Hyaluronic acid supplement side effects, benefit, allergy, toxicity, adverse events, and medical benefits for joint health information
March 1 2014 by
Ray Sahelian, M.D.

Hyaluronic acid is a component of synovial fluid, and is found in the vitreous humor of the eye, the synovia of joints, and in subcutaneous tissue where it functions is as a cementing agent. It is a glycosaminoglycan with anti-inflammatory and anti-edematous properties. In osteoarthritis, changes occur in the hyaluronic acid found in cartilage leading to degradation of the cartilage.

Benefit
Hyaluronic acid oral supplements are promoted for arthritis and many other conditions including skin health. I have come across a human study with an oral form from chicken comb which showed some improvement in joint pain. Many studies have been conducted with it in the injectable form into knees and I have listed some of them below. Some of the studies with the injectable form of hyaluronic acid directly into the joint show it to be effective, while others have not shown much benefit. As of October 2010, I am aware of one published human study regarding its oral use. As to the injectable form, the results are mixed. At this time I don't have a strong opinion on the benefit of oral form of hyaluronic acid since I have not come across many studies evaluating its effectiveness for joints or skin.

Buy Hyaluronic Acid, 50 mg per pill
Joint Power Rx with glucosamine, chondroitin, MSM, CMO, turmeric, boswellia for joint health
Hyaluronic
Hyaluronic acid plays an integral role in maintaining and regulating moisture with the tissues and facilitates the transport of nutrients into the cells and the removal of metabolic waste. it is found in all of the body's tissue, with the highest concentrations located in the extracellular matrix of the skin and the synovial fluid that bathes the joints and cartilage. Optimum levels are essential for the health of the joints and cartilage. Hyaluronic acid has undergone a natural enzyme cleaning technique for greater absorption. Whether ingested as a pill it is able to easily enter joint tissue is not fully understood at this time.


 

 

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Supplement Facts
Hyaluronic acid 50 mg

Suggested Use: 1 softgel once or twice daily with a meal.

Would there be a problem taking Joint Power Rx and hyaluronic acid together?
   We have not had any adverse reports yet regarding this combination but it is too soon to tell. Try each one separately at first for a week or so, and when combining use lower dosage initially. Have approval by your doctor if you are taking medications or have medical conditions.

Joint Power Rx Formulated

Because joint pain is so debilitating, glucosamine sulfate and chondroitin alone are sometimes not enough. This powerful formula includes several additional herbal extracts and nutrients that play a role in joint health.  

Supplement Facts:
Glucosamine sulfate (from shellfish)
Chondroitin sulfate
MSM
CMO complex
Boswellia serrata extract
Curcumin
Cat's claw extract
Devil's claw extract
Grape seed extract
Sea Cucumber

Hyaluronic acid review and summary
At this time I don't have a strong opinion on the oral form since I have come across only one small study evaluating its effectiveness. There is no mention in the medical literature at this time that it has side effects when used orally, however we have had reports from several users of a side effect in form of a skin rash. If you wish to give it a try, a high quality product  For joint support consider other nutrients that play a role and have been studied more thoroughly, including glucosamine, chondroitin, MSM, or a combination of the above found in Joint Power Rx.

Diabetes
Q. Does hyaluronic acid raise blood sugar or does it have an anti-diabetic effect? I don't find specific mention of effect on blood sugar. Can you provide some clarification please? I tried Injuv 140-210 mg/day and noticed positive effects in plumping of skin and improved quality of hair. It actually does have a facelift effect and also seems to improve libido. Pretty amazing.
  A. I am not aware of research that has looked into its influence on blood sugar but I doubt it has any significant effect.

Hyal-Joint supplement information
Hyal-Joint is a natural extract with a high content of oral hyaluronic acid (60 percent) plus other constituents such as collagen and glycosaminoglycans. It is promoted by BioIberica, a company in Spain. A small pilot study shows that it could help those with joint problems.

Effect of a natural extract of chicken combs with a high content of hyaluronic acid ( Hyal-Joint ) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial.
Nutrition Journal. 2008.
Twenty subjects aged 40 years and older with knee osteoarthritis participated in a randomized double-blind controlled trial. Ten subjects received Hyal-Joint (80 mg/day) and 10 subjects received placebo for 8 weeks. This pilot clinical trial showed that daily supplementation with oral hyaluronic acid from a natural extract of chicken combs ( Hyal-Joint ) was useful to reduce body pain and to enhance several markers of quality of life in adults with osteoarthritis of the knee.
   Comments: Additional studies are needed to confirm the results of this pilot study. Plus, we don't know the influence of the other constituents found in this product versus the effect of hyaluronic acid itself.

Hyaluronic acid side effects, safety, allergy, caution, reports from users
Since hyaluronic acid oral tablets are relatively a new introduction, side effects are not fully known. We have received a few emails by users that they experienced a skin rash. Caution is advised regarding its use since we don't know much about the long term effects of this nutrient taken orally.

I someone is allergic to shellfish, would they be able to take hyaluronic acid?
   This nutrient comes from rooster combs, not shellfish.

Have been using LubriSyn Hyaluronic Acid (Sodium) 150 mg for humans orally for a couple of weeks and have noticed my skin breaking out, mostly on my forehead. After about 5 or 6 days of not using the product, my skin is clearing up.

I am presently taking hyauluronic acid with OptiMSM. I seems to help the pain and stiffness in joints. However I have developed an itching on both lower legs. Can this be coming from the combination? I plan to stop taking it for a couple of days and see what happens.
    It's not possible to say which supplement is causing this adverse event without taking time off and reintroducing one at a time, the HA and the MSM.

I recently bought a skin cream called Tautinol, which has as its main component, hyaluronic acid to help with skin rejuvenation. I am a 50 yr. old female, and my skin actually is in pretty good shape. I’ve always had a nice complexion but alas age and time have caused a few lines around the eyes. I had heard it advertised on the radio, ordered some and used it for 2 weeks. Almost immediately I started getting little itchy pimples on the areas I applied it to, mainly the forehead and brow area. The itching was actually pretty intense and I picked at the pimples enough to relieve the itch. It’s been about two weeks since I quit, and almost all the pimples are gone.

I appreciate your research on hyaluronic acid side effects which Google led me to. I haven't experienced a rash like others have, but have had an unusual reaction. I have been taking Synerflex (Northstar Nutritionals) for 3 months. I have had enormous good luck with it's ability to end pain in legs radiating from knee problems (which won't be fixed until surgery in two more months). My husband now takes it, too. I take two a day, usually with evening meal. He has just started taking it last month. I've also been recommending it to other people. Recently, I developed a furriness on my teeth that didn't go away with brushing, flossing, and ordinary mouth care. After using a Stimudent stick to clean between my teeth (after having brushed with electric toothbrush and flossing), the results were scary - a yellow substance came from between almost allmy teeth. My eyes had become excessively watery and had a cloudiness of vision at times. I was constantly clearing my throat. I decided to stop the Synerflex, it being the most recent addition to the supplements we take. Two days later, the furriness is gone and my breath smells sweeter; eyes are drier and vision has cleared up. Throat is less croupy. We live a very healthy lifestyle. I am concerned about these results and wonder if you have had any other complaints about Synerflex. Contents include Hyal-joint (60% min. HyaluronicAcid w/5% hydrolyzed collagen and 15% min other glucosaminoglycans totalling 60 mgs; Hops flower extract 500 mgs; Boswellia serrata extract 300 mg; Boron as calcium fructoborate 2.5mg;and bioenhancer blend of ginger root, black pepper, and long pepper 50mg. The jel-caps are filled with a yellow substance.
    This is the first I have heard of this kind of reaction. It is interesting and I will await to see if others have a similar reaction.

I was doing some research for my mother-in-law who broke out in a chicken-pox-like rash. We can't figure any cause for the rash except I was looking up hyaluronic acid since she had begun taking that about two months before the rash broke out. Her rash is not on her face but is bad on her arms, some on her legs and a few on her back and stomach. Since she stopped taking it about a week and a half ago, it is gradually getting better.

Source of hyaluronic acid supplements
A common, natural source is rooster combs but other sources are also available.

What is the molecular weight range and the starting material of sodium hyaluronate from ingredient suppliers?
   Sodium hyaluronate is the sodium salt of hyaluronic acid, which is a straight chain macromolecular mucopolysaccharide composed of repeat disaccharide units of glucuronic acid and N-acetylglucosamine. The molecular weight from of one supplier of sodium hyaluronate, DNP international, is around 1-2 million Daltons and it is derived from glucose fermentation.

Hyaluronic Acid Research study
Menopause. 2013. Hyaluronic acid concentration in postmenopausal facial skin after topical estradiol and genistein treatment: a double-blind, randomized clinical trial of efficacy. After 24 weeks of treatment, HA concentration increased in both groups, but the effect was greater for estradiol treatment than for genistein treatment. Our data suggest that both treatments may enhance HA concentration in postmenopausal skin but that estrogen produces results that are greater than those produced by isoflavones.

Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin.
J Eur Acad Dermatol Venereol. 2005.
Hyaluronic acid is a naturally occurring polyanionic, polysaccharide that consists of N-acetyl-d-glucosamine and beta-glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock-absorbing role. The unique viscoelastic nature of Hyaluronic acid  along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, Hyaluronic acid  has been investigated as a drug delivery agent for various routes of administration, including ophtalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% Hyaluronic acid  gel, Solaraze(R), for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost-effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5-fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of Hyaluronic acid  together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.

Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis.
CMAJ. 2005.
Osteoarthritis of the knee is frequently treated by intra-articular injection of hyaluronic acid. We performed a systematic review and meta-analysis of randomized controlled trials to assess the effectiveness of this treatment. We searched MEDLINE, EMBASE, CINAHL, BIOSIS and the Cochrane Controlled Trial Register from inception until April 2004 using a combination of search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. We extracted data on pain at rest, pain during or immediately after movement, joint function and adverse events. Twenty-two trials that reported usable quantitative information on any of the predefined end points were identified and included in the systematic review. Even though pain at rest may be improved by hyaluronic acid, the data available from these studies did not allow an appropriate assessment of this end point. According to the currently available evidence, intra-articular hyaluronic acid has not been proven clinically effective and may be associated with a greater risk of adverse events. Large trials with clinically relevant and uniform end points are necessary to clarify the benefit-risk ratio.

Hyaluronic acid for the treatment of knee osteoarthritis: long-term outcomes from a naturalistic primary care experience.
Am J Phys Med Rehabil. 2005.
Patients were referred to a large primary care center for management of osteoarthritis of the knee. All were naive to intraarticular hyaluronic acid therapy and met our entry criteria, including resting visual analog scale pain of > 45 mm, radiographic confirmation of unilateral knee grade 1-3 osteoarthritis, and willingness to receive intraarticular therapy. Patients received a three-intraarticular injection series with Suplasyn (10 mg/ml, 2-ml injection) over 3 wks. Intraarticular hyaluronic acid injections were highly effective in improving resting and walking pain in patients with osteoarthritis of the knee on a first and a second treatment series. Duration of symptom control was about 6 mos, and the therapy was highly satisfactory to patients and was associated with very few local adverse events and limited use of concomitant therapeutic modalities. These data support the potential role of intraarticular hyaluronic acid as an effective long-term therapeutic option for patients with osteoarthritis of the knee.

Treatment of gingivitis with hyaluronan
J Clin Periodontol. 2003.
Our data suggest that a hyaluronic acid containing gel has a beneficial effect in the treatment of plaque-induced gingivitis.

Hyaluronic acid injection of the knees is no more effective than placebo. Arch Int Med 2002.

The FDA has ordered Hyalogic LLC to stop making unsubstantiated claims that its hyaluronic acid product, Synthovial 7, can increase cushioning, joint lubrication, and motility of painful arthritic joints.

Hyaluronan is an important structural element in the vitreous humor of the eye, synovial fluid, and skin of vertebrates. Moreover, hyaluron interacts with proteins such as CD44, RHAMM, and fibrinogen, thereby influencing many natural processes such as angiogenesis, cancer, cell motility, wound healing, and cell adhesion. Reflecting such a variety of functions, HA has attracted attention from a wide range of application fields such as medicine (including surgery), cosmetics, and health foods. Traditionally hyaluron was extracted from rooster combs, but nowadays is produced by the fermentation of streptococci. At present, quality issues such as purity and molecular weight distribution, rather than quantity, have been the focus of strain and process development in hyaluron production.

Emails
Q. I'm looking for people that are doing or have done research regarding hyaluronic acid. My mother, had the hyaluronic acid injected in her face approximately one year ago, and she has recently developed a reaction in her face. It feels as if the product had hardened inside her skin, she is very swollen and has redness around the area.

Q. I noticed one of your e-mails stating that someone who had been taking hylauronic acid orally for some time had a rash break out on his skin like chicken pox. I too had been taking hyaluronic acid for over two months when suddenly over the week-end my face developed a rash that looks like chicken pox? The rash is actually under the skin. Erie coincidence?
   A. Well, it looks like this is our second report regarding hyaluronic acid and skin symptoms, if we get a few more reports then it may be a serious issue to look into.

Q. I have taken many forms of hyaluronic acid orally for knee problems, they work very well but my skin broke out like I had chicken pox.

Q. I got an allergic type rash / hives on the skin surrounding my hysterectomy surgical scar. Only on the abdomen.

Q. I have found that glucosomine and the like alone may not be sufficient for my pain. However if I use Hyaluronic acid and type ll collagen the relief may be rather fast. It seems the ligaments are easily irritated and can even make standing very difficult. But if I take the Hyaluronic acid it disappears rather quickly. I stumbled upon it one day, and wonder why more isn't done to give
people that information.

Q. I thought you might be interested to hear of a happy but unexpected side effect of Gengigel which has hyaluronic acid. I started to use the mouthwash when my dentist told me that I had severe gingivitis and that my gums would need a lot of attention. For some 50 years I have suffered from Psoriatic Arthritis and have been given virtually every possible treatment to counter its effects. Most of the treatments produced unwelcome side effects of one kind or another and I have had to discontinue virtually all of them. As a result I have, for many years, been taking Indomethacin as my main defence as it is the only drug that did not produce any side effects as far as I was concerned. However, it only had limited impact in damping down the inflammation. As a result I developed severe inflammation in both wrists and the right wrist has suffered bone damage as a result. I generally also suffer from pain in most joints as a result of the Psoriatic Arthritis which is very wearing on a day to day basis. My consultant gave me a quarterly, low dose shot of depomedrone to ‘damp down’ the general inflammation. I was just about due to have another quarterly injection at the time I started to use the Gengigel. A few days after starting to use the mouthwash I noticed that the general pain levels seemed to be reducing and that the swelling in my wrists and the pain in the joints had significantly reduced. I obtained some Gengigel Gel and started to apply this to my gums twice a day. Within two weeks the swelling in my wrists had totally disappeared. There was quite a large swollen lump on my right wrist and six weeks after starting to use Gengigel this has also subsided and my wrists look quite normal. It is a dramatic result in respect of the Psoriatic Arthritis and my Consultant is amazed. (By the way, the gingivitis has also disappeared.)
     A. We'll wait to see if this was coincidence or a real response to the gel.

Q. Was watching the horse racing network and one of the trainers was talking about a product that they are using on all their horses to help maintain their health and performance. The product is Lubrisyn which is a hyaluronic acid product that is given orally. The trainer said that they have reduced their injections by 1/2 and the horses seem to be holding up better than ever. Is this product or a similar product available for humans? I'm a 55 year old Professional Golfer and very interested in maintaining my joints.
     A. According to their website, "LubriSyn, Sodium Hyaluronate, is patented oral hyaluronic acid for the treatment of joint pain and inflammation. Hyaluronic acid is the same glycosaminoglican found in synovial fluid, and the cartilage matrices, which cushion and lubricate articulating joints. Supplemental HA improves soundness and joint function. Daily oral ingestion of HA avoids the peaks and valleys associated with injectable products by maintaining a consistent bio-available serum level. In a comparative study of five HA products in the treatment of traumatic arthritis in horses in athletic or race training, horses treated with HA of molecular mass greater than 2 million Daltons exhibited significantly longer durations of soundness than those treated with HA of molecular mass less than 2 million Daltons. Compared to alternatives, LubriSyn (Sodium Hyaluronate) has the highest molecular weight (2.4 million Daltons) for sustained joint function improvement."
      Now, I am not a vet and I am not familiar with research with horses. However, up to know, I have not seen studies in humans using hyaluronic acid in an oral form. When I searched Medline to find a published study in animals on LubriSyn, I could not find one. The website that sells LubriSyn mentions a study that they have done, but it does not say if the study was published in a veterinary journal. Therefore, at this time, unless the manufacturer can provide a published study regarding the benefit of LubriSyn, it may be premature to make claims about this joint health product. Plus, even if LubriSyn works, we are not sure if it is any better than glucosamine, chondroitin, or a combination of these nutrients and other joint supplements such as CMO and MSM.

I have been taking 140 mg of hyaluronic acid supplement for 1 month and I noticed that the floaters in my eyes have turned from dark brown to clear with an overall reduction in all noticeable floaters. I do consume 4 oz of broccoli sprouts a day, and I have noticed that my night vision has dramatically improved.
   We would be interested to hear from other users to see if this is a real benefit from the nutrient or whether the broccoli sprouts had an influence, or the combination, or pure coincidence.

I have been having stiffness, binding, and pain in my neck for over a year now. If I were driving, watching TV or looking at a computer screen for a few minutes, I would lose mobility in my neck. To look down was very painful, my neck would bind until I would hear a very audible SNAP in my neck, and I would regain some temporary mobility. This has progressively gotten worse over the past 4 months or so, and the binding would happen maybe 40-50 times a day. I was beginning to think my neck was full of dry spaghetti.. A customer of mine introduced my to Hyalun, a horse supplement containing hyaluronic acid. I was very skeptical at first, researched the active ingredient and found no serious side effects from hyaluronic acid. I cannot believe how quickly and how well hyaluronic acid has worked for me. Literally, 3 days into the regiment, I had full mobility in the neck and haven't had it bind, snap, or crack once.
   That's great. Keep us updated to potential hyaluronic side effects or further benefits.

I came across your website while looking for some hyaluronic acid to buy. I have been using hyaluronic acid for approximately three years. I saw a clip in the Star magazine about how it helped skin. I didn't find a lot for sale at that time (2003) but purchased some Injuv, from someone, can't remember. I used to wear glasses to see up close and distance. I used to have burning in my hip joints. I used to have really bad allergies. After using hyaluronic acid for a few months I noticed I could see without my glasses. I also noticed the burning in my hips disappeared. My skin always looked good because I spend a fortune on it, (ha, ha - I am 59 years old), so I haven't seen much change there. But I live on a ranch with hundreds of cattle, horses, cats, dogs, chickens and peacocks. I sneeze every so often but the dust and hay and other stuff (we have no paved roads) do not seem to bother me like it used to. I have told others about hyaluronic acid, my mother (she is 82) thinks it helps her skin. I KNOW it helps me. I am on a horse working cattle (sometimes 8 hours a day) and I think this helps me stay pain free. Let's see, I don't always buy the same brand. I try to get the most mg. 100 to 140mg. And I take two or three a day. My boyfriend was at Kaiser recently with a knee problem. He has horrible arthritus and when I mentioned hyaluronic acid the doctor said studies have not proven the absorption of hyaluronic acid in the body. But I can certainly tell you that it works for me. I know my body so I know when the changes took place and what changed. Anyway, just thought I'd share that information with you.

I found your website looking for information about hyaluronic acid after hearing about its benefits for joints from a horse veterinarian, who uses it a lot for joint problems in sport horses. After having two years of knee pain and arthroscopic surgery that helped only marginally and temporarily, I tried taking hyaluronic acid orally. I've now been pain-free for 3 months. Going down stairs used to be painful, but now I can take them two-at-a-time again. Moreover, some minor pain in both hips and one shoulder disappeared at the same time. I use a liquid form of hyaluronic acid (Synthovial Seven) and take it under my tongue so that it doesn't go through my digestive system. (When I took it as directed by swallowing it with water, its benefits disappeared, but they returned when I went back to the under-the-tongue method. Weird, but true. Moreover, I've had chronic voice problems for years, and taking the hyaluronic acid seems to be helping that as well as my skin. It's a minor miracle.

I'm looking to purchase hyaluronic acid injection to the knee joints. I think two such products are available, hyaluronan and hylan G-F 20, Five different brands of hyaluronan are available: Euflexxa, Hyalgan, Orthovisc, Supartz, and Synvisc.
   Hyaluronic acid injection require a medical doctor's prescription and a qualified medical doctor to do the injection.

A couple of years ago, my wife tried an oral hyaluronic acid supplement. I don't remember the brand. But a couple of weeks after she developed a Baker's Cyst, which she never had before. I contacted the company and they said to discontinue the HA supplement. Have you heard of this possible connection as a side effect? Can a similar side effect occur with hyaluronic acid injections?
   I have not heard of a Baker's cyst associated with oral hyaluronic acid ingestion. As to hyaluronic acid injections, I do not have enough experience to know for sure.

I have very severe osteoarthritis, including multiple ruptured cervical-spine disks (caused by bone spurs and stenosis), one of which was "repaired" by fusion procedure 14 years ago, resulting in collateral damage to the median sensory nerve that continues today. Furthermore, the nerve damage left the thumb and forefinger of my left hand insensitive enough that constant use on a computer keyboard (my job prior to retirement required my to be at the computer 9-to-5, 5 days a week) has aggravated the forefinger joint (one doesn't type much with the thumb.) Now in retirement, I am a full-time musician / music teacher, and the arthritis is quite problemmatic. The pain and inflexibility in my hands / fingers is quite debilitating and I am interested in the possibility that Hyaluronic Acid might be of some help. However, I noticed several reports of rash side effects, but no indication of the dosage being taken. I would think that this information would be of benefit - perhaps there is a limit to how much supplemental hyaluronic acid can be tolerated. Are you aware of any such information? Finally, I would like to mention that several years prior to my fusion procedure, I tried glucosamine / condroitin briefly, but discontinued it after developing a rash, almost like hives. To be fair, I never did resolve whether the glucosamine / condroitin was the culprit or whether it was the natural, raw honey I started eating at about the same time - I never returned to ingesting either of these. At the time I remember reading reports that either of these could cause such reactions.
    I am not sure at this time if the rash some people have reported are dosage related. Some substances cause an allergic reaction even in tiny amounts whereas other substances cause an allergic reaction with higher dosages.

Suppliers
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