Managing magnesium deficiency: Strategies for diagnosis and treatment

The daily requirement of Mg varies with an individual’s age, sex and current health condition. For adults, the generally accepted daily requirement of Mg is around 300–400 mg. Main food groups that contribute to Mg intake are grains and grain-based products, milk and dairy products, as well as coffee, cocoa, tea and infusions [3, 4]. Table 1 depicts the recommended daily intake of Mg expressed as adequate intake (AI) for infants and other age groups [4].

Tab. 1. Summary of adequate intake for magnesium (Mg); adapted from EFSA NDA Panel (2015) [4].

Mg deficiency can lead to neuromuscular and cardiovascular disorders (CVDs) and may act as a risk factor for osteoporosis and impair insulin secretion, resulting in insulin resistance and type 2 diabetes. Several epidemiological studies demonstrate an inverse correlation between normal serum Mg levels and cardiovascular risk factors, such as arterial hypertension, type 2 diabetes and metabolic syndrome. Mg offers diverse cardioprotective benefits, including anti-hypertensive, anti-arrhythmic, anti-inflammatory and anti-platelet properties [3]. Low levels of Mg ions in blood (hypomagnesaemia) may interfere with the synthesis and secretion of parathormone, leading to hypocalcaemia.

There are numerous causes and possible consequences associated with Mg deficiency (Fig. 1). Mild hypomagnesaemia is usually asymptomatic, but severe Mg deficiency can manifest itself as persistent asthenia, tiredness, impaired concentration, increased susceptibility to infections, mental stress, hand tremor and tingling, eyelid and lip twitching, psychomotor agitation, anxiety and palpitations or tetany attacks [3].

The negative consequences of stress and hypomagnesaemia reinforce each other in a vicious circle; that is, mental stress could lead to increased Mg loss and mineral deficiency. Conversely, Mg deficiency could worsen the effects of mental stress (fatigue and insomnia, dizziness, headaches, palpitations, muscle cramps, eyelid twitching, tics and increased susceptibility to infections). Mg supplementation reduces stress, anxiety and serum cortisol and increases Mg levels in the serum and erythrocytes [5].

Moreover, symptoms of Mg deficiency can also arise with normal levels of Mg in the body due to the pathological transfer of Mg into the bones, which can affect overall balance [3]. Diagnosis of Mg deficiency based on the symptoms alone is challenging as they are not specific in nature. Additionally, only 1% of Mg is present in blood, and there are multiple risk factors that can contribute to the development of Mg deficiency. Routine assessment of Mg in blood has a limited diagnostic value since it does not correlate with its contents in the tissue [3].

Mg deficiency is common in growing children, pregnant/lactating women, people under chronic stress or those practicing professional sports. The primary care physician should assess the patient for symptoms of Mg deficiency and provide adequate supplementation if needed [3, 5]. 

Correction and prevention of Mg deficiency usually involves oral supplementation with Mg products. There are numerous products in the market that contain different Mg compounds. It is noteworthy that among the abundant Mg products in the pharmaceutical market, approved Mg products with thorough chemical, pharmacological and clinical documentation are accessible (Fig. 2) [3]. The key factor in determining their efficacy is the type of salt used, which influences the absorption of Mg ions. Inorganic salts, such as oxides and chlorides, have a significantly lower absorption rate (around 10%–16%) than more commonly used organic salts, such as citrate, gluconate, lactate and aspartate that may enhance Mg absorption. Product selection also depends on the condition of the gastrointestinal tract; organic salts (citrate, lactate and aspartate) resembling Mg compounds in daily foods are recommended when the stomach and intestines are functioning properly. In patients with hyperacidity and gastritis, Mg oxide is better tolerated but with a low bioavailability. Mg chloride is recommended for patients with hypochlorhydria as it delivers chloride ions as an additional benefit. In case of peptic ulcers, enteric-coated formulation of Mg is recommended; however, bioavailability is a limitation. It is recommended to take Mg products with food and plenty of water for optimal absorption [4]. 

Considering that the symptoms of Mg deficiency are not specific and there are several risk factors that can contribute to the development of this mineral deficiency, diagnosis of Mg deficiency can be challenging. To educate healthcare professionals (HCPs) on accurate diagnosis of Mg deficiency and recommend appropriate treatment, an algorithm was developed as a valuable tool [3], which:

• Contains lists of common risk factors for Mg deficiency, such as diseases, medicines and physiological conditions;
• Specifies the choice of Mg treatment, dosage and time frame;
• Facilitates and expedites HCP recommendation on Mg products based on evidence-based medicine. 

The family physician’s practice algorithm for using Mg products is presented in Fig. 3. Patient eligibility for Mg treatment is determined based on pathophysiological considerations. The algorithm does not require testing blood Mg levels, and it underlines a need for the systematic and chronic use of Mg products. Treatment or prevention of Mg deficiency involves oral supplementation with approved medicinal products [3]. 

Mg is a macroelement essential for the normal functioning of the body. It plays a vital role in maintaining overall human health. Inadequate dietary intake of Mg may directly contribute to the development of numerous diseases of affluence, such as CVDs, type 2 diabetes, cancer, depression and other metabolic disorders. It is essential to have Mg deficiency tracking tools in place for effective treatment and prevention. A recent publication proposed a tool that can be easily incorporated in HCPs’ practice to support the diagnosis and help determine the best course of action for managing Mg deficiency in their patients.

_{Acknowledgements: The authors thank Paula Fontanilla, PhD, for critically reviewing the scientific content of this manuscript and Avinash Bardia, PhD, an employee of Sanofi, for providing medical writing and editorial support.}

_{Conflict of interest: K. Wielgus, M. Dan and T. Tavares are employees of Sanofi.}

_{Disclosure: This study was funded by Sanofi.}