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Information, effects, deficiency, dosage, side effects
Hyaluronic acid has been an integral part of the cosmetics industry for many years. The active ingredient that occurs naturally in the body is particularly valued for its anti-aging properties. But the possible uses go far beyond that, for example in various areas of medicine.
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).
The French chemist Portes first noticed in 1880 that the mucin in the vitreous body, which was examined by him - he called them hyalomucine - behaved differently. Mucins are part of the mucus in many organisms and have a protective and structuring function.
The German scientist Karl Meyer later isolated the hyaluronic acid from the vitreous body. He described that the compound consisted of a uronic acid and an amino sugar among other things.
In the naming, Meyer combined the terms hyaloid - the scientific name for the vitreous - and uronic acid. This is how the term hyaluronic acid came into being.
Hyaluronan is a linear, unbranched, alternating polymer with a high molecular weight. In contrast to other glycosaminoglycans found in the ECM, such as heparin, it is not sulfated.
A special property of hyaluronic acid is the high binding ability of water. Because the chemical compound is hydrophilic, negatively charged and can absorb large amounts of water due to the long polymer chain.
This creates a viscoelastic solution, the solution viscosity increasing with increasing concentration. In this way, hyaluronic acid is able to bind many times its own weight in water.
It was originally thought that hyaluronic acid acts as a kind of molecular filling in connective tissues. As mentioned earlier, one of the most important properties is the ability to bind large amounts of water. Even at low concentrations, hyaluronic acid can form an entangled network.
Researchers also identified various specific hyaluronan-binding proteins. These proteins are called hyaladherins. Their investigation has shown that hyaluronic acid fulfills many other important functions:
Their physical properties make hyaluronic acid resistant to water loss. It acts as a natural barrier in the tissue against rapid changes in the water content and the resulting drying out.
The joints, such as elbows and knees, are surrounded by a membrane called the synovial membrane. It forms a capsule around the ends of the two bones. The membrane secretes a fluid, the synovial fluid.
Hyaluronic acid is an essential component of the synovial fluid. It is viscous and has a high viscosity, which is guaranteed primarily by its water-binding property. Between the synovial joints, such as the knee joint, it acts like a damper or lubricant.
In addition to the elastic and shock-absorbing function for the joint, hyaluronic acid has another important function: to carry nutrients into the cartilage and to transport the waste materials out of the joint capsule.
Hyaluronic acid can be found in all bones and cartilage structures in the body. It gives both structures the necessary elasticity.
Cartilaginous structures, especially the hyaline cartilage, contain a lot of hyaluronic acid. The hyaline cartilage often covers the ends of the bones and, due to the cushioning effect, is often between joints that can be bent. Other hyaline cartilages are located at the connection between the ribs and the sternum, the tip of the nose or the supporting cartilage of the trachea and bronchial tubes in the lungs.
Connective tissue can be found everywhere in the body. It can therefore train many different forms and perform different functions, such as binding, support, protection or insulation.
One such example of connective tissue is the cord-like structures that connect muscles to bones in the form of tendons. Another variant connects bones to bones. In this case, they are bands.
There are 3 structural elements in all connective tissues. The basic substance is hyaluronic acid, the stretchable fibers consist of collagen and elastin and, depending on the organ, a basic cell type.
While all other primary tissues in the body consist mainly of living cells, the connective tissue consists largely of a non-living basic substance, hyaluronic acid. It separates the living cells of the connective tissue and cushions them.
The separation and padding allow the tissue to endure weight, tension and strain. All of this is possible due to the presence of hyaluronic acid and its ability to form the gelatinous base liquid.
The gums also consist of connective tissue. This is comparatively dense and fibrous - it is called a ligament. It secures the teeth to the jawbone. In the ligament, like in other connective tissues, hyaluronic acid plays an important role in the structure.
Without the presence of hyaluronic acid, the gum tissue could not stay healthy and tight. It gives the fabric its tensile strength and helps by providing moisture and nutrients. The result is healthy gums.
The scalp is structurally identical to any other skin tissue in the body. However, the difference is made by the average of around 100,000 hair follicles that grow in it. The hair and hair follicles are a derivative of the skin tissue.
There are 2 different skin layers. The epidermis is the outer layer. It is the protective shield and the body's natural barrier to the outside world. The lower or inner layer is the dermal layer and makes up the main part of the skin.
The hair follicles grow in the dermal layer. This skin layer consists of connective tissue and the hyaluronic acid contained therein, which supports, nourishes and hydrates the deep layers of the scalp with its gel-like, liquid-like properties. The result is healthy, shiny hair and a scalp with sufficient moisture.
Hyaluronan is part of all vertebrates and the capsule of some strains of streptococci. It is a major component of the extracellular matrix and other differentiated tissues and organs. The concentration varies depending on the tissue and function.
In addition to the ECM, hyaluronic acid is the main component of the following organs and liquids with the appropriate concentration:
The largest amount of hyaluronan, about 2.5 g/l, is in the skin. This makes a total of about 7 to 8 g of hyaluronic acid in an adult, which corresponds to about 50% of the total amount in the body.
Researchers assume that the total amount of hyaluronic acid in an adult's body is between 11 and 17 g. The highest concentration so far detected in human tissue is found in the umbilical cord at around 4 mg/ml.
Like almost every biological material, hyaluronic acid is degradable. It can be broken down in the organism in two different ways. Hyaluronidases and special enzymes are required in both cases. There are several variants of this enzyme that work at different points:
Hyaluronidase, Hyal-1, is responsible for the catabolism of hyaluron within the cell. It mainly works in the lysosome. The final breakdown products are simple sugars that can either be processed in other metabolic pathways or broken down.
The hyaluronidase, Hyal-2, is responsible for the breakdown of extracellular hyaluronan. After cleavage, it is carried away by the lymphatic system. If it is then in the bloodstream, the liver removes about 80%, the kidney another 10% and the rest is filtered through the lymphatic system.
Hyaluronic acid is broken down in the body at different rates. Researchers have found that the half-life in the extracellular matrix is only a few hours to weeks - in the synovial fluid even just a few hours.
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:
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:
There are many known factors that can affect hyaluronic acid levels. Genes are just one of them. There are many environmental factors that you can influence.
For example, smokers are more likely to develop deeper wrinkles. An in vitro study in 1989 showed that cigarette smoke can break down hyaluronic acid. The researchers assumed that this effect is caused by the free radicals contained in the smoke.
The hormone level can also influence the hyaluronic acid concentration in the body. Studies have shown that estrogen treatment increases the activity of hyaluronic acid. The hormone is known to increase the use of nutrients like magnesium and zinc - nutrients that are known to affect hyaluronic acid levels.
Skin aging shows itself as a progressive decrease in the functional and reserve capacity of the skin tissue. It is a complex process and an interaction of different biological events.
You can distinguish the natural inner process from the external influences. The human body is able to produce hyaluronic acid itself. However, this ability wears off over time.
Possible reasons for this are the decrease in estrogen and progesterone. The lack of estrogens and androgens is known to lead to collagen breakdown, dryness, loss of elasticity and wrinkling of the skin.
The decrease in the hyaluronic acid concentration in the skin means that less water can be bound. The skin becomes dry and less elastic. This promotes the accrual of wrinkles.
Joints and tendons are essential to enable movement. As already mentioned, hyaluronic acid is the main component of the synovial fluid and ensures elasticity and shock absorption.
If the hyaluronic acid level decreases, this also affects the consistency of the synovial fluid. The effect as a lubricant decreases and cartilage and joints are no longer adequately protected against impacts.
This leads to friction of joints and cartilage, which is associated with severe pain. The result is that every movement is perceived as painful and avoided if possible. Mobility continues to decline.
Many different conditions can lead to painful joints. The most common diseases are osteoarthritis, rheumatic arthritis, gout, strains, sprains and overworking.
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 various cosmetics. Today hyaluronic acid is available in face creams, masks, serums and in the form of ampules for application.
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 amount administered and the consistency depend on the depth of the wrinkles and the area to be treated.
A thin gel is usually used for superficial wrinkles. For deeper furrows, a thick preparation is injected. In both cases, a cushioning effect is sought.
In the past, an alternative to hyaluronic acid was the injection of wrinkles with collagen. However, this trend has subsided, as complications and intolerance were more common with collagen. There were often allergic reactions and nodules under the skin.
This was mainly due to the origin of collagen: it was usually extracted from pig or cattle tissues. The body reacted more frequently with an immune response to the foreign collagen.
Another common method of wrinkle injection is to use botox. This is the botulinum toxin, a strong nerve poison. The toxin is synthesized by a bacterial strain, Clostridium botulinum. As little as 1 g of this neurotoxin could kill 1 million people.
Nevertheless, botulinum toxin has proven to be a successful and valuable therapeutic protein. It is not only used for esthetic purposes, but is also approved for the treatment of other complaints, such as chronic migraines or muscle spasms.
There are some major differences as compared to treatments with hyaluronic acid. One study showed that about 1% of people who received botulinum toxin injections develop antibodies to the toxin. Subsequent treatments with botox are ineffective.
A treatment with botox lasts about 3 to 6 months. The injected hyaluronic acid gel is broken down by the body over time.
Since botox relaxes the muscles, the facial expressions can suffer greatly from the treatment. The face often looks rigid and frozen. Treatment with hyaluronic acid, on the other hand, has a cushioning effect and does not affect facial expressions.
Another major difference between the two treatment methods is reversibility. Unsuccessful treatment with botox can't be reversed prematurely. By using hyaluronidases (enzymes that break down hyaluron) there is a possibility of reworking or even completely canceling the effect.
Basically, when choosing between botox and hyaluronic acid, the question arises as to what effect the therapy should have. As a rule, hyaluronic acid is used for static wrinkles, such as nasolabial folds or wrinkles around the corners of the mouth. The reason for this is that it fills up the age-related depressions.
Botox is more suitable for dynamic wrinkles, like crow's feet or frown lines. Since it has a paralyzing effect on the injected facial muscles, the facial expressions are no longer so pronounced. This completely prevents or reduces the appearance of these types of wrinkles.
Hyaluronic acid is not only used in esthetic medicine. In human medicine, it is also increasingly used in various areas.
For example, since it is a major component in the human eye, it is often used in eye surgery. Hyaluronic acid solutions are used to keep the eye moist during surgery and to promote wound healing. Eye drops containing hyaluronic acid can also be helpful after surgery or when eyes are dry and irritated.
Hyaluronic acid is generally thought to improve wound healing. Researchers assume this because the hyaluronan concentration in the skin is increased during the wound healing process.
A study from 2009 examined the treatment of eardrum perforations with a 1% hyaluronic acid solution. Of the 25 treated perforations, 17 regressed successfully, and 4 more could be significantly reduced in size. No side effects were observed in any of the cases.
In clinical medicine, the hyaluronic acid level is used as a diagnostic marker for various possible diseases. The content may indicate various liver disorders or a possible tumor disease.
Another application in human medicine is the treatment of osteoarthritis with hyaluronic acid injections. This method has been used for many years and has proven to be a useful therapy option in various studies.
Arthrosis, also called osteoarthritis, is the most common chronic joint disease. It usually arises from the natural wear and tear of joints and cartilage. If the synovial fluid decreases over time, there is an increased direct contact between the joint partners.
Over time, the cartilage becomes thinner or even completely destroyed through abrasion. This leads to direct bone-to-bone contact in the joints. The result is pain, stiffness and swelling of the joints.
Injections of hyaluronic acid into the joint are a treatment option that many doctors offer. This usually happens when a patient can no longer relieve the pain of arthrosis with other pain relievers such as Ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs). Other reasons can be the intolerance or the side effects of pain relievers.
The idea of using hyaluronic acid to treat osteoarthritis was originally proposed in 1971 by Hungarian scientist Endre A. Balazs. He had discovered the synovial fluid and its possible composition in earlier electron micrographs of joints.
Since then, the treatment of arthrosis with hyaluronic acid injections has been investigated in various studies and its effectiveness tested. In 2006, a team led by Nicholas Bellamy from the University of Queensland in Brisbane, Australia, collected 76 studies of the use of hyaluronic acid in the treatment of knee osteoarthritis and evaluated the results.
This was the largest and most comprehensive review of its kind at the time. The team found that pain in patients receiving injections was reduced by an average of 28 to 54%.
The authors concluded that hyaluronic acid treatment offers approximately the same pain-relieving effects as non-steroidal agents. The advantage of hyaluronic acid, however, was that it also improved mobility. Patients were able to perform their daily activities 9 - 32% better than before.
Initially, hyaluronic acid was extracted exclusively from animal tissues. The process was increasingly optimized and improved in the 1940s to 1970s. During the same period, research was carried out on the synthesis of hyaluronan by bacteria.
The first patent for the extraction of hyaluronic acid from cockscombs was registered in 1979. Plants also contain hyaluronic acid, which is released from the cells by a special process. Finally, researchers also discovered in vitro enzyme synthesis as a third production process.
Hyaluronic acid can be extracted from various animal tissues. These included cattle or fish eyes, pig skin, cartilage, joints or rooster combs. The latter was used most frequently because they contained the highest concentration ever documented.
In the beginning, hyaluronic acid from animal tissues was only suitable for laboratory tests. The risk of transmitting pathogens or other fragments was too great for medical use.
Hyaluronic acid is now increasingly synthesized using biotechnological processes and with the help of various bacteria in the laboratory. This has the advantage that it can be obtained in larger quantities.
The process is called cascade fermentation. Certain plants and fungi are used as a breeding ground for the microorganisms.
The fermentation takes place in several steps. The addition of sugar stimulates the microorganisms to digest and multiply the parts of the plant. Mostly certain strains of bacteria or yeast are used.
The addition of sugar leads to fermentation. The microorganisms form a capsule around them. These capsules also contain hyaluronic acid.
The hyaluronic acid is enriched in several stages and different fermentation tanks and can then be isolated using special biotechnological processes. The hyaluronan is produced with a particularly low molecular weight. As already mentioned, the body absorbs these smaller connections better.
Another decisive advantage over hyaluronic acid from animal origin is its tolerance. A contamination with animal proteins or pathogens with synthetically produced hyaluronic acid is ruled out.
The hyaluronic acid produced by microorganisms is therefore increasingly used in medicine today. The risk of transmitting diseases is eliminated. The likelihood of an allergic reaction is also minimized.
The extraction of hyaluronic acid from animal tissue is the oldest method. The process is a lot more expensive than the plant based variant.
Plants do not contain hyaluronic acid themselves. However, they can be used as a starting material for fermentation with the help of micro-organisms. This process is cheaper as compared to the animal version, since the hyaluronic acid can be produced in large quantities.
The consistently high quality speaks for the production by fermentation. Furthermore, undesirable reactions that could be triggered by animal proteins can be excluded.
For people who value a vegan lifestyle, non-animal hyaluronic acid is a good, safe and generally well tolerated alternative.
Hyaluronan is offered in various oral forms. These include, for example:
Hyaluronic acid capsules and drinks are usually used as a cure, which should be refreshed every 3 to 4 months. The effectiveness of taking hyaluronic acid has been confirmed in various studies. Food supplements with hyaluronan are very popular in Japan.
Two independent studies also examine the absorption of hyaluronic acid into the body and its distribution when taken orally. One of the research groups was able to confirm that this also alleviates the symptoms of knee osteoarthritis. The direct injection into the joints is therefore not absolutely necessary.
Hyaluronic acid lozenges can be helpful for coughs and dry mucous membranes. Since the hyaluronic acid binds water, it has a moisturizing effect on the mucous membranes in the throat and pharynx. This naturally inhibits a cough and sore throat.
The advantage of oral hyaluronic acid as compared to hyaluronic acid cream or hyaluronic acid serum is that it can penetrate deeper into the body and be distributed. The applied hyaluronic acid preparations do not penetrate all skin layers and only have a topical effect.
Depending on the area of application, various combinations with hyaluronic acid are available. If the focus is generally on increasing hyaluronic acid production, the combination with magnesium or zinc can be appropriate. As already mentioned, these nutrients play an important role in hyaluronic acid biosynthesis.
Many cosmetics combine collagen or the co-enzyme Q10 with hyaluronic acid. Collagen is also a component of the connective tissue. The co-enzyme Q10 is particularly valued for its antioxidant effect and its functions in the metabolism of the cells.
A study with 20 randomly selected subjects over a long period of time examined the combination effects of hyaluronic acid, collagen and succinate, also known as succinic acid. In vitro studies had previously shown that succinic acid stimulates fibroblast growth.
The research group came to the conclusion that the combination of hyaluronic and succinic acid can increase the body's ability to develop collagen. The long-term effect would therefore be a firmer and more youthful complexion.
In a 2015 study, researchers investigated the short-term effects of a combination of hyaluronic acid, chondrotine sulfate and a keratin matrix on the treatment of knee osteoarthritis. In this study, 40 people took the combination described in tablet form over a period of one month.
The investigation was aimed at people in whom the arthrosis was still at an early stage. On average, the pain sensation was reduced by the treatment by about 40%. There were no side effects.
The molecular size plays a crucial role in how well the body absorbs hyaluronic acid. Low molecular weight hyaluronic acid is more mobile due to its small size and penetrates the cells more easily.
In addition to the molecular size, the concentration also plays a decisive role. Highly dosed preparations with an active ingredient concentration of at least 100 mg are better absorbed by the body due to the carrier effect.
Carriers are transport proteins that are embedded in cell membranes. They enable the absorption and transport of essential substances such as salts, sugar or amino acids. The transport via carrier proteins is significantly faster and more effective than classic diffusion.
A Japanese research team discovered that eating at least 120 mg of hyaluronic acid a day contributes to increased skin moisture and improves dry skin.
The manufacturer's dosage information should be followed exactly. Overdosing with hyaluronan may lead to:
The symptoms usually dissolve fast and are usually not life-threatening.
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 that injections of hyaluronic acid gel can lead to allergic reactions or hypersensitivity in individual cases. Other documented side effects included bruising, lump formation, color changes and fluid retention. The described side effects only occurred in about 10% of the test persons.
The intake of hyaluronic acid capsules is safe, provided the dosage recommended by the manufacturer is observed. Hyaluronic acid creams and gels are also well tolerated. Since hyaluronic acid is a comparatively mild acid, minor skin irritation rarely occurs.
If hyaluronic acid is applied to the skin in the form of cream or gel or is used in the form of lozenges and eye drops, there are no known interactions with other medications.
Interactions between hyaluronic acid tablets and other medications have not yet been scientifically proven. Nevertheless, the intake should not take place without consultation with the family doctor - especially if other medications are taken on a regular basis.
If the hyaluronic acid is applied to the skin, disinfectants containing benzalkonium chloride, for example, should be avoided. The consequence of this is that the hyaluronan crystallizes out and therefore loses its effectiveness.
A hyaluronic acid allergy occurs very rarely, since it is a compound in the body. However, people with food allergies should pay attention to the manufacturing process and other ingredients.
For example, an allergic reaction can occur if the hyaluronan comes from an animal source e.g. rooster's combs and an allergy to chicken protein exists. This may make it unsuitable for people with an allergy.
The composition and the origin should therefore be checked carefully before taking it, if incompatibilities are known.
The effects of hyaluronic acid treatment show up at different speeds depending on the type of therapy. For wrinkle injections, the effect can be seen immediately after the injection.
Hyaluronic acid syringes for the treatment of arthrosis only show their full effect after a few weeks or months. However, a pain-relieving effect can appear after a few days. Various studies with repeat treatments showed that the positive effect can last up to 40 months.
The oral intake of hyaluronic acid also shows the first results after a few weeks. A Japanese study has shown that the effects of hyaluronan on the skin appear after 3 to 6 weeks. The result of this study also indicated that the effects may persist for several weeks even after the treatment is discontinued.
Caring for the skin with hyaluronic acid cream or gel has an immediate plumping effect due to its water-binding power. The connective tissue can also be strengthened with long-term use.
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