Our uric acid is trying to keep us alive

Or maybe I'm holding this thing upside down.

http://high-fat-nutrition.blogspot.com/search/label/Worms%20and%20Stress%3A%20Live%20long%20and%20Prosper

Peter says it better than I will, but I'll give a quick run through. You block glucose metabolism in some worms, and it doubles their lifespan. When the worm's mitochondria switch to burning fat, they start spewing out all kinds of free radicals. Lots of fat being burned, the energy is used for repair, to attack invading bacteria, to fight cancer, lots of good stuff. Antioxidants are crucial enzymes, not just generic antioxidants.
Feed the worms some antioxidants, vitamin c, vitamin e, or n-acetyl cysteine, and the increase in the worms lifespan disappears, along with the dangerous free radicals. It's not about wear and tear, wear and repair is the rule.

So what's been established? The mitochondrial fires can be severely decreased by changing the antioxidants present.

Uric acid is itself an antioxidant, as is allantoin. So introducing either one of these into the environment of a cell will change the antioxidant status of the cell, which could have consequences to energy production. Energy availability is enormously important to cell proliferation.

Human beings have a thing called physiological insulin resistance, where cells are resistant to insulin and glucose. This has the obvious benefit of sparing glucose for tissues that need glucose even when glucose is short, such as the brain. It has another benefit; if the body hopes to benefit in some way by the production of free radicals, insulin resistance is just the thing. Insulin resistant cells will switch over to burning fat. (If the body is busy fighting something or producing energy to heal a wound, dousing the fire with a little vitamin e, vitamin c, or n acetyl cysteine at this point might not be wise.)

http://jama.ama-assn.org/cgi/reprint/266/21/3008

Based on the data presented herein, it seems reasonable to conclude that differences in the ability of insulin to stimulate glucose uptake play a role in the regulation of serum uric acid concentration within a normal, healthy population, and this action is mediated by changes in the renal handling of uric acid. Furthermore, the relationships defined in the study (summarized in Fig 4) provide the experimental basis for this conclusion. We suggest that resistance to insulin-mediated glucose uptake and/or the compensatory hyperinsulinemia associated with this defect decrease urinary uric acid clearance, with a subsequent increase in serum uric acid concentration. More specific, we propose that the greater the degree of insulin resistance, the lower the uric acid clearance. Based on the data presented herein, it seems reasonable to conclude that differences in the ability of insulin to stimulate glucose uptake play a role in the regulation of serum uric acid concentration within a normal, healthy population, and this action is mediated by changes in the renal handling of uric acid. Furthermore, the relationships defined in the study (summarized in Fig 4) provide the experimental basis for this conclusion. We suggest that resistance to insulin-mediated glucose uptake and/or the compensatory hyperinsulinemia associated with this defect decrease urinary uric acid clearance, with a subsequent increase in serum uric acid concentration. More specific, we propose that the greater the degree of insulin resistance, the lower the uric acid clearance and the higher the serum uric acid concentration

Dr Richard Bernstein has been teaching diabetic patients how to achieve normal blood sugar levels using a very low carbohydrate diet and minimal insulin injections. In his book Dr Bernstein's Diabetic Solution, Dr Bernstein reveals that it is virtually impossible to achieve good blood sugars if an infection is present. Infection is a major insulin-resistance culprit. Time for repair. Time for the free radicals to come out to play? Mitochondrial fat-munchers to the rescue, again.

And, in insulin resistance, serum uric acid goes up? Part of the healing process?

Fructose has been proposed as the cause of gout and excess uric acid, through depletion of ATP in the liver (the adenosine part of adenosine tri phosphate is a purine.) But fructose is also seriously implicated in the invasion of the body by lipopolysaccharides (biofilm, a matrix of complex sugars and yeasties and microbes and stuff.) Lipopolysaccharides release endotoxins into the body that can cause cancer, fatty liver, etc.

Fructose gives mice and rats fatty liver, high blood pressure, etc. This can be lessened by glycine and taurine, both of which protect the body against endotoxins, (although I'm not sure endotoxins are the villain here) and are actually involved in their removal from the body through bile. Glycine used to be used to treat gout, back before they discovered allopurinol, which disrupts purine metabolism so that less uric acid is produced.

Glycine increased the output of uric acid in the urine. That's why they used it. But glycine is also a purine--and very cheap-- so of course it fell out of favour. They worried that the uric acid in the urine was formed from the breakdown of the glycine. I sort of doubt it.

So something that basically helps the body to fight infection has been seen reversing "metabolic syndrome" in rodents. Remove the infection, remove the insulin resistance? Remove the infection, reverse the uric acid elevation? Because both of these are just part of the body's defence and repair system?

http://www.cababstractsplus.org/abstracts/Abstract.aspx?AcNo=20053171423

Accumulation of collagen and changes in its physiochemical properties contribute to the development of secondary complications of diabetes. We undertook this study to determine the effects of taurine on the content and characteristics of collagen isolated from the tail tendon of rats fed with high fructose diet. The rats were divided into four groups of six each: control group (CON), taurine-supplemented control group (CON+TAU), taurine supplemented (FRU+TAU) group, and non-supplemented fructose-fed group (FRU). The physicochemical properties of collagen were studied. Fructose administration caused the accumulation of collagen in tail tendon. Enhanced glycation and advanced glycation end products (AGE)-linked fluorescence together with alterations in aldehyde content, solubility pattern, susceptibility to
denaturing agents and shrinkage temperature were observed in fructose-fed rats. An elevated β component of type I collagen was observed from the SDS gel pattern of collagen from the fructose-fed rats. Simultaneous administration of taurine alleviated these changes. Taurine administration to fructose-fed rats had a positive influence on both quantitative and qualitative properties of collagen. Results indicate the role of taurine in delaying diabetic complications. It can be used as an adjuvant therapeutic measure in the management of diabetes and its complications.

Thickened tails as a reaction to infection? Does it have to be a real infection?

Inactivation of Kupffer cells prevents alcohol-induced liver injury, and hypoxia subsequent to a hypermetabolic state caused by activated Kupffer cells probably is involved in the mechanism. Glycine is known to prevent hepatic reperfusion
injury. The purpose of this study was to determine whether glycine prevents
alcohol-induced liver injury in vivo.

METHODS: Male Wistar rats were exposed to ethanol (10-12 g.kg-1.day-1) continuously for up to 4 weeks via an intragastric feeding protocol. The effect of glycine on the first-pass metabolism of ethanol was also examined in vivo, and the effect on alcohol metabolism was estimated specifically in perfused liver.

RESULTS: Glycine decreased ethanol concentrations precipitously in urine, breath, peripheral blood, portal blood, feces, and stomach contents. Serum aspartate amino-transferase levels were elevated to 183 U/L after 4 weeks of ethanol-treatment. In contrast, values were significantly lower in rats given glycine along with ethanol. Hepatic steatosis and necrosis also were reduced significantly by glycine. Glycine dramatically increased the first-pass elimination of ethanol in vivo but had no effect on alcohol metabolism in the perfused liver.

CONCLUSIONS: Glycine minimizes alcohol-induced liver injury in vivo by preventing ethanol from reaching the liver by activating first-pass metabolism in the stomach.

http://www.ncbi.nlm.nih.gov/pubmed/8613061



Just the abstract again. Kupffer cells are macrophages, part of the immune system. So if glycine reduced activation of Kupffer cells, reversing the implied infection? In a human, would this reversal of infection also permit removal of more uric acid in the urine?

http://ajpcell.physiology.org/cgi/reprint/293/2/C584


I love this one.

Our results support previous epidemiological studies and animal models
of hyperuricemia, which suggests an involvement of uric acid in the pathogenesis of the metabolic syndrome,and provide a possible molecular mechanism for this role based on the finding that soluble uric acid affects adipocytes directly by inducing NADPH oxidase-dependent oxidative stress.
We suggest that hyperuricemia can be one of the causal factors inducing oxidative stress followed by a proinflammatory process and endocrine dysfunction in the adipose tissue, thereby contributing to the pathogenesis of the metabolic
syndrome and cardiovascular disease.

So, whatta we got here? Uric acid causes fat cells to start spewing out free radicals. Uric acid facilitates the oxidation of fat. Uric acid is associated with inflammation. Inflammation is a cause of insulin resistance, which is the preference for fatty acid oxidation over glucose.

Inflammation is the body trying to heal or fight off invaders. Uric acid is part of that process.

Human beings and birds are both long-lived. Human beings and birds both lack uricase, which breaks down uric acid. Uric acid is an antioxidant/pro-oxidant, affecting oxidation status. Uric acid can promote high-gear mitochondria fat-munching. Causing an increase in free radicals.

http://www.drproctor.com/rev/ascorbicuric.htm

Similar Functions of Uric Acid and Ascorbate in Man

Pointing out the structural similarity between uric acid and the stimulant purines caffeine and theophylline, Orowan (1) first proposed that the emergence of intelligence in the primate line might arise from a single evolutionary event, the loss of the enzyme uricase, with the result that uric acid became the end product of purine metabolism. The only non-primate mammalian strain whose final purine metabolite is uric acid is the Dalmatian dog.
Haldane (2), taking issue with this suggestion, proposed two hypotheses: thatindividuals with high serum uric acid levels should show increased intellectual abilities , and that such individuals should be unusually resistant to certain types of fatigue. Neither one of these has received much experimental support, although serum uric acid levels have been correlated with social class, achievement, and achievement -oriented behavior. ( for a review of such work, see Muller et al (3)).
I would like to propose that the loss of uricase in the primate line may be connected with another biochemical lesion which is unique to the primates, namely, the loss of
the ability to synthesise ascorbic acid de novo, As in the case of loss of uricase, this lesion is found in only one non-primate mammalian species ( the guinea pig (4) ). ( Post-publication addendum: also the flying fox.)
The reasoning behind this suggestion is this: a number of the physiological functions of ascorbate are generally considered to be related to the unique electron-donor properties of this compound. Uric acid (along with the rest of the purines ) is also a strong electron-donor (5). In fact, on the somewhat tenuous basis of molecularorbital indices, uric acid may be a better electron-donor than is ascorbate.(6). It therefore seems possible that ( in primates at least ) uric acid has taken over some of the functions of ascorbate.
This suggestion is not to deny any other physiological or psychological function for uric acid, but is advanced to suggest an evolutionary mechanism for the loss of the ability to synthesize ascorbate de novo ( the latter lesion might not be very important in a fruit-eating animal except in times of famine or in the event of a change in diet. ). Any further selective advantage of higher systemic levels of uric acid would tend to establish the double lesion in the population.

Hmm.

This was before the glucose-blocking worm study, of course. The secret to our longevity is little focused bursts of mitochondrial respiration, mediated by uric acid. That's how it looks to me, anyways.