PMID 35719159 Effectiveness of Dietary Supplement for Skin Moisturizing in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Meta-analysis · Front Nutr, 2022 Review of 66 randomized trials of moisturizing supplements - hyaluronan significantly raised skin hydration; its effect on transepidermal water loss is unknown for lack of trials.
Key summary
A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of moisturizing supplements in healthy adults. Searching three databases from January 2000 to November 2021, it identified 66 randomized trials and meta-analyzed only supplements with four or more trials. Hyaluronan showed a statistically significant positive effect on skin hydration, while its effect on transepidermal water loss was unknown for lack of trials. The abstract gives no placeboAn inert dummy treatment used as the comparison baseline.-adjusted effect size, but the full text reports SMD +0.40 (95% CI 0.11–0.68) pooled from 4 hyaluronan-only trials (196 people). All the supplements were safe over the study periods, normally 24 weeks or less. An author works for a pharmaceutical company (Haisco).
Show original abstract
BACKGROUND: The dietary supplement industry offers many oral cosmetics that purportedly assist in skin moisturization often with unclear evidence supporting efficacy and safety. To update the accessible proofs pertaining to the safety and effectiveness of oral dietary supplements to facilitate skin moisturizing via an all-around review and meta-analysis. METHODS: Three on-line databases [Pubmed, Embase, and Cochrane Library (CENTRAL)] were retrieved from January 2000 to November 2021. An overall 66 randomized controlled trials (RCTs) of skin care were recognized. Meta-analysis was performed for dietary supplements with four or more available research. RESULTS: Oral collagen or ceramide resulted in a statistically significant increase in skin hydration and a decrease in transepidermal water loss (TEWL) compared to placebo. No benefits regarding the improvement of skin conditions in terms of water content and TEWL were observed for lactic acid bacteria or Lactobacillus fermented foods. A statistically significant and positive effect on skin hydration was observed for both hyaluronan and procyanidin, with an unknown effect on TEWL due to insufficient RCTs. There was a non-significant improvement in the water content of stratum corneum for astaxanthin based on subgroup analyses. Among the dietary supplements trialed in ≤ 3 RCTs, the judgment regarding their effects on skin moisturizing was prevented by inconsistent conclusions as well as insufficient research. All food supplements were safe throughout the research (normally ≤ 24 weeks). CONCLUSION: Oral dietary supplements, including collagen, ceramides, hyaluronan, and procyanidin, were proven to be effective for skin moisturization. At present, for skin moisturization, the proofs supporting the recommendation of other dietary supplements, such as lactic acid bacteria and astaxanthin, are insufficient. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021290818. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
Show what the full text adds
Pooling 4 hyaluronan-only trials (196 people), the effect on skin hydration was SMD +0.40 (95% CI 0.11–0.68).
"The meta-analysis of four researches (n = 196) on hyaluronan as a single preparation generated remarkable effects on skin hydration, with an SMD + 0.40 (95% CI 0.11, 0.68; p = 0.007) in comparison to placebo (Figure 6)."
One of those trials (Hsu 2021) was rated at high risk of bias because two researchers were employees of the company that owned the product.
"The research of Hsu 2021 was at high risk of other biases, as two researchers were the employees of the corporation owing the dietary supplement."
※ Quotes machine-checked against the open full text in PMC (CC BY, 2026-11-07) View original ↗ PMID 40911749 Oral Hyaluronic Acid Supplement: Efficacy in Skin Hydration, Elasticity, and Wrinkle Depth Reduction Meta-analysis · J Drugs Dermatol, 2025 7 randomized trials of oral hyaluronic acid - hydration, elasticity, and wrinkle depth were significant; firmness, wrinkle volume, and transepidermal water loss were not.
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. limited to randomized trials of oral hyaluronic acid. It found 7 trials through PubMed and Google Scholar and compared standardized mean differences. Skin hydration, elasticity, and wrinkle depth improved significantly, while firmness, wrinkle volume, and transepidermal water loss did not. The abstract gives no effect size figures, and the authors wrote that limited sample size and heterogeneity call for larger, more robust trials.
Show original abstract
BACKGROUND: Hyaluronic acid (HA) is a key component naturally present in the skin and is commonly used in skincare formulations and dermal fillers. Recently, there has been growing interest in oral HA supplementation for maintaining skin health and preventing aging due to its potential systemic benefits. OBJECTIVE: This study aims to provide a comprehensive analysis of the efficacy of oral HA supplementation on various skin parameters, including hydration, elasticity, firmness, wrinkle reduction, and transepidermal water loss. METHOD: Electronic databases (PubMed and Google Scholar) were searched for relevant articles. A total of 7 randomized controlled trials (RCTs) on the use of oral HA as a supplement were identified. A meta-analysis was performed to compare the standardized mean differences between the treatment (HA) and control (placebo) groups. RESULTS: The meta-analysis revealed statistically significant improvements in skin hydration, elasticity, and wrinkle depth following oral HA supplementation. Although the effects of oral HA on skin firmness, wrinkle volume, and transepidermal water loss were not statistically significant, a general trend of improvement was observed in these parameters. CONCLUSION: The findings of this analysis align with existing literature, underscoring the potential of oral HA supplementation as a valuable component in anti-aging and skincare regimens. However, the study's limited sample size and heterogeneity among included studies call for larger, more robust trials to confirm these findings and further explore the effects of oral HA on skin health. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 40761858 Effectiveness of dietary supplements for skin photoaging in healthy adults: a systematic review and meta-analysis of randomized controlled trials Meta-analysis · Front Med (Lausanne), 2025 Review of 40 randomized trials of supplements for photoaging - hyaluronic acid showed no significant benefit on photoaging or on MED and R2 elasticity.
Key summary
A systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of supplements for skin photoaging in healthy adults. Searching four databases through October 2024, it screened 40 randomized trials. Collagen, flavanols, and other polyphenols beat placeboAn inert dummy treatment used as the comparison baseline., while hyaluronic acid, lycopene, and carotenoidA family of yellow, orange, and green plant pigments; lutein, zeaxanthin, and beta carotene belong to it.s showed no significant benefit on photoaging, minimal erythema dose (MED), or the skin elasticity measure R2. Oral supplements were safe over study periods typically of 24 weeks or less.
Show original abstract
BACKGROUND: The dietary supplement industry offers a wide range of orally consumed products that claim to combat skin photoaging, however, there is a lack of research on the proof of safety and effectiveness of dietary supplements in anti-skin photoaging. To further confirm their safety and efficacy, this article provides a detailed review and meta-analysis. METHODS: Four databases, including PubMed, Embase, Web of Science, and the Cochrane Library (Central Database), were searched for relevant literature up to October 2024. A total of forty English-language randomized controlled trials (RCTs) investigating the relationship between dietary supplements and skin photoaging were screened for an in-depth review and meta-analysis. RESULTS: Collagen, flavanols, and other polyphenol supplements have been found to alleviate skin photoaging and increase MED or overall skin elasticity (R2) when compared to a placebo. However, hyaluronic acid, lycopene, and carotenoids did not show any significant benefits in improving skin photoaging or MED/R2. Due to inconsistent findings and limited research, the effects of dietary supplements on skin photoaging could not be determined in randomized controlled trials with two or fewer studies. It is important to note that, during the study period (typically ≤ 24 weeks), all orally administered dietary supplements were found to be safe. CONCLUSION: Oral dietary supplements, such as collagen, flavanols, and polyphenols, have demonstrated effectiveness in addressing skin photoaging. However, there is currently insufficient evidence to support the recommendation of other dietary supplements, such as astaxanthin, for the treatment of skin photoaging. This research serves as an initial step in exploring the benefits of dietary supplements in combating skin photoaging. It underscores the need for more focused studies to further investigate the effects of dietary supplements on skin photoaging and gather additional evidence supporting their efficacy. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023472473, identifier CRD42023472473. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 41422283 Oral sodium hyaluronate improves skin hydration, barrier function and signs of aging: a randomized, double-blind, placebo-controlled trial in 150 healthy adults Randomized controlled trial · Sci Rep, 2025 150 people for 12 weeks at 1.8 MDa - 120 mg/day beat placeboAn inert dummy treatment used as the comparison baseline. on hydration, elasticity, and periorbital wrinkle depth, with 60 mg weaker. Most authors are employees of a manufacturer.
Key summary
The largest hyaluronic-acid-only oral trial identified in this review. It assigned 150 healthy Caucasian adults to 60 mg/day or 120 mg/day of 1.8 MDa sodium hyaluronate or placeboAn inert dummy treatment used as the comparison baseline. for 12 weeks. The 120 mg group beat placebo on hydration and elasticity, with lower transepidermal water loss, sebum, and periorbital wrinkle depth, plus greater epidermal thickness and dermal density. The 60 mg group was similar but more modest, and color, red areas, pores, and gloss did not change. The abstract gives no effect size figures. According to the full text, the hyaluronic acid manufacturer Contipro funded the research, the trial was run at Contipro's facilities, and six of the seven authors were Contipro employees. The paper declares that the company was not involved in design or analysis. ClinicalTrials.gov registration was retrospective.
Show original abstract
Oral hyaluronan has been reported to improve various aspects of skin physiology, but existing trials often lack methodological rigor, comprehensive outcome assessment, and diverse populations. This randomized, double-blind, placebo-controlled trial evaluated the effects of sodium hyaluronate (SH) supplementation at two daily doses on skin parameters in healthy Caucasian adults. A total of 150 participants were randomized to receive SH (1.8 MDa) at 60 mg/day (SH60), 120 mg/day (SH120), or placebo for 12 weeks. Facial hydration, transepidermal water loss (TEWL), sebum, elasticity, wrinkle depth, skin gloss, colorimetric parameters, epidermal thickness, dermal density, red areas, and pore size were assessed at baseline and monthly. Subjective skin condition was evaluated every two weeks, and components of natural moisturizing factor (NMF) in forearm skin were quantified by LC-MS/MS. SH120 significantly enhanced skin hydration and elasticity, while reducing TEWL, sebum, and periorbital wrinkle depth versus placebo. It also improved skin structure by increasing epidermal thickness, dermal density, and NMF levels. SH60 showed similar but more modest effects. No changes were observed for colorimetric parameters, red areas, pore size, or gloss. In conclusion, oral SH supplementation improved multiple aspects of skin physiology, supporting its use as a functional food ingredient with measurable benefits for skin health and healthy aging.Trial registration: ClinicalTrials.gov, NCT07065110 (retrospectively registered on 15 Jul 2025); EFSA (European Food Safety Authority) registry: EFSA202400027979 (prospectively filed on 06 Jun 2024). ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
Show what the full text adds
The research was funded by the hyaluronic acid manufacturer Contipro.
"Funding This research was funded by Contipro a.s."
Six of the seven authors were Contipro employees.
"ID, PK, VB, MŠ, IM, and FP were employees of Contipro a.s."
The trial was conducted at Contipro's facilities.
"The study was conducted at the facilities of Contipro a."
※ Quotes machine-checked against the open full text in PMC (CC BY 4.0, 2026-11-07) View original ↗ PMID 38931263 The Effects of Dietary Supplementation with Collagen and Vitamin C and Their Combination with Hyaluronic Acid on Skin Density, Texture and Other Parameters: A Randomised, Double-Blind, Placebo-Controlled Trial Randomized controlled trial · Nutrients, 2024 87 people for 16 weeks - adding 30 mg of hyaluronic acid to 5 g collagen and 80 mg vitamin C gave no added benefit, and neither product significantly affected hydration or elasticity.
Key summary
A three-arm double-blind trial completed by 87 women, comparing placeboAn inert dummy treatment used as the comparison baseline., 5 g collagen with 80 mg vitamin C, and the same product plus 30 mg hyaluronic acid over 16 weeks. Both products improved dermis density, skin texture, and wrinkle severity, with no significant effect on elasticity or hydration. The authors concluded that added benefit from hyaluronic acid beyond collagen alone cannot be confirmed. This is not a hyaluronic-acid-only trial, and the 30 mg/day dose is on the low side. A company (Tosla) produced the study products, and the paper declares it was not involved in design or analysis.
Show original abstract
Collagen dietary supplements are becoming increasingly popular as a means to reduce signs of skin ageing. The objective of this three-way, randomised, placebo-controlled, double-blind study was to examine and contrast the effects of dietary supplementation with a daily dose of 5 g hydrolysed collagen with 80 mg of vitamin C (CP product) and their combination with 30 mg of hyaluronic acid (CPHA product) over 16 weeks. Validated methods were utilised for the objective evaluation of skin parameters. In total, 87 subjects (women, 40-65 years) completed the entire trial, distributed across the groups as follows: placebo group (n = 29), CPHA group (n = 28), and CP group (n = 30). The results showed beneficial effects of both test products, with notable enhancements in dermis density, skin texture, and a reduction in the severity of wrinkles. In contrast, the administration of either of the products did not yield any significant impacts on skin elasticity or hydration. Observation of the investigated skin parameters did not show superior effects of the addition of hyaluronic acid (HA) to collagen. Therefore, the ability of supplementation with HA to improve the effects on investigated skin parameters beyond the supplementation of collagen alone cannot be confirmed. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 28761365 Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period Randomized controlled trial · Clin Cosmet Investig Dermatol, 2017 60 people with crow's feet for 12 weeks at 120 mg/day - the result the abstract names as significant versus placeboAn inert dummy treatment used as the comparison baseline. is the 300 k group at week 8. Most authors are Kewpie employees.
Key summary
It assigned 60 Japanese adults aged 22-59 with crow's feet to 120 mg/day of 2 k or 300 k hyaluronic acid or placeboAn inert dummy treatment used as the comparison baseline. for 12 weeks. On image analysis of wrinkle replicas the hyaluronic acid groups did better than placebo, and the result stated as significant versus placebo is the 300 k group at week 8. Skin luster and suppleness improved from baseline in all groups. The abstract gives no effect size figures. Most authors are employees of Kewpie, which sells hyaluronic acid ingredients, and according to the full text Kewpie also carried out the trial.
Show original abstract
BACKGROUND: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. METHODS: The mean molecular weight (MW) of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22-59 years who presented with crow's feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey. RESULTS: During the study period, the HA groups showed better level of the whole sulcus volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline. CONCLUSION: The results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
Show what the full text adds
The trial itself was carried out by the hyaluronic acid ingredient company Kewpie.
"This study was conducted by Kewpie Corporation, who carried out a randomized, double-blind, placebo-controlled trial."
※ Quotes machine-checked against the open full text in PMC (CC BY-NC 3.0, 2026-11-07) View original ↗ PMID 25834304 Ingestion of hyaluronans (molecular weights 800 k and 300 k) improves dry skin conditions: a randomized, double blind, controlled study Randomized controlled trial · J Clin Biochem Nutr, 2015 61 people with dry skin for 6 weeks at 120 mg/day - both 800 k and 300 k raised moisture more than placeboAn inert dummy treatment used as the comparison baseline.. Authors are affiliated with Kewpie.
Key summary
It assigned 61 people with dry skin to 120 mg/day of 800 k or 300 k hyaluronic acid or placeboAn inert dummy treatment used as the comparison baseline. for 6 weeks. Moisture rose more than placebo in both groups during ingestion, and the 300 k group remained significantly better than placebo 2 weeks after ingestion ended. Dermatologists found no adverse events related to ingestion. The abstract gives no effect size figures. The author affiliation listed in the PubMed record is the R&D division of Kewpie, which sells hyaluronic acid ingredients. According to the full text, Kewpie also made the test products, yet no conflicts of interest were declared.
Show original abstract
Hyaluronan (HA) has been increasingly used as a dietary supplement to improve the skin. However, the effect of ingested HA may depend on its molecular weight (MW) because its physiological activities in the body vary with its MW. In this study, we examined the effects of ingested HA with varying MW on the skin. In this randomized, double blind, placebo controlled study, 61 subjects with dry skin received oral HA (120 mg/day), of MWs 800 k and 300 k or placebo, for 6 weeks. The skin moisture contents of the first two groups increased more than those of the placebo group during the ingestion period. In addition, group HA 300 k exhibited significant improvements in skin moisture content 2 weeks after ingestion ended compared with the placebo group. A questionnaire survey about subjective facial aging symptoms showed that the HA treated groups exhibited significantly improved the skin condition compared with the placebo treated group. Furthermore, dermatologists objectively evaluated the clinical symptoms of the facial and whole body skin, showing that no adverse events were related to daily ingestion of HA. This study shows that both of ingesting HAs (MWs 800 k and 300 k) improved the skin condition by increasing the moisture content. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
Show what the full text adds
Both test products were made by Kewpie.
"The two types of HA, Hyaluronsan HA-F and Hyabest® (S) LF-P, used in this study were manufactured by Kewpie Corporation (Tokyo, Japan)"
Although most authors were affiliated with Kewpie, no conflicts of interest were declared.
"Conflict of Interest No potential conflicts of interest were disclosed."
※ Quotes machine-checked against the open full text in PMC (CC BY, 2026-11-07) Correction or update checked: The 2015 correction (open text in PMC) was read. In Figure 3A on subjective skin condition, the lines for the 800k and 300k groups were swapped, and the statistical test named in the figure (Dunnett to Steel Dwass) and units and values in Tables 2 and 5 were corrected. The skin hydration results this dossier uses were not among the corrections, so the rating is unaffected.
View original ↗ PMID 39886281 Oral Hyaluronic Acid in Osteoarthritis and Low Back Pain: A Systematic Review Systematic review · Mediterr J Rheumatol, 2024 11 articles and 597 patients at 30-300 mg/day - 9 reported improvement in pain, function, and related measures, but the abstract reports no pooled estimate.
Key summary
A systematic review of papers on oral hyaluronic acid and rheumatic disease, searched in PubMed. It included 11 articles and 597 patients, 10 on osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). and 1 on low back pain. Doses ran 30 to 300 mg/day and follow-up from 4 weeks to 12 months. Nine of the 11 observed improvement in pain, WOMACA standard index scoring pain, stiffness, and function in knee or hip osteoarthritis., joint function, quality of life, the Lequesne index, or stiffness, and adverse effects were rare and mild. The outcomes are symptoms and inflammatory markers, with no cartilage structure measure named in the abstract. The abstract gives no pooled effect size.
Show original abstract
BACKGROUND: Hyaluronic acid (HA) has been largely used in clinical practice for rheumatic diseases. However, the effects of oral HA on these diseases are poorly understood. AIM: To review articles evaluating oral HA's effects on rheumatic patients. METHODS: PubMed was searched for articles on oral HA and rheumatic diseases between 1966 and May 2024. RESULTS: Eleven articles were found with 597 patients. The diseases investigated were OA (n=10) and low back pain (n=1). Age varied from 40 to 70 years old, and female gender ranged from 43% to 75%. Follow-up ranged from 4 weeks to 12 months. The oral HA dosage varied from 30 mg to 300 mg/day. Concerning outcome, 9/11 articles observed improvement in rheumatic diseases in the following parameters: VAS pain, WOMAC, joint function, SF-36, Lequesne index, and stiffness. Two studies evaluated cytokines and observed a reduction of them after oral HA therapy. Adverse effects were rare and mild. CONCLUSION: Oral HA seems to be a safe and effective therapy for OA and low back pain patients, although more studies should be done on the latter condition. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 23226979 Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period Randomized controlled trial · ScientificWorldJournal, 2012 60 people with knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). for 12 months at 200 mg/day - both groups improved, with a significant difference only in those aged 70 or younger at months 2 and 4.
Key summary
It assigned 60 people with Kellgren-Lawrence grade 2 or 3 knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). to 200 mg/day of hyaluronic acid or placeboAn inert dummy treatment used as the comparison baseline. for 12 months, with both groups doing daily quadriceps strengthening. Symptom scores (JKOM) improved over time in both groups, with a trend favoring hyaluronic acid. Results significantly better than placebo were limited to patients aged 70 or younger at the 2nd and 4th months. The authors cautiously wrote that symptoms may improve in those aged 70 or younger when combined with exercise. According to the full text, the hyaluronic acid used was a product of the ingredient company Kewpie.
Show original abstract
This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects' symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
Show what the full text adds
The hyaluronic acid used was Kewpie's product (Hyabest J).
"The hyaluronic acid used in this study was manufactured by kewpie Corporation (Tokyo) (Hyabest (J))."
※ Quotes machine-checked against the open full text in PMC (CC BY, 2026-11-07) View original ↗ PMID 34622845 Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain: A randomized controlled study Randomized controlled trial · Medicine (Baltimore), 2021 80 people with moderate knee pain for 8 weeks - a liquid combining 50 mg hyaluronan, 750 mg glucosamine, and 250 mg chondroitin did not beat placeboAn inert dummy treatment used as the comparison baseline..
Key summary
A double-blind trial in osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA). patients with moderate knee pain. Participants drank 20 mL of a liquid with 50 mg hyaluronan, 750 mg glucosamine, and 250 mg chondroitin, or placeboAn inert dummy treatment used as the comparison baseline., for 8 weeks, with 80 in the modified intent-to-treat population. KOOS, WOMACA standard index scoring pain, stiffness, and function in knee or hip osteoarthritis., SF-36, and a sleep measure showed no significant difference from placebo, and no product-related adverse event was reported. The authors added that results need caution because of design limitations. As a combination product, it does not isolate hyaluronan's own effect. According to the full text, the product company sponsored the trial and supplied the product and placebo, yet the result was null.
Show original abstract
BACKGROUND: Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4-6 points). METHODS: This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population. RESULTS: Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups. CONCLUSIONS: This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based on this text and the full-text quotes below.
Show what the full text adds
The trial was sponsored by the product company Top Pharm.
"This study was sponsored by the Top Pharm & Medicalware, Taiwan."
Top Pharm also made and supplied the test product and placeboAn inert dummy treatment used as the comparison baseline..
"Both the study product and the placebo were manufactured and provided by TOP Pharm."
※ Quotes machine-checked against the open full text in PMC (CC BY 4.0, 2026-11-07) View original ↗ PMID 37182970 Molecular weight and gut microbiota determine the bioavailability of orally administered hyaluronic acid Animal study · Carbohydr Polym, 2023 13C-labeled mouse study - oral bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act. of about 0.2%. Gut microbes must cut it into fragments under 3 kDa before part of it is absorbed.
Key summary
It fed 13C-labeled hyaluronan to germ-free and conventional mice and compared absorption and metabolism by LC-MS. Gut Bacteroides were crucial for absorption, and specific microbes had to cleave hyaluronan into unsaturated oligosaccharides under 3 kDa before part of it crossed the intestinal wall. The remaining fragments were metabolized into short-chain fatty acids. Bioavailability was about 0.2%, which the authors read as pointing to systemic regulatory action rather than direct effects at the skin or joints. This is not a human trial. Some authors are affiliated with Contipro, and the paper declares no competing interests.
Show original abstract
The ability of hyaluronan as a dietary supplement to increase skin moisture and relieve knee pain has been demonstrated in several clinical studies. To understand the mechanism of action, determining hyaluronan's bioavailability and in vivo fate is crucial. Here, we used 13C-hyaluronan combined with LC-MS analysis to compare the absorption and metabolism of oral hyaluronan in germ-free and conventional wild-type mice. The presence of Bacteroides spp. in the gut was crucial for hyaluronan absorption. Specific microorganisms cleave hyaluronan into unsaturated oligosaccharides (<3 kDa) which are partially absorbed through the intestinal wall. The remaining hyaluronan fragments are metabolized into short-chain fatty acids, which are only metabolites available to the host. The poor bioavailability (~0.2 %) of oral hyaluronan indicates that the mechanism of action is the result of the systematic regulatory function of hyaluronan or its metabolites rather than the direct effects of hyaluronan at distal sites of action (skin, joints). ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 18959406 Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs Animal study · J Agric Food Chem, 2008 99mTc-labeled high-molecular-weight hyaluronan in rats and dogs - 86.7-95.6% of radioactivity was recovered, almost all in feces, with the remaining signal appearing in joints, vertebrae, and other tissues.
Key summary
It gave a single oral dose of 99mTc-labeled high-molecular-weight hyaluronan to rats and dogs and tracked absorption, distribution, and excretion. In rats, 86.7-95.6% of the radioactivity was recovered, almost all in feces. Radioactivity appeared in tissues from 15 minutes to 48 hours and concentrated in joints, vertebrae, and salivary glands at four hours. The authors called this the first evidence of uptake and distribution to connective tissues. The method shows where the label goes, so the abstract alone cannot settle whether the signal is the intact molecule or fragments.
Show original abstract
The purpose of this study was to determine the absorption, distribution and excretion of (99m)technetium-labeled, high-molecular-weight hyaluronan (((99m)Tc-HA) and (99m)technetium pertechnetate ((99m)Tc-P) after single dose, oral administration to Wistar rats and Beagle dogs. A pilot study utilized (99m)Tc-HA alone, and a second confirmatory study compared uptake of labeled (99m)Tc-HA with (99m)Tc-P. Urinary and fecal excretion after (99m)Tc-HA ingestion by rats showed 86.7-95.6% of radioactivity was recovered, almost all in feces. All tissues examined showed incorporation of radioactivity from (99m)Tc-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from (99m)Tc-P. Whole-body scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from (99m)Tc-HA concentrated in joints, vertebrae and salivary glands four hours after administration. Autoradiography of skin, bone and joint tissue pieces after 24 h showed incorporation of radioactivity from (99m)Tc-HA, but not from (99m)Tc-P. Conversely, absorption, distribution and excretion of (99m)Tc was completely different from (99m)Tc-HA, showing an expected pattern of rapid absorption and excretion in urine, with accumulation in thyroid glands, stomach, kidney and bladder. This report presents the first evidence for uptake and distribution to connective tissues of orally administered, high-molecular-weight HA. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 42914415 Hyaluronic acid in functional foods and oral supplements: linking molecular weight, bioavailability, and food matrix effects to clinical translation Review · Food Res Int, 2026 Overall oral bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act. is low, no molecular-weight hierarchy is established, and frequent multi-ingredient products prevent attributing effects to hyaluronic acid alone.
Key summary
A review linking molecular characteristics, gastrointestinal fate, and clinical evidence for hyaluronic acid in foods and oral supplements. It finds low overall oral bioavailabilityThe fraction of an ingested substance that actually reaches the blood and tissues to act., with very small oligosaccharides the more plausible candidates for epithelial passage and larger polymers generally needing further gastrointestinal degradation. It states explicitly that these tendencies do not establish a universal molecular-weight hierarchy for systemic exposure, local activity, or clinical efficacy. Reported clinical improvements in hydration, wrinkles, and joint discomfort are constrained by incomplete molecular characterization, varied doses and formulations, short periods, and multi-ingredient products.
Show original abstract
Hyaluronic acid (HA) has attracted growing interest as a multifunctional ingredient in functional foods and oral supplements because of its techno-functional properties and proposed benefits for skin and joint health. However, the physiological relevance of orally administered HA remains difficult to interpret because its gastrointestinal fate, exposure, and clinical outcomes may depend on molecular weight distribution, dose, formulation, processing history, food-matrix interactions, and host-related factors. This review integrates evidence on HA molecular characteristics, gastrointestinal transformation, food applications, and clinical translation. Current evidence indicates low overall oral bioavailability and suggests that very small HA-derived oligosaccharides are more plausible candidates for epithelial passage, whereas larger polymers generally require further gastrointestinal degradation. These tendencies do not establish a universal molecular-weight hierarchy for systemic exposure, local activity, or clinical efficacy. In food systems, HA has been investigated in dairy products, protein gels, emulsions, edible films, coatings, and delivery systems, but most evidence remains based on model or in vitro studies, with limited characterization of HA after processing and digestion. Clinical studies have reported improvements in selected skin hydration, wrinkle-related, and joint discomfort outcomes; nevertheless, interpretation is constrained by incomplete molecular characterization, heterogeneous doses and formulations, short intervention periods, and frequent use of multi-ingredient products, which prevent HA-specific attribution. Overall, HA has potential as a techno-functional food ingredient and oral supplement, but progress requires standardized molecular reporting, adequately controlled HA-only trials, and matrix-specific studies linking processing, gastrointestinal fate, exposure, and clinically relevant outcomes. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 36333100 Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis Meta-analysis · injection route · BMJ, 2022 Evidence on intra-articular injection, not oral products. 24 large placeboAn inert dummy treatment used as the comparison baseline.-controlled trials in 8,997 participants gave a pain SMD of -0.08, below the minimal clinically important difference.
Key summary
A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of intra-articular viscosupplementation (hyaluronic acid injection) in the knee, not of oral products. It included 169 trials and 21,163 participants, with the main analysis on 24 large placeboAn inert dummy treatment used as the comparison baseline.-controlled trials of at least 100 per group, totaling 8,997 participants. The pain SMD was -0.08 (95% CI -0.15 to -0.02), equal to -2.0 mm on a 100 mm scale and short of the prespecified minimal clinically important difference of -0.37. In 15 large trials with 6,462 participants, the relative risk of serious adverse events was 1.49 (95% CI 1.12 to 1.98) versus placebo. The authors concluded the findings do not support broad use for knee osteoarthritisThe most common degenerative joint disease, in which cartilage wears down causing pain and stiffness (OA)..
Show original abstract
OBJECTIVE: To evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis. DESIGN: Systematic review and meta-analysis of randomised trials. DATA SOURCES: Searches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment. MAIN OUTCOME MEASURES: The prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was -0.37 SMD. Serious adverse events were analysed as relative risks. METHODS: Two reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias tool. The predefined main analysis was based only on large, placebo controlled trials with ≥100 participants per group. Summary results were obtained through a random effects meta-analysis model. Cumulative meta-analysis and trial sequential analysis under a random effects model were also performed. RESULTS: 169 trials provided data on 21 163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function (Egger's tests with P<0.001 and asymmetric funnel plots). Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD -0.08, 95% confidence interval -0.15 to -0.02), with the lower bound of the 95% confidence interval excluding the minimal clinically important between group difference. This effect corresponds to a difference in pain scores of -2.0 mm (95% confidence interval -3.8 to -0.5 mm) on a 100 mm visual analogue scale. Trial sequential analysis for pain indicated that since 2009 there has been conclusive evidence of clinical equivalence between viscosupplementation and placebo. Similar conclusions were obtained for function. Based on 15 large, placebo controlled trials on 6462 randomised participants, viscosupplementation was associated with a statistically significant higher risk of serious adverse events than placebo (relative risk 1.49, 95% confidence interval 1.12 to 1.98). CONCLUSION: Strong conclusive evidence indicates that viscosupplementation leads to a small reduction in knee osteoarthritis pain compared with placebo, but the difference is less than the minimal clinically important between group difference. Strong conclusive evidence indicates that viscosupplementation is also associated with an increased risk of serious adverse events compared with placebo. The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021236894. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ 식품의약품안전처 MFDS (식품안전나라 Open API I-0040) Recognition status of functional ingredients for health functional foods - hyaluronic acid entries
This is an institutional information source. Verify directly in the original below.
View original ↗ 