Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Magnesium and COVID-19 - Some Further Comments - A Commentary on Wallace TC. Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition? J Am Coll Nutr. 2020;1-9. doi:10.1080/07315724.2020.1785971. Cited in: PMID: 32649272.

The paper "Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition?" by TC Wallace, which was published in the Journal of the American College of Nutrition highlights the importance of adequate magnesium (Mg) supply in relation to COVID-19. Wallace notes that Mg deficiency is associated with low-grade chronic inflammation. Furthermore, hypokalemia and a lack of active Vitamin D are consequences of a Mg deficit. In this way, Mg deficiency may exacerbate the course of COVID-19. Therefore, in patients with Covid-19 permanent monitoring of the Mg status and, if necessary, supplementation should be carried out. The possible importance of Mg in COVID-19 was only recently discussed also by Iotti et al. and the German Society for Magnesium Research e.V. Considering the meaningful connections between Mg and COVID-19 there are relevant research topics that should be addressed: Does Mg deficiency increase the risk of infection with COVID-19 or the risk of a severe course of the disease? Is there an increased prevalence of Mg deficiency in COVID-19 patients? Could Mg supplementation alleviate the course of the disease in COVID-19 or reduce complications? Does pharmacological induction of hypermagnesemia via intravenous Mg provide clinical benefits for COVID-19 patients in the intensive care unit (for example with regard to lung function or thromboembolism)?

Important drug-micronutrient interactions: A selection for clinical practice.

Interactions between drugs and micronutrients have received only little or no attention in the medical and pharmaceutical world in the past. Since more and more pharmaceutics are used for the treatment of patients, this topic is increasingly relevant. As such interactions - depending on the duration of treatment and the status of micronutrients - impact the health of the patient and the action of the drugs, physicians and pharmacists should pay more attention to such interactions in the future. This review aims to sensitize physicians and pharmacists on drug micronutrient interactions with selected examples of widely pescribed drugs that can precipitate micronutrient deficiencies. In this context, the pharmacist, as a drug expert, assumes a particular role. Like no other professional in the health care sector, he is particularly predestined and called up to respond to this task. The following article intends to point out the relevance of mutual interactions between micronutrients and various examples of widely used drugs, without claiming to be exhaustive.

[Vitamin D in oncology: Update 2015]. / Vitamin D in der Onkologie--Komplementäre Medizin: Update 2015.

Vitamin D deficiency is associated with increased incidence of breast and colon cancer as well as with an unfavourable course of non-Hodgkin lymphoma. Vitamin D deficiency is common in cancer patients and is associated with poor cancer prognosis and disease progression. In breast cancer patients under polychemotherapy with anthracycline and taxane, a significant drop in 25(OH)D levels was observed. Osteo-malacia represents a new and previously unreported risk factor for the development of bisphosphonate-related osteonecrosis of the jaw. In vitamin D deficiency (until it is corrected) oral and parenteral bisphosphonates should not be used. Vitamin D status should be monitored in all cancer patients and treated by adequate vitamin D3 supplementation. This applies in particular to cancer patients with poor nutritional status, treatment with aromatase inhibitors, bisphosphonates, and CTX containing anthracycline, taxane and monoclonal antibodies as well as in cases of muscular or mucocutaneous disorders, fatigue and tumor cachexia.

[Micronutrients in diabetology: complementary medicine update 2014]. / Mikronährstoffe in der Diabetologie. Komplementäre Medizin: Update 2014.

Diabetes mellitus is one of the most prevalent endocrine diseases that is associated with high oxidative stress and vascular inflammation. Type 1 and 2 diabetes are characterized by significant losses of important micronutrients such as vitamin C, magnesium, zinc or vitamin D due to metabolic basis of the disease, medication and/or its complications. The evidence of changes in micronutrient metabolism as a consequence of the disease and the influence of selective supplementation are reviewed in this paper. The importance of micronutrients, notably vitamin C, B-group vitamins, vitamin D, vitamin K, coenzyme Q10, magnesium, zinc, chromium and copper under practical conditions are assessed. There is a lot of evidence that demonstrates the positive influence ofmicronutrient supplementation on glycemic control and the risk of diabetic complications.

[Micronutrients in oncology. Current data about vitamin D, selenium, L-carnitine and vitamin C]. / Mikronährstoffe in der Onkologie. Aktuelles zu Vitamin D, Selen, L-Carnitin und Vitamin C.

Many patients receiving cancer treatment use micronutrient supplements, with the intention to complement their cancer treatment, or help them cope with the therapy- and disease-associated side-effects. Up to 90% of the cancer patients are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants and other micronutrients, such as selenium, L-carnitine and vitamin D are added to conventional cytotoxic therapies. It is imperative that physicians discuss the use ofantioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative, but also potentially beneficial effects.

[Essential trace elements, vitamins, and selected electrolytes in complementary medicine for cancer patients]. / Essentielle Spurenelemente, Vitamine und ausgewählte Elektrolyte in der Komplementärmedizin für Tumorpatienten.

OBJECTIVE: Are there any evidence-based medicine (EBM)-supported treatment approaches of complementary and alternative medicine (CAM) methods for urological oncologists? METHODS: We reviewed the actual German S3 guidelines "Supportive Care" and "Complementary Medicine" as well as the online-tool Onkopedia for recommendations about essential trace elements (Zn, Se, Mn, Fe), vitamins (A, B, C, D, E), and electrolytes (Mg, Ca). Furthermore, we added results of randomized trials to present potential future developments. RESULTS: Each therapy with micronutrients should be based on laboratory observation of a deficit. There are selected guideline recommendations for selenium, iron and vitamin D. Potential indications were registered for manganese, vitamin A derivates, and vitamin C. No benefit was observed for vitamin B, zinc, and vitamin E. CONCLUSION: Micronutrients should be substituted in the case of deficit. General supplementation of daily nutrition is not recommended for cancer patients.

Influence of erythropoietin on arterial stiffness and endothelial function in renal transplant recipients.

BACKGROUND/AIMS: Recent retrospective studies suggest an association of therapy with erythropoiesis-stimulating agents (ESAs) and increased mortality in renal transplant recipients (RTR). Large artery structure and function are significantly impaired in RTR which contributes to their high cardiovascular morbidity and could be altered by erythropoietin. We aimed to examine the influence of ESA therapy on large artery stiffness and endothelial function in RTR. METHODS: 63 RTR with chronic allograft dysfunction and renal anemia were randomized to a group receiving darbepoetin alfa (Dar) and a control group (Co). At baseline and after 8 months of treatment (cumulative Dar dose 11.1 µg/kg b.w.) brachial and common carotid artery distensibility coefficients, aortic pulse wave velocity, brachial artery flow-mediated and nitroglycerin-mediated vasodilation were measured as well as the following biomarkers of vascular function: vWF, sVCAM, sICAM, E-selectin, t-PA and PAI-1. RESULTS: 23 patients in the Dar group and 17 patients in the Co group were available for per-protocol analysis. Hemoglobin increased significantly from 10.9 to 12.6 g/dl after 8 months in the Dar group, whereas it remained stable at 11.3 g/dl in the Co group. Effects on large artery stiffness, endothelial function and biomarkers of vascular function did not differ significantly between the two groups. CONCLUSION: Therapy with Dar during 8 months did not significantly impact parameters of large artery stiffness and endothelial function in RTR. These data suggest that therapy with erythropoietin does not deteriorate arterial stiffness and endothelial function in RTR.

Autotransplantation for the treatment of severe renal artery stenosis in a solitary kidney after repeated percutaneous transluminal angioplasty: a case report.

A 66-year-old female suffering from massive atherosclerosis with a long history of renal artery stenosis in the left solitary kidney was admitted to reevaluate an in-stent restenosis. Advanced peripheral arterial disease had formerly been treated by aortobifemoral bypass surgery and a highly eccentric infrarenal abdominal aortic stenosis of 70 - 80% had been treated by patch angioplasty. In this patient several percutaneous transluminal renal angioplasties after a former stent deployment had resulted in recurrent in-stent restenoses. The renal artery stenosis was reevaluated and a re-angioplasty attempt was unsuccessful due to technical failure. Blood pressure remained difficult to manage. Renal function decreased as a result of presumed acute renal failure. A further progression of the renal artery stenosis was found. Autotransplantation to the left iliac fossa was done, because aortorenal bypass was considered impossible. Renal function normalized and follow-up Doppler ultrasonography examinations revealed a newly developed ostial anastomotic stenosis of 60 - 70%. While medical therapy and percutaneous transluminal angioplasty with stent deployment are common treatment options, surgical interventions are reserved for cases of complex stenoses. Autotransplantation as a complex option in the treatment of renal artery stenosis seems to be an adequate alternative in patients with severe, generalized atherosclerosis after failure of interventional procedures and the impossibility of standard surgical techniques.

[Drug-induced magnesium deficiency]. / Magnesium-Mangel und Arzneimittel.

A lot of drugs can induce hypomagnesemia as side effect. On the other hand, magnesium deficiency may be a risk factor for digitalis and drugs known to prolong the QT-interval and thus favour the development of torsades-de-pointes tachycardias. Controversely, the indication for most oral magnesium supplements in Germany is: proven magnesium deficiency if this is the cause for muscular troubles (neuromuscular disturbances, calf cramps). Due to this cutback magnesium attracts poor attention in clinical practice and the determination of serum magnesium concentrations is seldom ordered. Moreover, the lower level of the reference range for serum magnesium is often kept too low. As a consequence hypomagnesemia as side effect remains frequently undetected.

Predictors of impaired SARS-CoV-2 immunity in healthcare workers after vaccination with BNT162b2.

Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.

[Vitamin D and drugs]. / Vitamin D3 und Arzneimittel.

Interactions between drugs and vitamin D have received only little or no attention in the medical and pharmaceutical world in the past. Since more and more drugs are used for the treatment of patients, this topic is increasingly relevant. As such interactions impact the health of the patient and the action and side effects of the drug, physicians and pharmacists should pay more attention to such interactions in the future. A number of drugs can interfere with the vitamin D and bone metabolism. The drug-induced activation of the pregnane X receptor (PXR) is likely to enhance CYP24 expression and the catabolism of 25(OH)D, leading to vitamin D deficiency. PXR-ligands include a wide variety of pharmaceutical agents, such as antiepileptic drugs, taxol, rifampicin, and human immunodeficiency virus protease inhibitors such as ritonavir and saquinavir. Beside this, the medication oriented supplementation of vitamin D can also ameliorate the pharmacologic action of many drugs, such as bisphosphonates, statins and cytostatic drugs.

Serum magnesium: time for a standardized and evidence-based reference range.

Magnesium deficiency can have serious health consequences. Low magnesium intake or low serum levels are risk factors for e.g. type 2 diabetes and cardiovascular diseases. Despite its scientifically recognized importance, too little attention is paid to magnesium in clinical practice. This may be due to the fact that there is no uniform and evidence-based reference range for serum magnesium as is the case for other electrolytes such as sodium and potassium. The serum magnesium concentration is also of a limited informative value, as it is maintained for a long time by releasing magnesium from body pools. A low serum magnesium is a definite sign of magnesium deficiency; however, values within the reference range do not rule out deficiencies. Nevertheless, serum magnesium should become part of routine diagnostics in order to be able to better detect deficiency states. For serum magnesium, a reference range of 0.75 to 0.95 mmol/L (1.82 to 2.31 mg/dL) can often be found. However, according to the current data situation, serum magnesium values of less than 0.85 mmol/L are associated with increased health risks. Therefore, the lower limit of the reference range should be raised to 0.85 mmol/L (2.07 mg/dL).

Magnesium citrate supplementation decreased blood pressure and HbA1c in normomagnesemic subjects with metabolic syndrome: a 12-week, placebo-controlled, double-blinded pilot trial.

Magnesium (Mg) supplementation was shown to improve metabolic syndrome (MetS) parameters in hypomagnesemic patients. The current study evaluated the role of Mg in normomagnesemic individuals with MetS. Patients were randomly assigned to 400 mg Mg as Mg citrate or placebo daily for 12 weeks. Blood pressure (BP), HbA1c, plasma concentrations of glucose, Mg and Ca, blood-ionized Mg, serum concentrations of cholesterol, triglycerides, vitamin D, creatinine, interleukin-6, and C-reactive protein were measured at baseline and after 12 weeks. Data were obtained from n = 13 in the Mg supplemented and n = 11 in the placebo group. Mg supplementation led to a significant increase in plasma Mg concentration (0.78 ± 0.07 mmol/L to 0.83 ± 0.07 mmol/L) and a decrease in systolic and diastolic BP (baseline: 145 ± 10/85 ± 3 mmHg; 12 weeks: 121 ± 5/79 ± 3 mmHg). HbA1c decreased significantly in the Mg group (6.43 ± 0.64% to 6.15 ± 0.55%), and the difference in change between placebo and Mg group was significant. Serum vitamin D levels significantly increased only in the Mg group. In normomagnesemic individuals with MetS, oral Mg citrate supplementation reduced HbA1c and BP.

The role of biofactors in the prevention and treatment of age-related diseases.

The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.

[Magnesium: Relevance for general practitioners - a position paper of the Society for Magnesium Research e. V.] / Magnesium: Bedeutung für die hausärztliche Praxis ­ Positionspapier der Gesellschaft für Magnesium-Forschung e. V.

Magnesium deficiency is to be expected in the population and particularly among risk groups. Magnesium deficiency can cause numerous symptoms, is per se pathological and thus requires treatment. Diagnostics is based on clinical symptoms in conjunction with anamnestic criteria and laboratory parameters. Insufficient magnesium supply is associated with an increased risk for many diseases, e. g. metabolic syndrome, type 2 diabetes and cardiovascular diseases. Magnesium deficiency often appears as comorbidity and may exacerbate diseases. Physicians should pay more attention to magnesium in order to avoid deficits as a cause for multiple symptoms and risk factor for diseases. Optimisation of magnesium status may make an important contribution to the prevention of diseases. Oral magnesium therapy is safe and cost effective.

Whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy male inhabitants (HMI) and prostatic tissue selenium levels (PTSL) in patients with PC and BPH.

BACKGROUND: The aim of this exploratory study was to evaluate whether significant differences exist between whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH), healthy male inhabitants (HMI) in northern Bavaria and the normal value. Furthermore, we investigated whether differences exist between prostatic tissue selenium levels (PTSL) in patients with PC, BPH and the benign tissue surrounding the PC. MATERIAL AND METHODS: We prospectively evaluated WBSL in 24 patients with PC, 21 patients with BPH, and 21 HMI. Measurements of PTSL were performed in 17 patients with PC and 22 patients with BPH. In 9 cases with PC, measurements were also done in the benign tissue surrounding the carcinoma. Measurements were performed using automated graphite furnace atomic absorption spectrophotometry. RESULTS: In patients with PC, there is a significantly lower WBSL in comparison to HMI (p=0.04). There is no significant difference in WBSL between BPH-patients and HMI (p=0.13) and between PC- and BPH-patients (p=0.67). In all patients and the HMI, there is a significantly lower WBSL in comparison to the recommended normal value of 85-162 microg/l (p<0.01). There is no significant difference in PTSL between PC and BPH (p=0.49), and between PC and the tissue compartment surrounding the PC (p=0.56). PTSL seemed to be reduced in the compartment surrounding the PC in comparison to BPH (p=0.03). In PC-patients, there is no significant correlation between WBSL and prostate specific antigen (PSA) (? = -0.20; p=0.36), Gleason score (? = 0.32, p=0.13), and T-stage (? = 0.22; p=0.23). CONCLUSION: Since the WBSL measured in all men with PC and BPH, and in HMI participating in our study were significantly lower than the recommended normal range, our findings may support the recommendation of selenium supplementation.

Selenium in oncology: from chemistry to clinics.

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more and more the attention of both laypersons and expert groups. The interest of oncologists mainly focuses in the following clinical aspects: radioprotection of normal tissues, radiosensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that Se has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas, as well as in the head and neck region, including endolaryngeal edema. Another randomized phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. The aim was to evaluate whether sodium selenite is able to compensate a preexisting selenium deficiency and to prevent radiation induced diarrhea in adjuvant radiotherapy for pelvic gynecologic malignancies. Through this study, the significant benefits of sodium selenite supplementation with regards to selenium deficiency and radiotherapy induced diarrhea in patients with cervical and uterine cancer has been shown for the first time in a prospective randomized trial. Survival data imply that supplementation with selenium does not interfere with the positive biological effects of radiation treatment and might constitute a valuable adjuvant therapy option especially in marginally supplied individuals. More recently there were emerging concerns coming up from two large clinical prevention trials (NPC, SELECT), that selenium increases the possible risk of developing diabetes type II. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantage and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, even if further research is needed.

Malnutrition and Survival - Bioimpedance Data in Head Neck Cancer Patients.

BACKGROUND/AIM: Bioimpedance analysis (BIA) reflects the nutritional status of patients. The aim of this study was to examine whether BIA is able to document the possible impact of malnutrition on survival. MATERIALS AND METHODS: The registered data of 42 head and neck cancer patients were analyzed. Survival data of 22 women and 20 men were included. The mean age was 67.3±10.77 years. BIA was measured by the Biocorpus 4000 RX (MEDIcal Health Care GmbH Karlsruhe) and summarized in individual phase angle (PA) of each patient. RESULTS: Patients with normal PA>5.0 had a significantly better survival (p=0.016). The median survival time was 13.84 months (range=0.69-125.19 months) in malnourished patients (PA<5.0) compared to 51.16 months (range=7.02-116.79 months) in normally nourished head and neck cancer (HNC) patients (PA>5.0). Age adjusted body mass index had a similar impact on prognosis, but was not statistically significant (p=0.068) in the investigated study groups. CONCLUSION: BIA is able to document the impact of malnutrition on the survival of head and neck cancer patients.