Transdermal Magnesium and Evidence to Support Its Efficacy

White Paper by Alison Smith Ph.D.

Magnesium is required in over 300 physiological processes in the body and is essential to human health¹. Surprisingly, 43% of Canadians and 68% of Americans are not consuming even the minimum daily requirement of magnesium^2,3; therefore, supplementation is necessary^4,5. There is a breadth of scientific evidence that oral magnesium supplements, containing organic magnesium salts, readily absorb through the intestinal mucosa to become bioavailable in the bloodstream^6-10.

Oral magnesium supplements, however, are not the only commercially available form of magnesium on the market––transdermal or topical preparations of magnesium are also accessible; although, are they just as effective as oral magnesium supplements in terms of absorbability and bioavailability? Can one simply apply a topical magnesium cream, gel, ointment, or spray, or bathe in water containing magnesium salts and expect to absorb the magnesium through the skin to increase bioavailability within the blood?

Göber et al. ¹¹ asserts that transdermal magnesium absorption is a myth. Here we’ll discuss whether this assertion is supported or refuted in the scientific literature.

Skin Structure and Permeability

The skin is the largest organ of the body¹² and functions to provide a robust barrier between the internal body and the external environment. Designed primarily to keep harmful substances out and internal structures and moisture within¹³, the skin is composed of three layers: stratum corneum, epidermis, and dermis¹². The strength and seemingly impenetrable nature of the skin is due in part to the stratum corneum––the outer layer of the skin that shields the epidermis¹⁴.

The stratum corneum is made up of tough keratinized epithelial cells surrounded by layers of lipids (fats). The layers of lipids prevent moisture loss from within the body and block entry of most substances applied to the skin, topically. It is continually renewed and regenerated as the outermost stratum corneum cells slough off from the surface of the skin.

Interspersed throughout the stratum corneum are pores (sweat glands) and hair follicles that form passageways that lead directly to the deeper layers of the skin and systemic circulation¹³.

The outstanding questions are whether magnesium can penetrate the stratum corneum or can magnesium enter the bloodstream via the pores or hair follicles. The proceeding sections of this white paper will present all evidence pertaining to transdermal magnesium absorption in hopes of answering these two questions.

Scientific Evidence of Transdermal Magnesium Absorption

Magnesium is a metallic ion, and there is evidence that metallic ions can penetrate the stratum corneum of the skin¹⁵. There are very few studies that have measured blood serum, urine, or intracellular concentration of magnesium following transdermal magnesium application; however, here is a synopsis of the current scientific findings:

• Using an Environmental Scanning Electron Microscope (ESEM), Piccini et al. ¹⁶ measured intracellular magnesium absorption within exfoliating epithelial cells from the mouth mucosa. For 4 months, study participants applied, twice daily, a concentrated magnesium chloride spray to their skin. Compared to baseline measures, intracellular magnesium was shown to increase by 100% by months two and four, while serum blood levels of magnesium remained constant. Unfortunately, this study, which was published in the Italian Journal of Anatomy and Embryology, did not report how many subjects were included in the experiment; therefore, it is difficult to assess the strength of the results.
• In a study by Waring¹⁷ from the University of Birmingham, 19 subjects soaked in a 50-55˚C bath of dissolved magnesium sulphate (Epson salts), once daily for 12 minutes, for 7 consecutive days. Results indicated that blood plasma levels of magnesium increased from 68 ± 20.76 ppm/ml to 140.98 ± 17.00ppm/ml. Urine concentration of magnesium also increased from 94.81 ± 44.26 ppm/ml to 198.93 ± 97.52 ppm/ml. Unfortunately, this is an unpublished study that did not include a control group or statistical analyses––it simply reported the mean values.
• In a study by Watkins and Josling¹⁸, over the course of 12 weeks, 9 subjects applied 20 sprays of magnesium chloride (magnesium oil) to their body, plus a twice weekly, 20-minute foot soak using 100 mL of magnesium chloride solution. Using hair analysis to measure magnesium concentration in the body, results indicated that subject magnesium levels increased by 59.7% and calcium-magnesium ratio improved by 25.2%. Unfortunately, this is an unpublished study. The report does list that it is published in the European Journal of Nutraceutical Research; however, the existence of that journal cannot be substantiated.
• In a study by Kass et al. ¹⁴, 25 subjects participated in a single-blind pilot study to measure blood serum and urine magnesium concentration following the application of 56 mg of magnesium suspended in a cream vehicle, once a day for 2 weeks. Subjects were randomized into two groups: the magnesium cream group and the placebo group. The overall results showed a trend toward an increase in serum magnesium concentration following 2 weeks of transdermal magnesium. However, if the athletic subjects in the study were excluded from the analysis, there was a significant increase in serum magnesium observed in the non-athletic subject pool. Exercise can affect magnesium status; therefore, it is possible that the athletic subjects skewed the data. There were no significant findings for the urinary analysis. In order to definitively determine if transdermal magnesium is effective for increasing the bioavailability of magnesium, authors suggest further studies with a higher subject number and a more potent magnesium cream administered for a longer duration.
• A study by Chandrarasekaran et al. ¹⁹ measured transdermal magnesium absorption through excised human abdominal skin and through hair follicles of the skin. Investigators applied 5 mM, 52 mM, and 1.9 M of magnesium chloride solution to the excised skin for 5, 15, 30 and 60 minutes at 23-25˚C. To assess whether hair follicles facilitated transdermal magnesium absorption, investigators plugged the hair follicles of a section of excised skin and applied 1.9 M of magnesium chloride solution for 15 minutes. The skin samples were then stained with Mag-fura-2, tetrapotassium salt to visualize the magnesium in the skin using multiphoton microscopy. Results showed that topical magnesium can penetrate the stratum corneum, and permeability depends on magnesium concentration and time of exposure. Also, hair follicles play a key role in transdermal magnesium absorption.

Transdermal Magnesium in the Treatment of Health Conditions

While little quantitative data is currently available to confirm magnesium absorption transdermally, topical magnesium preparations are frequently used by the medical community to successfully treat various medical conditions.

Most readers will be aware that transdermal administration of medications is common in the treatment of local skin-related conditions and more systemic issues. Applying a medication directly to the skin avoids the breakdown of the medication in the gastrointestinal tract or filtering by the liver­­––two processes that affect oral medication administration¹³.

Transdermal Magnesium for Ileostomy Complications

An ileostomy is a surgical procedure whereby a portion of the ileum (small intestine) is rerouted to an external opening (stoma) on the side of the abdomen and connected to an external bag to allow feces to leave the body. This type of procedure is necessary for those who must have their colon removed for medical reasons²⁰.

A high-output ileostomy is a common complication of this procedure, which results in a rapid and high-yield elimination of waste from the body in 51% of patients, resulting in dehydration, undernutrition, and magnesium deficiency (hypomagnesemia) ²⁰. To treat magnesium deficiency, ileostomy patients receive intravenous (IV) magnesium infusions rather than oral magnesium supplements since intestinal absorption is compromised.

In a study of 6 ileostomy patients, Al Bakir et al. ²¹ investigated the efficacy of transdermal magnesium to treat ileostomy patients with hypomagnesemia.  Results indicated that 50% of patients who received 150 mg of transdermal elemental magnesium per day for 6 weeks increased their serum and urine concentration of magnesium, and one patient was able to cancel their scheduled magnesium IV infusion. Also, 83% of patients reported an improvement or complete resolution of muscle cramping by week two of the study.

This pilot study, unfortunately, only included 6 subjects, but it does provide preliminary evidence that transdermal magnesium in an oil-based vehicle can potentially increase the bioavailability of magnesium in ileostomy patients.

Topical Magnesium and Psoriatic Arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease, linked to genetic and environmental influences, which affect the skin and joints. PSA is associated with psoriasis and can cause red, swollen, and scaly skin lesions; nail deformity; swollen, red, and painful fingers; and, inflamed, painful tendon attachments to bone. It is often treated with pharmaceutical interventions²².

There is one study by Elkayam et al. ²³ that measured the effectiveness of soaking in the Dead Sea on PsA signs and symptoms. (The predominant mineral in the Dead Sea according to Proksch²⁴ is magnesium.) The study divided 42 PsA patients into two groups: both groups soaked in the Dead Sea every day for 4 weeks, while Group 1 received an additional topical application of Dead Sea mud and sulfur baths.

Following the 4-week intervention, patients reported a decrease in psoriasis area, severity index (PASI) score, morning stiffness, distance from finger to floor when bending forward, and self-assessment of disease severity. There was also an increase in the Schober test (lumbar spine range of motion) and right and left-hand grip.

This study did not assess pre and post-serum or urinary magnesium levels; therefore, it is difficult to make any conclusions on the effectiveness of magnesium salt exposure from the Dead Sea to increase the bioavailability of magnesium in PsA patients.

Transdermal Magnesium and Psoriasis

Psoriasis is an autoimmune condition that is characterized by red, scaly skin with raised plaques. Under normal conditions, the outer stratum corneum sloughs off dead skin cells from the surface of the skin, while the epidermis produces new stratum corneum cells beneath. With psoriasis, however, there is an overproduction of stratum corneum cells and a reduction in sloughing off; therefore, the skin thickens over time, and patients experience severe pain, itching, and stiffness²⁵.

In a study by Levi et al. ^26, the rate of skin cell proliferation by the various minerals in Dead Sea water was measured in psoriatic skin specimens. The results indicated that it was the magnesium content of Dead Sea water that improved psoriatic skin symptoms compared to the other minerals present.

Magnesium was shown to inhibit the production of epidermal stratum corneum skin cells thus reducing psoriatic skin lesion severity. Even-Paz et al. ²⁷ also found psoriatic skin lesion size and severity to improve following 4 weeks of Dead Sea bathing; however, the result was much greater in those that also sunbathed since ultraviolet light also benefits psoriatic skin lesions.

Topical Magnesium and Rheumatoid Arthritis

In a double-blind study by Sukenik²⁸, 30 patients with rheumatoid arthritis (RA) were randomized to two groups. All patients soaked in a 35˚C bath containing either Dead Sea water (Group 1) or sodium chloride (Group 2), every day for 2 weeks. Dead Sea water is a rich mixture of minerals with the predominant being magnesium²⁴.

The results showed that Group 1 patients improved on most of the following clinical and laboratory factors: duration of morning stiffness, fifteen-meter walk time, hand-grip strength, activities of daily living, the circumference of proximal interphalangeal joints, number of active joints, Ritchie index, the patient’s own assessment of disease activity, erythrocyte sedimentation rate and serum levels of amyloid A, rheumatoid factor, sodium, potassium, calcium, and magnesium. Patients observed maximal benefit by the end of the 2-week protocol, and improvements lasted for a month following the study.

Transdermal Magnesium and Diaper Rash

Diaper rash is the most common form of contact dermatitis in children. The rash is characterized by scaly, itchy, burning, and dry inflamed patches caused by mechanical friction, moisture, urinary and fecal contact, and pH changes^29,30. Known for its anti-inflammatory and wound-healing properties, Nourbakhsh³⁰ measured the effectiveness of a magnesium cream on the duration of diaper rash.

The study randomly assigned 64 children with diaper rash to two groups: Group 1 received a 2% magnesium cream with calendula (a flower extract), and Group 2 received a cream with calendula only.

The results showed that the magnesium cream significantly decreased the duration of diaper rash skin lesions (down to 1.5 days) compared to the calendula-only cream. The authors concluded that magnesium was an effective diaper rash treatment.

Topical Magnesium and Arterial Thrombosis      

An arterial thrombosis or blood clot is a serious medical condition that can lead to a stroke or heart attack^31,32. Magnesium has been shown to decrease platelet aggregation: a process that creates blood clots³³. Knowing that magnesium has the potential to prevent blood clotting, Toft et al.³⁴ measured the efficacy of using intravenous magnesium infusions or topical magnesium application to treat arterial thrombi in healing wounds.

30 male rats were randomly assigned to three groups: Group 1 received no magnesium intervention; Group 2 received intravenous magnesium; and, Group 3 received topical magnesium cream. A cut was placed in the femoral artery before administering the various treatments to induce the formation of a blood clot.

The results of the study showed that both intravenous and transdermal magnesium significantly reduced arterial thrombus formation; therefore, both interventions were equally as effective at preventing a blood clot. Interestingly, the application of topical magnesium did not affect serum magnesium levels; however, the cream was still absorbed into the skin to work locally to prevent blood clots.

Transdermal Sinusitis

Sinusitis is defined as inflammation of one or two of the paranasal sinuses with a non-infectious, allergy, viral, or bacterial origin. It causes increased nasal secretion, mucosal swelling, and pain.  The primary treatment is antibiotics, but nasal irrigation is effective as well³⁵.

In a study by Friedman et al. ³⁵, 42 rhinosinusitis patients completed a double-blind study that measured 16 signs and symptoms of sinusitis and quality of life. Patients were randomized to two groups: Group 1 received a 1.8% hypertonic saline solution to irrigate their nasal passages and Group 2 received a 1.8% hypertonic Dead Sea water solution.

Following 30 days of treatment, twice daily, 95.5% of patients who used the Dead Sea water solution experienced an improvement in nasal symptoms, and 100% reported improvement in rhinitis-related quality of life. Whereas, 60% of the hypertonic saline solution group experienced an improvement in nasal symptoms and 40% had an improvement in quality of life.

The authors concluded that the Dead Sea water solution, which was rich in magnesium, provided the most benefit because magnesium has anti-inflammatory effects and it can influence epidermal proliferation, and differentiation, and enhance epidermal repair ^24,35.

Magnesium Chloride and Skin Barrier Function

Bathing in the Dead Sea has been used as a therapeutic treatment for the skin for centuries. The Dead Sea contains a high concentration of magnesium chloride (46% in its crystalline form), along with calcium, potassium, and bromine²⁴. Magnesium has important wound healing and anti-inflammatory effects^24,36-38.

Diezel et al. ³⁹ reported that an ointment containing magnesium chloride significantly inhibited croton-oil-induced inflammation just as well as a 0.5% hydrocortisone ointment. Schempp et al. ⁴⁰ further demonstrated that the application of Dead Sea water to the forearm skin of 19 subjects resulted in the inhibition of the antigen-presenting capacity of Langerhans cells, which may explain why Dead Sea water exposure or topical magnesium cream application has such effective anti-inflammatory effects on the skin.

In a study by Proksch et al. ²⁴, 30 subjects with atopic dry skin on the forearms were directed to submerge one of their forearms in a bath containing 5% Dead Sea salt for 15 minutes. Then, they submerged their other forearm in tap water for 15 minutes. Subjects repeated this process every day for 6 weeks.

The results of this study showed that baths containing Dead Sea salt, which is high in magnesium chloride, significantly improved skin barrier function, stratum corneum hydration, and reduced skin inflammation. Investigators attributed the beneficial effects to the magnesium content in the Dead Sea salt since magnesium binds water and influences epidermal proliferation and differentiation.

Conclusion

Too few studies have been conducted to gather quantitative data on the absorption of magnesium transdermally. However, there are a number of medical conditions that are beneficially treated with topical magnesium preparations. Positive results in such conditions would not be observed unless the product was absorbed into the skin. Whether transdermal magnesium can significantly increase the bioavailability of magnesium within the blood requires more published investigation with control over magnesium dose, duration, application area, subject number, and statistical analysis.

References:

1. Shechter M. Body magnesium–the spark of life. Harefuah. 2011;150(1):41.
2. Moshfegh A, Goldman JD, Ahuja J, Rhodes D, LaComb R. What we eat in America, NHANES 2005–2006: Usual nutrient intakes from food and water compared to 1997 dietary reference intakes for vitamin D, calcium, phosphorus, and magnesium. Washington (DC): USDA; 2009.
3. Health Canada. Percentage of adults with a usual intake of magnesium below the estimated average requirement (EAR) in Canada. https://www.hc-sc.gc.ca/fn-an/surveill/atlas/map-carte/adult_magnesium-eng.php. Accessed June 24, 2017.
4. Durlach J, Durlach V, Bac P, Bara M, Guiet-Bara A. Magnesium and therapeutics. Magnesium Research. 1994;7(3-4):313-328.
5. Guerrera MP, Volpe SA, Mao JJ. Therapeutic uses of magnesium. Am Fam Physician. 2009;80(2):157.
6. Walker AF, Marakis G, Christie S, Byng M. Mg citrate found more bioavailable than other mg preparations in a randomised, double-blind study. Magnesium research. 2003;16(3):183.
7. Coudray C, Rambeau M, Feillet-Coudray C, et al. Study of magnesium bioavailability from ten organic and inorganic mg salts in mg-depleted rats using a stable isotope approach. Magnesium research. 2005;18(4):215.
8. Ranade VV, Somberg JC. Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. American Journal of Therapeutics. 2001;8(5):345.
9. Schuette SA, Lashner BA, Janghorbani M. Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. Journal of Parenteral and Enteral Nutrition. 1994;18(5):430-435.
10. Lindberg JS, Zobitz MM, Poindexter JR, Pak CY. Magnesium bioavailability from magnesium citrate and magnesium oxide. Journal of the American College of Nutrition. 1990;9(1):48.
11. Gröber U, Werner T, Vormann J, Kisters K. Myth or reality-transdermal magnesium? Nutrients. 2017;9(8):813.
12. Tortora G, Derrickson B. Introduction to the human body. 9th ed. Hoboken, NJ: John Wiley & Sons; 2012.
13. Prausnitz M, Elias P, Franz T, et al. Skin barrier and transdermal drug delivery. In: Bolognia J, Jorizzo J, Schaffer J, eds. Dermatology. Third Edition ed. Philadelphia: Elsevier Saunders; 2012:2065-2073.
14. Kass L, Rosanoff A, Tanner A, Sullivan K, McAuley W, Plesset M. Effect of transdermal magnesium cream on serum and urinary magnesium levels in humans: A pilot study. PLoS One. 2017;12(4):e0174817.
15. Hostýnek JJ, Hinz RS, Lorence CR, Price M, Guy RH. Metals and the skin. CRC Critical Reviews in Toxicology. 1993;23(2):171-235.
16. Piccini F, Ragazzoni G, Valentini L, Faloia E, Gobbi P. Intracellular absorption of transdermal magnesium demonstrated by ESEM-EDS. Italian Journal of Anatomy and Embryology. 2014;119(1):1.
17. Waring R. Report on absorption of magnesium sulfate (epsom salts) across the skin. https://www.epsomsaltcouncil.org/wp-content/uploads/2015/10/report_on_absorption_of_magnesium_sulfate.pdf. Accessed November 6, 2018.
18. Watkins K, Josling PD. A pilot study to determine the impact of transdermal magnesium treatment on serum levels and whole body CaMg ratios. The Nutrition Practitioner. 2010;14:1-7.
19. Chandrasekaran NC, Sanchez WY, Mohammed YH, Grice JE, Roberts MS, Barnard RT. Permeation of topically applied magnesium ions through human skin is facilitated by hair follicles. Magnesium Research. 2016;29(2):35.
20. Baker ML, Williams RN, Nightingale JMD. Causes and management of a high‐output stoma. Colorectal Disease. 2011;13(2):191-197.
21. Al Bakir I, Adaba F, Patel K, Nightingale J. Topical magnesium therapy treats hypomagnesaemia in some ileostomy patients. Clinical Nutrition. 2018;37(Supp 1):S69.
22. Mease P, Armstrong A. Managing patients with psoriatic disease: The diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014;74(4):423-441.
23. Elkayam O, Ophir J, Brener S, et al. Immediate and delayed effects of treatment at the dead sea in patients with psoriatic arthritis. Rheumatology International. 2000;19(3):77-82.
24. Proksch E, Nissen H, Bremgartner M, Urquhart C. Bathing in a magnesium‐rich dead sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin. International Journal of Dermatology. 2005;44(2):151-157.
25. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007;445(7130):866-873.
26. Levi-Schaffer F, Shani J, Politi Y, Rubinchik E, Brenner S. Inhibition of proliferation of psoriatic and healthy fibroblasts in cell culture by selected dead-sea salts. Pharmacology. 1996;52(5):321-328.
27. Even-Paz Z, Gumon R, Kipnis V, Abels D, Efron D. Dead sea sun versus dead sea water in the treatment of psoriasis. Journal of Dermatological Treatment. 1996;7(2):83-86.
28. Sukenik S, Neumann L, Buskila D, Kleiner-Baumgarten A, Zimlichman S, Horowitz J. Dead sea bath salts for the treatment of rheumatoid arthritis. Clinical and Experimental Rheumatology. 1990;8(4):353-357.
29. Fölster-Holst R, Buchner M, Proksch E. Diaper dermatitis. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2011;62(9):699.
30. Nourbakhsh S, Rouhi-Boroujeni H, Kheiri M, et al. Effect of topical application of the cream containing magnesium 2% on treatment of diaper dermatitis and diaper rash in children A clinical trial study. Journal of clinical and diagnostic research: JCDR. 2016;10(1):WC04.
31. Ruggeri ZM. Platelets in atherothrombosis. Nature Medicine. 2002;8(11):1227-1234.
32. Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: Novel insights and targets for treatment. Blood. 2008;112(9):3555-3562.
33. Gawaz M, Ott I, Reininger AJ, Neumann FJ. Effects of magnesium on platelet aggregation and adhesion. magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo. Thrombosis and haemostasis. 1994;72(6):912-918.
34. Toft G, Ravn HB, Hjortdal VE. Intravenously and topically applied magnesium in the prevention of arterial thrombosis. Thrombosis Research. 2000;99(1):61-69.
35. Friedman M, Vidyasagar R, Joseph N. A randomized, prospective, Double‐Blind study on the efficacy of dead sea salt nasal irrigations. The Laryngoscope. 2006;116(6):878-882.
36. Shani J, Barak S, Levi D, et al. Skin penetration of minerals in psoriatics and guinea-pigs bathing in hypertonic salt solutions. Pharmacological Research Communications. 1985;17(6):501-512.
37. Lahl H, Azizkabiri A, Ständer M, Unterhalt B. Analysis of elements in psoriatic and non-psoriatic skin. Die Pharmazie. 1999;54(9):708.
38. Grzesiak JJ, Pierschbacher MD. Shifts in the concentrations of magnesium and calcium in early porcine and rat wound fluids activate the cell migratory response. The Journal of Clinical Investigation. 1995;95(1):227-233.
39. Diezel W, Schulz E, Laskowski J, Shanks M. Magnesium ions: Topical application and inhibition of the croton oil-induced inflammation. 1994;69(Zschr Hautkrh):759-760.
40. Schempp CM, Dittmar HC, Hummler D, et al. Magnesium ions inhibit the antigen-presenting function of human epidermal langerhans cells in vivo and in vitro. involvement of ATPase, HLA-DR, B7 molecules, and cytokines. The Journal of Investigative Dermatology. 2000;115(4):680.