© Whole Foods Magazine

April 2003

Oral Hyaluronic Acid: Anti-aging, Skin, Joints and Healing:

An Interview with Bill Sardi.

By Richard A. Passwater, Ph.D.

My interest in oral hyaluronic acid (HA) was first sparked in early 2001 by my older son, Richard, Jr. Richard was in contact with Professor Akio Kobayashi of the Biochemistry Department at Osaka University regarding the health benefits of HA. I had been aware of the importance of HA in maintaining the proper viscosity of synovial fluid and vitreous gel of the eye, but the importance of HA to skin smoothness and brain was new to me. It wasn’t a complete surprise, considering that HA is the principal compound in the body for retaining water in connective tissue, skin and some organs, but I hadn’t seen studies demonstrating these health benefits before.

Over a year ago, I recommended oral HA to a close friend in the veterinary dietary supplements business. A few months ago, my friend showed me several unsolicited letters he has received from his customers. Notice that I said " customers," but I could have said "users." Often, it seems that when horse owners find a product that helps their horses, they try the product themselves if they have the same condition.

One letter reported, "After three and one-half weeks taking your oral HA, I am off my prescription medicine. My hands quit hurting, and the rest of my body followed. Last year, my doctor told me that I was about two years away from knee replacement. Even with my meds, my right knee hurt. All the pain is gone now. My 13-year old German shepherd has stopped dragging her back feet and doesn’t cry at night. She is also off of her meds. My vet started giving HA to his old lab last week and says he was very skeptical, but saw differences the next day. He started taking it himself after seeing the dramatic improvement in his dog."

This really got my interest. Knowing that Bill Sardi had just written a book on oral HA, I called Bill to ask him to share some of his research with us. Many readers know Bill from his other health books and articles. Bill is a health journalist and has written numerous books, including The Iron Time Bomb, In Search of the World’s Best Water, Why Babies Die, and his latest book, How To Live 100 Years Without Growing Old.


Passwater: Bill, your book captures your excitement about HA. What aroused your initial interest in oral HA?

Sardi: The startling ABC News Prime Time Live TV program (Nov. 2000) in which Connie Chung went to Yuzurihara, Japan (the "village of long life" ) and showed pictures of people who were in their 80’s and 90’s, and who had flawless skin (no wrinkles, no age spots), flexible joints, good eyesight (few wore glasses) and a full head of hair. Some had even habitually worked in the sun much of their lives, smoked tobacco and drunk copious amounts of saki. A World Health Organization (WHO) survey of 990 villages and towns in Japan found Yuzurihara had the oldest population. There are 10 times more people living beyond the age of 80 in Yuzurihara than any place in the United States. This report came on the heels of the WHO announcement that the Japanese live the most disease-free years of any country in the world.

I eventually traveled to Japan to see this for myself. Farmers were still working in their fields into their 70s and 80s and looked like men half their age. One woman in Yuzurihara was in her 90s and had perfect skin, no age spots, no wrinkles whatsoever. This was all confirmed by Dr. Komori, the town doctor. Unlike in other parts of the world where human populations claim to live long but have a difficult time substantiating their claim—like the Hunzas in Eastern Pakistan—the people of Yuzurihara have real birth certificates to prove their longevity.

These people live an hour and a half north of Tokyo, next to the town of Nishi, on a slope where rice, the traditional staple of Japan, cannot be grown. So they eat root vegetables, fish and low iron foods. This diet helps these people retain HA (the root vegetables themselves provide no HA).

HA is the naturally produced water-holding molecule in the connective tissue of the body. Just one gram of HA holds about six liters of water. Think of how the skin of very young babies looks—it won’t even create a scar if cut or scratched. That’s what HA acid does. It is nature’s healing agent and scaffolding or "space filler" for the skin, hair, eyes and joints. It also serves as a barrier against disease.

Passwater: At what point did you become excited enough about HA to write the book?

Sardi: When I began to see it work. The first convincing evidence was when my dog of 17 years, a 10 pound Maltese with arthritis, regained his ability to run up stairs again. Animals don’t know what the placebo effect is. Then my twin brother came to my front door with his knee brace in hand and said he didn’t need it anymore. He had a very bad Baker’s cyst problem from running cross-country races. I could tell there was a difference in my own skin when I shaved. It was now smoother and small nicks from shaving healed right up. These results were observed within two to three weeks. I have since noticed the bounce is back in my legs. In recent years if I jumped three or four feet onto hard pavement my knees would hurt. But now the spring is back in my legs, just as it was when I was younger.

Passwater: Who should be interested in reading your book?

Sardi: Anybody who is going to live past 50 years of age should learn more about HA. There are a lot of claims about anti-aging effects from growth hormone, or this herb or that. There is no question that the loss of HA over time is responsible for the visible signs of aging, wrinkled skin, hair loss, voice changes, diminished eyesight, wear-and-tear, osteoarthritis, yet little is known of this wonderful molecule.

A remarkable finding is that these visible aging signs can be reversed with oral HA supplements. A 57-year old woman called me from Florida. She works at a golf course. Her knees were painful and "clicked" when she moved. She called to say, after just two weeks of taking 300 mg of daily oral HA, that her knee pain had disappeared, her husband had told her that her facial skin looked better than following two previous plastic surgeries, her hair dresser noted that her hair had begun to grow and was thicker, and, most astonishing of all, she had no need for her reading glasses any longer! Others have written or called to say they had canceled knee operations, their crow’s feet (wrinkles on the temples) had disappeared, and friends began asking if they had undergone plastic surgery. The visible results of oral HA supplementation can sometimes be remarkable and rapid.

Passwater: We focus much on the main proteins in skin—collagen and elastin—when we look at skin health. A primary cause of the degeneration of collagen is the decrease in hydrated HA, which supports collagen. This is why skin moisture is so important. Putting moisturizers on the skin surface helps, but this is like using a small Band-Aid on a large cut. Replenishing skin HA is much more important. Drinking plenty of fluids also helps keep the HA hydrated. HA helps keep the collagen intact and smoothes out the skin to prevent wrinkling.

Are there common foods that are high in HA?

Sardi: There was a misconception that since the people in Yuzurihara retained HA because of their diet that others can do the same. One would have to eat that diet throughout life. The diet in Yuzurihara is instructive since the root vegetables and low iron content produced longevity and youthfulness. In Yuzurihara this is attributed to a small sweet-potato-like vegetable called tamaji. Actually, a good example of an equivalent would be Echinacea, which helps to protect and retain HA levels in the body. Other nutrients such as bioflavonoids (quercetin, bilberry, cranberry, green tea, grape seed, others), ferulic acid from Ginkgo biloba and oryzanol in rice bran, as well as IP6 phytic acid, all of which bind to iron and copper and some which inhibit viral replication, help to retain HA levels.

Passwater: One form of oral HA is derived from rooster combs. I’m not aware of many instances where rooster combs have been dietary staples, but I have come across accounts where during a famine in China, rooster combs were consumed in an effort to get more calories out of chicken, and people noted improved skin health. Soon rooster combs were sought after as a beautifying food. There are reports that Marie Antoinette favored rooster combs for her complexion. Eventually, rooster combs were eaten as a delicacy in France, northern Italy and China.

Are you aware of any other instance where unusual dietary items rich in HA have been used?

Sardi: Well, I know that ancient Egyptians had some rather odd glandulars that they ate as medicines. They ate eyeballs from animals. The eyeball is a very rich source of HA. You might say it was the first HA supplement. Today rooster combs and chicken sternum collagen are sources used to produce oral HA supplements. Also, HA is cultured and produced by a microbial fermentation process. These are all good sources of HA. What distinguishes one form of HA from another is its molecular weight, solubility, dosage and cost. Results are observed much more quickly with daily dosage of 150-300 mg. This dose would be cost prohibitive for some oral forms of HA. Benefits are reported from the use of all the oral HA products.

Passwater: Are oral HA supplements legal for sale, according to the 1994 Dietary Supplement Health and Education Act (DSHEA)?

Sardi: DSHEA allows structure and function claims. Companies marketing oral HA supplements, and their retailers, can say oral HA helps to create healthy skin, hair, eyes and joints. The manufacturers will have to provide data before they can make claims of a cure for osteoarthritis or other diseases.

Passwater: How about the part of DSHEA that stipulates that pre-existing drugs can’t be introduced as new supplements?

Sardi: This question arose with red yeast rice used to lower cholesterol. Since the statin drugs are synthetic statin molecules, and statin molecules were also found in red yeast rice, the subject arose as to whether red yeast rice was a drug or a food supplement? (A closer definition would be a nutraceutical, but I’m not sure if the FDA uses that nomenclature.) So, to answer your question, HA has been used in injectable form during eye surgery for over a decade and recently has been used in high molecular weight injected into joints and skin. Does that make oral HA a drug or a dietary supplement? The oral HA products are mostly of low molecular weight. HA in an injectable form ranges from 3 million to 6 million daltons molecular weight, while some oral forms are as low as about 1,500 to 3,000 daltons. A dalton is a unit of mass equal to the mass of a single hydrogen atom.

Passwater: I have seen test results of one oral HA supplement that determined it was about 5,000 daltons. It seems logical that the smaller molecular weight forms of HA are more easily absorbed in the intestines, but that may not be the complete story. Clinical results are what are important.

Sardi: By the way, this is the same problem that some of the medicinal mushrooms and Beta glucans have—too high a molecular weight and poor solubility. Some mushrooms and beta glucans have only been demonstrated to work in injectable form. When they are formulated into oral products, they simply aren’t absorbed through the gut. Some doctors question whether oral HA is absorbed, mistakenly believing it is the same high molecular weight molecule as injectable HA.

Passwater: When did oral HA supplements become available?

Sardi: Oral HA supplements have been available for a number of years, but the manufacturers didn’t know how to market them. They kept bundling them in with or calling them collagen supplements. HA isn’t collagen. Think of cells in the body as bricks and the collagen or connective tissue between cells as the mortar in a brick wall. The HA is the agent that keeps the mortar from drying out and cracking.

Passwater: What does the body normally use HA for? Where can it be found in the body?

Sardi: HA is the water-holding molecule of the body. It holds water in connective tissues, in between cells. Thus it cushions nerves and ends of bones, provides shape and form to the human eye and skin, and forms a barrier against the spread of disease. It’s interesting to note that the female egg is wrapped in HA and that the male sperm produces hyaluronidase, the enzyme that breaks down HA. Hyaluronidase then permits sperm to invade the egg and enable it to be fertilized. This knowledge opens the door to creating a natural form of birth control. Taking natural hyaluronidase inhibitors in high doses, either by the male or female, might prevent conception. This is unproved—just on the drawing boards, so to speak.

Passwater: How does the body make HA? And does this production decrease with age or illness?

Sardi: HA is naturally produced, a few grams a day, and some is degraded and excreted through the liver. Vitamin C in combination with iron helps to break down HA and creates a healthy turnover of fresh HA every day. Unfiltered sunlight (UV rays), viruses and malignancies can cause accelerated breakdown of HA. For instance, in some cancer patients the HA is being broken down at a rapid rate and this can be used as a marker for bladder cancer. Degraded HA is what clogs the lymph glands and blocks the downstream spread of tumors.

In very young children with a disease called progeria, HA is excreted in the urine at a rate 17 times that of healthy children. These progeria kids, at age 2 and 3, look like they are old, very old. They have facial wrinkles, they are bald, and they have cataracts. Progeria serves as evidence that aging is not a function of the number of birthdays but a process involving the loss of HA. Lose HA and a person will look old, regardless of his or her birth date.

Passwater: Seems like it would be more efficient to absorb HA from the diet. How well is oral HA absorbed?

Sardi: For quantification, I think the manufacturers of the oral HA supplements are going to have to conduct tracer studies so the absorption and excretion of oral HA can be measured. For now, we are left with observing the changes in the body, some of which are quite visible, particularly in the skin.

Passwater: Are there any side effects from taking oral HA supplements?

Sardi: Yes, there are, though they are not common. First, understand that oral HA causes water to gel up, like Jell-O in the refrigerator. Now if a person were to be dehydrated, or be taking extra doses of a diuretic, he or she might experience a whopping headache due to a rise in blood pressure. This actually happened to a woman who inadvertently doubled up on her water pills and had a hypertensive crisis while taking oral HA. Fortunately, the problem subsided. Patients with high blood pressure on diuretics should be aware and take lower doses of HA, let’s say no more than 150 mg per day, and they must remember to drink water. Many hypertensive patients take oral HA supplements and report no problems. One of the pieces of advice I offer in my book is to not to forget to drink water. HA plus H2O is the way it all works.

Then there are cancer patients who have lymphedema, a condition in which the lymph glands are filled with HA degraded by the tumor and the HA has blocked the drainage from the lymph glands. This results in swelling in the legs. Oral HA would be contraindicated in cancer patients with lymphedema.

Probably, oral HA should be avoided by patients with rheumatoid arthritis, which comprises less than 5% of the cases of arthritis. The classic symptoms of morning stiffness in a rheumatoid arthritis patient are caused by an autoimmune reaction degrading HA during sleep. Upon awakening, the rheumatoid patients find their joints are rigid because they are filled with excessive amounts of degraded HA. Once physical activity and the circulation gets moving, the stiffness disappears.

Passwater: What do we know about how well the various sources of HA work?

Sardi: All of the oral HA products work. I hesitate to say that one type is superior to another because it may create the false impression that one source is problematic or even undesirable. Manufacturers are often too eager to oversell their products, and in seeking to point out the weaknesses in their competitors’ products, they destroy any interest or demand for the product in general.

Therefore, I prefer to say that HA is good for the aging body, and you’d better get some. Period. Even higher molecular weight products seem to yield some benefits. To be accurate, HA is a long, thin molecule, which is how it gets its high molecular weight. In simplistic terms, it isn’t a wide molecule, it’s a long one. It is a disaccharide, that is, two sugar-like molecules strung together and repeated over and over. Some manufacturers appear a bit reluctant to reveal their molecular weight for fear it will be used against them. The lowest number is not necessarily superior. It just helps to have low molecular weight material. Someday there will be a study comparing the various sources.

Passwater: How does oral HA compare to glucosamine and chondroitin sulfate?

Sardi: HA is a double molecule, glucosamine that holds hands with glucuronic acid. Glucosamine (technically in the form of N-acetyl-glucosamine while a constituent of the complex molecule of HA) is only one half of the HA molecule, hence the reason why glucosamine only yields mild benefits for arthritis sufferers who usually have to take it in high doses (1,500 mg) for prolonged periods of time to experience any results. Just 150-300 mg of oral HA will work better and faster at restoring joint health.

Chondroitin sulfate raises the production of HA in the body. Dr. Lester Morrison, a cardiologist at Loma Linda University in the 1970s, used very high doses of chondroitin sulfate (5,000 mg tapered to 1,500 mg over three or four months) following a heart attack or bouts of angina to successfully rebuild and heal cardiac tissue. Some of these patients also experienced anti-aging benefits, such as renewed hair growth, cancellation of prostate surgery and disappearance of angina.

Passwater: I’ve put some basic information about the structure of HA in a box (Page XX) for readers wishing to know more about the biochemistry of HA. How much HA does the body lose each day?

Sardi: The body makes and degrades a few thousand mg of HA per day. With advancing age or disease, the degradation rate is not completely made for up by the rate of synthesis, resulting in what we know as the slow progressive signs of visible aging. Not all HA loss is systemic. HA wears out in localized tissues where there is repetitive use, the knees, the wrist (carpal tunnel), the shoulder, the temporomandibular joint (symptoms of TMJ), or where there is greater exposure to the sun (crow’s feet, shrinkage of the HA gel inside the eyes that leads to vitreous detachment and floaters).

Passwater: What dosage of oral HA do you recommend for various conditions—joints, skin, and so on?

Sardi: HA is appropriate for adults, age 40 or 50 and up, or anyone who has worn out HA in a particular area. I had a 32-year old piano mover write to me that he was ready to give up his job and undergo knee surgery. He took oral HA and within a month had no pain. The loss of HA can occur early, depending upon wear and tear. Imagine what oral HA supplements could do to extend the career of athletes. I expect Olympic athletes to be using oral HA soon. Oral dosage should be 150 mg per day, with possibly a loading dose for one month of 300 mg per day. More HA is not always better.

Passwater: Let’s get back to aging. You mentioned that the aging process results in a loss of hydration due to a loss of HA. How would oral HA help besides making skin look younger?

Sardi: I have predicted that oral HA supplements will result in people literally walking out of their wheelchairs. I would like to see actor Christopher Reeve try a course of oral HA. Recall that Reeve suffered paralysis following a horse riding accident. The healing of nerves simply can’t take place adequately without the cushioning provided by HA.

I also have observed other profound effects of oral HA. For example, as oral HA refills the eyes, it slightly lengthens the front-to-back length of the eye. This means the focus point of the eyes is altered. Therefore, farsighted people who take oral HA supplements may find their vision improving without glasses. Since all adults become a bit farsighted with advancing age, this has enormous possibilities to keep people out of reading glasses.

Also, the other half of the HA molecule, glucuronic acid, is similar to the food supplement calcium D-glucarate, which helps maintain hormone levels. Many women taking oral HA supplements have reported that their hot flashes and symptoms of menopause have abated with use. This is not surprising. Women have been advised that oral estrogen supplementation doesn’t prevent disease, and may in fact slightly increase the risk of disease. An alternative to estrogen would be oral HA. Why do women have beautiful skin? Because estrogen elevates HA levels in the skin and body. Once natural estrogen production has ceased (menopause), the natural alternative would be oral HA.

Passwater: What impact will oral HA make upon the natural products industry?

Sardi: There is so much hyperbole, so much pseudoscience, among all the natural products now available, it is difficult today to determine the good "waterholes" from the bad ones. Understand, the natural products industry often doesn’t fully understand what it is selling.

For example, take red yeast rice, which now has been removed from the market by the Food and Drug Administration (FDA) because it has been declared a drug. Patients sought red yeast rice because they wanted an alternative to the sometimes troublesome statin drugs. But red yeast rice contained statin molecules and posed the same risk for side effects. The industry simply wasn’t helping the public find a good non-toxic alternative when it began selling red yeast rice.

Similarly, there are a lot of collagen products being marketed for joint health, and they are cause for confusion. Even though Type II collagen accompanies some oral HA products, the collagen is a sideshow. It’s the HA that is doing all the healing. Collagen products promoted for joint health simply aren’t going to produce the results that HA does. Once the industry sorts all this out, there will be a stampede for these HA products. Go into a health food store today and ask about hyaluronic acid. They haven’t a clue what you are talking about.

There are so many natural products that lay claim to "anti-aging" benefits it is often confusing. There is no argument that the visible signs of aging—baldness, voice change, skin wrinkling and dryness, shrinkage in height, joint pain and dependency upon eyeglasses—all emanate from the loss of HA and not to direct shortages of any hormones like DHEA, or minerals like coral calcium, or any other widely promoted natural remedies.

Passwater: Thanks Bill for sharing this information about HA with us.

Sardi: It’s my pleasure. What I have shared with you here should have profound impact on anyone who reads this interview. It should have a profound impact upon medicine and in particular natural medicine. Understand, just like glucosamine, the demand for oral HA is being led by the public. It is not a doctor-driven revolution. This is probably the way it should be. For readers who want to learn more about HA’s age reversing properties, they might be interested in picking up a copy of my new book How to Live 100 Years Without Growing Old, available at www.hereandnowbooks.com. For further questions about HA, readers may wish to contact me at my website www.askbillsardi.com. WF



How and Why HA Promises Benefits

Hyaluronic acid (HA) is not a single compound, but a family of similar structures. Let’s start with a brief review of the compounds and nomenclature involved with HA. The monosaccharide glucose, the principal sugar of the body, is the most important carbohydrate in the body. This is true not only because it is the primary fuel for producing energy, but because it is used for building many complex compounds.

When an amino group is added to glucose, glucosamine is formed. The body uses glucosamine to form several other larger compounds, but when it uses glucosamine this way, an acetyl group is added. Thus, the form of glucosamine found in complex compounds is actually N-acetyl-glucosamine.

Glucuronic acid is formed from glucose when it is converted into an organic acid by essentially replacing the hydroxyl group on carbon #6 with a carboxylic acid group. Galactose is another monosaccharide. It has almost the same structure as glucose, except that the hydroxyl group on carbon #4 points in the opposite direction. Galactosamine is formed with the addition of an amino group. Likewise, in complex molecules, galactose is converted into N-acetyl-glactosamine.

Hyaluronic acid (HA) is a member of the glycosaminoglycan (GAG) family, which includes chondroitin sulfate, dermatin sulfate and heparin sulfate. Unlike other members of this family, HA is not bound covalently to proteins. HA is comprised of linear, unbranching, polyanionic disaccharide units consisting of glucuronic acid and N-acetyl-glucosamine joined alternately by beta 1-3 and beta glycosidic bonds.

Figure 1 (Page XX) shows the chemical structure of HA. The ring structure on the left is glucuronic acid and the ring structure on the right is N-acetyl-glucosamine. The brackets indicate that these two components are repeated " n" times. Thus, HA is not a single compound having a single formula. Technically, any compound where " n" is greater than 10 can be called HA. However, the final synthesis of HA normally produces compounds where " n" can range widely from a few thousand to several million.

Chondroitin sulfate is a closely related family member, but it doesn’t hold as much water. The structure is similar, but the difference is biochemically significant. In chondroitin sulfate, there is the same glucuronic acid ring, but the other ring is n-acetyl-galatosamine. Chitin is also very similar except that it is basically a polymer of N-acetyl-glucosamine.


© 2003 Whole Foods Magazine and Richard A. Passwater, Ph.D.

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