The following information was sent to me by Bill Sardi, a writer who specializes in Hyaluronic Acid. His opinion contradicts those expressed in my newsletter. At some point I will find time to figure out if I need to retract my earlier opinion expressed in our newsletter:
From Bill Sardi:
The information provided at your website concerning oral hyaluronic acid and breast cancer is grossly misleading. It is written by novice medical people who have little understanding of this topic, nor of proper discrimination between causes and associations with disease. There is not a shred of evidence that oral hyaluronic acid increases the risk of, or promotes the spread of, cancer. To the contrary, supplemental hyaluronic acid has been used experimentally to treat cancer. To blame HA for the spread of cancer is like blaming the road for auto accidents. It needs to removed from your website. --Bill Sardi, Knowledge of Health, Inc. September 28, 2005
Does hyaluronic acid promote or accelerate the spread of cancer?
Bill Sardi, Knowledge of Health, Inc.
For inexplicable reasons the first website listed by internet search engines for hyaluronic acid (HA) is a poorly founded opinion by a health writer that hyaluronic acid promotes cancer. This report has misled many people into mistakenly thinking oral hyaluronic acid, taken as a dietary supplement, may in some way promote cancer. Numerous times the author of that misleading report has been sent contrary studies, but has refused to remove the misleading information. So you will have to examine the topic for yourself.
Hyaluronic acid is produced continually throughout life, more so when very young and during pregnancy, when cancer rates are almost nonexistent. Yet the opinion prevails that somehow, taking oral HA might cause cancer.
For the naïve viewer of the medical literature, there are many reports indicating elevated levels of HA are associated with the spread of tumors, what is called invasion. Tumor cells can mobilize and spread (become metastatic) by using HA as a kind of biological “slide and slide.” However, taking oral HA supplements has little to do with this biological phenomenon. More HA shows up at tumor site because it is a healing agent. Anywhere there is a wound in your body, cells called fibroblasts make more HA.
A recent study, conducted by researchers in Finland , investigated the role of hyaluronic acid in squamous cell carcinoma (oral cancer). “At the end of the follow-up (median 52 months) 43% of patients had died because of this type of cancer. A significant difference in overall survival and disease free survival was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival . These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.”
Notice the words “prognostic marker.” Since more HA is produced in tissues that are damaged by trauma, burns, toxic chemicals, or tumors, broken down (degraded) HA can be used to detect or measure the progression of tumors. This is akin to fire fighters who show up at fires. They are “associated with,” but not considered a cause, of the fires. The fire fighters are there to put the fire out, just like HA is attempting to heal the damaged tissue.
The difference between cause and association is easily understood by the following example. Let's say investigators want to know the causes of childhood pedestrian accidents. They collect data from all cases where children were hit by automobiles and they find that nearly all of the children were wearing tennis shoes. So, can we conclude that tennis shoes caused the accidents? Obviously not. The tennis shoes are only by-standers. So is HA.
Here is a study to examine. Finnish researchers noted that “hyaluronic acid is involved in the growth and progression of malignant tumors.” The researchers stated that “a high proportion of HA-positive cells of all cancer cells was significantly associated with deep tumor invasions, spreading to lymph nodes, and is associated with tumor progression and poor survival rate.” Sounds pretty terrible, to the uninformed reader, doesn't it? Notice the report says HA is “involved” and “associated,” but never indicates it was a cause of tumors or increased their severity. [Br J Cancer 79:1133-8, 1999] Hard paved roads are responsible for the severity of trauma when people are thrown out of cars in auto accidents, but we can't say the road caused the accident, can we?
Recently a study examined the role of various components of the connective tissue (the goo in between living cells, like mortar in between bricks). Tumor tissue from 86 patients with breast cancer that had not spread to lymph nodes yet was examined by staining the tissues so each type of connective tissue component could be identified (versican, chondroitin sulfate, tenascin, and hyaluronan. Researchers at the Hanson Institute in Adelaide , Australia , said: “analyses indicated that elevated expression of versican predicted increased risk and rate of relapse in this cohort. Elevated expression of tenascin was predictive of increased risk and rate of death only…… neither chondroitin or hyaluronic acid were predictive of disease outcome in this group.” [Clinical Cancer Research 10: 2491-98, 2004]
Shown above are slides, at different magnification, revealing stained areas where HA concentration is high within tumor cells. In this study researchers have noted that “cancer patients with a scattered and weak HA staining had a significantly higher probability of recurrent disease and unfavorable outcome.” [Oral Oncology 40:257-63, 2004]
If hyaluronic acid is a suspected cancer-causing agent, then why is it being used along with other molecules to treat cancer? Researchers in Italy indicate HA combined with other compounds are “promising” and responsible for the “arrest” of tumor cell growth. [Investigative New Drugs 22: 207-17, 2004]
Hyaluronic acid is actually being used experimentally to treat cancer, with great effectiveness. One alternative medical practitioner notes HA, when added to other intravenous compounds, increases the effectiveness of cancer treatment. See report at: http://www.smartlifeforum.org/newsletters/Morris_2004_11_18.htm
Here is another report, re-published intact (below), which indicates HA is a promising anti-cancer agent. While no company that makes oral HA supplements can make any claims that their products cure, prevent or even diagnose cancer, the citations listed herein should dispel poorly founded concerns that oral HA promotes cancer in any way.
This is taken from the Winnipeg Free Press, Saturday, July 15th, 1995 :
Manitobans stop disease in mice;
discovery grabs world's atttention
By Bill Redskop (Staff Reporter)
Manitoba scientists have found that they can stop the spread of cancer in mice by turning off a cancer cell's sensing ability.
Testing on animals will continue for about two years before human treatment is tried.
The treatment, hailed as a huge breakthrough in the fight against cancer, involves knocking out a cell's RHAMMs (receptors for hyaluronic acid mediated motility.)
The receptors sit on the surface of a cell and act as its eyes and ears.
But when the Manitoba scientists used genetic engineering to knock out those senses, the cancer cells would simply lie inert and not reproduce.
Even more astonishing, the receptorless cancer cells soon turned to their normal, non-cancerous state.
"If you blind it, the cancer cell just dies," said Dr. Arnold Greenberg, one of three molecular biologists making up the research team. "It surprised us, and everyone else who saw it."
"Resarchers never thought of this before. It's quite novel," said team leader Dr. Eva Turley , who discovered and named the RHAMM receptor three years ago.
Turley, 45, has been traveling the globe in recent months sharing her findings with other scientists, with stops in Atlanta , Colorado , Hawaii , Australia , Sweden , Switzerland , and London , England . She travels to Japan later this year.
"When I gave a talk in Colorado , I was the last speaker to talk, and everyone was restless and talking about going out skiing. After I finished, there was stunned silence,"said Turley, a microbiologist with the University of Manitoba .
Turley cautioned that they only studied the gene called ras, responsible for 20 to 30 per cent of cancers. And experiments have only been conducted on mice so far.
But in theory, the treatment - using high concentrations of hyaluronic acid, which cells generally use in small amounts - should work in humans, she said.
It's hoped the findings will lead to biotechnological treatment of cancer that would be more effective than radiation chemotherapy, and without the negative side effects she said.
Dr. Jim Wright is the third member of the team.
The scientists, who work out of the Manitoba Institute of Cell Biology, are funded by the Terry Fox Program of the National Cancer Institute of Canada.
Turley said all the travel and attention in recent months has been overwhelming.
The discovery was written up in yesterday's edition of Cell Magazine, the most prestigious biomedical sciences journal in the world.
In a message dated 9/28/2005 4:13:48
PM Pacific Standard Time, DRJACOBSCHOR1@MSN.COM, Bill Sardi writes:
Yes, you are not the first to be misled by the literature............
"A hyaluronan-rich environment often correlate with tumor progression. and
may be one mechanism for the invasive behavior of malignancies. Eradication
of hyaluronan by hyaluronidase administration could reduce tumor
aggressiveness and would provide, therefore, a new anti-cancer strategy. "
Yes, if you assume researchers are correct........ to do this you would have to shut down HA synthesis all over the body......... it is impractical and would then make it possible for cancer cells to migrate........... the connective tissue and HA create a barrier to block tumor cell movement. Few know how to interpret what they are reading. Researchers are always justifying their research to gain more grants. If this were true, you would see massive tumors during pregnancy when HA levels are very high. Also in childhood. Cancer risk is lowest during youth when HA levels are very, very high. Oral HA has little to do with what is going on at the tumor site.
Your logic is also flawed. That you could not find any abstracts that support oral HA would inhibit tumor growth is not evidence of the opposite. Furthermore, you admit to a cursory view. The literature is very misleading. It is easy to understand your being swayed by the literature.
There is over 8 years of experience with oral HA, without any known reports of tumor growth or increased risk or metastasis. Glucosamine is one half of the HA molecule and attempts to create HA. Do you prescribe oral glucosamine, or chondroitin? They work by boosting the synthesis of HA. Estrogen attempts to stimulate HA. Estrogen-blockers like tamoxifen or aromatase inhibitors, attempt to block estrogen production, which sends a signal to produce HA in fibroblasts. Women are then left with hair loss, depressed mood, collapse of collagen (a barrier against the spread of cancer), bone loss, joint problems, etc. Eventually, after 5 years of taking tamoxifen, the collagen and HA is sufficiently broken down, and the drug turns on women and increases their risk of recurrent tumors. This is not a practical or harmless anti-cancer strategy.
See below where HA was used to lower drug resistance and improve cancer therapy with the toxic anti-cancer drugs.
Treatment with hyaluronan oligomers sensitizes drug-resistant carcinoma cells to chemotherapeutic drugs. A, MCF-7/Adr drug-resistant human mammary carcinoma cells were grown in the presence of various concentrations of doxorubicin (Doxo) with or without 100 µg/ml hyaluronan oligomers (o-HA), then cell numbers were measured. B, MCF-7 human mammary carcinoma cells, which are much more sensitive to drug treatment than the MCF-7/Adr cells (13), were treated as described in the legend to A. C, MDA-MB231 human mammary carcinoma cells were treated with various concentrations of methotrexate in the presence or absence of 100 µg/ml hyaluronan oligomers. The results in A–C are expressed as the means (±S.D.) of cell numbers from three independent experiments performed in triplicate.. J. Biol. Chem., Vol. 278, Issue 28, 25285-25288, July 11, 2003
It could be said that the culprit in metastasis is hyaluronidase, the enzyme that breaks down HA. Hyaluronidase is synthesized at tumor sites, breaking down the HA which then facilitates the spread of the tumor cells. You were able to dig up the statement...
"Eradication of hyaluronan by hyaluronidase administration could reduce tumor
aggressiveness and would provide, therefore, a new anti-cancer strategy."
By doing this, the barrier effect of HA and collagen is removed. It is a statement by experimental scientists who have no idea of its impracticality.
To give you a better understanding of the duplicitous nature of the medical literature regarding HA and cancer, read the following report. Here, depending upon the concentration of hyaluronidase, it can inhibit tumor growth (if HA is not broken down by hyaluronidase) or at high concentrations of hyaluronidase, it can also prevent tumor growth.
Cancer Res. 2005 Sep 1;65(17):7782-9.
HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor.
Lokeshwar VB, Cerwinka WH, Isoyama T, Lokeshwar BL.
Department of Urology, Miller School of Medicine, University of Miami, Miami, Florida 33101, USA. firstname.lastname@example.org
Hyaluronidases degrade hyaluronic acid, which promotes metastasis. HYAL1 type hyaluronidase is an independent prognostic indicator of prostate cancer progression and a biomarker for bladder cancer. However, it is controversial whether hyaluronidase (e.g., HYAL1) functions as a tumor promoter or as a suppressor. We stably transfected prostate cancer cells, DU145 and PC-3 ML, with HYAL1-sense (HYAL1-S), HYAL1-antisense (HYAL1-AS), or vector DNA. HYAL1-AS transfectants were not generated for PC-3 ML because it expresses little HYAL1. HYAL1-S transfectants produced < or = 42 milliunits (moderate overproducers) or > or = 80 milliunits hyaluronidase activity (high producers). HYAL1-AS transfectants produced <10% hyaluronidase activity when compared with vector transfectants (18-24 milliunits). Both blocking HYAL1 expression and high HYAL1 production resulted in a 4- to 5-fold decrease in prostate cancer cell proliferation. HYAL1-AS transfectants had a G2-M block due to decreased cyclin B1, cdc25c, and cdc2/p34 expression and cdc2/p34 kinase activity. High HYAL1 producers had a 3-fold increase in apoptotic activity and mitochondrial depolarization when compared with vector transfectants and expressed activated proapoptotic protein WOX1. Blocking HYAL1 expression inhibited tumor growth by 4- to 7-fold, whereas high HYAL1 producing transfectants either did not form tumors (DU145) or grew 3.5-fold slower (PC-3 ML). Whereas vector and moderate HYAL1 producers generated muscle and blood vessel infiltrating tumors, HYAL1-AS tumors were benign and contained smaller capillaries. Specimens of high HYAL1 producers were 99% free of tumor cells. This study shows that, depending on the concentration, HYAL1 functions as a tumor promoter and as a suppressor and provides a basis for anti-hyaluronidase and high-hyaluronidase treatments for cancer.
Much depends upon where HA is in play. The normal state of the body is to have youthful levels of HA, and that is the goal, to retain a youthful state and prevent the spread of cancer. Without angiogenesis, and intact connective tissue and HA, tumor cells will just die off. Once tumor cells are present, they utilize HA as a "slip and slide" to escape into the blood circulation. However, if administering oral HA of low molecular weight, the HA will intercept circulationg cancer cells, they stick together, and the tumor cells are taken out of action. That was demonstrated by Turley. (see earlier references).
1. HA with collagen in connective tissue serves to create a barrier against the spread of cancer. Breakdown of HA by hyaluronidase facilitates tumor spread.
2. Once collagen and HA is broken donw, existing tumor cells use the slippery HA to escape into the blood circulation. More HA is made at tumor sites as a natural healing agent and the idea of inhibiting HA is not realistic and creates side effects. Anti-angiogenic agents would possibly serve as a better alternative, but have undesirable side effects as well.
3. Once tumor cells are roaming in the blood circulation they are vulnerable to the immune system (NK cells, phagocytes). Introduction of oral HA in low molecular weight would intercept tumor cells and take them out of action.