What Are Hyaluronic Acid Supplements?

This daily supplement may improve joint function and reduce wrinkles

Hyaluronic acid (HA) is a polysaccharide (a type of carbohydrate) that is widely distributed in body tissues and is found at high concentrations in the synovial fluid, vitreous humor (colorless, gel-like fluid in the eye), and skin. Since HA has a thick and sticky consistency and retains moisture, it helps the knee joint move smoothly and moisturizes the skin.

Some factors that reduce the amount of HA in the body include aging, solar ultraviolet radiation, smoking, and air pollutants. Due to such risk factors, HA supplementation has gained popularity in the health, food, and cosmetic industries.

This article discusses HA supplements' potential uses, side effects, and dosage.

Dietary supplements are not regulated like drugs in the United States, meaning the Food and Drug Administration (FDA) does not approve them for safety and effectiveness before products are marketed. When possible, choose a supplement tested by a trusted third party, such as USP, ConsumerLabs, or NSF. However, even if supplements are third-party tested, that doesn’t mean they are safe for all or effective in general. Therefore, it is important to talk to your healthcare provider about any supplements you plan to take and check in about potential interactions with other supplements or medications.

Supplement Facts

  • Active ingredient(s): Hyaluronic acid 
  • Alternate name(s): Hyaluronan, sodium hyaluronate
  • Legal status: Oral supplements and topical products are available over the counter (US). Intra-articular (within the joint) hyaluronic acid is classified as a class III medical device.
  • Suggested dose: For thumb osteoarthritis, the dose is 5 milligrams (mg) for one cycle of three injections (one per week). For skin wrinkles, studies have used a dose of 120 milligrams (mg) by mouth daily for 12 weeks.
  • Safety considerations: Although no serious side effects of HA were reported in several clinical studies, caution should be taken if you are allergic to poultry or have cancer. Further studies are needed to clarify HA's efficacy and safety in pregnant children and people.

Uses of Hyaluronic Acid

Supplement use should be individualized and vetted by a healthcare professional, such as a registered dietitian, pharmacist, or healthcare provider. No supplement is intended to treat, cure, or prevent disease.

Hyaluronic acid has been studied in osteoarthritis, aging skin, dry eyes, acid reflux, and wound healing. It comes in topical, oral, and injectable forms–the latter is considered a medical device.

This article will primarily focus on the oral supplement use of HA.

Joint Function and Pain in Osteoarthritis

Because HA functions as a lubricating agent in synovial fluid, it plays a role in inflammatory joint conditions like osteoarthritis.

A randomized controlled study of 100 people with osteoarthritis of the first carpometacarpal (thumb) joint showed that the intra-articular (within the joint) HA injections were superior to betamethasone (a corticosteroid) injections in improving joint function and pain. Additionally, the improvement due to HA injections was more prolonged, persisting after six months. However, the study was limited because it did not have a placebo group.

Guidelines for using intra-articular (within the joint) HA injection vary. For instance, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends IAHA for managing knee osteoarthritis as a second-line treatment in people who remain severely symptomatic despite using non-steroidal anti-inflammatory drugs (NSAIDs).

On the other hand, the American College of Rheumatology guideline does not recommend IAHA or conditionally recommend IAHA if there is no satisfactory response to prior treatments.

Reduces Skin Wrinkles

In a double-blind, randomized, placebo-controlled study of 60 Japanese people aged 22 to 59 who had crow's feet wrinkles (wrinkles near the corner of the eyes), taking 120 milligrams (mg) of HA in capsule form by mouth per day for 12 weeks decreased skin wrinkles.

A similar 12-week double-blind, randomized, placebo-controlled study conducted in 41 Taiwanese people aged 30 to 65 revealed that taking a 120 milligram (mg) HA capsule by mouth for 12 weeks improved skin wrinkles compared to the placebo. Further research involving more people from different populations is needed despite the positive result.

Dry Eyes

A randomized clinical trial of 76 people over 19 years of age with dry eye disease showed that applying a single drop of both 0.3% and 0.15% HA improved signs and symptoms in people with moderate to severe dry eye disease. However, further research with large sample sizes is needed to determine the effectiveness of HA on dry eye disease. 

A meta-analysis indicated that treatment with HA eye drops alone reduced dry eye signs and symptoms in people with dry eye disease compared with non-HA-based eye drops. Yet, one limitation is that it is not known whether the statistical significance of the beneficial effects of HA drops compared with non-HA-based eye drops implies clinical improvement.

Acid Reflux Symptoms

A study of 51 people aged 25 to 75 with laryngopharyngeal reflux (LPR) symptoms showed that HA combined with chondroitin sulfate significantly reduced LPR-related symptoms such as chronic cough and hoarseness when given with proton pump inhibitor (PPI) therapy.

Since HA was used in combination with chondroitin sulfate, the effect of HA alone when combined with PPI therapy is unclear.

Wound Healing

A randomized controlled study was conducted in 30 healthy people designated female at birth aged 20 to 60 years, undergoing tooth extraction. It showed a higher wound closure after tooth removal using the HA gel and spray treatment groups compared to the control group. It is important to note that the study was limited due to a smaller sample size.

In a randomized, double-blind, multicenter study of 168 people with chronic leg ulcers of venous or mixed (venous and arterial) origin, the treatment with 0.2% HA cream daily for 20 weeks resulted in a higher healing rate than a neutral comparator cream. Nonetheless, the generalizability of the result is limited because the study was conducted in people from Poland.

Other Uses

In addition to the conditions listed above, some people use HA to support the following conditions, although there’s a lack of data demonstrating HA’s efficacy for some:

  • Chronic pain: A randomized, double-blind, placebo-controlled clinical study of 72 people taking 45 milliliters (three tablespoons) of high molecular weight HA by mouth during the first two weeks of the study resulted in reduced pain and pain medication usage. Of note, during the last two weeks of the study, the dose was reduced to 30 milliliters (two tablespoons), and no further decrease in chronic pain was observed.
  • Gingivitis (gum disease): A double-blind parallel three-arm (0.12% chlorhexidine, 0.025% HA, and a water-based antioxidant mouthwash containing beta-carotene and vitamin E and C as active ingredients) clinical trial was conducted in 75 people 18-23 years with biofilm-induced gingivitis. It showed that all three interventions significantly reduced the plaque index (PI) after seven days compared to the baseline data. However, chlorhexidine showed a larger PI reduction than the HA and antioxidant mouthwashes.
  • Fibromyalgia: Blood levels of HA were measured in 69 Korean people designated female at birth with fibromyalgia, and it was found that the levels did not differ from those in the control group. Thus, the study indicated that HA levels did not correlate with disease severity.
  • Osteoporosis: Despite the lack of studies assessing the effect of HA alone on osteoporosis, one combination study showed that glucosamine plus sodium hyaluronate was superior to glucosamine alone at relieving pain in people with osteoporosis associated with knee osteoarthritis. Due to the combination therapy, the efficacy of HA alone for osteoporosis is unclear. 
  • Urinary tract infections: A study conducted in 10 children aged two to 18 years with spina bifida and neurogenic bladder who performed clean intermittent catheterization (a technique for bladder drainage) showed that the instillation of 40 milligrams (mg) HA into the bladder weekly for four weeks then monthly for the following three months reduced symptomatic recurrent urinary tract infections. However, further multicenter randomized, controlled clinical trials with larger sample sizes and longer follow-ups are needed to confirm such promising results.
  • Vaginal dryness: In a multicenter, open-label, randomized, parallel-group, comparative study with a non-inferiority design of 53 people aged 45 to 55 years in menopausal transition, vaginal dryness decreased in both the polycarbophil (one gram vaginal gel on the skin twice a week for 30 days) and HA (three grams vaginal gel every three days for 30 days) treatment groups. Moreover, the study indicated that polycarbophil was equally effective as HA.

What Are the Side Effects of Hyaluronic Acid ?

No side effects were noted in a review of several safety studies of HA. While HA as a dietary supplement exhibits no side effects, potential side effects may occur depending on the application method, such as an injection into the joint or topical application.

Common Side Effects

When injected into the joint, HA may cause the following:

  • Minor or moderate local pain: In a single-center, randomized, prospective, active-controlled, and single-masked study assessing whether the efficacy of intra-articular HA injection was superior to corticoid injections for the treatment of osteoarthritis of the thumb, 10 (five betamethasone group and five of the HA group) out of 88 people experienced minor or moderate local pain after intra-articular injection.
  • Swelling: In the same study cited above, five (two of the betamethasone group and three of the HA group) out of 88 people experienced swelling, which resolved by the following visit.

A prospective, multicenter randomized controlled trial that looked at the effectiveness of 0.2% HA cream on the skin compared to a neutral cream in the treatment of people with chronic leg ulcers reported the following treatment-related side effects.

  • Skin and subcutaneous tissue disorders: In the HA cream group, 21.2% reported skin and subcutaneous tissue disorders compared to 16.9% in the neutral cream group. 
  • Infections and infestations: In the HA cream group, 11.8% reported infections and infestations compared to 15.7% in the neutral cream group.

Severe Side Effects

No serious side effects were reported in several randomized controlled trials and cohort studies when HA was given as an injection into the joint, taken by mouth, or applied topically to the skin. Nonetheless, conflicting results regarding the serious side effects of HA injections have also been reported.

Despite the conflicting results, seek medical attention if you experience the following:

  • Bleeding: Although it aids wound-healing, HA has been shown to make the platelet less sticky and thus prolongs the bleeding time. A comparative, prospective randomized study of 40 people who had undergone third molar extraction found that local injection of 0.8% HA increased bleeding time.

Avoid hyaluronic acid derived from animal sources if you have an allergy to avian-derived products. While it is rare to experience an allergic reaction since HA is naturally produced in your body, stop taking HA immediately and seek medical attention if you experience any signs of an allergic reaction.

Precautions

Hyaluronic acid is generally safe, although some conditions require caution.

  • Allergy to avian or avian-derived products: HA may be derived from rooster combs. Caution is advised if you have an allergy to eggs, feathers, or poultry. In addition to obtaining HA from animals, HA can also be obtained from bacteria.
  • Vegan or vegetarian diets: Since some HA products may be derived from animal sources, it may not be appropriate for people following a strict vegetarian or vegan diet. Check the label or call the manufacturer for further information. Look for vegan sources of hyaluronic acid derived from microbial fermentation, or consider eating foods that may increase HA levels.
  • Cancer: Hyaluronic acid has been shown to facilitate metastasis in colorectal cancer in laboratory models. However, it is unclear how this may translate into “real-life” settings. If you have a history of cancer, do not use hyaluronic acid supplements without consulting your healthcare provider. 
  • Children: Studies have been performed to evaluate the efficacy of HA inhalation in the treatment of the upper and lower airways in children, but evidence of such efficacy is limited. Moreover, topical HA gel has been studied in children to treat mouth ulcers. Despite the use of HA in children, the safety of the consumption of HA by mouth in children is yet to be known.
  • Pregnancy: An expert opinion suggested the therapeutic potential of high molecular weight HA for recurrent miscarriage, preeclampsia, and pre-term birth. However, further clinical studies are needed to confirm such findings. Please do not use hyaluronic acid for these conditions without first discussing it with your healthcare provider.

Dosage: How Much Hyaluronic Acid Should I Take?

Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs.

In humans, HA supplementation by mouth was confirmed to be safe at dosages of up to 200 milligrams (mg) per day ingested for periods of up to 12 months.

The dose and dosage form of HA used varies depending on what HA is used for. Listed below are some examples.

  • Osteoarthritis: In a randomized study comparing the effect of intra-articular (within the joint) HA injection to betamethasone injection, people with osteoarthritis of the thumb underwent one cycle of three injections (one per week) of 0.5 cubic centimeters (cm3) of HA 5 milligrams (mg). Intra-articular HA injection requires a prescription and is given as a shot to your knee joint by a trained healthcare professional.
  • Skin wrinkles: The typical HA dose for use in the setting of skin wrinkles is 120 milligrams (mg) HA capsule by mouth daily for 12 weeks. Although intradermal (within the skin) injection of HA has been studied in the field of esthetic dermatology, the effect of HA alone in serum-containing HA is unclear given that most products combine HA with other active ingredients (e.g., vitamins C and E) known to enhance skin health.
  • Dry eyes: A clinical trial reported using two drops of 0.15% HA or 0.3% HA or a single drop of both 0.3% and 0.15% HA for treating dry eye disease.

What Happens If I Take Too Much Hyaluronic Acid ?

Body tissues typically use hyaluronic acid taken by mouth. Taking HA is unlikely to build up in the body at excessive levels. This is because about 90% of it is metabolized and eliminated via expiration and urine.

Furthermore, your body’s natural production of hyaluronic acid may decrease with age.

Interactions

In a randomized, prospective study comparing the efficacy and safety of intra-articular (within the joint) HA injection and betamethasone injection in people with osteoarthritis of the thumb, people who were also being treated with anti-epileptic drugs, oral anticoagulants, lithium, potassium-sparing diuretics, digoxin, minocycline, or other medications were excluded from the study. Interactions between HA and these prescription drugs are unclear. 

While there is no clear documentation of clinically significant drug interactions noted in the literature, it is essential to consult with your healthcare provider before starting an HA supplement.

It is essential to carefully read a supplement's ingredient list and nutrition facts panel to know which ingredients and how much of each ingredient is included. Please review this supplement label with your healthcare provider to discuss potential interactions with foods, other supplements, and medications. 

How to Store Hyaluronic Acid 

Store HA supplement in a cool, dry place and keep HA away from direct sunlight. Discard per packaging instructions.

Similar Supplements

Besides HA, other dietary supplements that have been studied for osteoarthritis include the following:


Whereas HA, glucosamine, chondroitin, and collagen seem to exert their pain-relieving effect by acting as a joint lubricant or providing structural support to the joints, turmeric, Boswellia serrata, and omega-3 fatty acids seem to alleviate joint pain by reducing inflammation.

The effect of combination therapy (glucosamine, chondroitin, and HA) on knee osteoarthritis has been studied.

Additionally, a pilot study looked at the effect of an oral preparation containing hydrolyzed collagen type II, chondroitin sulfate, HA, and hydrolyzed keratin on knee osteoarthritis.

It’s not uncommon to use multiple anti-arthritis dietary supplements together. Be sure to inform your healthcare provider about all supplements and medicines you take.

Frequently Asked Questions

  • What does hyaluronic acid do?

    Hyaluronic acid is a polysaccharide (a type of carbohydrate) that keeps body tissues hydrated and lubricated. It's a naturally occurring compound found in high amounts within the skin, joints, and eyes. As you age, your hyaluronic acid levels may decrease.

  • Does hyaluronic acid have an anti-aging effect?

    Taking HA by mouth for 12 weeks significantly improved skin moisturization and wrinkles. Due to its ability to retain moisture, HA helps keep the skin plump. Thus, HA has gained traction within the beauty industry.

  • What is the difference between high molecular weight and low molecular weight hyaluronic acid?

    High molecular weight HA (HMWHA) is HA in its long molecule (repeating subunits of large molecules) form. When the long molecule breaks down into small fragments, it’s referred to as low molecular weight HA (LMWHA). The difference in the molecular weight of HA can mean different effects. For example, since HMWHA decreases inflammation and may weaken the immune system, intra-articular (within the joint) injection of HMWHA is used to treat osteoarthritis. One study has shown that LMWHA can penetrate deeper into the skin compared to HMWHA, which does not pass through the skin. Thus, LMWHA may be more favorable when applied to the skin (topically).

Sources of Hyaluronic Acid & What To Look For

Not only is HA derived from animals and bacteria, but it can also be derived from marine sources such as bivalve mollusks, the liver of stingrays, and the eyeballs of swordfish and sharks.

Dietary supplements are not strictly regulated in the United States, making it difficult to know which brands are reliable and which are not.

One sign of quality is a stamp of approval from the U.S. Pharmacopeia, NSF, or ConsumerLab. These independent certifying bodies ensure that the ingredients listed on a product label are correct and pure. Only supplements voluntarily submitted for testing are eligible for certification.

Food Sources of Hyaluronic Acid

In addition to being present in articular cartilage (tissue at the ends of bones) and synovial fluid (protective liquid in between your joints), HA is also usually present in the bone marrow of mammals. Thus, bone broth is a source of hyaluronic acid. 

Topical application of creams, gels, and lotions containing phytoestrogens (plant-based estrogens) for 12-24 weeks has increased hyaluronic acid levels. Food sources of phytoestrogens include the following:

  • Soybeans
  • Garlic
  • Celery
  • Carrots
  • Red clover
  • Sweet potatoes
  • Fruits (apples, pomegranates, and chaste berries)
  • Coffee

Hyaluronic Acid Supplements

Industrial uses of HA utilize either low or high molecular weight HA. The salt form of hyaluronic acid, namely, sodium hyaluronate, is considered to be a low molecular weight HA (LMWHA). It is the sodium hyaluronate form that is listed as an ingredient in most skin care products due to its lower molecular weight that allows it to penetrate deeper into the skin. On the other hand, intra-articular (within the joint) injection of high molecular weight HA (HMWHA) is used to treat osteoarthritis due to its anti-inflammatory property and its high molecular weight that allows it to bind large amounts of water.

Hyaluronic acid is available in the following dosage forms:

  • Intra-articular (within the joint) injection
  • Intradermal (within the skin) injection
  • Powder
  • Tablets
  • Capsules
  • Softgels
  • Eye drops
  • Gel
  • Spray
  • Cream
  • Liquid
  • Serum

As hyaluronic acid is derived from animals, if you are allergic to poultry or eggs, look for vegan sources of hyaluronic acid, which are derived from microbial fermentation.

Summary

Hyaluronic acid is a natural polysaccharide touted for its use in osteoarthritis, skin wrinkles, and dry eyes. However, guidelines vary for using intra-articular (within the joint) HA injection for osteoarthritis. Other uses of HA include alleviating acid reflux symptoms and promoting wound healing. Hyaluronic acid is generally well-tolerated and plays a role within the cosmetic, nutraceutical, and food industries.

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By Trang Tran, PharmD
Trang Tran, PharmD, is a pharmacist who is passionate about integrative health.