Hyaluronic Acid

EFFECTIVE SCORE:  7          SAFETY SCORE: 3 (OUT OF 10)

Another trick or treat ingredient. Hyaluronic acid is involved in moisture retention, such as for limiting skin wrinkles and for joint lubication. The treat is to get Hyaluronic acid (HA) to help maintain cartilage and prevent joint pain without any side effects. The trick is that while both large and small HA molecules may prevent tissue damage especially in joints, the small HA molecules also feeds tumor growth simply due to their natural method of action. Thus, both the large and the very tiny size molecules have positive actions, while the small to medium size molecules should be avoided. ref Supplements of Hyaluronic acid come in many different size molecular weights. Click on the following reference for good info, BUT note they also sell HA ref

Here is the bottom line: High molecular weight hyaluronic acid (HMW-HA) is a regulator, found in vessel walls and joints to maintain integrity and control against inflammation.  ref ref <injections When there is tissue injury, especially around joints, body wisdom breaks off a part of this HMW-HA forming a small size fragment of hyaluronic acid called LMW-HA, low molecular weight, and sends it to the injury site to begin the healing process. LMW-HA adds moisture, creating swelling or inflammation, and also increases blood flow by building new blood vessels to bring needed nutrients. ref  These actions limit joint movement to speed up healing, especially for skin wounds. Eventually, as healing progresses, HMW-HA increases while LMW-HA decreases until the site is back to normal. A problem arises at cancer tumor sites where these small LMW-HA are found in abundance. It could be that the body looks at the tumor as an injury and sends out lots of LMW-HA to attempt to heal the tissue. But instead, the function of LMW-HA to increase blood flow by building new blood vessels unfortunately aids the growth of tumors. It has now been discovered that some cancer cells increase the production of an enzyme that works on the large size HA to break it down into smaller size molecules. ref Plus, people naturally produce different amounts of this enzyme, HYAL1-S, and its counter enzyme that blocks this tumor promotion action, called HYAL1-AS. Both HYAL1-S and HYAL1-AS influence the way HA functions. Doctors measure these enzyme levels to help determine who is at greater risk for relapse after cancer treatment. It was discovered that some cancer cells probably have the ability to increase HYAL1-S production. Prostate cancers are influenced more than breast cancers. ref  Both low HYAL1-S and extremely high might not be desirable. ref  ref

CAUTION:  The different molecular weights of HA can be influenced by various related enzymes that degrade HA and generate secondary forms. DIFFERENT CANCER CELLS MAY OR MAY NOT HAVE THE SAME NUMBER OF RECEPTORS FOR HA which could completely REVERSE the roles of the different molecular weight HA elements. This unique aspect allows scientists to use the size of HA that attracts to each cancer type as a chemo-drug targeting vehicle.** This takes advantage of different cancer enzyme profiles. BUT, AS A SUPPLEMENT, Hyaluronic Acid MAY NOT BE WISE SINCE AT MANY DIFFERENT SIZES, IT HAS OPPOSING EFFECTS. ref 

ABSORPTION OF HA

The vitamin industry discovered that the first supplements of HMW-HA exhibited a very low absorption rate. So they found a way to increase absorption by creating supplements of smaller molecules, LMW-HA. This was possibly before the complete picture of how LMW-HA functions in the body was known. There are still questions on absorption of HA, especially the HMW size. It most likely breaks down with limited absorption. Many studies and medical applications use injectible HA. And YES, the smaller size may indeed feed tumors, ref and inflammation. ref  This reference also mentions how antioxidants prevent fragmentation. Smaller size HA is related to increased scar tissue formation. More research is needed to verify the exact processes that occur in humans and if LMW-HA taken orally gets into the bloodstream intact or is broken apart during digestion, plus how enzyme levels modify actions.

SCIENTIFIC PROOF FOR LMW-HA AT TUMOR SITES

Cancer cells placed in a test tube with LMW-HA show greater growth rates. When an enzyme to breakdown the LMW-HA is added (PEP-1 in next reference), the cancer cell growth rate declines.  ref

SIDEBAR: What science does know is that since LMW-HA goes to tumor sites, in the nanoparticle size, it has proven to be a good combining agent with cancer drugs to get the drugs to just target tumors and leave healthy tissues alone. HA has the ability to increase the building of certain anticancer drug induced structures and helps keep these elements in solution. ref ref   But, next, the slightly larger HA molecules soon formed a non-penetrating shield that blocked chemo-drugs from getting to and killing cancer cells.  

NOTE: Some Nutritionists take the view from early research that HA does not cause cancer (correct but may contribute) and might actually help protect against it. And that HA is found at cancer sites because it it attempting to heal (correct again). But the way it tries to heal, creating inflammation and building new blood vessels, is exactly why it is problematic. HA's other functions also participate in cancer cell migration, proliferation, and adhesion, all devious cancer cell ploys to grow faster and spread. The direction HA contributes to cancer development, growth, and spreading may depend upon the relationship between the 3 enzymes (HAS-1, -2, -3) that influence HA production and activity. ref

Cancer cells might also send out enzymes to further breakdown more HMW-HA to continue using the bodies own protective mechanisms against itself. And this is exactly the POINT, large molecular weight HA is (usually) protective while the smaller low molecular weight fragments (potentially) create inflammation and other nasty actions at cancer sites. This is also seen with folic acid, and a few other nutrients.  

Again, a balance point must be found where HA protects and heals without promoting undo inflammatory stress and tumor growth. There are two different applications here to consider. First is tissue repair at injury sites. The next is chronic inflammation from damaged joints. At just the right levels and molecular size, HA controls both the creation of healing inflammation at injury sites and also limits this action so it does not get out of control. Plus, measuring the different production levels of the related HA enzymes gives Scientists an idea of the progression rate for in cancer types.

ON LIVER AND HA: Serum Hyaluronate is measured to indicate level of inflammation in liver fibrosis condition instead of using the more invasive liver biopsy. Liver fibrosis is associated with liver diseases. For people with impaired livers, consuming hyaluronic acid may be problematic.

ARTERIES AND HA: Inflammation is also a major player in artery health. ref HA and size of molecules is a concern for atherosclerosis plaque stability as well as for cancers. The size of HA and related enzymes that impact production and size of HA structures is simply not to messed with until Science determines exact actions in health and disease.

HOW TO SUPPLEMENT 

Since it is still in question as to how large the molecular weight of HA needs to be to not stimulate tumor promotion, or what determines the type of HA enzyme that is action dominate, the prudent supplement approach for Hyaluronic acid is NOT TO USE at this time. Look for ways to get the body to build its own HMW-HA.

The following research section is copied here to explain why HA should not be used without proper knowledge and correct forms:

"Extra-cellular matrix (ECM) is closely correlated with tumor progression. Hyaluronic acid (HA) is a component of the ECM, it is an unsulfated anionic linear glycosaminoglycan polymer comprised of a repeating glucuronic acid and N-acetylglucosamine disaccharide motif [1]. HA keeps tissues hydrated, maintains osmotic balance and cartilage integrity [2]–[3]. HA also actively regulates cell adhesion, migration, and proliferation by interacting with specific cell surface receptors such as CD44 and RHAMM [4]. The concentration of HA is elevated in several inflammatory diseases and various carcinomas, including bladder, prostate, breast, lung, colon, and so forth [5]–[10]. Small fragments of HA, generated by Hyaluronidase (HAase), stimulate angiogenesis [11], [12]. In tumor tissues, it may promote tumor growth and metastasis probably by actively supporting tumor cell migration and offering protection against immune surveillance [13]."  ref

Can you see why this nutrient needs caution for its use? Many Protective functions, but look what happens when there is runaway inflammation at cancer sites, at artery wall lesions, or in liver disease. ref  It is just the way this nutrient functions that gets it into trouble. There may still be mitigating elements waiting to be discovered that control HA actions as to direction, such as the enzyme mix and any other gene variations. More research is vitally needed.

IF YOU WANT THE BENEFITS OF HA, there are some Brands with higher molecular weight HA. Size would have to be over 300,000 daltrons, preferable over 500,000 or more. Researchers usually have to inject HMW-HA to bypass limited digestive absorption. While larger size limits absorption, the consequences of small fragments may not be worth the price. And there is always the unwelcome possibility that HA breaks down during digestion. Plus, add the effect of different enzyme conditions and the only safe usage of HA is the precautionary one of not to use unless under Medical supervision. Maybe short periods of consumption might be OK but not chronic usage. Remember, many disease conditions are present many years before they are manifested to an observable result.

What helps the natural body production of HMW-HA? It is known that Vitamin C increases collagen production. But what about glycosaminoglycans, the building blocks of HA. Collagen and HA levels naturally reduce with age. This reference shows that Vitamin C did increase glycosaminoglycan amounts. And there might be ways to slow the breakdown of HA, but balance is vital as 1/3 of the 15 grams in the average body are broken down and built back up every day. Information on protecting cartilage here.

Another study showing positive Vitamin C effects on collagen production. Comparing fast cell rates from young babies to the slow producing cells in Elders, Vitamin C made the old cells produce faster with increased densities of collagen. This is of vital importance.

IS HYALURONIC SAFE TO TAKE?

While WEBMD says probably safe, there are far to many situations where it might be contra-indicated and have an acceleration effect on some disease conditions. Best to support body wisdom for production and distribution of HA and let nature determine size and amounts to produce. Remember, HA appears to increase inflammation when the body needs it for healing at an injury site, but this condition becomes adverse if it continues chronic and long term, situations that LMW-HA supplementation might enhance.

**Since Hyaluronic acid in nanoparticle size has the ability to target and penetrate certain types of cancer cells, it is being used by Scientists as a vehicle to combine with and deliver chemotherapeutic drugs into those cancer cells. This is beyond any nutritional or health aspect relating to HA action. The nanoparticle size is only 6-10 disaccharides. Large HA molecules might contain 500,000. Most small LMW-HA supplements contain 50,000 to 250,000.