Collection of studies

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 orally administered hyaluronic acid daily over a period of 12 months, accompanied by standardized muscle training. The results showed significant improvements in pain and joint function, especially in participants ≤ 70 years compared to placebo.

Publication: Scientific World Journal

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

Study design: Double-blind, randomized, placebo-controlled clinical study with 60 participants (grade 2–3 knee osteoarthritis). The subjects were randomly divided into two groups:

• Intervention group: 200 mg orally taken 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.

Results: Both groups showed improvements in symptoms and function over time. In the hyaluronic acid group, JKOM scores were significantly better than placebo after 2 and 4 months – especially in younger participants (≤ 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 antioxidative potential of oral hyaluronan

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

Publication: Genes & Nutrition

Study objective: To determine whether an oral dose of hyaluronic acid with accompanying resveratrol increases the total antioxidant capacity of the blood (measured by ORAC) and the 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 approx. 300 kDa) combined with resveratrol.
2. Placebo: equivalent control preparation without active ingredients.

An appropriate wash-out period was observed between the two test days. Blood samples were repeatedly taken over 8 hours after intake to measure:

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

Results: Directly after intake, a significant increase in ORAC values was observed compared to placebo, along with a parallel increase in hyaluronic acid in the blood serum. These results suggest 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 a 4-week daily intake of a liquid dietary supplement with 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 goal: The aim was to evaluate the effect of orally administered hyaluronic acid on chronic pain as well as 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 completed the study
• 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-blinded, placebo-controlled study

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

Publication: Clinical, Cosmetic and Investigational Dermatology (CCID)

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

Study design: Randomized, double-blind, placebo-controlled study with 60 healthy Japanese participants (22–59 years). Subjects 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 duration was 12 weeks, with skin analyses before, and after 4, 8, and 12 weeks. Measurement methods:

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

Questionnaire survey on skin radiance and smoothness

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) consistently showed lower sulcus, wrinkle area, and wrinkle volume ratios over time compared to placebo.
• After 12 weeks, skin radiance and smoothness improved significantly in all verum groups (p < 0.05).
• No unwanted 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 doubleblind placebocontrolled trial

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

Publication: Journal of Functional Foods

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

Study design: Randomized, double-blind, placebo-controlled study with 47 adult knee osteoarthritis patients (VAS ≤ 3). Participants received daily for 8 weeks 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 time points were at study start, 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 parameters and laboratory values (few side effects)

Results:

• WOMAC: Significant reduction of pain, stiffness, and function in verum vs. placebo after 8 weeks (p < 0.01).
• SF36: Significant improvement in physical function (p = 0.001) and bodily pain scale (p < 0.05) in the verum group compared to placebo.
• Overall SF36: Increase in the verum group, but without statistical significance (P = 0.12).
• Safety profile: Well tolerated without serious side effects; laboratory and vital values 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 a 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: Investigation of the preventive effect of oral hyaluronic acid on transient or mild knee symptoms in healthy seniors without radiologically confirmed osteoarthritis.

Study design: Randomized, double-blind, placebo-controlled study with 31 healthy older adults (average age ≈ 60 years). Participants received either over 12 weeks:

• Verum group: 111 mg hyaluronic acid daily
• Placebo group: identical capsule without active ingredient

Measurement time points: baseline, week 4, week 8, week 12 Assessments:

• Subjective knee complaints using VAS (0–100 mm)
• Functional tests (e.g., one-leg stand, going down stairs)
• Blood parameters for inflammation markers (secondary)

Results:

• Significant reduction of subjective knee symptoms in the verum group compared to placebo (statistically significant).
• Placebo group showed slight improvements, but significantly less.
• Functional tests and inflammation markers remained largely unchanged in both groups.
• No serious side effects; overall tolerance good.

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 intake of low- and high-molecular-weight hyaluronic acid over 12 weeks significantly improves skin moisture, skin tone, and epidermis thickness in both young and older women regardless of skin type.

Publication: Skin Research and Technology

Study objective: Evaluation of 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 structure.

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 (partly 300 kDa).
• Duration: 12 weeks
• Measurement time points: baseline, week 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 verum groups (p < 0.05)
• Epidermis 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&Out study shows that the combination of oral and topical hyaluronic acid over 8 weeks acts synergistically and enables significant improvements in skin moisture, 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: Evaluation of 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. Approximately 88 healthy subjects were randomized in total. Measurement time points and methods:

• Baseline, 4 weeks, 8 weeks
• Instrumental skin analyses: moisture (Corneometer), elasticity (Cutometer), wrinkle depth (replica technique), skin roughness & skin density
• Subjective assessment via 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 compared to placebo (p < 0.05), but less pronounced than the combined group

Safety & tolerability:

• No serious adverse effects
• Skin irritations and systemic parameters unremarkable

https://www.mdpi.com/2079-9284/12/2/52