AUA 2007 - Parsons Produces Another Powerful Study - Sialic Acid

[icnmgrjill]

C. Lowell Parsons, MD, one of the most prolific IC researchers, has presented a fascinating study which offers an explanation as to why the IC bladder is struggling to heal. He determined that the TAMM-HORSFALL protein, which helps to repel irritating cations from the bladder wall, has less Sialic Acid than normal patients. Sialic acid provides the electrical potential that provides repelling power. The less Sialic Acid, the less protection offered. This is a fascinating study which may lead to new diagnostic methods and potential treatments. I'll offer more on this later - Jiill.

SIALIC ACID CONTENT OF URINARY TAMM-HORSFALL PROTEIN IS REDUCED IN INTERSTITIAL CYSTITIS PATIENTS

C Lowell Parsons, MD, Mahadevan Rajasekaran, PhD, Marianne Chenoweth, RN, BSN, Paul Stein, PhD. University of California, San Diego, San Diego, CA; Veterans Medical Research Foundation, San Diego, CA

Introduction and Objective: Normal urine contains cationic factors that can injure bladder epithelium and are neutralized by Tamm-Horsfall protein (THP). To test the hypothesis that THP from interstitial cystitis (IC) patients has an electrochemical abnormality that reduces its capacity to neutralize cationic urinary toxic factors, we compared sialic acid content and zeta potential from urinary THP of IC patients and control subjects.

Methods: THP was isolated by selective ultrafiltration of 30 ml of urine from 29 normal and 28 IC patients. THP was quantified by ELISA, 150 ?L aliquots hydrolyzed in 2.5M acetic acid at 80º C for 3 hr, the hydrolysate passed through a minicon filter to remove remaining protein, and the sialic acid fraction dried prior to sialic acid determination by DMB derivatization and fluorometric detection. Zeta potential was measured in 6 THP samples from each group.

Results: THP from urine of IC patients had significantly lower sialic acid content than THP from controls (224 ± 218 vs. 1001 ± 1443 pM/?g THP; P < 0.01, t test). Zeta potential was also significantly lower in THP from IC patients, indicating significantly less surface charge (electronegativity). Urinary THP concentrations were identical in IC patients and controls.

Conclusions: These findings support the concept of THP as a urinary protective factor whose protective function appears to reside in the sialic acid content and is compromised in individuals who have IC, a potentially significant development in the understanding of IC pathogenesis.

[mesafire]

Thanks for this!
Now, how do we get more sialic acid back into our system?

Thanks, Phil

[Trishann]

I am not sure what this all means yet but it is good knowing research is still going on. Thank you Jill.

Take care, Trishann

[purpleviolet]

OTC sialic acid

This substance is available OTC from Ecologic Formulas via the VitaminShoppe and Amazon. BUT - who knows if it is the is same thing. You google it and you come up with a lot of chemical sites way beyond my knowledge and small amounts for sale for researchers for way more than the OTC stuff. I KNOW I have wasted thousands on products and I can't even swallow them all, but I just can't help myself. I'm now trying that forskolin and sea buckthorn extract. What the heck - sailic acid is next! ( You know I have pills in a draw like sarsaparilla, pumpkin seed, and others that are supposed to be good for the bladder that I haven't even got around to trying. I'm crazy for trying but I think the side effects from synthetic drugs are generally worse in the long term. I want a cure. I've had this for over 35 years and time is running out. Bless you all today. PV

[purpleviolet]

more on sialic acid

http://cat.inist.fr/?aModele=afficheN&cpsidt=15416638

Interesting from what I can see - the anti-adherence molecules including pentosan sulphate (sp) which is Elmiron and heparin (which my uro instills in bladders) and dermanic (sp?)acid (I've seen this in skin formulas and may be in shark cartilege along with chrondoitin I THINK) and this siliac acid. Does anyone with more science knowledge than me understand this study. Does it it say these substance repel certain molecules such as oxalic acid that may be irritating. Also sialic acid is low in some heart disease patients I THINK - Please check out yourself. This is my preliminary and rushed research on the net. PV

[purpleviolet]

Whoa! I read wrong - the sialic acid and the urine made the crystals stick onto the bladders! Oh heck, I don't know what this study means except it seems to say they removed the protective lining of the bladder in the rat and restored the protection using heparin, etc.

[mayray]

i know what you mean

I used to dash to the store and buy every alternative offered but then i found myself looking at more than a thousand dollars worth of stuff that didnt work. and who has the money to waste when you are facing SSI disability. its ashame that we have to experiment to find the right thing. of course any new studies are wonderful and I find it interesting that a protein is mentioned. in my case, I have the APF factor in my urine and I believe this is what caused my IC. I have found relief with elmiron and elavil.

[mesafire]

Looks like the product you are referencing is Sialex:

http://www.vitaminshoppe.com/store/en/browse/sku_detail.jsp?id=CV-1084

[CCB]

Interesting postings from all, thanks for the research.
This really does helps reading the stories from all and I pray that the answers are here somewhere that will offer relief is not hope for a cure.

[IcyAngel23]

I have a call into Parsons nurse to see what the details are on this new finding. It normally takes her a week or so to get back to me since she is so busy. i'll let you know what she tells me.

[purpleviolet]

more info

I came across this about sialic acid from some pharmaceutical company (does not sell OTC products). Apparently, this stuff is in saliva (but I did read somewhere else that bacteria in the saliva can destroy it). I'm wondering if this is the substance that makes the slime (mucus) left behind in my dog's food bowl so tough to clean - it takes the dishwasher to get it out. Is this the same stuff that is supposed to line our bladder and protect it? If so, I understand why, because it is almost inpenentrable (atleast in the dog bowl!)
N-Acetylneuraminic acid(Neu5Ac). Note, that in animals atleast this stuff appears in the urine after ingestion -
"
(Sialic acid)

Assay: 98.0% Min, 99% Min

Description: Purity white powder

Acetic acid: 0.1% Max (no acetic acid smell)

CAS No.: 131-48-6

APPLICATION

N-Acetylneuraminic acid is usually called sialic acid or Neu5Ac,naturally widespread carbohydrate with numerous biological functions, including blood protein half-life regulation, variety of toxin neutralization, cellular adhesion and glycoprotein lytic protection. Starting reagent of biochemical derivatives for the synthesis pharmaceuticals.

Sialic acid is a derivative of a nine-carbon monosaccharide.

Sialic Acid was named from the Greek Sialos for Saliva. It is the negative charge of this ubiquitous chemical that is responsible for the slippery feel of saliva and mucins coating the body’s organs. Despite its role of acting as ‘decoy’ for invading pathogens, sialic acid is increasingly becoming known as an agent necessary for mediating ganglioside distribution and structures in the brain. Work in the 1980’s identified sialic acid supplementation in (suckling) rats to alter behaviour and increase performance in various mazes, suggesting a role in learning and memory. However work in out lab is focussing on the role of virility that sialic acid endow.

With the use of adult rat models, we have shown that sialic acid (namely the NeuAc form) acts as an agent to increasing the number of copulations between mating pairs. A transgenic rodent with reduced sexual appetite (kindly donated by the Kitawaga lab, Japan) was used to see whether oral and intraperitoneal doses of sialic acid increased sexual drive. Within one week the number of copulations of this rat model increased to amounts close to that of rats of virility. Numerous other mating pairs have been set up and we are currently waiting for the exciting results.

N-acetylneuraminic Acid

N-acetylneuraminic acid (sialic acid) is found in a wide variety of substances and tissues in animals and humans, occurring most abundantly in glycoproteins and glycolipids.
An acidic aminosugar was first isolated and named sialic acid by one scientist. Another isolated a similar crystallized form and called it neuraminic acid. When both were found to be the same molecule, the correct structure was proposed by a third scientist. All three finally agreed to use sialic acid as the family name covering all of the more than thirty derivatives of neuraminic acid, with N-acetylneuraminic acid and N-glycolylneuraminic acid forming the core structures.

Sialic acid is widely distributed throughout human tissues and found in several fluids, including serum, cerebrospinal fluid, saliva, urine, amniotic fluid, and mother's milk. In experimental mammals, it is found in high levels in the brain, adrenal glands, and the heart. In humans, concentrations are found in the brain and kidney as well as many other tissues.


Absorption

Although specific information is not yet known, it is assumed that sialic acid is readily absorbed when ingested. This is based on its appearance in numerous glycoconjugates (a molecule with one or more sugars attached to a protein or lipid) throughout the body and its excretion in the urine.
Enzymes involved in sialic acid metabolism also appear to be important in the metabolic regulation of other essential sugars and glycoconjugates. Sialic acid can be manufactured, by certain enzyme action in the body, from Glucosamine and N-acetylmannosamine.


Excretion

Sialic acid is rapidly eliminated via the kidneys. In lab animals, at least 98% of ingested sialic acid is found in the urine six hours after ingestion while about 90% appears in the urine within 10 minutes of an IV dose. During lactation, excretion of the sugar is markedly increased. When this data is applied to humans, most of the sugar would be expected to be excreted within 8 hours of ingestion. Therefore, it, or the other sugars, does not accumulate in body tissues.

Functions

Sialic acid is an immune moderator that affects the flow resistance of mucus which, in turn, repels bacteria, viruses, and other harmful microbes. In several in vitro and animal studies, the saccharide has been shown to inhibit strains of influenza A and B viruses more effectively than any prescription antivirals. In the April 2001 issue of Protein Science, scientists from Australia reported findings that showed sialic acid was an effective antiflu agent. Another study reported in a 1995 issue of Antimicrobial Agents and Chemotherapy, stated that a sialic acid mixture was up to 1000 times more effective in fighting influenza than potent antiviral drugs. Such viruses can also cause cold sores, hepatitis, viral pneumonia, as well as the common cold. Therefore, this helpful information is nothing to sneeze at!!
Since high levels are found in the human brain and kidney, it is speculated that sialic acid may play a key role in brain development and learning and in lessening the risk of kidney stone formation. Animal studies indicate that this essential saccharide does appear to improve both memory and cognitive performance.
Sialic acid is also found in such other tissues as the skin and testes leading to speculation that disruptions like skin diseases and reproductive problems could be reversed with supplementation of this essential sugar.
Sialic acid also influences blood coagulation and cholesterol levels, lowering LDL (bad cholesterol).
In alcoholics as well as those with Sjgrens syndrome, the levels of this saccharide are altered, suggesting that supplementation could reverse these disorders.
Abnormalities in sialic acid metabolism are seen in infants who fail to grow, who regress in development, who have enlarged livers and/or spleens, who show a coarsening of facial features, and who display a failure to produce pigmentation of the skin and hair.
Sialic acid, like the other essential sugars, appears to be important during pregnancy and lactation. The fact that levels are increased during these stages indicates the need for these sugars by the developing infant both for establishing immunity and for its physical and mental development.
In severely ill patients, sialic acid levels are markedly decreased in the upper airway cells, which is an important barrier for preventing opportunistic respiratory infections seen in many of these patients.
Sialic acid levels are markedly reduced in those with rheumatoid arthritis, confirming that this saccharide plays an important part in the immune system.
Researchers at Kumamoto University in Japan discovered that sialic acid blocked the release of histamine, thus decreasing the severity of allergic reactions as well as asthmatic bronchial spasms.

Safety

There does not appear to be any data that indicates any adverse reactions to a supplementation of sialic acid. On the contrary, researchers who, consistantly used high doses in experimental animals, found that the learning abilities of these animals increased. Nor did it seem to matter whether the dose was given orally or intravenously, the result was the same, indicating that the sugar is just as reactive using either route.
However, if there is a metabolic disorder that prevents the proper absorption of the sugar, disorders can be aggravated, causing a reversal in the positive effects seen in others. Malabsorption could result in mental retardation and ataxia (muscle coordination failure), as well as enlarged livers, developmental delays, and an excess excretion of sialic acid in the urine. Therefore, establishing whether this or other sugars are properly assimilated is very important. This is just one reason why taking all eight essential sugars together is much better than trying to take them individually and guessing the amounts. All work together to help each other, thereby drastically reducing the risk of problems when taking only one sugar.

It is suggested that the maximum safe dosage would be 140 mg. for a healthy 150-pound adult.


Dietary Sources

Whey protein isolate or concentrate ?not the powder (even those allergic to dairy products are able to tolerate this substance. It appears that the concentrate has a higher amount of sialic acid than the isolate.)
Hen's egg (organic, of course!)
" PV

[jillyg5661]

hmm...interesting

[enip41]

What combination?

My first doctor was new and tried new things. Hepirin, marcane etc. I just got worse. New doctor tried DMSO. No help there either. He added 12.5mg of Elavil and 2mg Valium every 6 hours to my hydroxizine and Elmiron. I had tried estrogen cream but am even allergic to the specially compounded one. He said to try Marshmellow root. I am also taking cysta Q or Querctin, msm, glucosimine chondroitin sulfate combined with hyluronic acid and aloe. Also trying Spurlina. Pyidium Plus. My diet is very limited. Can't even eat turkey or red meat. Not good with vegetables. In a flare over trying cooked spinach. He wants me to go to the Cleveland Clinic for botox. My daughter in Law wants me to try University of Maryland. Thinks instills don't work because of so much urethra involvement. Should I try to add this new idea? I am running out of counter space I am taking so much stuff but will try anything.