Interaction of mineral salts with the skin: a literature survey

Authors


Correspondence: Thomas G. Polefka, Life Science Solutions, LLC, 79 Ellison Rd, Somerset, NJ 08873-2257, USA. Tel.: +1 732 221 6889; e-mail: tpolefka@lifescisolutions.com

Synopsis

There is growing scientific evidence that the health, well-being and the attractiveness of the skin are strongly influenced by nutrition. Consumers recognize this and have supported the creation of a global cosmeceuticals market estimated in 2010 at $27.2 billion. Early in 2011, the US Department of Health and Human Services and Department of Agriculture issued the Dietary Guidelines for Americans, 2010. Twelve vitamins and nine minerals were recognized as essential. The minerals include calcium, copper, iron, magnesium, phosphorus, selenium, zinc, potassium and sodium. Although the topical benefits of several minerals such as zinc, magnesium and iron are recognized and, in some cases, approved by the FDA, the topical benefits of the others to the skin are largely unexplored and unexploited. This review attempts to summarize what has been published in the literature on the interactions of the eight of the nine essential elements with the skin.

Résumé

Les preuves s'accumulent pour indiquer que la nutrition influence fortement la santé, le bien-être et l'attractivité de la peau. Les consommateurs en sont conscients et ont permis d’établir un marché mondial de compléments alimentaires “nutracosmétiques” estimé en 2010 à 27,2 milliards de dollars. Début 2011, les Ministères de la Santé et de l'Agriculture des USA ont édité un guide diététique adressé à la population américaine. Ce guide reconnaît douze vitamines et neuf minéraux en tant qu’éléments essentiels. Les minéraux incluent le calcium, le cuivre, le fer, le magnésium, le phosphore, le sélénium, le zinc, le potassium et le sodium. Bien que les bienfaits cutanés des minéraux tels que le zinc, le magnésium et le fer sont reconnus et parfois approuvés par la FDA, les bénéfices au niveau de la peau des autres sont, à ce jour, largement sous-explorés et sous-exploités. La présente revue se propose de résumer ce qui a été publié dans la littérature sur les interactions entre les huit (sur neuf) éléments minéraux essentiels avec la peau.

Introduction

Over the past several years, consumers have begun to recognize and appreciate the role proper nutrition plays in the health, well-being and attractiveness of their skin. Responding to this trend, the cosmetic industry has begun to offer the consumer topical products – better known as cosmeceuticals – to topically nourish their hair and skin. In a 2010 report, RNCOS estimated the global cosmeceuticals market at $27.2 billion [1]. In early 2011, the US Departments of Agriculture and Health and Human Services issued their 7th edition of the Dietary Guidelines for Americans, 2010 [2]. Accordingly, twelve vitamins (e.g. vitamin A, vitamin D, vitamin C, vitamin E, vitamin K, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12 and choline) and nine minerals (e.g. calcium, iron, magnesium, phosphorus, sodium, zinc, copper and selenium) are recognized as necessary for health and well-being. Table 1 lists the nine minerals and their daily-recommended intakes [2].

Table 1. Mineral goals for adults based on dietary reference intakes and dietary guideline recommendations
Mineral FemaleMaleFemaleMale
19–50 year19–50 year51 + year51 + year
  1. a

    Recommended dietary allowance.

  2. b

    Adequate intake.

  3. c

    Upper limit.

  4. Adapted from reference [2].

Calcium (mg)RDAa1000100012001200
Iron (mg)RDA18888
Magnesium (mg)RDA310–320400–420320420
Phosphorus (mg)RDA700700700700
Potassium (mg)AIb4700470047004700
Sodium (mg)ULc<2300<2300<2300<2300
Zinc (mg)RDA811811
Copper (μg)RDA900900900900
Selenium (μg)RDA55555555

Interestingly, Voet and Voet [3] estimate that nearly one-third of all known enzymes require the presence of metal ions for catalytic activity. Table 2 lists several examples for each mineral. However, discussions on the benefits of dietary vitamin and mineral supplementation almost always generate a debate on what level is needed to prevent deficiency or disease and what level is required for optimum health and/or well-being. The latter is much more difficult to demonstrate scientifically. In contrast to other cosmetic ingredients such as vitamins [4] and botanicals [5], the benefits of topically applied mineral salts have been largely ignored and unexploited. Indeed, to the best of our knowledge, few, if any clinical studies have been published to support a specific claim or benefit for a given mineral in terms of optimal ‘skin health’. The objective of this review is to summarize the scientific evidence available on the benefits and risks of topical application of mineral salts. Although humans are exposed to various mineral salts each day, this review will focus on the metal ions identified in the Dietary Guidelines for Americans 2010 as essential to health and well-being. Please note, however, we will not review phosphorus because we believe its role in human nutrition is more systemic.

Table 2. Examples of Metalloenzymes
ElementMetalloenzymeFunction
CuSuperoxide DismutaseSuperoxide decomposition (Antioxidant)
Lysyl OxidaseCollagen, Elastin synthesis
Collagen Proline DioxygenaseCollagen synthesis
Cytochrome OxidaseEnergy production
TyrosinaseMelanin formation
FeCytochrome C ReductaseEnergy production
AconitaseIntermediary metabolism
MgGlucose 6-PhosphataseIntermediary metabolism
AconitaseIntermediary metabolism
HexokinaseIntermediary metabolism
MnCatalasePeroxide decomposition (Antioxidant)
SeGlutathione PeroxidasePeroxide decomposition (Antioxidant)
ZnMatrix MetalloproteasesMatrix remodelling, Wound healing
Numerous Protein KinasesSignal Transduction
Numerous tRNA synthasest RNA synthesis
DNA/RNA PolymeraseDNA/RNA synthesis

Interaction of metal salts with skin

In his authoritative 1995 review on the interactions of metal ions with the skin, Lansdown recognizes 15 elements essential to human nutrition and noted seven elements as carcinogens or potential carcinogens [6]. However, the 2010 Dietary Guidelines for Americans (Table 1) recognize only nine minerals as nutritionally essential. Additionally, the most recent edition of the Report on Carcinogens [7] now includes cobalt salts, in addition to the seven noted by Lansdown [6]. It should be recognized that a number of variables may contribute to the safety (or toxicity) of any given mineral including (i) inherent toxicity of the mineral, (ii) dosage of exposure, (iii) frequency of exposure and (iv) genetic background of the individual [7].

For the purpose of this review, we will follow the US Dietary Guidelines that recognize nine minerals essential to human nutrition (Table 1), but will follow the general classification system used by Lansdown [6] based largely on their preponderance; namely, macronutrients (e.g. requirements ≥ 100 g d−1; calcium, sodium, potassium, magnesium), micronutrients (e.g. requirements on only several mgs/d; iron, zinc, copper) and trace metals (e.g. minimal requirements not established; selenium). As noted earlier, phosphorus will not be covered in this review.

Macronutrients

Calcium (Ca)

Calcium is the most abundant metal in the human body [8, 9]. For an average adult, the recommended dietary intake of calcium is 1000–1200 mg day−1 (Table 1) depending on age and gender. Interestingly, calcium requirements are biphasic, higher for young adults and elders. Calcium not only promotes several key events, especially haemostasis, but also is a key regulator of epithelialization. Of critical importance to the skin is the role calcium plays in regulating the differentiation of basal keratinocytes to corneocytes [10, 11]. Figure 1 schematically shows the relationship of Ca++ with skin barrier homoeostasis. In addition to its role in differentiation, Ca++ appears to be a key modulator of directional locomotion of human keratinocytes and likely promotes wound healing in vivo [12]. Moreover, there is also evidence to suggest that the proper combination of calcium and magnesium (Mg) enhances barrier repair (cf. later section on magnesium benefits in topical skin care products). Indeed, calcium gluconate solution or gel is frequently used to treat acid-induced burns [13].

Figure 1.

Relationship of epidermal Ca++ with skin barrier properties. Reprinted with permission from Nature Publishing Group Journal Investigative Dermatology [10].

Potassium/Sodium (K/Na)

Potassium [14] and sodium [15] represent the dominant cellular and extracellular electrolytes and osmolytes, noted for maintenance of the cellular membrane potential. Table 1 shows the nutritional goals for these two minerals. For men and women >14 years, the recommendation for potassium is 4700 mg day−1. However, because of sodium's ubiquity in the American diet, especially in processed foods, the Dietary Guidelines limits the intake of sodium to <2300 mg day−1 for this same age group [2]. With regard to the skin, the benefits of bathing in salt water, especially solutions prepared from the Dead Sea salts, have nourished the body and soul of humans since antiquity [15]. As will be discussed subsequently, the putative benefits of bathing in Dead Sea salts have been attributed to the magnesium in the sea composition, not the sodium or potassium [16].

Magnesium (Mg)

Although not as prevalent as the other three macronutrients, Mg is the fourth most abundant mineral in the body [17]. Over 60% of the body's magnesium is found in the skeleton, and the remainder is distributed in the cells where it is essential for energy metabolism and cell replication. Mechanistically, Mg is a cofactor in many metalloenzymes [18]. Table 2 provides several examples of enzymes that depend on Mg for catalytic activity. According to the 2010 American Dietary Guidelines [2], healthy adult men and women require an intake between 310 and 420 mg day−1. Unlike some of the other metal elements, there is little evidence for dietary restrictions [18].

Two well-known consumer products are based on magnesium salts, namely talc (magnesium silicate) and Epsom salts (MgSO4). Talc is most frequently found in baby powders, where it functions as an astringent to prevent diaper rash. Many adults also use baby powders to reduce wetness in the perineal and axilla areas and as a lubricant to enhance skin feel on other areas of the body. Talc can also be found in colour cosmetics and other topical products (i.e. anti-fungal, etc.) where it functions as an anti-caking agent. In recent years, the use of talc has decreased in response to the perceived risk that dusting with talc-containing products causes health problems. This risk was largely attributable to the contamination of the mineral with asbestos. However, a recent critical review of the literature by Muscat and Huncharek found little evidence that talc was carcinogenic, mechanistically or clinically [19].

The other magnesium-containing consumer product is Epsom salts (MgSO4). Epsom salt can be used internally; as a laxative, and topically in bath water to enhance skin softening and exfoliation, relieve muscle tension and to promote relaxation. Although little evidenced-based research is available in the medical literature to support these claims, mechanistically, Mg++ and Ca++ play a key role in regulating keratinocyte proliferation and differentiation and have been shown to activate keratinocyte migration, down-regulating E-cadherin and up-regulating α1β2-integrin function [20]. Denda et al.[21] studied the effects of topical application of magnesium and calcium salts on skin barrier repair in hairless mice. All of the Mg salts, except Mg bis (dihydrogen phosphate), accelerated barrier repair in this animal model. Moreover, optimum barrier repair required a Ca++ to Mg++ ratio less than unity, suggesting a complex and often antagonistic relationship between Mg++ and Ca++ in cornification. In a small human clinical study (n = 12), Schempp et al.[22] showed that topical treatment with 5% MgCl2 prior to UVB irradiation not only significantly reduced the number of Langerhan cells in the epidermis compared with NaCl, but also reduced antigen-presenting activity (mixed lymphocyte reaction) in the skin in the MgCl2-treated subjects.

In contrast to Epsom salt, efforts to understand the medicinal benefits of bathing in saline or Dead Sea salts (balneotherapy) are substantial [23]. Interest in balneotherapy is driven by the perceived benefits of bathing in the saltiest sea in the world (320 g L−1 vs. an average 40 g L−1) that also has the highest concentration of Mg (49 g L−1) [24]. Moreover, this therapy is consistent with several modern social movements, including complementary medicine and the rediscovery of Spas for relaxation, health and well-being [25].

Despite substantial clinical research, the evidence supporting the medicinal benefits of balneotherapy for the treatment of psoriasis must be considered inconclusive. Several human clinical studies [26, 27] present findings that support the efficacy of balneophototherapy for psoriasis. However, these studies have been criticized for study design deficiencies. In contrast to these studies, Halevy et al. [28] were unable to discern any meaningful improvements in psoriasis vulgaris when daily soaking in Dead Sea salts was compared with tap water. Several studies also looked at the benefit of pre-soaking psoriasis patients in saline or Dead Sea salts prior to phototherapy. Interestingly, when relevant controls were included in the phototherapy study, the investigators failed to observe meaningful clinical differences [29-31]. To explain these results, Gambichler et al. [32] propose that soaking the skin prior to phototherapy increases UV gain, regardless of salt concentration.

In terms of atopic dermatitis, fewer studies are reported in the literature. Proksch and co-workers reported significant improvement in skin barrier properties (i.e. decreased TEWL, increased hydration, reduced skin roughness and erythema) when patients soaked in 5% Dead Sea salts daily compared with tap water [33]. In a more recent study, Portugal-Cohen et al. [34] explored in a randomized, double-blind vehicle-controlled study involving 86 children with atopic dermatitis, the therapeutic benefit of twice-daily application of emollient with and without Dead Sea salts. Efficacy was based on SCORing Atopic Dermatitis (SCORAD), TEWL and several different subjective assessments. Despite observable and measurable improvements in objective and subjective parameters, none of the Dead Sea salt emollient formulations were statistically better than the vehicle control [34].

Taken together, we must conclude that based on the relevant published clinical literature, the evidence supporting the efficacy of balneotherapy for the treatment of psoriasis and atopic dermatitis is inconclusive. However, this treatment does appear to offer patients a palliative benefit in term of alleviating some symptoms (e.g. pruritus, flakiness, etc.) of these conditions. For a more thorough discussion on this complementary therapy, the reader is referred to the following reviews [35, 36].

Micronutrients

Zinc (Zn)

The daily requirement for zinc in men and women is 11 and 8 mg day−1, respectively (Table 1). Interestingly, approximately 11% of the body's Zn is associated with the epidermis [37]. From a biochemical point of view, Zn represents a dominant cofactor for many enzymes (Table 2) [38, 39], including those involved in wound healing [40], and most recently has been hypothesized to function as a non-traditional antioxidant [41].

Although Zn appears to be safe and effective in many topical applications, it is not totally innocuous. For example, in wound-healing studies, topical application of ZnCl2 and ZnSO4 were not only irritating, but also delayed barrier repair [40]. However, despite several exceptions, Zn compounds appear to offer the greatest therapeutic potential of all the metal minerals as evidence by the number of FDA-approved usages [35]. Table 3 lists the four product categories and zinc compounds approved for over-the-counter (OTC) uses [42-47].

Table 3. Use of Zinc salts and compounds approved by the FDA for over- the-counter human use
ProductCompoundIndicationConc. (%)Ref
Anti-fungalZn undecylenateFor the treatment of athlete's foot, jock itch and ringworm10–25[36]
Dandruff and Seborrhoea DermatitisZn pyrithioneFor the control or relief of dandruff and/or seborrhoeic dermatitis. To control flakes and scalp itch0.1–2.0[37]
Skin ProtectionZn acetate

Skin protectant

Promotes healing of minor skin irritation and sunburn

0.1–2.0[38]
Zn carbonateProtects chafed skin associated with diaper rash and helps protect from wetness0.2–2.0[40]
Zn oxideDries the oozing and weeping of poison ivy, oak, and sumac, insect bites.1.0–25[58]
Sun ProtectionZn OxideHelps to prevent sunburn…Up to 25[39]

In the United States, the FDA recognizes three Zn compounds: zinc acetate (0.1–2%), zinc carbonate (0.2–2%) and zinc oxide (1–25%), as safe and effective for use as topical skin protectants [45]. However, despite the opportunity to use the carbonate and acetate salts of zinc, almost all skin protectants are based on ZnO, probably because it is cost-effective, easily formulated and stable under aerobic conditions.

According to Lansdown et al. [40], the medicinal properties of zinc, in the form of calamine, were first documented more than 2000 years ago in the Ebers Papyrus. Calamine is a mixture of ZnO with approximately 0.5% Fe2O3 [45]. As noted earlier, zinc is an essential micronutrient. Requirements are satisfied by a well-balanced diet, leading to an average daily intake of 10–15 mg day−1, consistent with a recommended daily allowance of 8 mg day−1 and 11 mg day−1 for women and men, respectively (Table 1). Clinical deficiencies of Zn were first reported in 1961 [37]. However, from a public health perspective, this deficiency appears to be limited to developing countries.

Approximately 50% of the available Zn is localized to the cytoplasm, 30–40% in the nucleus, and the remainder is associated with the plasma membrane [37]. Within the cytoplasm, approximately 20% is associated with the zinc-binding protein, metallothioneins (MTs); MTs are low molecular weight proteins (6–7 Kd) with a high (approximately 30%) cysteine content that appear to function as Zn and copper (Cu) storage molecules [48]. Although the MTs are expressed constitutively in skin cells, expression is significantly up-regulated in cells exhibiting high mitotic activity such as those found in wound margins. Importantly, Zn is a cofactor in numerous biochemical reactions. Indeed, the prevalence of genes encoding zinc proteins is estimated at over 3% of the 32 000 identified genes [49]. According to Schwartz et al. [39], over 300 Zn-dependent enzymes have been identified and characterized. Table 2 lists several examples. Since the early phases of wound healing requires the action of metalloproteases, it is believed that MTs function as a source of Zn++ and Cu++ necessary for metalloenzyme synthesis [48].

In human skin, the Zn concentration in the epidermis (50–70 μg g−1 dry weight) is higher than in the dermis (10–15 μg g−1 dry weight) [39]. Within the epidermis, the Zn++ concentration gradient is inverted to Ca++, with higher levels localized to metabolically active basal cell layer and much less at the stratum corneum [48]. This is not surprising because low Ca++ and high Zn++ stimulate keratinocyte proliferation [10, 11].

Studies in experimental wound models suggest that supplemental Zn enhances wound healing [40, 49]. In the rat model, Zn levels in the wound margin increase 15–20% within 24 h and increase to 30% by the time re-epithelialization begins. Although zinc's anti-microbial activity may accelerate healing, this hypothesis is not universally accepted. As noted above, proliferating cells require Zn++ and metallothioneins for the production of the Zn-requiring metalloproteinases (MMPs), RNA and DNA polymerases and many other Zn-containing enzymes. Some wound healing research suggests that the manner in which Zn is presented to the tissue may be important. Agren et al. [50] found ZnO to be superior to ZnSO4 in terms of mitigating inflammation and enhancing re-epithelialization of partial thickness porcine skin. The authors attributed the efficacy of ZnO to its lower water solubility, and ability to provide sustained release of Zn++ to the wound site at non-toxic levels. It is worth noting that the aqueous solubility of ZnO is much lower than almost any other Zn salt with the exception of ZnCO3 (ZnO Ksp = 3.86 × 10−10 vs. ZnCO3 Ksp = 1.4 × 10−11) [51]. In a double-blind, placebo-controlled human clinical study, topically applied ZnO significantly promoted healing of leg ulcers [52]. Others investigators recognize ZnO as a topical debriding agent for pressure ulcer [53, 54] and as an occlusive dressing for diabetic foot ulcers [55]. In smaller clinical studies, investigators claim ZnO enhances healing of burn wounds [56], suction-blister wounds [57], superficial (i.e. 1 mm deep) small incisions [58] and the epithelialization donor graft sites [59]. However, as noted by Lansdown [40] larger-scale trials are urgently required to verify the benefits of topical zinc oxide in acute human wounds.

The percutaneous penetration of ZnO has been studied [60, 61]. Although the FDA accepts the concept that penetration of ZnO through intact skin is extremely low [45], abrogation of the stratum corneum barrier enhances the penetration of Zn because of increased hydration. Most recently, Newman et al. [62] reviewed the safety of nanosized titanium dioxide and zinc oxide particles, as it relates to sunscreen products, and concluded ‘Although we found no evidence of significant penetration of titanium dioxide and zinc oxide nanosized particles beyond the stratum corneum, further studies must be carried out to simulate real-world conditions particularly in sunburned skin and under ultraviolet exposure’.

ZnO has been used in topical products for quite some time. As noted previously, one of the first FDA-approved usages of ZnO is as a skin protectant [45]. Accordingly, products containing between 1% and 25% ZnO can claim on their label to be a ‘poison ivy, oak, sumac protectant’ and ‘to dry the oozing and weeping of poison ivy, oak, sumac’. Additionally, ZnO is approved as a broad-spectrum sunscreen agent [66]. Unlike the organic sunscreens, the mineral sunscreens such as ZnO and TiO2 not only reduce skin penetration by UVB radiation, but also provide protection against UVA radiation. As noted in Table 3, ZnO can be used in topical sunscreen formulations up to 25% [63]. Interestingly, consumer interest in sunscreen products based on ZnO and TiO2 has grown in recent years because of heightened consumer awareness of the damage to skin caused by increasing exposure to solar radiation and has led to the marketing of several commercial sunscreen products based solely on these mineral sunscreens. Clearly, ZnO has a long history of safe and effective use and is recognized for skin rashes such as diaper rash, prickly heat and skin conditions such as eczema, impetigo, ringworm, ulcers, pruritus and psoriasis [45].

Iron (Fe)

Iron is one of the most abundant trace metals in the body and functions largely in oxygen transport and oxidation–reduction reactions, especially in respiration [64, 65]. As can be seen in Table 2, Fe plays a role in various oxygenases, including the skin-relevant procollagen-proline dioxygenase. One estimate suggests that 70% of the body's Fe is associated with haemoglobin [6]. Levels in normal epidermis and psoriatic epidermis vary over a broad range [66, 67]. Much like calcium, the body's requirement for iron varies with gender and age (Table 1). For adult males, the daily iron requirement is 8 mg. Actively menstruating women require 15–18 mg day−1, whereas post-menopausal women require significantly less, only 8 mg day−1 [1].

Toxicity of Fe appears route specific. Higdon and Drake [65] note that accidental overdose of iron-containing products is the single largest cause of poisoning fatalities in children <6 year of age. In contrast to this, colour cosmetics containing iron oxide have been applied to the facial skin to beautify and/or camouflage minor imperfections since antiquity [68, 69]. Although there are few reports on the topical toxicity of iron or iron compounds, there is significant evidence from experimental animal models implicating the release of Fe from haemoglobin by UVR in the induction of cutaneous oxidative stress [70, 71]. Interestingly, iron analysis of epidermis derived from sun-exposed and unexposed skin revealed that the sun-exposed skin exhibited significantly higher levels of free iron than unexposed skin (53.0 vs. 17.8 ppm), respectively [69]. In subsequent work, Bissett and McBride showed in guinea pig and mouse models that topical application of an iron chelator (2-furildioxime) significantly delayed UVB-induced tumour onset [70]. To the best of our knowledge, we are unaware of any specific therapeutic usage of topical iron delivery.

Copper (Cu)

Copper is an important trace mineral found throughout the body where it serves as a cofactor for several enzymes, including lysyl oxidase, the enzyme involved in cross-linking collagen, and tyrosinase, the enzyme involved in skin pigmentation [72]. Indeed, at least one study reports the benefits of dietary supplementation on this enzyme in skin [73]. The recommended daily allowance for Cu for healthy adult men and women over the age of 19 is 900 μg day−1 (Table 1). Although deficiencies of Cu appear rare, conditions that give rise to intestinal malabsorption (i.e. coeliac disease, bowel resection, etc.) or defective transport of Cu is frequently diagnosed because of the visible changes in skin pigmentation and/or hair growth (i.e. Menke's kinky hair syndrome) [74]. Conversely, excessive exposure to Cu compounds is easily diagnosed by the characteristic green hue it produces in hair [74].

In 1973, Pickard and Thaler [75] isolated a tripeptide–copper complex from serum that enhanced collagen formation in cultured cells. Several commercial cosmetic products are based on a proprietary copper–peptide complex (Cu-GHK, Cu-AHK). According to a website managed by Loren Pickart, PhD, copper–peptides have been proven to calm irritated skin, improve skin elasticity and firmness, repair photodamaged skin, reduce fine lines and wrinkles, accelerate wound healing and a host of other benefits [76]. Recently, Mazurowska and Mojski [77] reported on the ability of GHK-Cu and GSH-Cu to penetrate liquid crystalline liposomal membranes. Interestingly, using the same tripeptides, but with manganese as the metal ion, Hussain and Goldberg [78] report that topical application of a serum formulation twice daily for 12 weeks, significantly improved the visual signs of photoaged skin, especially hyperpigmentation.

Other applications of Cu compounds are related to their well-known antibacterial, anti-fungal and antiviral activities [79]. Borkow et al. recently reported a more provocative use of Cu [80]. In a 4-week double-blinded, randomized study involving 57 volunteers, this team observed that subjects sleeping on pillowcases containing 0.4% copper oxide exhibited significantly reduced facial wrinkles, crow's feet/lines and a global improvement in appearance. The authors attribute the improvement in skin appearance to copper's ability to penetrate the skin and stimulate the formation of extracellular matrix proteins.

Topical use of Cu appears limited because of its potential to induce oxidation–reduction reactions and general toxicity. However, one cosmetic company recently created a bimineral complex composed of copper and zinc that is claimed to generate a galvanic signal capable of reducing inflammation [81]. In a double-blind, placebo-controlled study, Chantalat et al. [82, 83] compared the performance of a placebo formula (gel + activating moisturizer) to an active system (bimineral complex gel + activating moisturizer) to improve the appearance of individuals with photoaged skin. Although both treatments significantly (P < 0.05) improved visual signs of ageing from baseline, the bimineral complex formulation provided significantly greater improvement than the vehicle control (P < 0.05) for attributes such as skin tone and colour, skin texture, fine lines, crow's feet wrinkles, wrinkles and dark circles around the eyes. Despites its attractiveness from a marketing perspective, we believe more rigorous clinical studies are necessary to establish the value of ‘galvanic’ treatments.

Selenium (Se)

Selenium is commonly found in the soil, particularly, in Western United States, where it accumulates in plants as selenomethionine and selenocysteine [84]. In humans, these two amino acids are key components of antioxidant enzymes such as glutathione peroxidase and thioredoxin reductase [85]. Although deficiencies in humans are rare, animal studies have implied a possible link between selenium deficiency and cancer [86]. Oral administration of Se to mice has been shown to mitigate UVR-induced inflammation, pigmentation, hyperkeratosis and carcinogenesis [87, 88]. In a small human clinical study with 8 subjects, topical application of lotions containing selenomethionine (0.002–0.05%) – the most effective way of delivering selenium into the skin – for 2 weeks was shown to mitigate the acute effects of UV exposure [88]. In addition to inhibiting photodamage, research in animal models suggests that selenomethionine may also reverse photoageing [89]. However, in a recently published Cochrane Review, Dennert et al. [90] systematically reviewed 55 studies involving more than one million participants and was not able to establish reliable conclusions regarding a causal relationship between low selenium exposure and increased the risk of cancer and the benefits of selenium supplementation in reducing the incidence of cancer in humans.

Mechanistically, Se is believed to protect the skin and other organs through its involvement in antioxidant enzymes, especially glutathione peroxidase and thioredoxin reductase [91]. Rafferty et al.[92] have shown that human fibroblasts, keratinocytes and melanocytes express between 10 and 15 selenoproteins. Supplementation of culture media with either selenium or selenomethionine significantly reduced UV-induced death of keratinocytes and melanocytes [92]. In a more recent study, Sengupta et al.[93] used a mouse model where the Sec tRNA (the unique tRNA that codes for selenocysteine) was knocked out, limiting the animal's ability to make selenoproteins. The results of this deficiency included epidermal hyperplasia, aberrant hair follicle development progressing to alopecia and ultimately to premature death [93]. Taken together, these results support the crucial role of selenium and selenoproteins in the well-being of skin.

In the United States, topical application of selenium sulphide is approved in rinse-off products for the treatment of dandruff and seborrhoeic dermatitis [44].

Trace elements

Interestingly, the Dietary Guidelines for Americans, 2010 [2] do not establish recommendations for dietary intakes for any of the trace metals (i.e. manganese, chromium, molybdenum, etc.). However, one should not interpret the absence of an RDI to mean that these trace elements are unimportant.

Non-nutrient metal elements

In addition to the metal elements recognized for their nutritional value, several others (i.e. aluminium, zirconium, silver, gold, mercury and tin) are frequently found in the human body. However, except for aluminium and zirconium salts that represent the active ingredients in topic antiperspirant products [94, 95], contact with most of these metal ions is attributed to environmental exposure [6].

Conclusion

Human skin is the largest organ of the integumentary system and is made up of multiple layers of ectodermal tissue. It is a dynamic organ containing complex biological processes. Our skin interfaces with the environment, where its serves as a barrier that protects the body against pathogens, foreign bodies, water loss, solar radiation and has a key role in temperature regulation, sensation and vitamin D production. The skin is dependent on the systemic circulatory system to supply it with nutrients and thus reflects systemic nutritional deficiencies. For individuals with adequate nutritional status, the question remains: what value does topical supplementation provides to overall skin health? The cosmetic industry has demonstrated the benefits for topical supplementation of the skin with vitamins such as vitamin A, vitamin C, vitamin E and nicotinamide as well as numerous other natural antioxidants. However, evidences supporting the benefits of minerals have been limited to several such as ZnO, TiO2 and Se (anti-fungal agent). Although there is much work published on Mg-rich Dead Sea salts, Cu and Se, additional rigorous, hypothesis-driven clinical studies are necessary.

Acknowledgement

Merck Consumer Care funded this work.

Ancillary