ArticlePDF Available

The Role of Carotenoids in Human Skin


Abstract and Figures

The human skin, as the boundary organ between the human body and the environment, is under the constant influence of free radicals (FR), both from the outside in and from the inside out. Carotenoids are known to be powerful antioxidant substances playing an essential role in the reactions of neutralization of FR (mainly reactive oxygen species ROS). Carotenoid molecules present in the tissue are capable of neutralizing several attacks of FR, especially ROS, and are then destroyed. Human skin contains carotenoids, such as alpha-, gamma, beta-carotene, lutein, zeaxanthin, lycopene and their isomers, which serve the living cells as a protection against oxidation. Recent studies have reported the possibility to investigate carotenoids in human skin quickly and non-invasively by spectroscopic means. Results obtained from in-vivo studies on human skin have shown that carotenoids are vital components of the antioxidative protective system of the human skin and could serve as marker substances for the overall antioxidative status. Reflecting the nutritional and stress situation of volunteers, carotenoids must be administered by means of antioxidant-rich products, e. g., in the form of fruit and vegetables. Carotenoids are degraded by stress factors of any type, inter alia, sun radiation, contact with environmental hazards, illness, etc. The kinetics of the accumulation and degradation of carotenoids in the skin have been investigated.
Content may be subject to copyright.
Molecules 2011, 16, 10491-10506; doi:10.3390/molecules161210491
ISSN 1420-3049
The Role of Carotenoids in Human Skin
Maxim E. Darvin 1 *, Wolfram Sterry 1, Juergen Lademann 1 and Theognosia Vergou 2
1 Department of Dermatology, Venerology and Allergology, Center of Applied and Cutaneous
Physiology (CCP), Charité University Medicine Berlin, Charitéplatz 1, Berlin 10117, Germany
2 A. Sygros’ Hospital, Department of Dermatology, University of Athens, Athens 16121, Greece
* Author to whom correspondence should be addressed; E-Mail:;
Tel.: +49-30-450-518-208; Fax: +49-30-450-518-918.
Received: 17 November 2011; in revised form: 3 December 2011 / Accepted: 8 December 2011 /
Published: 16 December 2011
Abstract: The human skin, as the boundary organ between the human body and the
environment, is under the constant influence of free radicals (FR), both from the outside in
and from the inside out. Carotenoids are known to be powerful antioxidant substances
playing an essential role in the reactions of neutralization of FR (mainly reactive oxygen
species ROS). Carotenoid molecules present in the tissue are capable of neutralizing
several attacks of FR, especially ROS, and are then destroyed. Human skin contains
carotenoids, such as α-, γ-, β-carotene, lutein, zeaxanthin, lycopene and their isomers,
which serve the living cells as a protection against oxidation. Recent studies have reported
the possibility to investigate carotenoids in human skin quickly and non-invasively by
spectroscopic means. Results obtained from in-vivo studies on human skin have shown that
carotenoids are vital components of the antioxidative protective system of the human skin
and could serve as marker substances for the overall antioxidative status. Reflecting the
nutritional and stress situation of volunteers, carotenoids must be administered by means of
antioxidant-rich products, e.g., in the form of fruit and vegetables. Carotenoids are
degraded by stress factors of any type, inter alia, sun radiation, contact with environmental
hazards, illness, etc. The kinetics of the accumulation and degradation of carotenoids in the
skin have been investigated.
Keywords: β-carotene; lycopene; antioxidants; free radicals; ageing; fruit; vegetables
Molecules 2011, 16 10492
1. Introduction
Free radicals (FR) are highly reactive molecules formed as a result of metabolic processes [1-4].
They play an important signaling function in the human organism [1,5] as well as acting against
viruses and bacteria [6,7]. In addition, there is an ample variety of external factors leading to the
formation of FR and especially reactive oxygen species (ROS) in human skin. The solar UV radiation
is one of these factors [8-10], but pollutants can also induce ROS formation upon contact with human
skin [11,12]. If the concentration of FR in tissue exceeds a critical value both cell and cell components
are destroyed, entailing tissue damage and even cancer [13-17].
Human skin is continuously exposed to FR. The latest findings of Zastrow et al. have shown that it
is not only the solar UV radiation, which induces the formation of FR (mainly ROS) in human skin [18],
but also the visible and infrared range of the spectra [19]. Utilizing the antioxidative protective system,
the human body has developed a complex defence mechanism against the harmful effects of these
highly reactive substances [20-22]. The antioxidants in human skin include, inter alia, the vitamins,
the carotenoids, and a variety of enzymes [23-28]. Most of these substances cannot be produced by the
human body independently, but must be taken up with food rich in carotenoids, for instance, with fruit
and vegetables [29]. The digestion and metabolism of dietary carotenoids by humans is a complex
process [30], which could be genetically dependent [31]. After digestion, the carotenoids accumulate
in high amounts in the adipose tissue, liver and the blood [32].
There are two main pathways for the accumulation of carotenoids in the epidermis—Diffusion from
the adipose tissue, blood and lymph flows; and the secretion via sweat glands and/or sebaceous glands
onto the skin surface and their subsequent penetration [33,34]. The group of carotenoids available in
human skin includes α-, γ-, β-carotene, lycopene, lutein, zeaxanthin and their isomers [35]. They are
known as potent quenchers of singlet oxygen [36] and other FR [37] in biological systems. Recent
investigations have shown that the carotenoids could serve as marker substances for the entire
antioxidative network of human skin [38,39]. This is due to the fact that the antioxidants form
protective chains in the human tissue, acting synergistically, in order to protect each other against the
destructive action of the FR and in particular ROS [38,40-42]. If any of the substances in this chain are
detected, information about the other components of the antioxidative protective system is
automatically provided. However, it has to be taken into account that the kinetics of the individual
components of the antioxidants could differ during accumulation and degradation.
So far, carotenoids in biological samples have mainly been analyzed by High Pressure Liquid
Chromography (HPLC) [43]. This process requires biopsies taken from tissue and blood. The samples
taken are then prepared and analyzed. As this invasive measuring method requires a high number of
biopsies, and it is unsuitable for analyzing the kinetics of the carotenoids in human skin.
In recent years, it has become possible to detect carotenoids in human skin non-invasively,
selectively and highly sensitively using optical methods [44-47]. In the following paragraphs the non-
invasive techniques used in the studies for measurement of carotenoids in human skin are summarized.
Carotenoids are Raman active molecules characterized by three prominent Stokes lines at 1005 cm1
(rocking motion of the methyl group), 1156 cm1 (carbon-carbon single-bond stretch vibration of the
conjugated backbone) and 1523 cm1 (carbon–carbon double-bond stretch vibration of the conjugated
backbone). Namely, the C=C bonds are responsible for the action of carotenoids as antioxidants [48,49].
Molecules 2011, 16 10493
Based on the absorption properties of carotenoids, the resonance excitation should be performed in the
blue-green range of the optical spectrum. The intensity of the prominent Raman line at 1523 cm1,
which originated under excitation at 488 nm and 514.5 nm, was measured for determination of
carotenoid concentrations in human skin [50,51]. The high fluorescence background of human skin
was substantially reduced by the use of a photo bleaching effect [52,53]. The resonance Raman
spectroscopy (RRS) based system utilized by our group has been described in detail previously [45].
Another possibility is Raman microscopy (RM). The in vivo Raman microscopic measurements
were performed using the skin composition analyzer (River Diagnostics, Model 3510, Rotterdam, The
Netherlands) in the fingerprint range between 400 and 1800 cm1. The utilized excitation wavelength
was 785 nm, which permitted the investigation of the deep-located skin areas. The carotenoids were
measured non-resonantly by the intensity of the corresponding Stokes line at 1523 cm1, from the skin
surface down to a depth of 30 µm in 2 µm increments. This method has previously been described in
detail by Caspers et al. [54,55].
Dermal carotenoids can also be measured with reflection spectroscopy (RS) [47,56]. For this
purpose, the LED-based miniaturized spectroscopic system (MSS) was developed. A LED emitted
bright spectrum in the range between 440 and 490 nm was sufficient to overlap the absorption of
carotenoids. The backscattered signal provides information about the carotenoid concentration. The
small dip in the diffusely reflected spectrum measured in the range between 458 and 472 nm, is
correlated to the concentration of carotenoids in human skin. The RS measurements could only be
performed on the palm or heel areas, where the epidermis is thick enough and the influence of other
skin chromophores is negligible. A comparison between the results of the MSS with those of the RRS
yielded an excellent correlation. Contrary to the relatively large Raman system, the size of the MSS is
that of a computer mouse and can be directly controlled by the Bluetooth system of a laptop or mobile
phone. The utilized MSS for measurement of carotenoids in human skin has been previously described
in detail by our group [57].
In-vitro measurements of carotenoids can also be performed with these optical methods. For
example, porcine ear skin does not contain a high amount of carotenoids, as only a very low
concentration lies near the detection limit. Otherwise, bovine udder skin contains a high concentration
of carotenoids and is well suited as an in-vitro model for measurement of carotenoids in the skin [58].
In the present review paper the in-vivo investigations carried out at the Center of Experimental and
Applied Cutaneous Physiology (CCP) at the Department of Dermatology of the Charité - Universitätsmedizin
Berlin are described. In various studies different volunteers were investigated. The investigations were
carried out on the palm, forehead, forearm and back of healthy volunteers aged between 20 and 70 years
with skin types II or III in accordance with the Fitzpatrick classification [59]. All volunteers had normal
skin without visible abnormalities, such as extremely dry or fatty skin, wounds, or skin diseases. All
studies had been approved by the Ethics Committee of the Charité - Universitätsmedizin, Berlin. The
importance of the related results to medicine, cosmetology and dietary sciences is discussed.
Molecules 2011, 16 10494
2. Results and Discussion
2.1. In Vivo Analysis of the Concentration of Carotenoids in Human Skin
After the development of the RRS for the in vivo detection of carotenoids in human skin, the system
was tested on volunteers at the CCP during a one-year study. Every day before having lunch, the
volunteers placed their hands on the sensor head and the carotenoid concentration was measured in the
palm region. The entire measurement took only a few seconds. The measurements were complemented
by questionnaires, in which the volunteers gave information about their daily diet and stress factors. As
a result of these measurements it could be clearly demonstrated that the concentration of the dermal
carotenoids represented a fingerprint of the dietary habits and stress situations of the volunteers.
Smokers and volunteers with unhealthy food habits exhibited very low values, whilst the volunteers
with a healthy diet and moderate stress showed high carotenoid values. Moreover, the results for all
volunteers demonstrated that the antioxidant concentration was higher by approximately 25% in
summer and autumn than in winter and springtime (“seasonal increase”, p = 0.001). This may be due
to the fact that higher amounts of fruit and vegetables are consumed in the summer and autumn
months [60]. Also, there are indications that the degree of freshness and ripeness of the products could
play a decisive role [61,62]. Whereas in summer and autumn the fruit and vegetables consumed by the
volunteers were supplied by regional producers, these products were imported from Latin America or
Asia in winter and springtime. Figure 1 shows a “seasonal increase” in the concentration of
carotenoids in the skin of one volunteer, obtained during a one-year period, which is typical among all
volunteers participating in the study.
Figure 1. Average monthly values of the dermal carotenoid concentration for one
volunteer during a one-year period measured on the inner palm.
Concentration of carotenoids, nmol/g
Molecules 2011, 16 10495
Under constant dietary and stress conditions, the carotenoid concentration in the skin remains
constant for a considerable length of time. Diseases, for instance, such as the common cold, lead to a
strong degradation of carotenoids in human skin [60]. Smoking also reduces the concentration of
carotenoids in human skin [45,63]. On the other hand, a change in the nutritional behaviour, for
instance, an increased intake of fruit and vegetables as well as carotenoid-rich supplements, result in an
increased concentration of cutaneous carotenoids [64-67], which may well protect the skin against
oxidative stress [36,68]. In the present study it could be shown that the nutritional behaviour and stress
situation of the volunteers are well reflected by the concentration of dermal carotenoids. These results
are in agreement with the results obtained by other groups [69-71].
2.2. Distribution of Carotenoids in Human Skin
The distribution of cutaneous carotenoids in human skin, measured by RRS, depends strongly on
the skin area examined (forehead, palm, forearm, back) and drastically changes inter-individually [72].
Figure 2 shows the average value ± standard deviation for dermal beta-carotene and lycopene
measured on different body sites.
Figure 2. Concentration of β-carotene (grey column) and lycopene (white column) on
different body sites measured with resonance Raman spectroscopy.
The spatial distribution of carotenoids in the epidermis within one skin area was investigated by the
use of RM. It was found that carotenoids distributed non-homogeneously showing a prominent
maximum close to the skin surface, lying in a depth of approx. 4–8 µm [46]. Subsequently, the
concentration of carotenoids continuously decreased, at least until the measured depth of 30 µm,
appropriated for RM measurements [33]. Topical application of cosmetic formulations containing
carotenoids, give rise to their increase in the stratum corneum [46,73], which could be investigated
with both the RRS and RM methods.
Palm Forearm Forehead Back
Concentration of carotenoids, nmol/g
Molecules 2011, 16 10496
The highest concentration of carotenoids measured in the top layer of epidermis, in stratum
corneum, could be explained by the delivery of fat-soluble carotenoids with sebum and/or sweat
secretion on the skin surface. Reaching the skin surface, carotenoids penetrate inside the epidermis like
topically applied substances, thus increasing their concentration in superficial areas [33,46]. The same
mechanism was previously observed by Thiele et al. for vitamin E [74].
2.3. Factors Influencing the Concentration of Carotenoids in Human Skin
In various follow-up studies the influence of different stress factors on the dermal antioxidative
status was investigated. It is known from the literature that the solar UV radiation could lead to the
formation of FR in human skin [8,75], which at high concentrations are capable of damaging the
antioxidative network [76]. Therefore, the volunteers were exposed to a minimal erythema dose
(MED) emitted by a sun simulator. The MED is the radiation dose necessary to induce mild sunburn in
the irradiated volunteers. The carotenoid measurements taken prior to and after UV irradiation for a
period of four days showed that after irradiation, the β-carotene concentration remained constant for a
period of 30 to 60 min, but subsequently declined drastically. Contrary to the β-carotene, the lycopene
concentration dropped strongly immediately after irradiation [76]. This is comprehensible as lycopene
is a highly efficient antioxidant, whose quenching rate constant in the reaction of neutralization of FR
(mainly ROS) is higher in comparison to other carotenoids [77,78]. The original level of the
carotenoids was restored not before 2 to 4 days, depending on the individual volunteer. Application of
tissue tolerable plasma on human skin, which is used for microbial disinfection, reduces the
concentration of carotenoids in the epidermis because of the formation of FR (mainly ROS),
subsequent to UVB radiation (310 nm). The carotenoid concentration was markedly reduced in the
upper part of the stratum corneum at least to a depth of 10 µm, which was measured with RM [79].
In another study, infrared radiation as used in clinical and private applications was investigated.
Here also, a strong degradation of both β-carotene and lycopene was observed [80-82]. Whereas, it is
known that the UV radiation could induce FR and especially ROS formation, which at increased doses may
even destroy the antioxidants in the skin, this effect is surprising in the case of the infrared spectral
range, due to the fact that the energy of the photons in this range is insufficient to form FR directly.
By means of electron spin resonance it was possible to demonstrate that, indeed, human skin is
subjected to a radical formation process subsequent to infrared irradiation, as a consequence of which
the antioxidants are destroyed [83,84]. Heat shock-induced radicals and/or enzymatic processes are
probably involved in the transfer of the energy of IR quanta in the skin [85]. Thus, human skin must
have structures, which absorb and accumulate the energy of the photons and then induce radical
formation. Mitochondria, e.g., are known for such processes. The results of this study are in good
agreement with the findings of Zastrow et al., who determined the FR action spectrum for the whole
spectrum of the solar radiation [19]. The results showed that 50% of the FR in the skin are generated by
solar UV radiation, whereas the remaining 50% are produced in the visible and infrared spectral ranges.
We strongly believe that these results will influence the development of sunscreens. It is assumed
that future sunscreens will not only provide UV protection, but also photo protection in general, which
could partially be based on the utilization of antioxidants [73,81,86,87].
Molecules 2011, 16 10497
2.4. Carotenoids and Skin Aging
Resulting from a variety of studies performed at the CCP with the RRS it was established that
individuals with high carotenoid concentrations in their skin looked young for their age, whilst
individuals with low carotenoid concentrations appeared older. This very subjective observation was
objectively investigated in another study, for which purpose the skin was measured using optical skin
surface topography [88]. The dermal roughness determined with this system is characterised by the
density and depth of furrows and wrinkles, thus serving as an objective criterion for skin aging. This
parameter is measured non-invasively, whereby the measurements were taken on the light-exposed
skin area of the forehead. The same area was measured also for its carotenoid concentration using the
RRS. Originally, within the study, it had been intended to investigate volunteers of the same age. For
this purpose, volunteers at 40 years of age were to be recruited, who already exhibited considerable
skin aging and who had not changed their lifestyle for years. Consequently, smokers, who had
meanwhile desisted from smoking, e.g., were excluded from the study. However, it proved to be very
difficult to find a large number of volunteers who had constantly kept their lifestyle unchanged.
Therefore, the age segment was extended, now ranging from 40 to 50 years. Following the successful
completion of this study, it was analyzed whether the dermal roughness, which is a measure of skin
aging, correlated with the age of the volunteers. If the group of volunteers had included persons at
different ages, i.e., between 18 and 80 years, it would have been expected, of course, that age indeed
influenced the skin surface structure. In the present study it could be shown, however, that no
correlation exists between age and skin aging. This is not surprising because the age segment
investigated was very narrow, compared to the actual age of the volunteers. However, after comparison
of the dermal roughness with the concentration of carotenoid lycopene in the skin, a clear correlation
was found showing that individuals with a high lycopene concentration in their skin exhibited less
dermal roughness [89]. These objective findings proved the accuracy of the earlier subjective
observation. Consequently, a healthy diet, rich in antioxidants including carotenoids, could serve as the
best preventive strategy against skin aging. However, it was found that it is impossible to recover one’s
youthful appearance by eating increased amounts of fruit and vegetables. Once induced, skin damage
cannot be repaired subsequently by changing one’s lifestyle. In any case, a healthy diet is also
advisable for older people as it has a positive effect on the years to come.
2.5. Topical and Systemic Application of Antioxidants
In the previous studies, it could be demonstrated that high antioxidant concentrations in human skin
present the best protection strategy against skin aging [24,39]. In follow-up studies methods for the
accumulation of the carotenoids in human skin were investigated. In general, there are two possibilities
of inducing carotenoid accumulation, one being systemic administration by carotenoid-rich food or
intake of food supplements, and the other being topical application of antioxidants in the form of
creams and lotions. In a comprehensive study involving several groups of volunteers, the effects of
placebo and carotenoid-containing verum tablets were compared to a placebo cream and a verum
cream. These products were applied both individually and in a combined form. In the investigations,
no increase in the carotenoid concentration in human skin was detected when the placebo products
Molecules 2011, 16 10498
were applied. On the other hand, verum products administered both as cream and as tablets, resulted in
an up to 100% increase in the dermal carotenoid concentration of individual volunteers. The maximum
accumulation of the carotenoids in human skin was achieved by combined administration of the verum
tablets and the verum cream, which however, fell below the sum of the carotenoid concentrations
of the two individual applications [86]. This is obviously due to the fact that the systemically
administered carotenoids escape onto the skin surface with the sweat and the sebum, spriting there and
penetrating into the skin like topically applied [90]. In this process, the reservoir of the horny layer, the
stratum corneum, plays an important role. Should this reservoir have already been saturated by a
topically applied cream, the sweat cannot penetrate optimally into the stratum corneum, thus rendering
the accumulation of the systemically applied carotenoids less efficient [86]. Obtained results are
summarized on Figure 3.
Figure 3. Comparison of the carotenoid concentration on the cheek before treatment (black
column), after 4 weeks (grey column) and after 8 weeks (white column) of treatment with
carotenoid-containing supplements.
The results of this study clearly show, that both the systemic and the topical application of
antioxidants lead to an accumulation of these substances in the human skin. For topical application,
which can produce the best results, it is essential that the topically applied component is well adapted
to the one systemically administered.
2.6. Pro-Oxidative Action of Carotenoids and Its Prevention
It should be taken into consideration that carotenoids can also possess a pro-oxidative action in
human tissue [91,92]. This action depends on the carotenoid concentration, oxygen tension and the
surrounding substances.
The pro-oxidative action of carotenoids is usually observed at relatively high concentrations of
applied carotenoids [26,93,94], which strongly exceed the doses of normal dietary intake, the
concentrations presented in fruit and vegetables and the physiological concentration in the cells [91].
Placebo Topical Systemic Combined
Concentration of carotenoids
(normalized to 100%)
Application of carotenoids on human skin
Molecules 2011, 16 10499
Moreover, the oxygen tension in the tissue could highly influence the anti- and pro-oxidant properties
of carotenoids. The high oxygen pressure gives rise to the pro-oxidative action of carotenoids in
biological tissue [95,96]. Under normal physiological conditions, high oxygen tensions could be
reached in the lung, but not in the skin [91,97]. The other aspect is the presence of other antioxidants
(for example vitamins C and/or E), which possess a synergistic action and could substantially reduce
the pro-oxidative action of carotenoids under the above-mentioned conditions [42,91,98,99].
In healthy individuals, a balanced nutrition including antioxidant-rich food, such as fruit and
vegetables, could warrant the absence of a pro-oxidative action of carotenoids on the tissue and
especially on human skin. Using this approach, any chance of reaching the critical concentration of
single antioxidants is excluded [100]. The application of carotenoid-containing supplements or extracts
containing balanced physiological concentrations and compositions of antioxidants could serve as an
alternative to fruit and vegetables.
2.7. Analysis of the Antioxidative Status in Clinical Practice
The aforementioned studies address in particular nutritional sciences and cosmetology. However,
the analysis of the carotenoids in human skin is also directly applied in the clinical sector; the analysis
of side effects during chemotherapy being just one example [101]. Currently, a wide range of highly
efficient chemotherapeutics exists, many of which entail side effects [102-104]. Such side effects are
often due to the fact that part of the chemotherapeutics or metabolites penetrate together with the sweat
out onto the skin surface, where they sprite and penetrate into the skin, again like topically applied
substances [105]. Since the reservoir of the stratum corneum is very large and the density of the sweat
glands is high on the palms of the hand and the heels of the foot, the penetrated substances are
accumulated there to an increased extent. This leads to the development of a hand-foot-syndrome,
an inflammatory symptom, the severest degree of which is open wounds [105]. The effect of
the chemotherapeutics on these skin areas is often due to radical forming processes. The systemic
administration of antioxidants is contra-productive, as it would reduce the effect of the chemotherapeutics
in the tumour. Therefore, a prevention strategy was developed based on the fact that the skin is
provided with antioxidants through a specific preventive cream, containing a balanced mixture of
antioxidants including carotenoids. This cream was applied prior to and during the chemotherapy.
Consequently, it is very important to analyze the antioxidative status of the skin prior to and during
chemotherapy. This is an essential field of application for RRS.
3. Conclusions
Results obtained in-vivo and non-invasively show that the concentration of carotenoids in human
skin reflects the current lifestyle conditions of volunteers. High concentrations of carotenoids in the
skin of volunteers are usually associated with a lifestyle free of stress and a carotenoid-rich
supplementation. Low carotenoid concentration is usually attributed to an unhealthy lifestyle, as well
as nutrition, illness and smoking. The kinetics of the degradation of dermal carotenoids, subsequently
influencing stress factors (sun radiation, illness, fatigue, etc.) is a relatively fast process, lasting up to a
number of hours, in order to reach maximal degradation, whilst the subsequent recovery is a more
prolonged effect, which requires a number of days before levelling.
Molecules 2011, 16 10500
The importance of the obtained results, with the focus on dermal carotenoids, medicine,
cosmetology, dietary sciences and development of protection strategies based on topical, systemic and
the combined application of antioxidants are discussed.
The results described and discussed in this review show that optical technologies are excellently
suited to determine the antioxidative status in human skin non-invasively, selectively and sensitively,
using carotenoids as marker substances. As research and development in the field of optical and
spectroscopic systems, as well as miniaturization of light sources and spectrometers is progressing,
more efficient, smaller and simpler measuring systems will soon be available on the market at
reasonable prices.
We would like to thank the Foundation “Skin Physiology” of the Donor Association for German
Science and Humanities for financial support.
Conflict of Interest
The authors declare no conflict of interest pertaining to commercial or other support. The authors
alone are responsible for the contents and writing of the paper.
1. Droge, W. Free radicals in the physiological control of cell function. Physiol. Rev. 2002, 82, 47-95.
2. Halliwell, B. Biochemistry of oxidative stress. Biochem. Soc. Trans. 2007, 35, 1147-1150.
3. Iannone, A.; Marconi, A.; Zambruno, G.; Giannetti, A.; Vannini, V.; Tomasi, A. Free radical
production during metabolism of organic hydroperoxides by normal human keratinocytes.
J. Invest. Dermatol. 1993, 101, 59-63.
4. Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and
antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol.
2007, 39, 44-84.
5. Jackson, M.J. Free radicals in skin and muscle: Damaging agents or signals for adaptation?
Proc. Nutr. Soc. 1999, 58, 673-676.
6. Rivero, A. Nitric oxide: An antiparasitic molecule of invertebrates. Trends Parasitol. 2006, 22,
7. Akaike, T. Role of free radicals in viral pathogenesis and mutation. Rev. Med. Virol. 2001, 11, 87-101.
8. Black, H.S. Potential involvement of free radical reactions in ultraviolet light-mediated cutaneous
damage. Photochem. Photobiol. 1987, 46, 213-221.
9. Krutmann, J. Ultraviolet A radiation-induced biological effects in human skin: Relevance for
photoaging and photodermatosis. J. Dermatol. Sci. 2000, 23 (Suppl. 1), S22-S26.
10. Regensburger, J.K.A.; Maisch, T.; Landthaler, M.; Bäumler, W. Fatty acids and vitamins generate
singlet oxygen under UVB irradiation. Exp. Dermatol. 2012, doi: 10.1111/j.1600-0625.2011.01414.x.
11. Stone, V.; Johnston, H.; Clift, M.J. Air pollution, ultrafine and nanoparticle toxicology: Cellular
and molecular interactions. IEEE Trans. Nanobiosci. 2007, 6, 331-340.
Molecules 2011, 16 10501
12. Mogel, I.; Baumann, S.; Bohme, A.; Kohajda, T.; von Bergen, M.; Simon, J.C.; Lehmann, I. The
aromatic volatile organic compounds toluene, benzene and styrene induce COX-2 and
prostaglandins in human lung epithelial cells via oxidative stress and p38 MAPK activation.
Toxicology 2011, 289, 28-37.
13. Valko, M.; Izakovic, M.; Mazur, M.; Rhodes, C.J.; Telser, J. Role of oxygen radicals in DNA
damage and cancer incidence. Mol. Cell. Biochem. 2004, 266, 37-56.
14. Bickers, D.R.; Athar, M. Oxidative stress in the pathogenesis of skin disease. J. Invest. Dermatol.
2006, 126, 2565-2575.
15. Kawaguchi, Y.; Tanaka, H.; Okada, T.; Konishi, H.; Takahashi, M.; Ito, M.; Asai, J. Effect of
reactive oxygen species on the elastin mRNA expression in cultured human dermal fibroblasts.
Free Radic. Biol. Med. 1997, 23, 162-165.
16. Monboisse, J.C.; Poulin, G.; Braquet, P.; Randoux, A.; Ferradini, C.; Borel, J.P. Effect of oxy
radicals on several types of collagen. Int. J. Tissue React. 1984, 6, 385-390.
17. Sander, C.S.; Chang, H.; Hamm, F.; Elsner, P.; Thiele, J.J. Role of oxidative stress and the
antioxidant network in cutaneous carcinogenesis. Int. J. Dermatol. 2004, 43, 326-335.
18. Ranadive, N.S.; Menon, I.A.; Shirwadkar, S.; Persad, S.D. Quantitation of cutaneous inflammation
induced by reactive species generated by UV-visible irradiation of rose bengal. Inflammation
1989, 13, 483-494.
19. Zastrow, L.; Groth, N.; Klein, F.; Kockott, D.; Lademann, J.; Renneberg, R.; Ferrero, L. The
missing link—Light-induced (280–1,600 nm) free radical formation in human skin.
Skin Pharmacol. Physiol. 2009, 22, 31-44.
20. Darvin, M.; Zastrow, L.; Sterry, W.; Lademann, J. Effect of supplemented and topically applied
antioxidant substances on human tissue. Skin Pharmacol. Physiol. 2006, 19, 238-247.
21. Rhie, G.; Shin, M.H.; Seo, J.Y.; Choi, W.W.; Cho, K.H.; Kim, K.H.; Park, K.C.; Eun, H.C.;
Chung, J.H. Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants
in the epidermis and dermis of human skin in vivo. J. Invest. Dermatol. 2001, 117, 1212-1217.
22. Kohl, E.; Steinbauer, J.; Landthaler, M.; Szeimies, R.M. Skin ageing. J. Eur. Acad. Dermatol.
Venereol. 2011, 25, 873-884.
23. Lademann, J.; Schanzer, S.; Meinke, M.; Sterry, W.; Darvin, M.E. Interaction between
carotenoids and free radicals in human skin. Skin Pharmacol. Physiol. 2011, 24, 238-244.
24. Thiele, J.J.; Schroeter, C.; Hsieh, S.N.; Podda, M.; Packer, L. The antioxidant network of the
stratum corneum. Curr. Probl. Dermatol. 2001, 29, 26-42.
25. Krinsky, N.I. Carotenoids as antioxidants. Nutrition 2001, 17, 815-817.
26. Palozza, P.; Krinsky, N.I. Antioxidant effects of carotenoids in vivo and in vitro: An overview.
Methods Enzymol. 1992, 213, 403-420.
27. Masaki, H. Role of antioxidants in the skin: anti-aging effects. J. Dermatol. Sci. 2010, 58, 85-90.
28. Mueller, L.; Boehm, V. Antioxidant activity of beta-carotene compounds in different in vitro
assays. Molecules 2011, 16, 1055-1069.
29. Khoo, H.E.; Prasad, K.N.; Kong, K.W.; Jiang, Y.M.; Ismail, A. Carotenoids and their isomers:
Color pigments in fruits and vegetables. Molecules 2011, 16, 1710-1738.
30. Nagao, A. Absorption and metabolism of dietary carotenoids. Biofactors 2011, 37, 83-87.
Molecules 2011, 16 10502
31. Borel, P. Genetic variations involved in interindividual variability in carotenoid status. Mol. Nutr.
Food Res. 2011, doi: 10.1002/mnfr.201100322.
32. Olson, J.A. Absorption, transport, and metabolism of carotenoids in humans. Pure Appl. Chem.
1994, 66, 1011-1016.
33. Darvin, M.E.; Fluhr, J.W.; Caspers, P.; van der Pool, A.; Richter, H.; Patzelt, A.; Sterry, W.;
Lademann, J. In vivo distribution of carotenoids in different anatomical locations of human skin:
comparative assessment with two different Raman spectroscopy methods. Exp. Dermatol. 2009,
18, 1060-1063.
34. Maharshak, N.; Shapiro, J.; Trau, H. Carotenoderma—A review of the current literature. Int. J.
Dermatol. 2003, 42, 178-181.
35. Stahl, W.; Sies, H. Bioactivity and protective effects of natural carotenoids. Biochim. Biophys. Acta
2005, 1740, 101-107.
36. Terao, J.; Minami, Y.; Bando, N. Singlet molecular oxygen-quenching activity of carotenoids:
relevance to protection of the skin from photoaging. J. Clin. Biochem. Nutr. 2011, 48, 57-62.
37. Krinsky, N.I.; Yeum, K.J. Carotenoid-radical interactions. Biochem. Biophys. Res. Commun.
2003, 305, 754-760.
38. Haag, S.F.; Taskoparan, B.; Darvin, M.E.; Groth, N.; Lademann, J.; Sterry, W.; Meinke, M.C.
Determination of the antioxidative capacity of the skin in vivo using resonance Raman and
electron paramagnetic resonance spectroscopy. Exp. Dermatol. 2011, 20, 483-487.
39. Lademann, J.; Meinke, M.C.; Sterry, W.; Darvin, M.E. Carotenoids in human skin. Exp. Dermatol.
2011, 20, 377-382.
40. Wrona, M.; Korytowski, W.; Rozanowska, M.; Sarna, T.; Truscott, T.G. Cooperation of
antioxidants in protection against photosensitized oxidation. Free Radic. Biol. Med. 2003, 35,
41. Palozza, P.; Krinsky, N.I. beta-Carotene and alpha-tocopherol are synergistic antioxidants.
Arch. Biochem. Biophys. 1992, 297, 184-187.
42. Darvin, M.E.; Sterry, W.; Lademann, J. Resonance Raman spectroscopy as an effective tool for
the determination of antioxidative stability of cosmetic formulations. J. Biophotonics 2010, 3, 82-88.
43. Talwar, D.; Ha, T.K.; Cooney, J.; Brownlee, C.; O'Reilly, D.S. A routine method for the
simultaneous measurement of retinol, alpha-tocopherol and five carotenoids in human plasma by
reverse phase HPLC. Clin. Chim. Acta 1998, 270, 85-100.
44. Ermakov, I.V.; Ermakova, M.R.; Gellermann, W.; Lademann, J. Noninvasive selective detection
of lycopene and beta-carotene in human skin using Raman spectroscopy. J. Biomed. Opt. 2004, 9,
45. Darvin, M.E.; Gersonde, I.; Meinke, M.; Sterry, W.; Lademann, J. Non-invasive in vivo
determination of the carotenoids beta-carotene and lycopene concentrations in the human skin
using the Raman spectroscopic method. J. Phys. D Appl. Phys. 2005, 38, 2696-2700.
46. Lademann, J.; Caspers, P.J.; van der Pol, A.; Richter, H.; Patzelt, A.; Zastrow, L.; Darvin, M.;
Sterry, W.; Fluhr, J.W. In vivo Raman spectroscopy detects increased epidermal antioxidative
potential with topically applied carotenoids. Laser Phys. Lett. 2009, 6, 76-79.
Molecules 2011, 16 10503
47. Stahl, W.; Heinrich, U.; Jungmann, H.; von Laar, J.; Schietzel, M.; Sies, H.; Tronnier, H.
Increased dermal carotenoid levels assessed by noninvasive reflection spectrophotometry correlate
with serum levels in women ingesting Betatene. J. Nutr. 1998, 128, 903-907.
48. Stahl, W.; Sies, H. Photoprotection by dietary carotenoids: Concept, mechanisms, evidence and
future development. Mol. Nutr. Food Res. 2011, doi: 10.1002/mnfr.201100232.
49. Krinsky, N.I.; Johnson, E.J. Carotenoid actions and their relation to health and disease.
Mol. Aspects Med. 2005, 26, 459-516.
50. Darvin, M.E.; Gersonde, I.; Ey, S.; Brandt, N.N.; Albrecht, H.; Gonchukov, S.A.; Sterry, W.;
Lademann, J. Noninvasive detection of beta-carotene and lycopene in human skin using Raman
spectroscopy. Laser Phys. 2004, 14, 231-233.
51. Darvin, M.E.; Gersonde, I.; Albrecht, H.; Meinke, M.; Sterry, W.; Lademann, J. Non-invasive
in vivo detection of the carotenoid antioxidant substance lycopene in the human skin using the
resonance Raman spectroscopy. Laser Phys. Lett. 2006, 3, 460-463.
52. Darvin, M.E.; Brandt, N.N.; Lademann, J. Photobleaching as a method of increasing the accuracy
in measuring carotenoid concentration in human skin by Raman spectroscopy. Opt. Spectrosc.
2010, 109, 205-210.
53. Lihachev, A.; Lesinsh, J.; Jakovels, D.; Spigulis, J. Low power cw-laser signatures on human
skin. Quantum. Electron. 2010, 40, 1077-1080.
54. Caspers, P.J.; Lucassen, G.W.; Carter, E.A.; Bruining, H.A.; Puppels, G.J. In vivo confocal
Raman microspectroscopy of the skin: Noninvasive determination of molecular concentration
profiles. J. Invest. Dermatol. 2001, 116, 434-442.
55. Caspers, P.J.; Williams, A.C.; Carter, E.A.; Edwards, H.G.; Barry, B.W.; Bruining, H.A.; Puppels,
G.J. Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo
by confocal Raman spectroscopy. Pharm. Res. 2002, 19, 1577-1580.
56. Niedorf, F.; Jungmann, H.; Kietzmann, M. Noninvasive reflection spectra provide quantitative
information about the spatial distribution of skin chromophores. Med. Phys. 2005, 32, 1297-1307.
57. Darvin, M.E.; Sandhagen, C.; Koecher, W.; Sterry, W.; Lademann, J.; Meinke, M.C. Comparison
of two methods for non-invasive determination of carotenoids in human and animal skin: Raman
spectroscopy versus reflection spectroscopy. J. Biophotonics 2012, In Press.
58. Haag, S.F.; Bechtel, A.; Darvin, M.E.; Klein, F.; Groth, N.; Schafer-Korting, M.; Bittl, R.;
Lademann, J.; Sterry, W.; Meinke, M.C. Comparative study of carotenoids, catalase and radical
formation in human and animal skin. Skin Pharmacol. Physiol. 2010, 23, 306-312.
59. Fitzpatrick, T.B. The validity and practicality of sun-reactive skin types I through VI.
Arch. Dermatol. 1988, 124, 869-871.
60. Darvin, M.E.; Patzelt, A.; Knorr, F.; Blume-Peytavi, U.; Sterry, W.; Lademann, J. One-year study
on the variation of carotenoid antioxidant substances in living human skin: Influence of dietary
supplementation and stress factors. J. Biomed. Opt. 2008, 13, 044028:1-044028:9.
61. Rodriguez, D.B.; Raymundo, L.C.; Lee, T.C.; Simpson, K.L.; Chichester, C.O. Carotenoid
pigment changes in ripening momordica-charantia fruits. Ann. Bot.-London 1976, 40, 615-624.
62. Zhou, C.; Zhao, D.; Sheng, Y.; Tao, J.; Yang, Y. Carotenoids in fruits of different persimmon
cultivars. Molecules 2011, 16, 624-636.
Molecules 2011, 16 10504
63. Meinke, M.C.; Lauer, A.; Taskoparan, B.; Gersonde, I.; Lademann, J.; Darvin, M.E. Influence on
the carotenoid levels of skin arising from age, gender, body mass index in smoking/non-smoking
individuals. Free Radic. Antioxid. 2011, 1, 15-20.
64. Darvin, M.E.; Gersonde, I.; Albrecht, H.; Sterry, W.; Lademann, J. Resonance Raman
spectroscopy for the detection of carotenolds in foodstuffs. Influence of the nutrition on the
antioxidative potential of the skin. Laser Phys. Lett. 2007, 4, 452-456.
65. Blume-Peytavi, U.; Rolland, A.; Darvin, M.E.; Constable, A.; Pineau, I.; Voit, C.; Zappel, K.;
Schaefer-Hesterberg, G.; Meinke, M.; Clavez, R.L.; Sterry, W.; Lademann, J. Cutaneous lycopene
and beta-carotene levels measured by resonance Raman spectroscopy: High reliability and
sensitivity to oral lactolycopene deprivation and supplementation. Eur. J. Pharm. Biopharm.
2009, 73, 187-194.
66. Meinke, M.C.; Darvin, M.E.; Vollert, H.; Lademann, J. Bioavailability of natural carotenoids in
human skin compared to blood. Eur. J. Pharm. Biopharm. 2010, 76, 269-274.
67. Hesterberg, K.; Lademann, J.; Patzelt, A.; Sterry, W.; Darvin, M.E., Raman spectroscopic analysis
of the increase of the carotenoid antioxidant concentration in human skin after a 1-week diet with
ecological eggs. J. Biomed. Opt. 2009, 14, 024039:1-024039:5.
68. Tsuchihashi, H.; Kigoshi, M.; Iwatsuki, M.; Niki, E. Action of beta-carotene as an antioxidant
against lipid peroxidation. Arch. Biochem. Biophys. 1995, 323, 137-147.
69. Mayne, S.T.; Cartmel, B.; Scarmo, S.; Lin, H.; Leffell, D.J.; Welch, E.; Ermakov, I.; Bhosale, P.;
Bernstein, P.S.; Gellermann, W. Noninvasive assessment of dermal carotenoids as a biomarker of
fruit and vegetable intake. Am. J. Clin. Nutr. 2010, 92, 794-800.
70. Rerksuppaphol, S.; Rerksuppaphol, L. Effect of fruit and vegetable intake on skin carotenoid
detected by non-invasive Raman spectroscopy. J. Med. Assoc. Thai. 2006, 89, 1206-1212.
71. Lima, X.T.; Kimball, A.B. Skin carotenoid levels in adult patients with psoriasis. J. Eur. Acad.
Dermatol. Venereol. 2011, 25, 945-949.
72. Darvin, M.E.; Gersonde, I.; Albrecht, H.; Gonchukov, S.A.; Sterry, W.; Lademann, J.
Determination of beta carotene and lycopene concentrations in human skin using resonance
Raman spectroscopy. Laser Phys. 2005, 15, 295-299.
73. Darvin, M.E.; Fluhr, J.W.; Meinke, M.C.; Zastrow, L.; Sterry, W.; Lademann, J. Topical beta-
carotene protects against infra-red-light-induced free radicals. Exp. Dermatol. 2011, 20, 125-129.
74. Thiele, J.J.; Weber, S.U.; Packer, L. Sebaceous gland secretion is a major physiologic route of
vitamin E delivery to skin. J. Invest. Dermatol. 1999, 113, 1006-1010.
75. Murphy, G.M. Ultraviolet radiation and immunosuppression. Br. J. Dermatol. 2009, 161 (Suppl. 3),
76. Darvin, M.E.; Gersonde, I.; Albrecht, H.; Sterry, W.; Lademann, J. In vivo Raman spectroscopic
analysis of the influence of UV radiation on carotenoid antioxidant substance degradation of the
human skin. Laser Phys. 2006, 16, 833-837.
77. Ribaya-Mercado, J.D.; Garmyn, M.; Gilchrest, B.A.; Russell, R.M., Skin lycopene is destroyed
preferentially over beta-carotene during ultraviolet irradiation in humans. J. Nutr. 1995, 125,
78. Di Mascio, P.; Kaiser, S.; Sies, H. Lycopene as the most efficient biological carotenoid singlet
oxygen quencher. Arch. Biochem. Biophys. 1989, 274, 532-538.
Molecules 2011, 16 10505
79. Fluhr, J.W.; Sassning, S.; Lademann, O.; Darvin, M.E.; Schanzer, S.; Kramer, A.; Richter, H.;
Sterry, W.; Lademann, J. In vivo skin treatment with tissue tolerable plasma influences skin
physiology and antioxidant profile in human stratum corneum. Exp. Dermatol. 2012, doi:
80. Darvin, M.E.; Gersonde, I.; Albrecht, H.; Zastrow, L.; Sterry, W.; Lademann, J. In vivo Raman
spectroscopic analysis of the influence of IR radiation on the carotenoid antioxidant substances
beta-carotene and lycopene in the human skin. Formation of free radicals. Laser Phys. Lett. 2007,
4, 318-321.
81. Schroeder, P.; Lademann, J.; Darvin, M.E.; Stege, H.; Marks, C.; Bruhnke, S.; Krutmann, J.
Infrared radiation-induced matrix metalloproteinase in human skin: Implications for protection.
J. Invest. Dermatol. 2008, 128, 2491-2497.
82. Darvin, M.E.; Zastrov, L.; Gonchukov, S.A.; Lademann, J. Influence of IR radiation on the
carotenoid content in human skin. Opt. Spectrosc. 2009, 107, 917-920.
83. Darvin, M.E.; Haag, S.; Meinke, M.; Zastrow, L.; Sterry, W.; Lademann, J. Radical production by
infrared A irradiation in human tissue. Skin Pharmacol. Phys. 2010, 23, 40-46.
84. Darvin, M.E.; Haag, S.F.; Lademann, J.; Zastrow, L.; Sterry, W.; Meinke, M.C. Formation of free
radicals in human skin during irradiation with infrared light. J. Invest. Dermatol. 2010, 130, 629-631.
85. Darvin, M.E.; Haag, S.F.; Meinke, M.C.; Sterry, W.; Lademann, J. Determination of the influence
of IR radiation on the antioxidative network of the human skin. J. Biophotonics 2011, 4, 21-29.
86. Darvin, M.E.; Fluhr, J.W.; Schanzer, S.; Richter, H.; Patzelt, A.; Meinke, M.C.; Zastrow, L.;
Golz, K.; Doucet, O.; Sterry, W.; Lademann, J. Dermal carotenoid level and kinetics after topical
and systemic administration of antioxidants: Enrichment strategies in a controlled in vivo study.
J. Dermatol. Sci. 2011, 64, 53-58.
87. Bogdan Allemann, I.; Baumann, L. Antioxidants used in skin care formulations. Skin Ther. Lett.
2008, 13, 5-9.
88. Jacobi, U.; Chen, M.; Frankowski, G.; Sinkgraven, R.; Hund, M.; Rzany, B.; Sterry, W.;
Lademann, J. In vivo determination of skin surface topography using an optical 3D device.
Skin Res. Technol. 2004, 10, 207-214.
89. Darvin, M.; Patzelt, A.; Gehse, S.; Schanzer, S.; Benderoth, C.; Sterry, W.; Lademann, J.
Cutaneous concentration of lycopene correlates significantly with the roughness of the skin.
Eur. J. Pharm. Biopharm. 2008, 69, 943-947.
90. Fluhr, J.W.; Caspers, P.; van der Pol, J. A.; Richter, H.; Sterry, W.; Lademann, J.; Darvin, M.E.
Kinetics of carotenoid distribution in human skin in vivo after exogenous stress: Disinfectant and
wIRA-induced carotenoid depletion recovers from outside to inside. J. Biomed. Opt. 2011, 16,
91. Palozza, P.; Serini, S.; Di Nicuolo, F.; Piccioni, E.; Calviello, G. Prooxidant effects of beta-
carotene in cultured cells. Mol. Aspects Med. 2003, 24, 353-362.
92. Paolini, M.; Abdel-Rahman, S.Z.; Sapone, A.; Pedulli, G.F.; Perocco, P.; Cantelli-Forti, G.;
Legator, M.S. Beta-carotene: A cancer chemopreventive agent or a co-carcinogen? Mutat. Res.
2003, 543, 195-200.
93. Palozza, P. Prooxidant actions of carotenoids in biologic systems. Nutr. Rev. 1998, 56, 257-265.
Molecules 2011, 16 10506
94. Lowe, G.M.; Booth, L.A.; Young, A.J.; Bilton, R.F. Lycopene and beta-carotene protect against
oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher
doses. Free Radic. Res. 1999, 30, 141-151.
95. Zhang, P.; Omaye, S.T. DNA strand breakage and oxygen tension: Effects of beta-carotene,
alpha-tocopherol and ascorbic acid. Food Chem. Toxicol. 2001, 39, 239-246.
96. Kennedy, T.A.; Liebler, D.C. Peroxyl radical scavenging by beta-carotene in lipid bilayers. Effect
of oxygen partial pressure. J. Biol. Chem. 1992, 267, 4658-4663.
97. Spence, V.A.; Walker, W.F. Measurement of oxygen tension in human skin. Med. Biol. Eng.
1976, 14, 159-165.
98. Palozza, P.; Calviello, G.; Bartoli, G.M. Prooxidant activity of beta-carotene under 100% oxygen
pressure in rat liver microsomes. Free Radic. Biol. Med. 1995, 19, 887-892.
99. Chen, H.; Tappel, A.L. Protection of vitamin E, selenium, trolox C, ascorbic acid palmitate,
acetylcysteine, coenzyme Q0, coenzyme Q10, beta-carotene, canthaxanthin, and (+)-catechin
against oxidative damage to rat blood and tissues in vivo. Free Radic. Biol. Med. 1995, 18, 949-953.
100. Lademann, J.; Patzelt, A.; Schanzer, S.; Richter, H.; Meinke, M.C.; Sterry, W.; Zastrow, L.;
Doucet, O.; Vergou, T.; Darvin, M.E. Uptake of antioxidants by natural nutrition and
supplementation: pros and cons from the dermatological point of view. Skin Pharmacol. Physiol.
2011, 24, 269-273.
101. Werncke, W.; Latka, I.; Sassning, S.; Dietzek, B.; Darvin, M.E.; Meinke, M.C.; Popp, J.; Konig, K.;
Fluhr, J.W.; Lademann, J. Two-color Raman spectroscopy for the simultaneous detection of
chemotherapeutics and antioxidative status of human skin. Laser Phys. Lett. 2011, 8, 895-900.
102. Crawford, J.H.; Eikelboom, J.W.; McQuillan, A. Recurrent palmar-plantar erythrodysaesthesia
following high-dose cytarabine treatment for acute lymphoblastic leukemia. Eur. J. Haematol.
2002, 69, 315-317.
103. Iurlo, A.; Fornier, M.; Caldiera, S.; Bertoni, F.; Foa, P. Palmar-plantar erythrodysaesthesia
syndrome due to 5-fluorouracil therapy—An underestimated toxic event? Acta Oncol. 1997, 36,
104. Gordon, K.B.; Tajuddin, A.; Guitart, J.; Kuzel, T.M.; Eramo, L.R.; VonRoenn, J. Hand-foot
syndrome associated with liposome-encapsulated doxorubicin therapy. Cancer 1995, 75, 2169-2173.
105. Lademann, J.; Martschick, A.; Jacobi, U.; Richter, H.; Darvin, M.; Sehouli, J.; Oskay-Oezcelik, G.;
Blohmer, J.U.; Lichtenegger, W.; Sterry, W. Investigation of doxorubicin an the skin:
A spectroscopic study to understand the pathogenesis of PPE. J. Clin. Oncol. 2005, 23, 477s.
© 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
... 6,36,[38][39][40][41][42][43] The group of carotenoids in human skin includes a-carotene, g-carotene, ß-carotene, lycopene, lutein, and zeaxanthin and their isomers. 44,45 The distribution of carotenoids in human skin depends on the areas of skin examined and significantly varies from individual to individual. 44,46 The protective role of carotenoids in the skin centers on the powerful antioxidant capacity of the molecules, especially as quenchers of reactive oxygen species (ROS). ...
... 44,45 The distribution of carotenoids in human skin depends on the areas of skin examined and significantly varies from individual to individual. 44,46 The protective role of carotenoids in the skin centers on the powerful antioxidant capacity of the molecules, especially as quenchers of reactive oxygen species (ROS). 44,47,48 VL-mediated pathologies/reactions VL-induced/exacerbated pathologies and reactions include erythema, post-inflammatory hyperpigmentation, melasma, and photodermatoses. ...
... 44,46 The protective role of carotenoids in the skin centers on the powerful antioxidant capacity of the molecules, especially as quenchers of reactive oxygen species (ROS). 44,47,48 VL-mediated pathologies/reactions VL-induced/exacerbated pathologies and reactions include erythema, post-inflammatory hyperpigmentation, melasma, and photodermatoses. 6 In FSTs I to III, VL has been shown to induce immediate ...
Until recently, the primary focus of photobiology has centered on the impact of UV radiation on skin health, including DNA damage and oncogenesis; however, the significant effects of visible light (VL) on skin remains grossly underreported. VL has been reported to cause erythema in light skin, Fitzpatrick skin types (FST) I-III, and pigmentary changes in individuals with darker skin types, FST IV-VI. These effects have importance in dermatologic diseases and potentially play a role in conditions aggravated by sun exposure, including phototoxicity in FST I-III patients and post-inflammatory hyperpigmentation and melasma, in FST IV-VI patients. Induction of free radicals leading to generation of reactive species is one driving mechanism of VL-induced skin pathologies, leading to induction of melanogenesis and hyperpigmentation. Initial clinical studies have demonstrated effectiveness of topical sunscreen with antioxidant combinations in inhibiting VL+UVA1- induced erythema in FST I-III and reducing pigmentation in FST IV-VI. Antioxidants may help prevent worsening of pigmentary disorders and can be incorporated into photoprotective strategies. It is essential that dermatologists and the public are aware of the impact of VL on skin, especially in patients of skin of color, and understand the available options for VL protection.
... The antioxidant power of carotenoids is linked to the high number of conjugated double bonds in their structure and their lipophilicity. Carotenoids such as lycopene, α-, β-, and γ-carotene, β-cryptoxanthin, lutein, and zeaxanthin are found in the epidermis, dermis, and subcutaneous fat [54,55]. Research results suggest that β-carotene and lycopene are present in greater amounts than zeaxanthin and lutein in human skin [56]. ...
... Main Effects The content of carotenoids in human skin varies, with the highest levels found in parts of the body with a high concentration of sweat and with sebaceous glands. The total content of carotenoids in the skin is influenced by many factors, such as season, exposure to UV radiation, and intake of fruit, vegetables, and carotenoid-rich supplements, as well as air pollution, alcohol consumption, cigarette smoking, stress, and the use of cosmetics containing provitamin A [55]. The external application of preparations containing carotenoids in combination with oral supplementation has been shown to increase the concentration of these compounds in the skin [43,63]. ...
... Due to the ability of β-carotene to scavenge radicals such as singlet oxygen or hydroxyl radical, it plays an important role in the treatment of photodermatoses caused by UVR [38]. According to the research findings reported thus far, carotenoid supplementation has beneficial results, especially in protection against UVR and ROS [55,57]. ...
Full-text available
Natural substances have traditionally been used in skin care for centuries. There is now an ongoing search for new natural bioactives that not only promote skin health but also protect the skin against various harmful factors, including ultraviolet radiation and free radicals. Free radicals, by disrupting defence and restoration mechanisms, significantly contribute to skin damage and accelerate ageing. Natural compounds present in plants exhibit antioxidant properties and the ability to scavenge free radicals. The increased interest in plant chemistry is linked to the growing interest in plant materials as natural antioxidants. This review focuses on aromatic and medicinal plants as a source of antioxidant substances, such as polyphenols, tocopherols, carotenoids, ascorbic acid, and macromolecules (including polysaccharides and peptides) as well as components of essential oils, and their role in skin health and the ageing process.
... In the RR spectrum of normal dermis skin, the resonance-enhanced intrinsic molecular fingerprints of β-carotenes (here we consider β-carotenes, because the β-carotenes and lycopene account for about 60%-70% of the total of the five most concentrated carotenoids content in human organisms), at 1,161 cm -1 and 1,521 cm -1 are thought to play a significant role in the normal dermis skin anti-oxidant defense system, as shown in Figure 2 (top) and Figure 3 (left). These two resonance bands are active because carotenoids have a pre-resonance absorption band which falls in the pre-resonance range of the excitation wavelength of 532 nm [37,[63][64][65][66][67] . The RR peaks of 1,161 cm -1 and 1,521cm -1 disappeared in the BCC sliced sample at a depth of 100 µm as shown in Figure 2 (middle) and Figure 3 (left). ...
... Carotenoids are the organic and natural fat-soluble pigments and exist in plants. Human beings can obtain carotenoids from diet, such as fruits and vegetables, and its concentration depends on their daily diet and stress factor [67,68] . Carotenoids accumulate in the epidermis through (1) diffusion from the fat tissue, blood and lymph flows, or (2) secretion via sweat glands, and sebaceous glands onto the surface of the skin and subsequent penetration. ...
Full-text available
Aim: The aim of the study is to test visible resonance Raman (VRR) spectroscopy for rapid skin cancer diagnosis, and evaluate its effectiveness as a new optical biopsy method to distinguish basal cell carcinoma (BCC) from normal skin tissues. Methods: The VRR spectroscopic technique was undertaken using 532 nm excitation. Normal and BCC human skin tissue samples were measured in seconds. The molecular fingerprints of various native biomolecules as biomarkers were analyzed. A principal component analysis - support vector machine (PCA-SVM) statistical analysis method based on the molecular fingerprints was developed for differentiating BCC from normal skin tissues. Results: VRR provides a rapid method and enhanced Raman signals from biomolecules with resonant and near-resonant absorption bands as compared with using a near-infrared excitation light source. The VRR technique revealed chemical composition changes of native biomarkers such as tryptophan, carotenoids, lipids and proteins. The VRR spectra from BCC samples showed a strong enhancement in proteins including collagen type I combined with amide I and amino acids, and a decrease in carotenoids and lipids. The PCA-SVM statistical analysis based on the molecular fingerprints of the biomarkers yielded a 93.0% diagnostic sensitivity, 100% specificity, and 94.5% accuracy compared with histopathology reports. Conclusion: VRR can enhance molecular vibrational modes of various native biomarkers to allow for very fast display of Raman modes in seconds. It may be used as a label-free molecular pathology method for diagnosis of skin cancer and other diseases and be used for combined treatment with Mohs surgery for BCC.
... The human body cannot produce most of these substances independently, so they must be obtained through a diet rich in carotenoids, like fruit and vegetables [36]. In addition, they are an important antioxidant in seaweeds, demonstrating strong radical scavenging activity [9], which makes algae-derived carotenoids useful against oxidative stress-induced diseases [29]. ...
... The human body cannot produce most of these substances independently, so they must be obtained through a diet rich in carotenoids, like fruit and vegetables [36]. In addition, they are an important antioxidant in seaweeds, demonstrating strong radical scavenging activity [9], which makes algae-derived carotenoids useful against oxidative stressinduced diseases [29]. ...
Full-text available
Seaweeds represent a rich source of biologically active compounds with several applications, especially in the food, cosmetics, and medical fields. The beneficial effects of marine compounds on health have been increasingly explored, making them an excellent choice for the design of functional foods. When studying marine compounds, several aspects must be considered: extraction, identification and quantification methods, purification steps, and processes to increase their stability. Advanced green techniques have been used to extract these valuable compounds, and chromatographic methods have been developed to identify and quantify them. However, apart from the beneficial effects of seaweeds for human health, these natural sources of bioactive compounds can also accumulate undesirable toxic elements with potential health risks. Applying purification techniques of extracts from seaweeds may mitigate the amount of excessive toxic components, ensuring healthy and safer products for commercialization. Furthermore, limitations such as stability and bioavailability problems, chemical degradation reactions during storage, and sensitivity to oxidation and photo-oxidation, need to be overcome using, for example, nanoencapsulation techniques. Here we summarize recent advances in all steps of marine products identification and purification and highlight selected human applications, including food and feed applications, cosmetic, human health, and fertilizers, among others.
... To measure the effect on child health outcomes, we will use Resonance Raman Spectroscopy (RRS), which measures skin carotenoid levels as a biomarker for colorful FV intake [62] with an optical hand scan [63,83]. RRS reflects intake over the prior 4 weeks and is sensitive to individual differences and experimental changes [64,85]. ...
Full-text available
Background: Despite the potential for Early Care and Education (ECE) settings to promote healthy habits, a gap exists between current practices and evidence-based practices (EBPs) for obesity prevention in childhood. Methods: We will use an enhanced non-responder trial design to determine the effectiveness and incremental cost-effectiveness of an adaptive implementation strategy for Together, We Inspire Smart Eating (WISE), while examining moderators and mediators of the strategy effect. WISE is a curriculum that aims to increase children's intake of carotenoid-rich fruits and vegetables through four evidence-based practices in the early care and education setting. In this trial, we will randomize sites that do not respond to low-intensity strategies to either (a) continue receiving low-intensity strategies or (b) receive high-intensity strategies. This design will determine the effect of an adaptive implementation strategy that adds high-intensity versus one that continues with low-intensity among non-responder sites. We will also apply explanatory, sequential mixed methods to provide a nuanced understanding of implementation mechanisms, contextual factors, and characteristics of sites that respond to differing intensities of implementation strategies. Finally, we will conduct a cost effectiveness analysis to estimate the incremental effect of augmenting implementation with high-intensity strategies compared to continuing low-intensity strategies on costs, fidelity, and child health outcomes. Discussion: We expect our study to contribute to an evidence base for structuring implementation support in real-world ECE contexts, ultimately providing a guide for applying the adaptive implementation strategy in ECE for WISE scale-up. Our work will also provide data to guide implementation decisions of other interventions in ECE. Finally, we will provide the first estimate of relative value for different implementation strategies in this setting. Trial registration: NCT05050539 ; 9/20/21.
... Rhodophyceae are red algae because of the presence of photosynthetic pigments such as phycobilins (r-phycoerythrin and r-phycocyanin), chlorophyll, and carotenoids (β-carotene, zeaxanthin, and lutein) [72]. Carotenoids have pro-vitamin A activity and remain active in neutralizing ROS even at low oxygen rates, thus being vital components of the antioxidative protective system of the human skin [78]. These molecules also improve tone, brightness, firmness, and skin photoprotection. ...
... Scytonemin and carotenoids also have potential antiaging activity. Antiaging carotenoids are α-Carotene, β-carotene, lycopene, zeaxanthin, and lutein (Darvin et al. 2011;Crowe-white et al. 2019). It is typically accepted that photoaging is the consequence of UVR induced activation of a group of proteins known as the matrix metalloproteinases (MMPs). ...
Cyanobacteria have received much attention in recent years due to their promising applications in the field of biotechnology and pharmaceutics. Ultraviolet radiation (UVR) has detrimental effects on the skin which has led to the commercial success of synthetic UV filters to diminish the deleterious effects of harmful highly energetic radiations. Cyanobacterial photoprotective metabolites (CPMs) such as mycosporine-like amino acids (MAAs), scytonemin and carotenoids increases skin's ability to retain water and because of this they are used in sunscreen products. Present day UV filters and synthetic moisturizing chemicals may also have disadvantageous effects on the skin. To overcome the devastating effects of UVR, CPMs are considered as natural photoprotectants and an alternative to the present day contrived UV filters. MAAs are considered to be a potential source of innovative bioactive metabolites that are highly fascinating from a biotechnological perspective showing multifarious biotechnological activities ranging from photoprotection to antioxidants, anti-inflammatory, anticancer, antiaging, immunomodulatory and visual venture. This review focuses on the gene cluster, biosynthetic pathway, protection against various stress and biotechnological exploitation of certain CPMs. These true multifunctional secondary metabolites have various important biotechnological applications and thus an attractive area for future research.
... On the other hand, unless this review is widely focused on phenolic compounds application, carotenoids importance cannot be ignored. These natural dietary products, broadly found in consumed products, such as tomatoes, carrots, citrus and derivatives, are known to be powerful antioxidant substances, playing an essential role in the reactions of ROS neutralization [60]. Some of them have been important as well for the their function as provitamin A, decreasing non-communicable diseases' development risks and remarking their indisputable value in the context of nutricosmetic [61]. ...
Full-text available
The increasing production of tropical fruits followed by their processing results in tons of waste, such as skins or seeds. However, these by-products have been reported to be rich in bioactive compounds (BACs) with excellent properties of interest in the cosmeceutical industry: antioxidant, anti-aging, anti-inflammatory, antimicrobial and photoprotective properties. This review summarizes the tropical fruits most produced worldwide, their bioactive composition and the most important and studied therapeutic properties that their by-products can contribute to skin health, as well as the different approaches for obtaining these compounds using techniques by conventional (Soxhlet, liquid-liquid extraction or maceration) and non-conventional extractions (supercritical fluid extraction (SFE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), pressurized liquid extraction (PLE) and two-phase aqueous system), followed by their identification by HPLC-MS or GC-MS analysis. Moreover, this work encompasses several studies that may prove the effects of seeds and skins from tropical fruits against oxidative stress, hyperpigmentation, acne, aging or UV radiation. Therefore, the investigation of functional components present in tropical fruit by-products under a circular bioeconomy model could be of great interest for the cosmeceutical industry and a very promising option for obtaining new cosmeceutical formulations.
... Due to the resonance enhancement of carotenoid Raman band intensities under the excitation in the blue spectral range, Raman spectroscopy is a highly sensitive, informative and reliable technique to analyze carotenoids not only in the pure form, but also in biological tissues and various blends [11][12][13]. One of the most promising directions in this field is in vivo Raman analysis of carotenoids in human skin [14,15]. ...
Using the density functional theory (DFT), we calculated the structures and Raman spectra of trans-isomers of α-carotene, β-carotene, γ-carotene and lycopene as well as trans-isomers of modified β-carotene and lycopene molecules with substituted end or/and side groups. The DFT calculations showed that the position of the C=C stretching band depends mainly on the number of conjugated C=C bonds and decreases with an increase in the conjugation length. The weak dependence of the position of the C=C stretching band on the structure of the carotenoid side and end groups suggests that this band can be used to evaluate the conjugation length for trans-isomers of various molecules containing polyene chains. The C-C stretching band shifts towards lower wavenumbers with growth of the conjugation length or masses of the end groups and to higher wavenumbers in the presence of the side CH3 groups. The intensities of the C-C and C=C stretching bands are enhanced with growth of the conjugation length or masses of the end groups. The presence of the side CH3 groups results in bending of the carotenoid backbone, splitting and dumping of intensities of the C-C and C=C stretching bands.
Full-text available
The effect of the partial pressure of oxygen (pO2) on the antioxidant reactions of all-trans-beta, beta-carotene (BC) was investigated in a soybean phosphatidylcholine liposome system. Peroxyl radicals generated by thermolysis of azo-bis(2,4-dimethylvaleronitrile) at 37-degrees-C initiated lipid peroxidation. BC inhibited lipid peroxidation, which was monitored by conjugated diene formation, by up to 70% versus control at 160 and 15 torr O2. In contrast, at 760 torr O2 the maximum inhibition was approximately 40% versus control and inhibition was less reproducible. Peroxyl radicals oxidized BC to 5,6-epoxy-beta,beta-carotene and several unidentified polar products. The rates of both product formation and BC consumption were significantly higher at 160 torr than at 15 torr O2. However, at 160 and 760 torr O2, the rates of product formation and BC depletion were similar. In liposomes without azo-bis(2,4-dimethylvaleronitrile), BC depletion at 160 torr was only 64% that at 760 torr O2. These results suggest that both radical trapping and autoxidation reactions consume BC and that the latter are accelerated by high pO2. Autoxidation consumes BC without scavenging peroxyl radicals and may attenuate BC antioxidant activity, especially at high pO2. The similarity in its antioxidant effects at 15 and 160 torr O2 suggests that BC could provide antioxidant protection to any tissue within the normal physiologic range of pO2.
Full-text available
The antioxidant β-carotene and lycopene substances were detected noninvasively, in vivo in human skin using Raman resonance spectrpscopy. Both substances were detected simultaneously. To distinguish between the substances, the Raman signals were excited at 488 nm and 514.5 nm simultaneously using a multiline Ar+ laser. The application of a fiber-based optical imaging system allowed the detection of β-carotene and lycopene on any skin area. The disturbance of the measurements because of nonhomogeneous skin pigmentation was avoided by using a measuring area of 28 mm2. The Raman spectroscopic method is well suited for the evaluation of the efficacy of topically or systemically applied amounts of β-carotene and lycopene.
The carotenoid composition of Momordica charantia fruit (pericarp) at four levels of maturity was extensively investigated. The number of carotenoids isolated increased from five in the immature fruit to six at the mature-green and 14 at the partly-ripe and ripe stages. Cryptoxanthin, which could not be isolated at the immature and mature stages, accumulated rapidly at the onset of ripening to become the principal pigment of the ripe fruit. Moderate increases were seen in β-carotene, zeaxanthin and lycopene concentrations as ripening progressed. The reverse trend was observed with lutein and α-carotene which were the major pigments of the immature fruit. Prior to the colour break, only the hydroxy derivatives of α-carotene (zeinoxanthin and lutein) could be detected; the β-hydroxy compounds (cryptoxanthin and zeaxanthin) appeared and predominated thereafter. The hydroxy carotenoids of the ripe fruit were almost entirely esterified in contrast to those of the unripe fruit which were mainly unesterified. Traces of flavochrome, 5,6-monoepoxy-β-carotene, mutatochrome, ζ-carotene, δ-carotene, γ-carotene and rubixanthin were detected in the partly-ripe and ripe fruits but not in the immature and mature-green samples. Phytofluene was observed in trace levels at all stages.
Aiming at the development of strategies to prevent the hand-foot-syndrome, we propose to evaluate the amount of chemotherapeutics in the human skin together with carotenoids the latter serving as marker substances for the dermal antioxidative status. This approach is demonstrated by applying two-color Raman spectroscopy at 785 and 532 nm excitation for selective detection of chemotherapeutics and carotenoids, respectively. Porcine ear skin has proven to be suited as a model for corresponding spectroscopic basic in-vitro investigations. (© 2011 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) (© 2011 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA)
The defense mechanism of the human body is based on the action of antioxidant substances such as carotenoids. Beta carotene and lycopene represent more than 70% of the carotenoids in the human organism. The topical or systemic application of beta carotene and lycopene are general strategies for improving the defense system of the human body. For the evaluation and optimization of this treatment, it is necessary to measure the beta carotene and lycopene concentrations in tissue and especially in human skin, which is the barrier to the environment. We have used resonance Raman scattering as a fast and noninvasive optical method for measuring the absolute concentrations of beta carotene and lycopene in living human skin. Beta carotene and lycopene have different absorption values at 488 and 514.5 nm. As a result, the Raman lines for beta carotene and lycopene have different scattering efficiencies at the 488- and 514.5-nm excitations. These differences were used for the determination of the concentrations of beta carotene and lycopene. Using multiline Ar + laser excitation, clearly distinguishable Raman spectra of carotenoids are obtained, which are then superimposed on a large fluorescence background. The Raman signals are characterized by two prominent Stokes lines at 1160 and 1525 cm-1, which have nearly identical relative intensities. Both substances were detected simultaneously. The Raman spectra were obtained rapidly, i.e., within about 10 seconds, and the required laser-light-exposure level is well within safety standards. Any disturbance of the measurements by nonhomogeneous skin pigmentation was avoided by using a relatively large measuring area of 33 mm2.
Introduction Intakes of fruit and vegetables rich in carotenoids are associated with a lower risk for a variety of chronic diseases. Therefore, the carotenoid levels in the skin have been measured in various studies to investigate the effects of nutrition and lifestyle. However, statistically clear data regarding the influence of age, gender, body mass index, and smoking behaviour were not documented. Methods Thus, non-invasive resonance Raman measurements were performed on 151 healthy volunteers in Berlin, Germany. Results The investigations have shown significantly enhanced total carotenoid values in the skin for women and non-smokers; individuals with a BMI lower than 30 also showed a trend to higher values. In the case of lycopene, significantly enhanced values were found in people younger than 40 and nonsmokers. Conclusion Influences of gender, and smoking or non-smoking must be taken into account when carrying out a study with respect to the carotenoids. Age does not play any role for total carotenoids but for lycopene.
Evidence from both epidemiological and experimental observations have fueled the belief that the high consumption of fruits and vegetables rich in carotenoids may help prevent cancer and heart disease in humans. Because of its well-documented antioxidant and antigenotoxic properties, the carotenoid β-carotene (βCT) gained most of the attention in the early 1980s and became one of the most extensively studied cancer chemopreventive agents in population-based trials supported by the National Cancer Institute. However, the results of three randomized lung cancer chemoprevention trials on βCT supplementation unexpectedly contradicted the large body of epidemiological evidence relating to the potential benefits of dietary carotenoids. Not only did βCT show no benefit, it was associated with significant increases in lung cancer incidence, cardiovascular diseases, and total mortality. These findings aroused widespread scientific debate that is still ongoing. It also raised the suspicion that βCT may even possess co-carcinogenic properties. In this review, we summarize the current data on the co-carcinogenic properties of βCT that is attributed to its role in the induction of carcinogen metabolizing enzymes and the over-generation of oxidative stress. The data presented provide convincing evidence of the harmful properties of this compound if given alone to smokers, or to individuals exposed to environmental carcinogens, as a micronutrient supplement. This has now been directly verified in a medium-term cancer transformation bioassay. In the context of public health policies, while the benefits of a diet rich in a variety of fruits and vegetables should continue to be emphasized, the data presented here point to the need for consideration of the possible detrimental effects of certain isolated dietary supplements, before mass cancer chemoprevention clinical trials are conducted on human subjects. This is especially important for genetically predisposed individuals who are environmentally or occupationally exposed to mutagens and carcinogens, such as those found in tobacco smoke and in industrial settings.