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9 Benefits and Side Effects of Hyaluronic Acid (5 Contraindications To Be Noted)

The discovery of hyaluronic acid (also known as hyaluronan) was proposed by Karl Meyer, the father of mucopolysaccharide chemistry, who subsequently isolated the substance from the vitreous body of cattle and named it hyalos, which means “hyaluronic acid”.

The word hyalos comes from the Greek word meaning glass, refers to a transparent, glass-like appearance, and due to its effects such as high viscosity, high water retention (can absorb thousands of times the volume of water), etc., the first commercial use appeared in the food processing industry (as a substitute for protein).

After decades of continuous research, hyaluronic acid is like the body’s innate essence liquid, which can lubricate joints, moisturize and remove wrinkles, and interstitial filling, which has irreplaceable characteristics, so it has become one of the most important anti-aging care products in the beauty industry.

What is hyaluronic acid?

Hyaluronic acid is one of the main elements in the extracellular matrix of vertebrate tissue, a type of mucopolysaccharide. It is found in almost all body fluids and tissues, such as skin, muscles, synovial fluid, vitreous and cartilage of the eye, and can bind to other molecules to produce scaffold effects and give structural elasticity. Note 8

In addition, hyaluronic acid is involved in several important physiological functions, such as regulating cell adhesion, cell motility, cell differentiation and proliferation, and providing mechanical properties to tissues.

With aging and external stimuli such as sunlight, ultraviolet rays, smoking, air pollution, etc., the stock of hyaluronic acid in the body will decrease year by year, resulting in dry skin, wrinkles, joint damage and other phenomena, so a variety of supplementation methods are derived, such as subcutaneous injection, application or internal administration.

What are the proven benefits of hyaluronic acid?

1. Hyaluronic acid is beneficial for diabetic foot

Diabetic foot syndrome includes several pathological features, mainly diabetic peripheral neuropathy and peripheral artery disease, resulting in foot ulcers.

It is estimated that people with diabetes have a 15% to 25% lifetime risk of developing diabetic foot ulcers, with a higher prevalence in men and over 60 years of age.

Diabetic foot ulcers may lead to amputation, especially when wound infection or osteomyelitis is involved, and associated complications such as nephropathy, retinopathy, ischaemic heart disease, and cerebrovascular disease may occur.

A systematic literature review and meta-analysis (4 randomized controlled trials, 328 diabetic foot patients) suggested that hyaluronic acid (hyaluronic acid)-based topical prescriptions increased wound healing and aided in the treatment of affected areas. Note 1

*Conclusion: For diabetic foot, topical hyaluronic acid may bring positive help, but limited by the small sample size, more long-term large-scale trials are still needed for further verification

2. Hyaluronic acid improves skin condition

The skin is a versatile organ with important defensive functions, both as a physical barrier to the external environment and as an immune defense against potentially pathogenic microorganisms.

However, the aging of organs begins when a person is born, and the skin is no exception, and the skin is affected by internal (time) and external (environmental) aging, resulting in loss of function, wrinkles, loss of elasticity, sagging, roughness, dryness, atrophy and other phenomena.

Several randomized, double-blind, placebo-controlled clinical studies have shown that hyaluronic acid intake can increase skin moisture in patients with dry skin. Note 1

A double-blind, placebo-controlled study (12 weeks, 60 adults with crow’s feet) showed that oral hyaluronic acid improved wrinkles and skin condition (e.g., radiance and suppleness). Note 2

In addition, topical hyaluronic acid can also improve the moisture content and elasticity of the skin, thereby improving the depth of wrinkles. Note 3

*Conclusion: Hyaluronic acid, whether oral or topical, may help to improve skin condition

3. Hyaluronic acid is beneficial for sinusitis

Rhinosinusitis, a broad term covering a wide range of diseases, including acute and chronic sinusitis, and nasal polyposis, has many subtypes and different etiologies, varies greatly in severity and clinical presentation, and lacks simple, accurate in-office tests.

Acute sinusitis is defined as inflammation of the nose and paranasal sinuses characterized by two or more of the following symptoms: blockage, congestion, facial pain, loss or loss of smell, lasting less than 12 weeks.

Chronic sinusitis is defined as nasal congestion or nasal congestion that lasts more than 12 weeks and is accompanied by one of three symptoms: facial pain or pressure, colorless nasal discharge or rhinorrhea, and reduced or loss of smell.

Patients with allergies, especially those with IgE-mediated allergic rhinitis, have a higher incidence of sinusitis than the general population (approximately 25% – 50%).

A systematic review (five studies) noted that topical hyaluronic acid nebulisation minimizes sinusitis symptoms because it avoids systemic side effects and increases local drug activity, and prevents retreatment by significantly improving quality of life. Note 2

*Conclusion: For acute and chronic sinusitis, local hyaluronic acid atomization therapy may be helpful for symptom improvement, but limited by the small sample size, more large trials are still needed to support it

4. Hyaluronic acid is beneficial for dry eyes

Dry eye disease, a multifactorial disease caused by tears and ocular surface, which causes symptoms such as discomfort, visual disturbances and tear film instability, and can cause damage to the ocular surface, is one of the most common eye diseases, and about 25% of patients who visit an eye clinic report symptoms of dry eye.

Due to the unstable tear film of dry eye patients, unable to maintain its structure and function, the related discomfort symptoms include: burning sensation, tingling sensation, gritty sensation, foreign body sensation, tearing, eye fatigue, dryness, etc., which adversely affect visual function, daily activities, social and physical functions, and work efficiency.

A prospective randomized controlled trial (3 months, 54 patients with dry eye) divided into two groups, with 0.15% hyaluronic acid ophthalmic drops in the control group and hyaluronic acid ophthalmic drops and oral hyaluronic acid capsules (daily dose 240 mg). Note 1

The results found that the ocular surface disease index, tear break up time, and corneal fluorescein staining in the study group were significantly better than those in the control group.

*Conclusion: For dry eye syndrome, oral and topical hyaluronic acid may help improve corneal epithelial wound healing and related dry eye symptoms, but limited by small sample sizes, more studies are needed to support this

5. Hyaluronic acid is beneficial for osteoarthritis

Osteoarthritis is the most common joint disease, with a prevalence ranging from 60% in people over 33 years old to 80.43% over 7 years old, characterized by cartilage loss, subchondral bone changes, synovitis, and meniscal degeneration.

In addition to aging factors, common osteoarthritis risk factors include obesity, previous joint damage, genetic factors, and anatomical factors such as joint morphology and alignment, and other factors: gender, ethnicity, and nutritional factors (vitamin D deficiency).

A randomized, double-blind controlled study (60 people over 50 years of age with knee arthritis) found that oral hyaluronic acid (200 mg daily for 12 months) combined with quadriceps strengthening training helped improve symptoms of knee osteoarthritis (e.g., knee pain, stiffness, quality of life, mobility, etc.) compared with placebo Measures/Japanese Osteoarthritis Scale). Note 4

However, the same study also pointed out that the improvement effect is only significant for patients under 70 years old, and there is no obvious effect after 70 years old, which may be related to cell metabolism differences.

*Conclusion: Oral hyaluronic acid may be of positive help to improve the symptoms of knee osteoarthritis, but it is limited by factors such as small sample size and short execution period, and more studies are still needed to support it

6. Hyaluronic acid is beneficial to gastroesophageal reflux

Gastroesophageal reflux disease is defined as symptoms or mucosal damage caused by abnormal reflux of stomach contents back into the esophagus or other parts and into the mouth (including larynx) or lungs.

Typical symptoms include heartburn and acid reflux, and atypical symptoms such as stomach pain, indigestion, nausea, bloating, and hiccups.

Depending on the presence or absence of esophageal mucosal injury on endoscopy, gastroesophageal reflux disease can be classified as non-erosive reflux disease or erosive reflux disease.

A randomized, double-blind, placebo-controlled study (14-day study of 20 patients with non-erosive GERD treated with PPIs) showed that a fixed combination of oral hyaluronic acid and chondroitin sulfate significantly improved symptoms associated with gastroesophageal reflux disease, such as heart burn and acid regurgitation. Note 5

In addition, the data on rapid disappearance of action and total disappearance of symptoms in participants taking hyaluronic acid and chondroitin sulfate were superior to placebo.

*Conclusion: For patients with non-erosive gastroesophageal reflux syndrome who do not respond well to drug control, hyaluronic acid and chondroitin sulfate can help improve symptoms rapidly, but more studies are needed to support this due to small sample sizes

7. Hyaluronic acid is beneficial for periodontitis

Periodontitis is an inflammatory disease of the tooth support tissue caused by a specific microbiota, resulting in the gradual destruction of periodontal ligaments and alveolar bone, periodontal pocket formation, gum recession, etc., affecting about 20% to 50% of the global population.

The relationship between periodontal infection and organ systems such as cardiovascular system, endocrine system, reproductive system, respiratory system and other organs makes it a complex multiphasic disease.

A randomized trial (12 weeks, 33 patients with moderate to severe chronic periodontitis) showed that hyaluronon gel after calculus removal significantly improved bleeding on probing, pocket probing depth, and clinical attachment level. Note 6

*Conclusion: For patients with chronic periodontitis, the use of hyaluronic acid gel after calculus removal can help further improve symptoms

8. Hyaluronic acid is beneficial for urinary tract infections

Urinary tract infections are a common infection, second only to respiratory infections. It is estimated that at least one third of women will experience a urinary tract infection requiring a course of antibiotics before the age of 24.

In addition, there is a recurrence rate of 3–6% within 25 to 35 months after the initial urinary tract infection, which is difficult to prevent.

A double-blind controlled study (57 women with recurrent urinary tract infections) found that intrabladder hyaluronic acid and chondroitin sulfate/chondroitin sulphate helped reduce the incidence of urinary tract infections (up to 86.6%) compared with 9.6% in the placebo group (which showed significant improvements in quality of life and overall symptoms). Note 9

In addition, the mean time to recurrence was significantly different, with approximately 185.2 days in the perfusion treatment group compared to 52.7 days in the placebo group.

9. Beneficial for interstitial cystitis

Interstitial cystitis is a chronic, inflammatory disease that affects the urinary system, with acute urination, frequent urination, bladder and pelvic pain lasting for more than 6 months. Women diagnosed with the disease were higher than men, and the prevalence rate of women was about 2.71%, compared with 1.22% of men.

The pathogenesis of this disease is not fully understood, and the possible causes include autoimmune diseases, occult infections, toxic substances in urine and defects in the mucosal layer of the bladder.

There is numerous evidence that defects in the mucosal layer of the bladder (damage to the mucopolysaccharide layer) cause direct contact of epithelial cells with pathogenic bacteria or agents in the urine and cause infection as a major factor.

Because hyaluronic acid and chondroitin sulfate/sulphate are the main constituent molecules in the mucosal layer, they are often used in treatment.

One study (non-double-blind and controlled) found that intravesical hyaluronic acid and chondroitin sulfate helped improve various symptoms and overall scores of interstitial cystitis, such as a decrease in acute urine fraction from 5.6 to 3.2 and an increase in mean urine output from 129.7 ml to 162 ml. In addition, the interstitial cystitis problem index decreased from 25.7 to 20.3, and the frequency of compressive pain decreased from 14 to 11.6. Note 10

What are the side effects of hyaluronic acid?

Hyaluronic acid is generally considered a safe ingredient and is highly tolerated, both topical and oral lozenges, but by medical injection (perfusion) it needs to be evaluated by a physician.

Oral side effects have been reported as stomach upset, gastroesophageal reflux, and loss of appetite.

The source of hyaluronic acid is divided into animal (chicken comb-derived) and microbial fermentation (microbial fermentation), if it is animal, pay attention to the possibility of causing allergies, and related products may be adulterated with other ingredients, please pay attention to the label before use.

Safety precautions (5 contraindications to use)

1. Do not use by pregnant women, nursing mothers, children, patients with abnormal liver and kidney function or major diseases (related safety unknown)

2. Do not use if the coagulation function is abnormal or taking anticoagulants (may increase the risk of bleeding)

3. People with cancer or a history of cancer should avoid supplementation with hyaluronic acid, as some studies believe that hyaluronic acid may promote the growth of cancer cells. Note 7

4. Use with caution if you have had any unusual allergic reaction to drugs, foods, colors, preservatives or animal products

5. Medical injections need to be performed by qualified physicians, and most of the common adverse reactions are related to injections, which may include skin bleeding, burning, muscle pain, stiffness, headache, dizziness, nausea, itching, sensitivity, pain, swelling, redness, bruising, chills, tenderness, infection, lumps, numbness, rash, redness, tingling, tenderness, ulcers or fever at the injection site, which will resolve on their own within a few weeks. In addition, if the raw material is animal-based, an allergy test must be performed to reduce possible allergic reactions

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