Hyaluronic acid (HA) is also called hyaluronan.  It is a polysaccharide found in most of the bodies’ cells. the body makes HA by using an enzyme called hyaluronic acid synthase to combine two sugars, D-glucuronic acid and N-acetyl glucosamine.  There are foods that either provide small amounts of HA, or the building blocks of it.  See the list at the end of the article.  Facial products are usually made from bacteria synthesized from poultry (rooster combs) and other sources (1).  HA is a main part of the skin, and 50 percent of HA is found here. It plumps, firms, and moisturizes skin.  It acts as a natural support for the dermis, and it delivers nutrients and keeps the skin moist by pulling water from your body. It’s a lubricating fluid found in connective tissue, skin, joints, eyes, and the fluid of the body (1).  HA is used in supplements for skin and joint health, including joint pain reduction, and in skincare items. This is as HA can help reverse cartilage and collagen loss.  It can lessen inflammation and assist in immune functioning, including wound healing.   It is in eye moistening drops, and in pharmaceutical eye serums and eye drops.  The last is to provide structure and moisture to damaged tissue while it heals.

Hyaluronic acid (HA) can slow down the loss of collagen while it reduces fluid or water loss in tissues. so, it can make, skin glow, improve joint health, and treat problems with, and lubricate, eyes.  This is all without the side effects of harmful, toxic, products. Hyaluronic acid, or hyaluronan, has the ability to improve skin’s texture and appearance. It also reduces the symptoms associated with aging, like joint pain.  HA does all of this as it is a clear, lubricating, secretion naturally produced in the body.  High concentrations of hyaluronic acid are found in the skin, inside the joints, in the eye’s sockets as well as other tissues. HA improves the skins flexibility, elasticity and moisture content, while assisting in the retention of collagen.

Hyaluronic acid is  found  in  bone broth, so simply by adding  it, or protein powder made from  it,  to your diet can automatically increase your consumption of HA. Regarding skincare products, since hyaluronic acid itself can’t penetrate cells for absorption, skincare products use sodium hyaluronate.   It is the salt of hyaluronic acid, and because it has a much lower molecular size, sodium hyaluronate can penetrate the skin when applied topically.

How HA improves ageing skin via hydration.  HA supplements, taken orally, have been shown in clinical trials of people (men and women) to improve the luster and suppleness of skin while supressing wrinkles, both by inhibiting new wrinkle formation and by reducing the appearance of already formed wrinkles (2). In one study, using people, after eight weeks of supplementation, subjects in the HA group, but not the placebo group, presented with significantly decreased maximum mean, or average, wrinkle depth (2).

The improvements to skin are maximized after eight weeks in the studies because it takes about 28 days for the skin to turn over a new layer. The   It also improved the moister contents while protecting the skin from sun damage (799).   HA, along with collagen and elastin fibers, is synthesized within the dermal skin’s fibroblasts. Fibroblasts are skin cell that generate connective tissue and allow the skin to recover from injury.   HA prompts the production of fibroblasts in the dermis, and so taking HA supplements promotes this synthesis in fibroblasts. These supplements can help to maintain skin health, while suppressing wrinkle formation.   This effect is partially due to HA promoting collagen synthesis in the skin (2).  HA has a high-water content, so it improves moisture retention in the epidermis (upper layer of skin). HA also helps to normalize skin cell functioning, keeping it healthy (2). And, if the tissues of the body are harmed, HA production increases.  In fact, HA regulates many aspects of tissue repair, including the activation of inflammatory cells to enhance an immune response.  HA also improves the response of fibroblasts and epithelial cells (which form the outer lay of the body and other areas of the body, including the gut) to injury (3).

HA hydrates skin. Many people report that their skin feels “dewier,” that their under-eye bags become lighter, and that the texture of their skin feels and looks smoother after applying serums containing hyaluronic acid. The main way that HA helps improve the appearance of sun related skin damage, called chrono-aged skin, is by reducing water loss.   HA’s ability to increase moisture content is one of the reasons that hormone replacement therapy (HRT) improves skin’s health and appearance.  HRT increases the skin’s natural amount of HA (3).

As we age molecules in our skin lose some of their ability to bind and retain water.  this leads to dryness, drooping lips and eyes, and sagginess as well as dandruff.  The loss of our ability to get molecules to bind to, or retain, moisture also reductions skin’s volume. The process of aging in skin is a response to extrinsic (outside of the body) and intrinsic (inside the body) factors. Extrinsically, environmental pollutants and UV light, as well as damage from blue light emitting devices, can impact skin.  Intrinsically, as we age, we slowly loose the ability to make HA, which naturally occurs in the body.  Research has show that there are numerous sites in the skin involved in the control of HA synthesis, deposition, cell and protein association, and degradation. For instance, it has been found that dryness of the stratum corneum is the result of prolonged exposure to the sun.  this results in the development of wrinkles. Wrinkles are much more likely to be visible in low humidity environments, where it is harder for the skin to maintain its elasticity and moisture retaining abilities. HA, which attracts moisture to the skin, can reduce these signs of aging. It decreases the loss of water from the epidermis (outer layer of skin), that related to dry and flaky skin and sun damage.

How HA Helps in fighting wrinkles, including improving their appearance.   Within two to six weeks of using a topical HA product, you should experience a noticeable improvement to the skin’s hydration. One clinical study of 40 women experiencing mild to moderate (clinical) signs of aging skin (changes to their skin’s surface and decreased volume) showed that within 30 days, HA can improve skin sagging, and decreased the appearance of wrinkles. Some subjects even reported increased volume to cheeks and lips (35). Here, for 30 days, the subject received either a product named Fillerina, that had six types of HA in it, or a placebo cream.  The results were measured at three hours, and then at seven days, fourteen days, and thirty days from application.  The subjects in the active group started seeing improvements within 14 to 30 days. The active group experienced reductions in sagging of the face and the contours of the cheeks, as well as improvements to lip volume.  At the same time, the active group also experienced decreased depth of wrinkles and decreased volume of wrinkles (35).  An eight-week study, using females approximately 45 year of age, assessed a topical low molecular nano-hyaluronic acid preparation. This was used to treat wrinkles, and improve skin elasticity and skin hydration. The subjects experienced statistically significant moisturizing effects, improved (finer) skin texture, as well as improvements to skin’s elasticity. The researchers stated that within eight weeks this product had decreased wrinkle depth by as much as 40 percent, while improving skin elasticity and firmness by up to 55 percent, and skin hydration by up to 96 percent (43).  You can also get prescription injectables made from HA (Allergan, Ultra Plus & Juvederm).  These can take months to show their maximum effects. If hyaluronic acid and is mixed with hydrolyzed collagen supplements and essential vitamins (B6, C, D3, E) and minerals (Zinc, Copper, D-biotin), it has been found to significantly improve skin hydration, wrinkle depth, and elasticity (23).   Collagen has amino acids (cysteine and proline) that form building blocks of the outer layer of skin, called the stratum corneum (39).  Type I collagen can improve the appearance of aging skin (40) and reduces age related changes to skin (44). After four weeks of supplementation, Collagen has been shown to greatly improve skin elasticity, skin thickness and after 8 weeks of supplementation, help improve skin moister (45).  Collagen even reduces moister evaporation from skin (46).   

How HA sooths and repairs damaged, sunburned, and wounded skin.  Hyaluronic acid can help repair damaged tissue. It keeps damaged tissue moist, so it can treat many ailments, including cold sores, ulcers, wounds, burns, bites, and mouth sores. It also helps repair sun damaged skin. HA is naturally part of tissue, which is made partially from water and collagen. So, HA helps build the tissue of the mouth and lips.  In fact, HA, along with collagen, help give structure and shape to lips.  As HA binds to water, it hydrates skin tissues, including oral tissues. HA also controls inflammation, keeps skin junctions tight, brings nutrients to damaged tissues, and helps fluids carry away waste. This is why many remedies for lip and mouth problems, like cold sores, contain HA.  It prevents bleeding or cracking, while speeds up the healing process.

Hyaluronic Acid helps to produce and repair cells (42). Collagen uses Hyaluronic Acid to bind elastin and collagen.  This then protects cartilage and improves elasticity in tissue.  You can buy it in supplement form.

Information on HA for skin.   Regarding skincare, there are a variety of HA acid creams, lotions and serums available to purchase.  These can have differing concentrations of, and types of, HA molecules.  It is beneficial to have a variety of molecule sizes in one product to maximize the various ways the different sized molecules work within the body, including the skin.  Studies have shown that applying serums etc., on a daily basis work well if they contain a   0.1 percent HA. These products are reports as leading to significant improvements to the skin regarding elasticity, hydration, and   the appearance of wrinkles (38). In the U.S. injectable HA based derma fillers are approved for use in those over 21 years of age keep in mind that these are temporary, as the materials will be absorbed by the body. Short term negative reactions include sensitivity to sunlight, and mild inflammation.  These should resolve themselves within two to seven days.  Very rarely, serious side effects like changes to eyesight and vascular changes to the eyes like damage due to blocked blood vessels (29).

Side effects of HA injection.  If an individual gets a permanent type of filler, they are more likely to experience side effects. In such cases, for at least 24 hours, do not wear makeup; for several days, avoid direct exposure to sunlight or excessive heat; use sunscreen with an SPF of 30 or more; for several days, avoid intense activities or sports.  If there is a problem, the medical professional may use hyaluronidases to reverse it.  This is an enzyme that breaks down HA.  

Side effects are more common when someone receives permanent fillers. It’s important that patients follow their doctor’s instructions after treatments, including avoiding wearing makeup for 24 hours after the injection, avoiding direct exposure to the sun or excessive heat for several days, using SPF 30 sunscreen daily and avoiding sports/vigorous activities during the week of the application. This helps limit the risk for inflammation and other adverse reactions. When there are complications from HA filler injections, hyaluronidase is sometimes used to reverse the effects of the fillers. Hyaluronidases are enzymes that are able to break down HA.

If you use a commercial or prescription HA product keep in mind that it is probably mad with bacteria from bird protein or cartilage. If you are allergic to poultry products, including eggs and feathers, be cautious.

Hyaluronic acid: food sources of hyaluronic acid (HA) include: bone broth and organ meats. Starchy root vegetables contain some HA, and they boost production of it as they have many helpful nutrients (fiber, potassium, vitamins B6 & C), this is especially true of yams, but also potatoes, sweet potatoes, tubers like jicama & Jerusalem artichoke.  Isoflavone rich soy-based foods enhance the production of HA. Also eat fruits high in naringenin, which inhibits the breakdown of HA, these include citrus fruits, tomatoes, and bananas. Bananas also contain a bit of HA, magnesium and vitamin C.  Vitamin C and magnesium both help galvanize the production of HA.  Foods high in both are: citrus fruits like grapefruits & oranges, tomatoes avocados, cherries, grapes, and mangoes, bananas. Sweet peppers are high in vitamin C. Magnesium rich foods help include nuts, seeds, leafy greens like spinach, kale and swiss chard, and avocados. Almonds and cashews are high in magnesium. Dark chocolate has small amounts of magnesium, it has zinc which helps HA production and it contains flavanols (bioactive compounds or plant derived nutrients which promote healthy blood vessel function).  Beans also contain both zinc and magnesium. Red wine has phytoestrogens which help in HA production (3).

Take between 120 and 240 mg per day for about four weeks.  This has shown significant increases to skin moisture and a reduction in dry skin in adults (4). 

As we age we loose the ability to make HA, and thuse our skin holds less moisture. This is why older skin is more likely to scare if injured (5). And, it is why skin care products often contain HA. Because HA molecules in their natural form are too large to easily penetrate skin, skincare often has low molecular weight HA serums in it.  This improves the skin’s moisture and can provide noticeable improvement to wrinkle depth within weeks. HA helps reduce skin damage done by oxidative stress that is rooted in external (pollution, sun damage & blue light damage from devices) and internal (hormonal changes, diet, lack of sleep etc.) causes.

HA can hold up to 1000 times its weight in water, but because it has molecules that are larger than other acids it is not easily absorbable by the skin.  Recently, skin care companies have started using a lower molecular weight HA that can penetrate skin. Studies of these products show that they do improve skin moisture and reduce wrinkle depth within several weeks of starting to use them.  HA can also help with damage done to skin by oxidative stress, caused externally by pollution and UV rays as well as by internal factors like hormonal changes, including loss of estrogen, which can lead to the degradation of collagen and so dryer, less elastic and more wrinkled skin.  

How HA assists with joint health.  Hyaluronic acid is a component of human bone, joints, and connective tissues like tendons and cartilage, particularly hyaline cartilage. The last is especially important as it provides cushioning to bones by covering their ends. So, in this way HA assists in bone health by protecting it from wear and tear, and thus it lessens the pain and tenderness connected to degenerative joint diseases. HA can also a component of the joint’s synovial membrane.  This part of the joint coats or covers the articulating bones.  This coating secretes a viscous fluid called synovial fluid.  This is what absorbs shock, and assists in keeping the joints elastic.  Synovial fluid also carries nutrients to cartilage.  HA is FDA approved in the U.S., in injection form, to treat osteoarthritis (provided by a healthcare professional).  it is also found in osteoarthritis pain/injury related supplements (6). 

Hyaloroinic acid (HA) may help to preserve bone strength.  Two animal studies have shown that HA suppliments can slow rates of bone loss in animals with osteopenia, a condition that often precedes osteoporosis (30 806;31 807).  And, in test tube studies, high doses of HA can increase the activity of osteoblast, the cells from which new bone tissue grows (32;33).  HA has been shown in clinical research to relieve joint pain an lubricate bones.  This substance is found in the joints and it helps lubricate the space where the bone meets the joint (34).

Some research indicates that low dose HA supplementation can effectively reduce joint (especially those of the knees and elbows) related stiffness and chronic pain (7). 

Hyaluronic acid supplements for joint pain are available in the U.S. There are several treatments based on HA that have been approved for osteoarthritis of the knee.  Four such products, made from rooster or chicken combs and sometimes bacteria, are Hyalgan, Orthovisc, Supartz and Synvisc (8). 

Taking 80 to 200 mg per day of hyaluronic acid (HA) supplements for two or more months has been shown in clinical research to significantly reduce knee pain in those aged 40 to 70 who were suffering from osteoarthritis (9 803).  HA injected into the joint seems to only lead to a modest reduction in pain, and it can lead to mild pain reduction, but this treatment often leads to complications (10).  Those over the age of 18 can take 50 milligrams of HA by mouth once or twice a day, with food. Those with osteoarthritis have found relief after eight weeks by taking supplements of 80 milligrams, with a percentage of HA at 60 to 70 percent.

Injections to control inflammation and pain are also available from a medical professional.  These can involve injection 20 milligrams into the joint once a week, for serval weeks. That said, mixing injections with oral supplements has been shown to lengthen the pain-relieving benefits, while stretching the time between injections (11). 

How HA assists in eye health and comfort.  Hyaluronic acid is the main component of a fluid within the eye socket, called the vitreous humor.  This is why HA based eye drops (brand name Hyalistil) are now used to treat chronic dry eye.  This product helps in tear production, the restoration of fluid balance, and the replenishing of moisture in the eye socket (12). HA is being shown in studies, to suppress UV light based oxidative damage to the cornea (13). Eyes are made in part of hyaluronic acid and type II collagen, in the forms of gelatinous tissue and fibrous tissue.  With age, production of both of these can slow. This can result in glaucoma and cataracts (14).  After the age of 50, the risk of developing cataracts increases (15).  Glaucoma (increased pressure in the eye due to an inability to drain normally accumulating fluids) is in part due to an age related loose of collagen, which helps support the eye and allows for proper fluid drainage.  Glaucoma leads to blindness. 

HA based lubricants are now commonly used to treat eye disorders (including cataracts) and injuries.  They are also used pre and post operatively to aid in the recovery form surgeries for cataracts, detached retinas, and corneal transplants.  To help lessen the likelihood of developing either glaucoma or cataracts take collagen or collagen rich foods, consume hyaluronic acid rich foods (poultry, beans, and red coloured fruits), and take omega 3 fatty acids (16).

To treat dry eye with HA, use eye drops three to four times per Day, for up to three months.  Try to find drops with a concentration of HA at 0.2 to 0.4 percent. Read directions carefully.

Hyaluronic acid (a) supplements may be an alternative treatment for dry eye. This is as it is great at retaining moisture. You can also get eye drops which contain from 0.2 to 0.4% HA.  These have been shown to improve eye health and reduce the symptoms of dry eye (47;48;49).

To help reduce the likelihood of developing either glaucoma or cataracts take collagen supplements, or collagen rich foods, and consume hyaluronic acid rich foods (poultry, beans, and red coloured fruits), and take omega 3 fatty acids (16).

How HA can help protect the gastro-intestinal tract.  Taking hyaluronic acid (HA) supplements may help reduce acid reflux symptoms.  In a study using HA on tissue samples in a test tube, HA mixed with chondroitin healed acid-damaged tissue quicker than no treatment (17). So, it is possible that HA can help to soothe and repair the damage done to the esophagus by stomach acid, which is regurgitated into the throat during acid refluxA human study of HA, mixed into a supplement form with chondroitin and administered with an acid reducing medication, decreased reflux symptoms by 60% more than only taking acid reducing meds alone (18 821). When this supplement mix was compared to a placebo, the supplement mix was found to be five times more effective (19).  Taking chicken-based collagen can help the body make HA.

HA is naturally present in the large particles of the gut that protect it from, and repair damage done by inflammatory bowel diseases (Chhorn’s, leaky gut syndrome, and ulcerative colitis). You can encourage your body to naturally heal from such issues by consuming HA rich foods or supplements.  These include bone broth, protein powder made from it.

Please, keep in mind that the overuse of isolated HA, which has smaller particles than naturally occurring ones, can sometimes result in increased inflammation in the gut (20). 

Information about HA and how it works in the body tissues.  Hyaluronic acid is a glycosaminoglycan, meaning it has the capability to maintain a high viscosity while holding a lot of water. It is considered to be a lengthy link of carbohydrate molecules which are bound together.  These molecules hold water, so they provide a way for fluids to move in the body and for fluid related pressure to be absorbed.  The most important fact about HA is its ability to retain water throughout the body (skin, eyes, joints).  In short, hyaluronic acid has a great capacity for retaining water, whether on the skin, in the eyes or within soft tissue. It is present in a variety of bodily tissues, but the majority of it, 50%, is in the skin.  It is here where HA provides structure and moisture. Aside from the skin, HA is prevalent in joints, tendons, skeletal tissues, synovial fluid, the eyes, heart (aorta and valves), lungs, and prostate.

Emerging research on HA has shown that it has many important roles in the body. These include the following: repairing injury of fibroblasts (these are the cells that synthesize collagen, produce the structural framework for tissue, and play a critical role in wound healing); HA helps to sustain epithelial cells (cells on the outer surfaces of organs and blood vessels, and the inner surfaces of cavities in many internal organs); it hydrates tissues; it fills the spaces in tissues and between cells; HA helps to build a framework via which cells can migrate; HA  assists in controlling  inflammation via regulating the activation of inflammatory cells; it assists in the immune response; it  partakes in the repair of tissues and wounds; it even lubricates joints (21).

How Hyaluronic Acid Works in the tissues.  There are a variety of HA molecule sizes.  This is a main reason that HA can have so many different functions within the body.  The larger molecules are antiangiogenic and immunosuppressive. Antiangiogenic means the process through which new blood vessels form from pre-existing vessels. This is the process that continues the growth of the vasculature by processes of spurting and splitting.  Immunosuppressive means the larger HA molecules can slow or stop an immune response. These larger molecules can be found in healthy tissues.  These control dehydration, inflammation, and free radical damage.  Smaller HA polymers can send signals of distress to the immune system, and so can raise or increase inflammation to help in the repair or wounds or assist in healing injury.

Hyaluronic acid is in a class of (essential) membrane proteins called hyaluronan synthases.  These proteins form the basis of hyaluronan synthesis within the body tissues. this process is vital to maintaining health. These are the basis of hyaluronan synthesis in the body, which is vital to health. People have three kinds of hyaluronic acid synthases for creating HA (HAS1, HAS2 and HAS3). HA plays a significant role in the central nervous system, CNS, in that it plays a role in cell migration and cell signaling. Hyaluronan does this by binding to two hyaluronan receptors, DC44 and RHAMM (22).

Hyaluronic acid supplements for joint pain are available in the U.S. There are several treatments based on HA that have been appr9oved for osteoarthritis of the knee.  Four such products, made from rooster or chicken combs and sometimes bacteria, are Hyalgan, Orthovisc, Supartz and Synvisc (23).   

Please, keep in mind that the overuse of isolated HA, which has smaller particles than naturally occurring ones, can sometimes result in increased inflammation in the gut (24). 

Adding hyaluronic acid-rich foods and supplements to an existing diet can encourage the body to heal itself by supporting the gastrointestinal systems in protecting and repairing itself.  These supplements include   bone broth or protein powder made from bone broth (25;27).

Hyaluronic acid, HA, is naturally found in the body, and is in every connective tissue and organ (skin, blood vessels, serum, cartilage, brain, heart valves, and synovial fluid).  HA production diminishes with age. A person 75 years old has only 25% of the HA naturally present in the body that a 19-year-old would have (2).

Hyaluronic acid: food sources of hyaluronic acid (HA) include the following: grass fed meats , especially beef, poultry and pork; bone broth and organ meats; starchy root vegetables contain some HA, and they boost production of it as they have many helpful nutrients (fiber, potassium, vitamins B6 & C), this is especially true of yams, but also potatoes, sweet potatoes, tubers like jicama & Jerusalem artichoke;  isoflavone rich soy-based foods enhance the production of HA. Also eat fruits high in naringenin, which inhibits the breakdown of HA, these include citrus fruits, tomatoes, and bananas. Bananas also contain a bit of HA, magnesium and vitamin C.  Vitamin C and magnesium both help galvanize the production of HA; foods high in both are: citrus fruits like grapefruits & oranges, tomatoes avocados, cherries, grapes, and mangoes, bananas; sweet peppers are high in vitamin C; magnesium rich foods help include nuts (almonds and cashews are high in magnesium), seeds, leafy greens like spinach, kale and swiss chard, and avocados, dark chocolate has small amounts of magnesium, but it also has zinc, which helps HA production and it contains flavanols (bioactive compounds or plant derived nutrients which promote healthy blood vessel function);  beans also contain both zinc and magnesium;  and, red wine has phytoestrogens which help in HA production (26).

Cautions about HA.  If you take medications that thin the blood, like aspirin or warfarin (Coumadin), don’t take HA supplements, these can increase the risk of bleeding.  If you have a history of cancer be cautious about taking HA. Keep in mind that HA is associated with increased blood vessel formation and fibroblast migration in tumor formation. And, the correlation of the aggressiveness of a tumor with the level of HA on the tumor cell’s surface has also been reported (3). 

The U.S. federal drug administration (FDA) states that HA related products are usually safe when used topically or taken orally.  Those who are pregnant, or breast feeding, should avoid using it as may negatively affect the development of a baby or fetus. 

References:

1    Website: Mercola take control of your health.  webpage: hyaluronic acid: a bodily fluid crucial for joint and skin health.  Accessed at: https://mercola.com/vitamins-suppliments/hyaluronic-acid/aspx

 2    Oe, M., Sakai, S., Yoshida, H., Kaneda, H., Okado, N., & Masuda, Y., (2017).  Oral hyaluronan relieves wrinkles: a double-blind, placebo-controlled study over a 12-week period.  Clinical Cosmet Investig Dermatol, 10: 267-273.

 3   Papakonstantinou, E., Roth, M, & Karakiulakis, G, (2012).  Hyaluronic acid: a key molecule in skin aging.  Dermato-endocrinology, 4(3):253-258.  DOI: 10.4161/derm.21923

 4    Kawada C Yoshida, T., Yoshida, H., Matsuoka, R., Sakamoto, W., Odanaka, W., Sato, T., Yamasaki, T.,  Kanemitsu, Masuda, Y., & Urushibata, O., (2014).  Ingested hyaluronan moisturizes dry skin.  Nutrition              Journal 13(70).    DOI: 10.1186/1475-2891-13-70.

 5      Larson, B. J., Longaker, M. T., & Lorenz, H. P., (2010).  Scarless fetal wound healing: a basic science review.   Plastic and reconstructive surgery, 126(4), 1172-80.) 

 6     Web MD website. Webpage: Hyaluronic acid.  Accessed at:                https://www.webmd.com/vitamins/ai/ingredientmono-1062/hyaluronic-acid). 7    Wang, C.T., Lin, J., Chang, C.J., Lin, Y.T., & Hou, S.M., (2004). Therapeutic effects of hyaluronic acid on           osteoarthritis of the knee. A meta-analysis of randomized controlled trials. J Bone Joint Surg Am., 86-A             (3):538-45).

 8      Gower, T., Hyaluronic Acid Injections for Osteoarthritis.  The weight of evidence suggests that a shot in the knee may bring some OA patients relief.   Arthritis Foundation website.  Accessed at:                https://www.arthritis.org/living-with-arthritis/treatments/medication/drug-types/other/hyaluronic-acid-injections.php

 9      Tashiro, T., Seino, S., Sato, T., Matsuoka, R., Masuda, Y., & Fukui, N., (2012).  Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period.  Scientific World Journal.  2012;2012;167928.  DOI:  10.1100/2012/167928.

 10     Rutjes, A.W., Juni, P., da Costa, B.R., Trelle, S., Nuesh, E., & Reichenbach, S., (2012).   Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis.  Ann Intern Med. 157(3):180-191.  DOI: 10.7326/0003-4819-157-3-201208070-00473.

11    Bowman, S., Awad, M.E., Hamrick, M.W., Hunter, M., & Fulzele, S., (2018). Recent advances in hyaluronic  acid-based therapy for osteoarthritis.  Clinical & Traditional Medicine 7(6). Published online 2018, 02, 16. DOI: 10.1186/s40169-017-0180-8

12    Troiano, P., & Monaco, G., (2008).  Effect of hypotonic 0.4% hyaluronic acid drops in dry eye patients: a   cross-over study. Cornea., 27(10):1126-30. DOI: 10.1097/ICO.0b013e318180e55c. 

13    Čejka, Č., Luyckx, J., Ardan, T., Pláteník, J., Širc, J., Michálek, J., & Čejková J., (2010). The effect of   actinoquinol with hyaluronic acid in eye drops on the optical properties and oxidative damage of the rabbit cornea irradiated with UVB rays. Photochem Photobiol., ;86(6):1294-306. DOI: 10.1111/j.1751-       1097.2010.00796.x. Epub 2010 Sep 22. 

14   Mishra, G., Das, G.B., & Behera, H.N., (1997).  Possible role of lens collagen in cateractogenesis.  Indian    Journal of Ophthalmology, 45 (4):227-231.

15   Rosenberg, M. (2011).  Save your eyes with collagen, the amazing nutrient.  Website: Food Trients, recipe for aging beautifully.  Accessed on: July 20th, 2017.  Accessed at: www.foodtrients.com/inside/save-your-eyes- with-collagen-the-amazing-multi-tasking- nutrient/

16  New York Times website.  Webpage: The New York Times Health Guide, Anemia.  Retrieved from:                www.nytimes.com/health/guides/disease/anemia/symptoms.html

17     Di Simone, M. P., Baldi, F., Vasina, V., Scorrano, F., Bacci, M. L., Ferrieri, A., & Poggioli, G. (2012). Barrier   effect of Esoxx(®) on esophageal mucosal damage: experimental study on ex-vivo swine model. Clinical and                         experimental gastroenterology, 5, 103-7.

18      Savarino, V., Pace, F., Scarpignato, C., & Esoxx Study Group (2017). Randomised clinical trial: mucosal protection combined with acid suppression in the treatment of non-erosive reflux disease – efficacy of Esoxx,     a hyaluronic acid-chondroitin sulphate-based bio adhesive formulation. Alimentary pharmacology &     therapeutics, 45(5), 631-642.

19 Palmieri, B., Merighi, A., Corbascio, D., Rottigni, V., Fistetto, G.,&  Esposito, A., (2013). Fixed combination of     hyaluronic acid and chondroitin-sulphate oral formulation in a randomized double blind, placebo-controlled    study for the treatment of symptoms in patients with non-erosive gastroesophageal reflux.Eur Rev Med Pharmacol Sci.,17(24):3272-8.

20   Gerdin,B, & Hällgren, R., (1997).  Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation. J Intern Med.,242 (1):49-55.

21   Moskowitz, R.W., (2000).  Hyaluronic acid supplementation.  Curr Rheumatol Rep. 2(6):466-71.0.

22   Sherman, S.L., Matsumoto, S., Weiping, S, Taasin, S., & Back, S.A., (2015). Hyaluronan synthesis,                catabolism, and signaling in neurodegenerative diseases, a review article.  international Journal of Cell     Biology Vol. 2015, Article ID 368584, 10 pages DOI:  http://dx.doi.org/10.1155/2015/368584.

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