Monday, October 30, 2017

Transdermal Magnesium - Finally a Human Study Suggests That Low-Dose Mg2+ Cream Works, at Least in Non-Athletes

Supplement producers have built their business on the (unwarranted) premise that you cannot get enough magnesium from your diet, alone.
Unlike the effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency, which has been studied in detail, the ever more popular transdermal magnesium preparations are a "scientifically not yet proven form of magnesium application" (Gröber 2017)... that was true earlier this year when Gröber and colleagues from the Akademie für Mikronährstoffmedizin and the IPEV Institute for Prevention and Nutrition in Germany was written.

With the recent publication of a study from the University of Hertfordshire (Kass 2017), there's finally a single-blind, parallel designed pilot study that deserves the title "study".
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Conducted with n = 25 participants (aged 34.3+/-14.8y, height 171.5+/-11cm, weight 75.9 +/-14 Kg) who were randomly assigned to either a 56mg/day magnesium cream or placebo cream group for two weeks, the study is the first study to investigate the absorbency of transdermal magnesium cream in human subjects.
GeneralAnxiety, lethargy, weakness, agitation, depression, dysmenorrhea, hyperactivity, headache, irritability, dysacusis, low stress tolerance, loss of appetite, nausea, sleep disorders, impaired athletic performance.
MusculatureMuscle spasm, cramps in the soles of the feet, leg cramps, facial muscles, masticatory muscles, and calves, carpopedal spasm, back aches, neck pain, urinary spasms, magnesium deficiency tetany.
Nerves/CNSNervousness, increased sensitivity of NMDA receptors to excitatory neurotransmitters, migraine, depression, nystagmus, paraesthesia, poor memory, seizures, tremor, vertigo.
Gastrointestinal tractConstipation.
Cardiovascular systemRisk of arrhythmias, supraventricular or ventricular arrhythmias, hypertension, coronary spasm, decreased myocardial pump function, digitalis sensitivity, torsade de pointes, death from heart disease.
ElectrolytesHypokalaemia, hypocalcemia, retention of sodium.
MetabolismDyslipoproteinemia (increased blood triglycerides and cholesterol), decreased glucose tolerance, insulin resistance, increased risk of metabolic syndrome, disturbances of bone and vitamin D metabolism, resistance to PTH, low circulating levels of PTH, resistance to vitamin D, low circulating levels of 25(OH)D, recurrence of calcium oxalate calculi.
MiscellaneousAsthma, chronic fatigue syndrome, osteoporosis, hypertension, altered glucose homeostasis.
PregnancyPregnancy complications (e.g., miscarriage, premature labor, eclampsia).
Table 1: Magnesium: Deficiency signs and symptoms (Gröber 2016)
Magnesium serum and 24hour urinary excretion were measured at baseline and at 14 days intervention. Food diaries were recorded for 8 days during this period. Four participants were considered “athletes” as they engaged in at least 2hrs of physical exercise at least 5 days per week during the study, three who were assigned to the Mg2+ intervention group and one assigned to receive placebo. All other 20 participants who completed the study were considered “non-athletes”, i.e. engaging in less than 2 hrs physical exercise per day for no more than 3 d/wk during the study.
What to measure to know your real magnesium status? Since less than 1% of magnesium is contained in the blood, assessment by serum status may be problematic (Elin 2010). An often-used alternative, namely 24-hr urine excretion of Mg2+, on the other hand, is a good marker of intestinal absorption and the acute dietary/supplemental magnesium but is not a reliable marker of an individual’s Mg2+ status (Trauninger 2002). So what can be done?

Djurhuus et al. (Djurhuus 1995) point out that although it is unlikely that a single determination of serum Mg2+ can be used in assessing whole-body Mg2+ status in an individual, serial determinations of serum Mg2+ might prove useful as an indicator of changes in whole body Mg2+ status. To get the best of both worlds, Kass et al. "decided to use 24-hr urinary Mg2+ as well as serum Mg2+ in this pilot study" on the bioavailability and efficacy of magnesium cream.
After baseline measurements were taken, participants were randomly assigned to either the Mg2+ Cream or a placebo control cream and were instructed to apply 2 x 5ml spoonfuls of cream per day for two weeks.
Figure 1: Plasma an bone (primary axis) as well as red blood cell (RBC; 2ndary axis(!)) content after 14 days of supplementation with identical amounts of magnesium in different organic and inorganic forms (Coudray. 2005 | learn more)
The resulting daily Mg2+ dose received by subjects in the Mg2+ group consisted of 56mg of Mg2+. The placebo was a commercially available aqueous cream containing no magnesium (by analysis) and creams were packaged identically. Instructions to participants suggested that Mg2+ or placebo cream be applied to the stomach and torso in the first instance and then spread down to the legs. Time of day was not important, but no showering or washing could take place for a minimum of 3 hours after application. After 12–14 days, final urine and blood samples were collected.
Table 2: Influence of Trans-dermal Magnesium vs placebo cream application on Serum and Urinary Magnesium Concentrations (mean +/- S.D.) for non-athlete subjects (Kass 2017); p < 0.02 compared with pre-serum Mg2+ value.
The results will make transdermal advocates happy: While the Mg test and placebo groups’ serum and urinary Mg did not differ at baseline. There was a clinically relevant increase in serum magnesium (0.82 to 0.89 mmol/l,p = 0.29) after the Mg2+ cream intervention that was not seen in the placebo group (0.77 to 0.79 mmol/L).

What the same people are not going to like, though, is that this effect was only statistically significant (p = 0.02)) only in the subgroup of non-athletes and that there was no significant difference in magnesium urinary excretion between active treatment and placebo (p = 0.48).

Overall, the study does yet still suggest that transdermal magnesium works

While statistically significant inter-group differences were not observed for all relevant outcome parameters, the overall message of the study at hand is still that magnesium is absorbed through the skin. After all, the amount of magnesium in the cream was small. Small enough to put the 8.54% increase in serum Mg2+ and a 9.1% increase in urinary Mg2+ appear like a success when you compare them to the +2.6% for serum Mg2+ and -32% for urinary Mg2+ in the placebo group - despite the lack of statistical significance for the difference.
Magnesium Supplementation and its Potential Performance Effects: Study Finds Practically Relevant Improvements in 10k Times W/ 500mg per Day in Recreational Athletes | learn more
Bottom line: While Gröber et al. (2017) rightly point out that "a primary function of the skin is to act as a barrier, which normally restricts the absorption of exogenous chemicals into the body" (Gröber 2017) and remind us that "[e]xtensive studies of the Israel army with a magnesium-containing skin protectant lotion (IB1) showed that magnesium is not absorbed through the skin" (ibid.) Kass' pilot investigation on PLOS|One can give you hope that the money you spent on transdermal magnesium products may not have been completely wasted if your product has the same skin penetration as the Mg2+ cream that was used in Kass' study.

Speaking of which, the studied product contained a mix of magnesium chloride (10%), cetearyl olivate, sorbitan olivate, isopropyl palmitate, emulsifying wax, glycerine, butyrospermum parkii (shea butter), hydroxypropyl starch phosphate, iodopropynyl butylcarbamate, phenoxyethanol, and caprylyl glycol and was manufactured, in the course of research and development, for the Center for Magnesium Education & Research by Urist Cosmetics of Vancouver, B.C. Canada.

What we need now is/are (a) independent confirmation by researchers without financial interest in proving the efficacy of Mg2+ cream (here that's co-author Rosanoff), (b) studies using higher concentrations of magnesium, and (c) a longer-term follow-up in human beings that would also access the Mg2+ content of red blood or other cells | Comment!
References:
  • Djurhuus, M.S., Gram, J., Petersen, P.H., Klitgaard, N.A.H., Bollerslev, J. and Beck-Nielsen, H., 1995. Biological variation of serum and urinary magnesium in apparently healthy males. Scandinavian journal of clinical and laboratory investigation, 55(6), pp.549-558.
  • Elin, R.J., 2010. Assessment of magnesium status for diagnosis and therapy. Magnesium Research, 23(4), pp.194-198.
  • Gröber, U., Schmidt, J. and Kisters, K., 2015. Magnesium in prevention and therapy. Nutrients, 7(9), pp.8199-8226.
  • Gröber, U., Werner, T., Vormann, J. and Kisters, K., 2017. Myth or Reality—Transdermal Magnesium?. Nutrients, 9(8), p.813.
  • Kass, L., Rosanoff, A., Tanner, A., Sullivan, K., McAuley, W. and Plesset, M., 2017. Effect of transdermal magnesium cream on serum and urinary magnesium levels in humans: A pilot study. PloS one, 12(4), p.e0174817.
  • Trauninger, A., Pfund, Z., Koszegi, T. and Czopf, J., 2002. Oral magnesium load test in patients with migraine. Headache: The Journal of Head and Face Pain, 42(2), pp.114-119.