1Akademie für Mikronährstoffmedizin, Zweigertstr. 55, 45130 Essen, Germany; ed.latipsohanna@sretsik
2IPEV Institute for Prevention and Diet, Adalperostr. 37, D-85737 Ismaning, Germany; [email protected] (T.W.); ed.vepi@nnamrov (J.V.)
2IPEV Institute for Prevention and Diet, Adalperostr. 37, D-85737 Ismaning, Germany; [email protected] (T.W.); ed.vepi@nnamrov (J.V.)
1Akademie für Mikronährstoffmedizin, Zweigertstr. 55, 45130 Essen, Germany; ed.latipsohanna@sretsik
3Medizinische Klinik I, St. Anna-Hospital, 44649 Herne, Germany
Summary
1. Introduction
Magnesium has been acknowledged as a cofactor for greater than 300 enzymatic reactions, the place it’s essential for adenosine triphosphate (ATP) metabolism. Magnesium is required for DNA and RNA synthesis, copy, and protein synthesis. Furthermore, magnesium is crucial for the regulation of muscular contraction, blood stress, insulin metabolism, cardiac excitability, vasomotor tone, nerve transmission and neuromuscular conduction. Imbalances in magnesium standing—primarily hypomagnesaemia as it’s seen extra typically than hypermagnesemia—would possibly end in undesirable neuromuscular, cardiac or nervous issues.
Extreme hypermagnesemia or magnesium intoxication seems very seldom in human illness. Such circumstances solely happen in extreme renal insufficiency or iatrogen. Nonetheless, medical signs are noticed extra continuously in magnesium-deficient and -insufficient sufferers in inside medication. Magnesium deficiency shouldn’t be unusual among the many common inhabitants: its consumption has decreased over time, particularly within the Western world. Hypomagnesaemia is outlined as serum magnesium focus <0.75 mmol/L. Early signs of magnesium deficiency are non-specific and include loss of appetite, lethargy, nausea, vomiting, fatigue, and weakness. More pronounced magnesium deficiency presents with symptoms of increased neuromuscular excitability such as tremor, carpopedal spasm, muscle cramps, tetany and generalized seizures. Hypomagnesemia can cause cardiac arrhythmias including atrial and ventricular tachycardia, prolonged QT interval and torsades de pointes (see Table 1). Hypomagnesaemia is frequently associated with other electrolyte abnormalities such as hypokalemia and hypocalcaemia. Conditions that may lead to hypomagnesemia include alcoholism, poorly-controlled diabetes, malabsorption (e.g., Crohn’s disease, ulcerative colitis, coeliac disease, short bowel syndrome, Whipple’s disease), endocrine causes (e.g., aldosteronism, hyperparathyroidism, hyperthyroidism), renal disease (e.g., chronic renal failure, dialysis, Gitelman’s syndrome) and medication use. A variety of drugs including antibiotics, chemotherapeutic agents, diuretics and proton pump inhibitors can cause magnesium loss and hypomagnesemia. In addition, magnesium deficiency exacerbates potassium-mediated arrhythmia, in particular in the presence of digoxin intoxication [1]. Magnesium compounds are widely used as medicinal and dietary supplements. The effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency is beyond controversy [1,2,3,4,5]. Furthermore, a recent meta-analysis identified that a supplement of >370 mg magnesium/day exhibits better efficacy than a decrease dose in bettering blood stress and that magnesium supplementation offers a dose dependent response almost about blood stress [4].
In each, specialist and lay press in addition to on the web, there are growing numbers of articles claiming the effectiveness and superiority of transdermal magnesium over an oral utility. Transdermal magnesium utility needs to be the last word option to replenish mobile magnesium ranges since each cell within the physique bathes in it. It passes instantly into the tissues through the pores and skin, the place it ought to rapidly be transported to cells all through the physique. Moreover, the transdermal absorption of magnesium compared to oral utility is introduced as being simpler on the one hand resulting from almost 100% absorption, and as presenting fewer unwanted side effects however as it’s bypassing the gastrointestinal tract [6,7]. Scepticism based mostly on ignorance impairs scientific analysis as a lot as claims based mostly on extreme religion.
2. Magnesium Absorption Transdermal
The pores and skin is the most important organ of the physique, masking about 1.8 m2 and comprising roughly 10% of the overall physique mass of a median particular person. The first perform of the pores and skin is to offer a barrier between the physique and the exterior setting. This barrier protects in opposition to the permeation of ultraviolet (UV) radiation, chemical compounds, allergens and microorganisms, along with the lack of moisture and physique vitamins [8]. Which means that the absorptive capability of wholesome pores and skin for substances from the skin may be very restricted. This turns into evident significantly within the restricted utility for topical medicine. To get by the pores and skin, a substance should penetrate the dermis or must be absorbed by sweat glands or hair follicles. The stratum corneum is the outermost layer of the dermis consisting of lifeless cells (corneocytes). This layer consists of about 15 to twenty layers of flattened cells with no nuclei and cell organelles. Their cytoplasm exhibits filamentous keratin. These corneocytes are embedded in a lipid matrix composed of ceramides, ldl cholesterol, and fatty acids. The stratum corneum features to kind a water-repellent barrier to guard underlying tissue from an infection, dehydration, chemical compounds and mechanical stress [9]. Overcoming this layer in important portions is just attainable for lipophilic substances. In magnesium chloride answer, magnesium is current in ionized kind and due to this fact not capable of penetrate a lipophilic layer. As well as, the radius of the hydrated magnesium ion (86 pm) has been reported to be 400 instances greater than its dehydrated kind, resulting in the assertion that it’s nearly inconceivable for magnesium ions to cross by organic membranes [2].
Subsequently, mobile magnesium uptake is just being carried out by particular magnesium transporters and never by diffusion. Nonetheless, since lifeless cells of the higher pores and skin layer don’t comprise useful magnesium transporters, which haven’t but been recognized intimately, magnesium absorption could also be attainable solely on the small space of sweat glands and hair follicles. A just lately revealed research confirmed that magnesium ions can penetrate the stratum corneum in a focus and time dependent method which is considerably facilitated by hair follicles. Nonetheless, hair follicles and sweat glands represent solely 0.1% to 1% of the pores and skin floor. Even when a substance is absorbed on this space, the query of the medical relevance of absorbed quantities must be addressed. Within the research that examined the permeation of topically utilized magnesium no data is given on the amount of absorbed magnesium [10,11].
3. Effectiveness of Transdermal Magnesium Absorption
One of many first research on transdermal magnesium absorption was revealed by the naturopathic physician and founding father of the American Holistic Medical Affiliation Norman Shealy, M.D. Ph.D in 2000. He was an early advocate for the actual advantages of transdermal functions of magnesium [12]. Shealy argued {that a} magnesium deficiency might be compensated by transdermal utility inside 4 to six weeks, whereas an oral supplementation is efficient solely after 4 to 12 months. A full publication of this comparative research couldn’t be discovered. Solely an summary for a convention was revealed not displaying any extra information to substantiate this assertion [7].
One other research that’s typically cited for proving that transdermal magnesium absorption gives a easy, price efficient and environment friendly methodology to extend mobile magnesium ranges was a trial that happened over a 12-week interval and concerned a complete of 9 sufferers aged between 22 and 69 years (solely weak statistical energy). Following provision of a hair pattern, though recognized to be solely much less consultant for complete physique magnesium dealing with, for evaluation of mineral content material every affected person examined was instructed to use 20 sprays of magnesium oil. The unique remedy consisted of the each day spray, wherever on the physique, in addition to a 20-min foot soak utilizing 100 mL magnesium oil (utilizing a easy water footbath) twice weekly. On the finish of 12-week remedy an extra hair evaluation was carried out. After transdermal functions for 12 weeks all sufferers besides one had a big improve in mobile magnesium starting from −7.1% to 262%. One affected person ceased utility prematurely, three weeks earlier than the ultimate evaluation. General a median improve of 59.7% in hair was noticed. No information on serum magnesium focus was out there [6].
A research of comparable questionable high quality for proving transdermal magnesium absorption is an examination of Waring from the College of Birmingham, United Kingdom, the place 19 topics underwent a full physique tub (temperatures 50–55 °C) for 7 days in an answer of magnesium sulphate (Epsom salt) for 12 min. Blood samples had been taken earlier than the primary tub, at 2 h after the primary tub and at 2 h after the seventh consecutive tub. Baths had been taken each day on the identical time for 7 days for the experiment. Urine samples had been collected earlier than the primary tub after which 2 h after the primary tub and in any respect subsequent baths. Urine samples had been additionally taken 24 h after the final tub. All urine samples had been corrected for creatinine content material. Of the 19 topics, all besides three confirmed an increase in magnesium concentrations in plasma, although this was small in some instances. The values earlier than the primary tub had a imply of 104.68 ± 20.76 ppm/mL; after the primary tub, the imply was 114.08 ± 25.83 ppm/mL. The continuation of bathing for 7 days in all besides two people gave an increase to a imply of 140.98 ± 17.00 ppm/mL. Extended soaking in Epsom salts due to this fact will increase blood magnesium concentrations. The measurement of magnesium ranges in urine confirmed an increase from the management degree, imply 94.81 ± 44.26 ppm/mL to 198.93 ± 97.52 ppm/mL after the primary tub. These people the place the blood magnesium ranges weren’t elevated had correspondingly giant will increase in urinary magnesium displaying that the magnesium ions had crossed the pores and skin barrier and had been excreted through the kidney, presumably as a result of the blood ranges had been already optimum. Typically, urinary magnesium ranges 24 h after the primary tub fell from the preliminary values discovered after day 1 (imply 118.43 ± 51.95) suggesting some retention of magnesium in tissues after bathing as blood ranges had been nonetheless excessive. The measurement of magnesium ranges in urine 24 h after the seventh tub gave values nearly again to regulate ranges. Nonetheless, this research has solely been revealed on the web—on the business web site of the Epson-salt-council—however not in a scientific, peer-reviewed journal [13].
Essentially the most plentiful supply of biologically out there magnesium, nonetheless, is the hydrosphere (i.e., oceans and rivers). The Useless Sea, the deepest and most saline lake on earth, has been recognized from biblical instances for its therapeutic properties and the effectiveness of bathing within the Useless Sea is well-known (Determine 1). Within the sea, the focus of magnesium is about 55 mmol/L and within the Useless Sea as an excessive instance, the focus of magnesium is reported to be 198 mmol/L and has steadily elevated over time [14,15]. Compared, the standard human serum magnesium focus is just ~0.8 mmol/L [1]. Thus, there’s a substantial gradient into the human physique.
Close to-drowning within the Useless Sea is predicted to end in extreme electrolyte abnormalities and respiratory failure. This means that magnesium doesn’t pertain to the subject of dermal absorption. In a single cohort research, the information had been abstracted from the archives of Soroka College Medical Middle. The cohort comprised 69 sufferers who almost drowned within the Useless Sea. There have been two main manifestations of near-drowning within the Useless Sea: electrolyte imbalance and acute lung harm. Serum calcium, magnesium and phosphorus (however not sodium, potassium and chloride) had been irregular in most sufferers. Median serum electrolyte ranges (and vary) on admission had been 10.9 mg/dL (9–24) for calcium, 4.3 mg/dL (1–30) for magnesium, and 4.1 mg/dL (2–9) for phosphorus. These ranges rapidly normalized with compelled diuresis inside 24 h. Acute lung harm—particularly, hypoxic bilateral pneumonitis—occurred in 29 sufferers. Mechanical air flow was required in 11 sufferers. Sixty-five sufferers recovered absolutely, whereas the remaining 4 had minor sequelae [17].
The penetration of electrolytes by the human pores and skin was measured in wholesome volunteers and in psoriatic sufferers after bathing within the Useless-Sea (Useless Sea water balneotherapy) or in simulated bath-salt options. Important will increase within the ranges of serum Bromine, Rubidium, calcium and zinc had been observed solely within the psoriatic sufferers after each day bathing within the Useless-Sea for a four-week routine. Guinea-pigs “bathed” in simulated Useless-Sea bath-salt options containing radionuclides of calcium, magnesium, potassium and Br. Traces of every radionuclide had been detected within the blood and in some inside organs after 60 min of bathing. The radionuclides confirmed a physiological sample of their organ distribution. Though the entire investigation was carried out in hypertonic options, there’s a particular penetration of salts by wholesome (human and guinea-pig) and broken (psoriatic) dermis [17]. Nonetheless, Useless Sea water balneotherapy doesn’t result in the worsening of blood stress. Substantial ingestion of Useless Sea water (usually in uncommon near-drowning instances) is poisonous and may end up in cardiac rhythm disturbances due to electrolyte focus abnormalities. A laboratory evaluation of Useless Sea mud didn’t reveal mineral concentrations that would symbolize a well being concern for his or her meant use [18].
Eight regular topics had been immersed in Bathtub spa water for 2 hours and the renal, haematological, and cardiovascular responses had been in contrast with these within the management durations earlier than and after immersion. Immersion in Bathtub spa water resulted in extremely important diuresis in contrast with the management state earlier than immersion (p < 0.01). The imply (SEM) complete extra quantity of water excreted on account of immersion over the 2-h interval was 510 (85) ml. A twofold improve in sodium excretion resulted from immersion (the speed earlier than immersion was 86 (15) pmol/min and 170-8 (29) pmol/min through the second hour) (p < 0.01). A major improve in potassium excretion was additionally noticed on immersion and was of the identical quantity because the sodium excretion (from 78-6 (19) pmol/min earlier than immersion to 156-2 (28) pmol/min by the second hour) (p < 0.01). A imply lack of weight of 0-53 (0–14) kg occurred. This corresponds with the losses of water from diuresis and in addition some loss from sweating. No important change was seen in creatinine clearance all through immersion, which ranged from imply values of 109 to 121 ml/min. As an indication that an uptake of magnesium by the wholesome human pores and skin whereas bathing shouldn't be attainable or in that case, solely very restricted no change occurred within the plasma concentrations of electrolytes, calcium, phosphate, or magnesium after 2 h bathing (35 °C). A major fall in plasma albumin focus was noticed (from 44-5 to 41-5 g/L) (p < 0.001) [16]. In depth research of the Israel military with a magnesium-containing pores and skin protectant lotion (IB1) confirmed that magnesium shouldn't be absorbed by the pores and skin, as examined in preclinical animal research in pigs in distinction to the lipophilic nature of sulfur mustard and VX, potent chemical warfare brokers that penetrate quickly by the pores and skin, inflicting extreme extended accidents and generally dying [19]. The topical pores and skin protectant lotion (IB1) containing magnesium was examined in a human research. Preclinical research in a number of animal fashions have confirmed the protecting efficacy of IB1. In a randomized, placebo-controlled section I medical research it was examined whether or not a magnesium-rich lotion, after repeated topical utility, results in adjustments in serum magnesium concentrations in 34 wholesome volunteers. The 34 topics administered 10 mL of magnesium-rich lotion or placebo lotion 3 times each day over a interval of three days. The research examined the security of repeated functions, together with ruling out the transdermal permeation of magnesium, which can result in a harmful blood magnesium degree, because the lotion accommodates magnesium sulphate. Different targets included the detection of dermatological hostile results, the evaluation of utility comfort, and the impact on each day actions. Importantly, no severe hostile results had been recorded and the lotion didn't intervene with each day duties. There have been no important variations in magnesium ranges between the placebo and the research teams in any of the functions. No poisonous ranges of magnesium had been present in both group [20]. Additionally in a research on remoted human cadaver pores and skin, no important distinction may very well be discovered for the pores and skin penetration of magnesium from options containing magnesium chloride (MgCl2). The aim of this research was to check the passive permeation of magnesium throughout human pores and skin from pharmaceutical grade MgCl2 formulated in cream to that of pharmaceutical grade MgCl2 in answer. The transdermal permeation effectivity of magnesium from MgCl2 cream I and MgCl2 cream II was studied throughout pores and skin in comparison with the constructive management MgCl2 answer and the damaging management phosphate buffer answer. The cream or MgCl2 answer equal to 2.76 mg of magnesium was utilized per 2.52 cm2 of pores and skin and mounted on diffusion cell. Samples had been collected after 1, 2, 3, 4, 5 and 24 h and analyzed utilizing atomic absorption spectroscopy at 285 nm. The experiments had been carried out in triplicates. The outcomes had been analyzed utilizing unpaired t-test. The cumulative magnesium permeation from magnesium cream I, magnesium cream II, MgCl2 answer, and phosphate buffer throughout human pores and skin after 24 h had been discovered to be 29.79 ± 13.92, 24.53 ± 9.98, 6.18 ± 1.36, and 5.62 ± 1.83 μg respectively. This research confirmed {that a} magnesium cream results in statistically important (p < 0.05) magnesium permeation in contrast with the 2 management options; Magnesium cream I confirmed better magnesium permeation than magnesium cream II, however the distinction was not statistically important. The MgCl2 answer confirmed the same end result to that of phosphate buffer. A formulated magnesium cream was capable of efficiently ship the magnesium of pharmaceutical grade MgCl2 throughout human pores and skin. Transdermal magnesium might play an vital function treating signs of sub-optimal magnesium standing. Nonetheless, additional in vitro and animal research are warranted to ascertain the efficacy of formulations [21].
A current pilot research got down to decide whether or not magnesium in a cream may very well be absorbed transdermally in people to enhance magnesium standing (6). Present formulations embody magnesium oils and transdermal lotions, from which the magnesium could also be absorbed throughout the pores and skin and into the systemic circulation. This cream was manufactured, in the middle of analysis and growth, for the Middle for Magnesium Training & Analysis, by Urist Cosmetics of Vancouver, B.C. Canada. For full elements, see S1 textual content elements listing of firm. Nonetheless, in distinction to the gastrointestinal epithelium, a main perform of the pores and skin is to behave as a barrier, which usually restricts the absorption of exogenous chemical compounds into the physique. On this single blind, parallel designed pilot research members (n = 25 4 members dropped out, aged 34.3 ± 14.8 years, top 171.5 ± 11 cm, weight 75.9 ± 14 Kg) had been randomly assigned to both a 56 mg/day magnesium cream (n = 11) or a placebo cream group (n = 10) for 2 weeks. Magnesium serum and 24 h urinary excretion had been measured at baseline and at 14 days of the intervention. Meals diaries had been recorded for eight days throughout this era. Mg take a look at and placebo teams' serum and urinary magnesium didn't differ at baseline. After the Mg2+ cream intervention there was a clinically related improve in serum magnesium (0.82 to 0.89 mmol/L, p = 0.29) that was not seen within the placebo group (n = 10) (0.77 to 0.79 mmol/L), however this distinction was solely statistically important (p = 0.02)) in a subgroup of non-athletes (n = 20). Magnesium urinary excretion elevated from baseline barely within the Mg2+ group however with no statistical significance (p = 0.48). The Mg2+ group confirmed an 8.54% improve in serum Mg2+ and a 9.1% improve in urinary Mg2+ whereas these figures for the placebo group had been smaller, i.e., +2.6% for serum Mg2+ and −32% for urinary Mg2+. Within the placebo group, each serum and urine concentrations confirmed no statistically important change after the applying of the placebo cream. On this two-week pilot research, transdermal supply of 56 mg Mg/day (a low dose in contrast with business transdermal Mg2+ merchandise out there) confirmed a bigger proportion change in each serum and urinary markers from pre to publish intervention in contrast with topics utilizing the placebo cream. Nonetheless, based mostly on this information from the unique summary, Kass et al. solely present a slight improve of serum magnesium through transdermal magnesium-containing cream [22].4. Conclusions – “magnesium cream”
Quite a few research display the effectiveness of oral therapeutic or preventive magnesium supplementation. Thus, an enough magnesium provide is vital for wholesome being pregnant and lactation, in addition to in sufferers with diabetes and prediabetes. Magnesium supplementation can also be helpful when taking medicine similar to diuretics and proton pump inhibitors. Primarily based on the present research this can be very alarming if a profitable remedy of magnesium fails by propagation of transdermal magnesium, a scientifically not but confirmed type of magnesium utility. We propose that future analysis ought to concentrate on a bigger variety of human topics given greater concentrations of, for instance, a magnesium cream utility administered for longer durations to analyze whether or not transdermal utility might present a big contribution to enchancment in magnesium standing. Magnesium would possibly be capable to get into the lymphatic system beneath the dermis and enter the circulatory system, bypassing the regulation by the GI tract and hereby growing serum magnesium [23,24,25]. Nonetheless, we can’t but suggest the applying of transdermal magnesium.
Creator Contributions
Paper was written by all authors. Evaluate was performed by U. Gröber, Okay. Kisters.
Conflicts of Curiosity
The authors declare no potential battle of curiosity.