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A partially baked idea:
I have a theory but alas it probably cannot be proven or disproven. It goes like this:
First the corollaries:
1. We higher primates developed the need to allow a buidup of uiric acid…there is perforce an increase in species survival somehow connected to it. A possible reason is that it is somehow involved in thought processes (there is some evidence connected high IQ with high uric acid,)
2. In order to allow high levels of uric acid we must keep it in supersaturation. There are chemical processes, probably evolutionalrily developed and yet to be understood, that support this supersaturation (allowed on it's own a solution of 7.0 mg./dL will precipitate) and there are many people who spend their whole lives with high levels of uric acid but never precipitate it as gout. My guess is that we ALL have this ability to tolerate a supersaturated urate solution.
3. So here's the core of the theory: Occasionally those of us who eventually get gout have a localized SUPER-supersaturation, perhaps in the realm of 15 or 20 mg./dL SOMEWHERE in the body and precipitation will occur…we overwhelm supersaturative capability. We then have gout forever. The reason is that if one observes ANY supersaturated solution and drops a single tiny crystal of the substance in the whole works will crystallize (I have a chemisrty backround so I've seen it several times.) Some of the urate crystals are forever and will always provide a precipitation point thus no further supersaturation is possible. We are forever lost to gout.
If my theory holds water, another likely corollary is that gout can be prevented by diet only BEFORE it occurs (like being run over by a bus
?) Prevent that single incident of 15 or 20 level localized urate and you give youself a gout-free life.If someone can suggest any reasons why humans evolved to preserve uric acid, I'm all ears.
[Admin note: Original Poster lost during forum upgrade. Let me know if you want to claim it]
I've moved this here from a discussion in Gout Cures, where it seems to have got lost.
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Fascinating theory, and a fascinating final question. I'll have to give this some thought, but it makes for interesting discussion.
We've touched on this and Keith discussed it? a while ago. Knowing the benefits of SUA wouldn't necessariry help in gout cures but at least can justify its existence!
I understood UA to be an anti oxidant and helpful in immune response [ in this? 'good' mode']-
Pehaps in earlier times [like 100,ooo's years] we needed to survive many assaults on our systems from bog water, bites, bad food keeping etc. esp in hotter climates times/changes to.? Maybe it got driven up by default?
I think people with gout are unlikely to get MS and possibly Parkinsons [or similar CNS illness] This seems worth some reseach- but whatever happens,NO ONE is going to vote for it by preference, that's for sure!
Let me spout off on another old saw that I also have read dozens of times and that is that uric acid is an ANTIOXIDANT.
I disagree, it is NOT.
Firstly, I get antsy when anyone touts some “new” supplement as being an antoxidant because the phrase merely means a reducing agent, something that GETS oxidized. Thus wood, hydrogen, sugar,?and gasoline all qualify.
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That said, uric acid doesn't even qualify under that broad umbrella. Here's why: There are several steps in the oxidation of purines, enhanced by the presence of the enzyme xanthine oxidase, in the formation of STABLE uric acid. (It can be further oxidized to allantoin?by most species but not by man, so that pathway is irrelevant.)
Thus uric acid is the end product of the oxidation and thus CANNOT be further oxidized. It is NOT a reducing agent and thus NOT an “antioxidant.”
Yes, xanthine, hypohanthine, and a long list of derivatives CAN be further?oxidized and thus are antioxidants, but NOT uric acid. An analogy is that hydrogen is a reducing agent and an antioxidant but water is not?it is formed as the final oxidative product of hydrogen and oxygen.
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If anyone holds to the “uric acid as antioxidant” mantra, he must first demonstrate what iit is oxidized TO. Of course he cannot. Urate, in the human body, once formed, is pretty much inert; all it can do is be excreted or crystallize.
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(Nothing on you trev, the same thing is repeated ad?nauseum and without question all over?the web.)
zip2play said:
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If anyone holds to the “uric acid as antioxidant” mantra, he must first demonstrate what iit is oxidized TO. Of course he cannot. Urate, in the human body, once formed, is pretty much inert; all it can do is be excreted or crystallize.
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Yes, we really need to get this settled. “Uric acid as a potetent antioxidant” is not confined to unresearched Internet Chineses whispers. It is scattered throughout PubMed. There is even reference to “an antioxidant ? prooxidant urate redox shuttle” where uric acid stops being perceived as an anti-oxidant and becomes pro-oxidant. Given my science is strictly schoolboy, I'm competely at a loss to understand any of this. Unless…
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Are the biologists describing something different from the chemists take on oxidation. All the stuff I read talks of binding and scavenging and superoxides and reactive oxygen species and other related stuff that baffles me. It's almost as if the explanation (in my simple terms) is, metabolism/digestion produces stuff that can damage cell contents (“oxidize”), but uric acid and other substances like ascorbic acid (vitamin C), somehow “hold their hands” to prevent cell damage, without actually going through a chemical change.
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I was always better at understanding equations for inorganic chemical reactions than the organic chemistry touched on in biology class. Sometimes it seems that there are two languages operating here, though there is some common ground somewhere, as I see references for hydrogen peroxide getting reduced to water, which makes a very small light shine.
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Surely, somewhere there must be an explanation of this biological view of uric acid reacting with superoxides and reactive oxygen species? By which I mean an explanation why they see this as an anti-oxidant reaction, yet there is no chemical justification for it (or none that zip2play and I can see).
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Is it significant that most of the research I've seen where uric acid is described as anti-oxidant, is not related to gout? I'm beginning to think that there might be little or no relevance to gout. If this is the case, I can change the forum settings to ban “antioxidant” as a profanity, and we can set our minds to the best practical advice for helping gout sufferers. (I'd still like to understand it, though)
And when you have answered the above, your homework is to discuss:
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Uric acid and evolution.
?lvarez-Lario B, Macarr?n-Vicente J.
Department of Rheumatology, Complejo Asistencial de Burgos, Burgos, Spain. [email protected]
Abstract
Uric Acid? is the end product of purine metabolism in humans due to the
loss of uricase activity by various mutations of its gene during the
Miocene epoch, which led to humans having higher Uric Acid levels than other
mammals. Furthermore, 90% of Uric Acid filtered by the kidneys is reabsorbed,
instead of being excreted. These facts suggest that evolution and
physiology have not treated Uric Acid as a harmful waste product, but as
something beneficial that has to be kept. This has led various
researchers to think about the possible evolutionary advantages of the
loss of uricase and the subsequent increase in Uric Acid levels. It has been
argued that due to the powerful antioxidant activity of Uric Acid, the
evolutionary benefit could be the increased life expectancy of hominids.
For other authors, the loss of uricase and the increase in Uric Acid could be a
mechanism to maintain blood pressure in times of very low salt
ingestion. The oldest hypothesis associates the increase in Uric Acid with
higher intelligence in humans. Finally, Uric Acid has protective effects
against several neurodegenerative diseases, suggesting it could have
interesting actions on neuronal development and function. These
hypotheses are discussed from an evolutionary perspective and their
clinical significance. Uric Acid has some obvious harmful effects, and some,
not so well-known, beneficial effects as an antioxidant and
neuroprotector.?
Extra marks will be awarded for explanations that simpletons llike me can understand without spending half an hour looking up each word. Marks will be deducted for abbreviations.
Keith (Gout Admin) said:
And when you have answered the above, your homework is to discuss:
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Uric acid and evolution.
?lvarez-Lario B, Macarr?n-Vicente J.
Department of Rheumatology, Complejo Asistencial de Burgos, Burgos, Spain. [email protected]
? The oldest hypothesis associates the increase in Uric Acid with
?higher intelligence in humans. Finally, Uric Acid has protective effects
against several neurodegenerative diseases, suggesting it could have
interesting actions on neuronal development and function. These
hypotheses are discussed from an evolutionary perspective and their
clinical significance. Uric Acid has some obvious harmful effects, and some,
not so well-known, beneficial effects as an antioxidant and
?neuroprotector?
As part of MY homework, here is MY take on the subject:
?1) As is pointed out, a lot is nothing but hypothesis.
2)?If Uric Acid is an antioxident or not is, in all reality, academic. If it is: GREAT. I think, most will agree. If it is not: So what??? Nothing is lost, nothing is gained.
3) ?When/if it can be proven that Uric Acid is a poison for the body, then we need to get rid of it. It's as simple as that, since poisons generally do kill us.
And here is MY advice: Do not waste your time, energy, money on fighting for or against Uric Acid being an antioxidant or not.
If one wants additional antioxidants, buy some proven ones and live happily ever after.?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC349151/pdf/pnas00662-0320.pdf
Unless they are charlatans in this 20 year old report- it shows that acedemia does support UA as an antioxidant.
It seems that the actual pH at the time is not critical in that :
?”Urate is an effective antioxidant at alkaline and neutral pH (52) and in acid”
This report is not studying physiological attributes,as is stated, but?indicates both the character of UA and where it may ?apply in a positive way to the body.
For those here who like to learn about UA in any way, good or ill,?it's important that opinions are allowed freely.
Nothing to be gained fromm ignoring reality, in my book!
Hard to see why UA existing naturally in everyone should be a poison- or equally why medicating against its bad effects does not?need equal care in use -and effort to understand its use for the best end result.
Recent reports on the long term effects of meds as being not so secure in their harmlessness remind me that fashions come and go -depending on current thinking and who knows what can be thrown up in the future.
trev said:
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1)? “Urate is an effective antioxidant at alkaline and neutral pH (52) and in acid”
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2) For those here who like to learn about UA in any way, good or ill, it's important that opinions are allowed freely.
3) Nothing to be gained fromm ignoring reality, in my book!
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1) Trev, how many people on this planet with gout can show/prove that their pH is neutral or alkaline? I dare say: VERY FEW! So, to what extent does UA act as an antioxidant for all those with an acidic pH?
2) “Opinions are allowed freely”, however, an opinion on UA and it being an antioxidant is not going to help a gouty who is attacked by crystalline deposits of uric acid, being an antioxidant or not.
3) What is REALITY? UA is an antioxidant? That is hypothesis or just plain “believe” which is totally irrelevant. What IS relevant, is the fact that uric acid causes gout and we need to spend our time, energy, and money on fighting THAT!
Hans, if you look at the topic heading it's a question- Why do we need UA? If you don't like the topic just avoid it in the interest of free discourse.
It seems to be necessary for some reason otherwise we would excrete it straight away. If it is indeed an antioxidant this explains?some use for it.
Not difficult…and if there's a down side, understanding where it truly fits in could indicate how it could be better managed.
It could even play a part in mood enhancement/ reduction [ongoing research] 😉
There are many things that uric acid might or might not do.
But what it CANNOT do in the human body is be oxidized, hence it is NOT an antioxidant, no matter HOW many people, scientists included,?mistakenly?claim otherwise.
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In their defense, in most species uric acid CAN be oxidized to allantoin and then it is a reducing agent, aka antioxidant. The same can be done in a test tube?BUT NOT IN HUMANS.
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So for those fond of antioxidants (like wood, paper, sugar, hydrogen, cheese, or good salami and alcohol 😉 ) uric acid is an antioxidant, but NOT in human biology.
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Perhaps its evolutionary advantage might be upside down…maybe it's ALLANTOIN that keeps lower species lower? :D:D Is there anything special about the Dalmatian, vis a vie other dogs? Uric acid is not an antioxidant for them either.
OK Zip- we're moving forward?What if the human body recognizes this UA as a 'potential' antioxidant and hasn't learned that it can't process/excrete the stuff well?
Wouldn't the?first, if misled,?thing to do be to salt it away -and in gouties this gets done, just too damn?well.
I believe Vitamin C [an acid] helps reduce arterial deposition of 'bad' chlorestrol when inflammation is occuring in the arterial wallls-?thus stopping the?resulting higher BP?which?leads to a?higher risk of?Gout?.
This arterial inflammation has been itself proposed as a link between High BP and gout where?high?SUA is involved in both conditions.
[Sorry, haven't got the link- but I printed it out for my Dr. a while back]
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