The coronavirus disease (COVID-19) - A supportive approach with selected micronutrients.

Worldwide the pandemic of COVID-19 spreads rapidly and has had an enormous public health impact with substantial morbidity and mortality especially in high-risk groups, such as older people and patients with comorbidities like diabetes, dementia or cancer. In the absence of a vaccine against COVID-19 there is an urgent need to find supportive therapies that can stabilize the immune system and can help to deal with the infection, especially for vulnerable groups such as the elderly. This is especially relevant for our geriatric institutions and nursing homes. A major potential contributing factor for elderly is due to their high incidence of malnutrition: up to 80% among the hospitalized elderly. Malnutrition results when adequate macronutrients and micronutrients are lacking in the diet. Often missing in public health discussions around preventing and treating COVID-19 patients are nutritional strategies to support optimal function of their immune system. This is surprising, given the importance that nutrients play a significant role for immune function. Several micronutrients, such as vitamin D, retinol, vitamin C, selenium and zinc are of special importance supporting both the adaptive and innate immune systems. As suboptimal status or deficiencies in these immune-relevant micronutrients impair immune function and reduces the resistance to infections, micronutrient deficiencies should therefore be corrected as soon as possible, especially in the elderly and other vulnerable groups. According to epidemiological, experimental and observational studies, some case reports and a few intervention studies the supplementation of vitamin D and/or zinc are promising. The multiple anti-inflammatory and immunomodulatory effects of Vitamin D could explain its protective role against immune hyper reaction and cytokine storm in patients with severe COVID-19. A randomized, placebo-controlled intervention study even shows that high dose vitamin D supplementation promotes viral clearance in asymptomatic and mildly symptomatic SARS-CoV-2 positive individuals. Besides, the data of a recent prospective study with COVID-19 patients reveal that a significant number of them were zinc deficient. The zinc deficient patients had more complications and the deficiency was associated with a prolonged hospital stay and increased mortality. Thus, immune-relevant micronutrients may help to increase the physiological resilience against COVID-19.

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.

Diabetes Prevention: Vitamin D Supplementation May Not Provide Any Protection If There Is No Evidence of Deficiency!

The results of epidemiological and several interventional studies suggest an association between vitamin D deficiency and an increased risk of developing insulin resistance or type 2 diabetes. Various studies have indicated that a lack of vitamin D must be regarded as a pathogenic factor for type 2 diabetes and the metabolic syndrome, since a vitamin D deficiency (25(OH)D < 20 ng/mL) increases insulin resistance and reduces insulin secretion from beta cells in the pancreas. A recent study by Pittas et al. did not show a clear preventive effect of vitamin D supplementation with respect to the risk of developing type 2 diabetes. In terms of this study, it must be remembered that more than 70% of the participants in both the vitamin D supplement group and the placebo group did not have a vitamin D deficiency. In medical and pharmaceutical practice, more attention should be paid to vitamin D deficiency than has previously been accorded. Vitamin D status can be assessed objectively when necessary by laboratory testing of the serum 25(OH)D levels. Type 2 diabetes patients benefit from improving their vitamin D status with respect to their glucose metabolism and decreased mortality risk. Patients with insulin resistance who are vitamin D deficient should be treated with an appropriate amount of vitamin D to achieve circulating levels of 25(OH)D of 40-60 ng/mL.

Magnesium and Drugs.

Several drugs including diuretics and proton-pump inhibitors can cause magnesium loss and hypomagnesemia. Magnesium and drugs use the same transport and metabolism pathways in the body for their intestinal absorption, metabolism, and elimination. This means that when one or more drug is taken, there is always a potential risk of interaction with the magnesium status. Consequently the action of a drug may be adversely affected by magnesium (e.g., magnesium, calcium, and zinc can interfere with the gastrointestinal absorption of tetracycline antibiotics) and simultaneously the physiological function of minerals such as magnesium may be impaired by a drug (e.g., diuretics induce renal magnesium loss). Given the ever-increasing number of drugs on the market and the frequency with which they are used, greater attention must be paid in daily medical and pharmaceutical practice focused in particular on the adverse effects of drug therapy on magnesium status in order to minimize the potential risk to the health of patients.

Myth or Reality-Transdermal Magnesium?

In the following review, we evaluated the current literature and evidence-based data on transdermal magnesium application and show that the propagation of transdermal magnesium is scientifically unsupported. The importance of magnesium and the positive effects of magnesium supplementation are extensively documented in magnesium deficiency, e.g., cardiovascular disease and diabetes mellitus. The effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency has been studied in detail. However, the proven and well-documented oral magnesium supplementation has become questioned in the recent years through intensive marketing for its transdermal application (e.g., magnesium-containing sprays, magnesium flakes, and magnesium salt baths). In both, specialist and lay press as well as on the internet, there are increasing numbers of articles claiming the effectiveness and superiority of transdermal magnesium over an oral application. It is claimed that the transdermal absorption of magnesium in comparison to oral application is more effective due to better absorption and fewer side effects as it bypasses the gastrointestinal tract.

Micronutrients in Oncological Intervention.

Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%-90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that treatment is tolerated better-with an increase in patient compliance and a lower rate of treatment discontinuations-when micronutrients, such as selenium, are added as appropriate to the patient's medication. Nutritional supplementation tailored to an individual's background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician.

Magnesium in Prevention and Therapy.

Magnesium is the fourth most abundant mineral in the body. It has been recognized as a cofactor for more than 300 enzymatic reactions, where it is crucial for adenosine triphosphate (ATP) metabolism. Magnesium is required for DNA and RNA synthesis, reproduction, and protein synthesis. Moreover, magnesium is essential for the regulation of muscular contraction, blood pressure, insulin metabolism, cardiac excitability, vasomotor tone, nerve transmission and neuromuscular conduction. Imbalances in magnesium status-primarily hypomagnesemia as it is seen more common than hypermagnesemia-might result in unwanted neuromuscular, cardiac or nervous disorders. Based on magnesium's many functions within the human body, it plays an important role in prevention and treatment of many diseases. Low levels of magnesium have been associated with a number of chronic diseases, such as Alzheimer's disease, insulin resistance and type-2 diabetes mellitus, hypertension, cardiovascular disease (e.g., stroke), migraine headaches, and attention deficit hyperactivity disorder (ADHD).

Live longer with vitamin D?

The global burden of vitamin D deficiency or insufficiency is of great concern for public health. According to recent studies, vitamin D deficiency is an important etiological factor in the pathogenesis of many chronic diseases. Whether or not there is a connection between 25-hydoxyvitamin D (25(OH)D) status and overall mortality is a matter of considerable debate. A new meta-analysis confirmed that low 25(OH)D levels were associated with a significant increased risk for all-cause mortality. Individuals with severe vitamin D deficiency have almost twice the mortality rate as those with 25(OH)D level ≥ 30 ng/mL, (≥75 nmol/L). Unlike previous meta-analyses which suggested that serum 25(OH)D > 50 ng/mL was associated with increased mortality, this new analysis found that there was no increased risk even when 25(OH)D levels were ≥70 ng/mL. In general, closer attention should be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto. The results of these studies are consistent with the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations.

[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.

Neuroenhancement with vitamin B12-underestimated neurological significance.

Vitamin B12 is a cofactor of methionine synthase in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAMe), which is involved in different epigenomic regulatory mechanisms and especially in brain development. A Vitamin B12 deficiency expresses itself by a wide variety of neurological manifestations such as paraesthesias, skin numbness, coordination disorders and reduced nerve conduction velocity. In elderly people, a latent Vitamin B12 deficiency can be associated with a progressive brain atrophy. Moderately elevated concentrations of homocysteine (>10 µmol/L) have been associated with an increased risk of dementia, notably Alzheimer's disease, in many cross-sectional and prospective studies. Raised plasma concentrations of homocysteine is also associated with both regional and whole brain atrophy, not only in Alzheimer's disease but also in healthy elderly people. Clinician awareness should be raised to accurately diagnose and treat early Vitamin B12 deficiency to prevent irreversible structural brain damage.

[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.

Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare.

Vitamin D has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, infectious diseases and cardiovascular disease. The recent data on vitamin D from experimental, ecological, case-control, retrospective and prospective observational studies, as well as smaller intervention studies, are significant and confirm the sunshine vitamin's essential role in a variety of physiological and preventative functions. The results of these studies justify the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations. In general, closer attention should therefore be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto.

[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.

Influence of drugs on vitamin D and calcium metabolism.

In the past, interactions between drugs and vitamin D have received only little or no attention in the health care practices. However, since more and more drugs are used for the treatment of patients, this topic is increasingly relevant. Several drugs can interfere with the vitamin D and bone metabolism. Drugs that activate the pregnane X receptor can disrupt vitamin D metabolism and vitamin D function. Beside this, the medication oriented supplementation of vitamin D can ameliorate the pharmacologic action of some drugs, such as bisphosphonates, cytostatics and statins.

L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)--a randomized multicentre trial.

BACKGROUND: Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. FINDINGS: We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2.5 (SEM) kg. During treatment body-mass-index increased by 3.4 ± 1.4% under L-Carnitine and decreased (-1.5 ± 1.4%) in controls (p < 0.05). Moreover, nutritional status (body cell mass, body fat) and quality-of-life parameters improved under L-Carnitine. There was a trend towards an increased overall survival in the L-Carnitine group (median 519 ± 50 d versus 399 ± 43 d, not significant) and towards a reduced hospital-stay (36 ± 4d versus 41 ± 9d,n.s.). CONCLUSION: While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

[Mitochondrial toxicity of drugs]. / Mitochondriale Toxizität von Arzneimitteln.

Considering the complexity of mitochondria, it is not surprising that the pathogenesis of adverse drug events often develop on drug-induced mitochondrial injury. Drug induced mitochondrial toxicity can occur through several mechanisms, such as depletion of mtDNA (e.g. NRTI), inhibition of fatty acid beta-oxidation (e.g. valproic acid), opening of the mitochondrial permeability transition pore (e.g. anthracyclines), formation of mitochondrial oxidative stress and depletion of mitochondrial glutathione pool (e.g. acetaminophen), uncoupling of electron transport from ATP synthesis (e.g. tamoxifen) and inhibition of mitochondrial electron transport chain complexes (e.g. simvastatin). This review focuses on the mitochondrial toxicity of drugs in general and explains the practical relevance of these adverse drug events according to specific drugs (metformin, statins, acetaminophen, valproic acid). Furthermore the significance of mitotropic micronutrients such as coenzyme Q10, L-carnitine and glutathione in the prevention and management ofdrug-induced mitochondrial injury is discussed.