Magnesium

Magnesium is the fourth most abundant mineral in the human body and the second most concentrated intracellular cation, after Potassium. It is an indispensable cofactor in more than 300 enzymatic reactions — from ATP synthesis to DNA replication, from carbohydrate and Protein metabolism to the regulation of muscle tone and nerve transmission. It is difficult to find a relevant physiological process in which Magnesium does not play a role.

Despite its biological centrality, Magnesium deficiency is among the most prevalent in Western populations. It is estimated that more than 50 percent of adults do not reach their daily requirements through diet alone — a silent deficiency because plasma levels remain stable even in the presence of tissue depletion, making subclinical deficiency difficult to detect with standard tests.

Distribution in the body and requirements

The human body contains about 25 grams of Magnesium, distributed mainly in bones (60 percent), muscles (20 percent) and other soft tissues (20 percent). Less than 1% circulates in the bloodstream — which explains why magnesiemia is not a reliable indicator of the magnesium status of the body as a whole.

Reference values for daily intake (LARN — Fourth Revision) indicate a requirement of about 240 mg/day for adult women and 240–260 mg/day for adult men. The Ministry of Health Guidelines set the maximum tolerable level of supplementation at 250 mg/day for adults, referring only to Magnesium from supplements and fortified foods — not to Magnesium naturally present in food.

Mechanism of action and main functions

Magnesium acts primarily as an enzyme cofactor: it binds to enzymes or substrates of the reactions they catalyze, enabling or accelerating the process. The documented functions involve distinct and cross-cutting physiological areas:

  • Energy Metabolism — Magnesium is required for the synthesis and utilization of ATP (adenosine triphosphate), the main cellular energy transport molecule. All reactions involving ATP require Magnesium as a cofactor.
  • Muscle Function — regulates muscle contraction and relaxation by acting as a physiological Calcium antagonist. Magnesium deficiency is associated with muscle cramps, spasms, and fatigue.
  • Nervous System — participates in the regulation of neuromuscular transmission and modulates NMDA glutamate receptors, which has a calming effect on the central nervous system. It is involved in serotonin synthesis and sleep regulation.
  • Bone Health — Magnesium is a structural component of the bone hydroxyapatite crystal and influences the metabolism of Vitamin D and Parathormone. Prolonged deficiency contributes to reduced bone mineral density.
  • Glucose Metabolism — promotes insulin sensitivity and participates in the enzymatic reactions of glycolysis. Low Magnesium levels correlate with increased risk of insulin resistance.
  • Protein and DNA Synthesis — Magnesium is required for nucleic acid and Protein synthesis, with implications for cell growth and tissue repair.

Food sources

The richest food sources of Magnesium are dark green leafy vegetables-spinach, chard, kale-in which the mineral is a central component of the chlorophyll molecule. They are followed by legumes (black beans, chickpeas, lentils), nuts (almonds, cashews, peanuts), seeds (pumpkin, flax, chia), whole grains, and bitter cocoa.

However, Magnesium content in plant foods is subject to significant variation depending on soil composition. Decades of intensive agricultural practices have progressively reduced the concentration of Magnesium in cultivated soils, resulting in decreased content in foods. This factor, combined with dietary patterns that are less and less rich in whole vegetables and unrefined grains, contributes to the widespread insufficient intake in Western populations.

The forms available for formulation

Magnesium in supplements is not found in elemental form, but bound to other compounds that determine its bioavailability, gastric tolerance, and preferred application. The choice of form is one of the most important decisions during formulation.

  • Magnesium Bisglycinate — chelated form in which Magnesium is bound to two glycine molecules. Among the forms with the highest bioavailability: chelated with glycine facilitates absorption through amino acid transporters, bypassing ionic absorption mechanisms. Excellent gastric tolerance, also indicated for individuals with sensitive intestines. Supports muscle function, nervous system, and sleep quality.
  • Magnesium Citrate — organic salt with good bioavailability and high water solubility. It is the most common form in supplements in powder and effervescent sachets. At high doses it can have an osmotic laxative effect-which in some contexts is a sought-after effect, in others should be managed in dosage.
  • Magnesium Malate — related to malic acid, an intermediate in the Krebs cycle. Particularly indicated in the context of energy performance and muscle support due to the role of malic acid in mitochondrial energy metabolism.
  • Magnesium Pidolate — bound pidolic acid. Good cell penetration and affinity for nerve and muscle tissues. Often used in formulations geared to support the nervous system.
  • Magnesium Taurate — bound taurine. Suitable for formulations with cardiovascular focus: both Magnesium and taurine play a role in regulating heart rate and blood pressure.
  • Magnesium Oxide — inorganic form with high elemental Magnesium content by weight, but significantly lower bioavailability than organic forms. Used in high-dose formulations where the amount of active ingredient per tablet is prioritized over optimal absorption.
  • Magnesium Carbonate — inorganic form with an antacid effect. Used in specific formulations or as a component of mixtures.

In advanced formulations, the combination of multiple forms of Magnesium — for example, Bisglycinate + Citrate + Malate-is frequently used to take advantage of different absorption mechanisms and broaden the activity profile. The addition of Vitamin B6 is common: pyridoxine facilitates the entry of Magnesium into cells, further increasing its intracellular bioavailability.

EFSA claims approved

Magnesium is one of the minerals with the largest list of health claims approved by EFSA under EC Regulation 1924/2006. The main ones, under EU Reg. 432/2012:

  • Magnesium contributes to normal energy metabolism
  • Magnesium contributes to normal muscle function
  • Magnesium contributes to the normal function of the nervous system
  • Magnesium contributes to normal protein synthesis
  • Magnesium contributes to the maintenance of normal bones
  • Magnesium contributes to the maintenance of normal teeth
  • Magnesium contributes to normal psychological metabolism
  • Magnesium contributes to the reduction of fatigue and fatigue
  • Magnesium contributes to electrolyte balance.
  • Magnesium plays a role in the process of cell division

In order to use these claims, the product must provide at least 15 percent of the Daily Reference Dose (RDI) of Magnesium per 100 g, 100 ml, or per serving, as stipulated in EC Regulation 1924/2006.

Magnesium and Zinc: a frequent association in formulation

Magnesium and Zinc often appear together in formulas geared toward sports performance, muscle recovery, and nighttime wellness. The two best-known associations are ZMA (Zinc, Magnesium, Vitamin B6) and sleep formulas that combine Magnesium Bisglycinate with Zinc and melatonin. The synergy is based on complementarity of mechanisms of action: both minerals are involved in protein synthesis, muscle function, and immune system support, but with distinct biochemical pathways that enhance each other.

Magnesium from supplements may interfere with the absorption of some drugs, including antibiotics of the fluoroquinolone and tetracycline class, bisphosphonates, and some anticoagulants. Those taking ongoing drug therapies are urged to consult their physician or pharmacist before supplementing with Magnesium. High doses of Magnesium from supplements can cause gastrointestinal effects such as diarrhea, cramping, and nausea — particularly with the highly concentrated inorganic forms.

Always remember that it is important to consult a health care professional before starting any new supplement or treatment.