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Posted: Wed Jun 21, 2006 6:36 am Post subject: uric acid - VANISHING LESIONS AND HALTED DISEASE PROGRESS
someone else probably has posted this before but it's new to me thanks to a recent heads up from another site member. i just can't stand to bury this kind of stuff down in the 'natural approach' forum...
Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease
Authors: Spitsin S.1; Hooper D.C.1; Leist T.2; Streletz L.J.2; Mikheeva T.1; Koprowski H.1, *
Source: Multiple Sclerosis, Volume 7, Number 5, October 2001, pp. 313-319(7)
Publisher: Hodder Arnold Journals
Abstract:
Peroxynitrite has been implicated in the pathogenesis of multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Previously, we have shown that administration of uric acid (UA), a peroxynitrite scavenger, is therapeutic in EAE. We have also shown that MS patients have lower levels of serum uric acid than healthy individuals or those with other neurological diseases. The aim of this investigation was therefore to raise serum UA levels in MS patients. Oral administration of UA failed to increase low serum UA levels, evidently due to its degradation by gastrointestinal bacteria. However, serum UA could be raised and maintained at elevated levels for a year and more without reported side-effects by oral administration of its precursor inosine. Three of 11 patients given inosine showed some evidence of clinical improvement and there was no sign of disease progression in the remaining patients. Gadolinium-enhanced lesions, observed in two patients before receiving inosine, could not be detected after either 10 or 15 months inosine treatment. These data provide evidence that serum UA levels can be readily manipulated and that the benefit of higher levels to individuals with MS should be studied further in greater number of patients.
Posted: Wed Jun 21, 2006 6:47 am Post subject: the search for inosine supp
i could not find inosine on the natural factors site or at my usual store - nutrition house - but found it here: http://www.sourcenaturals.com/products/?id=GP1157 and will see if my store can order it in quick before i leave.
I could send you a hundred similar research papers and you would have to get another job to pay for all the different supplements and potions. This was a very small study and the benefits look a bit inconclusive to me. This disease is a researchers dream and if you are not careful, you could be spending all your money on bee stings, LDN, uric acid, abx, vit D tablets, live yogurts etc etc. And don't forget to cut out artifical sweetners, red meat etc etc. And read your bible everday. Science will work this disease out (eventually) and come up with ways to stops it etc. In the meantime, it's a snakeskin oil saleman's paradise - coming up with potions to sell to desperate people like us.
Posted: Wed Jun 21, 2006 7:26 am Post subject: it does work for me bromley!
it's true i try a lot of stuff. and notice improvement. at this point, my daily regimen includes:
personalized b-complex,
E,
C,
selenium,
turmeric,
calcium/magnesium/d liquid (with extra D by prescription),
multi-acidophilus,
multi-mineral, and
ginkgo biloba. oh and right now, some extra
iron. and soon, some
inosine.
i stage it so that the C goes with the iron, but not at the same time as the B vitamins, to help with absorption.
when i stick with it bromley, honestly, i get into really good shape. the only lingering problem is my sensory impairment in my hands. (i think that's because i actually physically damaged my neck right at C7/C8 a day before this attack started.) when i get off the program, i start to have issues again.
Joined: May 26, 2004 Posts: 1356 Location: London, ON, Canada
Posted: Wed Jun 21, 2006 7:47 am Post subject:
Hi Ian,
Quote:
This disease is a researchers dream and if you are not careful, you could be spending all your money on bee stings, LDN, uric acid, abx, vit D tablets, live yogurts etc etc.
I'm not so sure that the thousands of MS patients using LDN and gaining some benefit would like you lumping this very inexpensive drug into the pot of worthless spending.
Joined: Jun 18, 2004 Posts: 1472 Location: Bedfordshire UK
Posted: Wed Jun 21, 2006 8:00 am Post subject:
Yes, Bromley,
I don't think you can really dump bee stings in with antibiotics or live yoghurt, which is good for everyone, either
I probably wouldn't be here today without antibiotics.
Sarah _________________ An Itinerary in Light and Shadow
Completed Stratton/Wheldon antibiotic regime for aggressive secondary progressive MS in June 2007, after four years. Still slowly improving with no exacerbation since starting. EDSS was 7, now 2 or often less.
The point I was making was that every week there is some new "cure" which is promoted and people head down to their health shops and come back with bags of supplements etc. Many swore by bee stings but recent research has shown that they had no effect. On LDN, some report good results but other say did nothing for them and there have been no proper trials. ABX has worked for Sarah and some others, but I would place a bet that it hasn't worked for everyone who has taken them.
It was just a gentle warning to Jimmy that you can end up spending lots of money on supplements which may have little effect. Recent research in the UK concluded that eating a balanced diet was the best quarantee of getting all the vitamins and minerals required.
Ian
PS Harry - I see that you have moved your profits from your Biogen share sale to promote LDN.
PSS Sarah - you should take BeatMS's advice 'abx are bad for you'. And don't forget to read your bible tonight, I know you are a god-fearing woman underneath.
Quote:
I probably wouldn't be here today without antibiotics.
Yes, the inventors of anti-biotics have got a lot to answer for!
Posted: Wed Jun 21, 2006 9:28 am Post subject: diet and supplementation
lol re god-fearing brom. and thank you for the gentle warning.
yep i agree about balanced diet. however, i do not pretend that mine is perfect and therefore supplement. since i have recently given up veganism, i have to build up stores of nutrients seriously depleted over close to 15 years. i now eat fish and eggs and some tiny amount of dairy... but i just don't think i'll be having steak and kidney pie any time soon, to get the inosine. guess i'll be making sushi more often, and taking that supplement!
Joined: May 26, 2004 Posts: 1356 Location: London, ON, Canada
Posted: Wed Jun 21, 2006 11:01 am Post subject:
Ian,
Quote:
PS Harry - I see that you have moved your profits from your Biogen share sale to promote LDN.
Oh heavens no....I would never take my millions out of Biogen at the moment...they just raised the price of Tysabri by 22% so I'm counting my money before they even start using the drug again And nobody is going to make any money on LDN...no patent!! But there ARE a lot of LDN users out there who appear to be gaining some benefit.
Posted: Thu Jun 22, 2006 8:57 pm Post subject: On the subject of Inosine
My Summer 2006 issue of MSQR (Multiple Sclerosis Quarterly Report), arrived this week. In the section entitled, "Current Clinical Trials in MS," is the entry, "Treatment of MS Using Over-the-Counter Inosine."
Location: Hospital of the University of Pennsylvania, Philadelphia, PA.
Purpose: The purpose of this study is to determine whether raising low levels of the natural antioxidant uric acid by the administration of a precursor, inosine, has any therapeutic effect of the progression of RRMS and secondary progressive MS.
Eligibility: Males and females, 18 to 60 years of age. Non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test result within 60 days before the first dose of study material. Males and females must practice adequate contraception, in the judgment of the investigator, during the course of the study. Subjects must have a diagnosis of clinically definite relapsing-remitting MS based on medical history, physical examination, laboratory test results, and neurologic examination, and have had one clinical relapse in the last year. Alternatively, subjects may have clinically probable MS characterized by one attack and the presence of at least four lesions on MRI within 12 months before the initial baseline evaluation. Subjects must have an EDSS test result of less than or equal to 5.0 within 60 days before the first dose of study material. Subjects will have serum uric acid levels less than 5 mg/dl. There are also several exclusion criteria. For information contact Vanessa Zimmerman by phone at 215-349-5162, or via e-mail "vanessa.zimmerman@uphs.upenn.edu".
Posted: Thu Jun 22, 2006 10:39 pm Post subject: inosine background
another older study for review.
Ther Umsch. 2004 Sep;61(9):553-5.
[Uric acid and multiple sclerosis]
Mattle HP, Lienert C, Greeve I.
Neurologische Klinik und Poliklinik, Universitatsspital Bern, Inselspital, Bern.
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.
Posted: Thu Jun 22, 2006 10:45 pm Post subject: pick me!!
i think i would be interested in participating in this study, if i didn't think they would make me stop all my other supplements so as not to cloud the results!
Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock1
György Haskó2, David G. Kuhel, Zoltán H. Németh, Jon G. Mabley, Robert F. Stachlewitz, László Virág, Zsolt Lohinai, Garry J. Southan, Andrew L. Salzman and Csaba Szabó
Inotek Corp., Beverly, MA 01915
Extracellular purines, including adenosine and ATP, are potent endogenous immunomodulatory molecules. Inosine, a degradation product of these purines, can reach high concentrations in the extracellular space under conditions associated with cellular metabolic stress such as inflammation or ischemia. In the present study, we investigated whether extracellular inosine can affect inflammatory/immune processes. In immunostimulated macrophages and spleen cells, inosine potently inhibited the production of the proinflammatory cytokines TNF-, IL-1, IL-12, macrophage-inflammatory protein-1, and IFN-, but failed to alter the production of the anti-inflammatory cytokine IL-10. The effect of inosine did not require cellular uptake by nucleoside transporters and was partially reversed by blockade of adenosine A1 and A2 receptors. Inosine inhibited cytokine production by a posttranscriptional mechanism. The activity of inosine was independent of activation of the p38 and p42/p44 mitogen-activated protein kinases, the phosphorylation of the c-Jun terminal kinase, the degradation of inhibitory factor B, and elevation of intracellular cAMP. Inosine suppressed proinflammatory cytokine production and mortality in a mouse endotoxemic model. Taken together, inosine has multiple anti-inflammatory effects. These findings, coupled with the fact that inosine has very low toxicity, suggest that this agent may be useful in the treatment of inflammatory/ischemic diseases.
Vol. 96, Issue 23, 13486-13490, November 9, 1999
Neurobiology
Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury
Larry I. Benowitz*,,,§, David E. Goldberg*, Joseph R. Madsen*,, Deepa Soni*, and Nina Irwin*,
* Department of Neurosurgery, Children's Hospital, Program in Neuroscience, and Department of Surgery, Harvard Medical School, Boston, MA 02115
Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved September 16, 1999 (received for review July 19, 1999)
The purine nucleoside inosine has been shown to induce axon outgrowth from primary neurons in culture through a direct intracellular mechanism. For this study, we investigated the effects of inosine in vivo by examining whether it would stimulate axon growth after a unilateral transection of the corticospinal tract. Inosine applied with a minipump to the rat sensorimotor cortex stimulated intact pyramidal cells to undergo extensive sprouting of their axons into the denervated spinal cord white matter and adjacent neuropil. Axon growth was visualized by anterograde tracing with biotinylated dextran amine and by immunohistochemistry with antibodies to GAP-43. Thus, inosine, a naturally occurring metabolite without known side effects, might help to restore essential circuitry after injury to the central nervous system.
The uric acid connection with MS, like the vitamin D one, has been very under-explored by researchers. That is my frustration with the state of MS research: when there is highly suggestive epidemiology data, and supporting animal data, it still does not quickly ead to more definitive human trials even if the safety profile for the intervening agent is known - vitamin D and inosine are by no means new drugs. I'm like jimmylegs, Anecdote, and others, I would rather try something that is supported by some science and take my chances, than wait 20-30+ years, if ever, for the research to finally grind through some FDA-approved clinical study.
The abstract below is probably posted elsewhere on this site, but below is a PubMed abstract which addressed both aspects of uric acid, both animal and human epidemiology. Notably the authors searched through more than 20 million patient records and found that MS and gout (characterized by high uric acid) appeared to be almost mutually exclusive diseases. This number of patient records provides a lot of statistical power. The article can be viewed for free online. I remember reading an abstract of an older German study (can't remember authors) in which the authors noted that in a series of MS patients, they also saw none with gout, even though gout was common in the general population from which the patients came from.
I am glad lyndacarol reported that an early trial is ongoing for this. I think someone posted earlier that these Philadelphia researchers had been wanting to do a human study with inosine for some time, but it was a matter of funding. An OTC supplement can't become a trillion dollar blockbuster, no matter how good it is.
Lisa
^^^^^^^^^^^^^^^
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):675-80. Related Articles, Links
Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis.
Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowski H.
Center for Neurovirology, Thomas Jefferson University, Philadelphia, PA 19107-6799, USA. dchooper@reddil.uns.tju.edu
Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO) produced by lipopolysaccharide-stimulated cells of a mouse monocyte line. In this study, we used uric acid to treat experimental allergic encephalomyelitis (EAE) in the PLSJL strain of mice, which develop a chronic form of the disease with remissions and exacerbations. Uric acid administration was found to have strong therapeutic effects in a dose-dependent fashion. A regimen of four daily doses of 500 mg/kg uric acid was required to promote long-term survival regardless of whether treatment was initiated before or after the clinical symptoms of EAE had appeared. The requirement for multiple doses is likely to be caused by the rapid clearance of uric acid in mice which, unlike humans, metabolize uric acid a step further to allantoin. Uric acid treatment also was found to diminish clinical signs of a disease resembling EAE in interferon-gamma receptor knockout mice. A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS.
but failed to alter the production of the anti-inflammatory cytokine IL-10
I have been using inosine for quite some time (1000mg/day for 6+months), and cant say I noticed the difference. Except that my uric acid (froom blood tests) has gone from below normal, to within the normal range.
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