Hyaluronic acid (also called Hyaluronan) is a component of connective tissue whose function is to cushion and lubricate. Hyaluronan occurs throughout the body in abundant amounts in many of the places people with hereditary connective tissue disorders have problems such as joints, heart valves and eyes. Hyaluronic acid abnormalities are a common thread in connective tissue disorders. Interestingly, they are also common biochemical anomalies in most of the individual features of connective tissue disorders such as mitral valve prolapse, TMJ, osteoarthritis, and keratoconus.

Hyaluronic acid has been nicknamed by the press as the “key to the fountain of youth” because it has been noted that at least some people who ingest a lot of it in their diets tend to live to ripe old ages. ABC News had a show on a village in Japan and hyaluronic acid entitled, “The Village of Long Life: Could Hyaluronic Acid Be an Anti-Aging Remedy?”. (It should be noted that the people in the ABC news show were thought to get high amounts of HA from starchy root vegetables their natural diets. They were not taking supplements.)

While a number of studies have linked abnormal levels of HA to either connective tissue disorders (CTDs) or conditions common in CTDs, such as premature aging, there are also a number of studies on Pubmed noting associations of high levels of HA to some forms of cancer. With HA as with other substances in the human body, such as estrogen and cholesterol, there are most likely optimal levels, and disease often occurs when these levels become out of range in either direction. Low estrogen levels have been linked to bone loss, while high estrogen levels have been associated with breast cancer. High cholesterol levels have been linked to heart attacks and stroke, while low levels have been linked to bleeding problems and depression. HA has been studied less than either cholesterol or estrogen, but the prudent path would be to assume that the body has optimal levels of HA, as it does for cholesterol, estrogen and many other substances.

As such, it is always prudent to consult your doctor before you decide to take HA or any other type of supplement to make sure it is an appropriate treatment for your particular health condition.

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Hyaluronic Acid and Connective Tissue Disorders

The list below contains links to a sample of the studies where subjects with connective tissue disorders have been shown to have hyaluronic acid (HA) abnormalities:

Ehlers-Danlos syndrome
Marfan syndrome
Osteogenesis imperfecta
Stickler syndrome

Not surprisingly, these disorders all have a lot of overlapping features, and many of these overlapping features, when studied individually, are also linked to hyaluronic acid abnormalities. In every study I looked at for connective tissue disorders that examined hyaluronic acid, the levels were always abnormal in patients with connective tissue disorders.

In human and animal studies, hyaluronic acid abnormalities occur in:

Heart valves with MVP
Joint instability
Detached retinas
Muscle contractures
Rachitic skeletal features (pectus excavatum, pectus carinatum, scoliosis, bowed limbs, hypermobility, etc.)
Poor scar formation (fetuses do not scar because of the high content of HA in amniotic fluid)
Acrogeria (prematurely wrinkled skin)
Premature aging syndromes* (which share many features with connective tissue disorders, especially Ehlers-Danlos)

Hyaluronic acid, or commercial preparations containing hyaluronic acid, are in use, or being studied to be used, to prevent, treat or aid in the surgical repair for many the types of problems people with connective tissue disorders tend to have such as:
Detached retinas
Osteoarthritis (HA injections are the new breakthrough treatment for this condition)
Muscle contractures
Prevents scarring
Vocal cord insufficiency
Wrinkled skin
Cartilage damage
Wound healing
Ligament Healing

The list below contains a partial list of common features of several connective tissue disorders. Both the syndromes and the individual features of the syndrome (even when the individual features are studied in the general population, not just in people with genetic disorders), all have links to hyaluronic acid abnormalities.

Syndrome with hyaluronic acid abnormalities

Features linked to both the syndrome and hyaluronic acid abnormalities
Ehlers-Danlos syndrome mitral valve prolapse, prematurely wrinkled skin, pectus excavatum, pectus carinatum, scoliosis, bowed limbs, hypermobility, keratoconus, hernias, poor wound healing, joint instability, TMJ, contractures, osteoarthritis, fractures
Osteogenesis imperfecta mitral valve prolapse, pectus excavatum, pectus carinatum, scoliosis, keratoconus, fractures, bowed limbs, hernias
Stickler syndrome mitral valve prolapse, keratoconus, pectus excavatum, pectus carinatum, scoliosis, osteoarthritis, hypermobility, bowed limbs
Marfan syndrome mitral valve prolapse, scoliosis, pectus excavatum, pectus carinatum, osteoarthritis, keratoconus, hypermobility, bowed limbs, hernias, detached retinas, glaucoma

Since the ABC special on hyaluronic acid called it the “Fountain of Youth”, it is interesting that one of the defining characteristics of premature aging syndromes, such as Progeria, is hyaluronic acid abnormalities.

Related article:

Intra-articular Hyaluronic Acid Injections for Knee Osteoarthritis – Article from the American Academy of Family Physicians on beneficial effects of using HA for osteoarthritis.

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Hyaluronic Acid and Environmental Factors

There are many factors known to influence hyaluronic acid levels. Genes are likely to be a factor, but there are many environmental factors that are known to have an impact, including zinc and magnesium availability. Not surprisingly, magnesium and zinc deficiencies are known to be associated with many of the same symptoms associated with hyaluronic acid abnormalities, such as mitral valve prolapse and poor wound healing, respectively. Perhaps this is because the zinc or magnesium deficiency contributes to the hyaluronic acid abnormality, which in turn causes the symptom.

There are a multitude of studies on Medline regarding hyaluronic acid and a wide variety of environmental factors. Here is a sample of some of the interesting ones that relate to connective tissue disorders:

Hyaluronic acid becomes abnormally elevated in the skin of swine who have zinc deficiencies. Magnesium is needed for hyaluronic acid synthesis. Perhaps a lack of magnesium is one of the factors in some connective tissue disorders. Magnesium supplementation is an established treatment for many of the symptoms of connective tissue disorders, such as fibromyalgia, mitral valve prolapse and contractures. (See my related page on low magnesium levels and my section on mitral valve prolapse.)

Ascorbic acid can degrade hyaluronic acid. Estrogen treatment increases activity of hyaluronic acid. Estrogen is known to increase utilization of nutrients like magnesium and zinc – nutrients that are known to affect hyaluronic acid levels. Cigarette smoke is known to degrade hyaluronic acid.

In a study of rats, hyaluronic acid turnover and metabolism were affected by age, dietary composition, and caloric intake. If what rats ate affected their hyaluronic acid levels, then this may be a good clue that diet may well affect hyaluronic levels in humans, too. In another study on rats, hyaluronic acid deposition in rat cerebellum is affected by thyroid deficiency, thyroxine treatment and undernutrition. In a study of humans, hyaluronic acid levels were altered by physical activity and food ingestion.

In a study on rats, skin hyaluronic acid concentration was higher than normal in energy deficiency, but below normal levels in prolonged protein deficiency. In rats suffering from prolonged malnutrition, the collagen concentrations are reduced. (Reduced collagen concentrations are also found in some of the connective tissue disorders such as osteogenesis imperfecta, as are a plethora of other conditions also associated with hyaluronic acid abnormalities. Not surprisingly, zinc deficits are known to affect hyaluronic acid levels. In a study on rats, among other symptoms, a deficiency in zinc resulted in impaired collagen synthesis.)

Strep and staph bacteria emit an enzyme called hyaluronidase. Hyaluronidase is an enzyme which breaks down hyaluronic acid, thus allowing an entry point for the bacteria to enter the body. This may be why people may become hypermobile or develop heart aliments like mitral valve prolapse after illnesses such as rheumatic fever–because the hyaluronic acid in their connective tissue has been degraded by the bacteria that causes their illness. (See my section on “What Causes Mitral Valve Prolapse? Hyaluronic acid as a clue” for more on this topic.)

If animals that are genetically similar to humans such as rats can have reduced collagen levels and hyaluronic acid abnormalities from changes in their diets, then it would be logical to consider diet as a causative factor in people with the hyaluronic acid abnormalities.

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Hyaluronic acid occurs in abundant amounts in many of the places people with connective tissue disorders have problems such as the joints, the eyes, the skin and heart valves. Hyaluronic acid is needed to cushion and lubricate joints, eyes, skin and heart valves.

People with connective tissue disorders and related features all seem to have abnormalities of hyaluronic acid. In every study I found that analyzed hyaluronic acid levels in people with connective tissue disorders or related disorders, when compared to controls they always had hyaluronic acid abnormalities.

HA is influenced by nutrition and other environmental factors. Many of the features of premature aging syndromes and connective tissue disorders are also known to be caused by nutritional deficiencies, and not surprisingly these are often the same nutritional factors that influence the manufacture of hyaluronic acid. My theory is that this is not all one big coincidence. Logically, it is more likely to be a predictable sequence of causes and effects.

Hyaluronic acid is being used commercially or experimentally to correct a large portion of the problems found in connective tissue disorders such as fractures, eye disorders, poor wound healing and prematurely wrinkled skin. It would be highly logical to consider the possibility that hyaluronic acid works to correct these problems because defects or deficiencies of hyaluronic acid are what cause these problems in the first place.

Perhaps controlling or optimizing the environmental factors, such as modifying ones diet, to optimize hyaluronic acid levels would be helpful in treating many inherited connective tissue disorders and premature aging syndrome.

Also see my next section: Frequently Asked Questions About Hyaluronic Acid for answers to questions about food containing HA and vitamin C interactions with HA, and the studies linking high levels of HA with cancer.