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Information, effects, deficiency, dosage, side effects
Hyaluronic acid, a naturally occurring substance in the body, has been an integral part of the cosmetics industry for many years. Valued particularly for its anti-aging properties, it is commonly added to a wide range of creams, serums, and other face and body care products to help maintain skin hydration and youthful appearance.
Beyond its role in beauty products, hyaluronic acid has found important applications in various areas of medicine. It is also used as an ingredient in decorative cosmetics, such as lipsticks, demonstrating its versatility across both medical and cosmetic fields.
Hyaluronic acid is a polysaccharide, a multiple sugar. It is the simplest glycosaminoglycan, a class of negatively charged polysaccharides. The long-chain multiple sugar has in particular a structuring property.
The polysaccharide is synthesized in the plasma membrane of the cell and is found in almost all tissues and organs of vertebrates. However, the greatest concentration is in the connective tissue. Hyaluronic acid occurs in the body both in free, unbound form and in combination with other components of the extracellular matrix (ECM).
Hyaluronic acid has many different descriptions:
The discovery of hyaluronic acid began in the late 19th century:
1. Early Observations (1880):
In 1880, French chemist Portes was the first to observe a unique substance in the vitreous body of the eye. He called it hyalomucine, noting that it behaved differently from other mucins, gel-like substances found in mucus that serve protective and structural roles in many living organisms.
2. Scientific Isolation (1934):
The substance remained largely unexplored until 1934, when German scientist Karl Meyer, together with his colleague John Palmer, successfully isolated it from the vitreous humor of a cow’s eye.
3. Chemical Composition:
Upon analyzing the compound, Meyer found that it was made up of two main components:
4. Naming the Compound:
Meyer coined the term "hyaluronic acid" by combining:
Legacy and Importance
Since its discovery, hyaluronic acid has gained prominence due to its exceptional water-retention properties and biocompatibility. It is now widely used in:
Hyaluronic acid (also known as hyaluronan) is a linear, unbranched polymer composed of repeating disaccharide units: a uronic acid and an amino sugar. Unlike other glycosaminoglycans found in the extracellular matrix (ECM), such as heparin, hyaluronic acid is not sulfated and is known for its high molecular weight.
A key property of hyaluronic acid is its strong affinity for water. As a hydrophilic and negatively charged molecule, its long polymer chains can absorb and retain large volumes of water. This water-binding capability creates a viscoelastic solution, meaning the viscosity increases with concentration. In this way, hyaluronic acid can bind many times its own weight in water, making it essential for tissue hydration and lubrication.
1. Water Storage and Homeostasis
Hyaluronic acid helps regulate tissue hydration by resisting water loss. It acts as a natural barrier against rapid changes in tissue water content, preventing dehydration. Even at low concentrations, it forms an entangled molecular network that stabilizes the surrounding environment.
2. Joint Lubrication
In synovial joints (e.g., knees, elbows), hyaluronic acid is a key component of synovial fluid, which is secreted by the synovial membrane. This fluid is highly viscous and functions as a lubricant and shock absorber, reducing friction between bones during movement.
Additionally, hyaluronic acid helps:
These functions are essential for joint health and the long-term integrity of cartilage.
3. Structural Support in Bones and Cartilage
Hyaluronic acid is found throughout all bones and cartilage, contributing to elasticity and resilience. It is especially abundant in hyaline cartilage, which covers the ends of bones in joints and acts as a cushion during movement.
Other locations of hyaline cartilage include:
Its cushioning and load-distributing properties are crucial for joint flexibility and protection.
4. Fundamental Component of Connective Tissue
Connective tissue exists throughout the body in many forms, supporting, binding, protecting, and insulating other tissues. Examples include:
There are three structural elements common to all connective tissues:
Hyaluronic acid provides the gel-like ground substance that:
5. Role in Gum Health
Gum tissue is a type of dense, fibrous connective tissue. The ligament secures the teeth to the jawbone, and hyaluronic acid:
Without hyaluronic acid, the integrity and hydration of gum tissue would be compromised.
6. Skin Structure and Hydration
The skin is made up of two layers:
Hyaluronic acid resides in the dermis, where it maintains:
7. Scalp and Hair Health
The scalp, like all skin, contains connective tissue in its dermal layer. It is unique due to the presence of ~100,000 hair follicles. Hyaluronic acid in the scalp:
Hyaluronic acid, also known as hyaluronan, is found in all vertebrates and even in the capsule of some strains of streptococci bacteria. It is a major component of the extracellular matrix (ECM) and is present in various differentiated tissues and organs throughout the body. The concentration of hyaluronic acid varies depending on the tissue type and its specific function.
Hyaluronic acid is abundant in the ECM but is also a key constituent of several organs and bodily fluids, each containing different concentrations suitable for their functions. Notable examples include:
Tissue or Fluid | Concentration |
|---|---|
Umbilical cord | 4100 µg/g (4.1 mg/g) |
Synovial joint fluid | 1400 to 3600 µg/ml |
Vitreous body of the eye | 140 to 338 µg/ml |
Skin (largest reservoir) | About 2.5 g/l |
The skin contains the largest total amount of hyaluronic acid, estimated at about 7 to 8 grams in an average adult. This accounts for roughly 50% of the body’s total hyaluronic acid.
Overall, researchers estimate the total amount of hyaluronic acid in an adult body to be between 11 and 17 grams. The highest concentration measured in human tissue is in the umbilical cord, at around 4 mg/ml.
Like most biological molecules, hyaluronic acid is degradable and is continuously turned over in the body. Its breakdown occurs via two main pathways, both involving specialized enzymes called hyaluronidases:
Enzyme involved: Hyaluronidase-2 (Hyal-2)
Location: Acts on hyaluronic acid in the extracellular matrix
Process: Hyal-2 cleaves hyaluronic acid into smaller fragments, which are then removed via the lymphatic system. Once in the bloodstream:
The half-life of hyaluronic acid in the body varies significantly depending on its location:
This rapid turnover highlights the dynamic nature of hyaluronic acid in maintaining tissue homeostasis and function.
The human body is able to produce hyaluronic acid itself. But this ability decreases steadily with age. At around 40 years of age, the body can only synthesize 40%. At the age of 60, the production rate is only about 10% of the original amount.
As already described, hyaluronic acid is contained in many organs of the human body and takes on various functions, some of which are vital. Therefore, a hyaluronic acid deficiency can result in very different symptoms:
Diet and Hyaluronic Acid Production
The right diet can promote the body's production of hyaluronic acid to a certain degree. For example, one study showed that consuming fermented soy milk can stimulate hyaluronic acid production.
In order for the body to be able to produce hyaluronic acid, the necessary building blocks for synthesis must be supplied to it. Magnesium is essential for the synthesis of hyaluronan. Therefore, sufficient magnesium should be provided to promote the body's own production.
Magnesium is found in the following foods, among others:
Hyaluronic acid is also found in many animal products. These include, for example:
Several external factors influence the levels of hyaluronic acid in the body, some of which are modifiable:
Smoking: Smokers tend to develop deeper wrinkles, partly due to the breakdown of hyaluronic acid caused by cigarette smoke. A 1989 in vitro study suggested that free radicals in smoke accelerate the degradation of hyaluronic acid.
Hormones: Hormonal levels also affect hyaluronic acid concentration. Studies have shown that estrogen treatment increases hyaluronic acid activity. Estrogen is known to boost the utilization of nutrients like magnesium and zinc, which in turn support hyaluronic acid synthesis.
Skin aging is characterized by a gradual decline in the functional capacity and reserve strength of the skin tissue. It is a complex process influenced by multiple biological factors and can be divided into:
One of the key intrinsic factors is the body's decreasing ability to produce hyaluronic acid over time. This decline is closely linked to hormonal changes, particularly the reduction of estrogen and progesterone levels.
The decrease in these hormones contributes to:
As hyaluronic acid concentration in the skin diminishes, its capacity to bind water is reduced. This leads to drier, less elastic skin, which accelerates the appearance of wrinkles and other signs of aging.
Joints and tendons play a crucial role in enabling movement. As previously mentioned, hyaluronic acid is a major component of synovial fluid, where it provides elasticity and shock absorption.
When the levels of hyaluronic acid decrease, the consistency of synovial fluid changes, reducing its effectiveness as a lubricant. As a result, cartilage and joints lose their protection against mechanical stress and impacts.
This causes increased friction between joints and cartilage, leading to severe pain during movement. Consequently, individuals tend to avoid moving the affected joints, causing further decline in mobility and joint function.
Many different conditions can cause joint pain. The most common include:
The human body has about 100 real joints. Only those that consist of two opposite joint parts are labeled as real joints. These are protected with a cartilaginous protective layer that contains hyaluronic acid.
Joints that are particularly frequently used or subjected to greater stress are more often perceived as painful. This includes in particular the knee, shoulder or hip joint.
Joint pain can be mildly irritating to severely impairing. If the pain persists for up to a few weeks, it is said that the complaints are acute. If it lasts for several weeks or months, it can lead to a chronic illness.
Hyaluronic acid can help stop the natural wear and tear of the joints. The lubricant on the joints prevents irritation of the cartilage. This often leads to inflammation, which in the long term leads to degeneration of bone and cartilage tissue and causes pain.
Since researchers discovered the connection between hyaluronic acid and skin texture, it has become a popular active ingredient in many cosmetic products. Today, hyaluronic acid is commonly found in:
The effect of these cosmetics is primarily to improve skin moisture. The water-binding power also ensures a better complexion. The skin appears plumped up and pale or sunken parts of the face appear less pronounced.
However, cosmetic products can usually only offer a temporary effect. The natural skin barrier and the molecular structure prevent them from penetrating into the deeper skin regions.
Researchers showed that only low-molecular hyaluronic acid was able to penetrate the stratum corneum, the top layer of the epithelium of the skin. The high molecular weight variants are too large for this and can't pass the barrier.
Hyaluronic acid is used more and more in esthetic medicine. Since these are non-invasive procedures, they are less risky than procedures from plastic surgery.
The possible areas of application are diverse:
Depending on the area of application, a different type and crosslinking of the hyaluronic acid molecules must be selected. Cross-linked hyaluronic acid is used in the shaping because it is not as well broken down by the body. The effect lasts longer.
Another advantage of cross-linked hyaluronic acid is the stronger binding of water. The gel absorbs more water and thus reaches a higher volume. This property is particularly important for enlarging or modeling.
In this procedure, small amounts of hyaluronic acid gel are injected into the skin layer of the affected area. The quantity and consistency of the gel depend on the depth of the wrinkles and the area being treated.
In both cases, the goal is to provide a cushioning effect that smooths out the skin and reduces the appearance of wrinkles.
Previously, collagen injections were a common alternative for wrinkle treatment. However, this approach has become less popular due to a higher incidence of complications and intolerance. Many patients experienced allergic reactions and the formation of nodules under the skin.
These issues were largely due to the source of the collagen, which was typically extracted from pig or cattle tissues. As a foreign substance, the collagen often triggered an immune response, leading to these adverse effects.
Another common method for wrinkle treatment is the use of Botox, which contains botulinum toxin, a potent neurotoxin produced by the bacterium Clostridium botulinum. Although extremely toxic, just 1 gram could theoretically kill 1 million people, botulinum toxin has become a valuable therapeutic protein.
Besides aesthetic applications, Botox is also approved for treating various medical conditions such as chronic migraines and muscle spasms.
There are several key differences between Botox and hyaluronic acid treatments:
The choice between Botox and hyaluronic acid generally depends on the type of wrinkle:
Hyaluronic acid is not limited to aesthetic applications, it is also increasingly used in various areas of clinical and therapeutic medicine due to its biocompatibility and beneficial biological properties.
Ophthalmology (Eye Surgery and Care)
Since hyaluronic acid is a natural component of the eye, it is commonly used in eye surgeries, including cataract and corneal procedures. During surgery, hyaluronic acid solutions help to:
Post-surgical care and treatment for dry or irritated eyes often include eye drops containing hyaluronic acid, which soothe and hydrate the eye's surface.
Wound Healing
Hyaluronic acid is believed to accelerate wound healing. Research shows that the concentration of hyaluronic acid in the skin naturally increases during the healing process, suggesting its important role in:
A 2009 study investigated the treatment of eardrum perforations using a 1% hyaluronic acid solution. Of the 25 patients treated:
Diagnostic Use in Medicine
In clinical diagnostics, hyaluronic acid levels in the body are sometimes used as biomarkers for various health conditions. Elevated or altered levels may be indicative of:
These diagnostic applications take advantage of hyaluronic acid’s role in tissue turnover and inflammation, which tend to change in pathological conditions.
One well-established medical application of hyaluronic acid is its use in the treatment of osteoarthritis through intra-articular injections. This method has been in use for many years and has shown positive results in numerous clinical studies.
Arthrosis, also called osteoarthritis, is the most common chronic joint disease. It is typically caused by the natural wear and tear of joints over time.
As osteoarthritis progresses:
This leads to:
When pain can no longer be managed with oral medications such as ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs), or when side effects or intolerance prevent their use, hyaluronic acid injections become a viable alternative.
These injections aim to:
The concept of treating osteoarthritis with hyaluronic acid was first proposed in 1971 by Hungarian scientist Endre A. Balazs, who had previously studied the role of synovial fluid in joint function using electron microscopy.
Evidence from Clinical Studies
In 2006, a research team led by Nicholas Bellamy at the University of Queensland, Australia, conducted the largest review to date of hyaluronic acid in the treatment of knee osteoarthritis. The review included 76 studies and yielded promising results:
The researchers concluded that hyaluronic acid offers pain relief comparable to non-steroidal anti-inflammatory drugs (NSAIDs), with the added benefit of improving joint function and quality of life, a key advantage over most oral pain medications.
Early Extraction from Animal Tissues
Initially, hyaluronic acid was extracted exclusively from animal tissues, a practice that was refined and optimized between the 1940s and 1970s. During this time, researchers also began investigating the potential of bacterial synthesis of hyaluronic acid.
In 1979, the first patent for extracting hyaluronic acid from rooster combs was registered. Researchers also discovered other methods, including plant-based extraction (via cell processing) and in vitro enzymatic synthesis, expanding the production options.
Hyaluronic acid has been extracted from a variety of animal sources, including:
In the early stages, animal-derived hyaluronic acid was suitable primarily for laboratory use, due to a high risk of contamination with pathogens or residual animal proteins, making it unsuitable for medical applications.
Today, most hyaluronic acid is produced biotechnologically using bacterial fermentation. This method is safer, more scalable, and more cost-effective.
Cascade Fermentation Process:
This results in low-molecular-weight hyaluronic acid, which is more easily absorbed by the human body.
Advantages of Biotechnological Production:
For these reasons, microbial fermentation is now the preferred method for producing medical- and cosmetic-grade hyaluronic acid.
Feature | Animal-Based | Plant-Based / Fermentation |
|---|---|---|
Source | Rooster combs, pig skin, etc. | Microorganisms fed on plant materials |
Cost | Higher | Lower |
Risk of Contamination | Higher (animal proteins/pathogens) | Very low |
Allergen Potential | Moderate to high | Minimal |
Vegan-Friendly | No | Yes |
Medical/Cosmetic Suitability | Limited (past) | Widely used today |
While animal-derived hyaluronic acid was the foundation of early production, it is largely being replaced by vegan, plant-based alternatives created through microbial fermentation. These products are safer, more ethical, and better tolerated, making them ideal for use in modern medicine and cosmetics.
Hyaluronic acid is not only used in topical skincare or medical injections, it is also available in oral supplement form. This method of intake is gaining popularity due to its convenience and systemic effects.
These supplements are often taken as part of a cycle or “cure,” typically refreshed every 3 to 4 months to maintain optimal levels in the body.
Several studies have confirmed the efficacy of orally administered hyaluronic acid. Notably, Japan has been a pioneer in developing and popularizing nutritional hyaluronic acid products.
Two independent research groups conducted studies on:
One study demonstrated that oral hyaluronic acid can alleviate knee osteoarthritis symptoms, making it a non-invasive alternative to joint injections.
Lozenges containing hyaluronic acid can be particularly effective for:
Due to its water-binding properties, hyaluronic acid helps moisturize the mucous membranes in the throat and pharynx, naturally reducing irritation and easing discomfort.
Oral Hyaluronic Acid | Topical Hyaluronic Acid |
|---|---|
Reaches deeper layers of the body | Acts only on the outer skin layers |
Supports joints, skin, and mucosa | Limited to surface hydration |
May relieve systemic symptoms | Targets localized dryness |
While topical hyaluronic acid improves skin moisture externally, it cannot penetrate deeply due to the barrier function of the skin. Oral intake allows hyaluronic acid to be distributed throughout the body, supporting the skin, joints, connective tissues, and mucous membranes from within.
Hyaluronic acid (HA) is often combined with other bioactive substances to enhance its efficacy, bioavailability, or synergistic effects depending on the target application, whether in cosmetics, supplements, or medical treatments.
This trio is commonly used in cosmetics and oral supplements, targeting anti-aging and skin regeneration.
These ingredients work synergistically with hyaluronic acid:
A long-term in vivo study with 20 participants explored the combination of hyaluronic acid, collagen, and succinic acid.
This combination was tested in a 2015 clinical study involving 40 subjects with early-stage knee osteoarthritis.
Treatment duration: 1 month
Form: Oral tablets containing:
Results:
This suggests that such a combination therapy may be an effective, non-invasive option for early intervention in joint disorders.
Conclusion
Depending on the goal, anti-aging, joint support, or skin regeneration, hyaluronic acid can be effectively combined with:
Combination Partner | Primary Benefit |
|---|---|
Magnesium / Zinc | Stimulates endogenous HA production |
Collagen + Q10 | Enhances skin firmness and antioxidant protection |
Succinic Acid | Boosts fibroblast activity and natural collagen output |
Chondroitin + Keratin | Alleviates joint pain and supports cartilage health |
The effectiveness of hyaluronic acid (HA) in the body depends largely on two critical factors:
Why? The Carrier Effect:
A Japanese research team conducted a study that showed:
Daily intake of at least 120 mg of hyaluronic acid:
This supports the use of HA as an oral supplement for skin hydration and anti-aging purposes.
Factor | Effect |
|---|---|
Low molecular weight HA | Better cellular penetration and absorption |
High concentration (≥100 mg) | More effective uptake via carrier proteins |
Recommended daily intake | ≥120 mg for skin hydration (based on clinical studies) |
It is important to follow the manufacturer’s recommended dosage instructions carefully when using hyaluronic acid supplements or products.
Taking too much hyaluronic acid may lead to mild side effects, such as:
These symptoms are generally temporary and tend to resolve quickly without serious consequences. In most cases, they are not considered dangerous or life-threatening.
If any discomfort persists or worsens, it is advisable to stop use and consult a healthcare professional.
Since hyaluronan occurs naturally in the human body, it is generally well tolerated. The possible side effects rather depend on the type of intake.
Various studies have shown,
1. Injections (Hyaluronic acid gel):
2. Oral intake (capsules):
3. Topical application (creams and gels):
Topical use (creams, gels, lozenges, eye drops):
Oral use (tablets/capsules):
Wrinkle injections:
Injections for arthrosis (joint treatment):
Oral intake:
Topical application (creams/gels):
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