Hyaluronic Acid

What hyaluronic acid is

Hyaluronic acid, also called hyaluronan, is a long sugar molecule made of repeating building blocks. The body produces it itself. It fills the space between the cells of the skin, makes the joint fluid viscous and keeps the vitreous body of the eye in shape. Its most important property is that it can bind large amounts of water.

For supplements, hyaluronic acid is today mostly produced by bacterial fermentation and sold as sodium hyaluronate. Products differ in molecular size. The largest skin study used a high-molecular-weight material of 1.8 MDa.

How it is supposed to work

At first glance, it seems unlikely that such a large molecule reaches the skin when swallowed. The animal data paint a more nuanced picture. In a study in rats, about 90 % of the labeled hyaluronic acid was absorbed from the digestive tract, and radioactivity in the skin was higher than in the blood after 24 and 96 hours. A second paper shows the route there: gut bacteria break the molecule down into smaller fragments, which are absorbed in the large intestine and distributed all the way into the skin.

The common explanation is therefore that these fragments act as a signal and stimulate the body’s own production in the skin. This is plausible but has not been demonstrated directly in humans. The human studies measure the result at the skin surface, not the route there.

Skin, joints, eyes

The skin is the best-studied field. This is where the meta-analysis, the large study with 150 participants and several smaller papers pointing in the same direction are found.

For the joints, a systematic review summarizes 11 papers with 597 patients, most of them on osteoarthritis, with durations of 4 weeks to 12 months and amounts of 30 to 300 mg per day. In 9 of the 11 studies, pain, function or stiffness improved. For the eye, it is important to distinguish: hyaluronic acid eye drops are a standard for dry eyes; a meta-analysis covers 39 studies with 3,469 patients. For the capsule, there is only one pilot study, in which it was given in addition to drops.

Many joint products combine hyaluronic acid with other substances. A randomized study with 100 participants with mild osteoarthritis tested a mixture of krill oil, astaxanthin and low-molecular-weight hyaluronic acid over 12 weeks. Joint pain on a 100-millimeter scale fell by 20.8 mm compared with 10.6 mm under placebo, in the analysis of the 75 people who completed the protocol in full. That is a clear effect, but it belongs to the mixture. What share the hyaluronic acid has in it cannot be read from such studies.

Experience reports

A published practice study without a control group followed 20 women between 45 and 60 years of age over 40 days who took a liquid combination product with hyaluronic acid, biotin, vitamin C, copper and zinc. As measured, skin hydration and elasticity rose, roughness and wrinkle depth decreased, and no side effects occurred. That is a report, not proof of efficacy: without placebo, it is impossible to separate what the hyaluronic acid, the other ingredients or the season contributed.

What the studies show

150 adults, two doses

Randomized, double-blind, placebo-controlled: 60 mg or 120 mg sodium hyaluronate or placebo over 12 weeks. Under 120 mg, skin hydration and elasticity rose; water loss, sebum and wrinkle depth around the eyes decreased; the epidermis became thicker and the natural moisturizing factor rose. 60 mg had a similar but weaker effect. Skin color, redness, pore size and gloss did not change.

12 weeks with 120 mg

In a study with 40 healthy adults between 35 and 64 years of age, wrinkles, hydration of the stratum corneum, water loss and elasticity improved significantly compared with placebo. The differences were measurable after 8 and after 12 weeks.

One year in knee osteoarthritis

60 people with knee osteoarthritis of Kellgren-Lawrence grade 2 or 3 took 200 mg daily or placebo over 12 months; both groups did daily strengthening exercises. Both groups improved, somewhat more under hyaluronic acid. The difference was significant only in people up to 70 years of age, in the 2nd and 4th month.

Where the data stop

The skin results rest on cosmetic measurement methods such as moisture probes and wrinkle analyses. These are sensible endpoints for a skin question, but the studies are small, and the meta-analysis itself names sample size and heterogeneity as a limitation. Then there is the origin: the largest study comes predominantly from employees of a hyaluronic acid manufacturer and was only registered retrospectively at ClinicalTrials.gov; employees of another manufacturer were involved in the 12-week study with 40 people. This does not make the results wrong, but independent confirmations are missing.

In osteoarthritis, the longest placebo-controlled study was significant only in a subgroup. Absorption and distribution into the skin have only been shown in rats. For dry eyes, the capsule rests on a pilot study with 54 people in which everyone received eye drops and the study group additionally swallowed hyaluronic acid; their symptom score fell from 61.8 to 42.3 after 3 months. Whether the capsule has any effect without drops has not been studied. For wound healing after oral intake and for joint lubrication by capsules, there are no human data; these effects belong to injections and gels, not to the oral form.

Status, approval and legal

In the EU, sodium hyaluronate produced by fermentation is not considered a novel food in food supplements; a consultation by the European Commission established this in February 2023. There is no statutory maximum amount. The EU has not authorized advertising claims on joint mobility and joint lubrication after review by EFSA. Injections into joints or as fillers are medical applications with their own legal status. Relevance for doping is not described in the literature evaluated.

Safety

Taken orally, hyaluronic acid is considered well tolerated. In the osteoarthritis review, side effects were rare and mild; in the practice study, none occurred. Studies over 12 weeks and one over 12 months are available, but no real long-term data. Data on pregnancy and breastfeeding are lacking, as is an official upper limit from EFSA, BfR or NIH. Relevant interactions with medicines are not described in the literature evaluated.

Sources

• Amin et al., J Drugs Dermatol 2025
• Dolečková et al., Sci Rep 2025
• Hsu et al., Nutrients 2021
• de Carvalho, Davidson, Mediterr J Rheumatol 2024
• Tashiro et al., ScientificWorldJournal 2012
• Kimura et al., J Med Food 2016
• Oe et al., ScientificWorldJournal 2014
• Martinez-Perez et al., Cont Lens Anterior Eye 2026
• Hill et al., Nutrients 2023
• European Commission, novel food status of sodium hyaluronate 2023