Efficacy of Magnesium Supplementation in Cancer Patients Developing Hypomagnesemia Due to Anti-EGFR Antibody: A Systematic Review.

Background/Aim: Hypomagnesemia is a common side effect of anti-epidermal growth factor receptor (EGFR) antibodies, which may lead to arrhythmia. However, there are no evidence-based guidelines for magnesium (Mg) supplementation in the management of hypomagnesemia in patients with anti-EGFR antibodies. Therefore, we performed a systematic review to address clinical questions regarding these cancer patients. Materials and Methods: Three electronic databases were searched for articles published until June 18, 2021. The main outcomes used were "anti-EGFR antibody" and "hypomagnesemia". Results: After screening 78 references in PubMed, Cochrane Library, and ICHUSHI-web databases, three studies were included in the review. One study revealed the effectiveness of Mg supplementation in the management of hypomagnesemia in patients receiving cetuximab. However, no studies have investigated whether correcting hypomagnesemia can lead to the suppression of arrhythmias as a clinical outcome. Conclusion: Weak evidence suggests that Mg supplementation, as a preventive measure when developing hypomagnesemia following the initiation of anti-EGFR antibody therapy, may prevent the worsening of hypomagnesemia, and subsequently prevent associated arrhythmia occurrence.

Hypomagnesemia may be related to frailty, gait and balance problems, and basic activities of daily living in older adults.

OBJECTIVES: The study aims to investigate the relationship between hypomagnesemia, preclinical hypomagnesemia, and normomagnesemia as along with geriatric syndrome and comprehensive geriatric parameters(CGA). METHODS: 217 patients who applied to the geriatric clinic between November 2022 and December 2023 were included in the study. All patients underwent CGA. Patients were categorized into three groups: Magnesium (Mg) level ≤ 1.5 mg/dL, Mg level 1.5-1.8 mg/dL, and Mg level > 1.8 mg/dL. These three groups were compared in terms of demographic characteristics, comorbidities, CGA parameters, and geriatric syndromes. Regression analyses was conducted for significant parameters, adjusting for confounders. RESULTS: 74.9% of all participants were female, with an average age of 76.5 ± 6.6 years. The frequency of hypomagnesemia was 14.2%. Demographic characteristics and medication use, including proton pump inhibitors and diuretics, were similar in these three groups. While the FRIED frailty scale and the duration of the timed-up-and-go test were higher in the hypomagnesemia group, the Basic Activities Daily of Living (ADLs) and the Tinetti-POMA(performance-oriented mobility assessment) scores were lower in the hypomagnesemia group. When normomagnesemia was accepted as the reference category, FRIED frailty scale, Basic ADLs, and POMA score were more significant in the hypomagnesemia group (p = 0.025, p = 0.013 and p = 0.011,respectively), but there was no significance in the preclinical hypomagnesemia group regardless of the covariates. CONCLUSION: Hypomagnesemia, particularly serum Mg levels below 1.5 mg/dL, may be associated with frailty, basic ADLs, gait, and balance tests. In geriatric practice, patients with hypomagnesemia should be evaluated in terms of the risk of the mentioned disorders.

The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus.

OBJECTIVE: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). DESIGN, PATIENTS AND MEASUREMENTS: This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. RESULTS: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = -.117, r = -.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76-7.52, p = .001). CONCLUSION: Albuminuria is more frequently observed in patients with hypomagnesemia.

First Diagnosis of Gitelman Syndrome During Pregnancy in an Adolescent Female: A Case Report.

Gitelman syndrome (GS) is an inherited somatic recessive disorder characterized by hypokalemic metabolic alkalosis, accompanied by hypocalciuria and hypermagnesuria. It usually presents in late childhood or young adults with muscle weakness, tetany, or convulsions. Limited information is available in the literature regarding the proper management of this syndrome during pregnancy, as well as its effects on both the mother and the child. We herein present the case of a 16-year-old primigravida who was admitted to the emergency department with chief complaints of abdominal pain, weakness, and vomiting for the past three days during the 12th week of gestation. Routine blood investigations revealed hypokalemia and hypomagnesemia, and electrocardiography (ECG) showed ST-segment depressions. Further evaluation was performed due to persistent hypokalemia, and metabolic alkalosis, hypocalciuria, and hyperaldosteronism were found. Hence, a clinical diagnosis of GS took place. The pregnancy progressed smoothly without complications; potassium levels remained consistently below normal, requiring supplementation three times during pregnancy. Pregnant women with GS should be reported due to the rarity of cases, aiming to establish a standardized approach for monitoring and management.

Persistent hypocalcemia post total thyroidectomy in a case of Hashimoto's thyroiditis.

INTRODUCTION: Thyroidectomy is a surgical procedure commonly employed in the management of thyroid disorders. Complications include, but not limited to, postoperative hypocalcemia. In order to effectively manage hypocalcemia following thyroidectomy, a comprehensive approach is essential. CASE PRESENTATION: We present an intriguing case of a patient who developed severe transient hypocalcemia that was resistant to conventional therapeutic interventions following a total thyroidectomy. DISCUSSION: Hypocalcemia post total thyroidectomy is a well-established complication which can lead to devastating consequences. Some of the contributing factors include failure of pre-operative optimization, autoimmune disease, malignancy, and prolonged surgical time. A comprehensive approach to identify the contributors is essential in managing the risk factors associated with hypocalcemia. CONCLUSION: This case highlights the importance of pre-operative elevation and management as well as the close monitoring and individualized treatment plans for patients at risk for post-thyroidectomy hypocalcemia. The successful management of severe hypocalcemia in this patient involved a multidisciplinary team approach and consideration of alternative treatment options.

Magnesium Biology.

Magnesium (Mg2+) is essential for energy metabolism, muscle contraction, and neurotransmission. As part of the Mg-ATP complex, it is involved in over 600 enzymatic reactions. Serum Mg2+ levels are tightly regulated between 0.7 mmol/L and 1.1 mmol/L by interplay of intestinal absorption and renal excretion. In the small intestine, Mg2+ is absorbed paracellularly via claudin-2, and -12. In the colon, transcellular absorption of Mg2+ is facilitated by TRPM6/7 and CNNM4. In the kidney, the proximal tubule reabsorbs only 20% of the filtered Mg2+. The majority of the filtered Mg2+ is reabsorbed in the thick ascending limb (TAL), where the lumen-positive transepithelial voltage drives paracellular transport via claudin-16/-19. Fine-tuning of Mg2+ reabsorption is achieved in the distal convoluted tubule (DCT). Here, TRPM6/7 tetramers facilitate apical Mg2+ uptake, which is hormonally regulated by insulin and EGF. Basolateral Mg2+ extrusion is Na+ dependent and achieved by CNNM2 and/or SLC41A3. Hypomagnesemia (serum Mg2+ < 0.7 mmol/L) develops when intestinal and/or renal Mg2+ (re)absorption is disturbed. Common causes include alcoholism, type 2 diabetes mellitus, and the use of pharmacological drugs, such as proton-pump inhibitors (PPIs), calcineurin inhibitors (CNIs) and thiazide diuretics. Over the last decade, research on rare genetic and acquired Mg2+ disorders have identified Mg2+ channel and transporter activity, DCT length, mitochondrial function, and autoimmunity as mechanisms explaining hypomagnesemia. Classically, treatment of hypomagnesemia depended on oral or intravenous Mg2+ supplementation. Recently, prebiotic dietary fibers and SGLT2 inhibitors have been proposed as promising new therapeutic pathways to treat hypomagnesemia.

The Role of Sodium-Glucose Co-transporter 2 Inhibitors in Patients With Hypomagnesemia: A Systematic Review.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes, have demonstrated benefits in reducing heart failure hospitalizations, slowing chronic kidney disease, and decreasing major cardiovascular events. Recent studies have shown that SGLT2 inhibitors can elevate serum magnesium levels in patients with type 2 diabetes, suggesting potential benefits in managing refractory hypomagnesemia. This systematic review analyzed relevant case reports, observational studies, and randomized controlled trials (RCTs) to investigate the association between SGLT2 inhibitors and hypomagnesemia. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and study quality was assessed using the CAse REport (CARE) guidelines. It encompassed four case reports, one retrospective observational study, one post-hoc analysis of 10 RCTs, and one meta-analysis of 18 RCTs, with a total study population of 19,767 patients. The meta-analysis revealed that SGLT2 inhibitors significantly increased serum magnesium levels in patients with type 2 diabetes, with a linear dose-dependent increase noted particularly for canagliflozin. Additionally, the case reports and other studies suggested that SGLT2 inhibitors could exert extraglycemic effects, potentially enhancing magnesium balance beyond their impact on urinary magnesium excretion. This systematic review underscores the effectiveness of SGLT2 inhibitors in addressing refractory hypomagnesemia linked with urinary magnesium wasting. It also suggests promising avenues for the application of these drugs in diverse patient populations.

Frequency of Hypomagnesemia and Its Relationship With Severity Among Patients of Acute Ischemic Stroke Presenting to a Tertiary Care Hospital.

Objective The objective of this study was to assess the prevalence of hypomagnesemia and its association with the severity of acute ischemic stroke (AIS) in patients presenting at a tertiary care hospital. Methodology A total of 100 patients with AIS were included in the study. Demographic data, including age, gender, and severity of stroke, were collected. Serum magnesium levels were measured at admission, and the severity of stroke was classified as mild, moderate, or severe based on clinical criteria. The presence of hypomagnesemia was defined as a serum magnesium level below 1.8 mg/dL determined within 72 hours of onset of stroke. Statistical analysis was performed to assess the association between hypomagnesemia, stroke severity, age, and gender. Results The mean age of the patients with standard deviation was 65.45 ± 11.8 years, with the majority (38, 38%) aged 60-74 years. There were 53 (53%) male and 47 (47%) female patients. Hypomagnesemia was found in 35 (35%) patients, with an average magnesium level of 1.93 mg/dL and a standard deviation of 0.37 at admission. There was no statistically significant difference in the distribution of stroke severity (P = 0.779; P = 0.406) or hypomagnesemia (P = 0.287; P = 0.591) based on gender or age group, respectively. Stratification based on stroke severity showed that 16 (39%) patients with mild stroke, 10 (31.3%) with moderate stroke, and 9 (33.3%) with severe stroke had hypomagnesemia. The correlation between stroke severity and hypomagnesemia was weak (r = 0.099). Further, among hypomagnesemia patients, the majority were females aged 60-74 years. Conclusions This study found a weak positive relationship between the severity of AIS and the presence of hypomagnesemia. However, no statistically significant association was observed between gender or age group and stroke severity or hypomagnesemia. These findings suggest that further research is needed to understand the role of hypomagnesemia in AIS and its potential implications for patient management.

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.

BACKGROUND AND HYPOTHESIS: Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally. METHODS: Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28. RESULTS: Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1. CONCLUSIONS: In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.

Prevalence of Dysmagnesemia among Patients with Diabetes Mellitus and the Associated Health Outcomes: A Cross-Sectional Study.

Introduction: Magnesium is a vital intracellular cation crucial for over 320 enzymatic reactions related to energy metabolism, musculoskeletal function, and nucleic acid synthesis and plays a pivotal role in human physiology. This study aimed to explore the prevalence of dysmagnesemia in patients with diabetes mellitus and evaluate its correlations with glycemic control, medication use, and diabetic complications. Methods: A cross-sectional study was conducted at Sultan Qaboos University Hospital, including 316 patients aged 18 years or older with diabetes mellitus. Data included demographics, medical history, medications, and biochemical parameters. Serum total magnesium concentrations were measured, and dysmagnesemia was defined as magnesium ≤ 0.69 mmol/L for hypomagnesemia and ≥1.01 mmol/L for hypermagnesemia. Results: The prevalence of hypomagnesemia in patients with diabetes was 17.1% (95% CI: 13.3-21.7%), and hypermagnesemia was 4.1% (95% CI: 2.4-7.0%). Females were significantly overrepresented in the hypomagnesemia group, while the hypermagnesemia group showed a higher prevalence of hypertension, retinopathy, an increased albumin/creatinine ratio, chronic kidney disease (CKD), elevated creatinine levels, and a lower adjusted calcium concentration. The multinominal logistic regression exhibited that the female sex and higher serum-adjusted calcium were independent risk factors of hypomagnesemia. In contrast, the presence of hypertension, higher levels of albumin/creatinine ratio, and stage 5 CKD were independent risk factors of hypermagnesemia. Conclusions: Hypomagnesemia was common among patients with diabetes mellitus; however, hypermagnesemia was associated with microvascular complications.

Persistent Hypomagnesemia in the Context of Refeeding and Supplementation: A Case Report.

Refeeding syndrome is characterized by electrolyte imbalances that occur during nutritional replenishment in malnourished patients. Hypomagnesemia is a potential complication.  We present a unique case of a female, young adult patient with anorexia nervosa who experienced persistent hypomagnesemia during inpatient refeeding that did not resolve with magnesium supplementation. Extended diagnostic evaluation included genetic testing that revealed heterozygous variants of uncertain significance in the PKD1 and SCNN1G genes as well as a pathogenic variant in the SMARCAL1 gene. These variants are not currently associated with a known renal disorder.  While the extensive work-up for persistent hypomagnesemia in the context of appropriate supplementation did not yield a definitive diagnosis, this case emphasizes the need to pursue alternative etiologies and treatments of unexpectedly refractory electrolyte abnormalities during the course of refeeding.

Associations among diabetes medication use, serum magnesium, and insulin resistance in a cohort of older Puerto Rican adults.

BACKGROUND: Hypomagnesemia is commonly observed in individuals with diabetes, but how diabetes medications alter magnesium (Mg) status remains unclear. OBJECTIVES: We aimed to examine the association between diabetes medication and hypomagnesemia and evaluate whether serum Mg mediates the association between diabetes medication and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in a prospective cohort. METHODS: Adults from the Boston Puerto Rican Health Study were included (n = 1106). Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for cross-sectional association between diabetes medication and hypomagnesemia (serum Mg <0.75 mmol/L). Longitudinal mediation analysis was performed to evaluate the direct and indirect (via serum Mg) associations between diabetes medication and 4-y HOMA-IR in 341 participants with baseline hemoglobin A1c (HbA1c) of ≥6.5%. RESULTS: Mean age at baseline was 59.0 ± 7.6 y, with 28.0% male and 45.8% with hypomagnesemia. Use of metformin [OR (95% CI) = 3.72 (2.53, 5.48)], sulfonylureas [OR (95% CI) = 1.68 (1.00, 2.83)], and glitazones [OR (95% CI) = 2.09 (1.10, 3.95)], but not insulin, was associated with higher odds of hypomagnesemia. Use of multiple diabetes medications and longer duration of use were associated with higher odds of hypomagnesemia. Serum Mg partially mediated the association between metformin and HOMA-IR [indirect association: ß (95% CI) = 1.11 (0.15, 2.07)], which weakened the direct association [ß (95% CI) = -5.16 (-9.02, -1.30)] by 22% [total association: ß (95% CI) = -4.05 (-7.59, -0.51)]. Similarly, serum Mg mediated 17% of the association between sulfonylureas and elevated HOMA-IR. However, the mediation by serum Mg was weak for insulin and glitazones. CONCLUSIONS: Diabetes medication, especially metformin, was associated with elevated odds of hypomagnesemia, which may weaken the association between metformin and lowering of HOMA-IR. The causal inference needs to be confirmed in further studies.

Hypocalcaemic tetany linked to vitamin D deficiency and hypomagnesemia in primary intestinal lymphangiectasia: a literature review.

Primary intestinal lymphangiectasia (PIL) is a rare disorder in children causing protein-losing enteropathy. Vitamin D deficiency and hypomagnesemia contributed to the tetany. The literature review reflects the importance of screening for these deficiencies and regular serum magnesium monitoring in PIL cases with neuromuscular or ionic abnormalities.

Hypomagnesemia with Secondary Hypoparathyroidism and Hypocalcemia due to Novel Variants in the Transient Receptor Potential Cation Channel Subfamily M Member 6 ( TRPM6 ) Gene.

HOMG1 (hypomagnesemia 1, intestinal) or hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder of magnesium metabolism, characterized by impaired magnesium absorption. This disorder may mimic other conditions presenting with neonatal seizures. Here, we report an infant diagnosed to have hypomagnesemia with secondary hypocalcemia due to novel variants in TRPM6 gene.

Association of Hypomagnesemia With Diabetic Complications.

OBJECTIVE: The study aimed to study the association of hypomagnesemia with diabetic complications in type 2 diabetics. MATERIALS AND METHOD: This cross-sectional study, conducted at a Ghurki Trust Teaching Hospital, spanned from January to June 2023 and included 100 randomly selected diabetic patients aged 30-70. With institutional board approval and informed consent, the study focused on assessing hypomagnesemia, using a standard level of below 1.6 mg/dL, ensuring participant confidentiality and privacy. Data collected through physical assessments were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States), including descriptive statistics, analysis of variance (ANOVA), and paired t-test. RESULTS: A total of 100 diabetic admitted patients were randomly selected for the study ages from 30 to 70 years irrespective of their gender. The mean age of the participants was 53.86±9.74 years. The mean HbA1c of the participants was 8.7±2.32. Forty-eight percent of them had HbA1c less than 8, while 52% had greater than 8 HbA1c. The mean HbA1c in the hypomagnesemia group was 10.8±1.98, while in the normomagnesemia group, it was 8.9±2.2. There were 58.97% of foot ulcers in Group 1, while in Group 2, there were 31.14%. Around 38.46% and 14.75% had neuropathy in Groups 1 and 2, respectively. Nephropathy in Group 1 was 28.20%, while in Group 2, it was 11.47%. Around 69.23% of Group 1 had retinopathy and 37.70% had retinopathy in Group 2. Hypertension was 23.07% in Group 1 and 37.70% in Group 2; moreover, 7.69% and 8.19% had coronary diseases in Groups 1 and 2 accordingly. CONCLUSION:  The current study concluded that hypomagnesemia was found to have an association with diabetic complications like neuropathy, nephropathy, foot ulcers, and poor glycemic control as evidenced by HbA1c.

Severe Hypomagnesemia Caused by Proton-Pump Inhibitors in a Patient With an Ostomy.

Proton pump inhibitors (PPIs) are commonly used for many gastrointestinal issues, such as gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger-Ellison syndrome. Many patients are on life-long daily therapy with this class of medications. The adverse effects of long-term use of PPI have been studied, and over the last two decades, a link between hypomagnesemia and PPI has been established. In addition, other electrolyte derangements can also ensue, such as hypokalemia and hypocalcemia. Losses through the gastrointestinal or renal systems may also be responsible for this electrolyte disturbance. In this case, we present a "perfect storm" of a patient who, in addition to having ongoing gastrointestinal losses through an ostomy, had severe hypomagnesemia to less than 1 mg/dL compounded by PPI use. Through its unique mechanism of action on intestinal epithelial cells, PPI use in certain settings can potentially be catastrophic. Severe hypomagnesemia may manifest as tetany, convulsions, tremors, arrhythmias, or torsades de pointes.

Magnesium and vitamin D in long COVID syndrome; do they help?

Since the start of the COVID-19 pandemic, it has become increasingly clear that the disease can have relevant multisystemic and long-term effects, and several studies have attempted to identify key determinants of the disease course. Here we discuss recent evidence suggesting that, in long COVID patients, combined magnesium and vitamin D deficiencies associate with a higher number of clinical manifestations, as compared to patients with normal levels of both nutrients. We highlight the potential synergistic effects of these deficiencies and propose that future studies should explore a causal link with the risk of developing long COVID. Most importantly, randomized clinical trials are needed to determine if magnesium and vitamin D supplementation can improve long COVID symptoms, providing a safe and affordable support therapy to the benefit of patients and society.

Thinking Outside the Box: A Case of Persistent Symptomatic Hypomagnesemia.

Although present in a significant number of people, hypomagnesemia is still an undervalued diagnosis. Therefore, its awareness and comprehensive etiological investigation become imperative. Among its multiple possible causes, drug iatrogenesis plays an important and often overlooked role. Here, we present a case of a 78-year-old female with recurrent bouts of severe hypomagnesemia of unknown origin, which, after an extensive study, was determined to be induced by proton pump inhibitors (PPIs). As such, our goal is to raise awareness of the potential risk of this side effect even in monotherapy, as well as to elucidate its underlying mechanisms, which are still not fully understood. Furthermore, it is intended to foster a systematic therapeutic review in these patients and raise discussion about the potential benefits of systematic magnesium monitoring in patients on long-term PPIs.

A Case of Severe Proton Pump Inhibitor-Induced Hypomagnesemia Refractory to Continuous Oral and Intravenous Magnesium Replenishment.

Proton pump inhibitors (PPIs) are frequently used medications to treat a wide variety of gastrointestinal conditions. By irreversibly inhibiting the hydrogen-potassium ATPase pump, they remarkably reduce gastric acid secretion. However, chronic PPI intake can result in serious complications, including severe hypomagnesemia. The following case report presents a severe case of refractory PPI-induced hypomagnesemia (PPIH), resistant to continuous oral and intravenous magnesium replacement, in a 70-year-old male patient, with a long history of PPI use due to persistent epigastric pain. Upon each of the 10 admissions to the hospital, he presented with severe signs and symptoms of hypomagnesemia, such as nausea, muscle fasciculation, diffuse cramps, weakness, neuromuscular irritability, and ECG disturbances, including non-specific T-wave abnormalities. In fact, PPIH has been reported for the first time in 2006. It is believed that the excessive, chronic intake of PPIs can disturb the normal functioning of the transient receptor potential melastatin 6/7 (TRPM 6/7), which is the main pathway of active intestinal magnesium absorption, leading to hypomagnesemia. PPIH is typically characterized by stubborn resistance to oral and intravenous magnesium replenishment but usually resolves after PPI withdrawal. Hence, despite being among the safest and most commonly prescribed drugs, PPI intake should be closely monitored when prolonged usage is planned. Additionally, continuous follow-up and regular assessment of serum magnesium levels are crucial to avoid the occurrence of PPIH and to prevent its potentially deleterious complications, including life-threatening arrhythmias.