원료 ≫ 기능성 ≫ 미네랄

마그네슘 Mg 역할

마그네슘
- 마그네슘 역할
- 마그네슘 Mg 흡수 기작
- MgCl2 염화마그네슘, 응고제
- 간수(조제해수염화마그네슘) : 호주 간수

인체에 20~30 그람의 마그네슘을 함유한다. 골격에 60%, 연 조직에 40% 정도 분포한다. 신체는 하루에 체중 1 kg당 6 mg 정도의 마그네슘을 요구한다. 여성은 280 mg. 남성은 350 mg 정도다. 마그네슘의 RDA는 400 mg, ODI는 500-750 mg이다. 신장 기능이 정상이라면 하루에 6000 mg 까지 복
용해도 독성은 없다. 마그네슘을 3000~5000 mg 정도 대량 복용하면 사하(瀉下; 설사를 내보냄) 작용(Cathartic Effect)이 있다. 인체는 칼슘을 이용할때 마그네슘을 함께 요구한다. 칼슘을 섭취할 때 적정비율의 마그네슘을 함께 섭취해야 하는 이유다. 칼막 복용 적정 비율은 2 : 1 또는 2 : 1.5 정도다.

생물학적 기능 및 효과
마그네슘은 탄수화물, 지방, 단백질 대사와 칼슘, 인, 비타민 C 관련 활성에 필요하다. 마그네슘은 신경 및 근육 조직 건강에 매우 중요하다. 마그네슘 기능 및 효과는 다음과 같다
가)   심혈관 건강에 다방면으로 영향을 미친다.  혈소판 응집을 감소시킨다
나)   혈액을 묽게 하고 칼슘 uptake를 차단하며 혈관을 이완시킨다
다)   마그네슘은 심혈관 질환 위험을 감소시키고 심장 발작 후 생존율을 증가시킨다. 심장 발작 후 혈관 내로 마그네슘을 공급하면 한 달 내 사망율이 70% 낮아진다.
라)   30개 이상의 임상 연구 결과에서 마그네슘은 고혈압을 감소시키는 것으로 발표되었다. 그러나 단지 중간 정도의 혈압 강하를 보여 마그네슘을 고혈압의 1차 치료제로 사용하지 않는다
마)   PMS 증상을 보이는 여성은 마그네슘 수준이 낮다. 마그네슘은 PMS 증상을 경감시킨다
바)   천식 환자는 마그네슘 수준이 낮다. 따라서 적당량의 마그네슘은 천식 위험을 감소시켜 천식 치료 프로그램의 일부로 활용된다
사)   골 건강에 매우 중요하다. 칼슘 대사에 관여하고 비타민 D 합성, 골격 크리스탈(skeletal bone-crystal formation) 통합성에 관여한다.
아)   칼슘이 치아 상아질에 결합하는 것을 도와 충치를 효과적으로 차단하는 효과가 있다.

12 Common Magnesium Deficiency Symptoms:

1. Anxiety
2. Weak Bones
3. Low Energy
4. Weakness
5. Inability to Sleep
6. PMS and Hormonal Imbalances
7. Irritability
8. Nervousness
9. Headaches
10. Abnormal Heart Rhythm
11. Muscle Tension, Spasms, Cramps
12. Fatigue

뼈 건강의 핵심 미네랄은 칼슘과 마그네슘이다.

1) 마그네슘은 칼슘 조절자로 뼈 건강 미네랄이다(CALCIUM REGULATOR)
인체의 가장 큰 칼슘 창고는 뼈다. 뼈는 마그네슘 창고 역할도 한다. 마그네슘은 뼈 대사 조절 호르몬 또는 뼈 대사 조절 인자(因子)에 작용하여 칼슘 운반을 조절함으로써 뼈 광화 밀도(BONE MINERALIZATION DENSITY)를 증가시킨다. 뼈의 칼슘 IN & OUT를 조절하고 비타민 D 활성화 그리고 부갑상선 호르몬(PTH)에 대한 뼈 조직의 민감도를 증가시킨다. 마그네슘 결핍은 골 다공증을 유발한다. 따라서 뼈 건강(BONE HEALTH)에 필수 미네랄이다

2) 마그네슘은 에너지 미네랄이다.( ENERGY MINERAL)
300 종 이상 효소의 보조 인자로 단백질을 합성하고 지방 대사를 유도한다

3) 마그네슘은 천연 근육 이완제다(NATURAL MUSCLE RELAXANT
칼슘이 근육 세포 내로 유입하면 근육이 수축하고 칼슘이 마그네슘으로 대체되면 근육 이 이완된다. 마그네슘은 근육 긴장도(TONE) 조절에 중요한 기능을 하는 것이다. 마그네슘이 결핍되면 우선 피로, 무력감, 근육 경련 및 통증을 동반한다. 근육통, 근육 경련, 불안, 근육통을 동반한 만성 피로 증후군, 생리전 증후군에 마그네슘을 활용하는 이유가 여기에 있다.

4)마그네슘은 심장, 혈관 미네랄, 신경 기능 미네랄이다
칼막 균형(Ca-Mg Balance)은 세포막의 전기적 안전성을 조절하여 혈관 톤(Tone)을 형성한다. 근육 세포의 전기 활동과 신경 전도에 필수적 기능을 함으로써 심혈관 건강에 영향을 미친다. 실제로 마그네슘이 결핍되면 동맥 경화증이 촉진된다. 칼막 균형이 깨지면 칼슘이 뼈의 일부로 사용되지 못하고 사용되지 못한 칼슘이 동맥벽 일부가 되기 때문이다. 고 콜레스테롤 혈증인 사람의 경우 마그네슘이 결핍되면 부정맥, 빈맥, 고혈압 등 심장 질환을 야
기한다.

5)마그네슘은 수산칼슘 결정(CALCIUM OXALATE CRYSTAL) 형성을 방지한다

마그네슘 결핍증

근육 무력증, 근육 경련, 진전(떨림; tremor), 과민성(irritability), 심근의 전기적 변화 등을 초래한다. 초콜렛에는 마그네슘이 풍부하다. 마그네슘이 부족한 일부 생리 전 여성은 초콜렛에 대한 갈망(CHOCOLATE CRAVING)을 느낀다.경구용 피임약은 50여 종 이상의 신체 대사 변화를 야기한다. 경구 피임제 복용 여성은 아연, 마그네슘, 비타민 C, 비타민 B군, 베타카로틴을 증량 복용해야 한다

마그네슘은 체내에서 수 많은 주요 기능을 한다. 300가지 이상의 생화학적 과정에서 마그네슘을 요구 하기 때문이다. 심장에서 뼈까지, 신체의 일부 기본적인 체계 및 구조는 마그네슘에 의존한다. 마그네슘은 뼈 건강과 뼈 구조에 필수 미네랄이다. 마그네슘의 절반 가량이 뼈에 존재한다. 마그네슘은 칼시토닌이라는 호르몬 생성에 관여하여 뼈 속의 칼슘치를 증가시킨다. 또한 혈액 내 산도를 조절하여 뼈 건강을 지켜준다. 혈액이 산성화하면 뼈 구조가 약해질 수 있기 때문이다.

마그네슘은 당뇨병과 유관하다는 과학적 근거도 있다. 마그네슘이 인슐린 분비 및 인슐린 기능에 필요하기 때문이다. 그래서 마그네슘은 혈당 조절 효과가 있고 혈당을 에너지로 바꾸는데 기여한다.마그네슘은 여러 종류의 비타민, 미네랄, 기타 영양소와 파트너 관계에 있다. 마그네슘은 신체의 신경계 및 근육계 기능에 필수적 미네랄이며 근육 수축과 신경 기능에 영향을 미친다

성인 남자는 하루에 350 mg, 성인 여성은 280 mg, 임산부나 수유부는 420 mg까지 복용한다. 소아는 체구나 체중에 따라 다르지만 130-240 mg정도 복용한다.
마그네슘 결핍증은 심장 경련, 부정맥, 불안, 혼동, 식욕 부진, 구역질, 구토, 근육 경련, 피로, 무력감 등을 동반한다.

신체 건강은 신체 내 화학물질의 섬세한 균형에 기반을 둔다. 그러나 과량 복용하면 너무 소량 복용한 것과 같은 해를 끼친다.
Major mineral이다. 심장 기능, 근육 기능, 신경 기능 및 지방의 정상 대사에 관여하고 심부정맥, 고혈압, 불안증, 불면증 및 자간전증(pre-eclampsia)을 감소시킨다

- 뼈의 중요 구성 성분, 300종 이상의 효소 시스템에 관여한다
- 인체는 20-30 gm을 함유한다. 골격에 60%, 연조직에 40% 분포한다.
- 체중 1 kg 당 6 mg이 필요하다. 여성(하루 280 mg), 남성(하루 350 mg).
   심장 질환이나 신경성 문제 있는 사람은 하루 500-1000 mg 섭취한다
- 연료 목적의 포도당 연소, 근육 수축, 단백질 합성을 위한 필수 성분이다
- 최고 식품원은 legume(콩), whole grain(통곡)이다. 정제된 백미를 마그네슘이 80 % 이상 소실된다
- 탄수화물 대사에 필요한 8가지 영양소 중 한가지다.
- 심장 부정맥, 고혈압, 불안증, 불면, 임신 중독증, 월경전 증후군(menstrual cramp)에 유용하다
- 결핍증 : 경련, 근육 경련, 진전(tremors), 근육허약(m.weakness). 부족증상은 구역질, 근허약, 성급함(irritability), 심근의 전기적 변화 등이다.

칼슘과 마그네슘 상호 작용.
마그네슘도 건강한 뼈를 위한 핵심 미네랄이다.


1) 마그네슘은 칼슘과 인의 균형을 유지하고
2) 혈중에서 뼈 및 연조직으로 칼슘을 운반하는데 중요한 역할을 한다
3) 비타민 D의 활성화에 관여하여 칼슘이 뼈로 흡수될 수 있도록 한다
4) 인체에서 칼슘의 이용에는 마그네슘이 절대 필요하다. 칼슘 섭취를 증가시키면 마그네슘 섭취도  증가시켜야한다.칼슘과 마그네슘의 비율은 2:1이 이상적이다. 칼슘을 하루 1000 mg 소모할때 하루 500 mg의 마그네슘을 요구한다.
5) 알코홀, 경구용 피임제를 과다 투여할 때 또는 스트레스 시에 고갈된다
6) 마그네슘 부족증은 빈번하다. 특히 골다공증 환자에서 많다. 갱년기 여성이 칼슘 1000 mg 이상 복용할 때 마그네슘의 요구도를 더욱 증가시키기 때문이다. 따라서 낙농 제품의 과다 섭취는 피하는 것이 원칙이다. 이들 식품은 마그네슘보다 칼슘을 10 배 이상 함유하고 있기 때문이다.
7) 마그네슘의 RDA는 220 mg이다. 그러나 실제로는 하루 100 mg 이하를 섭취한다. 그 이유는 녹색잎 야채, 콩, 씨앗, 견과류 등 마그네슘이 풍부한 식품(magnesium-rich foods)을 간과하고 마그네슘이 소량 함유된 가공식품 및 스넥을 더 많이 섭취할 뿐 아니라 커피, 차, 콜라 및 알코홀과 같은 드링크를 많이 마시기 때문에 인체내 마그네슘이 소변으로 배설되기 때문이다.  

마그네슘은 천연의 근 이완제(natural m.relaxant)이다
1) 가장 중요한 역할이 근육 이완을 돕는 일이다. 칼슘이 근육 세포내로 유입되면 근육이 수축한다. 그러나 칼슘이 빠져 나오고 마그네슘으로 대체되면 근육은 이완된다. Mg은 근육 긴장도(m.tone)를 조절한다. 천연의 근육 이완제로 근육 경련, 불안증 등 증상 경감에 유용하다.
2) 마그네슘 부족증 : 근육 경련(m.spasm), 진전(tremor), 경련(convulsion), 섬유성 근육통(fibromyalgia) 치료에 magnesium malate 보충제를 투여한다. Mg 제제는 근육통, 통증을 수반한 만성피로 치료에 이용된다.


 

 

 

 


 


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455825/
Magnesium basics
Wilhelm Jahnen-Dechentcorresponding author1 and Markus Ketteler2

 

Introduction
Magnesium is the eighth most common element in the crust of the Earth [1, 2] and is mainly tied up within mineral deposits, for example as magnesite (magnesium carbonate [MgCO3]) and dolomite. Dolomite CaMg(CO3)2 is, as the name suggests, abundant in the Dolomite mountain range of the Alps [3]. The most plentiful source of biologically available magnesium, however, is the hydrosphere (i.e. oceans and rivers). In the sea, the concentration of magnesium is ∼55 mmol/L and in the Dead Sea—as an extreme example—the concentration is reported to be 198 mmol/L magnesium [4] and has steadily increased over time.
Magnesium salts dissolve easily in water and are much more soluble than the respective calcium salts. As a result, magnesium is readily available to organisms [5]. Magnesium plays an important role in plants and animals alike [2]. In plants, magnesium is the central ion of chlorophyll [3]. In vertebrates, magnesium is the fourth most abundant cation [5, 6] and is essential, especially within cells, being the second most common intracellular cation after potassium, with both these elements being vital for numerous physiological functions [6–9]. Magnesium is also used widely for technical and medical applications ranging from alloy production, pyrotechnics and fertilizers to health care. Traditionally, magnesium salts are used as antacids or laxatives in the form of magnesium hydroxide [Mg(OH)2], magnesium chloride (MgCl2), magnesium citrate (C6H6O7Mg) or magnesium sulphate (MgSO4).

Chemical characteristics
Magnesium is a Group 2 (alkaline earth) element within the periodic table and has a relative atomic mass of 24.305 Da [7], a specific gravity at 20°C of 1.738 [2, 3], a melting point of 648.8°C [2] and a boiling point of 1090°C [3]. In the dissolved state, magnesium binds hydration water tighter than calcium, potassium and sodium. Thus, the hydrated magnesium cation is hard to dehydrate. Its radius is ∼400 times larger than its dehydrated radius. This difference between the hydrated and the dehydrated state is much more prominent than in sodium (∼25-fold), calcium (∼25-fold) or potassium (4-fold) [5]. Consequently, the ionic radius of dehydrated magnesium is small but biologically relevant [6]. This simple fact explains a lot of magnesium’s peculiarities, including its often antagonistic behaviour to calcium, despite similar chemical reactivity and charge. For instance, it is almost impossible for magnesium to pass through narrow channels in biological membranes that can be readily traversed by calcium because magnesium, unlike calcium, cannot be easily stripped of its hydration shell [10]. Steric constraints for magnesium transporters are also far greater than for any other cation transport system [5]: proteins transporting magnesium are required to recognize the large hydrated cation, strip off its hydration shell and deliver the bare (i.e. dehydrated) ion to the transmembrane transport pathway through the membrane (Figure 1) [5, 11, 12]. There are obvious chemical similarities between calcium and magnesium but in cell biology, major differences often prevail (Table 1).

Physiological role of magnesium in the body
The body of most animals contains ∼0.4 g magnesium/kg [5]. The total magnesium content of the human body is reported to be ∼20 mmol/kg of fat-free tissue. In other words, total magnesium in the average 70 kg adult with 20% (w/w) fat is ∼1000 [7] to 1120 mmol [13] or ∼24 g [14, 15]. These values should be interpreted with caution, however, as analytical methods differ considerably throughout the years. In comparison, the body content of calcium is ∼1000 g (i.e. 42 times greater than the body content of magnesium) [16].

Distribution in the human body
About 99% of total body magnesium is located in bone, muscles and non-muscular soft tissue [17] (see also Table 2). Approximately 50–60% of magnesium resides as surface substituents of the hydroxyapatite mineral component of bone [14, 18]. An illustration of bioapatite is shown in Figure 2. Most of the remaining magnesium is contained in skeletal muscle and soft tissue [14]. The magnesium content of bone decreases with age, and magnesium stored in this way is not completely bioavailable during magnesium deprivation [5]. Nonetheless, bone provides a large exchangeable pool to buffer acute changes in serum magnesium concentration [19]. Overall, one third of skeletal magnesium is exchangeable, serving as a reservoir for maintaining physiological extracellular magnesium levels [19].
Hydroxyapatite crystal unit. Enamel apatite contains the lowest concentrations of carbonate and magnesium ions, and is rich in fluoride F. Dentin and bone have the highest levels of carbonate and magnesium ions, but have low fluoride content. Fluoride decreases solubility and increases chemical stability, carbonate, chloride and especially magnesium all increase solubility of the otherwise very insoluble mineral. Chemically the mineral comprises a highly substituted carbonated calcium hydroxyapatite (HAP). In the absence of exact compositional analysis the biogenic forms of this mineral are collectively alluded to as “bioapatite”. Ca, calcium; Na, sodium; Mg, magnesium; Sr, strontium; OH, hydroxide; Cl, chloride; F, fluoride; PO4, HPO4, phosphate; CO3, carbonate.
Intracellular magnesium concentrations range from 5 to 20 mmol/L; 1–5% is ionized, the remainder is bound to proteins, negatively charged molecules and adenosine triphosphate (ATP) [18].
Extracellular magnesium accounts for ∼1% of total body magnesium [14, 18, 20] which is primarily found in serum and red blood cells (RBCs) [5, 7, 21, 22]. Serum magnesium can—just like calcium—be categorized into three fractions. It is either free/ionized, bound to protein or complexed with anions such as phosphate, bicarbonate and citrate or sulphate (Table 1, Figure 3). Of the three fractions in plasma, however, ionized magnesium has the greatest biological activity [5, 7, 21, 22].
Magnesium is primarily found within the cell [7] where it acts as a counter ion for the energy-rich ATP and nuclear acids. Magnesium is a cofactor in >300 enzymatic reactions [8, 10]. Magnesium critically stabilizes enzymes, including many ATP-generating reactions [14]. ATP is required universally for glucose utilization, synthesis of fat, proteins, nucleic acids and coenzymes, muscle contraction, methyl group transfer and many other processes, and interference with magnesium metabolism also influences these functions [14]. Thus, one should keep in mind that ATP metabolism, muscle contraction and relaxation, normal neurological function and release of neurotransmitters are all magnesium dependent. It is also important to note that magnesium contributes to the regulation of vascular tone, heart rhythm, platelet-activated thrombosis and bone formation (see review by Cunningham et al. [28] in this supplement) [6, 7, 10, 29, 30]. Some of magnesium’s many functions are listed in Table 3.

Enzyme function
Enzyme substrate (ATP-Mg, GTP-Mg)
Kinases B
Hexokinase
Creatine kinase
Protein kinase
ATPases or GTPases
Na+ /K+-ATPase
Ca2+-ATPase
Cyclases
Adenylate cyclase
Guanylate cyclase
Direct enzyme activation
Phosphofructokinase
Creatine kinase
5-Phosphoribosyl-pyrophosphate synthetase
Adenylate cyclase
Na+/ K+-ATPase

Membrane function
Cell adhesion
Transmembrane electrolyte flux

Calcium antagonist
Muscle contraction/relaxation
Neurotransmitter release
Action potential conduction in nodal tissue

Structural function
Proteins
Polyribosomes
Nucleic acids
Multiple enzyme complexes
Mitochondria

In muscle contraction, for example, magnesium stimulates calcium re-uptake by the calcium-activated ATPase of the sarcoplasmic reticulum [14]. Magnesium further modulates insulin signal transduction and cell proliferation and is important for cell adhesion and transmembrane transport including transport of potassium and calcium ions. It also maintains the conformation of nucleic acids and is essential for the structural function of proteins and mitochondria.
It has long been suspected that magnesium may have a role in insulin secretion owing to the altered insulin secretion and sensitivity observed in magnesium-deficient animals [31]. Epidemiological studies have shown a high prevalence of hypomagnesaemia and lower intracellular magnesium concentrations in diabetics. Benefits of magnesium supplementation on the metabolic profile of diabetics have been observed in some, but not all, clinical trials, and so larger prospective studies are needed to determine if dietary magnesium supplementation is associated with beneficial effects in this group [32].

Recent epidemiological studies have suggested that a relatively young gestational age is associated with magnesium deficiency during pregnancy, which not only induces maternal and foetal nutritional problems but also leads to other consequences that might affect the offspring throughout life [33].

There is also evidence that magnesium and calcium compete with one another for the same binding sites on plasma protein molecules [13, 34]. It was shown that magnesium antagonizes calcium-dependent release of acetylcholine at motor endplates [6]. Thus, magnesium may be considered a natural ‘calcium antagonist’. While calcium is a powerful ‘death trigger’ [35], magnesium is not [34]: magnesium inhibits calcium-induced cell death [36]. It is anti-apoptotic in mitochondrial permeability transition and antagonizes calcium-overload-triggered apoptosis. Magnesium is important in health and disease, as will be discussed in more detail in this supplement in the article by Geiger and Wanner [37].


Regulation of magnesium influx and efflux
There is considerable variation in the plasma/tissue exchange of magnesium between various organs of an animal and also between animal species [5]. These observations indicate that various cell types handle magnesium quite differently, which is again different from calcium [10]. Myocardium, kidney parenchyma, fat tissue, skeletal muscle, brain tissue and lymphocytes exchange intracellular and extracellular magnesium at different rates. In mammalian heart, kidney and adipocytes, total intracellular magnesium is able to exchange with plasma magnesium within 3–4 h [38–42]. In man, equilibrium for magnesium among most tissue compartments is reached very slowly, if at all [17]. About 85% of the whole body magnesium, measured as [28]Mg is either non-exchangeable or exchanges very slowly with a roughly estimated biological half-life of ∼1000 h [43].

Magnesium consumption
Humans need to consume magnesium regularly to prevent magnesium deficiency, but as the recommended daily allowance for magnesium varies, it is difficult to define accurately what the exact optimal intake should be. Values of ≥300 mg are usually reported with adjusted dosages for age, sex and nutritional status. The Institute of Medicine recommends 310–360 mg and 400–420 mg for adult women and men, respectively. Other recommendations in the literature suggest a lower daily minimum intake of 350 mg for men and 280–300 mg magnesium for women (355 mg during pregnancy and lactation) [2, 7, 10, 18].

While drinking water accounts for ∼10% of daily magnesium intake [44], chlorophyll (and thus green vegetables) is the major source of magnesium. Nuts, seeds and unprocessed cereals are also rich in magnesium [15]. Legumes, fruit, meat and fish have an intermediate magnesium concentration. Low magnesium concentrations are found in dairy products [7]. It is noteworthy that processed foods have a much lower magnesium content than unrefined grain products [7] and that dietary intake of magnesium in the western world is decreasing owing to the consumption of processed food [45]. With the omnipresence of processed foods, boiling and consumption of de-mineralized soft water, most industrialized countries are deprived of their natural magnesium supply. On the other hand, magnesium supplements are very popular food supplements, especially in the physically active.

Magnesium absorption and excretion
Magnesium homeostasis is maintained by the intestine, the bone and the kidneys. Magnesium—just like calcium—is absorbed in the gut and stored in bone mineral, and excess magnesium is excreted by the kidneys and the faeces (Figure 4). Magnesium is mainly absorbed in the small intestine [21, 15, 46], although some is also taken up via the large intestine [7, 10, 47]. Two transport systems for magnesium in the gut are known (as discussed in the article by de Baaij et al. [48] in this supplement). The majority of magnesium is absorbed in the small intestine by a passive paracellular mechanism, which is driven by an electrochemical gradient and solvent drag. A minor, yet important, regulatory fraction of magnesium is transported via the transcellular transporter transient receptor potential channel melastatin member (TRPM) 6 and TRPM7—members of the long transient receptor potential channel family—which also play an important role in intestinal calcium absorption [21]. Of the total dietary magnesium consumed, only about 24–76% is absorbed in the gut and the rest is eliminated in the faeces [46]. It is noteworthy that intestinal absorption is not directly proportional to magnesium intake but is dependent mainly on magnesium status. The lower the magnesium level, the more of this element is absorbed in the gut, thus relative magnesium absorption is high when intake is low and vice versa. When intestinal magnesium concentration is low, active transcellular transport prevails, primarily in the distal small intestine and the colon (for details, see de Baaij et al. [48] in this supplement).

The kidneys are crucial in magnesium homeostasis [18, 49–51] as serum magnesium concentration is primarily controlled by its excretion in urine [7]. Magnesium excretion follows a circadian rhythm, with maximal excretion occurring at night [15]. Under physiological conditions, ∼2400 mg of magnesium in plasma is filtered by the glomeruli. Of the filtered load, ∼95% is immediately reabsorbed and only 3–5% is excreted in the urine [10, 52], i.e. ∼100 mg. It is noteworthy that magnesium transport differs from that of the most other ions since the major re-absorption site is not the proximal tubule, but the thick ascending limb of the loop of Henle. There, 60–70% of magnesium is reabsorbed, and another small percentage (∼10%) is absorbed in the distal tubules. The kidneys, however, may lower or increase magnesium excretion and re-absorption within a sizeable range: renal excretion of the filtered load may vary from 0.5 to 70%. On one hand, the kidney is able to conserve magnesium during magnesium deprivation by reducing its excretion; on the other hand, magnesium might also be rapidly excreted in cases of excess intake [18]. While reabsorption mainly depends on magnesium levels in plasma, hormones play only a minor role (e.g. parathyroid hormone, anti-diuretic hormone, glucagon, calcitonin), with oestrogen being an exception to this rule.

Magnesium is essential for man and has to be consumed regularly and in sufficient amount to prevent deficiency.
It is a cofactor in more than 300 enzymatic reactions needed for the structural function of proteins, nucleic acids and mitochondria.
Absorption is complex, depending on the individual’s magnesium status, and excretion is controlled primarily by the kidneys.


Assessment of magnesium status
Serum magnesium concentration
To date, three major approaches are available for clinical testing (Table 4). The most common test for the evaluation of magnesium levels and magnesium status in patients is serum magnesium concentration [21, 56], which is valuable in clinical medicine, especially for rapid assessment of acute changes in magnesium status [17]. However, serum magnesium concentration does not correlate with tissue pools, with the exception of interstitial fluid and bone. It also does not reflect total body magnesium levels [17, 57]. Only 1% of total body magnesium is present in extracellular fluids, and only 0.3% of total body magnesium is found in serum, and so serum magnesium concentrations [22] are poor predictors of intracellular/total body magnesium content [7]. This situation is comparable to assessing total body calcium by measuring serum calcium, which, too, does not adequately represent total body content. As with many reference values, laboratory parameters will also vary from laboratory to laboratory resulting in slightly varying ranges for the ‘healthy’ populations evaluated. What is considered the ‘normal level’ might actually be slightly too low, representing a mild magnesium deficit present in the normal population [17].

In addition, there are individuals—in particular those with a subtle chronic magnesium deficiency—whose serum magnesium levels are within the reference range but who still may have a deficit in total body magnesium. And vice versa: some people—though very few—have low serum magnesium levels but a physiological magnesium body content [17]. Moreover, serum magnesium might be higher in vegetarians and vegans than in those with omnivorous diets. The same applies to levels after short periods of maximal exercise as lower serum levels are observed after endurance exercises [58, 59] and also during the third trimester of pregnancy. There is also intra-individual variability [60]. Moreover, measurements are strongly affected by haemolysis (and therefore by a delay in separating blood), and by bilirubin [59].

In healthy individuals, magnesium serum concentration is closely maintained within the physiological range [13, 15, 18]. This reference range is 0.65–1.05 mmol/L for total magnesium concentrations in adult blood serum [61] and 0.55–0.75 mmol/L for ionized magnesium [62]. According to Graham et al. [46], blood plasma concentration in healthy individuals is similar to serum, ranging from 0.7 to 1.0 mmol/L.

Magnesium concentration in RBCs is generally higher than its concentration in serum [46] (i.e. 1.65–2.65 mmol/L) [61]. The magnesium concentration is even higher in ‘young’ RBCs [13], which might be particularly relevant in patients receiving erythropoietin. Thus, when measuring magnesium serum levels, it is important to avoid haemolysis to prevent misinterpretation [17, 22].

Although some limitations may apply, serum magnesium concentration is still used as the standard for evaluating magnesium status in patients [21]. It has proven helpful in detecting rapid extracellular changes. In addition, measuring serum magnesium is feasible and inexpensive [As an example: Mg in serum (photometric assessment/AAS)—Germany (Synlab, Augsburg): EBM 32248 (EBM = einheitlicher Bewertungsmaßstab für Ärzte, kassenärztliche Abrechnung; valuation standard) = 1.40 €; GOÄ 3621 1.00 (GOÄ = Gebührenordnung für Ärzte, private; scale of charges for physicians) = 2.33 €; Denmark (GPs laboratory, Copenhagen): 87.50 DDK = 11.66 €; France (Biomnis, Ivry-sur Seine) = 1.89 €] and should become more common in clinical routine.

Twenty-four-hour excretion in urine
Another approach for the assessment of magnesium status is urinary magnesium excretion. This test is cumbersome, especially in the elderly, since it requires at least a reliable and complete 24-h time frame [54]. As a circadian rhythm underlies renal magnesium excretion, it is important to collect a 24-h urine specimen to assess magnesium excretion and absorption accurately. This test is particularly valuable for assessing magnesium wasting by the kidneys owing to medication or patients’ physiological status [7]. The results will provide aetiological information: while a high urinary excretion indicates renal wasting of magnesium, a low value suggests an inadequate intake or absorption [7].

Magnesium retention test—‘loading test’
A further refinement is the magnesium retention test. This ‘loading test’ may serve for identification of patients with hypomagnesaemic and normomagnesaemic magnesium deficiencies. Retention of magnesium following acute oral or parenteral administration is used to assess magnesium absorption, chronic loss and status. Changes in serum magnesium concentration and excretion following an oral magnesium load reflect intestinal magnesium absorption [7, 63]. Magnesium retained during this test is retained in bone. Thus, the lower the bone magnesium content the higher the magnesium retention in this test [64]. The percentage of magnesium retained is increased in cases of magnesium deficiency and is inversely correlated with the concentration of magnesium in bone [65, 66]. This test quantifies the major exchangeable pool of magnesium, providing a more sensitive index of magnesium deficiency than simply measuring serum magnesium concentration. A urinary excretion of >60–70% of the magnesium load suggests that magnesium depletion is unlikely. Standardization of this test, however, is lacking [22].

Isotopic analysis of magnesium
Magnesium exists in three different isotopes: 78.7% occurs as [24]Mg, 10.1% as [25]Mg and 11.2% as [26]Mg [5]. [28]Mg is radioactive and was made available commercially for scientific use in the 1950s to the 1970s. Radioactive tracer elements in ion uptake assays allow the calculation of the initial change in the ion content of the cells. [28]Mg decays by emission of high-energy beta or gamma particles that can be measured using a scintillation counter. However, the radioactive half-life of the most stable radioactive magnesium isotope—[28]Mg—is only 21 h, restricting its use. [26]Mg was used to assess absorption of magnesium from the gastrointestinal tract, presenting nutritional and analytical challenges. Although studies with isotopes of magnesium can provide important information, they are limited to research [7]. Surrogates for magnesium (i.e. Mn2+, Ni2+ and Co2+) have been used [5]. They were used to mimic the properties of magnesium in some enzymatic reactions, and radioactive forms of these elements were successfully employed in cation transport studies. The most common surrogate is Mn2+ that can replace magnesium in the majority of enzymes where ATP-Mg is used as a substrate [5].

Assessment of total serum magnesium concentration is the most practicable and inexpensive approach for the detection of acute changes in magnesium status.

However, one should bear in mind that serum magnesium concentration does not reflect the patient's magnesium status accurately as it does not correlate well with total magnesium body content.

Pathophysiology
Hypomagnesaemia
The definition of magnesium deficiency seems simpler than it is, primarily because accurate clinical tests for the assessment of magnesium status are still lacking. Evaluation of serum magnesium concentration and collection of a 24-h urine specimen for magnesium excretion are at present the most important laboratory tests for the diagnosis of hypomagnesaemia. The next step would be to perform a magnesium retention test [7].

In the literature, patients with serum magnesium concentrations ≤0.61 mmol/L (1.5 mg/dL) [67–69] and ≤0.75 mmol/L, respectively, were considered hypomagnesaemic [70, 71].

Hypomagnesaemia is common in hospitalized patients, with a prevalence ranging from 9 to 65% [67, 69–72]. A particularly high incidence of hypomagnesaemia is observed in intensive care units. Furthermore, a significant association has been reported between hypomagnesaemia and esophageal surgery [70]. In these severely ill patients, nutritional magnesium intake was probably insufficient. Certain drugs have been associated with magnesium wasting (although the relationship between these factors remains unclear), putting the afflicted patients at an increased risk for acute hypomagnesaemia. Such medications include aminoglycosides, cisplatin, digoxin, furosemide, amphotericin B and cyclosporine A [67, 70] (Table 5). Moreover, it was observed that in patients with severe hypomagnesaemia, mortality rates increase [67, 70]. Therefore, assessment of magnesium status is advised, particularly in those who are critically ill. When hypomagnesaemia is detected, one should address—if identifiable—the underlying pathology to reverse the depleted status [73].

Hypomagnesaemia has been linked to poor condition (malignant tumours, cirrhosis or cerebrovascular disease) [70] and a number of other ailments. Magnesium deficiencies might stem from reduced intake caused by poor nutrition or parenteral infusions lacking magnesium, from reduced absorption and increased gastrointestinal loss, such as in chronic diarrhoea, malabsorption or bowel resection/bypass [6–8]. Deficiencies might also be triggered by increased magnesium excretion in some medical conditions such as diabetes mellitus, renal tubular disorders, hypercalcaemia, hyperthyroidism or aldosteronism or in the course of excessive lactation or use of diuretics (Table 5). Compartmental redistribution of magnesium in illnesses such as acute pancreatitis might be another cause of acute hypomagnesaemia [7]. In addition, several inherited forms of renal hypomagnesaemia exist [88]. These genetic changes led to the detection of various transporters (see de Baaij et al. [48] in this supplement, for further details).

Chronic hypomagnesaemia
Diagnosis of chronic hypomagnesaemia is difficult as there may be only a slightly negative magnesium balance over time. There is equilibrium among certain tissue pools, and serum concentration is balanced by magnesium from bone. Thus, there are individuals with a serum magnesium concentration within the reference interval who have a total body deficit for magnesium. Magnesium levels in serum and 24-h urine samples may be normal, and so parenteral administration of magnesium with assessment of retention should be considered if in doubt [7]. Chronic latent magnesium deficiency has been linked to atherosclerosis, myocardial infarction, hypertension (see also Geiger and Wanner [37] in this supplement.), malignant tumours, kidney stones, alteration in blood lipids, premenstrual syndrome and psychiatric disorders.

Clinical signs of hypomagnesaemia
Clinical signs of hypo- and hypermagnesaemia overlap often and are rather non-specific. Manifestations of hypomagnasaemia might include tremor, agitation, muscle fasciculation, depression, cardiac arrhythmia and hypokalaemia [6, 10, 67] (Table 6). Early signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue and weakness [67]. As magnesium deficiency worsens, numbness, tingling, muscle contractions, cramps, seizures, sudden changes in behaviour caused by excessive electrical activity in the brain, personality changes [67], abnormal heart beat and coronary spasms might occur. Severe hypomagnesaemia is usually accompanied by other imbalances of electrolytes such as low levels of calcium and potassium in the blood (for mechanisms, see de Baaij et al. [48] in this supplement). However, even in patients with severe hypomagnesaemia, clinical signs associated with magnesium deficiency may be absent [7]. In addition, there seems to be a greater likelihood of clinical symptoms with a rapid decrease in serum magnesium concentration compared with a more gradual change. Therefore, physicians should not wait for clinical signs to occur before checking serum magnesium levels [7].

Hypermagnesaemia
As the kidneys play a crucial role in magnesium homeostasis, in advanced chronic kidney disease, the compensatory mechanisms start to become inadequate and hypermagnesaemia may develop (see Cunningham et al [28] in this supplement). Symptomatic hypermagnesaemia may be caused by excessive oral administration of magnesium salts or magnesium-containing drugs such as some laxatives [89] and antacids [14], particularly when used in combination in the elderly and when renal function declines [8, 67, 90–94]. In addition, hypermagnesaemia may be iatrogenic, when magnesium sulphate is given as an infusion for the treatment of seizure prophylaxis in eclampsia [67, 95] or erroneously in high doses for magnesium supplementation [96, 97].

Prevalence of—mostly undiagnosed—hypermagnesaemia in hospitalized patients is reported, varying from 5.7% [98] to 7.9% [67] and 9.3% [69]. In intensive care patients, the prevalence of total hypermagnesaemia was reported as being 13.5%, whereas ionized hypermagnesaemia was 23.6% [99]. These studies did not specify whether hypermagnesaemia in hospitalized patients was a pathological consequence of severe disease, or if it was iatrogenic, perhaps reflecting excessive magnesium supplementation in intensive care.

Case reports exist of pre-term babies with extreme hypermagnesaemia—magnesium levels of 17.5 mmol/L [100] and 21.5 and 22.5 mmol/L [97]—which, in one case, was the result of a malfunctioning total parenteral nutrition mixing device. All three infants survived. There are other reports about affected neonates whose mothers had gestational toxicosis and who had been treated with magnesium sulphate because of eclamptic convulsion [7]. Excessive magnesium ingestion and intoxication was also reported in association with drowning in the Dead Sea. The average serum magnesium concentration in 48 adults who ‘nearly drowned’ in the Dead Sea was 3.16 mmol/L, with one patient recorded at 13.57 mmol/L [101–103].

Clinical signs of hypermagnesaemia
Serum magnesium concentrations, as reported in the literature, vary widely among patients with similar signs and symptoms. In the beginning, no immediate clinical signs may be present and hypermagnesaemia might stay undetected for sometime [67]. For example, increased magnesium concentrations (>1.07 mmol/L) were found in sera from 7.9% of 6252 patients, but no description of symptoms was noted in 80% of clinical charts, also not in patients with values >1.6 mmol/L (0.8%) [67]. Moderately elevated serum magnesium levels may be associated with hypotension, cutaneous flushing, nausea and vomiting, but these symptoms mostly occur only upon infusion of magnesium sulphate. At higher concentrations, magnesium might lead to neuromuscular dysfunction, ranging from drowsiness to respiratory depression, hypotonia, areflexia and coma in severe cases. Cardiac effects of hypermagnesaemia may include bradycardia; uncharacteristic electrocardiogram findings such as prolonged PR, QRS and QT intervals, complete heart block, atrial fibrillation and asystole. However, these findings are neither diagnostic nor specific for this metabolic abnormality [100] (Table 7).

Treatment of hypo- and hypermagnesaemia
In cases of mild hypomagnesaemia in otherwise healthy individuals, oral magnesium administration is used successfully [68]. Acute and chronic oral magnesium supplementation has been described as well tolerated with a good safety profile [104, 105]. Intravenous administration of magnesium, mostly as magnesium sulphate, should be used when an immediate correction is mandatory as in patients with ventricular arrhythmia and severe hypomagnesaemia [106].

Treatment of patients with symptomatic hypermagnesaemia includes discontinuation of magnesium administration, use of supportive therapy and administration of calcium gluconate [6, 107]. Treatment of severe, symptomatic hypermagnesaemia may require haemodialysis [7].
Mild hypo- and hypermagnesaemia are quite common, especially in hospitalized patients, and may not be associated with clinical symptoms.
Severe hypo- and hypermagnesaemia show partially overlapping symptoms, making diagnosis difficult without assessment of serum magnesium concentration.

Conclusions
The chemistry of magnesium is unique among cations of biological relevance. Magnesium is essential for man and is required in relatively large amounts. Magnesium is a cofactor in >300 enzymatic reactions and thus it is essential for many crucial physiological functions, such as heart rhythm, vascular tone, nerve function and muscle contraction and relaxation. Magnesium is also needed for bone formation and can also be referred to as a natural ‘calcium antagonist’. However, hypomagnesaemia is rather common, in particular, in hospitalized patients. Moreover, as the intake of refined foods increases—as appears to be the case in developed countries—magnesium deficiency will most likely evolve into a more common disorder. Nonetheless, total serum magnesium is rarely measured in clinical practice. Despite some limitations, the assessment of serum magnesium concentration is inexpensive and easy to employ and provides important information about magnesium status in patients.