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Interaction of mineral salts with the skin: A literature survey

  • Rodan and Fields, LLC


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.
Review Article
Interaction of mineral salts with the skin: a literature survey
T. G. Polefka*, R. J. Bianchiniand S. Shapiro
*Life Science Solutions, LLC, Somerset NJ, 08873, Merck Consumer Care, Summit NJ, 07901 and Skinnovations, LLC, Roseland NJ, 07068, USA
Received 19 January 2012, Accepted 29 May 2012
Keywords: copper, essential minerals, magnesium, nutrition, skin, zinc
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 glo-
bal 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 recog-
nized as essential. The minerals include calcium, copper, iron, mag-
nesium, phosphorus, selenium, zinc, potassium and sodium.
Although the topical benefits of several minerals such as zinc, mag-
nesium 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.
Les preuves s’accumulent pour indiquer que la nutrition influence
fortement la sante
´, le bien-e
ˆtre et l’attractivite
´de la peau. Les con-
sommateurs en sont conscients et ont permis d’e
´tablir un marche
mondial de comple
´ments alimentaires “nutracosme
´tiques” estime
en 2010 a
`27,2 milliards de dollars. De
´but 2011, les Ministe
`res de
la Sante
´et de l’Agriculture des USA ont e
´un guide die
`la population ame
´ricaine. Ce guide reconnaıˆt douze vita-
mines et neuf mine
´raux en tant qu’e
´ments essentiels. Les mine
aux incluent le calcium, le cuivre, le fer, le magne
´sium, le
phosphore, le se
´nium, le zinc, le potassium et le sodium. Bien que
les bienfaits cutane
´s des mine
´raux tels que le zinc, le magne
´sium et
le fer sont reconnus et parfois approuve
´s par la FDA, les be
au niveau de la peau des autres sont, a
`ce jour, largement sous-
´s et sous-exploite
´s. La pre
´sente revue se propose de re
ce qui a e
´dans la litte
´rature sur les interactions entre les
huit (sur neuf) e
´ments mine
´raux essentiels avec la peau.
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 B
, folate, vitamin B
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 I lists the nine minerals and their daily-
recommended intakes [2].
Interestingly, Voet and Voet [3] estimate that nearly one-third of
all known enzymes require the presence of metal ions for catalytic
activity. Table II lists several examples for each mineral. However,
discussions on the benefits of dietary vitamin and mineral supple-
mentation almost always generate a debate on what level is needed
to prevent deficiency or disease and what level is required for opti-
mum 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
Correspondence: Thomas G. Polefka, Life Science Solutions, LLC, 79
Ellison Rd, Somerset, NJ 08873-2257, USA. Tel.: +1 732 221 6889;
Table I Mineral goals for adults based on dietary reference intakes and die-
tary guideline recommendations
Female Male Female Male
1950 year 1950 year 51 +year 51 +year
Calcium (mg) RDA
1000 1000 1200 1200
Iron (mg) RDA 18 8 8 8
Magnesium (mg) RDA 310320 400420 320 420
Phosphorus (mg) RDA 700 700 700 700
Potassium (mg) AI
4700 4700 4700 4700
Sodium (mg) UL
<2300 <2300 <2300 <2300
Zinc (mg) RDA 8 11 8 11
Copper (lg) RDA 900 900 900 900
Selenium (lg) RDA 55 55 55 55
*Recommended dietary allowance.
Adequate intake.
Upper limit.
Adapted from reference [2].
Ó2012 Copyright ©2009-2012 Merck Sharp &Dohme Corp., a subsidiary of Merck &Co., Inc., Whitehouse Station, N.J., U.S.A.
All rights reserved.416
International Journal of Cosmetic Science,2012,34, 416–423 doi: 10.1111/j.1468-2494.2012.00731.x
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.
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 car-
cinogens [6]. However, the 2010 Dietary Guidelines for Americans
(Table I) 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 Lans-
down [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) fre-
quency 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 I), but will follow the general classification system
used by Lansdown [6] based largely on their preponderance;
namely, macronutrients (e.g. requirements 100 g d
; 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.
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
10001200 mg day
(Table I) 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 epithelializa-
tion. 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 differentia-
tion, 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].
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 I shows the nutritional
goals for these two minerals. For men and women >14 years, the
recommendation for potassium is 4700 mg day
. 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
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 subse-
quently, 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
Table II Examples of Metalloenzymes
Element Metalloenzyme Function
Cu Superoxide Dismutase Superoxide decomposition
Lysyl Oxidase Collagen, Elastin synthesis
Collagen Proline
Collagen synthesis
Cytochrome Oxidase Energy production
Tyrosinase Melanin formation
Fe Cytochrome C Reductase Energy production
Aconitase Intermediary metabolism
Mg Glucose 6-Phosphatase Intermediary metabolism
Aconitase Intermediary metabolism
Hexokinase Intermediary metabolism
Mn Catalase Peroxide decomposition
Se Glutathione Peroxidase Peroxide decomposition
Zn Matrix Metalloproteases Matrix remodelling,
Wound healing
Numerous Protein
Signal Transduction
Numerous tRNA
t RNA synthesis
DNA/RNA Polymerase DNA/RNA synthesis
Figure 1 Relationship of epidermal Ca
with skin barrier properties. Rep-
rinted with permission from Nature Publishing Group Journal Investigative
Dermatology [10].
Ó2012 Copyright ©2009-2012 Merck Sharp &Dohme Corp., a subsidiary of Merck &Co., Inc., Whitehouse Station, N.J., U.S.A.
All rights reserved.
International Journal of Cosmetic Science,34, 416–423 417
Interaction of Mineral Salts with the Skin T. G. Polefka et al.
and cell replication. Mechanistically, Mg is a cofactor in many met-
alloenzymes [18]. Table II 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
. Unlike some of
the other metal elements, there is little evidence for dietary restric-
tions [18].
Two well-known consumer products are based on magnesium
salts, namely talc (magnesium silicate) and Epsom salts (MgSO
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 per-
ceived 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 (MgSO
). 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-regulat-
ing E-cadherin and up-regulating a1b2-integrin function [20].
Denda et al.[21] studied the effects of topical application of magne-
sium 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
in cornification. In a small human clinical study (n =12),
Schempp et al.[22] showed that topical treatment with 5% MgCl
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 MgCl
-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 per-
ceived benefits of bathing in the saltiest sea in the world
(320 g L
vs. an average 40 g L
) that also has the highest con-
centration of Mg (49 g L
) [24]. Moreover, this therapy is consis-
tent 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 pso-
riasis must be considered inconclusive. Several human clinical
studies [26,27] present findings that support the efficacy of bal-
neophototherapy for psoriasis. However, these studies have been
criticized for study design deficiencies. In contrast to these stud-
ies, 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 improve-
ment 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. Effi-
cacy 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 thor-
ough discussion on this complementary therapy, the reader is
referred to the following reviews [35,36].
Zinc (Zn)
The daily requirement for zinc in men and women is 11 and
8 mg day
, respectively (Table I). 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 II) [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 ZnCl
and ZnSO
were not
only irritating, but also delayed barrier repair [40]. However,
despite several exceptions, Zn compounds appear to offer the great-
est therapeutic potential of all the metal minerals as evidence by
the number of FDA-approved usages [35]. Table III lists the four
product categories and zinc compounds approved for over-the-
counter (OTC) uses [4247].
In the United States, the FDA recognizes three Zn compounds:
zinc acetate (0.12%), zinc carbonate (0.22%) 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% Fe
[45]. As noted earlier, zinc is
an essential micronutrient. Requirements are satisfied by a
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All rights reserved.
International Journal of Cosmetic Science,34, 416–423418
Interaction of Mineral Salts with the Skin T. G. Polefka et al.
well-balanced diet, leading to an average daily intake of 10
15 mg day
, consistent with a recommended daily allowance of
8 mg day
and 11 mg day
for women and men, respectively
(Table I). 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 cyto-
plasm, 3040% in the nucleus, and the remainder is associated
with the plasma membrane [37]. Within the cytoplasm, approxi-
mately 20% is associated with the zinc-binding protein, metallothi-
oneins (MTs); MTs are low molecular weight proteins (67 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 sig-
nificantly 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 iden-
tified genes [49]. According to Schwartz et al. [39], over 300 Zn-
dependent enzymes have been identified and characterized. Table II
lists several examples. Since the early phases of wound healing
requires the action of metalloproteases, it is believed that MTs func-
tion as a source of Zn
and Cu
necessary for metalloenzyme
synthesis [48].
In human skin, the Zn concentration in the epidermis (50
70 lgg
dry weight) is higher than in the dermis (1015 lgg
dry weight) [39]. Within the epidermis, the Zn
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
stimulate keratinocyte proliferation [10,11].
Studies in experimental wound models suggest that supplemen-
tal Zn enhances wound healing [40,49]. In the rat model, Zn levels
in the wound margin increase 1520% 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
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 sug-
gests that the manner in which Zn is presented to the tissue may
be important. Agren et al. [50] found ZnO to be superior to ZnSO
in terms of mitigating inflammation and enhancing re-epithelializa-
tion 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 ZnCO
Ksp =3.86 910
vs. ZnCO
Ksp =1.4 910
) [51]. In a
double-blind, placebo-controlled human clinical study, topically
applied ZnO significantly promoted healing of leg ulcers [52]. Oth-
ers 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 epi-
thelialization donor graft sites [59]. However, as noted by Lans-
down [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 stra-
tum 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 partic-
ularly 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 sun-
screen agent [66]. Unlike the organic sunscreens, the mineral sunsc-
reens such as ZnO and TiO
not only reduce skin penetration by UVB
radiation, but also provide protection against UVA radiation. As
noted in Table III, ZnO can be used in topical sunscreen formulations
up to 25% [63]. Interestingly, consumer interest in sunscreen prod-
ucts based on ZnO and TiO
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 min-
eral 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].
Table III Use of Zinc salts and compounds approved by the FDA for over-
the-counter human use
Product Compound Indication Conc. (%) Ref
Anti-fungal Zn undecylenate For the treatment
of athlete’s foot,
jock itch and
1025 36
Dandruff and
Zn pyrithione For the control or
relief of dandruff
dermatitis. To
control flakes
and scalp itch
0.12.0 37
Skin Protection Zn acetate Skin protectant
Promotes healing
of minor skin
irritation and
0.12.0 38
Zn carbonate Protects chafed
skin associated
with diaper rash
and helps protect
from wetness
0.22.0 40
Zn oxide Dries the oozing
and weeping of
poison ivy, oak,
and sumac,
insect bites.
1.025 58
Sun Protection Zn Oxide Helps to prevent
Up to 25 39
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All rights reserved.
International Journal of Cosmetic Science,34, 416–423 419
Interaction of Mineral Salts with the Skin T. G. Polefka et al.
Iron (Fe)
Iron is one of the most abundant trace metals in the body and
functions largely in oxygen transport and oxidationreduction reac-
tions, especially in respiration [64, 65]. As can be seen in Table II,
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 nor-
mal 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 I). For adult males, the daily iron require-
ment is 8 mg. Actively menstruating women require
1518 mg day
, whereas post-menopausal women require signifi-
cantly less, only 8 mg day
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 tyrosi-
nase, 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 lg day
(Table I). Although deficiencies of Cu appear rare,
conditions that give rise to intestinal malabsorption (i.e. coeliac dis-
ease, 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 tripeptidecopper
complex from serum that enhanced collagen formation in cultured
cells. Several commercial cosmetic products are based on a proprie-
tary copperpeptide complex (Cu-GHK, Cu-AHK). According to a
website managed by Loren Pickart, PhD, copperpeptides have
been proven to calm irritated skin, improve skin elasticity and firm-
ness, 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 volun-
teers, this team observed that subjects sleeping on pillowcases con-
taining 0.4% copper oxide exhibited significantly reduced facial
wrinkles, crow’s feet/lines and a global improvement in appear-
ance. 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 oxidationreduction reactions and general toxicity. How-
ever, 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 selenomethio-
nine 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 inflam-
mation, pigmentation, hyperkeratosis and carcinogenesis [87,
88]. In a small human clinical study with 8 subjects, topical
application of lotions containing selenomethionine (0.0020.05%)
the most effective way of delivering selenium into the skin
for 2 weeks was shown to mitigate the acute effects of UV expo-
sure [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
Ó2012 Copyright ©2009-2012 Merck Sharp &Dohme Corp., a subsidiary of Merck &Co., Inc., Whitehouse Station, N.J., U.S.A.
All rights reserved.
International Journal of Cosmetic Science,34, 416–423420
Interaction of Mineral Salts with the Skin T. G. Polefka et al.
selenomethionine significantly reduced UV-induced death of kerati-
nocytes 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 defi-
ciency included epidermal hyperplasia, aberrant hair follicle devel-
opment progressing to alopecia and ultimately to premature death
[93]. Taken together, these results support the crucial role of sele-
nium 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 se-
borrhoeic 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, mer-
cury 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
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 radia-
tion and has a key role in temperature regulation, sensation and
vitamin D production. The skin is dependent on the systemic circu-
latory 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 supplementa-
tion 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 nicotin-
amide as well as numerous other natural antioxidants. However,
evidences supporting the benefits of minerals have been limited to
several such as ZnO, TiO
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 neces-
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International Journal of Cosmetic Science,34, 416–423 423
Interaction of Mineral Salts with the Skin T. G. Polefka et al.
... Particulates were removed by filtration through ashed glass fiber filter (0.45 μm) and stored at room temperature prior to analysis. Elemental determination was conducted in triplicates for seven of the nine mineral elements essential for skin health 16 . These include Na, Mg, Ca, K, Zn, Fe and Cu. ...
... Literature reports indicated nine crucial minerals for skin health. Among them, calcium, copper, iron, magnesium, phosphorus, selenium, zinc, potassium, and sodium are included in the list 16 . Moreover, the mineral makeup of a plant extract can affect its antioxidant effectiveness. ...
... Zinc is a skin protectant and is frequently used as a wound healing agent. Zn is occasionally regarded as an unconventional antioxidant 16 . Tyrosinase, an enzyme involved in skin pigmentation, collagen crosslinking, and healthy hair development, requires copper as a cofactor. ...
Full-text available
Recently, an interest has surged in incorporating extracts of medicinal plants as active ingredients in cosmetic formulations, highlighting the need to analyze medicinal plants of cosmetic interest for phytochemicals and bioactivities. The tuber of the Ethiopian medicinal plant Impatiens tinctoria A. Rich (Ensosila) is used to make traditional cosmetics. The aim of the study was to investigate the antioxidant and mineral content of the Impatiens tinctoria tuber. Water, ethanol, and methanol were used during the extraction process. High phenolic content was found in methanol extract (107.8 ± 0.025 µg/ml GAE) followed by water extract (92.4 ± 0.02 µg/ml GAE). High flavonoid content was also obtained in methanol extract (136.7 ± 0.04 µg/ml QE). Strong 2,2-diphenyl-1-picryl-hydrazyl (DPPH) scavenging activity was recorded for methanol extract with IC50 value of 44.4 µg/ml, compared with ethanol extract (97.54 µg/ml) and water extracts (98.24 µg/ml). The lower IC50 value of methanolic extract demonstrated strong antioxidant activity. The three elements that were most prevalent in Impatiens tinctoria tuber out of the eight elements examined were K (170 ± 0.05 mg/100 g sample), Ca (87 ± 0.08 mg/100 g sample), and Mg (16 ± 0.01 mg/100 g sample). The phenolics, flavonoids, and minerals found in Impatiens tinctoria A. Rich (Ensosila) tuber may protect against oxidative stress-related skin damage and thus deserving attention for future applications in cosmetics formulations.
... Most of the mineral elements present in living tissues occur in ionized form, dissolved in the body liquids and, obviously, do not interact as a dry mineral matter. This is also the case in the skin where they occur in ionized form in its three main components: the epidermis, dermis, and subcutaneous tissue [13,14]. Sulfur-rich so-called "hard keratins" of hair and nails are exceptions, and so are the protein-bound metals involved in transport and enzymatic processing of other molecules, e.g., iron in the heme, selenium in glutathione peroxidases [15], or zinc in matrix metalloproteinases. ...
... Anti-inflammatory action of ZnO is due to lowering levels of iNOS and NO production. [13,31,32,86,94,95,105,106,158,176] Copper Cu is essential for several fundamental processes due to its cofactor function in numerous enzymes, e.g., lysyl oxidase, superoxide dismutase 1, EC-superoxide dismutase, amine oxidase, cytochrome C oxidase, tyrosinase. Thus, copper is indispensable for angiogenesis, oxygen transport, energy production, antioxidant defence, iron metabolism, immunity, and pigmentation. ...
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As odd as it may seem at first glance, minerals, it is what we are all about…or nearly. Although life on Earth is carbon-based, several other elements present in the planet’s crust are involved in and often indispensable for functioning of living organisms. Many ions are essential, and others show supportive and accessory qualities. They are operative in the skin, supporting specific processes related to the particular situation of this organ at the interface with the environment. Skin bioenergetics, redox balance, epidermal barrier function, and dermal remodeling are amongst crucial activities guided by or taking advantage of mineral elements. Skin regenerative processes and skin ageing can be positively impacted by adequate accessibility, distribution, and balance of inorganic ions.
... Epsom salt (magnesium sulphate) is topically being used by many people to ease aching muscles, treat skin conditions and relieve tension. Studies have shown that magnesium found in epsom salt can be absorbed by the skin, which can provide a relief from skin condition [13]. Additionally, baking soda is now being revisited as a therapy in skin care for scaly skin and are also added in soap as an alternative to caustic soda [14,15]. ...
Purpose: This study investigated physicochemical properties and antimicrobial performance of soaps formulated from natural ingredients with the intention to apply them as alternative deodorizing soaps in personal care products. Methods: Soaps were formulated with natural ingredients including lemon, aloe vera and honey. Foam stability and capac-ity tests as well as pH were determined for the soaps. Deodorizing effectiveness of the soaps was tested theoretically using minimum inhibitory concentration (MIC) test by screening them against pathogenic organisms causing body odour: bacteria (Staphylococcus aureus, Candida albican, Staphylococcus hominis, Strephotococcus mutant, Staphylococcus epidemidis) and fungi (Tinnea annum, Tinneapedis and Trycrophyton rubrum) using agar well diffusion method and poisoned food technique respectively while having Dettol soap and ketoconazole as controls. Results: The soaps had a maximum foam capacity of 150% and foam stability of 100% with pH values in the range of 9.3–9.8 and inhibited the growth of the tested organisms for up to 6days at 0.1g/ml concentration. Conclusion: The soaps are mildly alkaline, possess good foaming capacity and stability and have considerably significant antimicrobial properties that can impede the growth of the organisms.
... The use of vegetable ashes is not yet substantiated, but it is known that they contain calcium, magnesium, sodium, iron, copper, zinc, among other minerals that are part of the composition of skin care products (Gutiérrez et al. 2014, Polefka et al. 2012. To treat diabetes, the consumption of the cold extract of the fresh leaves in the mornings for 30 days is reported, and as an antidote in snakebite, the decoction of the leaves is consumed, with Faique seeds and oil for two days, morning and evening (Bussmann & Sharon 2016). ...
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Background: Vallesia glabra (Cav.) Link (Apocynaceae) is traditionally used in dermatological infections and as a desinflammatory. This review aims to collect information on its traditional uses, phytochemical compounds, and pharmacological activities. Methods: The scientific literature was searched in the databases Scopus, Web of Science, Alicia Repository, ScienceDirect and PubMed Central; 38 documents were selected (26 original articles, 2 review articles, 4 books and 2 theses) from 1939 to 2022. Results: V. glabra is traditionally used for pain relief, in infections and inflammations, and as an antifungal. Seventeen indole alkaloids of V. glabra have been identified, several of these alkaloids present important pharmacological activities as antimalarial and bactericidal agents demonstrated in in vitro assays. Conclusions: The traditional use of V. glabra in infections has been pharmacologically demonstrated in in vitro assays, being the terpenoid indole alkaloids, which confer the activity. Keywords: Traditional uses, phytochemical compounds, pharmacological activities, Vallesia glabra.
... The fractions resultant from the cascade filtration process, namely the UF and the NF retentates, presented interesting characteristics for cosmetics applications, particularly significant amino acids and minerals contents, and high antioxidant capacity. Indeed, amino acids are highly desired in cosmetics for their capacity to improve skin and hair quality [1]; mineral based salts, including calcium and magnesium act as absorbents, abrasives, and astringent agents, promoting skin softening and moisture [2]. Powerful antioxidant and free radical scavenging properties are also extremely valuable in antiaging and skin protection products [3]. ...
Even though the scientific documentation is limited, microbiome of healing clay is gradually gaining attention of the scientific community, as a therapeutic force playing an indispensable role in skin disease management. The present study explores the metatranscriptome profile of the Chamliyal clay, widely known for its efficacy in managing various skin problems, using Illumina NextSeq sequencing technology. The gene expression profile of the clay microbial community was analyzed through SEED subsystems of the MG-RAST server. Due to the unavailability of metatranscriptomic data on other therapeutic clays, Chamliyal's profile was compared to non-therapeutic soils, as well as healthy and diseased human skin microbiomes. The study identified Firmicutes, Proteobacteria, and Actinobacteria as the primary active microbial phyla in Chamliyal clay. These resemble those abundant in a healthy human skin microbiome. This is significant as lower levels of these phyla in the skin are linked to inflammatory skin conditions like psoriasis. Interestingly, pathogenic microbes actively metabolizing in the clay were absent. Importantly, 6% of the transcripts annotated to sulfur and iron metabolism, which are known to play a major role in skin disease management. This study provides the most comprehensive and a novel overview of the metatranscriptome of any of the healing clay available worldwide. The findings offer valuable insights into the clay microbiome's potential in managing skin disorders, inspiring future endeavors to harness these insights for medical applications.
Anxiety disorders have become the number one mental health issue in developed countries. The number of people living with anxiety and depressive disorders rose significantly because of the COVID-19 pandemic. Although generally considered as safe and effective, the currently available anxiolytic therapy is responsible for numerous side effects and addiction. Therefore, there is an imperious demand for discovering more efficient and cheaper new groups of pharmaceuticals (“green anxiolytic”). There is a big number of research, studying plants containing coumarins as active compounds, especially those belonging to the Apiaceae family. Laboratory studies already suggest the anti-anxiety activity of various extracts of Angelica Archangelica. Therefore, the aim of our study was to obtain the methanolic extract of Angelica adzharica and evaluate the potential anxiolytic effect based on the zebrafish larvae model. According to our knowledge, this is the first report studying the anxiolytic effect of Angelica adzharica extract based on the zebrafish larvae.
Demographic changes in the world (the population aging) have resulted in increased efforts of many scientific groups to prevent the aging process and to develop safe and effective cosmetics and medicines for the elderly. For this reason, for over 40 years, skincare peptides have been the subject of interest for many research groups. From time to time, new peptides are introduced to the cosmetics industry as they are promising and attractive active ingredients in the growing and innovative cosmetics market. We report herein the results of a study on the interactions between Cu²⁺ ions and two tetrapeptides: a) peptide with sequence Ac -βAHSH-OH (B1), having cosmetic potential which is used in a preparation called Eyeseryl, and b) a new derivative of B1 with the following sequence: Ac-HAEH-OH (B2). Potentiometric titration was used to study acid-base properties as well as the binding properties of the investigated peptides. Furthermore, the stoichiometry of the peptide complexes with Cu²⁺ ions was evaluated by the isothermal titration calorimetry and mass spectrometry. Additionally, based on the density functional theory (DFT) calculations, we propose the most likely structures of the complexes of the peptides B1 and B2 with Cu²⁺ ions. It was found that both peptides are not toxic against human fibroblasts and keratinocytes and form thermodynamically stable complexes with the Cu²⁺ cation. A modification in the Eyeseryl sequence enhances the affinity of the investigated peptides towards Cu²⁺. The longer distance between histidine residues favors the formation of the main peptide chain in the complex without an excessive backbone tension and also has an impact on the stability of formed complexes.
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Magnesium has an established role in obstetrics and an evolving role in other clinical areas, in particular cardiology. Many of the effects involving magnesium are still a matter of controversy. Over the next decade, it is likely that improvements in the measurement of magnesium, a clearer understanding of the mechanisms of its actions and further results of clinical studies will help to elucidate its role, both in terms of treating deficiency and as a pharmacological agent.
This chapter describes some of the most effective, scientifically proven formulations to revitalize aging skin. There are two great advantages to applying an active formulation of topical antioxidants to the skin. First, the skin attains far higher levels of each antioxidant than can be achieved by only taking these supplements orally. For example, the level of vitamin C attained in the skin by topical application is 20-40 times the level achievable with oral vitamin C. With topical application, the concentration of vitamin E increases by a factor of 10.6 and selenium, by a factor of 1.7. While sunscreens are still mainstay for protecting skin from photodamage, they are not enough. Because most of us actually apply only about one-fourth of the amount of sunscreen needed to give the designated SPF. Frequent application is absolutely necessary even for "highly water-resistant" formulations because sunscreen is washed off not only by swimming and sweating, but also by imperceptible perspiration. Furthermore, while sunscreens reduce UV-induced erythema and the DNA damage of 8-OHdG and thymine dimer, they only block about 55 percent of the free radical production. This protection over time not only protects the skin by diminishing the ongoing free radical insult and inflammation, but also reverses the unattractive appearance of previous photodamage by directly enhancing collagen synthesis and elastic tissue repair. © 2009 William Andrew Inc. Published by Elsevier Inc. All rights reserved.