Abstract
Introduction
Aging leads to structural and compositional changes in the skin, contributing to more wrinkles, less smoothness, and dryness. There is growing interest in oral non-invasive interventions to help ameliorate visual signs of skin aging. The purpose of this study was to evaluate the efficacy of an oral skincare supplement containing hyaluronic acid and wheat oil extract on parameters of skin aging in a diverse population.
Methods
Healthy adults (ages 26–64) were recruited and randomly assigned to the intervention group (n = 31) or placebo group (n = 32). The intervention group received an oral skincare supplement consisting of wheat oil extract and low molecular weight sodium hyaluronate, with a 12-week follow-up period.
Results
The intervention group demonstrated a significant reduction in crow’s feet wrinkles and improvements in both facial and global skin smoothness beginning at week 8 and continuing to week 12, compared to the placebo group. Additionally, the intervention group exhibited significant increases in skin hydration and elasticity in the leg region relative to the placebo group. Dermatologists’ evaluations revealed significant reductions in global scores of both deep and fine wrinkles from baseline to week 12, but only in the intervention group. By week 12, a greater proportion of participants in the intervention group reported improvements in fine lines and wrinkles, skin radiance/glow, skin resilience/elasticity, and overall signs of aging, with these changes being significantly different from the placebo group.
Conclusion
An oral skincare supplement combining wheat oil extract and hyaluronic acid offers a comprehensive method for addressing skin aging, providing measurable clinical improvements in various skin parameters and enhancing subjective perceptions of skin health and appearance.
Trial Registration
ClinicalTrials.gov identifier, NCT06083402.
Keywords: Ceramides, Dietary supplement, Hyaluronic acid, Non-invasive, Skin aging
Plain Language Summary
As we age, our skin undergoes changes that result in wrinkles, dryness, and reduced smoothness. This study examined whether taking a daily oral supplement containing hyaluronic acid and wheat oil extract could improve signs of skin aging. We conducted a 12-week study with 63 adults aged 26–64 years who were randomly assigned to take either the skincare supplement or a placebo. Using specialized equipment and dermatologist evaluations, we found that participants taking the supplement showed significant improvements in crow’s feet wrinkles and skin smoothness starting at week 8. They also experienced better skin hydration and elasticity in the leg area compared to those taking the placebo. Dermatologists observed reductions in both deep and fine wrinkles in the supplement group. By the end of the study, more participants taking the supplement reported improvements in fine lines and wrinkles, skin radiance, elasticity, and overall signs of aging compared to the placebo group. These findings suggest that this oral supplement may provide a non-invasive approach to improving multiple aspects of skin aging in a racially diverse study population.
Key Summary Points
| Why carry out this study? |
| Aging leads to structural and compositional changes in the skin contributing to visible signs of aging, and there is growing interest in non-invasive oral interventions to address these changes. |
| This study aimed to evaluate whether an oral skincare supplement containing hyaluronic acid and wheat oil extract could improve various parameters of skin aging in a diverse population. |
| What was learned from the study? |
| The intervention group showed significant improvements in crow’s feet wrinkles, facial skin smoothness, and leg hydration and elasticity compared to placebo, with effects on wrinkles and smoothness starting at week 8. |
| This study demonstrates significant improvements in objective measures of crow’s feet wrinkles and skin smoothness with an oral skincare supplement in a racially diverse study population, offering a non-invasive approach to lessen visual signs of skin aging. |
Introduction
The skin, the largest organ in the human body, is a structurally complex system comprising multiple layers and diverse cell types, serving as the primary interface between the body and its external environment [1–3]. It is commonly divided into two main compartments: the epidermis and the dermis. The epidermis, along with its outermost layer, the stratum corneum, which is organized in a “brick and mortar” configuration where corneocytes are layered within a matrix of intercellular lipids such as ceramides, cholesterol, and free fatty acids, is crucial for the skin’s barrier function, protecting against environmental exposures and minimizing excessive water loss [3]. Beneath the epidermis lies the dermis, a layer rich in connective tissue, blood vessels, glands, nerves, and hair follicles, which supports the skin’s structural integrity, facilitates temperature regulation, and contributes to sensory perception [4]. Below the dermis, a subcutaneous fat layer provides mechanical shock protection and insulation against external cold and heat [5].
Aging induces natural structural and compositional changes in the skin driven by both intrinsic factors, such as genetics and hormonal changes, and extrinsic factors, including pollution and ultraviolet (UV) exposure [6–9]. These changes manifest as the progressive thinning of the epidermis, a reduction in the skin’s natural water and lipid content, flattening of the dermo-epidermal junction, and decreased turnover of three primary structural components of the dermis; hyaluronic acid, elastin, and collagen. Consequently, the skin becomes thinner, drier, and more prone to wrinkling [10]. While lifestyle modifications, such as avoiding UV radiation and pollution, abstaining from smoking, engaging in regular physical activity, and consuming a diet rich in fruits and vegetables, especially those high in carotenoids, polyphenols, and antioxidants, can confer antiaging benefits [11–13], the antiaging industry, valued at over $17 billion, has seen significant growth over the past two decades [14].
The majority of aesthetic antiaging research has focused on the topical application or injection of structural components of the dermis like collagen, elastin, and glycosaminoglycans (GAGs), as well as antioxidants in the forms of vitamins, polyphenols, and flavonoids, which are known to influence collagen degradation and production [7, 15]. However, these topical approaches primarily address localized areas of the skin rather than enhancing global skin health. In contrast, ingestible compounds have the potential to exert effects on the skin more comprehensively, although challenges related to their bioavailability and ability to reach skin tissues persist [16]. Recent research has highlighted the antiaging potential of orally ingested compounds such as collagen, antioxidants, algae, hyaluronic acid, and certain plant extracts such as oil extracts from wheat, rice, and konjac, which are rich in lipids like ceramides [17–23].
Hyaluronic acid, a GAG found abundantly in the skin, particularly in the dermis where it is synthesized by fibroblasts, plays a pivotal role in maintaining skin hydration and mitigating signs of aging owing to its ability to bind and retain water [9]. This molecule is a common ingredient in both topical and ingestible antiaging formulations, with its biological effects being dependent on its molecular weight [24]. Ceramides, which are a major intracellular lipid component in the stratum corneum, function as essential elements of the epidermal permeability barrier, preventing excessive water loss and blocking the penetration of harmful environmental substances [3, 25]. While topical ceramide-containing emollients have been shown to enhance skin hydration and barrier function, recent attention has also focused on the oral ingestion of lipid-rich oil extracts from wheat, rice, and konjac as a promising dietary intervention for alleviating skin wrinkles and improving hydration [19, 20, 26–28].
Both hyaluronic acid and wheat oil extract have demonstrated beneficial effects on skin health in human clinical studies, potentially through distinct mechanisms [19–23]. This suggests that their combination might offer synergistic benefits. However, these dietary components have not yet been tested together in a clinical setting, and their impact on overall skin condition remains largely unexplored. Therefore, this study aims to evaluate the efficacy of an oral skincare supplement combining hyaluronic acid and wheat oil extract on various skin aging parameters in healthy adults over the course of 12 weeks through a randomized, double-blind, placebo-controlled design.
Methods
Study Design and Ethics Approval
This was a prospective, single-center, randomized, double-blind, placebo-controlled clinical study conducted by an independent research organization (Princeton Consumer Research, Raritan, New Jersey, USA). All procedures were approved by Allendale Investigational Review Board and conformed to the standards set by the Declaration of Helsinki. All subjects provided consent to participate in the study and have their images taken and shared. The study was registered at ClinicalTrials.gov (NCT06083402).
Study Samples
The intervention group received an oral skincare supplement, HyaCera™ (manufactured by Ritual, Los Angeles, CA), which contained 350 mg of wheat oil extract and 120 mg of lower molecular weight (average 300–400 kDa) sodium hyaluronate (Hyabest®(S)LF-P; Kewpie Corporation, Japan) in a nested capsule. The placebo capsules contained high oleic safflower oil and microcrystalline cellulose and were designed to mimic the intervention supplement in appearance and sensory characteristics. Participants were instructed to consume one capsule per day for 12 weeks.
CONSORT Diagram and Study Participants
The CONSORT diagram of the study is presented in Fig. 1. Seventy adults consented to partake in the study. Two participants did not meet inclusion criteria upon pretesting and were excluded before beginning the study. Inclusion criteria included healthy adult volunteers aged 25–70 with mild to moderately dry skin and crow’s feet wrinkles as assessed by a dermatologist on a 10-point grading scale who were willing to abstain from any facial and body treatments during the study (i.e., fillers, microdermabrasion, peels, facials, laser treatments, toxin treatments, etc.). Exclusion criteria included self-reported pregnancy, breastfeeding, or plans to become pregnant during the study, known allergies or hypersensitivities to dietary/herbal supplements or any test product ingredients, use of omega-3 fatty acids (> 350 mg) and/or vitamin E (> 7.5 mg) supplements within 2 weeks of study start, use of isotretinoin/Accutane, Retin-A, or retinol in the last 3 months, or any medical condition deemed to compromise safety or confound study results. Sixty-eight subjects passed the screening and were randomly assigned to the intervention and placebo groups. Four people withdrew during the study for personal reasons, and one was lost to follow-up. None were discontinued because of adverse events.
Fig. 1.
CONSORT diagram. This figure illustrates the number of participants from enrollment to trial completion
Study Schedule and Measurements
The study was conducted over a period of 12 weeks. Participants reported to the study site to be assessed on three body sites: the face (crow’s feet area), arm (back of left arm), and leg (left thigh) and at four time points: week 0 (baseline), 4, 8, and 12. Participants were assessed for skin wrinkles, smoothness, scaliness, roughness, hydration, elasticity, and barrier function (as transepidermal water loss) using objective dermatologic measurement tools (Table 1). Visual and tactile inspection regarding fine lines, medium or deep lines and wrinkles, dryness, radiance/luminosity, and smoothness was completed by a dermatologist and clinical photographs of the face were taken from three angles. Participants were also given a subjective questionnaire to report the appearance of their skin on a variety of parameters to collect self-reported changes as well as a 19-food group Dietary Screener Questionnaire (DSQ) to assess their diet [29].
Table 1.
List of assessment parameters and measurement specifics
| Parameter | Measurement device | Measurement location | Unit of measure |
|---|---|---|---|
| Skin smoothness | VISIOSCANⓇ VC98 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
SEsm |
| Skin wrinkles | VISIOSCANⓇ VC98 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
SEw |
| Skin roughness | VISIOSCANⓇ VC98 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
SEsr |
| Skin scaliness | VISIOSCANⓇ VC98 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
SEsc |
| Skin hydration | CorneometerⓇ CM 825 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
Arbitrary units (AU) |
| Skin firmness | CutometerⓇ MPA 580 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
R0 |
| Skin elasticity | CutometerⓇ MPA 580 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
R2 |
| Skin barrier function/TEWL | TewameterⓇ TM300 (Courage & Khazaka) |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
g/h/m2 |
| Fine lines | Visual dermatologist evaluation |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
10-point grading scale |
| Medium/deep lines and wrinkles | Visual dermatologist evaluation |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
10-point grading scale |
| Skin dryness | Visual dermatologist evaluation |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
10-point grading scale |
| Skin radiance/luminosity | Visual dermatologist evaluation |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
10-point grading scale |
| Skin texture/smoothness | Visual dermatologist evaluation |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
10-point grading scale |
| Skin texture/smoothness | Tactile dermatologist evaluation |
Face (crow’s feet area) Arm (back of left arm) Leg (left thigh) |
10-point grading scale |
Statistical Analyses
Prior to enrollment of subjects, a power analysis was performed to determine the sample size needed to detect a difference between the intervention and placebo groups [21]. It was expected that a total of 60 participants would provide > 80% power and an alpha of 0.05 in detection of a difference between intervention and placebo groups in skin hydration.
Changes in objective and dermatologist skin measurements from baseline to post-intervention (week 12) were analyzed using analysis of covariance (ANCOVA) controlling for baseline measurement, gender, and age. If the effect was significant at the post-intervention assessment, the same analysis was conducted at the previous measurement point to identify the first instance where the effect was observed. Additionally, a global score for each measure was developed by summing face, arm, and leg scores. Paired t test was used to assess the change in global scores from baseline to week 12 within each group.
Self-report responses were categorized as either favorable responses (“agree” and “strongly agree”) or unfavorable responses (“neutral”, “disagree”, and “strongly disagree”). Differences between favorable and unfavorable responses were analyzed via a chi-squared test. Statistical analyses were performed in SPSS (Version 26; IBM SPSS Statistics Software, IBM Corp., Armonk, N.Y., USA).
Results
Participant Characteristics
From June to October 2023, 63 male and female participants completed the study. At baseline, all subjects had mild to moderate fine lines and wrinkles and dry skin as graded by a dermatologist. The participants were predominantly female (85.7% female and 14.3% male) and ranged in age from 26 to 64 years (mean 45.7 years). A summary of participant characteristics, including racial and ethnic distribution, can be found in Table 2. There were no significant differences between groups for these characteristics at baseline. The DSQ results showed no significant diet differences between the intervention and placebo groups at baseline or week 12.
Table 2.
Baseline characteristics of the study participants
| Characteristic | Group assignment | ||
|---|---|---|---|
| Intervention (n = 31) | Placebo (n = 32) | Total (n = 63) | |
| Age (years) | 45.2 ± 10.1 | 46.3 ± 10.3 | 45.7 ± 10.1 |
| Gender | |||
| Female | 28 (90.3%) | 26 (81.3%) | 54 (85.7%) |
| Male | 3 (9.7%) | 6 (18.7%) | 9 (14.3%) |
| Race | |||
| White | 16 (51.6%) | 16 (50%) | 32 (50.8%) |
| Black | 11 (35.5%) | 10 (31.3%) | 21 (33.3%) |
| Asian | 2 (6.5%) | 4 (12.5%) | 6 (9.5%) |
| American Indian or Alaskan Native | 0 (0%) | 1 (3.1%) | 1 (1.6%) |
| Other | 2 (6.4%) | 1 (3.1%) | 3 (4.8%) |
| Ethnicity | |||
| Hispanic or Latino | 3 (9.7%) | 4 (12.5%) | 7 (11.1%) |
| Non-Hispanic or Latino | 28 (90.3%) | 28 (87.5%) | 56 (88.9%) |
| Fitzpatrick skin type | |||
| I | 0 (0%) | 0 (0%) | 0 (0%) |
| II | 6 (19.4%) | 2 (6.3%) | 8 (12.7%) |
| III | 8 (25.8%) | 13 (40.6%) | 21 (33.3%) |
| IV | 7 (22.6%) | 9 (28.1%) | 16 (25.4%) |
| V | 7 (22.6%) | 4 (12.5%) | 11 (17.5%) |
| VI | 3 (9.7%) | 4 (12.5%) | 7 (11.1%) |
Skin Imaging and Biophysical Measures
Figure 2 shows changes in crow’s feet wrinkles (SEw) over the course of the study. Compared to the placebo group, the intervention group experienced a significant reduction in crow’s feet wrinkles starting at week 8 (F = 4.96, p < 0.05) and continuing to week 12 (F = 4.60, p < 0.05). Analysis of the global wrinkle score showed a significantly greater reduction at week 8 for the intervention group (F = 5.10, p < 0.05), but the significant difference did not continue to week 12 (p = 0.17). Both groups showed a significant reduction in global skin wrinkles from baseline to week 12 (p < 0.001).
Fig. 2.
Changes from baseline in crow’s feet wrinkles (SEw) after ingestion of test product (intervention) or placebo over the study period. SEw was measured at four time points: baseline (prior to ingestion), 4 weeks of ingestion, 8 weeks of ingestion, and 12 weeks of ingestion. Changes in SEw are shown relative to the baseline condition (Δ); higher change score indicates greater wrinkle reduction. ANCOVA was used to compare groups controlling for baseline, gender, and age. Data are presented as means ± SE. *p < 0.05, compared to the placebo group
Changes in facial and global skin smoothness (SEsm) over time are shown in Figs. 3 and 4, respectively. At the facial site, smoothness improved in the intervention group compared to the placebo group at week 8 (F = 4.92, p < 0.05) and 12 (F = 5.62, p < 0.05) while globally, improvements were also measured at week 8 (F = 4.67, p < 0.05) and 12 (F = 4.43, p < 0.05). Global hydration scores significantly improved from baseline to week 12 for both intervention and placebo groups (p ≤ 0.001), but there was no significant difference between groups. Looking at body sites, the intervention group experienced improved hydration in the leg (F = 4.13, p < 0.05), while the placebo led to improved hydration in the face (F = 5.03, p < 0.05) by week 12.
Fig. 3.
Changes from baseline in facial skin smoothness (SEsm) after ingestion of test product (intervention) or placebo over the study period. SEsm was measured at four time points: baseline (prior to ingestion), 4 weeks of ingestion, 8 weeks of ingestion, and 12 weeks of ingestion. Changes in SEsm are shown relative to baseline condition (Δ); higher change score indicates greater improvement in smoothness. ANCOVA was used to compare groups controlling for baseline, gender, and age. Data are presented as mean ± SE. *p < 0.05, compared to the placebo group
Fig. 4.
Changes from baseline in global skin smoothness (SEsm) after ingestion of test product (intervention) or placebo over the study period. SEsm was measured at four time points: baseline (prior to ingestion), 4 weeks of ingestion, 8 weeks of ingestion, and 12 weeks of ingestion. Changes in SEsm are shown relative to the baseline condition (Δ); higher change score indicates greater improvement in smoothness. ANCOVA was used to compare groups controlling for baseline, gender, and age. Data are presented as means ± SE. *p < 0.05, compared to the placebo group
At week 12, the intervention group experienced significantly improved R2, a measure of skin elasticity, on the leg compared to the placebo group (F = 4.35, p < 0.05). Global skin elasticity was found to be significantly improved from baseline to week 12 for the intervention group (p < 0.01), while the placebo group showed no significant change (p = 0.14). No difference between groups was found for R0, a measure of firmness. The global score for R0 increased from baseline to week 12 in the intervention group (p < 0.01) but not in the placebo group (p = 0.14).
By week 12, no significant differences were found between groups in regard to roughness (SEsr), skin scaliness (SEsc), or skin barrier function expressed as transepidermal water loss (TEWL). Global roughness values as SEsr decreased from baseline to week 12 for both groups (both p < 0.01), while global scaliness and transepidermal water loss remained stable throughout the study period.
Dermatologist Evaluation and Self-Report
Dermatologist evaluation of skin condition revealed no significant between-group differences on any of the graded parameters. However, when changes were examined within each group over time, dermatologist assessments indicated improvements from baseline to week 12 in several global skin parameters. Specifically, in the intervention group, global deep wrinkles decreased significantly by week 12 compared with baseline (p < 0.01), whereas no significant change was observed in the placebo group (p = 0.10). Similarly, dermatologist-graded global fine wrinkles were reduced from baseline to week 12 in the intervention group (p < 0.05), but not in the placebo group (p = 0.14). Improvements in global skin radiance/luminosity were observed relative to baseline at week 4 and persisted through week 12 in both groups (both p ≤ 0.001). By week 12, dermatologist-evaluated global tactile smoothness improved significantly compared with baseline in both the placebo (p < 0.05) and intervention (p < 0.01) groups, and visual smoothness also improved within both groups (p < 0.05).
Compared to the placebo group, more participants in the intervention group reported improvements in fine lines and wrinkles (χ2 = 5.72, p < 0.05), skin glow/radiance (χ2 = 6.02, p < 0.05), skin resilience/elasticity (χ2 = 8.47, p < 0.01), and general signs of aging (χ2 = 4.73, p < 0.05) by week 12.
Side Effects and Tolerability
No side effects as a result of consuming the intervention or placebo capsules were reported. The majority of the participants reported that the oral skincare supplement was easy to add to their existing skincare regimen (96.8%, n = 30) and easy to swallow/take daily (93.5%, n = 29). Additionally, participants taking the oral skincare supplement indicated that they would keep taking it if they could (80.6%, n = 25) and would recommend the product to a friend (74.2%, n = 23).
Discussion
Daily ingestion of an oral skincare supplement over 12 weeks resulted in significant improvements in crow’s feet wrinkles, skin smoothness, hydration, and elasticity compared to placebo. These results align with prior research showing that oral supplementation with wheat oil extract or hyaluronic acid can support various aspects of skin health [19–23]. What distinguishes the present study is the demonstration of significant improvements in objective measures of crow’s feet wrinkles and global skin smoothness, assessed by VisioscanⓇ, in a racially diverse sample of both women and men at 8 weeks. This suggests that the combination of these two ingredients may have relevance for a broad range of individuals, though further research is warranted to confirm the extent of their applicability across populations.
The exact mechanisms behind the observed skin benefits remain unclear. Hyaluronic acid is widely recognized for its exceptional water-retention capacity, which contributes to maintaining the extracellular matrix [9]. Additionally, in vitro studies have shown that hyaluronic acid can stimulate human fibroblast proliferation, potentially increasing collagen synthesis, thereby improving skin elasticity and reducing wrinkles [21, 23, 30]. Ceramides, on the other hand, are essential components of the skin barrier. They help restore and maintain the lipid barrier and protect the skin from environmental stressors [3]. Together, these ingredients likely influence multiple physiological pathways, though further research is needed to elucidate the specific mechanisms through which they exert their antiaging effects. Furthermore, although not an objective of the study, the research team observed that at least one participant in the intervention group showed improvement in facial dyschromia between baseline and follow-up. Given the prevalence of this condition, this observation may warrant further investigation in a targeted cohort of affected individuals.
Interestingly, while significant differences were observed in the intervention group for leg region elasticity and hydration, the placebo group unexpectedly experienced improved hydration measures at the facial site by week 12. This finding was surprising, given that both active ingredients in the oral skincare supplement are known to positively influence skin hydration [19–22]. An exploratory analysis using Pearson’s correlation test between dermatologist-rated visual dryness on the face and Corneometer® hydration measurements revealed no significant relationship at any time point (r varied between − 0.1 and 0.04, P values ranged between 0.23 and 0.97). In contrast, significant correlations were observed between instrument readings and dermatologist ratings for the leg at multiple time points. Although unexpected, the discrepancy between objective and subjective assessments of skin hydration is not uncommon in the literature [31]. Furthermore, the study was conducted during the summer when participants are more prone to UV exposure, which can exacerbate skin dryness [32].
Dermatologist evaluations revealed significant reductions in global deep and fine wrinkles for the intervention group by week 12 but not for the placebo group, indicating a positive clinical effect of the supplement on wrinkle reduction. This improvement in fine lines and wrinkles was also reflected in self-report data, with significantly more participants in the intervention group reporting improvements compared to the placebo group. This suggests that the improvements were visible without specialized equipment or professional evaluation (Fig. 5). Additionally, self-reported data showed favorable outcomes in skin glow/radiance, skin resilience/elasticity, and overall signs of aging. The multifaceted evaluation used in this study, combining objective medical tools, dermatologist evaluations, and subjective perceptions, underscores the potential of the oral skincare supplement to address both precise and quantifiable changes in visible signs of skin health.
Fig. 5.
Photographic images of 6 participants (A–F) from the placebo (A–C) and intervention groups (D–F) at baseline and week 12
Despite its robust design, this study has several limitations. First, the sample size, while adequately powered, was relatively small. Second, the majority of the sample consisted of women. Third, uncontrolled factors such as exercise, sleep, hormonal regulation, and UV exposure could have influenced the results. Nonetheless, this is one of the first studies, to our knowledge, to examine the effect of an oral skincare supplement in a racially diverse population, with approximately 50% of participants being people of color (> 30% were Black), spanning a wide age range (26 to 64 years) and including a variety of skin types.
Conclusion
The oral administration of a skincare supplement containing wheat oil extract and hyaluronic acid demonstrates the potential to address skin aging by reducing wrinkles and improving skin smoothness. This non-invasive approach offers a novel alternative to traditional topical applications or treatments, whose effects are typically limited to specific skin regions. Given the established efficacy of topical ceramides and hyaluronic acid, the results of this study support the notion that combining oral supplementation of these ingredients with topical application could be a valuable addition to an existing skincare regimen. However, future research is necessary to explore the potential synergies between these delivery methods and elucidate their mechanisms of action. The findings of this study may inform future developments in advanced formulations and personalized skin care strategies aimed at enhancing skin health and combating signs of aging.
Acknowledgements
The authors would like to thank the study participants for their involvement and adherence to the study protocols.
Medical Writing/Editorial Assistance
OpenAI’s ChatGPT (GPT-4, OpenAI, San Francisco, CA, USA) was used for language improvement and to ensure consistency among authors as well as reference style adjustment. The authors reviewed and approved all generated content.
Author Contributions
All authors (Adeline M Grier-Welch, Mastaneh Sharafi, Arianne Y Vance, and Nima Alamdari) contributed to the study conception and design. The study was conducted, and data were collected by an independent contract research organization located in New Jersey, USA. Data analyses were performed by Mastaneh Sharafi with assistance from Adeline M Grier-Welch. Material preparation was performed by Adeline M Grier-Welch, Mastaneh Sharafi, and Arianne Y Vance. The first draft of the manuscript was written by Adeline M Grier-Welch and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
Ritual financially supported this study along with contribution from Kewpie Corporation, which manufactures Hyabest®(S)LF-P, found in HyaCera™. The Rapid Service Fee was funded by Ritual.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of Interest
Adeline M Grier-Welch, Mastaneh Sharafi, Arianne Y Vance, and Nima Alamdari are employees of Natals Inc. dba Ritual, which manufactures the dietary supplement tested in this research, HyaCera™. Nima Alamdari is an Advisory Board Member of Pvolve LLC.
Ethical Approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Allendale Investigational Review Board and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All subjects provided consent to participate in the study and have their images taken and shared. The study was registered at ClinicalTrials.gov (NCT06083402).
Footnotes
Prior Presentation: The results of this work were presented as a poster at NUTRITION 2024 in Chicago, Illinois and the associated abstract may be found in Current Developments in Nutrition (10.1016/j.cdnut.2024.102198).
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. Int J Mol Sci. 2013;14(6):12222–48. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Dyring-Andersen B, Lovendorf MB, Coscia F, et al. Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin. Nat Commun. 2020;11:5587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Menon GK, Cleary GW, Lane ME. The structure and function of the stratum corneum. Int J Pharm. 2012;435(1):3–9. [DOI] [PubMed] [Google Scholar]
- 4.Brown TM, Krishnamurthy K. Histology, dermis. Treasure Island, FL: StatPearls; 2022. [PubMed]
- 5.Baroni A, Buommino E, De Gregorio V, et al. Structure and function of the epidermis related to barrier properties. Clin Dermatol. 2012;30(3):257–62. [DOI] [PubMed] [Google Scholar]
- 6.Choi E. Aging of the skin barrier. Clin Dermatol. 2019;37(4):336–45. [DOI] [PubMed] [Google Scholar]
- 7.Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E, Zouboulis CC. Skin anti-aging strategies. Dermatoendocrinol. 2012;4(3):308–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kim EJ, Han JY, Lee HK, et al. Effect of the regional environment on the skin properties and early wrinkles in young Chinese women. Skin Res Technol. 2014;20(4):498–502. [DOI] [PubMed] [Google Scholar]
- 9.Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol. 2012;4(3):253–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Farage MA, Miller KW, Elsner P, Maibach HI. Characteristics of aging skin. Adv Wound Care (New Rochelle). 2013;2(1):5–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Pappas A, Liakou A, Zouboulis CC. Nutrition and skin. Rev Endocr Metab Disord. 2016;17(3):443–8. [DOI] [PubMed] [Google Scholar]
- 12.Schagen SK, Zampeli VA, Makrantonaki E, Zouboulis CC. Discovering the link between nutrition and skin aging. Dermatoendocrinol. 2012;4(3):298–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Whitehead RD, Re D, Xiao D, Ozakinci G, Perrett DI. You are what you eat: within-subject increases in fruit and vegetable consumption confer beneficial skin-color changes. PLoS ONE. 2012. 10.1371/journal.pone.0032988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Andrade LF, Hernandez LE, Mashoudy KD, et al. A cost-based analysis of anti-aging products across four major United States retailers. Cureus. 2023. 10.7759/cureus.46596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Bravo B, Correia P, Gonçalves JE Jr, Sant’Anna B, Kerob D. Benefits of topical hyaluronic acid for skin quality and signs of skin aging: from literature review to clinical evidence. Dermatol Ther. 2022;35(12):e15903. [DOI] [PMC free article] [PubMed]
- 16.He X, Wan F, Su W, Xie W. Research progress on skin aging and active ingredients. Molecules. 2023;28(14):5556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Al-Atif H. Collagen supplements for aging and wrinkles: a paradigm shift in the fields of dermatology and cosmetics. Dermatol Pract Concept. 2022;12(1):e2022018. [DOI] [PMC free article] [PubMed]
- 18.Januszewski J, Forma A, Zembala J, et al. Nutritional supplements for skin health—a review of what should be chosen and why. Medicina (Kaunas). 2023;60(1):68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Boisnic S, Keophiphath M, Serandour AL, et al. Polar lipids from wheat extract oil improve skin damages induced by aging: evidence from a randomized, placebo-controlled clinical trial in women and an ex vivo study on human skin explant. J Cosmet Dermatol. 2019;18(6):2027–36. [DOI] [PubMed] [Google Scholar]
- 20.Guillou S, Ghabri S, Jannot C, Gaillard E, Lamour I, Boisnic S. The moisturizing effect of a wheat extract food supplement on women’s skin: a randomized, double-blind placebo-controlled trial. Int J Cosmet Sci. 2010;33(2):138–43. [DOI] [PubMed] [Google Scholar]
- 21.Hsu TF, Su ZR, Hsieh YH, et al. Oral hyaluronan relieves wrinkles and improves dry skin: a 12-week double-blinded, placebo-controlled study. Nutrients. 2021;13(7):2220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Kawada C, Yoshida T, Yoshida H, et al. Ingestion of hyaluronans (molecular weights 800 k and 300 k) improves dry skin conditions: a randomized, double-blind, controlled study. J Clin Biochem Nutr. 2015;56(1):66–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Oe M, Sakai S, Yoshida H, et al. Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period. Clin Cosmet Investig Dermatol. 2017;10:267–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Snetkov P, Zakharova K, Morozkina S, Olekhnovich R, Uspenskaya M. Hyaluronic acid: the influence of molecular weight on structural, physical, physico-chemical, and degradable properties of biopolymer. Polymers (Basel). 2020;12(8):1800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Coderch L, López O, de la Maza A, Parra JL. Ceramides and skin function. Am J Clin Dermatol. 2003;4(2):107–29. [DOI] [PubMed] [Google Scholar]
- 26.Draelos ZD. An oral supplement and the nutrition-skin connection. J Clin Aesthet Dermatol. 2019;12(7):13–6. [PMC free article] [PubMed] [Google Scholar]
- 27.Heggar Venkataramana S, Puttaswamy N, Kodimule S. Potential benefits of oral administration of Amorphophallus konjac glycosylceramides on skin health: a randomized clinical study. BMC Complement Med Ther. 2020;20(1):26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Leo TK, Tan ESS, Amini F, et al. Effect of rice (Oryza sativa L.) ceramides supplementation on improving skin barrier functions and depigmentation: an open-label prospective study. Nutrients. 2022;14(13):2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Thompson FE, Midthune D, Kahle L, Dodd KW. Development and evaluation of the National Cancer Institute’s dietary screener questionnaire scoring algorithms. J Nutr. 2017;147(7):1226–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Greco RM, Iocono JA, Ehrlich HP. Hyaluronic acid stimulates human fibroblast proliferation within a collagen matrix. J Cell Physiol. 1998;177(3):465–73. [DOI] [PubMed] [Google Scholar]
- 31.Park JH, Choi Y, Jung YJ, et al. Skin hydration measurement: comparison between devices and clinical evaluations. Ann Dermatol. 2024;36(5):275–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Amaro-Ortiz A, Yan B, D’Orazio JA. Ultraviolet radiation, aging, and the skin: prevention of damage by topical cAMP manipulation. Molecules. 2014;19(5):6202–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.