skin care research

• Research article
• Open access
• Published: 12 June 2019

The impact of skin care products on skin chemistry and microbiome dynamics

• Amina Bouslimani 1   na1 ,
• Ricardo da Silva 1   na1 ,
• Tomasz Kosciolek 2 ,
• Stefan Janssen 2 , 3 ,
• Chris Callewaert 2 , 4 ,
• Amnon Amir 2 ,
• Kathleen Dorrestein 1 ,
• Alexey V. Melnik 1 ,
• Livia S. Zaramela 2 ,
• Ji-Nu Kim 2 ,
• Gregory Humphrey 2 ,
• Tara Schwartz 2 ,
• Karenina Sanders 2 ,
• Caitriona Brennan 2 ,
• Tal Luzzatto-Knaan 1 ,
• Gail Ackermann 2 ,
• Daniel McDonald 2 ,
• Karsten Zengler 2 , 5 , 6 ,
• Rob Knight 2 , 5 , 6 , 7 &
• Pieter C. Dorrestein 1 , 2 , 5 , 8  

BMC Biology volume  17 , Article number:  47 ( 2019 ) Cite this article

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Use of skin personal care products on a regular basis is nearly ubiquitous, but their effects on molecular and microbial diversity of the skin are unknown. We evaluated the impact of four beauty products (a facial lotion, a moisturizer, a foot powder, and a deodorant) on 11 volunteers over 9 weeks.

Mass spectrometry and 16S rRNA inventories of the skin revealed decreases in chemical as well as in bacterial and archaeal diversity on halting deodorant use. Specific compounds from beauty products used before the study remain detectable with half-lives of 0.5–1.9 weeks. The deodorant and foot powder increased molecular, bacterial, and archaeal diversity, while arm and face lotions had little effect on bacterial and archaeal but increased chemical diversity. Personal care product effects last for weeks and produce highly individualized responses, including alterations in steroid and pheromone levels and in bacterial and archaeal ecosystem structure and dynamics.

Conclusions

These findings may lead to next-generation precision beauty products and therapies for skin disorders.

The human skin is the most exposed organ to the external environment and represents the first line of defense against external chemical and microbial threats. It harbors a microbial habitat that is person-specific and varies considerably across the body surface [ 1 , 2 , 3 , 4 ]. Recent findings suggested an association between the use of antiperspirants or make-up and skin microbiota composition [ 5 , 6 , 7 ]. However, these studies were performed for a short period (7–10 days) and/or without washing out the volunteers original personal care products, leading to incomplete evaluation of microbial alterations because the process of skin turnover takes 21–28 days [ 5 , 6 , 7 , 8 , 9 ]. It is well-established that without intervention, most adult human microbiomes, skin or other microbiomes, remain stable compared to the differences between individuals [ 3 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].

Although the skin microbiome is stable for years [ 10 ], little is known about the molecules that reside on the skin surface or how skin care products influence this chemistry [ 17 , 18 ]. Mass spectrometry can be used to detect host molecules, personalized lifestyles including diet, medications, and personal care products [ 18 , 19 ]. However, although the impact of short-term dietary interventions on the gut microbiome has been assessed [ 20 , 21 ], no study has yet tested how susceptible the skin chemistry and Microbiome are to alterations in the subjects’ personal care product routine.

In our recent metabolomic/microbiome 3D cartography study [ 18 ], we observed altered microbial communities where specific skin care products were present. Therefore, we hypothesized that these products might shape specific skin microbial communities by changing their chemical environment. Some beauty product ingredients likely promote or inhibit the growth of specific bacteria: for example, lipid components of moisturizers could provide nutrients and promote the growth of lipophilic bacteria such as Staphylococcus and Propionibacterium [ 18 , 22 , 23 ]. Understanding both temporal variations of the skin microbiome and chemistry is crucial for testing whether alterations in personal habits can influence the human skin ecosystem and, perhaps, host health. To evaluate these variations, we used a multi-omics approach integrating metabolomics and microbiome data from skin samples of 11 healthy human individuals. Here, we show that many compounds from beauty products persist on the skin for weeks following their use, suggesting a long-term contribution to the chemical environment where skin microbes live. Metabolomics analysis reveals temporal trends correlated to discontinuing and resuming the use of beauty products and characteristic of variations in molecular composition of the skin. Although highly personalized, as seen with the microbiome, the chemistry, including hormones and pheromones such as androstenone and androsterone, were dramatically altered. Similarly, by experimentally manipulating the personal care regime of participants, bacterial and molecular diversity and structure are altered, particularly for the armpits and feet. Interestingly, a high person-to-person molecular and bacterial variability is maintained over time even though personal care regimes were modified in exactly the same way for all participants.

Skin care and hygiene products persist on the skin

Systematic strategies to influence both the skin chemistry and microbiome have not yet been investigated. The outermost layer of the skin turns over every 3 to 4 weeks [ 8 , 9 ]. How the microbiome and chemistry are influenced by altering personal care and how long the chemicals of personal care products persist on the skin are essentially uncharacterized. In this study, we collected samples from skin of 12 healthy individuals—six males and six females—over 9 weeks. One female volunteer had withdrawn due to skin irritations that developed, and therefore, we describe the remaining 11 volunteers. Samples were collected from each arm, armpit, foot, and face, including both the right and left sides of the body (Fig.  1 a). All participants were asked to adhere to the same daily personal care routine during the first 6 weeks of this study (Fig.  1 b). The volunteers were asked to refrain from using any personal care product for weeks 1–3 except a mild body wash (Fig.  1 b). During weeks 4–6, in addition to the body wash, participants were asked to apply selected commercial skin care products at specific body parts: a moisturizer on the arm, a sunscreen on the face, an antiperspirant on the armpits, and a soothing powder on the foot (Fig.  1 b). To monitor adherence of participants to the study protocol, molecular features found in the antiperspirant, facial lotion, moisturizer, and foot powder were directly tracked with mass spectrometry from the skin samples. For all participants, the mass spectrometry data revealed the accumulation of specific beauty product ingredients during weeks 4–6 (Additional file  1 : Figure S1A-I, Fig.  2 a orange arrows). Examples of compounds that were highly abundant during T4–T6 in skin samples are avobenzone (Additional file  1 : Figure S1A), dexpanthenol (Additional file  1 : Figure S1B), and benzalkonium chloride (Additional file  1 : Figure S1C) from the facial sunscreen; trehalose 6-phosphate (Additional file  1 : Figure S1D) and glycerol stearate (Additional file  1 : Figure S1E) from the moisturizer applied on arms; indolin (Additional file  1 : Figure S1F) and an unannotated compound ( m/z 233.9, rt 183.29 s) (Additional file  1 : Figure S1G) from the foot powder; and decapropylene glycol (Additional file  1 : Figure S1H) and nonapropylene glycol (Additional file  1 : Figure S1I) from the antiperspirant. These results suggest that there is likely a compliance of all individuals to study requirements and even if all participants confirmed using each product every day, the amount of product applied by each individual may vary. Finally, for weeks 7–9, the participants were asked to return to their normal routine by using the same personal care products they used prior to the study. In total, excluding all blanks and personal care products themselves, we analyzed 2192 skin samples for both metabolomics and microbiome analyses.

Study design and representation of changes in personal care regime over the course of 9 weeks. a Six males and six females were recruited and sampled using swabs on two locations from each body part (face, armpits, front forearms, and between toes) on the right and left side. The locations sampled were the face—upper cheek bone and lower jaw, armpit—upper and lower area, arm—front of elbow (antecubitis) and forearm (antebrachium), and feet—in between the first and second toe and third and fourth toe. Volunteers were asked to follow specific instructions for the use of skin care products. b Following the use of their personal skin care products (brown circles), all volunteers used only the same head to toe shampoo during the first 3 weeks (week 1–week 3) and no other beauty product was applied (solid blue circle). The following 3 weeks (week 4–week 6), four selected commercial beauty products were applied daily by all volunteers on the specific body part (deodorant antiperspirant for the armpits, soothing foot powder for the feet between toes, sunscreen for the face, and moisturizer for the front forearm) (triangles) and continued to use the same shampoo. During the last 3 weeks (week 7–week 9), all volunteers went back to their normal routine and used their personal beauty products (circles). Samples were collected once a week (from day 0 to day 68—10 timepoints from T0 to T9) for volunteers 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, and 12, and on day 0 and day 6 for volunteer 8, who withdraw from the study after day 6. For 3 individuals (volunteers 4, 9, 10), samples were collected twice a week (19 timepoints total). Samples collected for 11 volunteers during 10 timepoints: 11 volunteers × 10 timepoints × 4 samples × 4 body sites = 1760. Samples collected from 3 selected volunteers during 9 additional timepoints: 3 volunteers × 9 timepoints × 4 samples × 4 body sites = 432. See also the “ Subject recruitment and sample collection ” section in the “ Methods ” section

Monitoring the persistence of personal care product ingredients in the armpits over a 9-week period. a Heatmap representation of the most abundant molecular features detected in the armpits of all individuals during the four phases (0: initial, 1–3: no beauty products, 4–6: common products, and 7–9: personal products). Green color in the heatmap represents the highest molecular abundance and blue color the lowest one. Orange boxes with plain lines represent enlargement of cluster of molecules that persist on the armpits of volunteer 1 ( b ) and volunteer 3 ( c , d ). Orange clusters with dotted lines represent same clusters of molecules found on the armpits of other volunteers. Orange arrows represent the cluster of compounds characteristic of the antiperspirant used during T4–T6. b Polyethylene glycol (PEG) molecular clusters that persist on the armpits of individual 1. The molecular subnetwork, representing molecular families [ 24 ], is part of a molecular network ( http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=f5325c3b278a46b29e8860ec5791d5ad ) generated from MS/MS data collected from the armpits of volunteer 1 (T0–T3) MSV000081582 and MS/MS data collected from the deodorant used by volunteer 1 before the study started (T0) MSV000081580. c , d Polypropylene glycol (PPG) molecular families that persist on the armpits of individual 3, along with the corresponding molecular subnetwork that is part of the molecular network accessible here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=aaa1af68099d4c1a87e9a09f398fe253 . Subnetworks were generated from MS/MS data collected from the armpits of volunteer 3 (T0–T3) MSV000081582 and MS/MS data collected from the deodorant used by volunteer 3 at T0 MSV000081580. The network nodes were annotated with colors. Nodes represent MS/MS spectra found in armpit samples of individual 1 collected during T0, T1, T2, and T3 and in personal deodorant used by individual 1 (orange nodes); armpit samples of individual 1 collected during T0, T2, and T3 and personal deodorant used by individual 1 (green nodes); armpit samples of individual 3 collected during T0, T1, T2, and T3 and in personal deodorant used by individual 3 (red nodes); armpit samples of individual 3 collected during T0 and in personal deodorant used by individual 3 (blue nodes); and armpit samples of individual 3 collected during T0 and T2 and in personal deodorant used by individual 3 (purple nodes). Gray nodes represent everything else. Error bars represent standard error of the mean calculated at each timepoint from four armpit samples collected from the right and left side of each individual separately. See also Additional file  1 : Figure S1

To understand how long beauty products persist on the skin, we monitored compounds found in deodorants used by two volunteers—female 1 and female 3—before the study (T0), over the first 3 weeks (T1–T3) (Fig.  1 b). During this phase, all participants used exclusively the same body wash during showering, making it easier to track ingredients of their personal care products. The data in the first 3 weeks (T1–T3) revealed that many ingredients of deodorants used on armpits (Fig.  2 a) persist on the skin during this time and were still detected during the first 3 weeks or at least during the first week following the last day of use. Each of the compounds detected in the armpits of individuals exhibited its own unique half-life. For example, the polyethylene glycol (PEG)-derived compounds m/z 344.227, rt 143 s (Fig.  2 b, S1J); m/z 432.279, rt 158 s (Fig.  2 b, S1K); and m/z 388.253, rt 151 s (Fig.  2 b, S1L) detected on armpits of volunteer 1 have a calculated half-life of 0.5 weeks (Additional file  1 : Figure S1J-L, all p values < 1.81e−07), while polypropylene glycol (PPG)-derived molecules m/z 481.87, rt 501 s (Fig.  2 c, S1M); m/z 560.420, rt 538 s (Fig.  2 c, S1N); m/z 788.608, rt 459 s (Fig.  2 d, S1O); m/z 846.650, rt 473 s (Fig.  2 d, S1P); and m/z 444.338, rt 486 s (Fig.  2 d, S1Q) found on armpits of volunteers 3 and 1 (Fig.  2 a) have a calculated half-life ranging from 0.7 to 1.9 weeks (Additional file  1 : Figure S1M-Q, all p values < 0.02), even though they originate from the same deodorant used by each individual. For some ingredients of deodorant used by volunteer 3 on time 0 (Additional file  1 : Figure S1M, N), a decline was observed during the first week, then little to no traces of these ingredients were detected during weeks 4–6 (T4–T6), then finally these ingredients reappear again during the last 3 weeks of personal product use (T7–T9). This suggests that these ingredients are present exclusively in the personal deodorant used by volunteer 3 before the study. Because a similar deodorant (Additional file  1 : Figure S1O-Q) and a face lotion (Additional file  1 : Figure S1R) was used by volunteer 3 and volunteer 2, respectively, prior to the study, there was no decline or absence of their ingredients during weeks 4–6 (T4–T6).

Polyethylene glycol compounds (Additional file  1 : Figure S1J-L) wash out faster from the skin than polypropylene glycol (Additional file  1 : Figure S1M-Q)(HL ~ 0.5 weeks vs ~ 1.9 weeks) and faster than fatty acids used in lotions (HL ~ 1.2 weeks) (Additional file  1 : Figure S1R), consistent with their hydrophilic (PEG) and hydrophobic properties (PPG and fatty acids) [ 25 , 26 ]. This difference in hydrophobicity is also reflected in the retention time as detected by mass spectrometry. Following the linear decrease of two PPG compounds from T0 to T1, they accumulated noticeably during weeks 2 and 3 (Additional file  1 : Figure S1M, N). This accumulation might be due to other sources of PPG such as the body wash used during this period or the clothes worn by person 3. Although PPG compounds were not listed in the ingredient list of the shampoo, we manually inspected the LC-MS data collected from this product and confirmed the absence of PPG compounds in the shampoo. The data suggest that this trend is characteristic of accumulation of PPG from additional sources. These could be clothes, beds, or sheets, in agreement with the observation of these molecules found in human habitats [ 27 ] but also in the public GNPS mass spectrometry dataset MSV000079274 that investigated the chemicals from dust collected from 1053 mattresses of children.

Temporal molecular and bacterial diversity in response to personal care use

To assess the effect of discontinuing and resuming the use of skin care products on molecular and microbiota dynamics, we first evaluated their temporal diversity. Skin sites varied markedly in their initial level (T0) of molecular and bacterial diversity, with higher molecular diversity at all sites for female participants compared to males (Fig.  3 a, b, Wilcoxon rank-sum-WR test, p values ranging from 0.01 to 0.0001, from foot to arm) and higher bacterial diversity in face (WR test, p  = 0.0009) and armpits (WR test, p  = 0.002) for females (Fig.  3 c, d). Temporal diversity was similar across the right and left sides of each body site of all individuals (WR test, molecular diversity: all p values > 0.05; bacterial diversity: all p values > 0.20). The data show that refraining from using beauty products (T1–T3) leads to a significant decrease in molecular diversity at all sites (Fig.  3 a, b, WR test, face: p  = 8.29e−07, arm: p  = 7.08e−09, armpit: p  = 1.13e−05, foot: p  = 0.002) and bacterial diversity mainly in armpits (WR test, p  = 0.03) and feet (WR test, p  = 0.04) (Fig.  3 c, d). While molecular diversity declined (Fig.  3 a, b) for arms and face, bacterial diversity (Fig.  3 c, d) was less affected in the face and arms when participants did not use skin care products (T1–T3). The molecular diversity remained stable in the arms and face of female participants during common beauty products use (T4–T6) to immediately increase as soon as the volunteers went back to their normal routines (T7–T9) (WR test, p  = 0.006 for the arms and face)(Fig.  3 a, b). A higher molecular (Additional file  1 : Figure S2A) and community (Additional file  1 : Figure S2B) diversity was observed for armpits and feet of all individuals during the use of antiperspirant and foot powder (T4–T6) (WR test, molecular diversity: armpit p  = 8.9e−33, foot p  = 1.03e−11; bacterial diversity: armpit p  = 2.14e−28, foot p  = 1.26e−11), followed by a molecular and bacterial diversity decrease in the armpits when their regular personal beauty product use was resumed (T7–T9) (bacterial diversity: WR test, p  = 4.780e−21, molecular diversity: WR test, p  = 2.159e−21). Overall, our data show that refraining from using beauty products leads to lower molecular and bacterial diversity, while resuming the use increases their diversity. Distinct variations between male and female molecular and community richness were perceived at distinct body parts (Fig.  3 a–d). Although the chemical diversity of personal beauty products does not explain these variations (Additional file  1 : Figure S2C), differences observed between males and females may be attributed to many environmental and lifestyle factors including different original skin care and different frequency of use of beauty products (Additional file  2 : Table S1), washing routines, and diet.

Molecular and bacterial diversity over a 9-week period, comparing samples based on their molecular (UPLC-Q-TOF-MS) or bacterial (16S rRNA amplicon) profiles. Molecular and bacterial diversity using the Shannon index was calculated from samples collected from each body part at each timepoint, separately for female ( n  = 5) and male ( n  = 6) individuals. Error bars represent standard error of the mean calculated at each timepoint, from up to four samples collected from the right and left side of each body part, of females ( n  = 5) and males ( n  = 6) separately. a , b Molecular alpha diversity measured using the Shannon index from five females (left panel) and six males (right panel), over 9 weeks, from four distinct body parts (armpits, face, arms, feet). c , d Bacterial alpha diversity measured using the Shannon index, from skin samples collected from five female (left panel) and six male individuals (right panel), over 9 weeks, from four distinct body parts (armpits, face, arms, feet). See also Additional file  1 : Figure S2

Longitudinal variation of skin metabolomics signatures

To gain insights into temporal metabolomics variation associated with beauty product use, chemical inventories collected over 9 weeks were subjected to multivariate analysis using the widely used Bray–Curtis dissimilarity metric (Fig.  4 a–c, S3A). Throughout the 9-week period, distinct molecular signatures were associated to each specific body site: arm, armpit, face, and foot (Additional file  1 : Figure S3A, Adonis test, p  < 0.001, R 2 0.12391). Mass spectrometric signatures displayed distinct individual trends at each specific body site (arm, armpit, face, and foot) over time, supported by their distinct locations in PCoA (principal coordinate analysis) space (Fig.  4 a, b) and based on the Bray–Curtis distances between molecular profiles (Additional file  1 : Figure S3B, WR test, all p values < 0.0001 from T0 through T9). This suggests a high molecular inter-individual variability over time despite similar changes in personal care routines. Significant differences in molecular patterns associated to ceasing (T1–T3) (Fig.  4 b, Additional file 1 : Figure S3C, WR test, T0 vs T1–T3 p  < 0.001) and resuming the use of common beauty products (T4–T6) (Additional file  1 : Figure S3C) were observed in the arm, face, and foot (Fig.  4 b), although the armpit exhibited the most pronounced changes (Fig.  4 b, Additional file 1 : Figure S3D, E, random forest highlighting that 100% of samples from each phase were correctly predicted). Therefore, we focused our analysis on this region. Molecular changes were noticeable starting the first week (T1) of discontinuing beauty product use. As shown for armpits in Fig.  4 c, these changes at the chemical level are specific to each individual, possibly due to the extremely personalized lifestyles before the study and match their original use of deodorant. Based on the initial use of underarm products (T0) (Additional file  2 : Table S1), two groups of participants can be distinguished: a group of five volunteers who used stick deodorant as evidenced by the mass spectrometry data and another group of volunteers where we found few or no traces suggesting they never or infrequently used stick deodorants (Additional file  2 : Table S1). Based on this criterion, the chemical trends shown in Fig.  4 c highlight that individuals who used stick deodorant before the beginning of the study (volunteers 1, 2, 3, 9, and 12) displayed a more pronounced shift in their armpits’ chemistries as soon as they stopped using deodorant (T1–T3), compared to individuals who had low detectable levels of stick deodorant use (volunteers 4, 6, 7, and 10), or “rarely-to-never” (volunteers 5 and 11) use stick deodorants as confirmed by the volunteers (Additional file  1 : Figure S3F, WR test, T0 vs T1–T3 all p values < 0.0001, with greater distance for the group of volunteers 1, 2, 3, 9, and 12, compared to volunteers 4, 5, 6, 7, 10, and 11). The most drastic shift in chemical profiles was observed during the transition period, when all participants applied the common antiperspirant on a daily basis (T4–T6) (Additional file  1 : Figure S3D, E). Finally, the molecular profiles became gradually more similar to those collected before the experiment (T0) as soon as the participants resumed using their personal beauty products (T7–T9) (Additional file  1 : Figure S3C), although traces of skin care products did last through the entire T7–T9 period in people who do not routinely apply these products (Fig.  4 c).

Individualized influence of beauty product application on skin metabolomics profiles over time. a Multivariate statistical analysis (principal coordinate analysis (PCoA)) comparing mass spectrometry data collected over 9 weeks from the skin of 11 individuals, all body parts, combined (first plot from the left) and then displayed separately (arm, armpits, face, feet). Color scale represents volunteer ID. The PCoA was calculated on all samples together, and subsets of the data are shown in this shared space and the other panels. b The molecular profiles collected over 9 weeks from all body parts, combined then separately (arm, armpits, face, feet). c Representative molecular profiles collected over 9 weeks from armpits of 11 individuals (volunteers 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12). Color gradient in b and c represents timepoints (time 0 to time 9), ranging from the lightest orange color to the darkest one that represent the earliest (time 0) to the latest (time 9) timepoint, respectively. 0.5 timepoints represent additional timepoints where three selected volunteers were samples (volunteers 4, 9, and 10). PCoA plots were generated using the Bray–Curtis dissimilarity matrix and visualized in Emperor [ 28 ]. See also Additional file  1 : Figure S3

Comparing chemistries detected in armpits at the end timepoints—when no products were used (T3) and during product use (T6)—revealed distinct molecular signatures characteristic of each phase (random forest highlighting that 100% of samples from each group were correctly predicted, see Additional file  1 : Figure S3D, E). Because volunteers used the same antiperspirant during T4–T6, molecular profiles converged during that time despite individual patterns at T3 (Fig.  4 b, c, Additional file  1 : Figure S3D). These distinct chemical patterns reflect the significant impact of beauty products on skin molecular composition. Although these differences may in part be driven by beauty product ingredients detected on the skin (Additional file  1 : Figure S1), we anticipated that additional host- and microbe-derived molecules may also be involved in these molecular changes.

To characterize the chemistries that vary over time, we used molecular networking, a MS visualization approach that evaluates the relationship between MS/MS spectra and compares them to reference MS/MS spectral libraries of known compounds [ 29 , 30 ]. We recently showed that molecular networking can successfully organize large-scale mass spectrometry data collected from the human skin surface [ 18 , 19 ]. Briefly, molecular networking uses the MScluster algorithm [ 31 ] to merge all identical spectra and then compares and aligns all unique pairs of MS/MS spectra based on their similarities where 1.0 indicates a perfect match. Similarities between MS/MS spectra are calculated using a similarity score, and are interpreted as molecular families [ 19 , 24 , 32 , 33 , 34 ]. Here, we used this method to compare and characterize chemistries found in armpits, arms, face, and foot of 11 participants. Based on MS/MS spectral similarities, chemistries highlighted through molecular networking (Additional file  1 : Figure S4A) were associated with each body region with 8% of spectra found exclusively in the arms, 12% in the face, 14% in the armpits, and 2% in the foot, while 18% of the nodes were shared between all four body parts and the rest of spectra were shared between two body sites or more (Additional file  1 : Figure S4B). Greater spectral similarities were highlighted between armpits, face, and arm (12%) followed by the arm and face (9%) (Additional file  1 : Figure S4B).

Molecules were annotated with Global Natural Products Social Molecular Networking (GNPS) libraries [ 29 ], using accurate parent mass and MS/MS fragmentation patterns, according to level 2 or 3 of annotation defined by the 2007 metabolomics standards initiative [ 35 ]. Through annotations, molecular networking revealed that many compounds derived from steroids (Fig.  5 a–d), bile acids (Additional file  1 : Figure S5A-D), and acylcarnitines (Additional file  1 : Figure S5E-F) were exclusively detected in the armpits. Using authentic standards, the identity of some pheromones and bile acids were validated to a level 1 identification with matched retention times (Additional file  1 : Figure S6B, S7A, C, D). Other steroids and bile acids were either annotated using standards with identical MS/MS spectra but slightly different retention times (Additional file  1 : Figure S6A) or annotated with MS/MS spectra match with reference MS/MS library spectra (Additional file  1 : Figure S6C, D, S7B, S6E-G). These compounds were therefore classified as level 3 [ 35 ]. Acylcarnitines were annotated to a family of possible acylcarnitines (we therefore classify as level 3), as the positions of double bonds or cis vs trans configurations are unknown (Additional file  1 : Figure S8A, B).

Underarm steroids and their longitudinal abundance. a – d Steroid molecular families in the armpits and their relative abundance over a 9-week period. Molecular networking was applied to characterize chemistries from the skin of 11 healthy individuals. The full network is shown in Additional file  1 : Figure S4A, and networking parameters can be found here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=284fc383e4c44c4db48912f01905f9c5 for MS/MS datasets MSV000081582. Each node represents a consensus of a minimum of 3 identical MS/MS spectra. Yellow nodes represent MS/MS spectra detected in armpits samples. Hexagonal shape represents MS/MS spectra match between skin samples and chemical standards. Plots are representative of the relative abundance of each compound over time, calculated separately from LC-MS1 data collected from the armpits of each individual. Steroids detected in armpits are a , dehydroisoandrosterone sulfate ( m/z 369.190, rt 247 s), b androsterone sulfate ( m/z 371.189, rt 261 s), c 1-dehydroandrostenedione ( m/z 285.185, rt 273 s), and d dehydroandrosterone ( m/z 289.216, rt 303 s). Relative abundance over time of each steroid compound is represented. Error bars represent the standard error of the mean calculated at each timepoint from four armpit samples from the right and left side of each individual separately. See also Additional file  1 : Figures S4-S8

Among the steroid compounds, several molecular families were characterized: androsterone (Fig.  5 a, b, d), androstadienedione (Fig.  5 c), androstanedione (Additional file  1 : Figure S6E), androstanolone (Additional file  1 : Figure S6F), and androstenedione (Additional file  1 : Figure S6G). While some steroids were detected in the armpits of several individuals, such as dehydroisoandrosterone sulfate ( m/z 369.19, rt 247 s) (9 individuals) (Fig.  5 a, Additional file  1 : Figure S6A), androsterone sulfate ( m/z 371.189, rt 261 s) (9 individuals) (Fig.  5 b, Additional file  1 : Figure S6C), and 5-alpha-androstane-3,17-dione ( m/z 271.205, rt 249 s) (9 individuals) (Additional file  1 : Figure S6E), other steroids including 1-dehydroandrostenedione ( m/z 285.185, rt 273 s) (Fig.  5 c, Additional file  1 : Figure S6B), dehydroandrosterone ( m/z 289.216, rt 303 s) (Fig.  5 d, Additional file 1 : Figure S6D), and 5-alpha-androstan-17.beta-ol-3-one ( m/z 291.231, rt 318 s) (Additional file  1 : Figure S6F) were only found in the armpits of volunteer 11 and 4-androstene-3,17-dione ( m/z 287.200, rt 293 s) in the armpits of volunteer 11 and volunteer 5, both are male that never applied stick deodorants (Additional file  1 : Figure S6G). Each molecular species exhibited a unique pattern over the 9-week period. The abundance of dehydroisoandrosterone sulfate (Fig.  5 a, WR test, p  < 0.01 for 7 individuals) and dehydroandrosterone (Fig.  5 a, WR test, p  = 0.00025) significantly increased during the use of antiperspirant (T4–T6), while androsterone sulfate (Fig.  5 b) and 5-alpha-androstane-3,17-dione (Additional file  1 : Figure S6E) display little variation over time. Unlike dehydroisoandrosterone sulfate (Fig.  5 a) and dehydroandrosterone (Fig.  5 d), steroids including 1-dehydroandrostenedione (Fig.  5 c, WR test, p  = 0.00024) and 4-androstene-3,17-dione (Additional file  1 : Figure S6G, WR test, p  = 0.00012) decreased in abundance during the 3 weeks of antiperspirant application (T4–T6) in armpits of male 11, and their abundance increased again when resuming the use of his normal skin care routines (T7–T9). Interestingly, even within the same individual 11, steroids were differently impacted by antiperspirant use as seen for 1-dehydroandrostenedione that decreased in abundance during T4–T6 (Fig.  5 c, WR test, p  = 0.00024), while dehydroandrosterone increased in abundance (Fig.  5 d, WR test, p  = 0.00025), and this increase was maintained during the last 3 weeks of the study (T7–T9).

In addition to steroids, many bile acids (Additional file  1 : Figure S5A-D) and acylcarnitines (Additional file  1 : Figure S5E-F) were detected on the skin of several individuals through the 9-week period. Unlike taurocholic acid found only on the face (Additional file  1 : Figures S5A, S7A) and tauroursodeoxycholic acid detected in both armpits and arm samples (Additional file  1 : Figures S5B, S7B), other primary bile acids such as glycocholic (Additional file  1 : Figures S5C, S7C) and chenodeoxyglycocholic acid (Additional file  1 : Figures S5D, S7D) were exclusively detected in the armpits. Similarly, acylcarnitines were also found either exclusively in the armpits (hexadecanoyl carnitines) (Additional file  1 : Figures S5E, S8A) or in the armpits and face (tetradecenoyl carnitine) (Additional file  1 : Figures S5F, S8B) and, just like the bile acids, they were also stably detected during the whole 9-week period.

Bacterial communities and their variation over time

Having demonstrated the impact of beauty products on the chemical makeup of the skin, we next tested the extent to which skin microbes are affected by personal care products. We assessed temporal variation of bacterial communities detected on the skin of healthy individuals by evaluating dissimilarities of bacterial collections over time using unweighted UniFrac distance [ 36 ] and community variation at each body site in association to beauty product use [ 3 , 15 , 37 ]. Unweighted metrics are used for beta diversity calculations because we are primarily concerned with changes in community membership rather than relative abundance. The reason for this is that skin microbiomes can fluctuate dramatically in relative abundance on shorter timescales than that assessed here. Longitudinal variations were revealed for the armpits (Fig.  6 a) and feet microbiome by their overall trend in the PCoA plots (Fig.  6 b), while the arm (Fig.  6 c) and face (Fig.  6 d) displayed relatively stable bacterial profiles over time. As shown in Fig.  6 a–d, although the microbiome was site-specific, it varied more between individuals and this inter-individual variability was maintained over time despite same changes in personal care routine (WR test, all p values at all timepoints < 0.05, T5 p  = 0.07), in agreement with previous findings that individual differences in the microbiome are large and stable over time [ 3 , 4 , 10 , 37 ]. However, we show that shifts in the microbiome can be induced by changing hygiene routine and therefore skin chemistry. Changes associated with using beauty products (T4–T6) were more pronounced for the armpits (Fig.  6 a, WR test, p  = 1.61e−52) and feet (Fig.  6 b, WR test, p  = 6.15e−09), while little variations were observed for the face (Fig.  6 d, WR test, p  = 1.402.e−83) and none for the arms (Fig.  6 c, WR test, p  = 0.296).

Longitudinal variation of skin bacterial communities in association with beauty product use. a - d Bacterial profiles collected from skin samples of 11 individuals, over 9 weeks, from four distinct body parts a) armpits, b) feet, c) arms and d) face, using multivariate statistical analysis (Principal Coordinates Analysis PCoA) and unweighted Unifrac metric. Each color represents bacterial samples collected from an individual. PCoA were calculated separately for each body part. e , f Representative Gram-negative (Gram -) bacteria collected from arms, armpits, face and feet of e) female and f) male participants. See also Additional file  1 : Figure S9A, B showing Gram-negative bacterial communities represented at the genus level

A significant increase in abundance of Gram-negative bacteria including the phyla Proteobacteria and Bacteroidetes was noticeable for the armpits and feet of both females (Fig.  6 e; Mann–Whitney U , p  = 8.458e−07) and males (Fig.  6 f; Mann–Whitney U , p  = 0.0004) during the use of antiperspirant (T4–T6), while their abundance remained stable for the arms and face during that time (Fig.  6 e, f; female arm p  = 0.231; female face p value = 0.475; male arm p = 0.523;male face p  = 6.848751e−07). These Gram-negative bacteria include Acinetobacter and Paracoccus genera that increased in abundance in both armpits and feet of females (Additional file  1 : Figure S9A), while a decrease in abundance of Enhydrobacter was observed in the armpits of males (Additional file  1 : Figure S9B). Cyanobacteria, potentially originating from plant material (Additional file  1 : Figure S9C) also increased during beauty product use (T4–T6) especially in males, in the armpits and face of females (Fig.  6 e) and males (Fig.  6 f). Interestingly, although chloroplast sequences (which group phylogenetically within the cyanobacteria [ 38 ]) were only found in the facial cream (Additional file  1 : Figure S9D), they were detected in other locations as well (Fig.  6 e, f. S9E, F), highlighting that the application of a product in one region will likely affect other regions of the body. For example, when showering, a face lotion will drip down along the body and may be detected on the feet. Indeed, not only did the plant material from the cream reveal this but also the shampoo used for the study for which molecular signatures were readily detected on the feet as well (Additional file  1 : Figure S10A). Minimal average changes were observed for Gram-positive organisms (Additional file  1 : Figure S10B, C), although in some individuals the variation was greater than others (Additional file  1 : Figure S10D, E) as discussed for specific Gram-positive taxa below.

At T0, the armpit’s microflora was dominated by Staphylococcus (26.24%, 25.11% of sequencing reads for females and 27.36% for males) and Corynebacterium genera (26.06%, 17.89% for females and 34.22% for males) (Fig.  7 a—first plot from left and Additional file  1 : Figure S10D, E). They are generally known as the dominant armpit microbiota and make up to 80% of the armpit microbiome [ 39 , 40 ]. When no deodorants were used (T1–T3), an overall increase in relative abundance of Staphylococcus (37.71%, 46.78% for females and 30.47% for males) and Corynebacterium (31.88%, 16.50% for females and 44.15% for males) genera was noticeable (WR test, p  < 3.071e−05) (Fig.  7 a—first plot from left), while the genera Anaerococcus and Peptoniphilus decreased in relative abundance (WR test, p  < 0.03644) (Fig.  7 a—first plot from left and Additional file  1 : Figure S10D, E). When volunteers started using antiperspirants (T4–T6), the relative abundance of Staphylococcus (37.71%, 46.78% females and 30.47% males, to 21.71%, 25.02% females and 19.25% males) and Corynebacterium (31.88%, 16.50% females and 44.15% males, to 15.83%, 10.76% females and 19.60% males) decreased (WR test, p  < 3.071e−05) (Fig.  7 a, Additional file  1 : Figure S10D, E) and at the same time, the overall alpha diversity increased significantly (WR test, p  = 3.47e−11) (Fig.  3 c, d). The microbiota Anaerococcus (WR test, p  = 0.0006018) , Peptoniphilus (WR test, p  = 0.008639), and Micrococcus (WR test, p  = 0.0377) increased significantly in relative abundance, together with a lot of additional low-abundant species that lead to an increase in Shannon alpha diversity (Fig.  3 c, d). When participants went back to normal personal care products (T7–T9), the underarm microbiome resembled the original underarm community of T0 (WR test, p  = 0.7274) (Fig.  7 a). Because armpit bacterial communities are person-specific (inter-individual variability: WR test, all p values at all timepoints < 0.05, besides T5 p n.s), variation in bacterial abundance upon antiperspirant use (T4–T6) differ between individuals and during the whole 9-week period (Fig.  7a —taxonomic plots per individual). For example, the underarm microbiome of male 5 exhibited a unique pattern, where Corynebacterium abundance decreased drastically during the use of antiperspirant (82.74 to 11.71%, WR test, p  = 3.518e−05) while in the armpits of female 9 a huge decrease in Staphylococcus abundance was observed (Fig.  7 a) (65.19 to 14.85%, WR test, p  = 0.000113). Unlike other participants, during T0–T3, the armpits of individual 11 were uniquely characterized by the dominance of a sequence that matched most closely to the Enhydrobacter genera . The transition to antiperspirant use (T4–T6) induces the absence of Enhydrobacter (30.77 to 0.48%, WR test, p  = 0.01528) along with an increase of Corynebacterium abundance (26.87 to 49.74%, WR test, p  = 0.1123) (Fig.  7 a—male 11).

Person-to-person bacterial variabilities over time in the armpits and feet. a Armpit microbiome changes when stopping personal care product use, then resuming. Armpit bacterial composition of the 11 volunteers combined, then separately, (female 1, female 2, female 3, male 4, male 5, male 6, male 7, female 9, male 10, male 11, female 12) according to the four periods within the experiment. b Feet bacterial variation over time of the 12 volunteers combined, then separately (female 1, female 2, female 3, male 4, male 5, male 6, male 7, female 9, male 10, male 11, female 12) according to the four periods within the experiment. See also Additional file  1 : Figure S9-S13

In addition to the armpits, a decline in abundance of Staphylococcus and Corynebacterium was perceived during the use of the foot powder (46.93% and 17.36%, respectively) compared to when no beauty product was used (58.35% and 22.99%, respectively) (WR test, p  = 9.653e−06 and p  = 0.02032, respectively), while the abundance of low-abundant foot bacteria significantly increased such as Micrococcus (WR test, p  = 1.552e−08), Anaerococcus (WR test, p  = 3.522e−13), Streptococcus (WR test, p  = 1.463e−06), Brevibacterium (WR test, p  = 6.561e−05), Moraxellaceae (WR test, p  = 0.0006719), and Acinetobacter (WR test, p  = 0.001487), leading to a greater bacterial diversity compared to other phases of the study (Fig.  7 b first plot from left, Additional file  1 : Figure S10D, E, Fig.  3 c, d).

We further evaluated the relationship between the two omics datasets by superimposing the principal coordinates calculated from metabolome and microbiome data (Procrustes analysis) (Additional file  1 : Figure S11) [ 34 , 41 , 42 ]. Metabolomics data were more correlated with patterns observed in microbiome data in individual 3 (Additional file  1 : Figure S11C, Mantel test, r  = 0.23, p  < 0.001), individual 5 (Additional file  1 : Figure S11E, r  = 0.42, p  < 0.001), individual 9 (Additional file  1 : Figure S11H, r  = 0.24, p  < 0.001), individual 10 (Additional file  1 : Figure S11I, r  = 0.38, p  < 0.001), and individual 11 (Additional file  1 : Figure S11J, r  = 0.35, p  < 0.001) when compared to other individuals 1, 2, 4, 6, 7, and 12 (Additional file  1 : Figure S11A, B, D, F, G, K, respectively) (Mantel test, all r  < 0.2, all p values < 0.002, for volunteer 2 p n.s). Furthermore, these correlations were individually affected by ceasing (T1–T3) or resuming the use of beauty products (T4–T6 and T7–T9) (Additional file  1 : Figure S11A-K).

Overall, metabolomics–microbiome correlations were consistent over time for the arms, face, and feet although alterations were observed in the arms of volunteers 7 (Additional file  1 : Figure S11G) and 10 (Additional file  1 : Figure S11I) and the face of volunteer 7 (Additional file  1 : Figure S11G) during product use (T4–T6). Molecular–bacterial correlations were mostly affected in the armpits during antiperspirant use (T4–T6), as seen for volunteers male 7 (Additional file  1 : Figure S11G) and 11 (Additional file  1 : Figure S11J) and females 2 (Additional file  1 : Figure S11B), 9 (Additional file  1 : Figure S11H), and 12 (Additional file  1 : Figure S11K). This perturbation either persisted during the last 3 weeks (Additional file  1 : Figure S11D, E, H, I, K) when individuals went back to their normal routine (T7–T9) or resembled the initial molecular–microbial correlation observed in T0 (Additional file  1 : Figure S11C, G, J). These alterations in molecular–bacterial correlation are driven by metabolomics changes during antiperspirant use as revealed by metabolomics shifts on the PCoA space (Additional file  1 : Figure S11), partially due to the deodorant’s chemicals (Additional file  1 : Figure S1J, K) but also to changes observed in steroid levels in the armpits (Fig.  5A, C, D , Additional file 1 : Figure S6G), suggesting metabolome-dependant changes of the skin microbiome. In agreement with previous findings that showed efficient biotransformation of steroids by Corynebacterium [ 43 , 44 ], our correlation analysis associates specific steroids that were affected by antiperspirant use in the armpits of volunteer 11 (Fig.  5 c, d, Additional file 1 : Figure S6G) with microbes that may produce or process them: 1-dehydroandrostenedione, androstenedione, and dehydrosterone with Corynebacterium ( r  = − 0.674, p  = 6e−05; r  = 0.671, p  = 7e−05; r  = 0.834, p  < 1e−05, respectively) (Additional file  1 : Figure S12A, B, C, respectively) and Enhydrobacter ( r  = 0.683, p  = 4e−05; r  = 0.581, p  = 0.00095; r  = 0.755, p  < 1e−05 respectively) (Additional file  1 : Figure S12D, E, F, respectively).

Despite the widespread use of skin care and hygiene products, their impact on the molecular and microbial composition of the skin is poorly studied. We established a workflow that examines individuals to systematically study the impact of such lifestyle characteristics on the skin by taking a broad look at temporal molecular and bacterial inventories and linking them to personal skin care product use. Our study reveals that when the hygiene routine is modified, the skin metabolome and microbiome can be altered, but that this alteration depends on product use and location on the body. We also show that like gut microbiome responses to dietary changes [ 20 , 21 ], the responses are individual-specific.

We recently reported that traces of our lifestyle molecules can be detected on the skin days and months after the original application [ 18 , 19 ]. Here, we show that many of the molecules associated with our personal skin and hygiene products had a half-life of 0.5 to 1.9 weeks even though the volunteers regularly showered, swam, or spent time in the ocean. Thus, a single application of some of these products has the potential to alter the microbiome and skin chemistry for extensive periods of time. Our data suggests that although host genetics and diet may play a role, a significant part of the resilience of the microbiome that has been reported [ 10 , 45 ] is due to the resilience of the skin chemistry associated with personal skin and hygiene routines, or perhaps even continuous re-exposure to chemicals from our personal care routines that are found on mattresses, furniture, and other personal objects [ 19 , 27 , 46 ] that are in constant contact. Consistent with this observation is that individuals in tribal regions and remote villages that are infrequently exposed to the types of products used in this study have very different skin microbial communities [ 47 , 48 ] and that the individuals in this study who rarely apply personal care products had a different starting metabolome. We observed that both the microbiome and skin chemistry of these individuals were most significantly affected by these products. This effect by the use of products at T4–T6 on the volunteers that infrequently used them lasted to the end phase of the study even though they went back to infrequent use of personal care products. What was notable and opposite to what the authors originally hypothesized is that the use of the foot powder and antiperspirant increased the diversity of microbes and that some of this diversity continued in the T7–T9 phase when people went back to their normal skin and hygiene routines. It is likely that this is due to the alteration in the nutrient availability such as fatty acids and moisture requirements, or alteration of microbes that control the colonization via secreted small molecules, including antibiotics made by microbes commonly found on the skin [ 49 , 50 ].

We detected specific molecules on the skin that originated from personal care products or from the host. One ingredient that lasts on the skin is propylene glycol, which is commonly used in deodorants and antiperspirants and added in relatively large amounts as a humectant to create a soft and sleek consistency [ 51 ]. As shown, daily use of personal care products is leading to high levels of exposure to these polymers. Such polymers cause contact dermatitis in a subset of the population [ 51 , 52 ]. Our data reveal a lasting accumulation of these compounds on the skin, suggesting that it may be possible to reduce their dose in deodorants or frequency of application and consequently decrease the degree of exposure to such compounds. Formulation design of personal care products may be influenced by performing detailed outcome studies. In addition, longer term impact studies are needed, perhaps in multiple year follow-up studies, to assess if the changes we observed are permanent or if they will recover to the original state.

Some of the host- and microbiome-modified molecules were also detected consistently, such as acylcarnitines, bile acids, and certain steroids. This means that a portion of the molecular composition of a person’s skin is not influenced by the beauty products applied to the skin, perhaps reflecting the level of exercise for acylcarnitines [ 53 , 54 ] or the liver (dominant location where they are made) or gallbladder (where they are stored) function for bile acids. The bile acid levels are not related to sex and do not change in amount during the course of this study. While bile acids are typically associated with the human gut microbiome [ 34 , 55 , 56 , 57 , 58 ], it is unclear what their role is on the skin and how they get there. One hypothesis is that they are present in the sweat that is excreted through the skin, as this is the case for several food-derived molecules such as caffeine or drugs and medications that have been previously reported on the human skin [ 19 ] or that microbes synthesize them de novo [ 55 ]. The only reports we could find on bile acids being associated with the skin describe cholestasis and pruritus diseases. Cholestasis and pruritus in hepatobiliary disease have symptoms of skin bile acid accumulation that are thought to be responsible for severe skin itching [ 59 , 60 ]. However, since bile acids were found in over 50% of the healthy volunteers, their detection on the skin is likely a common phenotype among the general population and not only reflective of disease, consistent with recent reports challenging these molecules as biomarkers of disease [ 59 ]. Other molecules that were detected consistently came from personal care products.

Aside from molecules that are person-specific and those that do not vary, there are others that can be modified via personal care routines. Most striking is how the personal care routines influenced changes in hormones and pheromones in a personalized manner. This suggests that there may be personalized recipes that make it possible to make someone more or less attractive to others via adjustments of hormonal and pheromonal levels through alterations in skin care.

Here, we describe the utilization of an approach that combines metabolomics and microbiome analysis to assess the effect of modifying personal care regime on skin chemistry and microbes. The key findings are as follows: (1) Compounds from beauty products last on the skin for weeks after their first use despite daily showering. (2) Beauty products alter molecular and bacterial diversity as well as the dynamic and structure of molecules and bacteria on the skin. (3) Molecular and bacterial temporal variability is product-, site-, and person-specific, and changes are observed starting the first week of beauty product use. This study provides a framework for future investigations to understand how lifestyle characteristics such as diet, outdoor activities, exercise, and medications shape the molecular and microbial composition of the skin. These factors have been studied far more in their impact on the gut microbiome and chemistry than in the skin. Revealing how such factors can affect skin microbes and their associated metabolites may be essential to define long-term skin health by restoring the appropriate microbes particularly in the context of skin aging [ 61 ] and skin diseases [ 49 ] as has shown to be necessary for amphibian health [ 62 , 63 ], or perhaps even create a precision skin care approach that utilizes the proper care ingredients based on the microbial and chemical signatures that could act as key players in host defense [ 49 , 64 , 65 ].

Subject recruitment and sample collection

Twelve individuals between 25 and 40 years old were recruited to participate in this study, six females and six males. Female volunteer 8 dropped out of the study as she developed a skin irritation during the T1–T3 phase. All volunteers signed a written informed consent in accordance with the sampling procedure approved by the UCSD Institutional Review Board (Approval Number 161730). Volunteers were required to follow specific instructions during 9 weeks. They were asked to bring in samples of their personal care products they used prior to T0 so they could be sampled as well. Following the initial timepoint time 0 and during the first 3 weeks (week 1–week 3), volunteers were asked not to use any beauty products (Fig.  1 b). During the next 3 weeks (week 4–week 6), four selected commercial beauty products provided to all volunteers were applied once a day at specific body part (deodorant for the armpits, soothing foot powder between the toes, sunscreen for the face, and moisturizer for front forearms) (Fig.  1 b, Additional file  3 : Table S2 Ingredient list of beauty products). During the first 6 weeks, volunteers were asked to shower with a head to toe shampoo. During the last 3 weeks (week 7–week 9), all volunteers went back to their normal routine and used the personal care products used before the beginning of the study (Fig.  1 b). Volunteers were asked not to shower the day before sampling. Samples were collected by the same three researchers to ensure consistency in sampling and the area sampled. Researchers examined every subject together and collected metabolomics and microbiome samples from each location together. Samples were collected once a week (from day 0 to day 68—10 timepoints total) for volunteers 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, and 12, and on day 0 and day 6 for volunteer 8. For individuals 4, 9, and 10, samples were collected twice a week. Samples collected for 11 volunteers during 10 timepoints: 11 volunteers × 10 timepoints × 4 samples × 4 body sites = 1760. Samples collected from 3 selected volunteers during 9 additional timepoints: 3 volunteers × 9 timepoints × 4 samples × 4 body sites = 432. All samples were collected following the same protocol described in [ 18 ]. Briefly, samples were collected over an area of 2 × 2 cm, using pre-moistened swabs in 50:50 ethanol/water solution for metabolomics analysis or in Tris-EDTA buffer for 16S rRNA sequencing. Four samples were collected from each body part right and left side. The locations sampled were the face—upper cheek bone and lower jaw, armpit—upper and lower area, arm—front of the elbow (antecubitis) and forearm (antebrachium), and feet—in between the first and second toe and third and fourth toe. Including personal care product references, a total of 2275 samples were collected over 9 weeks and were submitted to both metabolomics and microbial inventories.

Metabolite extraction and UPLC-Q-TOF mass spectrometry analysis

Skin swabs were extracted and analyzed using a previously validated workflow described in [ 18 , 19 ]. All samples were extracted in 200 μl of 50:50 ethanol/water solution for 2 h on ice then overnight at − 20 °C. Swab sample extractions were dried down in a centrifugal evaporator then resuspended by vortexing and sonication in a 100 μl 50:50 ethanol/water solution containing two internal standards (fluconazole 1 μM and amitriptyline 1 μM). The ethanol/water extracts were then analyzed using a previously validated UPLC-MS/MS method [ 18 , 19 ]. We used a ThermoScientific UltiMate 3000 UPLC system for liquid chromatography and a Maxis Q-TOF (Quadrupole-Time-of-Flight) mass spectrometer (Bruker Daltonics), controlled by the Otof Control and Hystar software packages (Bruker Daltonics) and equipped with ESI source. UPLC conditions of analysis are 1.7 μm C18 (50 × 2.1 mm) UHPLC Column (Phenomenex), column temperature 40 °C, flow rate 0.5 ml/min, mobile phase A 98% water/2% acetonitrile/0.1% formic acid ( v / v ), mobile phase B 98% acetonitrile/2% water/0.1% formic acid ( v / v ). A linear gradient was used for the chromatographic separation: 0–2 min 0–20% B, 2–8 min 20–99% B, 8–9 min 99–99% B, 9–10 min 0% B. Full-scan MS spectra ( m/z 80–2000) were acquired in a data-dependant positive ion mode. Instrument parameters were set as follows: nebulizer gas (nitrogen) pressure 2 Bar, capillary voltage 4500 V, ion source temperature 180 °C, dry gas flow 9 l/min, and spectra rate acquisition 10 spectra/s. MS/MS fragmentation of 10 most intense selected ions per spectrum was performed using ramped collision induced dissociation energy, ranged from 10 to 50 eV to get diverse fragmentation patterns. MS/MS active exclusion was set after 4 spectra and released after 30 s.

Mass spectrometry data collected from the skin of 12 individuals can be found here MSV000081582.

LC-MS data processing

LC-MS raw data files were converted to mzXML format using Compass Data analysis software (Bruker Daltonics). MS1 features were selected for all LC-MS datasets collected from the skin of 12 individuals and blank samples (total 2275) using the open-source software MZmine [ 66 ]—see Additional file  4 : Table S3 for parameters. Subsequent blank filtering, total ion current, and internal standard normalization were performed (Additional file  5 : Table S4) for representation of relative abundance of molecular features (Fig.  2 , Additional file  1 : Figure S1), principal coordinate analysis (PCoA) (Fig.  4 ). For steroid compounds in Fig.  5 a–d, bile acids (Additional file  1 : Figure S5A-D), and acylcarnitines (Additional file  1 : Figure S5E, F) compounds, crop filtering feature available in MZmine [ 66 ] was used to identify each feature separately in all LC-MS data collected from the skin of 12 individuals (see Additional file  4 : Table S3 for crop filtering parameters and feature finding in Additional file  6 : Table S5).

Heatmap in Fig.  2 was constructed from the bucket table generated from LC-MS1 features (Additional file  7 : Table S6) and associated metadata (Additional file  8 : Table S7) using the Calour command line available here: https://github.com/biocore/calour . Calour parameters were as follows: normalized read per sample 5000 and cluster feature minimum reads 50. Procrustes and Pearson correlation analyses in Additional file  1 : Figures S10 and S11 were performed using the feature table in Additional file  9 : Table S8, normalized using the probabilistic quotient normalization method [ 67 ].

16S rRNA amplicon sequencing

16S rRNA sequencing was performed following the Earth Microbiome Project protocols [ 68 , 69 ], as described before [ 18 ]. Briefly, DNA was extracted using MoBio PowerMag Soil DNA Isolation Kit and the V4 region of the 16S rRNA gene was amplified using barcoded primers [ 70 ]. PCR was performed in triplicate for each sample, and V4 paired-end sequencing [ 70 ] was performed using Illumina HiSeq (La Jolla, CA). Raw sequence reads were demultiplexed and quality controlled using the defaults, as provided by QIIME 1.9.1 [ 71 ]. The primary OTU table was generated using Qiita ( https://qiita.ucsd.edu/ ), using UCLUST ( https://academic.oup.com/bioinformatics/article/26/19/2460/230188 ) closed-reference OTU picking method against GreenGenes 13.5 database [ 72 ]. Sequences can be found in EBI under accession number EBI: ERP104625 or in Qiita ( qiita.ucsd.edu ) under Study ID 10370. Resulting OTU tables were then rarefied to 10,000 sequences/sample for downstream analyses (Additional file  10 Table S9). See Additional file  11 : Table S10 for read count per sample and Additional file  1 : Figure S13 representing the samples that fall out with rarefaction at 10,000 threshold. The dataset includes 35 blank swab controls and 699 empty controls. The blank samples can be accessed through Qiita ( qiita.ucsd.edu ) as study ID 10370 and in EBI with accession number EBI: ERP104625. Blank samples can be found under the metadata category “sample_type” with the name “empty control” and “Swabblank.” These samples fell below the rarefaction threshold at 10,000 (Additional file  11 : Table S10).

To rule out the possibility that personal care products themselves contained the microbes that induced the changes in the armpit and foot microbiomes that were observed in this study (Fig.  7 ), we subjected the common personal care products that were used in this study during T4–T6 also to 16S rRNA sequencing. The data revealed that within the limit of detectability of the current experiment, few 16S signatures were detected. One notable exception was the most dominant plant-originated bacteria chloroplast detected in the sunscreen lotion applied on the face (Additional file  1 : Figure S9D), that was also detected on the face of individuals and at a lower level on their arms, sites where stable microbial communities were observed over time (Additional file  1 : Figure S9E, F). This finding is in agreement with our previous data from the 3D cartographical skin maps that revealed the presence of co-localized chloroplast and lotion molecules [ 18 ]. Other low-abundant microbial signatures found in the sunscreen lotion include additional plant-associated bacteria: mitochondria [ 73 ], Bacillaceae [ 74 , 75 ], Planococcaceae [ 76 ], and Ruminococcaceae family [ 77 ], but all these bacteria are not responsible for microbial changes associated to beauty product use, as they were poorly detected in the armpits and feet (Fig.  7 ).

To assess the origin of Cyanobacteria detected in skin samples, each Greengenes [ 72 ] 13_8 97% OTU table (per lane; obtained from Qiita [ 78 ] study 10,370) was filtered to only features with a p__Cyanobacteria phylum. The OTU maps for these tables—which relate each raw sequence to an OTU ID—were then filtered to only those observed p__Cyanobacteria OTU IDs. The filtered OTU map was used to extract the raw sequences into a single file. Separately, the unaligned Greengenes 13_8 99% representative sequences were filtered into two sets, first the set of representatives associated with c__Chloroplast (our interest database), and second the set of sequences associated with p__Cyanobacteria without the c__Chloroplast sequences (our background database). Platypus Conquistador [ 79 ] was then used to determine what reads were observed exclusively in the interest database and not in the background database. Of the 4,926,465 raw sequences associated with a p__Cyanobacteria classification (out of 318,686,615 total sequences), at the 95% sequence identity level with 100% alignment, 4,860,258 sequences exclusively recruit to full-length chloroplast 16S by BLAST [ 80 ] with the bulk recruiting to streptophytes (with Chlorophyta and Stramenopiles to a lesser extent). These sequences do not recruit non-chloroplast Cyanobacteria full length 16S.

Half-life calculation for metabolomics data

In order to estimate the biological half-life of molecules detected in the skin, the first four timepoints of the study (T0, T1, T2, T3) were considered for the calculation to allow the monitoring of personal beauty products used at T0. The IUPAC’s definition of biological half-life as the time required to a substance in a biological system to be reduced to half of its value, assuming an approximately exponential removal [ 81 ] was used. The exponential removal can be described as C ( t )  =  C 0 e − tλ where t represents the time in weeks, C 0 represents the initial concentration of the molecule, C ( t ) represents the concentration of the molecule at time t , and λ is the rate of removal [ http://onlinelibrary.wiley.com/doi/10.1002/9780470140451.ch2/summary ]. The parameter λ was estimated by a mixed linear effects model in order to account for the paired sample structure. The regression model tests the null hypothesis that λ is equal to zero and only the significant ( p value < 0.05) parameters were considered.

Principal coordinate analysis

We performed principal coordinate analysis (PCoA) on both metabolomics and microbiome data. For metabolomics, we used MS1 features (Additional file  5 : Table S4) and calculated Bray–Curtis dissimilarity metric using ClusterApp ( https://github.com/mwang87/q2_metabolomics ).

For microbiome data, we used rarefied OTU table (Additional file 10 : Table S9) and used unweighted UniFrac metric [ 36 ] to calculate beta diversity distance matrix using QIIME2 (https://qiime2.org). Results from both data sources were visualized using Emperor ( https://biocore.github.io/emperor/ ) [ 28 ].

Molecular networking

Molecular networking was generated from LC-MS/MS data collected from skin samples of 11 individuals MSV000081582, using the Global Natural Products Social Molecular Networking platform (GNPS) [ 29 ]. Molecular network parameters for MS/MS data collected from all body parts of 11 individuals during T0–T9 MSV000081582 are accessible here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=284fc383e4c44c4db48912f01905f9c5 . Molecular network parameters for MS/MS data collected from armpits T0–T3 MSV000081582 and deodorant used by individual 1 and 3 MSV000081580 can be found here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=f5325c3b278a46b29e8860ec57915ad and here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=aaa1af68099d4c1a87e9a09f398fe253 , respectively. Molecular networks were exported and visualized in Cytoscape 3.4.0. [ 82 ]. Molecular networking parameters were set as follows: parent mass tolerance 1 Da, MS/MS fragment ion tolerance 0.5 Da, and cosine threshold 0.65 or greater, and only MS/MS spectral pairs with at least 4 matched fragment ions were included. Each MS/MS spectrum was only allowed to connect to its top 10 scoring matches, resulting in a maximum of 10 connections per node. The maximum size of connected components allowed in the network was 600, and the minimum number of spectra required in a cluster was 3. Venn diagrams were generated from Cytoscape data http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=284fc383e4c44c4db48912f01905f9c5 using Cytoscape [ 82 ] Venn diagram app available here http://apps.cytoscape.org/apps/all .

Shannon molecular and bacterial diversity

The diversity analysis was performed separately for 16S rRNA data and LC-MS data. For each sample in each feature table (LC-MS data and microbiome data), we calculated the value of the Shannon diversity index. For LC-MS data, we used the full MZmine feature table (Additional file  5 : Table S4). For microbiome data, we used the closed-reference BIOM table rarefied to 10,000 sequences/sample. For diversity changes between timepoints, we aggregated Shannon diversity values across groups of individuals (all, females, males) and calculated mean values and standard errors. All successfully processed samples (detected features in LC-MS or successful sequencing with 10,000 or more sequences/sample) were considered.

Beauty products and chemical standards

Samples (10 mg) from personal care products used during T0 and T7–T9 MSV000081580 (Additional file  2 : Table S1) and common beauty products used during T4–T6 MSV000081581 (Additional file  3 : Table S2) were extracted in 1 ml 50:50 ethanol/water. Sample extractions were subjected to the same UPLC-Q-TOF MS method used to analyze skin samples and described above in the section “ Metabolite extraction and UPLC-Q-TOF mass spectrometry analysis .” Authentic chemical standards MSV000081583 including 1-dehydroandrostenedion (5 μM), chenodeoxyglycocholic acid (5 μM), dehydroisoandrosterone sulfate (100 μM), glycocholic acid (5 μM), and taurocholic acid (5 μM) were analyzed using the same mass spectrometry workflow used to run skin and beauty product samples.

Monitoring beauty product ingredients in skin samples

In order to monitor beauty product ingredients used during T4–T6, we selected only molecular features present in each beauty product sample (antiperspirant, facial lotion, body moisturizer, soothing powder) and then filtered the aligned MZmine feature table (Additional file  5 : Table S4) for the specific feature in specific body part samples. After feature filtering, we selected all features that had a higher average intensity on beauty product phase (T4–T6) compared to non-beauty product phase (T1–T3). The selected features were annotated using GNPS dereplication output http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=69319caf219642a5a6748a3aba8914df , plotted using R package ggplot2 ( https://cran.r-project.org/web/packages/ggplot2/index.html ) and visually inspected for meaningful patterns.

Random forest analysis

Random forest analysis was performed in MetaboAnalyst 3.0 online platform http://www.metaboanalyst.ca/faces/home.xhtml . Using LC-MS1 features found in armpit samples collected on T3 and T6. Random forest parameters were set as follows: top 1000 most abundant features, number of predictors to try for each node 7, estimate of error rate (0.0%).

BugBase analysis

To determine the functional potential of microbial communities within our samples, we used BugBase [ 83 ]. Because we do not have direct access to all of the gene information due to the use of 16S rRNA marker gene sequencing, we can only rely on phylogenetic information inferred from OTUs. BugBase takes advantage of this information to predict microbial phenotypes by associating OTUs with gene content using PICRUSt [ 84 ]. Thus, using BugBase, we can predict such phenotypes as Gram staining, or oxidative stress tolerance at each timepoint or each phase. All statistical analyses in BugBase are performed using non-parametric differentiation tests (Mann–Whitney U ).

Taxonomic plots

Rarefied OTU counts were collapsed according to the OTU’s assigned family and genus name per sample, with a single exception for the class of chloroplasts. Relative abundances of each family-genus group are obtained by dividing by overall reads per sample, i.e., 10,000. Samples are grouped by volunteer, body site, and time/phase. Abundances are aggregated by taking the mean overall samples, and resulting abundances are again normalized to add up to 1. Low-abundant taxa are not listed in the legend and plotted in grayscale. Open-source code is available at https://github.com/sjanssen2/ggmap/blob/master/ggmap/snippets.py

Dissimilarity-based analysis

Pairwise dissimilarity matrices were generated for metabolomics and 16S metagenomics quantification tables, described above, using Bray–Curtis dissimilarity through QIIME 1.9.1 [ 71 ]. Those distance matrices were used to perform Procrustes analysis (QIIME 1.9.1), and Mantel test (scikit-bio version 0.5.1) to measure the correlation between the metabolome and microbiome over time. The metabolomics dissimilarities were used to perform the PERMANOVA test to assess the significance of body part grouping. The PCoA and Procrustes plots were visualized in EMPeror. The dissimilarity matrices were also used to perform distance tests, comparing the distances within and between individuals and distances from time 0 to times 1, 2, and 3 using Wilcoxon rank-sum tests (SciPy version 0.19.1) [ 19 ].

Statistical analysis for molecular and microbial data

Statistical analyses were performed in R and Python (R Core Team 2018). Monotonic relationships between two variables were tested using non-parametric Spearman correlation tests. The p values for correlation significance were subsequently corrected using Benjamini and Hochberg false discovery rate control method. The relationship between two groups was tested using non-parametric Wilcoxon rank-sum tests. The relationship between multiple groups was tested using non-parametric Kruskal–Wallis test. The significance level was set to 5%, unless otherwise mentioned, and all tests were performed as two-sided tests.

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Acknowledgements

We thank all volunteers who were recruited in this study for their participation and Carla Porto for discussions regarding beauty products selected in this study. We further acknowledge Bruker for the support of the shared instrumentation infrastructure that enabled this work.

This work was partially supported by US National Institutes of Health (NIH) Grant. P.C.D. acknowledges funding from the European Union’s Horizon 2020 Programme (Grant 634402). A.B was supported by the National Institute of Justice Award 2015-DN-BX-K047. C.C. was supported by a fellowship of the Belgian American Educational Foundation and the Research Foundation Flanders. L.Z., J.K, and K.Z. acknowledge funding from the US National Institutes of Health under Grant No. AR071731. TLK was supported by Vaadia-BARD Postdoctoral Fellowship Award No. FI-494-13.

Availability of data and materials

The mass spectrometry data have been deposited in the MassIVE database (MSV000081582, MSV000081580 and MSV000081581). Molecular network parameters for MS/MS data collected from all body parts of 11 individuals during T0-T9 MSV000081582 are accessible here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=284fc383e4c44c4db48912f01905f9c5 . Molecular network parameters for MS/MS data collected from armpits T0–T3 MSV000081582 and deodorant used by individual 1 and 3 MSV000081580 can be found here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=f5325c3b278a46b29e8860ec5791d5ad and here http://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=aaa1af68099d4c1a87e9a09f398fe253 , respectively. OTU tables can be found in Qiita ( qiita.ucsd.edu ) as study ID 10370, and sequences can be found in EBI under accession number EBI: ERP104625.

Author information

Amina Bouslimani and Ricardo da Silva contributed equally to this work.

Authors and Affiliations

Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, USA

Amina Bouslimani, Ricardo da Silva, Kathleen Dorrestein, Alexey V. Melnik, Tal Luzzatto-Knaan & Pieter C. Dorrestein

Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92037, USA

Tomasz Kosciolek, Stefan Janssen, Chris Callewaert, Amnon Amir, Livia S. Zaramela, Ji-Nu Kim, Gregory Humphrey, Tara Schwartz, Karenina Sanders, Caitriona Brennan, Gail Ackermann, Daniel McDonald, Karsten Zengler, Rob Knight & Pieter C. Dorrestein

Department for Pediatric Oncology, Hematology and Clinical Immunology, University Children’s Hospital, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

Stefan Janssen

Center for Microbial Ecology and Technology, Ghent University, 9000, Ghent, Belgium

Chris Callewaert

Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, 92307, USA

Karsten Zengler, Rob Knight & Pieter C. Dorrestein

Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA

Karsten Zengler & Rob Knight

Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, 92093, USA

Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92037, USA

Pieter C. Dorrestein

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Contributions

AB and PCD contributed to the study and experimental design. AB, KD, and TLK contributed to the metabolite and microbial sample collection. AB contributed to the mass spectrometry data collection. AB, RS, and AVM contributed to the mass spectrometry data analysis. RS contributed to the metabolomics statistical analysis and microbial–molecular correlations. GH, TS, KS, and CB contributed to the 16S rRNA sequencing. AB and GA contributed to the metadata organization. TK, SJ, CC, AA, and DMD contributed to the microbial data analysis and statistics. LZ, JK, and KZ contributed to the additional data analysis. AB, PCD, and RK wrote the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Rob Knight or Pieter C. Dorrestein .

Ethics declarations

Ethics approval and consent to participate.

All participants signed a written informed consent in accordance with the sampling procedure approved by the UCSD Institutional Review Board (Approval Number 161730).

Competing interests

Dorrestein is on the advisory board for SIRENAS, a company that aims to find therapeutics from ocean environments. There is no overlap between this research and the company. The other authors declare that they have no competing interests.

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Additional files

Additional file 1:.

Figure S1. Beauty products ingredients persist on skin of participants. Figure S2. Beauty product application impacts the molecular and bacterial diversity on skin of 11 individuals while the chemical diversity from personal beauty products used by males and females on T0 is similar. Figure S3. Longitudinal impact of ceasing and resuming the use of beauty products on the molecular composition of the skin over time. Figure S4. Molecular networking to highlight MS/MS spectra found in each body part. Figure S5. Longitudinal abundance of bile acids and acylcarnitines in skin samples. Figure S6. Characterization of steroids in armpits samples. Figure S7. Characterization of bile acids in armpit samples. Figure S8. Characterization of Acylcarnitine family members in skin samples. Figure S9. Beauty products applied at one body part might affect other areas of the body, while specific products determine stability versus variability of microflora at each body site. Figure S10. Representation of Gram-positive bacteria over time and the molecular features from the shampoo detected on feet. Figure S11. Procrustes analysis to correlate the skin microbiome and metabolome over time. Figure S12. Correlation between specific molecules and bacteria that change over time in armpits of individual 11. Figure S13. Representation of the number of samples that were removed (gray) and those retained (blue) after rarefaction at 10,000 threshold. (DOCX 1140 kb)

Additional file 2:

Table S1. List of personal (T0 and T7–9) beauty products and their frequency of use. (XLSX 30 kb)

Additional file 3:

Table S2. List of ingredients of common beauty products used during T4–T6. (PDF 207 kb)

Additional file 4:

Table S3. Mzmine feature finding and crop filtering parameters. (XLSX 4 kb)

Additional file 5:

Table S4. Feature table for statistical analysis with blank filtering and total ion current normalization. (CSV 150242 kb)

Additional file 6:

Table S5. Feature table for individual feature abundance in armpits. (XLSX 379 kb)

Additional file 7:

Table S6. Feature table for Calour analysis. (CSV 91651 kb)

Additional file 8:

Table S7. Metadata for Calour analysis. (TXT 129 kb)

Additional file 9:

Table S8. feature table with Probabilistic quotient normalization for molecular–microbial analysis. (ZIP 29557 kb)

Additional file 10:

Table S9. OTU table rarefied to 10,000 sequences per sample. (BIOM 9493 kb)

Additional file 11:

Table S10. 16S rRNA sequencing read counts per sample. (TSV 2949 kb)

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Bouslimani, A., da Silva, R., Kosciolek, T. et al. The impact of skin care products on skin chemistry and microbiome dynamics. BMC Biol 17 , 47 (2019). https://doi.org/10.1186/s12915-019-0660-6

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A long quest to improve the complexion of skin

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Autophagy, depicted in this illustration, is the body’s natural process for eliminating dysfunctional cells, and plays a role in controlling compounds called AGEs that affect the appearance of skin. Credit: getty

The skin is our largest organ. So, when it comes to ageing, it stands to reason that skin shows some of the most visible signs, such as loss of brightness. But what precisely happens to it throughout our lives is an intricate process, intriguing many researchers, such as Denny Deng.

As the skin research and clinical principal scientist at the Procter & Gamble (P&G) Singapore Innovation Center, Deng leads a team researching the fundamentals of skin science and skincare technologies in Asia. “We have to identify the underlying problems and causes first before attempting to solve them,” he says.

In 2006, Olay, part of P&G, launched the China Decades Longitudinal (CDL) study to gain an in-depth understanding of how women’s skin changes over time. As one of the first comprehensive long-term studies of this kind in China, it tracked changes, over 10 years, in healthy women of various age groups, aiming to reveal the patterns and factors behind skin changes.

Longitudinal power

“We initially designed a cross-sectional study of a large population of healthy Chinese women and children, all aged between 10 and 70,” says Deng, “Although large population surveys can provide a general relationship between skin features and age, we realised that the variations of individual skin remain poorly understood.”

Deng’s many years of clinical experience guided him in swiftly making a decision to switch strategy. “Longitudinal studies can effectively and faithfully uncover patterns and trends across time, revealing the true factors behind ageing. They are more powerful than cross-sectional studies which only look at data at a single point in time, but are much more challenging, complicated, expensive, and time-consuming,” explains Deng.

Denny Deng, skin research and clinical principal scientist at P&G Singapore Innovation Center. Credit: P&G

Deng led a team of 16 scientists to design and carry out the study. A total of 452 Chinese women and children were recruited in November 2006. Their facial images were taken and the scientists also measured factors including skin tone, pH, hydration, sebum, elasticity and the level of passive evaporation of water through the skin, which is an indicator of how effective the skin is as a barrier to prevent dehydration.

Ten years later, 185 of the participants rejoined the study and returned to be re-assessed, including 23 mother-daughter pairs. In addition to the images and biometric measurements as in 2006, questionnaires were also used to capture details of the women’s lives over the previous decade. The team also introduced in-vivo measurements and grading methods, resulting in enormous quantities of data.

Deng and colleagues used all of this information to try to answer some of the nagging questions researchers have had about the causes of skin changes. “To make sure the findings are valid, we had a clear focus on skin appearance, especially tone, but did not make any presumptions. The data should shed light on what the real issues are,” says Deng.

His team has attempted to reveal patterns in changes to complexion that Chinese women experience over time, hoping to identify the factors behind the changes.

The team has also studied the influence of environmental and lifestyle factors, hoping to confirm that what people often regard as undesirable changes to their skin can be reversed. The study and part of the results were reported at the 24th World Congress of Dermatology, Milan, held in Italy in 2019, and Deng says publication of the full results is pending.

Behind the changes

After identifying patterns of changes to complexion, the next question for the scientists has been: what could be the underlying reasons for these changes? The CDL study has acted as a launching point for additional Olay research looking at causes behind and potential solutions to skin changes.

For one study published in 2020, P&G collaborated with the Shanghai Skin Disease Hospital to look into an undesirable process in the epidermis called glycation, whereby excess glucose adheres to fibres of collagen and elastin 1 . The scientists showed in an ex vivo model that glycation is an important factor contributing to changes to complexion and loss of brightness.

For the study, the team collected and analysed facial biopsies from Chinese women aged 20–50. They noticed an accumulation of ‘advanced glycation end products’ (AGEs) in the epidermal samples among females even in their twenties. AGEs are compounds generated in the late stages of the glycation process. They can impact cellular homoeostasis and protein structure, leading to numerous changes in the skin.

Previous research from another team discovered that AGEs accumulate with time. In the 2020 study, Deng and scientists identified that higher AGEs levels were found in participants whose skin appeared less bright.

“Screening for and developing formulations that can improve skin dullness and reverse changes to complexion caused by glycation has become our top priority,” Deng says.

In their study, he and his colleagues hypothesized that AGEs might be removed through the activation of autophagy, a process through which the body destroys dysfunctional cells. After screening different substances for ones that can promote autophagy, they demonstrated in vitro that treating cultured keratinocytes — a primary cell type within the epidermis — with an extract from water lilies and a chemical called sucrose dilaurate, could induce autophagy and reduce cellular markers of AGEs.

The future is bright

The glycation findings have now been translated into new skincare ingredients and product formulations that the scientists say have the potential to improve complexion.

“As a result of this discovery, we have updated the formulation of our skin technologies. A water lily extract called Glycoxyl has been added to the classic ingredient nicotinamide in Olay’s skincare products,” says Deng. Nicotinamide has also been observed to have anti-glycation effect in another study 2 .

P&G started its Olay-related research and development centre in China in 1998 and is committed to science-based skincare research and development.

P&G started its Olay-related research and development centre, pictured here, in China in 1998. Credit: P&G

For Deng, product development is driven by data and evidence. It was the CDL study that enabled Olay to break new ground in finding solutions to help maintain the fresh appearance of skin — instead of focusing on suppressing other compounds, the scientists and product developers now focus on anti-glycation to slow the changing process and maintain complexion.

“We are looking forward to transforming the newest science into real results, testing ingredients and developing quality skincare products for Chinese women,” says Deng.

For more information about skincare technologies at P&G, please visit its official website: www.pg.com.cn

Laughlin, T. et al. JEADV 2020, 34 (Suppl. 3), 12–18

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The science behind skin care: Moisturizers

Affiliation.

• 1 Dermatology Consulting Services, PLLC, High Point, NC, USA.
• PMID: 29319217
• DOI: 10.1111/jocd.12490

Moisturizers provide functional skin benefits, such as making the skin smooth and soft, increasing skin hydration, and improving skin optical characteristics; however, moisturizers also function as vehicles to deliver ingredients to the skin. These ingredients may be vitamins, botanical antioxidants, peptides, skin-lightening agents, botanical anti-inflammatories, or exfoliants. This discussion covers the science of moisturizers.

Keywords: active cosmetics; botanicals; moisturizer; serums; skin creams; transepidermal water loss.

© 2018 Wiley Periodicals, Inc.

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Maybe She’s Born With It. Maybe It’s Neurocosmetics.

Skin care is coming for your brain.

For just $65, the skin-care company Selfmade will sell you a kit that will purportedly help you feel more stable and confident in your relationships—and get better skin all the while. According to the kit’s marketing copy, it comes with a serum that enhances “safety and comfort with self,” a moisturizer that “promotes awareness that past negative experience and emotional states can carry throughout your life,” and the best-selling relationship-psychology book Attached . Together, the “Securely Attached Kit” is a “ritual” that promises to reframe your attitudes to both your skin and self. It’s cheaper and arguably less involved than therapy.

The Securely Attached Kit is part of a new generation of “neurocosmetics” that blur the rhetoric of beauty, brain science, and mental health. “It's the era of the ‘neuro,’” says Amina Mire, a sociologist at Carleton University who studies cultural messaging surrounding women’s aging and wellness. Americans have long equated skin care with self-care, but the rise of neurocosmetics marks a new escalation in the industry’s messaging: Slather our product on your skin, and it will change your brain chemistry for the better. Or, as a recent blog post by the founder of Murad declared, “ Skincare = brain care .”

Such messaging draws from the established principle that the well-being of the skin and brain are interlinked. Certain aspects of so-called psychodermatology are well supported by research. For example, some skin conditions have psychiatric components and vice versa, says Mohammad Jafferany, a psychiatry professor at Central Michigan University. Acne and psoriasis can flare with stress—and they can in turn exacerbate poor mental health by lowering self-esteem. Psychological treatments such as cognitive behavioral therapy may improve certain skin conditions, including atopic dermatitis and psoriasis.

But acknowledging the link between mental and dermatological health is an entirely different prospect from claiming (or implying) that the active ingredients in some skin-care products can act directly on the nervous system. A “serotoner” by CAP Beauty, for example, touts its inclusion of griffonia, a plant whose seeds contain the molecule 5-HTP, a chemical precursor to serotonin, to encourage “happier, healthier and more joyful looking skin.” Balms by NEUR|AÉ, a brand under the Sisley group that professes to be “elevated by neuroscience,” combine “neuro-ingredients, neuro-fragrances and neuro-textures” to glaze users with feelings like harmony and serenity. A brand called Justhuman says its ingredients are formulated to control inflammation in the skin by stimulating the production of neuropeptides, chemical messengers that neurons use to signal one another.

Read: How skin care became an at-home science experiment

Both Justhuman and Selfmade say their ingredients stimulate beta-endorphins, a type of neuropeptide, to counteract the stress hormone cortisol and relax or rebalance the skin. Beta-endorphins are natural painkillers, mood enhancers, and mood stabilizers. There’s some early evidence that ingesting certain plant extracts or smelling some essential oils stimulates the body to produce beta-endorphins, Angela Lamb, an associate dermatology professor at the Icahn School of Medicine at Mount Sinai, told me. Similarly, 5-HTP supplements taken orally can boost serotonin production. But to Lamb’s knowledge, no double-blind placebo studies have shown that any substance applied topically will boost beta-endorphin or serotonin production, either locally in people’s skin or throughout the nervous system broadly.

Instead, much of the research on these ingredients has been performed on animals or cell cultures. In an emailed statement, NEUR|AÉ’s director of research, Jose Ginestar, wrote that the company’s plant extracts are tested for efficacy on cell cultures to see how they modulate excess cortisol or boost endorphins. A representative for Selfmade said in a statement that the company drew on existing cell-culture studies when formulating its products, and has conducted studies via a third party on how its products affect users. (CAP declined to provide any information about its products.) Kelly Dobos, a cosmetic chemist, told me that broad conclusions drawn from cell-culture studies can be misleading. For one thing, applying a substance directly to a cell is different from applying it to the skin, an organ that has evolved, in part, to resist penetration. Plus, Dobos said, researchers typically apply high concentrations of a single ingredient to cell cultures instead of testing a product in its complete formulation, or at realistic levels.

None of this is to say that skin-care products can’t affect the mental health of people who use them. But they’re almost certainly acting less directly than their labels might imply. If, say, the embarrassment of cystic acne weighs on your self-esteem, clearing your skin might have wonderful mood-boosting effects. Tara Well, a psychologist at Barnard College and the author of Mirror Meditation: The Power of Neuroscience and Self-Reflection to Overcome Self-Criticism, Gain Confidence, and See Yourself With Compassion , told me that applying products to your skin can also simply feel good. Some evidence suggests that soothing self-touch can lower physiological signs of stress . By repeating a morning or evening skin-care routine, enjoying the sensations and smells of various creams and getting your “me time,” you might also teach yourself to associate that routine and those products with an elevated mood, Well said.

Read: The real reason eye cream is so expensive

Psychologists even recommend lotion as a short-term coping mechanism for teens seeking mental-health treatment, Janet Lydecker, a psychiatrist at Yale School of Medicine, told me. Certain smells, such as lavender and rosemary, can have a calming effect, and self-soothing by feeling the texture of the lotion can also be grounding, Lydecker said. “If patients are in their head, preoccupied, ruminating on something that’s causing distress, it’s such a tangible way to cope,” she told me. But such effects have little to do with the chemical makeup of the lotion, and are definitely not meant to act as stand-alone, long-term interventions for poor mental health.

Stephanie Lee, the CEO and founder of Selfmade, insisted in an interview that her products’ formulas are boons to mental health. She acknowledged that a moisturizer alone won’t result in big, lasting psychological changes, but she nevertheless argued that the company’s products could have a role in helping young buyers cope with issues of anxiety and low self-worth, especially in the midst of America’s teen-mental-health crisis. The mission of Selfmade, Lee told me, is to teach young folks how to “use skin as data for what might be happening in our minds”—in other words, to look to their skin as a sign of, and potential solution to, inner turmoil.

Some experts argue that conflating skin care and mental health will only further stigmatize wrinkles, pimples, and other perceived flaws. “Any time that we entangle appearance with morality, then people who don’t look as good are judged for that in ways that are fundamentally unfair and problematic,” Kjerstin Gruys, a sociologist at the University of San Francisco, told me. If having good skin and good mental health is a matter of buying a $65 skin-care kit, then not having both, or either, must be your own fault.

Read: The best skin-care trick is being rich

Several decades ago, when wellness movements began to enter the mainstream and serious academics were debunking ill-advised health fads, the beauty industry embraced the practice of marketing products as “cosmeceuticals,” a blend of cosmetics and pharmaceuticals , to imply medicinal properties. Similar terms such as nutraceuticals and phytoceuticals followed. It’s all too fitting that “neuro” cosmetics have taken over at a time when having a therapist, setting boundaries, and being fluent in therapy-speak have become markers of good health and character. The beauty industry has always named its products to evoke aspirations that go beyond the cosmetic, Lee told me. And so far, it’s worked. After all, Lee said, “self-actualization sells.”

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Whether through injury or simple wear and tear, the skin’s integrity and function can be easily compromised. Although this impacts billions of people worldwide, little is known about how to prevent skin degeneration.

The Harvard Stem Cell Institute (HSCI) Skin Program is committed to understanding why skin sometimes fails to heal or forms scars, as well as why skin inevitably becomes thin, fragile, and wrinkled with age. The Skin Program’s ultimate goal is to identify new therapies for skin regeneration and rejuvenation.

How We Heal

Wound healing is a major problem for many older individuals. Furthermore, chronic, non-healing skin ulcers are a major source of health care costs and patient morbidity and mortality.

Human skin repairs itself slowly, via the formation of contractile scars which may cause dysfunction. In contrast, the axolotl salamander can readily regrow a severed limb, the spiny mouse has densely haired skin that heals with remarkable speed, and the skin of the growing human embryo can regenerate after trauma without the need for any scar formation. By studying these examples, scientists are finding clues for how to enhance skin healing through a more regenerative response.

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During normal wound healing, scars form from dermal cells that align in parallel. But when this alignment is disrupted by a biodegradable scaffold that directs cells to grow in a random orientation, the cells follow the diverse differentiation program necessary for true regeneration.

HSCI scientists have also identified biomarkers for the key cells involved in skin regeneration, and are developing therapeutic strategies for their enrichment and activation. Ongoing clinical trials are using skin stem cells to treat chronic, non-healing ulcers, and early results are promising.

Additional approaches include 3D bioprinting, where skin stem cells are layered into a complex structure that mimics skin and could be potentially used for transplantation.       

Beyond Wound Healing

Skin aging can be thought of as a form of wounding, in which stem cells no longer maintain normal skin thickness, strength, function, and hair density. Understanding how to harness stem cells for scarless wound healing will also provide key insights into regenerating aged skin, a process termed rejuvenation. Multidisciplinary collaborators in the HSCI Skin Program are investigating the biological basis for how the skin ages over time and when exposed to ultraviolet radiation.

In addition to aging, skin stem cells also may mistake normal regions of the skin as wounds, then erroneously attempt to fill them. HSCI investigators are exploring whether this may be one of the underpinnings of psoriasis, a common and devastating disorder.

These areas of investigation are just the beginning. Skin stem cell biology has the potential to provide key insights into the mechanisms of regeneration for other organs in the body.

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Everyday care, darker skin tones, cosmetic treatments, public health programs, find a dermatologist.

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Both the CDC and the FDA warn against treating this common childhood condition on your own with non-prescription treatments. See what they recommend.

Find answers to questions patients ask about this newer treatment option, including, “What’s involved in switching from a biologic to a biosimilar?”

Everyone's at risk for skin cancer. These dermatologists' tips tell you how to protect your skin.

Find out what may be causing the itch and what can bring relief.

Find out why dark spots appear and what can fade them.

If you have what feels like razor bumps or acne on the back of your neck or scalp, you may have acne keloidalis nuchae. Find out what can help.

You can expect permanent results in all but one area. Do you know which one?

If you want to diminish a noticeable scar, know these 10 things before having laser treatment.

It can smooth out deep wrinkles and lines, but the results aren’t permanent. Here’s how long botox tends to last.

Use these professionally produced online infographics, posters, and videos to help others find and prevent skin cancer.

Free to everyone, these materials teach young people about common skin conditions, which can prevent misunderstanding and bullying.

You can search by location, condition, and procedure to find the dermatologist that’s right for you.

A dermatologist is a medical doctor who specializes in treating the skin, hair, and nails. Dermatologists care for people of all ages.

How you care for your skin can greatly affect your appearance. Here you’ll find the everyday care that dermatologists recommend.

Global / English

• Research on Skin Care Linked with Emotions

“Being in love makes you more beautiful” is a well-known phrase used throughout the world. The good effects of positive emotions, such as happiness and satisfaction, on skin condition is well understood, though scientific evidence is scarce. Based on a hypothesis that the “mind” and “skin condition” are linked, Kao research staff members in the fields of formulation development, skin science, and sensory science performed a cooperative study. Those scientific results indicate that “skin condition improves when skin care generates a positive frame of mind”. Previously, we found that emotions experienced while performing skin care are greatly affected by the sense of touch. Therefore, we first identified cream textures related to positive emotions. Various sensations revealed by touch that enhance positive emotions were investigated, with “richness”, “blends well into skin”, and “moist texture” found to be especially important. These findings were confirmed not only by subjective questionnaire answers, but also from cerebral blood flow measurements showing that positive emotions increased when skin cream designed to enhance those three touch sensations was applied (Fig. 1). Furthermore, experiments were performed to study the effects of emotions on skin appearance by use of this cream. After applying the cream at home for 4 weeks, participants in the positive emotions high-score group demonstrated greater improvements in skin appearance as compared to the relatively low-score group (Fig. 2). Based on these findings, it is considered that positive emotions developed during skin care have effects to produce better skin conditions. Previously, the effect of skin care has been discussed only based on the function of active ingredients and formulation technology. The present novel findings suggest that an approach that focuses on emotions might be useful for developing skin care cosmetics that lead to beautiful skin (Fig. 3). Kao will continue to develop new products and approaches focusing on pleasurable skin care time as well as function.

Related Actions and Goals

Kao’s ESG Strategy Kirei Lifestyle Plan

• Moisture Retention Inspired by the Skin’s Natural Mechanisms
• Gentle Yet Effective Cleansing Technology
• Unique Anti-Aging Technology Grounded in Essential Skin Science
• A Holistic Care Approach to Skin Research: Targeting Vascular Reactivity
• Microencapsulation and Its Application in Sunscreens
• Seeing Inside the Face: Imaging Sebaceous Glands with Ultrasound Tomography
• Research & Development
• Product Development Research

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The skin care craze among teen and tweens has dermatologists wary

Maria Godoy

Teens and tweens are becoming major consumers of skin care products, fueled by social media influencers and their elaborate beauty routines. Are these products safe for younger kids?

Copyright © 2024 NPR. All rights reserved. Visit our website terms of use and permissions pages at www.npr.org for further information.

NPR transcripts are created on a rush deadline by an NPR contractor. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.

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Just wanted to say how much I love Epionce. I have never felt good about my skin, and have never tried products that actually did what they promised. It’s always been a struggle dealing with congested, clogged pores... When a dermatologist suggested products from Epionce, it totally changed the game. I love the Lytic Gel Cleanser, the Lytic TX, and the Renewal Lite Facial Lotion. These products have changed my oily, congested skin into a glowy, clear complexion. I have stopped skin picking altogether because my skin is so clear there’s nothing to pick! Thank you for exceptional, life-changing products. I’m so happy I found Epionce.

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I found Epionce...and my life was changed. My skin went from feeling hard and quite frankly stressed from breakouts between the harsh chemical components and the humidity here, to soft, stunning and thriving! My skin feels alive and well, [and] I would never again put all those harsh chemicals on my skin, especially knowing now how healthy my skin is thanks to Epionce! I wish I could sell this product to every beautiful face I see! Everyone needs these products in their life for skin success!

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I have been a fan of Epionce products from Day 1. I [have used] the Intense Defense Serum + Lytic Tx + Renewal for my skin type [for the] last 3 years and I look 20 years younger than my age. That's the secret of my youthfulness that I share with people. Epionce really works!

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I never knew my skin needed help until I began using Epionce. It took a turn for the better when I didn't even know I needed it! Thank you!

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Hands down the best products I've ever used. I tell all my friends & family about Epionce.

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I have struggled with my skin since my teenage years. After going on Accutane twice in undergrad, in my late 20s my skin was relatively breakout free, but rough, uneven and dull. Since high school, I’ve always used moderately priced “quality” skincare products so I wasn’t sure why now, in my late 20s, my skin now seemed so flawed. I [was] recommended the Intense Defense Serum and Lytic Tx. I walked out with both and it has transformed my skin in just weeks. I’m radiant with minimal makeup, and my face feels so soft and smooth.

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I have used Epionce for 4 years now. It's changed the texture of my skin.

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Heather G. - Florida

I've been using your [Renewal Facial Lotion] for about 8 months now and it's the best!! I have a sensitive skin and it's the one lotion that I've used that does not dull my skin or give me a fine mist of rash. Thank you for a great product.

I have problem skin. With my current regimen of Milky Lotion Cleanser and Intensive Nourishing Cream, my skin feels better than it has since puberty.

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I have been using the [Epionce] line for over two years now and will not carry any other line in my spa! I love the science behind it!

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I have oily/sensitive skin and the Renewal Lite [Facial Lotion] and Lytic Gel Cleanser alone have changed my face.

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I absolutely love this [Renewal] Calming Cream! I suffer from [dry skin] and compared to other products I have used, this cream delivers the perfect amount of hydration for my sensitive skin. I was very surprised and happy to see how quickly my skin has improved after using this cream in such a short amount of time. The formulation is so gentle I have also used it on my face. I feel the cream has worked wonders on my skin by providing an amazing protective barrier against hydration loss which has helped minimize flareups. My skin always feels great! This has become a go to product for myself and my children.

I have used several Epionce products over the years . . . the Renewal Calming Cream is one of my favorite Epionce products. This product is very rich and creamy . . . and it feels so good on the skin. It doesn’t leave a greasy feeling and I am able to wear it under my makeup. I have very sensitive skin and this product soothes my skin and helps with the sensitivity. I actually look forward to applying it every day.

I have very dry skin. I could not believe how great my skin felt and looked after using Epionce Enriched Body Cream for a short time! I LOVE this product!

Patty - Minneapolis, MN

The Epionce Renewal[s] have changed my skin as well as my clients. I can't keep them on the shelf.

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I have been using Epionce for two years and noticed a complete change in my skin in my 50s. People ask me all the time what I use on my skin.

Julie L. - Minneapolis, MN

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I have been using Intense Defense Serum and I love it. It has rejuvenated my skin.

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My skin has been forever changed and I have never been more satisfied with my skin care regimen. I am so happy to have been introduced to this amazing line!

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The compliments on my skin have increased significantly since beginning Epionce. My skin is smoother and brighter, and I'm definitely wearing less makeup to "cover" my imperfections.

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My skin continues to look younger, brighter and more dewy. The science behind the Epionce products is unsurpassed. I will never use any other product line.

Caitlin C. - Denver, CO

Not only has Epionce revolutionized our clinic and options for our patients, it has revolutionized by own personal skin appearance. This company has my utmost respect for their dedication to clinical studies and using only the best ingredients.

Janel Z. - Colorado

[Epionce] came out with Daily Shield Lotion Tinted SPF 50 and I absolutely LOVE it! I don't even use a foundation anymore, the light tint is a perfect foundation.

Pam B. - Bozeman, MT

I use and strongly recommend Epionce products. Epionce works for all skin types and you have noticeable results right away. The tone and texture of my skin has changed dramatically since using Epionce.

Lindsey M. - Helena, MT

Epionce is like clean eating for your skin. I never knew there was a line that all the natural ingredients and be able to back it up with research. It truly works and I am excited to finally use this line.

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My patient...noticed improvement in redness in only 2 days after having no results with any other product. AMAZING! and it has LASTED!

Jessica B. - Vail, CO

I truly believe in Epionce products and appreciate the studies behind the product.

Carrie R. - KS

The compliments on my skin have increased significantly since starting with Epionce. My skin is smoother and brighter and I’m definitely wearing less makeup to cover my imperfections.

Julie W. - IL

People who don’t know what I do for a living compliment my skin, even in the line at the grocery store! I only use Epionce products and always will.

Emily C. - MO

I began using Epionce six months ago. I followed the recommended system and my skin looks beautiful! I receive compliments from everyone – family, friends, and strangers. I love Epionce!

Laura M. - TX

The Medical Barrier Cream has made a huge difference in the recovery of our laser patients. Our staff is hooked!

Anathea B. - CA

I really appreciate having an effective skin care line that is also healthy.

Tabitha C. - CA

Lucy B. - CA

I have very sensitive skin and feel that Epionce is the perfect product for my anti-aging and skin protection regimen.

Joanna G. - CA

Epionce is the perfect product for our practice. It has made me much more successful and knowledgeable.

Helen T. - CA

I love that the products are user-friendly and made with ingredients I can explain to clients.

Ermy B. - TX

I love this line of skin care products, and have been using the line for over a year now. It's really great for sensitive skin and all types-dry to oily.

This is one of the best eye creams I have ever used. Just excellent.

I have very sensitive skin around my eyes. Most eye creams cause my eyes and the skin around my eyes to burn and become irritated. I received a sample of this product and have been very impressed. Usually anti-aging products dry the skin out in order to tighten it. This product however, somehow moisturizes and tightens the skin like no other product I've used. I am a makeup artist and cosmetologist. I have worked in cosmetics at department stores and have used literally hundreds of products on my skin and this eye cream is the best one I've ever used.

This face cream is not just like any other face cream. I have bought many other face creams that promise results of younger-looking skin if used as indicated. This is the first face cream that I have tried that actually delivers the promises that it makes. I'm a middle aged woman that has noticed a noticeable difference in my face wrinkles. My face is not only smoother, but the lines and wrinkles have really diminished after using this cream. Try it, and you too will see what I am talking about.

[The Intensive Nourishing Cream is] perfect for my hydration-starved skin in Colorado. Love the way it feels, smells, works...perfect for nighttime use. I highly recommend.

Asa W. - Colorado

Epionce Renewal Facial Cream is wonderful. It has been recommended by my dermatologist. It is remarkable. One has to try it to get the full value of what it does for your skin.

I love [Enriched Firming Mask]! I'm a mask addict, I will admit...and this one is really good! Not too harsh - I could probably use it daily - I love how it makes my skin feel. I'm 56 and have somewhat sensitive skin, prone to redness, and my skin gets dehydrated easily if I'm not careful. Epionce products keep my skin looking healthy.

[The Lytic Tx provided] immediate relief from inflamed, irritated skin. I struggled for days with redness on my face, my pores looked large, skin was tired, looked unhealthy. I got a sample at a plastic surgeon`s office and it calmed everything down like 70 percent the very first time I used it! Nothing ever worked that quickly and that well. Within 2 days my skin was beautiful, healthy, pores were hugely improved, it really worked amazingly!

EB - Seattle, WA

I started buying [Lite Lytic Tx] through my dermatologist for my redness...Love every thing about it; keeps my completion nice & even. I have tried to replace it with other cheaper lotions & such, always end up giving them away and using this one.

[Lytic Gel Cleanser] does the job of removing dirt, make-up, and impurities very very well. Feels amazing on the skin and does not dry out after wash. Highly recommend it!!!!

Epionce Renewal Facial Lotion is amazing! It just takes a tiny bit- a wee dollop the size of a pea to cover facial skin and throat. It so absorbs quickly that I can apply powder base right away. My skin is combination, oily, flaky, etc., but is balanced by using this product. Well worth the price since one 1.7 oz bottle lasts me 3-4 months. I am so grateful I discovered Epionce!

Epionce User

The Epionce Enriched Body Cream is incredible. It’s the only cream I’ve ever used that actually changed my hands (rather than just temporarily relieving dryness). I want to evangelize for you and the company. Incredible stuff!

Leslie - Washington State

I switched to Epionce from [another product line] and I love it! I have yet to find a product that I can truly say this about. Within 2 days the texture of my skin changed. It feels smooth, not like chicken skin anymore. My make-up goes on evenly and I feel like I use less makeup. When I look at my face in the mirror I can see my skin looks healthier. I can feel it working!

Casey - Washington State

I had a young man come in for a skin consultation. He had been on a topical steroid for very dry skin. His dermatologist took him off the steroid, and he was in a panic because he didn’t think there was anything else he could do. I gave him Epionce samples. He came in the next day and purchased all the products I had given him because it had totally worked!

A Medical Office - California

I have had dark spots for several years, and now that I'm in my early 40s it seems as though it's worsening. I have tried several products, including medical-strength ones. I can honestly say that Epionce is the only brand that has addressed my issues. My skin is brighter, more even, and smoother. I continue to tell people of my success with Epionce. I especially love the fact that the brand is cruelty-free, and paraben-free. I am thrilled to have found Epionce!

After just a few weeks of using Epionce, I could see a difference. I have never been a believer in creams and potions but Epionce is really amazing!

Rebecca S. - Washington State

I've been using Intensive Nourishing Cream for years! It keeps my face hydrated and I love the compliments that people give me regarding my skin.

Colleen H. - Washington State

I confidently recommend Epionce because of the science supporting the technology and the consistent positive feedback I get from my clientele.  I appreciate that it is botanically based, super effective and does not contain parabens, fragrances, or sulfates. It smells and feels wonderful to use and is cost effective. It’s one of the best all-around skin care lines, if not the best.

Victoria H. - Austin, TX

I have normal skin type and it can be dry in the colder months. When I wake up in the morning the redness has completely gone down. My skin looks brighter and feels more hydrated. I do not want to take this off EVER!

Emily J. - Lincolnshire, IL

I am thrilled I came across Epionce! I have depended on medications for years. With Epionce I have been able to completely eliminate [other products] and I am beyond thrilled with my skin. Not only has it cleared, but the texture and radiance have also improved.

Kasey J. - St. Louis, MO

I really love the Lite Lytic! It smooths out my skin and lightens brown spots.

Cindy - Laguna Hills, CA

I love Lytic and Intense Defense Serum! After using it for a couple of months, my skin looked years younger. I had a client ask me if I had a face lift.  

Linda W. - Kennett Square, PA

There is a Lytic product appropriate for every skin type and skin issue. It exfoliates, deep cleans the pores, helps with blemishes and brightens the skin with no drama!  We can sell with confidence to every client that walks in the door. Everyone needs a little Lytic in their life!

Megan C. - Winnetka, IL

I have been studying and using Epionce for about 8 months now and have seen nothing but good results. The products have given my skin a smoother and more even texture. I have used them in the treatment rooms and seen amazing results in...the overall health of the skin in my clients. Epionce is my favorite skin care line and I believe in it 100%. 

Katy A. - St. Louis, MO

It's total nutrition for your skin. I love the fact that it has vitamins A, B, C, D & E. I use it every morning under my Intensive Nourishing Cream. I notice a big difference in my skin texture and luminosity when I run out and don't use it. It's pretty incredible. You too will become a faithful follower!

Debbie B. - Oak Park, CA

The Medical Barrier Cream is also a favorite of mine. I use this with all dermaplaning and peel services. It is also useful for bites, burns and skin irritations. 

Tonja S. - Norman, OK

I have tried so many skin care lines and Epionce is the only one that made an incredible difference in my skin.

Bridget - Allentown, PA

My skin has improved 100% since using Epionce!

Donna F. - Medford, NJ

I am using the LyticTx and Intensive Nourishing Cream every single day and am really loving them! I’m noticing a difference in the texture and clarity of my skin. What I especially love is that I do not have any irritation or negative reaction at all! A nice change compared to retinol!

Julie L. - Chandler, AZ

Enriched Firming Mask was more effective than any exfoliants I've ever used! My skin is smooth and the itty bitty red spots that were beginning to form all over my face is almost nonexistent. My face is super smooth.

Kaylee S. - Boise, ID

My skin is often bumpy and clogged and now has some sun-damaged spots. Since I have been using the Epionce products, I can see and feel a real difference!

Carolyn S. - Newberg, OR

I went from having beautiful skin to hormonal skin due to menopause. I was experiencing irritation, sensitivity, scaling, breakouts and minor pigmentation. My skin is back to being complementary and I am a believer!

The [Essential Recovery] Kit with the Priming Oil has been a “skin savior” after an ablative treatment such as the CO2 or Pixel! Even my most sensitive patients can use the Epionce products without any irritation, less breakouts and fewer bumps develop after treatment. We literally see a full day to two days faster recovery time. Plus, our patients love the way it soothes the skin!

Hope C. - Grand Junction, CO

The Lytic Gel Cleanser is like liquid gold, I can’t imagine my life without it.

Stacie S. - Lemoyne, PA

I began using the Renewal Eye Cream to help with dark circles and puffiness. My face looks amazing! My dad said something to me about how nice my face looks, and so did my sister. I was so impressed with it for our anniversary my husband bought me the Lite Lytic Tx, Renewal Facial Cream, and Enriched Firming Mask.

Rachael - York, PA

My favorite Epionce product is Renewal Lite Facial Lotion, and I use it daily after my morning and evening showers. I love the feel of it on my face and how it absorbs and doesn't leave my face feeling greasy. It keeps my face moisturized all day!

Scott R. - Portland, OR

Research: Does Fruits Really Make Skin Glow?

Have you ever heard that fruits can make skin glow tap to check benefits of eating fruits for glowing skin., boosts collagen, fruits such as strawberries, oranges, kiwis, etc., are loaded with vitamin c that promote collgen synthesis in the skin (collagen is essential for healthy skin)., provides antioxidants, consumption of fruits like berries, oranges, and kiwi can provide antioxidants to the body that fight against free radical and promote natural glow of skin., provides hydration, consume a balanced diet rich in antioxidants and vitamins to keep yourself nourished from within., exfoliates skin, fruits like watermelons and kiwis are high in water content, which help in maintaining moisture in the skin and promotes its glow., exfoliates skin, fruits such as papaya contain enzymes that help gently exfoliate the skin, removing dead cells and revealing a fresher complexion., natural detoxification, consuming high-fibre fruits like pears, bananas, and papaya promote natural detoxification of the body that results in glowing skin., according to the study by harvard health, consumption of fruits is essential for maintaing a healthy skin as they provide many essential nutrients to the body., consume a balanced diet containing season fruits and vegetables to maintain glowing complexion of skin. consult a health expert for personalised advice..

Human Subjects Office

Medical terms in lay language.

Please use these descriptions in place of medical jargon in consent documents, recruitment materials and other study documents. Note: These terms are not the only acceptable plain language alternatives for these vocabulary words.

This glossary of terms is derived from a list copyrighted by the University of Kentucky, Office of Research Integrity (1990).

For clinical research-specific definitions, see also the Clinical Research Glossary developed by the Multi-Regional Clinical Trials (MRCT) Center of Brigham and Women’s Hospital and Harvard  and the Clinical Data Interchange Standards Consortium (CDISC) .

Alternative Lay Language for Medical Terms for use in Informed Consent Documents

A   B   C   D   E   F   G   H   I  J  K   L   M   N   O   P   Q   R   S   T   U   V   W  X  Y  Z

ABDOMEN/ABDOMINAL body cavity below diaphragm that contains stomach, intestines, liver and other organs ABSORB take up fluids, take in ACIDOSIS condition when blood contains more acid than normal ACUITY clearness, keenness, esp. of vision and airways ACUTE new, recent, sudden, urgent ADENOPATHY swollen lymph nodes (glands) ADJUVANT helpful, assisting, aiding, supportive ADJUVANT TREATMENT added treatment (usually to a standard treatment) ANTIBIOTIC drug that kills bacteria and other germs ANTIMICROBIAL drug that kills bacteria and other germs ANTIRETROVIRAL drug that works against the growth of certain viruses ADVERSE EFFECT side effect, bad reaction, unwanted response ALLERGIC REACTION rash, hives, swelling, trouble breathing AMBULATE/AMBULATION/AMBULATORY walk, able to walk ANAPHYLAXIS serious, potentially life-threatening allergic reaction ANEMIA decreased red blood cells; low red cell blood count ANESTHETIC a drug or agent used to decrease the feeling of pain, or eliminate the feeling of pain by putting you to sleep ANGINA pain resulting from not enough blood flowing to the heart ANGINA PECTORIS pain resulting from not enough blood flowing to the heart ANOREXIA disorder in which person will not eat; lack of appetite ANTECUBITAL related to the inner side of the forearm ANTIBODY protein made in the body in response to foreign substance ANTICONVULSANT drug used to prevent seizures ANTILIPEMIC a drug that lowers fat levels in the blood ANTITUSSIVE a drug used to relieve coughing ARRHYTHMIA abnormal heartbeat; any change from the normal heartbeat ASPIRATION fluid entering the lungs, such as after vomiting ASSAY lab test ASSESS to learn about, measure, evaluate, look at ASTHMA lung disease associated with tightening of air passages, making breathing difficult ASYMPTOMATIC without symptoms AXILLA armpit

BENIGN not malignant, without serious consequences BID twice a day BINDING/BOUND carried by, to make stick together, transported BIOAVAILABILITY the extent to which a drug or other substance becomes available to the body BLOOD PROFILE series of blood tests BOLUS a large amount given all at once BONE MASS the amount of calcium and other minerals in a given amount of bone BRADYARRHYTHMIAS slow, irregular heartbeats BRADYCARDIA slow heartbeat BRONCHOSPASM breathing distress caused by narrowing of the airways

CARCINOGENIC cancer-causing CARCINOMA type of cancer CARDIAC related to the heart CARDIOVERSION return to normal heartbeat by electric shock CATHETER a tube for withdrawing or giving fluids CATHETER a tube placed near the spinal cord and used for anesthesia (indwelling epidural) during surgery CENTRAL NERVOUS SYSTEM (CNS) brain and spinal cord CEREBRAL TRAUMA damage to the brain CESSATION stopping CHD coronary heart disease CHEMOTHERAPY treatment of disease, usually cancer, by chemical agents CHRONIC continuing for a long time, ongoing CLINICAL pertaining to medical care CLINICAL TRIAL an experiment involving human subjects COMA unconscious state COMPLETE RESPONSE total disappearance of disease CONGENITAL present before birth CONJUNCTIVITIS redness and irritation of the thin membrane that covers the eye CONSOLIDATION PHASE treatment phase intended to make a remission permanent (follows induction phase) CONTROLLED TRIAL research study in which the experimental treatment or procedure is compared to a standard (control) treatment or procedure COOPERATIVE GROUP association of multiple institutions to perform clinical trials CORONARY related to the blood vessels that supply the heart, or to the heart itself CT SCAN (CAT) computerized series of x-rays (computerized tomography) CULTURE test for infection, or for organisms that could cause infection CUMULATIVE added together from the beginning CUTANEOUS relating to the skin CVA stroke (cerebrovascular accident)

DERMATOLOGIC pertaining to the skin DIASTOLIC lower number in a blood pressure reading DISTAL toward the end, away from the center of the body DIURETIC "water pill" or drug that causes increase in urination DOPPLER device using sound waves to diagnose or test DOUBLE BLIND study in which neither investigators nor subjects know what drug or treatment the subject is receiving DYSFUNCTION state of improper function DYSPLASIA abnormal cells

ECHOCARDIOGRAM sound wave test of the heart EDEMA excess fluid collecting in tissue EEG electric brain wave tracing (electroencephalogram) EFFICACY effectiveness ELECTROCARDIOGRAM electrical tracing of the heartbeat (ECG or EKG) ELECTROLYTE IMBALANCE an imbalance of minerals in the blood EMESIS vomiting EMPIRIC based on experience ENDOSCOPIC EXAMINATION viewing an  internal part of the body with a lighted tube  ENTERAL by way of the intestines EPIDURAL outside the spinal cord ERADICATE get rid of (such as disease) Page 2 of 7 EVALUATED, ASSESSED examined for a medical condition EXPEDITED REVIEW rapid review of a protocol by the IRB Chair without full committee approval, permitted with certain low-risk research studies EXTERNAL outside the body EXTRAVASATE to leak outside of a planned area, such as out of a blood vessel

FDA U.S. Food and Drug Administration, the branch of federal government that approves new drugs FIBROUS having many fibers, such as scar tissue FIBRILLATION irregular beat of the heart or other muscle

GENERAL ANESTHESIA pain prevention by giving drugs to cause loss of consciousness, as during surgery GESTATIONAL pertaining to pregnancy

HEMATOCRIT amount of red blood cells in the blood HEMATOMA a bruise, a black and blue mark HEMODYNAMIC MEASURING blood flow HEMOLYSIS breakdown in red blood cells HEPARIN LOCK needle placed in the arm with blood thinner to keep the blood from clotting HEPATOMA cancer or tumor of the liver HERITABLE DISEASE can be transmitted to one’s offspring, resulting in damage to future children HISTOPATHOLOGIC pertaining to the disease status of body tissues or cells HOLTER MONITOR a portable machine for recording heart beats HYPERCALCEMIA high blood calcium level HYPERKALEMIA high blood potassium level HYPERNATREMIA high blood sodium level HYPERTENSION high blood pressure HYPOCALCEMIA low blood calcium level HYPOKALEMIA low blood potassium level HYPONATREMIA low blood sodium level HYPOTENSION low blood pressure HYPOXEMIA a decrease of oxygen in the blood HYPOXIA a decrease of oxygen reaching body tissues HYSTERECTOMY surgical removal of the uterus, ovaries (female sex glands), or both uterus and ovaries

IATROGENIC caused by a physician or by treatment IDE investigational device exemption, the license to test an unapproved new medical device IDIOPATHIC of unknown cause IMMUNITY defense against, protection from IMMUNOGLOBIN a protein that makes antibodies IMMUNOSUPPRESSIVE drug which works against the body's immune (protective) response, often used in transplantation and diseases caused by immune system malfunction IMMUNOTHERAPY giving of drugs to help the body's immune (protective) system; usually used to destroy cancer cells IMPAIRED FUNCTION abnormal function IMPLANTED placed in the body IND investigational new drug, the license to test an unapproved new drug INDUCTION PHASE beginning phase or stage of a treatment INDURATION hardening INDWELLING remaining in a given location, such as a catheter INFARCT death of tissue due to lack of blood supply INFECTIOUS DISEASE transmitted from one person to the next INFLAMMATION swelling that is generally painful, red, and warm INFUSION slow injection of a substance into the body, usually into the blood by means of a catheter INGESTION eating; taking by mouth INTERFERON drug which acts against viruses; antiviral agent INTERMITTENT occurring (regularly or irregularly) between two time points; repeatedly stopping, then starting again INTERNAL within the body INTERIOR inside of the body INTRAMUSCULAR into the muscle; within the muscle INTRAPERITONEAL into the abdominal cavity INTRATHECAL into the spinal fluid INTRAVENOUS (IV) through the vein INTRAVESICAL in the bladder INTUBATE the placement of a tube into the airway INVASIVE PROCEDURE puncturing, opening, or cutting the skin INVESTIGATIONAL NEW DRUG (IND) a new drug that has not been approved by the FDA INVESTIGATIONAL METHOD a treatment method which has not been proven to be beneficial or has not been accepted as standard care ISCHEMIA decreased oxygen in a tissue (usually because of decreased blood flow)

LAPAROTOMY surgical procedure in which an incision is made in the abdominal wall to enable a doctor to look at the organs inside LESION wound or injury; a diseased patch of skin LETHARGY sleepiness, tiredness LEUKOPENIA low white blood cell count LIPID fat LIPID CONTENT fat content in the blood LIPID PROFILE (PANEL) fat and cholesterol levels in the blood LOCAL ANESTHESIA creation of insensitivity to pain in a small, local area of the body, usually by injection of numbing drugs LOCALIZED restricted to one area, limited to one area LUMEN the cavity of an organ or tube (e.g., blood vessel) LYMPHANGIOGRAPHY an x-ray of the lymph nodes or tissues after injecting dye into lymph vessels (e.g., in feet) LYMPHOCYTE a type of white blood cell important in immunity (protection) against infection LYMPHOMA a cancer of the lymph nodes (or tissues)

MALAISE a vague feeling of bodily discomfort, feeling badly MALFUNCTION condition in which something is not functioning properly MALIGNANCY cancer or other progressively enlarging and spreading tumor, usually fatal if not successfully treated MEDULLABLASTOMA a type of brain tumor MEGALOBLASTOSIS change in red blood cells METABOLIZE process of breaking down substances in the cells to obtain energy METASTASIS spread of cancer cells from one part of the body to another METRONIDAZOLE drug used to treat infections caused by parasites (invading organisms that take up living in the body) or other causes of anaerobic infection (not requiring oxygen to survive) MI myocardial infarction, heart attack MINIMAL slight MINIMIZE reduce as much as possible Page 4 of 7 MONITOR check on; keep track of; watch carefully MOBILITY ease of movement MORBIDITY undesired result or complication MORTALITY death MOTILITY the ability to move MRI magnetic resonance imaging, diagnostic pictures of the inside of the body, created using magnetic rather than x-ray energy MUCOSA, MUCOUS MEMBRANE moist lining of digestive, respiratory, reproductive, and urinary tracts MYALGIA muscle aches MYOCARDIAL pertaining to the heart muscle MYOCARDIAL INFARCTION heart attack

NASOGASTRIC TUBE placed in the nose, reaching to the stomach NCI the National Cancer Institute NECROSIS death of tissue NEOPLASIA/NEOPLASM tumor, may be benign or malignant NEUROBLASTOMA a cancer of nerve tissue NEUROLOGICAL pertaining to the nervous system NEUTROPENIA decrease in the main part of the white blood cells NIH the National Institutes of Health NONINVASIVE not breaking, cutting, or entering the skin NOSOCOMIAL acquired in the hospital

OCCLUSION closing; blockage; obstruction ONCOLOGY the study of tumors or cancer OPHTHALMIC pertaining to the eye OPTIMAL best, most favorable or desirable ORAL ADMINISTRATION by mouth ORTHOPEDIC pertaining to the bones OSTEOPETROSIS rare bone disorder characterized by dense bone OSTEOPOROSIS softening of the bones OVARIES female sex glands

PARENTERAL given by injection PATENCY condition of being open PATHOGENESIS development of a disease or unhealthy condition PERCUTANEOUS through the skin PERIPHERAL not central PER OS (PO) by mouth PHARMACOKINETICS the study of the way the body absorbs, distributes, and gets rid of a drug PHASE I first phase of study of a new drug in humans to determine action, safety, and proper dosing PHASE II second phase of study of a new drug in humans, intended to gather information about safety and effectiveness of the drug for certain uses PHASE III large-scale studies to confirm and expand information on safety and effectiveness of new drug for certain uses, and to study common side effects PHASE IV studies done after the drug is approved by the FDA, especially to compare it to standard care or to try it for new uses PHLEBITIS irritation or inflammation of the vein PLACEBO an inactive substance; a pill/liquid that contains no medicine PLACEBO EFFECT improvement seen with giving subjects a placebo, though it contains no active drug/treatment PLATELETS small particles in the blood that help with clotting POTENTIAL possible POTENTIATE increase or multiply the effect of a drug or toxin (poison) by giving another drug or toxin at the same time (sometimes an unintentional result) POTENTIATOR an agent that helps another agent work better PRENATAL before birth PROPHYLAXIS a drug given to prevent disease or infection PER OS (PO) by mouth PRN as needed PROGNOSIS outlook, probable outcomes PRONE lying on the stomach PROSPECTIVE STUDY following patients forward in time PROSTHESIS artificial part, most often limbs, such as arms or legs PROTOCOL plan of study PROXIMAL closer to the center of the body, away from the end PULMONARY pertaining to the lungs

QD every day; daily QID four times a day

RADIATION THERAPY x-ray or cobalt treatment RANDOM by chance (like the flip of a coin) RANDOMIZATION chance selection RBC red blood cell RECOMBINANT formation of new combinations of genes RECONSTITUTION putting back together the original parts or elements RECUR happen again REFRACTORY not responding to treatment REGENERATION re-growth of a structure or of lost tissue REGIMEN pattern of giving treatment RELAPSE the return of a disease REMISSION disappearance of evidence of cancer or other disease RENAL pertaining to the kidneys REPLICABLE possible to duplicate RESECT remove or cut out surgically RETROSPECTIVE STUDY looking back over past experience

SARCOMA a type of cancer SEDATIVE a drug to calm or make less anxious SEMINOMA a type of testicular cancer (found in the male sex glands) SEQUENTIALLY in a row, in order SOMNOLENCE sleepiness SPIROMETER an instrument to measure the amount of air taken into and exhaled from the lungs STAGING an evaluation of the extent of the disease STANDARD OF CARE a treatment plan that the majority of the medical community would accept as appropriate STENOSIS narrowing of a duct, tube, or one of the blood vessels in the heart STOMATITIS mouth sores, inflammation of the mouth STRATIFY arrange in groups for analysis of results (e.g., stratify by age, sex, etc.) STUPOR stunned state in which it is difficult to get a response or the attention of the subject SUBCLAVIAN under the collarbone SUBCUTANEOUS under the skin SUPINE lying on the back SUPPORTIVE CARE general medical care aimed at symptoms, not intended to improve or cure underlying disease SYMPTOMATIC having symptoms SYNDROME a condition characterized by a set of symptoms SYSTOLIC top number in blood pressure; pressure during active contraction of the heart

TERATOGENIC capable of causing malformations in a fetus (developing baby still inside the mother’s body) TESTES/TESTICLES male sex glands THROMBOSIS clotting THROMBUS blood clot TID three times a day TITRATION a method for deciding on the strength of a drug or solution; gradually increasing the dose T-LYMPHOCYTES type of white blood cells TOPICAL on the surface TOPICAL ANESTHETIC applied to a certain area of the skin and reducing pain only in the area to which applied TOXICITY side effects or undesirable effects of a drug or treatment TRANSDERMAL through the skin TRANSIENTLY temporarily TRAUMA injury; wound TREADMILL walking machine used to test heart function

UPTAKE absorbing and taking in of a substance by living tissue

VALVULOPLASTY plastic repair of a valve, especially a heart valve VARICES enlarged veins VASOSPASM narrowing of the blood vessels VECTOR a carrier that can transmit disease-causing microorganisms (germs and viruses) VENIPUNCTURE needle stick, blood draw, entering the skin with a needle VERTICAL TRANSMISSION spread of disease

WBC white blood cell

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Volunteers needed for skin research study

By Hub staff report

Individuals between 18 and 75 years of age with generally healthy skin are needed to donate small skin samples and/or urine and/or sweat samples for a research study at the Johns Hopkins Department of Dermatology. Eligible participants will be compensated with up to $80 for their time and effort.

For more information, email/call: ctrep@jhmi.edu or 410-502-SKIN. Include protocol #: NA_00033375 on email subject line.

Principal Investigator: Luis Garza, MD, PhD Protocol #: NA_00033375

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These Russian Beauty Brands are Finally Available in the US

All products are independently selected by our editors. If you buy something, we may earn an affiliate commission.

It's difficult to imagine a time when American beauty enthusiasts couldn't rattle off the names of 10 Korean brands faster than you can say "K-beauty." But the reality is that less than a decade ago, it was rare to find a K-beauty product in an American cabinet. The sudden boom came thanks in large part to etailers like Glow Recipe , Soko Glam , and Peach & Lily — all of which began as e-commerce sites offering Korean exports — making K-beauty products readily available to U.S. consumers.

Rumore Beauty is poised to do the same for Russian products. Cofounder Maria Karr was born and raised in Russia, but moved to the United States nearly 15 years ago.  She began a career in the beauty industry, during which time she observed brands from around the world — from Australia, Iceland, and, of course, Korea — become available to U.S. consumers. But Russian products were almost never part of the global beauty conversation — perhaps because not long ago, they were few and far between.

"When I left Russia back in 2007, the very few Russian-made products that were available were the living remnants of the Soviet past — think creams in plain aluminum tubes and harsh soaps, with not enough options or the appeal of modern beauty products," says Karr. 

But during a visit to Moscow in 2019, she visited local beauty stores and found a treasure trove of brands she knew people across the world would want. "I was looking at a very healthy variety of clean, natural beauty products that looked amazing, smelled great, and felt wonderful on the skin," she says. 

And, as you may have guessed, that's how Rumore Beauty was born. Karr, along with her cofounder and husband Max, embarked on a mission to introduce these next-generation Russian beauty products to a wider audience. Since flying internationally wasn't possible amid the pandemic, they continued scouting brands virtually, meeting with founders and analyzing ingredient lists, ensuring the products met their "natural" standard. (But as Karr acknowledges, this word remains murky throughout the industry; Allure has a "clean" standard of its own .)

Botanicals have long been at the heart of traditional Russian beauty. "A strong bond with nature is in our DNA," says Anna Dycheva, CEO of Reed Exhibitions Russia, the organizer of InterCharm — the largest beauty expo in Russia — and a board member of the Cosmetics and Perfumery Association of Russia. "Historically, the majority of Russian women didn't have access to a variety of manufactured beauty products… therefore, many were turning to natural ingredients from forests, fields, and their own gardens, making homemade beauty remedies and health-boosting concoctions." As Karr observed during that visit to Moscow, that tradition is reflected in the more-elegant options available today.  But that's not to say Russian beauty products are stuck in the past. On the contrary, Karr has discovered new ingredients — including hydrolates, "much gentler relatives of essential oils that are made through the process of steam-distilling plants" — and product formats, like hydrophilic cleansing oils. "It's a hybrid between a cleansing oil and a cleansing balm that emulsifies upon contact with water and helps with completely removing your makeup while nourishing and softening the skin," she says.

For now, Rumore Beauty stocks an assortment of around 50 products from six Russian brands, all of which are available to U.S. shoppers for the very first time. If you're not sure where to start, you can survey some of our favorites — including a soothing eye cream and brightening serum — below. Much easier than lugging an overloaded suitcase back from Moscow, no?

Below, from left to right:  

True Alchemy Cleanser Fluid Proteins A lightweight gel cleanser that gets rid of every stitch of makeup — without leaving skin tight or dry.

G.Love Face Enzyme Mask Pumpkin & Calendula This soothing mask contains calendula, a plant with anti-inflammatory benefits that's been used in Russian beauty remedies for generations. 

Botavikos Anti-Stress Serum Niacinamide helps brighten, while sea buckthorn — another traditional Russian ingredient — calms redness.

Laboratorium Face Mask for All Skin Types Mix this spirulina-rich powder with water — or even milk — to create a nourishing face mask.

Mi&ko Honey and Raspberry Scrub Finely-milled raspberry pits provide gentle exfoliation, while a combination of peach seed, sunflower, and sweet almond oils help hydrate.

Innature Natural Eye Cream The star ingredient of this lightweight blend is cornflower, a Russian favorite for its hydrating, soothing, anti-inflammatory, and antioxidant properties.

True Alchemy

True Alchemy Cleanser Fluid Proteins

Rumore Beauty

G.Love Face Enzyme Mask Pumpkin & Calendula

Botavikos Anti-Stress Serum

Laboratorium

Laboratorium Face Mask for All Skin Types

mi&ko Honey and Raspberry Face Scrub

Innature Natural Eye Cream

Read more stories about beauty around the world:

• The Best Korean Skin-Care Products That'll Transform Your Complexion
• 5 Brazilian Influencers Who Are Changing the Country's Beauty Ideals
• Queer Nigerians Are Using Makeup as a Form of Resistance

Now watch Anitta's 10 Minute Sweat-Proof Beauty Routine:

Don't forget to follow Allure on Instagram and Twitter .

Allure Daily Beauty Blast

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• v.7(4); 2019 Apr

Lycopene presence in facial skin corneocytes and sebum and its association with circulating lycopene isomer profile: Effects of age and dietary supplementation

Ivan m. petyaev.

1 Lycotec Ltd, Cambridge, UK

Dmitry V. Pristensky

Elena y. morgunova.

2 Gamaleya Research Institute of Epidemiology and Microbiology, Moscow, Russia

Nailya A. Zigangirova

Valeriy v. tsibezov, natalia e. chalyk.

3 Saratov State Medical University, Research Institute of Cardiology, Saratov, Russia

Victor A. Klochkov

Victoria v. blinova, tatiana m. bogdanova, alexei a. iljin, larisa s. sulkovskaya, marina p. chernyshova, marina v. lozbiakova, nigel h. kyle, yuriy k. bashmakov.

Lycopene is a dietary antioxidant known to prevent skin photodamage. This study aimed to examine age‐dependent presence of this carotenoid on the surface of the facial skin and in the serum as well as to measure the same parameters during supplementation with lycopene. Serum samples and samples from facial skin surface were obtained from 60 young (under 25 years old) and 60 middle‐aged (over 50 years old) volunteers. Similar samples were taken from 15 middle‐aged subjects during 4‐week supplementation with lycopene (7 mg/day). Serum lycopene levels and isomer profiles were analyzed by HPLC . Lycopene in desquamated corneocytes and the sebum from facial skin surface was determined using lycopene‐specific fluorescent monoclonal antibodies. The results demonstrated that there was no age‐related difference in serum lycopene levels, but a higher proportion of (all‐E)‐lycopene was detected in the “young” group (37.5% vs 26.2% in the “middle‐aged” group; p  <   0.0001). “Young” volunteers also had a higher lycopene level in both corneocytes ( p  =   0.0071) and the sebum ( p  =   0.0139) from the skin surface. Supplementation with lycopene resulted in a sharp increase of lycopene concentrations in both serum and skin surface samples. There was also a clear change in the pattern of lycopene isomers in the serum manifested by a significant increase in the proportion of (all‐E)‐lycopene (from 22.1% to 44.0% after supplementation, p  <   0.0001). It can be concluded that dietary supplementation with lycopene results in its accumulation in the serum and skin. This process is accompanied by significant changes in the circulating lycopene isomer profile which becomes similar to that typical for young individuals.

1. INTRODUCTION

Carotenoids constitute a large group of plant pigments possessing strong antioxidant properties that are routinely ingested by humans with fruit and vegetables (Kaulmann & Bohn, 2014 ; Rao & Rao, 2007 ). Lycopene, a hydrocarbon carotenoid abundantly present in tomatoes, has recently attracted considerable attention as a common dietary factor, consumption of which is associated with a decreased risk of major chronic diseases (cardiovascular disease, cancer) and antiaging effects (Petyaev, 2016 ; Rao & Rao, 2007 ; Story, Kopec, Schwartz, & Harris, 2010 ). One of the actively investigated beneficial effects of lycopene is its photoprotective action against UV‐induced damage to human skin (Gretner‐Beck, Marini, Jaenicke, Stahl, & Krutmann, 2017 ; Rizwan et al., 2011 ; Stahl & Sies, 2012 ) that may also contribute to skin aging (Jenkins, Wainwright, Holland, Barrett, & Casey, 2014 ). The mechanisms behind these phenomena are not entirely clear, being currently explained by antioxidant action of the carotenoid (Gretner‐Beck et al., 2017 ; Jenkins et al., 2014 ; Rizwan et al., 2011 ; Stahl & Sies, 2012 ). Lycopene concentration in the skin correlates with its level in the plasma (Scarmo et al., 2010 ), and accumulation of this carotenoid in the skin during dietary supplementation is well documented (Blume‐Peytavi et al., 2009 ; Meinke, Darvin, Vollert, & Lademann, 2010 ; Ross et al., 2011 ; Walfisch, Walfisch, Agbaria, Levy, & Sharoni, 2003 ). Lycopene concentration is usually measured using HPLC that can be applied to skin biopsy samples (Scarmo et al., 2010 ; Walfisch et al., 2003 ). Biopsy taking is, however, invasive and unsuitable for assessing facial skin. Although resonance Raman spectroscopy was proposed as a feasible method for noninvasive carotenoid quantification in this location (Blume‐Peytavi et al., 2009 ; Ermakov, Ermakova, Gellermann, & Lademann, 2004 ; Mayne et al., 2010 ), the use of this technique requires expensive equipment that may not be easily available. For this reason, simpler alternative methods of noninvasive detection of lycopene and other carotenoids may be welcome.

Our group has generated a novel monoclonal antibody against lycopene that was demonstrated to be suitable for immunofluorescent recognition of this carotenoid in both cultured cells and material collected from the surface of human facial skin (Tsibezov et al., 2017 ). We decided to combine this new detection method with our recently described technique for noninvasive sampling of material rich in sebum and desquamated corneocytes from the surface of human facial skin (Chalyk, Bandaletova, Kyle, & Petyaev, 2017 ). In this study, we assessed feasibility of applying this approach to analyzing samples collected from skin surface of volunteers of different age in parallel with determining lycopene concentrations and lycopene isomer profiles in serum samples from the same subjects. In addition, lycopene accumulation in the serum and on the surface of the facial skin was analyzed in a subgroup of middle‐aged volunteers during dietary supplementation with lycopene for 4 weeks.

2. MATERIALS AND METHODS

2.1. subjects.

This study was conducted by Lycotec Ltd (Cambridge, UK) in collaboration with the Institute of Cardiology of the Ministry of Health of the Russian Federation (Saratov, Russian Federation) and the Gamaleya Research Institute of Epidemiology and Microbiology (Moscow, Russian Federation). The protocol of the study was approved by the local Ethics Committee (FGBU SarNIIK 18.02.2014) confirming that the study conformed to the European Medicines Agency Guidelines for Good Clinical Practice.

All study participants were informed about the purpose of the investigation and provided written informed consent. This study is a part of a larger project registered as ISRCTN89815519 in the ISRCTN registry.

Study participants were recruited in Saratov, from the existing pool of healthy volunteers. The main inclusion criteria corresponded with the target of forming two age‐defined groups of clinically healthy Caucasian males and females: under 25 years old (“young”) and over 50 years old (“middle‐aged”). All recruited volunteers were free of systemic chronic disorders, conditions affecting skin, and food allergies.

2.2. Study design

The total number of volunteers recruited to take part in the study was 120 (60 men and 60 women). Two age groups were formed as follows: 60 volunteers (30 men and 30 women) under 25 years of age (“young” group) and 60 volunteers (30 men and 30 women) over 50 years of age (“middle‐aged” group).

In addition, 15 volunteers from the “middle‐aged” group (seven men and eight women) took part in a substudy where they received daily 7 mg doses of lycopene (GA Lycopene capsules manufactured by Lycotec Ltd, Cambridge, UK) as a dietary supplement for 4 weeks. The study was conducted in February–March, when dietary lycopene intake in Saratov is at its lowest.

Once recruited, study participants had their body mass index (BMI) determined by measuring body mass and height in the morning and then calculating the index in kg/m 2 . Individuals with BMI below 18.5 kg/m 2 were regarded as underweight; subjects with normal weight were in the range between 18.5 and 25 kg/m 2 , those with BMI in the range between 25 and 30 kg/m 2 were classified as overweight, and BMI values over 30 kg/m 2 indicated obesity.

2.3. Sample collection and preparation

Blood samples were collected by phlebotomy from all study participants in the morning after night fast. In the substudy with lycopene supplementation, additional blood collections were performed after 2 weeks (day 15) and 4 weeks (day 29) of lycopene consumption. The serum was separated by centrifugation, aliquoted, placed in code‐labelled tubes for blinded analysis, and stored at −80°C until use.

For sample collection from the surface of the facial skin, all study participants were requested to avoid facial hygienic manipulations for 24 hr before sampling, which was carried out in the morning in parallel with blood sample collection. Skin surface sample collection and preparation was performed as previously described (Chalyk et al., 2017 ). Briefly, samples were collected using polyester swabs from the surface of the facial skin (the sides of the nose). During the procedure, two samples were taken (one swab per side). Each collected sample was placed on the surface of a microscope slide. A second microscope slide was pressed against the surface of the first one. This procedure provided a pair of identical smears. The smears were thoroughly dried.

All slides with collected samples were coded to provide sample anonymity for blinded analysis and stored at −20°C until use.

2.4. Lycopene quantification in serum samples

Lycopene concentration and isomer ratio measurement in all serum samples were carried out using high‐performance liquid chromatography (Diwadkar‐Navsariwala et al., 2003 ) with modifications. Briefly, 400 μl of serum was mixed with 400 μl of ethanol and extracted twice with 2 ml hexane. The combined hexane layers were evaporated to dryness under vacuum (Scan Speed 32 centrifuge) and the residue reconstituted to 100 μl in sample solution (absolute ethanol–methylene chloride, 5:1, v/v). The specimens were centrifuged again (15 min at 10,000  g ), and the supernatant was transferred to HPLC vials. The extract (5 μl) was injected into an Acquity HSS T3 75 × 2.1 mm 1.8 μm column (Waters, USA) preceded by a Acquity HSS T3 1.8 μm VanGuard precolumn (Waters, USA) and eluted isocratically at 45°C with the mobile phase (acetonitrile—0.08% phosphoric acid solution—tert‐butyl methyl ether, 70:5:25, v/v/v) at a flow rate of 0.5 ml/min. The peaks corresponding to lycopene isomers were detected by a Photodiode Array Detector (Waters, USA) at 474 nm. The peak areas were measured using Empower 3 software (Waters, MA). Lycopene concentrations in serum samples were calculated by reference to an analytical standard (lycopene from tomato, L9879, Sigma, USA). Relative concentrations of (all E) and (Z)‐lycopene isomers were calculated by comparing their peak areas to the standard curve as previously described (Fang, Pajkovic, Wang, Gu, & van Breemen, 2003 ).

2.5. Lycopene detection in facial sebum and desquamated corneocytes by immunofluorescent staining

Dried smears collected from the surface of the facial skin were used for immunofluorescent staining. Desquamated corneocytes and sebum present in the material were stained for direct immunofluorescence using fluorescein isothiocyanate‐conjugated monoclonal antibody against lycopene recently generated by our group (Tsibezov et al., 2017 ). Fluorescent staining was visualized using Nikon Eclipse 50i microscope with a fluorescence attachment. The semiquantitative analysis was based on visually assessing fluorescence levels in corneocytes and surrounding sebum in 20 random fields of view at ×200 magnification. Fluorescence intensity in the samples was classified using the following scoring system illustrated in Figure  1 : 0—no fluorescence; 0.5—traces of fluorescence; 1—weak fluorescence; 2—moderate fluorescence; 3—strong fluorescence of some cells or areas of sebum background; 4—extremely strong fluorescence (confluent fluorescent elements within corneocytes). Fluorescence assessment in each sample was repeated blindly three times.

Photomicrographs of samples noninvasively collected from the surface of the facial skin and stained using our immunofluorescent technique (magnification ×1,000 in all cases) exemplifying fluorescence scoring system used in the study: (a) Extremely strong fluorescence of corneocytes (score = 4) and weak fluorescence of sebum background (score = 1), (b) Strong fluorescence of a corneocyte (score = 3) and fluorescence traces in sebum background (score = 0.5), (c) Moderate fluorescence of a corneocyte (score = 2) and moderate fluorescence of sebum background (score = 2), (d) Weak fluorescence of a corneocyte (score = 1) and no fluorescence of sebum background (score = 0)

2.6. Data analysis

All quantitative results for comparing “young” and “middle‐aged” volunteers were calculated for each of the two groups and for male and female subjects separately. In the substudy with lycopene supplementation, results were calculated for the three sampling time points (before supplementation, at 2 weeks, and at 4 weeks).

Results of all quantitative measurements (or fluorescence score counts) were analyzed using descriptive statistics (mean, standard deviation, median and range values as well as 95% confidence intervals were determined). Paired t test (two‐sided p ‐values calculated) was applied to determine statistical significance for the differences between time points. t test for independent means was used for comparing groups. Pie charts were employed for presenting proportions of lycopene isomers in the serum for the age groups and for different time points of the supplementation substudy. All data handling and statistical analyses were performed using IBM SPSS 19.0 statistical package (IBM Inc., Armonk, NY, USA).

3.1. General characteristics of the study population

Age distributions in the two study groups were relatively compact. In “young” volunteers, the mean age was 18.7 (95% CI: 18.2–19.1) with similar distributions among male and female study participants. In the “middle‐aged” group, the mean age was 65.0 (95% CI: 63.4–66.5) without gender‐related differences. There was an obvious difference between the groups in BMI values. The mean BMI in the “young” group was 22.3 (95% CI: 21.3–23.2), which corresponds to normal weight. Among 60 study participants of this group, 45 (75%) were classified as normal, five (8.3%) as underweight, seven (11.7%) as overweight, and only three (5%) as obese. In contrast, in the “middle‐aged” group, the mean BMI was 29.4 (95% CI: 28.3–30.5), corresponding to overweight status. Only nine (15%) members of this group had normal weight, whereas 26 (43.3%) volunteers were classified as overweight and 25 (41.7%) were obese.

3.2. Lycopene measurement in the serum and material collected from the surface of the skin in “young” and “middle‐aged” groups of volunteers

Table  1 shows that serum lycopene concentrations in both “young” and “middle‐aged” volunteers were generally low. Among 120 study participants, only 37 had serum lycopene levels above 300 nM. In particular, low lycopene concentrations were observed in “young” women. The mean serum lycopene value in this subgroup (139.70 nM) was significantly lower than in either “young” men or “middle‐aged” women (Table  1 ).

Lycopene measurement in the serum and material from the surface of the skin of volunteers of different age groups

a / p  < 0.0001; b / p  = 0.0001; c / p  < 0.0001; d / p  < 0.0001; e / p  < 0.0001; f / p  < 0.0001; g / p  < 0.0001; h / p  = 0.0006; i / p  = 0.0003; j / p  = 0.0031; k / p  = 0.0002; l / p  < 0.0001; m / p  < 0.0001; n / p  < 0.0001; o / p  = 0.0126; p / p  = 0.0008; q / p  = 0.0017; r / p  = 0.0016; s / p  = 0.0071; t / p  = 0.0035; u / p  = 0.0139.

Values are given as means (95% CI).

An obvious difference between the age‐defined groups was observed in the proportions of lycopene isomers (Table  1 and Figure  2 ). Among “middle‐aged” volunteers, the proportion was significantly shifted toward cis ‐forms, especially because of the increase in the share of 13‐cis ‐lycopene which accounted for 31.52% of all serum lycopene in this group.

Pie charts showing lycopene isomer proportions in the serum of “young” (a) and “middle‐aged” volunteers (b). See Table  1 for precise results

Semiquantitative assessment of lycopene amount in the material collected from the surface of the skin indicated that lycopene presence in “young” subjects was significantly higher than in the “middle‐aged” group. This difference was observed for both desquamated corneocytes and surrounding sebum.

3.3. Lycopene measurement in the serum and material collected from the surface of the skin during dietary supplementation with lycopene

Results of the substudy that included 15 “middle‐aged” volunteers receiving dietary supplementation with lycopene for 4 weeks are presented in Table  2 and Figures  3 and ​ and4. 4 . Although general characteristics of the participants of the substudy (Mean age = 66.1; Mean BMI = 29.5) did not differ from the whole “middle‐aged” group (see Table  1 ), it should be noted that in terms of body composition, nine participants in this substudy were classified as obese, four as overweight, and only two as normal.

Lycopene measurement in the serum and material from the surface of the skin of 15 volunteers at different time points of dietary supplementation

a / p  < 0.0001; b / p  < 0.0001; c / p  = 0.0003; d / p  < 0.0001; e / p  < 0.0001; f / p  < 0.0001; g / p  = 0.0131; h / p  = 0.0005; i / p  = 0.0011; j / p  = 0.0126; k / p  < 0.0001; l / p  < 0.0001; m / p  < 0.0001; n / p  = 0.0001; o / p  = 0.0013; p / p  < 0.0001; q / p  < 0.0001; r / p  < 0.0001.

Results of serum lycopene analysis during lycopene supplementation: (a) Changes in serum lycopene concentration (Means and 95% CI ), (b) Pie chart showing lycopene isomer proportion before supplementation (see Table  2 for precise results), (c) Pie chart showing lycopene isomer proportion in the middle (2 weeks) of the supplementation period (see Table  2 for precise results), (d) Pie chart showing lycopene isomer proportion at the end (4 weeks) of the supplementation period (see Table  2 for precise results)

Results of lycopene analysis in samples obtained from facial skin surface: (a) Changes of lycopene level in desquamated corneocytes (Means and 95% CI ), (b) Changes of lycopene level in the sebum (Means and 95% CI )

Table  2 and Figure  3 a clearly demonstrate that serum lycopene concentration was significantly increasing throughout the supplementation period reaching a mean value of 632.07 nM by the end of the study. In parallel, changes in the proportion of lycopene isomers were observed (Figure  3 b–d), and these changes followed a clear pattern characterized by a significant increase in the proportion of (all‐E)‐lycopene accompanied by a relative decrease in (13Z)‐lycopene. While the profile of lycopene isomers in the 15 participants of the substudy before supplementation (Figure  3 b) did not differ from that of the whole “middle‐aged” group (Figure  2 b), after 2 weeks of supplementation (Figure  3 c), it became close to the pattern observed in the “young” group (Figure  2 a) and continued progressing further by the end of the study (Figure  3 d).

Gradual lycopene accumulation during supplementation was also evident in the material collected from the surface of the facial skin (Figure  4 ). However, there was a difference between desquamated corneocytes and unstructured sebum. Lycopene presence in desquamated corneocytes significantly increased for the whole period of supplementation (Figure  4 a). In contrast, sebum assessment revealed lycopene presence increasing only during the first 2 weeks of supplementation. No further lycopene concentration increase in the sebum was observed by the end of the study (Figure  4 b).

4. DISCUSSION

Parallel increase of lycopene concentrations in the serum and skin during consumption of lycopene‐rich diets or dietary supplementation is well‐documented (Meinke et al., 2010 ; Mayne et al., 2010 ; Scarmo et al., 2010 ; Walfisch et al., 2003 ), and our results indicating a steep increase in serum lycopene throughout the supplementation period are not surprising. It should be noted that serum lycopene concentrations in the participants of this study were considerably lower than those reported by others (Allen et al., 2003 ; Gamji & Kafai, 2005 ; Scarmo et al., 2010 ) and corresponded to a state of lycopene deficiency (Mackinnon, Rao, & Rao, 2011 ). This observation apparently reflects the seasonal decrease in dietary lycopene consumption patterns still common in some regions characterized by long winter periods. Nevertheless, the background of lycopene deficiency among study participants helped facilitate the detection of lycopene supplementation effects.

Our analysis of lycopene isomer profiles in serum samples from young and middle‐aged volunteers has resulted in one unexpected finding demonstrating an obvious difference in isomer proportions between the groups. Lycopene is present in dietary sources almost exclusively in the linear (all‐E) conformation, but following ingestion tends to be partially transformed to the (Z)‐forms that are deemed to be more bioavailable (Boileau, Boileau, & Erdman, 2002 ). In our study, the proportion of (all‐E)‐lycopene was significantly higher among young subjects, whereas middle‐aged volunteers had the highest proportion of (13Z)‐lycopene (Figure  2 b). It should be noted that the latter isomer is a major early product of lycopene degradation (Graham, Carail, Caris‐Veyrat, & Lowe, 2012 ). The difference between our age‐defined study groups in lycopene isomer patterns is clear, but its interpretation needs to be careful. Although it may seem that the age of volunteers is the main defining factor, the two groups were also characterized by a significant difference in body composition. Young volunteers typically were of normal weight, whereas most of those in the “middle‐aged” group were either overweight or obese. Therefore, the difference in lycopene isomer profiles could also be attributed to the influence of body composition.

It is interesting that the dynamics of lycopene isomer proportion changes during supplementation with capsules containing almost exclusively (all‐E)‐lycopene corresponded to a gradual replacement of the “middle‐aged” pattern with the “young” one. Low amplitude changes of the (E)/(Z) ratio in parallel to lycopene withdrawal or supplementation have been described previously, but without specifying different (Z)‐variants (Allen et al., 2003 ). In our study, we observed significant growth in the proportion of (all‐E)‐lycopene at the expense of (Z)‐lycopene, especially its (13‐Z)‐form (Figure  3 ). Given the parallel increase of the overall lycopene concentration in the serum, it can be assumed that absolute amounts of all isomers should be increasing, and isomer pattern changes may reflect partial saturation of some metabolic pathways possibly generating biologically active derivatives of lycopene, such as apo‐10′‐lycopenoids (Wang, 2012 ).

It may be tempting to conclude from lycopene isomer profile changes that lycopene supplementation produces a rejuvenating effect in “middle‐aged” subjects; however, it is equally likely that the dietary intervention may simply restore the normal pattern in overweight or obese individuals. In any case, the effect appears to be unconditionally beneficial. This conclusion is supported by reports on mediation of cardiovascular disease risk biomarkers by serum carotenoids (Kim et al., 2011 ; Wang et al., 2014 ) and even association between higher serum lycopene levels and reduced mortality in individuals with metabolic syndrome (Han, Meza, Soliman, Islam, & Watanabe‐Galloway, 2016 ). Regarding the skin, it can be manifested by increasing protection against UV (Gretner‐Beck et al., 2017 ; Rizwan et al., 2011 ; Stahl & Sies, 2012 ) and antiaging effect (Jenkins et al., 2014 ).

The stratum corneum (SC) of the epidermis is the most superficial layer of the skin and exerts key barrier functions protecting the human body from adverse environmental influences (Menon, Cleary, & Lane, 2012 ; Proksch, Brandner, & Jensen, 2008 ). It is important to emphasize that investigation by Raman spectrometry showed that the upper layers of the SC had the highest concentration of carotenoids in the skin (Darvin et al., 2009 ), but the authors of the report noted that it was technically difficult to use Raman spectrometry for analyzing the skin surface (Darvin et al., 2009 ). We believe that our new approach employing recently generated antilycopene antibodies (Tsibezov et al., 2017 ) presents an attractive alternative. The study described here convincingly demonstrates the feasibility of applying an immunofluorescent technique for detecting lycopene in the material collected from the surface of human facial skin. This material in fact corresponds to the residual skin surface components (RSSC) (Shetage et al., 2014 ), noninvasive collection and morphological analysis of which is described in our recent paper (Chalyk et al., 2017 ). Although it can be admitted that the semiquantitative method of fluorescence intensity assessment used in the current study may not be ideal, the results look convincing. Lycopene concentrations in both desquamated corneocytes and sebum were significantly higher in young volunteers. This finding corroborates previous observations of age‐associated decrease of lipophilic antioxidants in the sebum (Passi, De Pita, Puddu, & Littarru, 2002 ) and probably reflects the development of aging‐related deficiency in skin barrier functions (Boireau‐Adamezyk, Baillet‐Guffroy, & Stamatas, 2014 ) including antioxidant transport to the skin.

Our substudy with lycopene supplementation showed different patterns of lycopene accumulation in desquamated corneocytes and surrounding sebum (Figure  4 ). This difference appears to be easy to explain by the physiological necessity of the transit of terminally differentiated corneocytes through the SC that takes approximately 14 days (Haftek, 2014 ). Therefore, desquamation of the first corneocytes enriched with lycopene should start only by the end of the second week of supplementation and is likely to be fully manifested later as we observe (Figure  4 a). In contrast, the level of lycopene in the sebum appears to already reach a “plateau” after 2 weeks of supplementation.

Unfortunately, we were not able to assess relative amounts of lycopene isomers in the material collected from the skin surface. Nevertheless, it is interesting to note that some authors believe that the presence of (Z)‐lycopene in the skin provides increased UV absorption (Stahl & Sies, 2012 ), thus preventing UV‐induced damage.

5. CONCLUSION

Taken together, our results for the skin and serum complement each other and can be interpreted as manifestations of either the “normalizing” or “rejuvenating” action of lycopene in “middle‐aged” subjects. In view of these encouraging early results, we plan further developing our antibody‐based method and aim to eventually present it as a quantitative immunochemical point‐of‐care test that will not require immunofluorescent analysis. Achievement of this goal could facilitate investigation of the beneficial effects of dietary carotenoids on human skin.

CONFLICT OF INTEREST

Lycotec Ltd developed GA Lycopene, which is evaluated in this study. Ivan M. Petyaev and Nigel H. Kyle are employees of Lycotec; Dmitry V. Pristensky, Marina P. Chernyshova, Marina V. Lozbiakova, and Yuriy K. Bashmakov are independent scientists who collaborate with, but are not, and have never been employees of Lycotec; Natalya E. Chalyk, Victor A. Klochkov, Victoria V. Blinova, Tatiana M. Bogdanova, Alexei A. Iljin, Larisa S. Sulkovskaya and are employees of the Institute of Cardiology in Saratov, Russian Federation; Elena Y. Morgunova, Nailya A. Zigangirova and Valeriy V. Tsibezov are employees of the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow, Russian Federation. There have never been any financial relationships between Lycotec and these collaborating organisations.

ACKNOWLEDGMENTS

Volunteers who took part in the study are thanked for their cooperation. Dr Alexandre Loktionov (DiagNodus Ltd, Cambridge, UK) is thanked for his critical advice and help in manuscript preparation. This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.

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