Study collection

Original title: Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period

Summary: In this randomized, double-blind, placebo-controlled human study, knee osteoarthritis patients received 200 mg of oral hyaluronic acid daily for 12 months, accompanied by standardized muscle training. Results showed significant improvements in pain and joint function, particularly in participants ≤ 70 years of age, compared to placebo.

Publication: Scientific World Journal

Study objective: To evaluate the long-term efficacy and tolerability of orally administered hyaluronic acid (200 mg/day) in patients with knee osteoarthritis (Kellgren–Lawrence grade 2–3) compared to placebo – during concurrent quadriceps training.

Study design: Double-blind, randomized, placebo-controlled clinical trial with 60 participants (grade 2–3 knee osteoarthritis). Subjects were randomly assigned to two groups:

• Intervention group: 200 mg of oral hyaluronic acid daily for 12 months, plus daily quadriceps muscle training.
• Placebo group: Identical except for the substance (placebo instead of hyaluronic acid).

Evaluation was performed every 2 months using the Japanese Knee Osteoarthritis Measure (JKOM). Subgroup analyses were conducted for participants ≤ 70 years of age.

Results: Both groups showed improvements in symptoms and function over time. JKOM scores were significantly better in the hyaluronic acid group than in placebo at 2 and 4 months, particularly in younger patients (≤ 70 years). Long-term benefits persisted over 12 months, accompanied by good tolerability and few side effects.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3512263/

Original title: Biomarkers of Nutrition and Health: the antioxidant potential of oral hyaluronan

Summary: This study is the first to investigate in humans how a single oral dose of 240 mg of high-molecular-weight hyaluronic acid from chicken comb extract (containing resveratrol) affects blood antioxidant capacity (ORAC). The aim was to identify direct effects on biomarkers.

Publication: Genes & Nutrition

Study objective: To determine whether an oral dose of hyaluronic acid with concomitant resveratrol increases the total antioxidant capacity of the blood (measured by ORAC) and hyaluronic acid plasma levels.

Study design: Randomized, placebo-controlled crossover study with 13 healthy adults. Each participant received on two separate days:

1. Intervention: 240 mg orally administered hyaluronic acid (high molecular weight, probably about 300 kDa) combined with resveratrol.
2. Placebo: equivalent control preparation without active ingredients.

There was an appropriate washout period between the two test days. Repeated blood samples were taken over 8 hours after ingestion to measure:

• the antioxidant capacity (ORAC),
• Hyaluronic acid plasma levels using immunological methods.

Results: Immediately after administration, a significant increase in ORAC values compared to placebo was observed, as was a parallel increase in serum hyaluronic acid. These results indicate that hyaluronic acid is not only detectable in the blood, but can also exert antioxidant effects.

https://link.springer.com/article/10.1007/s12263-014-0417-3

Original title: Oral intake of a liquid high-molecular-weight hyaluronan associated with relief of chronic pain and reduced use of pain medication: results of a randomized, placebo-controlled double-blind pilot study

Summary: This pilot study shows that 4 weeks of daily intake of a liquid dietary supplement containing high molecular weight hyaluronic acid (HMW-HA) significantly relieves chronic pain, reduces the need for pain medication, and improves sleep quality and energy levels compared to placebo.

Publication: Journal of Medicinal Food

Study objective: The aim was to evaluate the effect of orally administered hyaluronic acid on chronic pain and to investigate the safety and tolerability of the preparation.

Study design: Randomized, double-blind, placebo-controlled study with:

• 78 adults (19–71 years), of which 72 university graduates
• Verum group: 45 ml/day (2 weeks), then 30 ml/day (2 weeks)
• Placebo group: identical, without active ingredient
• Measurement times: Baseline, 2 weeks, 4 weeks
• Endpoints: VAS pain, sleep quality, energy, safety (blood values, ECG)

Results:

• Significant pain reduction after 2 weeks (p < 0.001)
• Improved sleep quality (p < 0.005)
• Reduced need for painkillers (p < 0.05)
• No unwanted side effects

https://doi.org/10.1089/jmf.2013.0174

Original title: Oral hyaluronan relieves wrinkles: a double-blind, placebo-controlled study

Summary: This double-blind, placebo-controlled human study shows that daily oral intake of 120 mg of low or medium molecular weight (2 kDa or 300 kDa) hyaluronic acid for 12 weeks significantly reduces skin wrinkles and improves skin appearance, especially crow's feet.

Publication: Clinical, Cosmetic and Investigational Dermatology (CCID)

Study objective: To investigate whether oral hyaluronic acid in two different molecular weights is able to reduce wrinkles (crow's feet) and increase skin luster and suppleness compared to placebo.

Study design: Randomized, double-blind, placebo-controlled study with 60 healthy Japanese participants (22–59 years of age). Participants were randomly assigned to three groups:

• Hyaluronic acid 2 kDa – 120 mg/day (in 2 capsules of 60 mg each)


• Hyaluronic acid 300 kDa – 120 mg/day (in 2 capsules of 60 mg each)


• Placebo group – 2 capsules of filler/day

The study lasted 12 weeks, with skin analyses before, after 4, 8, and 12 weeks. Measurement methods:

Image analysis of skin replicas (crow's feet) to determine sulcus, wrinkle volume and area changes

Questionnaire survey on skin luster and suppleness

Results:

• After 8 weeks, the 300 kDa group showed significantly lower wrinkle volume compared to placebo (p < 0.05).


• Both hyaluronic acid groups (2 kDa & 300 kDa) showed consistently lower sulcus, wrinkle area and wrinkle volume ratios than placebo.
• After 12 weeks, skin shine and suppleness improved significantly in all verum groups (p < 0.05).


• No adverse side effects were observed

https://www.dovepress.com/oral-hyaluronan-relieves-wrinkles-a-double-blinded-placebo-controlled--peer-reviewed-fulltext-article-CCID

Original title: The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain: An 8-week randomized double-blind placebo-controlled trial

Summary: This double-blind, placebo-controlled study investigated whether 8 weeks of daily administration of a liquid supplement combination of low molecular weight hyaluronic acid, glucosamine, and chondroitin could relieve pain and improve joint function in patients with mild knee osteoarthritis (VAS ≤ 3).

Publication: Journal of Functional Foods

Study objective: To evaluate the effectiveness and safety of a combined dietary supplement (HA + glucosamine + chondroitin) in mild knee osteoarthritis with a focus on pain reduction and improvement of quality of life.

Study design: Randomized, double-blind, placebo-controlled study with 47 adult knee osteoarthritis patients (VAS ≤ 3). Participants received either:

• Verum group (A+HA): a 20 ml bottle with low molecular weight hyaluronic acid combined with glucosamine and chondroitin.
• Placebo group: a sensory identical liquid without active ingredients.

Measurement times were at baseline, after 4 weeks and after 8 weeks, with the evaluated parameters:

• WOMAC total and subscores (pain, stiffness, function)


• SF36 Quality of Life Questionnaire (physical function, pain)


• Safety: Vital signs and laboratory values (few side effects)

Results:

• WOMAC: Significant reduction of pain, stiffness and function in the active treatment vs. placebo after 8 weeks (p < 0.01).


• SF36: Significant improvement in physical function (p = 0.001) and physical pain scale (p < 0.05) in the verum group compared to placebo.


• Total SF36: Increase in the verum group, but without statistical significance (P = 0.12).


• Safety profile: Well tolerated with no serious side effects; laboratory and vital signs stable.

https://pubmed.ncbi.nlm.nih.gov/33592868/

Original title: Preventive effects of oral hyaluronic acid on knee discomfort in healthy older adults: A randomized, double-blind, placebo-controlled trial

Summary: A 12-week intake of 111 mg hyaluronic acid daily showed significant reduction of subjective knee symptoms in healthy older adults without manifest osteoarthritis – compared to placebo.

Publication: Nutrients, February 2023; Vol. 15, No. 2, Article 297. DOI: 10.3390/nu15020297 (mdpi.com)

Study objective: To investigate the preventive effect of oral hyaluronic acid on temporary or mild knee symptoms in healthy elderly people without radiologically confirmed osteoarthritis.

Study design: Randomized, double-blind, placebo-controlled study with 31 healthy older adults (mean age ≈ 60 years). Subjects received either:

• Verum group: 111 mg hyaluronic acid daily


• Placebo group: Identical capsule without active ingredient

Measurement times: Baseline, Week 4, Week 8, Week 12 Assessments:

• Subjective knee complaints using VAS (0–100 mm)


• Functional tests (e.g., one-legged stand, walking down stairs)


• Blood parameters for inflammatory markers (secondary)

Results:

• Significant reduction of subjective knee symptoms in the verum group compared to placebo (statistically significant).


• The placebo group showed slight improvements, but significantly less.


• Functional tests and inflammatory markers remained largely unchanged in both groups.


• No serious side effects; generally well tolerated.

https://www.mdpi.com/2072-6643/15/2/297

Original title: Efficacy of oral hyaluronic acid on skin hydration in younger vs. older women

Summary: This study demonstrates that oral administration of low and high molecular weight hyaluronic acid for 12 weeks significantly improves skin hydration, skin tone, and epidermal thickness in both young and older women, regardless of skin type.

Publication: Skin Research and Technology

Study objective: To evaluate the effect of oral hyaluronic acid on different skin types (dry, oily, normal) and age groups (young vs. old) regarding moisture, skin tone, and skin texture.

Study design: Randomized, double-blind, placebo-controlled study with a total of 129 women (61 young [18–35 years], 67 older [45–65 years]).

• Groups: placebo (erythritol), 100 mg HA/day, or 200 mg HA/day (partially 300 kDa).


• Duration: 12 weeks


• Measurement times: Baseline, weeks 2, 4, 8 and 12

Parameters examined:

• Skin moisture (Corneometer CM825)


• Epidermis thickness & skin density (ultrasound)


• Skin tone (Visia-CR & Chromameter ITAo)


• Controlled conditions (22 °C/50 % humidity, 30 min acclimatization)

Results:

• Skin moisture: Significant increase after 2–8 weeks in both HA groups, across all skin types and age groups (p < 0.05)


• Skin tone (ITA^o): Improved values after 4–8 weeks in both treatment groups (p < 0.05)


• Epidermal thickness: Increase in the HA groups after 12 weeks (p < 0.05)


• Placebo: no significant changes


• Safety: No side effects, stable health status

https://pubmed.ncbi.nlm.nih.gov/38009035/

Original title: Oral Intake and Topical Application of Hyaluronic Acid Ameliorates Skin Aging Signs: Efficacy Results of a Placebo-Controlled In&Out Trial

Summary: This randomized, placebo-controlled in-and-out study demonstrates that the combination of oral and topical hyaluronic acid over 8 weeks acts synergistically, providing significant improvements in skin hydration, elasticity, wrinkle reduction, and skin texture—better than oral or topical application alone.

Publication: Cosmetics (MDPI), 2025; Volume 12, No. 2, Article 52

Study objective: To evaluate the individual and combined effects of oral and topical hyaluronic acid on various skin aging parameters in healthy adults – compared to placebo.

Study design: Randomized, double-blind, placebo-controlled study with four groups:

• Oral application (120 mg HA/day) + topical placebo cream


• Topical application (cream with HA) + oral placebo capsule


• Combination of oral (120 mg HA/day) and topical HA cream


• Pure placebo (oral + topical)

The intervention lasted 8 weeks. A total of approximately 88 healthy volunteers were randomized. Measurement times and methods:

• Baseline, 4 weeks, 8 weeks


• Instrumental skin analyses: moisture (corneometer), elasticity (cutometer), wrinkle depth (replica technique), skin roughness & skin density


• Subjective evaluation through satisfaction questionnaires

Results:

Combined group (oral + topical):

• Greatest increase in skin moisture and elasticity


• Most significant reduction in wrinkle depth (p < 0.05)

Single applications (oral or topical):

• Both oral and topical HA showed significant improvements over placebo (p < 0.05), but less than the combined group

Safety & Tolerance:

• No serious side effects


• Skin irritation and system parameters unremarkable

https://www.mdpi.com/2079-9284/12/2/5