Uric acid

[Gondwanaland]

https://en.wikipedia.org/wiki/Uric_acid
Solubility[edit]
In general, the water solubility of uric acid and its alkali metal and alkaline earth salts is rather low. All these salts exhibit greater solubility in hot water than cold, allowing for easy recrystallization. This low solubility is significant for the etiology of gout. The solubility of the acid and its salts in ethanol is very low or negligible. In ethanol/water mixtures, the solubilities are somewhere between the end values for pure ethanol and pure water.

 

[Jonathan Edwards]

Thanks for the explanation.

I wonder why eating high purine foods makes all my joints ache. I know gout isn't typically symmetrical, nor are my aches. Additionally to the joint pain I have small painful nodules that sometimes form in the palms of my hands - they are more common in winter, but this time they are flaring in the summer.

Gouty joints do not ache. They are seriously painful or completely painless, no in between.

Urate can deposit in the palm but pretty much only in people with a history of severe recurrent gout. Subcutaneous rate deposits are easily recognised by their colour. The deposits do not come and go.

I am not sure how malate would solubilise urate. Urate in joints is monosodium urate. Malate ions are not going to compete for the sodium and form sodium malate crystals.

 

[Jonathan Edwards]

The low solubility of monosodium rate is what is relevant to gout, not the solubility of uric acid. Wikipedia is not always that good on chemistry!

 

[Gondwanaland]

Gouty joints do not ache. They are seriously painful or completely painless, no in between.

Thanks for pointing out the difference in English - the pain in my right hip was causing me to limp before taking magnesium malate.

@PennyIA Japanese patented product for gout:

https://www.google.com/patents/US20120190886
In the pharmaceutical composition of the present invention, for example, besides taurine, citric acid (which has an action of maintaining the weak alkalinity of urine so as to facilitate dissolution of uric acid into the urine), vitamin C (which has an action of promoting uric acid excretion by transferring uric acid accumulated in a joint or the like to the kidney), potassium (which has an action of promoting filtration of uric acid in the kidney), folic acid (which has an action of weakening the activation of a uric acid synthase), or the like may be blended as appropriate, as long as the effects of the present invention are not impaired.

Methylation in a pill

 

[PennyIA]

Dear PennyIA,

Gout pretty much never occurs without redness and swelling. The pain normally responds fairly well to NSAI although the course of the attack may still have to be run usually 12 hours to a few days. Gout pain never goes away in 20 minutes because the white cells take longer than that to disappear. The inflammation cannot move to another site because it is a section to monosodium rate in a particular place. The crystals tend to stay where they are pretty much permanently unless they are dissolved away by reducing serum urate levels.

The crystals in gouty joints are not uric acid. Uric acid crystals are common and normal in urine. Urine is the only place in the body where uric acid as such occurs because it can only crystallise under the acid conditions of urine.

As far as I know protein intake has no particular effect on circulating urate levels. Purine intake can have a slight effect but virtually all gout occurs largely for other reasons.

Are you sure you have gout? From what you describe it seems unlikely.

That's a great question. I know my current doctor disagrees (but offers no other explanation) and that I was diagnosed with gout based on a conference call (iffy, I know) with an Integrative MD when I was seeking assistance with methylation treatment (which I'm no longer on due to negative side affects).

His reasoning, frequent recurring severe pain in my big toe on my left side and my knee. Lasts around two weeks usually. At it's worst, accompanied by brown crystals in the urine. My son was initially diagnosed with gout at 22 and does experience redness and swelling when he has an attack (though his attacks seem to be more closely related to stress than diet). And his pain is described as manageable. For me, there is no visible swelling or redness (to your point). Eating high purine foods will create the problem within 24 hours of ingestion. For example, I had completely forgotten that shelfish are high in purines when I treated myself with a dozen boiled shrimp celebrating the new year two years ago. That triggered a flare. Eating even semi normal amounts of foods with medium levels of purines may or may not cause the trigger, depending on frequency of eating them (for example I might get away with it on day 1, but two days in a row or some other similar combination can trigger it then as well). So, to try to test the theory that the tart cherry supplements are helping me .. I had 6 oz of steak two days in a row on purpose (usually have to limit myself to less than 4 oz at any given meal). The flare up did not fire on day 1, but did on day 2.

The pain IS NOT managed well with NSAIDs. Nor anything else I've tried (heat, ice, acetaminophen, etc) with the exception of the tart cherry supplements. It feels like the pain decreases pretty quickly after taking about 4 of the supplements, though it seems like during a bad bout, I'm stuck taking them every four hours as the pain will return for several days.

I'm unable to handle any 'pressure' on the joints in question at the time of the flare ups. I do have very different pain in some joints that feel like loose connective tissue allowing the joints in my feet to feel 'out of place' or shifted or something... those are aches and I can feel the bones not quite lining up right. But it's very different. Those do respond well to NSAIDs are never severe pain and do cause mild swelling. Add some once in a while aching in my knee as the result of a an old ACL reconstruction, which is quite different. The pain that I thought was gout is very severe. And it's always the same joints (my big toe joint in my knee) and the pain comes with no other precipating factors that I can find.

I've been chatting about this online fairly often (prior to the integrative md diagnosis)and looking for other options (because if I can find an alternative diagnosis, then I might have options for treatment). I have debated pushing the issue with my current md who has refused to test me for gout, but haven't bothered because even if I could get a prescription for gout treatment, I'd rather manage it through diet then being on medications for life since I have trouble with a lot of medications. But if there were other diagnosis options that wouldmake more sense, that I wouldn't mind searching out.

 

[Gondwanaland]

even if I could get a prescription for gout treatment, I'd rather manage it through diet then being on medications for life since I have trouble with a lot of medications.

Same here. I have found some ideas here:
http://www.goutdiet.org/choosing-the-right-supplements-for-gout.php
http://www.naturalhealthnewsreport.com/page/nhn/articles/specialreport/2012-05-02-013.html

 

[Gondwanaland]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215161/
The purines are a group of molecules used by all cells of the body for many essential biochemical processes. They are synthesized by a multistep pathway known as the de novo synthetic pathway, they pass through several steps where they may be interconverted, and ultimately they are degraded and excreted as uric acid (Fig. 187.1). An example purine is adenosine triphosphate (ATP), which is required for many energy-requiring enzymatic reactions. ATP and guanosine triphosphate (GTP) also serve as building blocks for the synthesis of DNA and RNA. Some purine molecules, such as nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), serve as cofactors that are used in other reactions. The cyclic nucleotides, cAMP and cGMP, play a key role in many intracellular signaling pathways.

Especially interesting is Table 1 with Disorders of purine metabolism incl Exercise intolerance, myalgia,
cramping; Life-threatening infections; Immunological defects

 

[Jonathan Edwards]

His reasoning, frequent recurring severe pain in my big toe on my left side and my knee. Lasts around two weeks usually. At it's worst, accompanied by brown crystals in the urine. My son was initially diagnosed with gout at 22 and does experience redness and swelling when he has an attack (though his attacks seem to be more closely related to stress than diet). And his pain is described as manageable. For me, there is no visible swelling or redness (to your point). Eating high purine foods will create the problem within 24 hours of ingestion. For example, I had completely forgotten that shelfish are high in purines when I treated myself with a dozen boiled shrimp celebrating the new year two years ago. That triggered a flare. Eating even semi normal amounts of foods with medium levels of purines may or may not cause the trigger, depending on frequency of eating them (for example I might get away with it on day 1, but two days in a row or some other similar combination can trigger it then as well). So, to try to test the theory that the tart cherry supplements are helping me .. I had 6 oz of steak two days in a row on purpose (usually have to limit myself to less than 4 oz at any given meal). The flare up did not fire on day 1, but did on day 2.

The pain IS NOT managed well with NSAIDs. Nor anything else I've tried (heat, ice, acetaminophen, etc) with the exception of the tart cherry supplements. It feels like the pain decreases pretty quickly after taking about 4 of the supplements, though it seems like during a bad bout, I'm stuck taking them every four hours as the pain will return for several days.

I'm unable to handle any 'pressure' on the joints in question at the time of the flare ups. I do have very different pain in some joints that feel like loose connective tissue allowing the joints in my feet to feel 'out of place' or shifted or something... those are aches and I can feel the bones not quite lining up right. But it's very different. Those do respond well to NSAIDs are never severe pain and do cause mild swelling. Add some once in a while aching in my knee as the result of a an old ACL reconstruction, which is quite different. The pain that I thought was gout is very severe. And it's always the same joints (my big toe joint in my knee) and the pain comes with no other precipating factors that I can find.

I've been chatting about this online fairly often (prior to the integrative md diagnosis)and looking for other options (because if I can find an alternative diagnosis, then I might have options for treatment). I have debated pushing the issue with my current md who has refused to test me for gout, but haven't bothered because even if I could get a prescription for gout treatment, I'd rather manage it through diet then being on medications for life since I have trouble with a lot of medications. But if there were other diagnosis options that wouldmake more sense, that I wouldn't mind searching out.

Dear @PennyIA
As you know, I should try to give you a diagnosis. However, I can make some more general comments.

Severe pain in the 'bunion' joint of the big toe (the one affected by gout) is very common and in the great majority of cases is due to mechanical failure of the joint surface - in simple terms it is worn. The condition is sometimes called hallux rigid but is basically just a worn big toe joint. Something songs from time to time producing severe pain that can last for days or weeks. The joint is not red or hot. Normally there is no precipitating factor one can identify. In gout severe pain is always in my experience associated with redness and heat. In mechanical pain pressure that levers the joint can be excruciating. In gout what hurts is simply touching the skin where it is red. Severe pain in the knee is not common in gout and when gout affects the knee it makes the entire knee joint swell - the pain is not local. Local pain on the side of the knee is very very common and usually due to a disruption of the rim of the meniscus. Again, there is usually no obvious precipitating factor.

Gout quite often has a hereditary component but when recurrent gout occurs it always has the typical features.

Eating purine-rich foods does not precipitate gout. Gout is due to release of crystals from the synovial tissue into the joint fluid and the crystals almost certainly have been there over a period of months or years already. Certain metabolic shifts do have a reputation for precipitating gout but the most likely thing is that they do so by dissolving the crystals already there and loosening them out. That would tend to occur if blood rate levels went down a bit. This is the usual explanation for the fact that if rate levels are brought down by allopurinol gout attacks tend to become more frequent rather than less, until all the crystals have gone.

Uric acid crystals in the urine have nothing to do with gout. They are normal. Uric acid is called 'uric' because it is normally found in urine (like urea). The job of the kidney is to excrete it there. If anything gout tends to occur when the kidney is not exciting uric acid efficiently, so the rate goes up in the blood instead of going in to the urine.

So I guess it would be fair to say that from what you say there is nothing to suggest that you have gout. However, it is clearly not for me to diagnose and a blood urate level would be useful to exclude gout completely, as long as it is interpreted properly. Unfortunately, even a good proportion of rheumatologists are not that clear on how to interpret urate levels. I ran the urate crystal analysis service for gout diagnosis for the largest rheumatology unit in the UK for several years so got to know the pitfalls.

 

[PennyIA]

Dear @PennyIA
As you know, I should try to give you a diagnosis. However, I can make some more general comments.

This is all very helpful information. And I find it interesting that it's the release of the crystals already built up.

I'm really wishing I had studied more biology and chemistry - as it seems like most of my symptoms were worsened post my starting methylation treatment. I loved my initial energy gain from methylation treatment and it seems like it helped with both my chronic b12 deficiency and my b6 toxicity issues. But, I'm not getting the same lift from it any longer and I've had a lot of side effects from it lately.

I'm curious if the fact that I'd never had visible crystals in the urine prior to methylation and the folate connection to purine conversion to uric acid initiated some processing that wouldn't have been working as efficiently as previous?

That said, I'm also still curious about the timing of the flare ups. If it's truly not related to dietary intake... then I'm going to follow a test. I'm going to go out and really devour a good steak and shrimp dinner... and if my toe flare's up I'm going to take it in to see my regular doctor and ask him to diagnose it. I'm thinking you are right and it's not related to gout, and it might be related to something else, but if it's something else, it should be able to be diagnosed. And if it doesn't flare up - well, it always has in the past... but if it doesn't flare up, more evidence it's unrelated to diet.