Clinical Trials

The scientists and doctors at Ocean Seas Dermatology are convinced that Ocean Seas Dermatology Sea Treatment solution is effective to treat acne. This just agrees with what people tell us about their acne when they spend time at the beach.

The formulation of Ocean Seas Dermatology Sea Treatment solution has now been designated as an Investigational New Drug (IND) by the FDA. The Investigational New Drug Application number with the FDA is IND 105,774. These documents are on file with the FDA:

Food and Drug Administration
Center for Drug Evaluation and Research
Division of Dermatology and Dental Products
5901-B Ammendale Road
Beltsville, Maryland 20705-1266

The scientists and doctors at Ocean Seas Dermatology are authorized Investigators for clinical trials of Investigational New Drugs with the FDA. The current progress for Ocean Seas Dermatology Sea Treatment solution is that the Phase One Clinical Trials have been completed. There has also been acceptance of the Phase Two Clinical Trial protocol. At this time the Investigational New Drug process has not been completed and therefore legally no claims about effectiveness of Sea water with magnesium to treat acne are being made by Ocean Seas Dermatology.

However, during this process we discovered that this same formulation (that is an Investigational New Drug with the FDA) is a superior product to clean the skin. Since these products are cosmetics and NOT DRUGS, they are not subject to the FDA drug evaluation process.

The result is that this same formulation of Sea water with magnesium to precisely match the composition of the Dead Sea is available as a cosmetic to clean the skin. We believe the cleanest skin is the clearest skin! This is what you get with Ocean Seas Dermatology Sea Treatment Solution.


The FDA had requested scientific information to support the New Drug Application. The following is highly technical information which is currently on file with the FDA. This explains why it is believed that Sea Water with magnesium is effective to treat acne.

Scientific Rationale for Use of Synthetic Sea Water with Additional Magnesium for the Treatment of Acne Vulgaris

Acne vulgaris is a multifactorial inflammatory disease affecting the pilosebaceous follicles. The pilosebaceous unit is composed of epidermal cells lining the hair follicle and the sebaceous gland. Each hair follicle is associated with one or more sebaceous glands. The infundibulum communicates directly with the epidermis and extends to the opening of the sebaceous gland. In a normal follicle, sebum is secreted from the sebaceous glands and carries desquamated keratinocytes from the follicular epithelium up the follicular canal toward the infundibulum. Keratinocytes are shed as single cells and are moved to the follicle lumen and removed. In acne vulgaris, however, keratinocytes hyperproliferate and are shed as a group of cells rather than individual cells which obstruct the neck of the follicle. Acne vulgaris develops when the infundibulum becomes occluded, trapping sebum, shed cells, and bacterial products, and leading to inflammation.

Although the pathogenesis of acne is not completely understood (1) it is known that the initial event in the development of an acne lesion is keratinocyte hyperproliferation and abnormal desquamation. The accumulation of sebum and follicular keratinocytes in the sebaceous follicle results in the formation of a microenvironment that encourages the colonization of Propionibacterium acnes, which triggers the various immune and inflammatory responses implicated in the progression to inflammatory lesions.

Based on the portion of the pathophysiology of acne vulgaris that is known, treatment modalities which would affect this chain of events could be reasonably anticipated to have clinical benefits. Modalities which affect the earliest stages (keratinocyte hyperproliferation) would be expected to have the greatest effect with synergistic effects expected with modalities which affect the later stages (immune and inflammatory responses).

The use of synthetic sea water or natural sea water for the treatment of acne has never been specifically studied. However, despite the lack of evidence of demonstrated benefit there are physiologic reasons to anticipate effectiveness. There are many areas of commonality of this treatment for acne with well understood physiologic and disease processes. The most pertinent of these are keratinocyte hyperproliferation and the subsequent inflammation.

A central theme is the published evidence of effective treatment of other inflammatory conditions of the skin with natural sea water. One example is that sea water has been shown to decrease experimental irritant dermatitis in man. They began this study after an analysis of the literature revealed that selenium and strontium were thought to induce a moderate inhibitory effect on keratinocyte inflammatory cytokine production and that the chlorides and bromides of sodium, potassium, and magnesium reversibly inhibit cell proliferation of fibroblasts in cell culture. This study measured transepidermal water loss as an indicator of epidermal barrier function and capacitance as a parameter of stratum corneum water content (2). In the discussion the authors report, “Our results suggest the possible usefulness of sea water as the therapy for chronic dermatitis.”

Atopic dermatitis is another inflammatory skin disease that has been successfully treated using sea water (3). The basis of this study was the previous results of the anti-inflammatory effect of hypertonic solutions with elution of human leucocyte elastase and reduction of Langerhans cells in the skin, and the special effect of Dead Sea salt caused by its high Mg2+ ions. These patients with atopic dermatitis were treated with both Dead Sea water bathing and UVB phototherapy. The authors concluded, “safety and efficacy of out-patient synchronous balneophototherapy could be proven in both atp- and itt-population.” and “application seems to be most effective in patients with chronic type AD.”

A review of modalities used at the Dead Sea for skin diseases (4) concluded “existing evidence indicates the therapeutic potential of Dead Sea spa therapy modalities for psoriasis and psoriatic arthritis. A beneficial effect is hinted at for other skin diseases, but the absence of relevant methodological and clinical information precludes the drawing of any scientific conclusions.” They discuss the possible mechanisms of this effect and note the chemical effects of the Dead Sea spa therapy were evidenced by in vivo and in vitro studies, which disclosed increased level of minerals that may play a role in cell proliferation and differentiation. They also note the previous results demonstrating anti-inflammatory and immunomodulatory cytokine release, and cytokine receptor modulation.

A more recent study (5) has shown the minerals of the Dead Sea have “protective, anti-oxidant and anti-inflammatory properties that can antagonize biologic effects of UVB irradiation in skin. It may therefore be able to reduce photodamage and photoaging and more generally to reduce oxidative stress and inflammation in skin pathologies.” This is pertinent to the treatment of acne with sea water because of common chemical processes. The authors discuss the affect of biologic tissue by irradiation is believed to be through initiation of oxidative reactions, impairment of antioxidant balance and increase of reactive oxygen species (ROS) cellular levels. The activation of ROS-sensitive signaling pathways may actively participate in skin pathologies of inflammation. The authors report “topically applied substances able to modulate ROS-sensitive signaling pathways induced by UV exposure might provide a better protection, by interfering with UV-induced biochemical pathways that actually cause pathologic or undesired effects. Moreover, this protective role could be extended to other skin disorders where the same pathways are involved.”

In addition to these studies related to inflammation there are several studies pertaining to cell proliferation, which is a fundamental aspect of the pathophysiology of acne. These studies were interested in elucidating the mechanism of the observed benefit of Dead Sea salts in the treatment of psoriasis. Cell culture experiments (6) found reversible inhibition of cell proliferation and concluded “The favorable results of the Dead-Sea Spa treatment of psoriasis may thus be partly due to the penetration of minerals into the body, via the skin, with subsequent reinforcement of anti-proliferative mechanisms.” The authors reasoned that psoriasis is a skin disease characterized by epidermal hyperplasia and that topical application of minerals might be used therapeutically to normalize cellular proliferation by the promotion of cyclic-AMP synthesis from topically applied minerals.

These results were confirmed with experiments of both psoriatic and healthy skin biopsy specimens in cell culture (7). This study was done to look for the mechanism of the antiproliferative effect of selective Dead-sea minerals in improving the psoriatic condition. They concluded that “these results suggest that selected Dead-sea salts inhibit the proliferation of both psoriatic and healthy fibroblasts and that magnesium chloride and magnesium bromide are the most active salts. They also reaffirm our previous finding that the inhibitory effect of the magnesium salts on cell proliferation is not simply due to changes in osmolarity and is much more profound than that of sodium chloride.” The number of cells and their cyclic AMP content were used as parameters for cell division and for proving the selective involvement of magnesium salts in the antiproliferative effect.

This essential role of magnesium in the mechanism of these effects was supported by a clinical study of atopic dermatitis (8) which demonstrated bathing in the salt solution improved skin barrier function, enhanced stratum corneum hydration, and reduced skin roughness and inflammation. They “suggest that the favorable effects of bathing in the Dead Sea salt solution are most likely related to the high magnesium content. Magnesium salts are known to bind water, influence epidermal proliferation and differentiation, and enhance permeability barrier repair.” They make note of the German results that magnesium ions exhibit anti-inflammatory properties and inhibit contact dermatitis. They also discuss the fact that magnesium regulates adhesion molecules E-catherin and α1α2-integrin-mediated migration of keratinocytes. The authors also summarize the findings that magnesium ions have beneficial effects when applied topically to the skin of patients with contact dermatitis and that magnesium ions inhibit the antigen-presenting capacity of Langerhans’ cells, most important for sensitization and elicitation of allergic reaction; contributing to the efficacy of Dead Sea salt in the treatment of inflammatory skin diseases.

These authors also discuss the importance of the distribution of ions in the skin. In normal skin, magnesium and calcium ions are localized with a high concentration in the upper epidermis. However, after barrier disruption, the gradients of calcium, magnesium, and potassium in the epidermis disappeared while the pH was not altered (9). This loss of the ion gradient is a signal for an increase in proliferation, differentiation, and lipid synthesis aimed to repair the perturbed barrier (10). These authors discuss the consistency of their results with previous reports that demonstrate that calcium plays an important role in mediating keratinocyte function as well as tissue culture results where addition of calcium (in concentrations as low as 0.1 mM in mouse keratinocytes) results in inhibition of proliferation and terminal differentiation of both murine and human keratinocytes (10). Dead Sea salt as well as synthetic sea water with additional magnesium both contain high concentrations of magnesium ions in the presence of calcium consistent with the reported finding that magnesium chloride solution containing calcium chloride accelerated barrier repair more effectively than a solution of magnesium chloride alone (9).

The role of magnesium is further discussed by Shani et. al. (11). Here it is noted that the concentration of magnesium in the Dead Sea is 30 times higher than that in the ocean. Magnesium is the rate limiting factor in the activation of epidermal adenylate-cyclase, and consequently in the production of cyclic-AMP. Imbalance of cyclic-AMP (decrease) and cyclic-GMP (increase) has been implicated in the excessive cellular proliferation which is a major part of the psoriatic state. It is also known that magnesium, in concentrations of 50 millimolar inhibits the synthesis of some polyamines that are involved in the pathogenesis of psoriasis and that the reduction of these polyamines improves the psoriatic condition.

In addition to the role of the gradients of magnesium and calcium in the normal cutaneous physiology, the role of potassium has also been studied (10). Calcium and potassium have been shown to have a synergistic effect and the calcium-induced differentiation of keratinocytes in culture requires an increase in intracellular potassium. When potassium levels in the media are decreased, the addition of calcium is unable to induce keratinocyte differentiation. The authors conclude “These results indicate that calcium and potassium ions may regulate a wide spectrum of metabolic events involved in barrier homeostasis.” The biochemical documentation of the mechanisms and effects of these minerals is important to the scientific rationale for the use of synthetic sea water with additional magnesium because the ability to absorb the topically applied solutions and the penetration of salts through healthy and psoriatic epidermis has been documented. Penetration rates were felt to be higher due to capillary dilatation and damaged stratum corneum (12).

Further insights into the mechanisms of regulation of immune responses have been elucidated through research on contact hypersensitivity (CHS). Epidermal Langerhans Cells (LCs) were previously thought to function in the immune response by acquiring antigen in the skin and then migrating to draining lymph nodes where adaptive immune responses were initiated. However, the LCs have been shown to act during the priming and not the effector phase with CHS (13). They felt it was very likely that the observed enhanced contact hypersensitivity response was due to a dynamic lack of regulation from LCs during the priming response. The authors noted that this regulatory response was a previously unknown function of LCs and concluded “Our finding that LCs have regulatory properties in CHS has obvious implications for their role in other cutaneous immune processes...”

It had previously been reported that magnesium ions specifically inhibit the antigen-presenting capacity of Langerhans cells (14). These authors suggest the mechanism by which magnesium ions exert their anti-inflammatory properties may be the competitive displacement of calcium ions from their binding sites. The competitive inhibition of the Ca 2+-sensitive phospholipase A2 would result in the suppression of cutaneous inflammation.

Concurrent with these processes are the inhibition of calcium-dependent mechanisms by magnesium ions involved in the reduced expression by LCs of HLA-DR molecules. It is known that interferon-γ-induced HLA-DR molecule expression is associated with a rapid increase of calcium ions and that the induction of HLA-DR expression can be blocked by the inhibition of the interferon-γ-induced calcium influx. The finding of the concomitant downregulation of HLA-DR and B7 molecules by magnesium ions suggests that the regulation of B7 is also dependent on calcium-sensitive mechanisms.

A third effect of magnesium on cutaneous immunity is related to the finding that the addition of magnesium ions to unstimulated epidermal cell suspensions resulted in a reduced production of TNF-α and IL-12 in vivo. In the epidermis TNF-α is primarily produced by human keratinocytes. The downregulation of the constitutive TNF-α production by epidermal cell suspensions suggest the involvement of keratinocytes in the modulation of the antigen-presenting function of LCs. The ability to present antigen is acquired by LCs during culture and is modulated by epidermal cytokines, most importantly TNF-α. TNF-α is also involved in the induction and maintenance by LCs of major histocompatibility complex class II antigens and B7 costimulatory molecules. So, in addition to the direct effects on LCs by blocking the ATPase and HLA-DR expression, magnesium ions are thought to indirectly inhibit the antigen presenting function of LCs by the reduction of keratinocyte-derived cytokines such as TNF-α.

The authors (14) conclude “this study demonstrates specific inhibitory effects of MG 2+ ions on epidermal Langerhans cell function that may account for the efficacy of Dead Sea water and MgCl2 containing topical applications in the treatment of inflammatory skin diseases.”

Further insight into magnesium’s role in cutaneous physiology during chronic inflammation has been provided with experiments of kerotinocyte migration (15). It is known that during cutaneous wound repair and in chronic inflammatory diseases of the skin, keratinocytes become “activated” for migration. The migratory phenotype is characterized by dissolution of most intercellular desmosomes and a “loosening” of cell-cell contacts, formation of focal adhesions, and redistribution of β1 integrins from the lateral membrane to the migrating front. Integrins are a family of heterdimeric cell-surface transmembrane receptors that function to mediate the binding of cells to the extracellular matrix. Several studies have suggested that extracellular magnesium and calcium may differentially regulate the function of β1 and β3 integrin-mediated adhesion and migration. These authors conclude, “Together these data suggest that changes in the concentrations of extracellular magnesium and calcium can regulate the competitive interplay between calcium dependent E-cadherin-mediated and magnesium dependent α2β1-integrin-mediated adhesion, promoting the development of an activated keratinocyte phenotype.” This is further evidence of the effect of magnesium and calcium in kerotinocyte proliferation and migration, and these are known to be involved in the pathogenesis of acne vulgaris.

In summary, although neither artificial sea water nor natural sea water has been studied with acne, Dead Sea water has been shown to be effective for the treatment of other inflammatory skin diseases such as atopic dermatitis and psoriasis. The mechanism of the effect in these diseases processes as well as in contact hypersensitivity and experimental irritant dermatitis has been studied and has been shown to include effects on keratinocyte proliferation, inflammation and immune function, all of which are common pathways with acne vulgaris.

The anti-inflammatory and immunomodulatory effects of various minerals are well established. These include the inhibitory effect on keratinocyte inflammatory cytokine production and cytokine receptor modulation by selenium and strontium. This anti-inflammatory effect is partially mediated through effects on human leucocyte elastase as well as reduction of Langerhans cells in the skin. In addition, magnesium ions specifically inhibit the antigen-presenting capacity of Langerhans cells and are thought to exert their anti-inflammatory properties by competitive displacement of calcium ions from their binding sites. The competitive inhibition of the Ca 2+-sensitive phospholipase A2 results in the suppression of cutaneous inflammation. Magnesium also inhibits the synthesis of some polyamines that are involved in the pathogenesis of psoriasis and the reduction of these polyamines correlates with improvement in the psoriatic condition. Further evidence of the role of magnesium in these conditions comes from the observation that magnesium reduces the expression by Langerhans cells of HLA-DR molecules and reduces the production of keratinocyte-derived cytokines such as TNF-α and IL-12 in vivo. Artificial sea water with additional magnesium can be reasonably expected to be beneficial for the treatment of acne through modulation of these biochemical pathways involved in the pathogenesis of acne vulgaris.

However, the most pertinent scientific evidence for the treatment of acne vulgaris with artificial sea water with additional magnesium is the results concerning the effects of minerals on keratinocyte proliferation, since this is the initiating event in the disease process. Calcium and potassium have been shown to have a synergistic effect on the differentiation of keratinocytes. More specifically, the chlorides and bromides of sodium, potassium, and magnesium reversibly inhibit cell proliferation in cell culture and the loss of the ion gradient has been shown to be a signal for an increase in proliferation and differentiation. In separate experiments, magnesium and calcium have demonstrated effects on keratinocyte proliferation and migration, and these effects are mediated through differential regulation of the function of β1 and β3 integrin-mediated adhesion and migration. Magnesium salts have synergistic antiproliferative effects through the promotion of cyclic-AMP synthesis because magnesium is the rate limiting factor in the activation of epidermal adenylate-cyclase. Decreases in the production of cyclic-AMP cause the imbalance of cyclic-AMP and cyclic-GMP that contributes to excessive cellular proliferation. These mineral effects, particularly those of magnesium, on the regulation and proliferation of keratinocytes have specific applicability to the proposed mechanism of artificial sea water with additional magnesium for the treatment of acne.

Taken together, the collection of scientific evidence provides a plausible mechanism for the treatment of acne vulgaris with artificial sea water with additional magnesium through the inhibition of keratinocyte proliferation, anti-inflammatory properties, and immune modulation effects of the mineral components. This body of evidence includes cell culture results and mechanistic investigations as well as clinical studies.


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