Heggar Venkataramana et al. BMC Complementary Medicine and Therapies(2020) 20:26
https://doi.org/10.1186/s12906-019-2721-3

BMC Complementary
Medicine and Therapies

RESEARCH ARTICLE

Open Access

Potential benefits of oral administration of
AMORPHOPHALLUS KONJAC
glycosylceramides on skin health – arandomized clinical study
Sudeep Heggar Venkataramana*, Naveen Puttaswamy and Shyamprasad Kodimule

Abstract
Background: Ceramides play a fundamental role in maintaining the skin health as a function of improved barrier
permeability. Reduced ceramide content results in skin dryness and wrinkledness. Intake of dietary ceramides
potentially compensates the skin ceramide content. In the present study we have assessed the skin health benefitsof oral supplementation of a hydroalcoholic extract from Amorphophallus konjac tubers standardized to 5%
glycosylceramides, in a placebo-controlled clinical trial.
Methods: Fifty-one healthy human volunteers (aged 18–60 years) were supplemented with 100 mg/day of either aplacebo or A. konjac extract capsules (5 mg glycosylceramides) for 6-weeks. The skin parameters were evaluatedthrough dermatological diagnosis. Subject perceived efficacy of the product was further evaluated by a selfassessment questionnaire.
Results: Oral intake of A. konjac extract significantly decreased the skin dryness, hyperpigmentation, redness, itchingand oilyness (p < 0.05). The improvement in skin health following intake of A. konjac extract was observed to betime-dependent from the start. Further, A. konjac extract was well-tolerated throughout the study, as no adverse
events or toxic changes were recorded.
Conclusion: The study demonstrates the skincare properties of orally ingested glycosyl ceramides from konjac
tubers.
Trial registration: CTRI/2018/12/016661 dated 13/12/2018 retrospectively registered, http://ctri.nic.in/Clinicaltrials/
showallp.php?mid1=19851&EncHid=&userName=SkinCera
Keywords: Phytoceramides, Skin barrier function, Human clinicalBackground
Ceramides are a variety of sphingolipids, present in theskin keeping it moist and healthy [1]. Human epidermis
is composed of the stratum basale, stratum spinosum,
granulosa, and stratum corneum from the inner layer towards outside. In the stratum basale, phospholipids andcholesterol are the main components while granulosa
majorly contains glycosylceramides. Ceramide in thestratum corneum plays a key role in barrier functions* Correspondence: sudeepkashyap.82@vidyaherbs.com;
sudeepkashyap.82@gmail.com
Research Scientist, No. 14A, KIADB, R & D Center for Excellence, Vidya Herbs(P) Ltd., Jigani Industrial Area, Bangalore, Anekal Taluk 560 105, India

such as moisture retention, maintenance of skin architecture, prevention of invasion of foreign bodies [2, 3].
During the recent past, studies have demonstrated thebeneficial effects of orally supplemented ceramides against
dry skin, skin aspect, and associated discomforts. Animalstudies have been conducted to describe the oral bioavailability of ceramide. Dietary glycosylceramides are metabolized in rat small intestine and found in portal blood afterhydrolysis by ceramidases in the gastrointestinal tract [4].
Nevertheless, a large proportion of ingested sphingolipids
are excreted in the feces, animal studies suggest that after
oral intake radiolabeled ceramides are metabolized,
absorbed and distributed to many tissues, including the© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies(2020) 20:26

Page 2 of 9

Fig. 1 Analysis of glycosylceramides in SkinCera by LCMS/MS

skin [5]. Ueda et al., showed that orally administrated radiolabeled D2-sphingosine is transferred to the skin, fromdermis to epidermis in an unchanged structural form, andfurther generates radiolabeled glucosylceramides and ceramides by in vivo biosynthesis in mice [6]. The orally
ingested sphingolipids in human beings could be hypothesized to follow a similar track of metabolism as describedin animal studies. Not all the ingested sphingolipids arehydrolyzed and absorbed. However, some components ofsphingolipids (sphingosine) reach the systemic circulation
following transport through the mucosa. The dietary ceramides may activate the ceramide synthesis in the skin
improving the barrier function, rather than direct
reutilization reaching the skin [7]. In addition, previous
studies have demonstrated that oral supplementation withceramides may be beneficial for skin permeability barrier
homeostasis and parameters such as hydration and/or
barrier function, elasticity, and recovery after induced
disruption of barrier dysfunction [8–10].
Loss of ceramides causes dry skin and dermatitis that
subsequently leads to the appearance of wrinkle in theskin [11]. Supplementation of ceramides thus is essential
for maintaining skin barrier permeability and hydration.
Nevertheless, synthetic ceramides are used in general ascosmetics; natural ceramides have drawn much attention
during the recent past due to the safety [12]. Plant derived ceramides are chemically identical to those foundin our skin. Currently there are several types of ceramides available in the market commercially derived fromplant sources such as rice, wheat, soy, and spinach.
Glycosylceramides have been reported to improve skinbarrier function in hairless mice by intake of extract offood materials containing glycosylceramide. Oral intakeof glycosylceramide reduces transepidermal water loss innormal adult or in atopic dermatitis patients [13].
Amorphophallus konjac (Family: Araceae) is a perennial plant commonly known as konjak or konnyaku.
Konjac is a traditional food ingredient and medicine
used in China, Japan and South East Asia. konjac is usedin the Chinese folk medicine as a tumour suppressor,
detoxification and phlegm liquefaction. A. konjac is arich source of glycosyl ceramides and glucomannan.
Table 1 Quantitative formula of treatments (per capsule)
Composition

SkinCera (mg)Placebo (mg)Maltodextrin

70

120

A. konjac extract50

0Dicalcium phosphate

100

100

Magnesium carbonate

50

50

Magnesium stereate

55Silica micronized25

25

Total weight

300

300

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies(2020) 20:26

Page 3 of 9

Fig. 2 Subject participation flow chart

Konjac tuber-derived glycosylceramides have been commercially exploited as dietary supplements for dry skin[14]. Previous studies in mice have shown that konjac
glycosylceramides are effective against trans-epidermal
water loss [9]. Usuki et al. [14] have reported the efficacyof konjac ceramides on itch-causing neurite outgrowthin PC12 cells [15]. Based on the experimental and clinical evidences from previous studies we have evaluatedthe effects of orally ingested konjac extract containing
glycosylceramides on skin care properties in a placebocontrolled, randomized, single-blind clinical trial withhealthy human volunteers.

(ICH) Good Clinical Practice (GCP) Guidelines, including
ICH E6, and applicable local regulatory requirements andlaws. This clinical trial adheres to the CONSORT guidelines. The information on the nature, purpose, and risks ofthe study were provided to each subject or subject’s legallyauthorized representative before their participation. Written
informed consent for participation and publication of thedata was obtained prior to the subject entering the study(before initiation of protocol-specified procedures). The
subjects were randomized to two intervention groups: placebo and A. konjac extract (capsule form, 100 mg/day).
Ethics, consent and permissions

Methods
Investigational productThis study was conducted to investigate the efficacy of
SkinCera™, a proprietary extract from the tubers of A.
konjac. The formal identification of the plant material
was done at Vidya Japan K.K., Minato-ku, Tokyo, Japan.
SkinCera is a hydroalcoholic extract standardized to 5%of glycosyl ceramides.
Trial design

This was a monocentric single-blinded, placebo-controlled,
randomized study performed on 50 healthy human volunteers. The study was conducted in compliance with theprotocol, International Conference on Harmonization

The study protocol and informed consent form were approved by institutional ethics committee (SKAMC/96/
2017–18, Sri Kalabyraveshwara Swamy Ayurvedic Medical
College, Hospital and Research Center, India). This clinicalstudy was registered in Clinical Trials Registry – India
Table 2 Baseline demographics of subjects
SkinCera

PlaceboNumber of subjects

26

25

Age (years)

28.08 ± 7.3

32.56 ± 5.3

Height163.2 ± 10.3

165.8 ± 7.27

Weight62.4 ± 14.63

65.9 ± 6.82

The data were statistically analyzed at p < 0.05 and represented as mean ± SD

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies(CTRI/2018/12/016661). Informed consent and consent topublish were obtained prior to subject randomization. Subjects meeting all inclusion and no exclusion criteria signed
a written informed consent and enrolled in the study.
Participants
Eligibility criteria

Healthy adult male and female volunteers aged 18–60
years presenting symptoms such as skin dryness, roughness, itching, redness, hyperpigmentation, blackheads andwhiteheads were recruited. Subjects with chronic medical
disorders were excluded from the study. Other exclusion
criteria were pregnant or lactating women, smokers andalcoholics, subjects undergoing other cosmetic treatments.
Further, subjects unwilling/unable to comply with theprotocol requirements were excluded from the study.
Study site

The study was performed at Sri Kalabyraveshwara Swamy
Ayurvedic Medical College, Hospital and Research Center,
Bangalore, India.
Interventions

A standardized extract from A. konjac tubers was prepared according to a proprietary manufacturing processusing solvent based extraction strategy. The raw material
was procured from Gunma prefecture, Japan and authenticated internally at Vidya Herbs Pvt. Ltd., Japan. A.
konjac extract is standardized to ≥5% glycosylceramides(ceramide 1–4, Fig. 1) by LCMS/MS analysis. Further
details on the constituents of A. konjac extract are provided in supplementary file (Additional file 3).

(2020) 20:26

Page 4 of 9

During the 6-week treatment period, the daily oral intake was two capsules containing either placebo (maltodextrin) or A. konjac extract (=100 mg/day). Indeed,
SkinCera group received 5 mg/day of glycosylceramides.
All capsules were of the same appearance, color andodor. Table 1 shows the composition of capsules. The
subjects had to record their daily food consumption during the intervention period to ensure that there was nochange in the dietary habits throughout study period.
Outcomes

The primary end point was to assess the effect of A. konjac extract consumption on skin health. The efficacy
evaluation was performed after a regular interval of 3
weeks of ingestion: Visit 1 (day 1), visit 2 (third week oftreatment) and visit 3 (after 6 weeks of treatment). The
skin parameters included in the study were evaluatedas overall symptoms through dermatological diagnosis
and inquiry. Diagnosis score is usually a number thatconveys the response of a subject to the treatment(Additional file 2). With reference to the previously
validated subjective scoring scales, the diagnosis scoretest was developed by the investigator before the conduct of study [16, 17]. In each evaluation, anchor points
were prepared and evaluated by the investigator. A total ofeight skin parameters were considered for the study andthe subjects were evaluated by the investigator at every
scheduled visit. The safety analysis was summarized forvital signs and adverse event monitoring.
The subject perception of the product efficacy wasevaluated by a validated self-assessment questionnaire atfollow-up visit.

Table 3 Dermatological diagnosis before and after 6-week treatment with SkinCera
SkinCera group

Placebo group

Parameter

Number of subjects
with symptoms

Beforetreatment

After 3 weeks After 6 weeks Number of subjects
with symptoms

Beforetreatment

After 3weeks

Dryness8

1.88 ± 0.99 0.5 ± 0.75**

0.63 ± 0.51**

12

1.33 ± 0.49 1.58 ± 0.51

1.67 ±
0.65

Whiteheads/
blackheads

10

1.56 ± 0.72 1.0 ± 0.86

1.11 ± 0.78

11

1.91 ± 0.83 2.46 ± 0.52

2.55 ±
0.69

Hyperpigmentation 21

1.47 ± 0.77 1.05 ± 0.52

1.05 ± 0.40*

11

2.46 ± 0.52 2.36 ± 0.5

2.14 ±
0.69

Redness10

1.7 ± 0.67

1.2 ± 0.91

0.6 ± 0.84*

51.20 ± 0.44 1.8 ± 0.44

LTF

Lesions11

1.3 ± 0.48

1.1 ± 0.87

0.7 ± 0.82

51.4 ± 0.54

LTF

1.8 ± 0.45

After 6weeks

Itching

10

1.67 ± 0.5

0.88 ± 0.78

0.67 ± 0.86*

3

1.33 ± 0.57 2.33 ± 0.57

LTF

Oilyness

12

1.46 ± 0.52 0.90 ± 0.83

0.73 ± 0.78*

9

1.11 ± 0.33 1.22 ± 0.44

1.71 ±
0.48*

Roughness

7

1.29 ± 0.48 0.71 ± 0.75

0.57 ± 0.78

11

1.91 ± 0.83 2.27 ± 0.47

2.36 ±
0.81

Overall

26

1.53 ± 0.66 0.95 ± 0.76*** 0.79 ± 0.71*** 25

1.67 ± 0.74 1.98 ± 0.63* 2.10 ±0.75**The values are the mean in each group; analyzed by one-way ANOVA followed by Dunnet’s t test. The data were statistically significant at *p < 0.05, **p < 0.01,***p < 0.001 within the group. LTF, Lost to follow-up
0 (no symptoms) - 1 (mild) - 2 (moderate) - 3 (severe)

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies

Sample size

The sample size calculation was based on the expecteddifference between mean scores of the two treatments
considered to be medically relevant. Assuming a common standard deviation of 1.8 for the number of assessment parameters at the end of treatment, 20 per groupwould be enough to detect a difference of 1.63 in meanscore difference between the two treatments withpower of 80% and a 0.05 two-sided level of significance.
Considering a dropout rate of 10% the sample size was
finalized as 50 (25 per group). The details of the sample
size calculation are presented as supplementary file
(Additional file 4).

(2020) 20:26

Page 5 of 9

reason, regardless of whether the IP was taken or not,retained their randomization number. Subjects were kept
blind to treatment group assignment.
Statistical analysis

The primary analysis was based on the full analysis set
which included all randomized subjects and followed theintent-to-treat principle. Statistical analysis was performed using SPSS software version 16.0. All statisticalsignificance tests were 2-sided and performed at the 5%
significance level. Data were analyzed by one-way
ANOVA followed by Dunnet test.

Results
Subject enrollment and baseline data
Randomization and blinding

The subjects were randomly assigned to the study
groups in a 1:1 ratio to receive active treatment andplacebo. Block randomization was used to assign thesubjects to treatment groups. Each randomized subject
received a xx-digit randomization number. Randomized
subjects who terminated their study participation for any

A total of 75 subjects were screened from single study
center and 51 volunteers were enrolled into the study.
Out of these 51 subjects, 40 subjects completed thestudy and 11 were withdrawn from the study due to lost
to follow-up/failed to return (Fig. 2). Subject baseline
demographic data are presented in Table 2. Further
details are provided in Additional file 1.

Fig. 3 Effect of SkinCera on dermatological diagnosis score. a Mean diagnosis score at baseline, 3 weeks and 6 weeks after SkinCera intake (b)Change in mean score from baseline to end of study. Values are expressed as mean ± SD. The data were analyzed by one-way ANOVA followedby Dunnet’s t test. ***p < 0.001 compared to placebo. ns, not significant

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies

Dermatological diagnosis

The mean dermatological diagnosis score, before and afteringestion of A. konjac extract is presented in Table 3. In
A. konjac extract treated group, the skin dryness was evident among 8 subjects with a mean severity symptomscore of 1.88 at the screening visit (before treatment). The
subjects showed significant improvement during the study
having a mean score of 0.63 after 6 weeks treatment (p <0.01). Similarly, A. konjac extract treatment markedly decreased the mean score of hyperpigmentation from 1.58 atbaseline to 1.053 after the 6-week treatment (p < 0.05).
Skin redness was observed initially among ten subjects in
the A. konjac extract group with a mean score of 1.7. The
subject response to skin redness, itching and oilyness
following A. konjac extract treatment were significant at
p < 0.05 after 6 weeks. A. konjac extract treatment was(2020) 20:26

Page 6 of 9

appreciable for skin roughness though the data were notsignificant. Subject response in the A. konjac extract groupfor other skin parameters such as whiteheads/blackheads
and lesions were moderate. It was further observed thatthe study parameters were aggravated among the subjects
in the placebo group during the study. The overall mean
diagnosis score decreased significantly (p < 0.001) aftersix-week oral ingestion of A. konjac extract (Fig. 3).
The percentage response of subjects following 6-weektreatment with 100 mg/day treatment with A. konjac extract, to individual skin parameters is presented in Fig. 4.
The recovery percentage of subjects from skin dryness
and roughness were highly appreciable among the various parameters assessed. Figure 5 shows the percentage
improvement in the subject population following A.
konjac extract treatment. A. konjac extract considerably

Fig. 4 Subject response (%) to SkinCera treatment for individual skin parameters (at follow-up visit)

(2020) 20:26

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies

Page 7 of 9

Fig. 5 Effect of SkinCera on the improvement in skin health from baseline to follow-up

alleviated the skin condition as evident from the increasein the percentage of subjects showing improvement for
respective parameters.
Adverse events

A. konjac extract treatment did not induce any significant adverse or serious adverse effects throughout the
study period as evident from the vital signs and healthmonitoring (Data not shown).

skin health benefits in healthy human volunteers. A sixweek ingestion of A. konjac extract at 100 mg/day (glycosylceramide, 5 mg/day) significantly improved the skinparameters such as dryness, hyperpigmentation, itchingand oilyness compared to placebo group. Interestingly,
these beneficial effects were evident after 3-weeks ofTable 4 Results of self-assessment questionnaire after 6-week ofsupplementation with SkinCera
Questions and self assessment

Results of self-assessment questionnaire

The subjects’ perception as evaluated through selfassessment questionnaire was consistent with the resultsof the diagnosis. Results of the self-assessment questionnaire are presented in Table 4.

Discussion
Ceramides from edible plants have emerged as a safeand preferred alternative to animal ceramides for cosmetic applications [18]. Research on several plant-based
ceramides are intended to supplement effective amountof the ceramide content to the skin which otherwise has
reduced content of natural ceramides due to defective
skin barrier function [9, 19]. Human clinical trials on
ceramide-based products from various plant sources likewheat, rice, beet and konjac tubers have been documented to improve the skin barrier functions [8, 10, 20].
The clinical evidence on the efficacy of konjac glycosylceramides in other skincare properties apart from skindryness is lacking. This clinical trial was undertaken to
study the effect of supplementation of small quantity ofglycosylceramides (5 mg/day) from konjac on overall

SkinCera

Placebo

How do you rate the efficacy of the product in skin dryness
improvement?
Insufficient

0%

65%

Sufficient

30%

30%

Fairly good

35%

5%

Excellent

350%

Do you think your skin texture is improved?
Yes

75%

30%

No

20%

60%

No opinion

5%

10%

How do you evaluate the product efficacy concerning improvement inskin pigmentation?
Insufficient

20%

75%

Sufficient

30%

20%

Fairly good

45%

5%

Excellent

5%0%

Do you think your skin is smoother and softer?
Yes

80%

20%

No

15%

65%

No opinion

5%

15%

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies

supplementation and continued over the entire study
period. It is assumed that the ingested sphingolipids converted to sphingolipid metabolites which are absorbed
through the intestine and distribute in the blood. Subsequently these metabolites reach the skin and play their
physiological role to restore skin dryness [20].
In the present study a scoring scale for the diagnosis of
the symptom severity was used to assess the efficacy of A.
konjac extract. As a preliminary clinical trial this study included only the subjective measurement. Subjective scoresare validated and clearly reflect the symptom severity.
Even though the extent and intensity of skin condition are
central to measure the severity, the symptoms of patientsare subjective; hence an ideal scoring system should
include the subjective symptoms [21, 22]. The overall
efficacy of A. konjac extract was found to be increasing
significantly with time compared to the baseline. Our
results agreed with the subject perception of the productefficacy as determined through the self-assessment questionnaire. Importantly, oral intake of A. konjac extract did
not induce any toxic signs and was well tolerated throughout the study period. The present study, however, lacks
the performance data collected via objective assessment.

Conclusion
In this clinical trial, we have shown that daily oral intake of
A. konjac extract (glycosylceramides) significantly improved
the skin health compared to placebo. However, considering
the limitations of study being single-blinded and subjective,
further trials are required using a double-blinded study design including the objective measurements to further explore the efficacy of A. konjac extract, and its effect on theenhancement of ceramide content in the skin.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s12906-019-2721-3.
Additional file 1. Additional data. Characterization of SkinCera, Study
event schedule, subject disposition, subject demographic data analysis,
effect of SkinCera treatment on percentage subject response to skinparameters, analysis of vital signs and diagnosis scoring scale.
Additional file 2. Questionnaire. Diagnosis questionnaire including thesymptom scoring scale.
Additional file 3. Characterization of constituents in SkinCera. Details ofother constituents of SkinCera apart from glycosylceramides 1–4.
Additional file 4. Sample size calculation.

Abbreviations
GCP: Good Clinical Practice; ICH: International Conference on Harmonization;
LCMS/MS: Liquid chromatography-Mass Spectrometry
Acknowledgements
We sincerely express our gratitude for Syncorp Clincare Technologies (P) Ltd.,
India for their valuable support.

(2020) 20:26

Page 8 of 9

Funds
The present study is a part of research activities conducted by Vidya Herbs
Pvt. Ltd., Bangalore, India. This clinical trial was funded by Vidya Herbs Pvt.
Ltd. All the authors involved in the conceptualization, design and conduct of
the study, and manuscript writing are employees of Vidya Herbs Pvt. Ltd.
Author contributions
SHV designed the study protocol and monitored the clinical trial. SHV also
wrote the manuscript. NP performed the phytochemical analysis of theinvestigational product and assisted in manuscript preparation. SK conceivedof the study and participated in its design and coordination and helped todraft the manuscript. All authors read and approved the final manuscript.
Availability of data and materials
The data sets used and/or analysed during the current study available fromthe corresponding author on reasonable request.
Ethics approval and consent to participate
This clinical trial was approved by the institutional ethics committee of Sri
Kalabyraveshwara Swamy Ayurvedic Medical College, Hospital and ResearchCenter, India. Subjects meeting all inclusion and no exclusion criteria signed
a written informed consent and enrolled in the study.
Consent for publication
A statement that consent to publish is included in the manuscript. ‘Consent
to publish’ is provided as supplementary file.
Competing interests
We have read and understood the BMC policy on declaration of interestsand declare the following interests: All authors had financial support fromthe Vidya Herbs Pvt. Ltd. and declare the authors have a potential financial
competing interest. The funding was oriented to institutional researchsupport. The funding received from Vidya Herbs may in any way gain or losefinancially from the publication of the article, either now or in the future.
Received: 27 August 2018 Accepted: 21 October 2019

References
1. Feingold KR, Elias PM. Role of lipids in the formation and maintenance of the
cutaneous permeability barrier. Biochim Biophys Acta. 1841;2014:280–94.
2. Jungersted JM, Hellgren LI, Jemec GB, Agner T. Lipids and skin barrier
function–a clinical perspective. Contact Dermatitis. 2008;58:255–62.
3. Rabionet M, Gorgas K, Sandhoff R. Ceramide synthesis in the epidermis.
Biochim Biophys Acta. 1841;2014:422–34.
4. Nilsson A, Duan RD. Alkaline sphingomyelinases and ceramidases of thegastrointestinal tract. Chem Phys Lipids. 1999;102:97–105.
5. Ueda O, Hasegawa M, Kitamura S. Distribution in skin of ceramide after oral
administration to rats. Drug Metab Pharmacokinet. 2009;24:180–4.
6. Ueda O, Uchiyama T, Nakashima M. Distribution and metabolism ofsphingosine in skin after oral administration to mice. Drug Metab
Pharmacokinet. 2010;25:456–65.
7. Duan J, Sugawara T, Hirose M, Aida K, Sakai S, Fujii A, et al. Dietarysphingolipids improve skin barrier functions via the upregulation ofceramide synthases in the epidermis. Exp Dermatol. 2012;21(6):448–52.
8. Kajimoto O. Clinical investigation of skin-beautifying effect of a beauty
supplement containing rice-derived ceramide. J New Rem Clin. 2002;51:62–72.
9. Uchiyama T, Nakano Y, Ueda O, Mori H, Nakashima M, Noda A, et al. Oral
intake of glucosylceramide improves relatively higher level oftransepidermal water loss in mice and healthy human subjects. J Health Sci.
2008;54:559–66.
10. Hori M, Kishimoto S, Tezuka Y, Nishigori H, Nomoto K, Hamada U, et al.
Double-blind study on effects of glucosyl ceramide in beet extract on skinelasticity and fibronectin production in human dermal fibroblasts. AntiAging Med. 2010;7:129–42.
11. Imokawa G, Ishida K. Role of ceramide in the barrier function of the stratum
corneum: implications for the pathogenesis of atopic dermatitis. J Clin Exp
Dermatol Res. 2014;5:1.
12. Tessema EN, Gebre-Mariam T, Neubert RHH, Wohlrab J. Potential
applications of phyto-derived ceramides in improving epidermal barrier
function. Skin Pharmacol Physiol. 2017;30:115–38.

Heggar Venkataramana et al. BMC Complementary Medicine and Therapies

13. Coderch L, De Pera M, Fonollosa J, De La Maza A, Parra J. Efficacy of stratum
corneum lipid supplementation on human skin. Contact Dermatitis. 2002;47:139–46.
14. Usuki S, Tamura N, Sakai S, Tamura T, Mukai K, Igarashi Y.
Chemoenzymatically prepared konjac ceramide inhibits NGF-induced
neurite outgrowth by a semaphorin 3A-like action. Biochem Biophys Rep.
2016;5:160–7.
15. Usuki S, Tamura N, Yuyama K, Tamura T, Mukai K, Igarashi Y. Konjac
ceramide (kCer) regulates NGF-induced neutrite outgrowth via the Sema3A
signaling pathway. J Oleo Sci. 2018;67(1):77–86.
16. Zhang J, Hou W, Feng S, Chen X, Wang H. Classification of facial wrinkles
among Chinese women. J Biomed Res. 2017;31(2):108–15.
17. Beer KR. Combined treatment for skin rejuvenation and soft-tissue
augmentation of the aging face. J Drugs Dermatol. 2011;10(2):125–32.
18. Ono J, Kinoshita M, Aida K, Tamura M, Ohnishi M. Effects of dietary
glucosylceramide on dermatitis in atopic dermatitis model mice. Eur J Lipid
Sci Technol. 2010;112:708–11.
19. Shimoda H, Terazawa S, Hitoe S, Tanaka J, Nakamura S, Matsuda H, et al.
Changes in ceramides and glucosylceramides in mouse skin and humanepidermal equivalents by rice-derived glucosylceramide. J Med Food. 2012;
15:1064–72.
20. Bizot V, Cestone E, Michelotti A, Nobile V. Improving skin hydration andage-related symptoms by oral administration of wheat glucosylceramides
and digalactosyl diglycerides: a human clinical study. Cosmetics. 2017;4:37.
21. Luger T, Van Leent EJ, Graeber M, Hedgecock S, Thurston M, Kandra A, et al.
An emerging safe and effective treatment for atopic dermatitis. Br J
Dermatol. 2001;144:788–94.
22. Paller A, Eichenfield LF, Leung DY, Stewart D, Appell M. A 12-week study oftacrolimus ointment for the treatment of atopic dermatitis in pediatricpatients. J Am Acad Dermatol. 2001;44:47–57.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

(2020) 20:26

Page 9 of 9