer itself can also directly cause low magnesium levels through several mechanisms that alter the body’s internal chemistry. Some tumors produce substances that mimic hormones, leading to what are called paraneoplastic syndromes. These secreted substances can interfere with magnesium homeostasis, often by promoting kidney loss or severe diarrhea.
For example, certain neuroendocrine tumors can release vasoactive substances that induce secretory diarrhea, which leads to significant loss of magnesium through the gastrointestinal tract. Other tumors may secrete substances that affect the kidneys’ ability to reabsorb magnesium, similar to the effect of some chemotherapy drugs.
Metabolic crises related to the disease also cause acute changes in magnesium status. Tumor Lysis Syndrome (TLS), which occurs when a large number of cancer cells rapidly break down, causes the release of cellular contents into the bloodstream. The initial rush of phosphate from the dying cells can bind with magnesium, forming complexes that reduce the amount of free, active magnesium in the blood. Widespread inflammation, a common feature of advanced cancer, can also alter the distribution and utilization of magnesium.
Issues with Nutritional Intake and Absorption
Low magnesium often results from the inability to ingest and absorb adequate amounts of the mineral from the diet. Many patients experience reduced appetite, or anorexia, and a profound wasting syndrome known as cachexia, which severely limits dietary intake. When food intake is restricted, the body does not take in magnesium found in foods like leafy greens, nuts, and whole grains.
Even when intake is sufficient, the ability to absorb magnesium can be compromised by the disease or its interventions. Gastrointestinal tumors or surgical procedures (like removing parts of the stomach or intestine) can reduce the surface area available for nutrient absorption. Radiation therapy directed at the abdomen or pelvis can also damage the lining of the intestines, causing chronic malabsorption.
Physical losses of magnesium through the digestive tract are also common. Persistent vomiting and severe diarrhea, which are frequent side effects of chemotherapy or symptoms of the underlying cancer, lead to the direct excretion of magnesium. Additionally, some supportive medications, such as Proton Pump Inhibitors (PPIs) used to manage stomach acid, can interfere with intestinal magnesium absorption over time.