Magnesium in the crosshairs of oncology: where it helps, where it hinders, and where it is too early to draw conclusions

Nutrients has published a practical narrative review that brings together everything that is currently known about magnesium (Mg²⁺) in oncology - from the risk of cancer development and side effects of therapy to controversial data on the "magnesium boost" of antitumor drugs. The authors remind: Mg²⁺ is a cofactor of hundreds of enzymes, a participant in DNA/RNA synthesis and an "electrolyte of calm" for the nervous and cardiovascular systems. But in cancer, its role is dual: sufficiency is needed for normal immune and metabolic tissue function, while deficiency is sometimes paradoxically accompanied by a better response to individual targeted drugs. The review carefully places emphasis and offers clinicians pragmatic guidelines for monitoring and correction.

Background

Magnesium is one of the key "invisible" modifiers of the internal environment: a cofactor of hundreds of enzymes, a stabilizer of DNA/RNA and membranes, an obligatory companion of ATP (Mg-ATP is the working currency of the cell), a regulator of ion channels and myocardial conductivity. This is especially important for oncology: any treatment that "hits" dividing cells or the epithelium of the intestine and kidneys easily shifts the magnesium balance - and even moderate hypomagnesemia increases the risk of arrhythmia, seizures, weakness, attention disorders, aggravates nausea and worsens the quality of life.

In the clinic, magnesium deficiency most often appears against the background of cisplatin and other platins (renal tubular channelopathy → magnesiuria), as well as during therapy with anti-EGFR antibodies (cetuximab, panitumumab), where EGFR blockade in the tubules disrupts Mg²⁺ reabsorption. Additional "accelerators" are proton pump inhibitors, loop and thiazide diuretics, chronic diarrhea, old age, nutritional deficiency. Hence the routine need: at the start and during treatment, measure Mg²⁺, potassium and calcium, correct the deficiency and think through hydration - primarily in schemes with platins, where magnesium has been proven to reduce nephrotoxicity.

At the same time, the role of magnesium in the antitumor response is ambiguous. On the one hand, "normomagnesemia" maintains the anti-inflammatory background, genomic stability and immune effector functions - everything that potentially helps the patient to endure therapy and rehabilitate. On the other hand, in a number of observations in metastatic colorectal cancer on anti-EGFR, low levels of Mg²⁺ were associated with better survival without progression; the effect of magnesium on signaling pathways and the tumor microenvironment is discussed mechanistically. This is not a reason to specifically cause a deficiency, but an argument for individualization of correction: "treat the patient, not the number in the analysis."

Finally, prevention and “adjuvant” goals go beyond a single molecule. Dietary magnesium (whole grains, legumes, nuts, green vegetables, “hard” water) has been associated with more favorable metabolic profiles and, in some cohort studies, with a modestly lower risk of some tumors, especially colorectal. But these are correlations: universal recommendations for supplementation in the cancer population are impossible without RCTs that take into account tumor type, treatment regimen, concomitant medications, and baseline nutritional status.

It is in this mixed reality - where magnesium is both a treatment safety factor and a variable in complex tumor biology - that a practical review is needed: it systematizes the mechanisms, risks, clinical scenarios and offers common sense guidelines for monitoring and correction, avoiding the extremes of "prescribe to everyone" or "no one needs it".

What was discussed in the review

• What mechanisms link Mg²⁺ with carcinogenesis (TRPM/CNNM/SLC41 transporters, effects on DNA repair, mitochondria, inflammation).
• Where and why does hypomagnesemia occur in oncotherapy (platinum-containing regimens, anti-EGFR antibodies, PPIs, age, concomitant diseases).
• What do the clinical data say about the prevention of nephrotoxicity, neuropathy, cardiac risks, pain, constipation with opioids?
• How dietary magnesium intake and serum levels are associated (or not associated) with the risk of individual tumors.

Perhaps the most practical part is about the side effects of treatment. Platinums (primarily cisplatin) "expel" Mg²⁺ through the kidneys: hence seizures, arrhythmias and an increased risk of nephrotoxicity. Systematic reviews show that hydration + Mg²⁺ supplementation significantly reduce the likelihood of cisplatin-induced nephrotoxicity; one of the meta-assessments gives an odds ratio of ~0.22. Hypomagnesemia is a common class effect against the background of anti-EGFR therapy (cetuximab/panitumumab). Interestingly, in wild-type KRAS in mCRC, lower blood Mg²⁺ was associated with better progression-free survival and overall survival, but this is not a "recommendation to induce deficiency", but a signal for careful monitoring and individualization of correction. Additional risk factors for hypomagnesemia include proton pump inhibitors and diuretics.

Briefly on the sections where magnesium “makes the difference” in oncotherapy

• Platinum nephrotoxicity (prophylaxis):
  hydration + Mg²⁺ (8-16 mEq) is a standard measure in cisplatin regimens; more recent reviews confirm a protective effect, although the optimal regimen is still being clarified.
• Anti-EGFR (cetuximab/panitumumab):
  hypomagnesemia is common; the relationship with outcomes is contradictory: meta-analyses show better PFS/OS with low Mg²⁺, but there are also studies on worsening prognosis with an early drop in Mg²⁺ during chemo-immunotherapy. Correction - according to the clinical picture and the degree of deficiency, under ECG/electrolyte monitoring.
• Radiation therapy (radioprotection):
  maintaining adequate micronutrient status, including Mg²⁺, is part of nutritional support, especially in cases of gastrointestinal involvement.
• Polyneuropathy (CIPN):
  prophylactic Mg²⁺ (or Ca²⁺/Mg²⁺) infusions have not shown consistent benefit in RCTs; with oxaliplatin, pretherapeutic hypomagnesemia is associated with more severe CIPN and higher dietary Mg²⁺ with lower prevalence and severity of neuropathy.
• Pain and opioid-induced constipation:
  Magnesium-L-threonate and intravenous MgSO₄ have given mixed results in pain relief; in opioid-induced constipation, magnesium oxide is considered as one of the working options (along with osmotic/laxatives and peripheral μ-opioid receptor antagonists), but RCT data are limited.

Part of the review is devoted to cancer risks and diet. The picture is mixed. The most consistent signals are for colorectal cancer: higher dietary Mg²⁺ intake and/or "hard" water correlate with a reduced risk (the effect is small, but reproducible in aggregates). For the liver against the background of non-alcoholic fatty liver disease, higher serum Mg²⁺ was associated with a lower risk of HCC. For the mammary gland, lungs, thyroid gland and esophagus, the results are heterogeneous and depend on the design and associated factors. The authors' conclusion is sober: dietary Mg²⁺ can participate in the prevention of individual tumors, but there is no reason to recommend supplements "just in case". It is better to maintain adequacy through nutrition (whole grains, legumes, nuts, green vegetables) and correct the deficiency as indicated.

What should a doctor and a patient do?

• Measure before and during treatment:
  for everyone on platinum and anti-EGFR - baseline Mg²⁺, then regular monitoring taking into account risk (PPI, diuretics, diarrhea, old age).
• Adjust according to degree and symptoms:
  from diet and oral salts to intravenous MgSO₄ in case of severe deficiency or symptoms (convulsions, arrhythmia), not forgetting potassium/calcium and ECG monitoring.
• Prevention of nephrotoxicity:
  in cisplatin regimens, adhere to hydration with magnesium supplementation; this is the measure with the best evidence-to-benefit ratio.
• Don't "treat the marker", but the person:
  with anti-EGFR, avoid automatic "catching up" of Mg²⁺ to the norm without clinical signs - keep in mind that mild hypomagnesemia sometimes accompanies a better response, but always balance with the risks of arrhythmia and quality of life.

In the big picture, the authors emphasize the paradox: magnesium is both “for” and “against.” On the one hand, sufficient Mg²⁺ maintains genomic stability, immune surveillance, and an anti-inflammatory background. On the other hand, models show that reduced availability of Mg²⁺ can suppress proliferation and angiogenesis in a tumor, while hypomagnesemia against the background of a number of targeted drugs is associated with a better response. The solution is not in extremes, but in contexts: stratify patients by the risk of deficiency, by type of therapy and comorbidity, and then act according to the clinical picture, without losing sight of the kidneys and heart. And most importantly, do not replace the diet with “preventive” capsules until there are convincing grounds for this.

Summary

Magnesium is an important environmental modifier in oncology, but not a universal “cure-all” for cancer. It is definitely worth monitoring and adjusting in cisplatin and anti-EGFR regimens; changing the diet so that it contains enough magnesium; taking supplements only when indicated and under the control of tests. Everything else is the subject of future RCTs: when, for whom, how much, and in what form magnesium actually improves outcomes and safety.

Source: Sambataro D. et al. A Practical Narrative Review on the Role of Magnesium in Cancer Therapy. Nutrients 17(14):2272, 2025. Open access. https://doi.org/10.3390/nu17142272