Effect of Transdermal Magnesium Cream on Serum and Urinary Magnesium Levels in Humans: A Pilot Study

© 2017 Kass et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Oral magnesium supplementation is commonly used to support a low magnesium diet. This investigation set out to determine whether magnesium in a cream could be absorbed transdermally in humans to improve magnesium status. Methods and findings In this single blind, parallel designed pilot study, n=25 participants (aged 34.3+/-14.8y, height 171.5+/-11cm, weight 75.9 +/-14 Kg) were randomly assigned to either a 56mg/day magnesium cream or placebo cream group for two weeks. 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. Mg test and placebo groups’ serum and urinary Mg did not differ at baseline. After the Mg2+ cream intervention there was a clinically relevant increase in serum magnesium (0.82 to 0.89 mmol/l,p=0.29) that was not seen in the placebo group (0.77 to 0.79 mmol/L), but was only statistically significant (p=0.02)) in a subgroup of non-athletes . Magnesium urinary excretion increased from baseline slightly in the Mg2+ group but with no statistical significance (p=0.48). The Mg2+ group showed an 8.54% increase in serum Mg2+ and a 9.1% increase in urinary Mg2+ while these figures for the placebo group were smaller, i.e. +2.6% for serum Mg2+ and -32% for urinary Mg2+. In the placebo group, both serum and urine concentrations showed no statistically significant change after the application of the placebo cream. Conclusion No previous studies have looked at transdermal absorbency of Mg2+ in human subjects. In this pilot study, transdermal delivery of 56 mg Mg/day (a low dose compared with commercial transdermal Mg2+ products available) showed a larger percentage rise in both serum and urinary markers from pre to post intervention compared with subjects using the placebo cream, but statistical significance was achieved only for serum Mg2+ in a subgroup of non-athletes. Future studies should look at higher dosage of magnesium cream for longer durations.Peer reviewe

CD36 and Na/K-ATPase-α1 Form a Proinflammatory Signaling Loop in Kidney

Pro-atherogenic, hyperlipidemic states demonstrate increases in circulating ligands for scavenger receptor CD36 (e.g. oxidized LDL (oxLDL)) and the Na/K-ATPase (e.g. cardiotonic steroids). These factors increase inflammation, oxidative stress, and progression of chronic kidney disease. We hypothesized that diet-induced obesity and hyperlipidemia potentiate a CD36/ Na/K-ATPase -dependent inflammatory paracrine loop between proximal tubule cells (PTC) and their associated macrophages and thereby facilitates development of chronic inflammation and tubulointerstitial fibrosis. ApoE(−/−) and apoE(−/−)/cd36(−/−) mice were fed a high-fat diet (HFD) for up to 32 weeks and examined for physiologic and histologic changes in renal function. Compared to apoE(−/−), apoE(−/−)/cd36(−/−) mice had improved creatinine clearance and blood pressure which corresponded histologically to less glomerular and tubulointerstitial macrophage accumulation, foam cell formation, oxidant stress, and interstitial fibrosis. Co-IP and a cell surface fluorescence-based crosslinking assay showed CD36 and Na/K-ATPase α-1 co-localized in PTC and macrophages, and this association was increased by oxLDL or the cardiotonic steroid ouabain. OxLDL and ouabain also increased activation of Src and Lyn in PTC. Cell-free conditioned media from PTC treated with oxLDL or ouabain increased macrophage migration. OxLDL, ouabain, or plasma isolated from HFD-fed mice stimulated reactive oxygen species production in PTC which was inhibited by N-acetyl-cysteine, apocynin or Na/K-ATPase α-1 knockdown. These data suggest that ligands generated in hyperlipidemic states activate CD36 and the Na/K-ATPase, and potentiate an inflammatory signaling loop involving PTC and their associated macrophages which facilitates the development of chronic inflammation, oxidant stress, and fibrosis underlying the renal dysfunction common to pro-atherogenic, hyperlipidemic states