Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100-200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

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).

Magnesium is involved in numerous processes that affect muscle function including oxygen uptake, energy production and electrolyte balance. Thus, the relationship between magnesium status and exercise has received significant research attention. This research has shown that exercise induces a redistribution of magnesium in the body to accommodate metabolic needs. There is evidence that marginal magnesium deficiency impairs exercise performance and amplifies the negative consequences of strenuous exercise (e.g., oxidative stress). Strenuous exercise apparently increases urinary and sweat losses that may increase magnesium requirements by 10-20%. Based on dietary surveys and recent human experiments, a magnesium intake less than 260 mg/day for male and 220 mg/day for female athletes may result in a magnesium-deficient status. Recent surveys also indicate that a significant number of individuals routinely have magnesium intakes that may result in a deficient status. Athletes participating in sports requiring weight control (e.g., wrestling, gymnastics) are apparently especially vulnerable to an inadequate magnesium status. Magnesium supplementation or increased dietary intake of magnesium will have beneficial effects on exercise performance in magnesium-deficient individuals. Magnesium supplementation of physically active individuals with adequate magnesium status has not been shown to enhance physical performance. An activity-linked RNI or RDA based on long-term balance data from well-controlled human experiments should be determined so that physically active individuals can ascertain whether they have a magnesium intake that may affect their performance or enhance their risk to adverse health consequences (e.g., immunosuppression, oxidative damage, arrhythmias).

Awareness of the clinical relevance of magnesium in medicine has increased over the last years, especially for people with chronic kidney disease (CKD), due to magnesium's role in vascular calcification and mineral metabolism. The inverse association between serum magnesium and clinically relevant, adverse outcomes is well-established in people with CKD. Subsequent intervention studies have focused on the effect of magnesium administration, mainly in relation to cardiovascular diseases, mineral bone metabolism, and other metabolic parameters. The most commonly used routes of magnesium administration are orally and by increasing dialysate magnesium. Several oral magnesium formulations are available and the daily dosage of elemental magnesium varies highly between studies, causing considerable heterogeneity. Although data are still limited, several clinical studies demonstrated that magnesium administration could improve parameters of vascular function and calcification and mineral metabolism in people with CKD. Current clinical research has shown that magnesium administration in people with CKD is safe, without concerns for severe hypermagnesemia or negative interference with bone metabolism. It should be noted that there are several ongoing magnesium intervention studies that will contribute to the increasing knowledge on the potential of magnesium administration in people with CKD.

Magnesium is an essential element that regulates membrane stability and neuromuscular, cardiovascular, immune, and hormonal functions and is a critical cofactor in many metabolic reactions. The Dietary Reference Intake for magnesium for adults is 310 to 420 mg/day. However, the intake of magnesium in humans is often suboptimal. Magnesium deficiency may lead to changes in gastrointestinal, cardiovascular, and neuromuscular function. Physical exercise may deplete magnesium, which, together with a marginal dietary magnesium intake, may impair energy metabolism efficiency and the capacity for physical work. Magnesium assessment has been a challenge because of the absence of an accurate and convenient assessment method. Recently, magnesium has been touted as an agent for increasing athletic performance. This article reviews the various studies that have been conducted to investigate the relationship of magnesium and exercise.

The relationship between magnesium and hypertension has been intensively investigated in the last few decades. Most of the so far reviews were focused on either dietary magnesium or serum magnesium or magnesium supplements. Our goal was to merge these findings with a more comprehensive approach. Internet search was performed in PubMed database without date limits, using the following search terms "dietary magnesium," "serum magnesium," "magnesium supplements," "hypertension," "drinking water," "food," "endothelial dysfunction," "arterial smooth muscle," and "arterial spasms." In general, there exists an inverse dose-dependent relationship between dietary magnesium intake and serum magnesium and the risk of hypertension. A negative correlation has been found between the serum magnesium concentration and Framingham risk score and intima-media carotid thickness and cardiovascular mortality. On the other hand, concentration of extracellular magnesium in the normal range acts as a natural calcium channel blocker, eliminates endothelial dysfunction, increases nitric oxide, and induces direct and indirect vasodilatation. In conclusion, an average magnesium dietary intake is below the recommended values and magnesium supplementation in the prevention and treatment of hypertension might be justified.