Hyaluronic Acid Side Effects

Hyaluronic acid is considered one of the safest supplements: it is a natural substance of our body, and clinical studies of oral forms rarely record adverse events. However, "safe" does not mean "without any risks." Moreover, the side-effect profile differs dramatically for capsules, cosmetics, and injections. The editorial team examined each option separately.

The overall safety picture

Hyaluronic acid is synthesized and broken down in the human body every day: according to Fraser and colleagues (1997), a third of the total reserve is renewed per day. Against this background, servings from supplements (usually tens or hundreds of milligrams) are relatively small, which partly explains the good tolerability.

In addition, a significant part of orally taken hyaluronic acid is broken down in the intestine into oligosaccharides. The body "sees" it approximately the same way as other carbohydrate components of food.

However, safety must be assessed taking into account the form of use. For capsules, the main questions are digestion, allergy to the raw material, and product quality. For injections — infections, inflammatory reactions and, in cosmetology, vascular complications.

It should also be remembered that the data are limited: most supplement studies lasted from a few weeks to a year, and participants were mostly adults without serious comorbidities. Less is known about long-term use over many years and about vulnerable groups.

Oral use: what studies record

In randomized studies of oral hyaluronic acid — in particular Kalman and colleagues (2008), Tashiro and colleagues (2012), Oe and colleagues (2017) — the frequency of adverse events in the supplement groups did not differ significantly from placebo. The authors did not report serious side effects associated with the product.

The most frequently mentioned complaints when taking any encapsulated supplements are mild stomach discomfort, nausea, bloating, or a change in stool. They are usually associated not so much with hyaluronic acid itself as with taking it on an empty stomach or with excipients.

Interactions of hyaluronic acid with prescription medications during oral use are not described as significant in the clinical literature. However, complex products often contain glucosamine, chondroitin, collagen, vitamin C, or plant extracts — and these may have their own restrictions, in particular in people taking anticoagulants.

If side reactions have appeared, it is logical to first rule out the "companions": try a mono-product of hyaluronic acid without additives or taking it with food. If the symptoms persist, the supplement should be discontinued.

Allergy and raw material quality

Hyaluronic acid for supplements is obtained in two ways: by bacterial fermentation (most often using Streptococcus strains) and by extraction from rooster combs. The profile of possible allergens depends on the source.

Products from rooster combs may contain residues of bird proteins. People with an allergy to chicken, feathers, or eggs (with cross-sensitivity to bird proteins) should choose fermentation-derived hyaluronic acid, where the source is stated directly on the label.

Fermentation-derived raw material is considered "vegan" and cleaner with respect to animal proteins, but its quality depends on purification: poorly purified raw material may retain bacterial components. Quality manufacturers control endotoxins and protein impurities.

A separate risk is adulteration. Hyaluronic acid is an expensive raw material, and products with a reduced content or low-molecular-weight raw material of dubious origin appear on the market. A certificate of analysis from an independent laboratory reduces this risk.

• Allergy to birds or eggs — choose a fermentation-derived source.
• Look for an indication of the source and molecular weight.
• Avoid products without a composition and certificates.
• In complexes, check each ingredient separately.

Theoretical risks and the cancer question

The most frequent reader question is whether hyaluronic acid "feeds" tumors. The question does not arise out of nowhere: in tumors there is often increased production of hyaluronan, and its interaction with the CD44 receptor participates in the migration and invasion of cancer cells. This connection is described in detail in a review by Toole (2004).

However, it is important to distinguish tumor biology from the effect of a supplement. Tumor cells themselves synthesize hyaluronan in the microenvironment; there is no clinical evidence that oral hyaluronic acid, which is largely broken down in the intestine, increases the risk of the occurrence or progression of cancer in humans.

The absence of evidence of harm is also not proof of safety for this group. For people with active cancer or during antitumor treatment, the editorial team advises not taking hyaluronic acid, like any other supplements, without the agreement of an oncologist.

Pregnancy and breastfeeding are another zone with a lack of data. There are no special studies of oral hyaluronic acid in these groups, so without necessity and without consulting a doctor, it is better not to take the supplement.

Injections and topical forms: a different level of risk

Intra-articular injections of hyaluronic acid are a medical procedure. Among the possible adverse events are pain and swelling at the injection site, reactive synovitis (the so-called pseudoseptic reaction) and, rarely, joint infection. These risks are much higher than with taking capsules, which is precisely why the procedure is performed by a doctor under aseptic conditions.

Cosmetic fillers based on cross-linked hyaluronic acid carry their own risks: bruises, swelling, nodules, inflammatory reactions and, most seriously — accidental injection into a vessel with disruption of the blood supply to the skin, and in rare cases — of vision. Injections should be performed only by qualified doctors.

Creams and serums with hyaluronic acid are tolerated best. Possible reactions are usually associated with preservatives, fragrances, or other components of the formula, rather than with the hyaluronate itself.

It is important not to transfer data between forms: the safety of capsules does not mean the safety of self-administered injections, and complications after fillers do not indicate a risk from oral supplements.

Editorial conclusions

Oral hyaluronic acid is well tolerated in studies; the most frequent complaints are mild digestive reactions, and allergy occurs rarely and is more often associated with raw material from birds.

The cancer question remains theoretical, but people with cancer, pregnant women, and breastfeeding women should refrain from the supplement without the agreement of a doctor.

Injectable forms have a completely different, much higher risk profile and belong to medical practice.

We also recommend reading "Who Should Not Take Hyaluronic Acid," "Hyaluronic Acid: Product Forms and Which to Choose," and "Hyaluronic Acid: What It Is and How It Works."

References

1. Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997;242(1):27–33.
2. Kalman DS, Heimer M, Valdeon A, Schwartz H, Sheldon E. Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint) on pain relief and quality of life in subjects with knee osteoarthritis. Nutr J. 2008;7:3.
3. Tashiro T, Seino S, Sato T, et al. Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period. ScientificWorldJournal. 2012;2012:167928.
4. 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;10:267–273.
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7. Bannuru RR, Osani MC, Vaysbrot EE, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–1589.