Uric acidFrom Wikipedia, the free encyclopediaJump to: navigation, searchFor the Romanian village of Uric, see Pui. Uric acid Preferred IUPAC name[hide] 7,9-Dihydro-1H-purine-2,6,8(3H)-trione Other names[hide] 2,6,8-Trioxypurine Identifiers CAS number 69-93-2 PubChem 1175 ChemSpider 1142 UNII 268B43MJ25 EC number 200-720-7 DrugBank DB01696 KEGG C00366 MeSH Uric+Acid ChEBI CHEBI:27226 ChEMBL CHEMBL792 Beilstein Reference 156158 3DMet B00094 Image 1 Jmol-3D images Image 2 SMILES [show]
InChI [show] Properties Molecular formula C5H4N4O3 Molar mass 168.1103 g mol-1 Exact mass 168.028340014 g mol-1 Appearance White crystals Melting point 300 °C, 573 K, 572 °F Solubility in water 60 mg dm-3 (at 20 °C) log P -1.107 Acidity (pKa) 5.6 Basicity (pKb) 8.4 Thermochemistry Std enthalpy of o -619.69--617.93 kJ mol-1 formation ΔfH 298 Std enthalpy of o -1.9212--1.91956 MJ mol-1 combustion ΔcH 298 Standard molar 173.2 J K-1 mol-1 entropySo298 Specific heat capacity, C 166.15 J K-1 mol-1 (at 24.0 °C) (verify) (what is: / ?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox referencesUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with theformula C5H4N4O3. It forms ions and salts known as urates and acid urates such asammonium acid urate. Uric acid is created when the body breaks down purine nucleotides.High blood concentrations of uric acid can lead to a type of arthritis known as gout. Thechemical is associated with other medical conditions like ammonium acid uratekidney stones.
Contents[hide] 1 Chemistry o 1.1 Solubility of uric acid and its salts 2 Biology 3 Genetics 4 Medicine o 4.1 High uric acid 4.1.1 Causes of high uric acid 4.1.2 Gout 4.1.3 Lesch-Nyhan syndrome 4.1.4 Cardiovascular disease 4.1.5 Type 2 Diabetes 4.1.6 Metabolic syndrome 4.1.7 Uric acid stone formation o 4.2 Low uric acid 4.2.1 Causes of low uric acid 4.2.2 Multiple sclerosis 4.2.3 Normalizing low uric acid o 4.3 Oxidative stress 5 Sources 6 References 7 Further reading 8 External links ChemistryUric acid is a diprotic acid with pKa1=5.4 and pKa2=10.3. Thus in strong alkali at high pH,it forms the dually charged full urate ion, but at biological pH or in the presence of carbonicacid or carbonate ions, it forms the singly charged hydrogen or acid urate ion as its pKa2 isgreater than the pKa1 of carbonic acid. As its second ionization is so weak, the full urate saltstend to hydrolyze back to hydrogen urate salts and free base at pH values around neutral. It isaromatic because of the purine functional group.As a bicyclic, heterocyclic purine derivative, uric acid does not protonate like carboxylicacids. X-Ray diffraction studies on the hydrogen urate ion in crystals of ammomiumhydrogen urate, formed in vivo as gouty deposits, reveal the keto-oxygen in the 2 position ofa tautomer of the purine structure exists as a hydroxyl group and the two flanking nitrogenatoms at the 1 and 3 positions share the ionic charge in the six membered pi-resonance-stabilized ring.Thus, whereas most organic acids are deprotonated by the ionization of a polar hydrogen-to-oxygen bond, usually accompanied by some form of resonance stabilization (resulting in acarboxylate ion), uric acid is deprotonated at a nitrogen atom and uses atautomericketo/hydroxy group as an electron-withdrawing group to increase the pK1 value.The five membered ring also possesses a keto group (in the 8 position), flanked by two
secondary amino groups (in the 7 and 9 positions), and deprotonation of one of these at highpH could explain the pK2 and behavior as a diprotic acid. Similar tautomeric rearrangementand pi-resonance stabilization would then give the ion some degree of stability. (On thestructure shown at the upper right, the NH at the upper right on the six membered ring is "1",counting clockwise around the six membered ring to "6" for the keto carbon at the top of thesix membered ring. The upper most NH on the five membered ring is "7", counting counterclockwise around this ring to the lower NH, which is "9".)Uric acid was first isolated from kidney stones in 1776 by Scheele. As far as laboratorysynthesis is concerned, in 1882, Horbaczewski claimed to have prepared uric acid by meltingurea hydrogen peroxide with glycine, trichlorolactic acid, and its amide. Soon after, repetitionby Eduard Hoffmann shows that this preparation with glycine gives no trace of uric acid, buttrichlorolactimide produces some uric acid. Thus, Hoffmann was the first to synthesize uricacid. Solubility of uric acid and its saltsGenerally, the water solubilitity of uric acid and its alkali metal and alkaline earth salts israther low. All these salts exhibit greater solubility in hot water than cold, allowing for easyrecrystallization. This low solubility is significant for the etiology of gout. The solubility ofthe acid and its salts in ethanol is very low or negligible. In ethanol water mixtures, thesolubilities are somewhere between the end values for pure ethanol and pure water.Compound Cold Water Boiling WaterUric Acid 15000 2000NH4HUrate - 1600LiHUrate 370 39NaHUrate 1175 124KHUrate 790 75Mg(HUrate)2 3750 160Ca(HUrate)2 603 276Na2Urate 77 -K2Urate 44 35CaUrate 1500 1440SrUrate 4300 1790BaUrate 7900 2700The figures given indicate what mass of water is required to dissolve a unit mass ofcompound indicated, the lower the number, the more soluble the substance in the saidsolvent. Biology
The enzyme xanthine oxidase makes uric acid from xanthine and hypoxanthine, which in turnare produced from purines. Xanthine oxidase is a large enzyme whose active site consists ofthe metal, molybdenum, binded to sulfur and oxygen. Within cells, xanthine oxidase canexist as xanthine dehydrogenase and xanthine oxireductase, which has also been purifiedfrom bovine milk and spleen extracts. Uric acid is released in hypoxic conditions.In humans and higher primates, uric acid is the final oxidation (breakdown) product of purinemetabolism and is excreted in urine. In most other mammals, the enzymeuricase furtheroxidizes uric acid to allantoin. The loss of uricase in higher primates parallels the similarloss of the ability to synthesize ascorbic acid, leading to the suggestion that urate maypartially substitute for ascorbate in such species. Both uric acid and ascorbic acid arestrong reducing agents (electron donors) and potent antioxidants. In humans, over half theantioxidant capacity of blood plasma comes from uric acid. The Dalmatian dog has agenetic defect in uric acid uptake by the liver and kidneys, resulting in decreased conversionto allantoin, so this breed excretes uric acid, and not allantoin, in the urine.In birds and reptiles, and in some desert dwelling mammals (e.g., the kangaroo rat), uric acidalso is the end product of purine metabolism, but it is excreted in feces as a dry mass. Thisinvolves a complex metabolic pathway that is energetically costly in comparison toprocessing of other nitrogenous wastes such as urea (from urea cycle) or ammonia, but hasthe advantage of reducing water loss.In humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5-25% ofhumans, impaired renal (kidney) excretion leads to hyperuricemia. GeneticsA proportion of people have mutations in the proteins responsible for the excretion of uricacid by the kidneys. Nine genes have so far been identified: SLC2A9; ABCG2; SLC17A1;SLC22A11; SLC22A12; SLC16A9; GCKR; LRRC16A; and PDZK1.SLC2A9 is known totransport both uric acid and fructose. MedicineIn human blood plasma, the reference range of uric acid is between 3.6 mg/dL (~214 µmol/L)and 8.3 mg/dL(~494 µmol/L) (1 mg/dL=59.48 µmol/L). This range is considered normalby the American Medical Association Manual of Style. Uric acid concentrations in bloodplasma above and below the normal range are known, respectively, as hyperuricemia andhypouricemia. Similarly, uric acid concentrations in urine above and below normal areknown as hyperuricosuria and hypouricosuria. Such abnormal concentrations of uric acid arenot medical conditions, but are associated with a variety of medical conditions.Reference ranges for blood tests, comparing blood content of uric acid (shown in yellow)with other constituents
 High uric acidHigh levels of uric acid is called hyperuricemia. Causes of high uric acid In many instances, people have elevated uric acid levels for hereditary reasons. Diet may be a factor. High intake of dietary purine as well as fructose (and table sugar which is roughly 50% fructose) can cause increased levels of uric acid. Serum uric acid can be elevated due to reduced excretion by the kidneys. Fasting or rapid weight loss can temporarily elevate uric acid levels. Iron (Fe) activates xanthine oxidase (XO) and copper (Cu) deactivates it, so as men accumulate Fe with age (ferritin levels rise above 45 ng/dl) and Cu levels decline as testosterone levels drop with age (testosterone increases Cu half life), eventually the high Fe/Cu results in more active XO and higher urate levels. Excess Fe can be eliminated through phlebotomy (blood donation) and low Cu can be corrected through daily intake of 2 mg Cu per day, reducing urate levels. GoutExcess serum accumulation of uric acid can lead to a type of arthritis known as gout. Thispainful condition is the result of needle-like crystals of uric acid precipitating in joints andcapillaries. Kidney stones can also form through the formation and deposition of sodiumurate microcrystals.It has also been found that men who drank two or more sugar-sweetened beverages a dayhave an 85% higher chance of developing gout than those who drank such beveragesinfrequently.Gout can occur where serum uric acid levels are as low as 6 mg/dL (~357 µmol/L), but anindividual can have serum values as high as 9.6 mg/dL (~565 µmol/L) and not have gout.One treatment for gout, in the 19th century, had been administration of lithium salts;lithium urate is more soluble. Today, inflammation during attacks is more commonly treatedwith NSAIDs, and urate levels are managed with allopurinol. Allopurinol, developed over30 years ago by Elion et al., weakly inhibits xanthine oxidase. It is an analog of hypoxanthinethat is hydroxylated by xanthine oxireductase at the 2-position to give oxipurinol. Oxipurinolhas been supposed to bind tightly to the reduced molybdenum ion in the enzyme and thusinhibits uric acid synthesis. Lesch-Nyhan syndromeLesch-Nyhan syndrome, an extremely rare inherited disorder, is also associated with veryhigh serum uric acid levels. Spasticity, involuntary movement and cognitive retardation aswell as manifestations of gout are seen in cases of this syndrome.
 Cardiovascular diseaseAlthough uric acid can act as an antioxidant, excess serum accumulation is often associatedwith cardiovascular disease. It is not known whether this is causative (e.g., by acting as aprooxidant ) or a protective reaction taking advantage of urates antioxidant properties.The same may account for the putative role of uric acid in the etiology of stroke. Type 2 DiabetesThe association of high serum uric acid with insulin resistance has been known since theearly part of the 20th century, nevertheless, recognition of high serum uric acid as a riskfactor for diabetes has been a matter of debate. In fact, hyperuricemia has always beenpresumed to be a consequence of insulin resistance rather than its precursor. However, aprospective follow-up study showed high serum uric acid is associated with higher risk oftype 2 diabetes, independent of obesity, dyslipidemia, and hypertension. Metabolic syndromeHyperuricemia is associated with components of metabolic syndrome. A study has suggestedfructose-induced hyperuricemia may play a pathogenic role in the metabolic syndrome.This is consistent with the increased consumption in recent decades of fructose-containingbeverages (such as fruit juices and soft drinks sweetened with sugar and high-fructose cornsyrup) and the epidemic of diabetes and obesity. Uric acid stone formationSaturation levels of uric acid in blood may result in one form of kidney stones when the uratecrystallizes in the kidney. These uric acid stones are radiolucent and so do not appear on anabdominal plain X-ray. Their presence must be diagnosed by ultrasound for this reason. Verylarge stones may be detected on X-ray by their displacement of the surrounding kidneytissues.Uric acid stones, which form in the absence of secondary causes such as chronic diarrhea,vigorous exercise, dehydration, and animal protein loading, are felt to be secondary to obesityand insulin resistance seen in metabolic syndrome. Increased dietary acid leads to increasedendogenous acid production in the liver and muscles, which in turn leads to an increased acidload to the kidneys. This load is handled more poorly because of renal fat infiltration andinsulin resistance, which are felt to impair ammonia excretion (a buffer). The urine istherefore quite acidic, and uric acid becomes insoluble, crystallizes and stones form. Inaddition, naturally present promoter and inhibitor factors may be affected. This explains thehigh prevalence of uric stones and unusually acidic urine seen in patients with type 2 diabetes.Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seedcrystals" (heterogeneous nucleation). Low uric acid Causes of low uric acidLow uric acid (hypouricemia) can have numerous causes.
Low dietary zinc intakes cause lower uric acid levels. This effect can be even morepronounced in women taking oral contraceptive medication.Xanthine oxidase is an Fe-Mo enzyme, so people with Fe deficiency (the most commoncause of anemia in young women) or Mo deficiency can experience hypouricemia.Xanthine oxidase loses its function and gains ascorbase function when some of the Fe atomsin XO are replaced with Cu atoms. Accordingly, people with high Cu/Fe can experiencehypouricemia and vitamin C deficiency, resulting in oxidative damage. Since estrogenincreases the half life of Cu, women with very high estrogen levels and intense blood lossduring menstruation are likely to have a high Cu/Fe and present with hypouricemia.Sevelamer, a drug indicated for prevention of hyperphosphataemia in patients with chronicrenal failure, can significantly reduce serum uric acid. Multiple sclerosisLower serum values of uric acid have been associated with multiple sclerosis (MS). MSpatients have been found to have serum levels ~194 µmol/L, with patients in relapseaveraging ~160 µmol/L and patients in remission averaging ~230 µmol/L. Serum uric acid inhealthy controls was ~290 µmol/L. Conversion factor: 1 mg/dL=59.48 µmol/LA 1998 study completed a statistical analysis of 20 million patient records, comparing serumuric acid values in patients with gout and patients with multiple sclerosis. Almost no overlapbetween the groups was found.Uric acid has been successfully used in the treatment and prevention of the animal (murine)model of MS. A 2006 study found elevation of serum uric acid values in multiple sclerosispatients, by oral supplementation with inosine, resulted in lower relapse rates, and no adverseeffects. Normalizing low uric acidCorrecting low or deficient zinc levels can help elevate serum uric acid.Inosine can beused to elevate uric acid levels. Zn inhibits Cu absorption, helping to reduce the highCu/Fe in some people with hypouricemia. Fe supplements can ensure adequate Fe reserves(ferritin above 25 ng/dl), also correcting the high Cu/Fe. Oxidative stressUric acid may be a marker of oxidative stress, and may have a potential therapeutic role asan antioxidant. On the other hand, like other strong reducing substances such as ascorbate,uric acid can also act as a prooxidant, particularly at elevated levels. Thus, it is unclearwhether elevated levels of uric acid in diseases associated with oxidative stress such as strokeand atherosclerosis are a protective response or a primary cause.For example, some researchers propose hyperuricemia-induced oxidative stress is a cause ofmetabolic syndrome. On the other hand, plasma uric acid levels correlate with longevityin primates and other mammals. This is presumably a function of urates antioxidantproperties.
 Sources In humans, purines are excreted as uric acid. Purines are found in high amounts in animal food products, such as liver and sardines. A moderate amount of purine is also contained in beef, pork, poultry, fish and seafood, asparagus, cauliflower, spinach, mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat bran and wheat germ. Examples of high purine and Fe sources include: sweetbreads, anchovies, sardines, liver, beef kidneys, brains, meat extracts (e.g., Oxo, Bovril), herring, mackerel, scallops, game meats, and gravy. Moderate intake of purine-containing food is not associated with an increased risk of gout.HyperuricemiaFrom Wikipedia, the free encyclopediaJump to: navigation, searchNot to be confused with hypouricemia. Asymptomatic hyperuricemia Classification and external resources Uric acid ICD-10 E79.0 ICD-9 790.6 DiseasesDB 5375 eMedicine med/1112
MeSH D033461Hyperuricemia (British English: hyperuricaemia) is a level of uric acid in the blood that isabnormally high. In humans, the upper end of the normal range is 360 µmol/L (6 mg/dL) forwomen and 400 µmol/L (6.8 mg/dL) for men.Contents[hide] 1 Causes o 1.1 Increased production o 1.2 Decreased excretion o 1.3 Mixed o 1.4 Unclassified 2 Treatment o 2.1 Concentration o 2.2 pH o 2.3 Temperature 3 Prognosis 4 Dalmatian dogs 5 Genetics 6 History 7 See also 8 References 9 External links CausesMany factors contribute to hyperuricemia, including: genetics, insulin resistance,hypertension, renal insufficiency, obesity, diet, use of diuretics, and consumption of alcoholicbeverages. Of these, alcohol consumption is the most important.Causes of hyperuricemia can be classified into three functional types: increased productionof uric acid, decreased excretion of uric acid, and mixed type. Causes of increased productioninclude high levels of purine in the diet and increased purine metabolism. Causes ofdecreased excretion include kidney disease, certain drugs, and competition for excretionbetween uric acid and other molecules. Mixed causes include high levels of alcohol and/orfructose in the diet, and starvation. Increased productionA purine-rich diet is a common but minor cause of hyperuricemia. Diet alone generally is notsufficient to cause hyperuricemia. Purine content of foods varies (see Gout). Foods high inthe purines adenine and hypoxanthine may be more potent in exacerbating hyperuricemia.
Hyperuricemia of this type is a common complication of solid organ transplant. Apart fromnormal variation (with a genetic component), tumor lysis syndrome produces extreme levelsof uric acid, mainly leading to renal failure. The Lesch-Nyhan syndrome is also associatedwith extremely high levels of uric acid. Decreased excretionThe principal drugs that contribute to hyperuricemia by decreased excretion are the primaryantiuricosurics. Other drugs and agents include diuretics, salicylates, pyrazinamide,ethambutol, nicotinic acid, ciclosporin, 2-ethylamino-1,3,4-thiadiazole, and cytotoxicagents.The gene SLC2A9 encodes a protein that helps to transport uric acid in the kidney. Severalsingle nucleotide polymorphisms of this gene are known to have a significant correlation withblood uric acid.A ketogenic diet impairs the ability of the kidney to excrete uric acid, due to competition fortransport between uric acid and ketones.Elevated blood lead is significantly correlated with both impaired kidney function andhyperuricemia (although the causal relationship among these correlations is not known). In astudy of over 2500 people resident in Taiwan, a blood lead level exceeding 7.5 microg/dL (asmall elevation) had odds ratios of 1.92 (95% CI: 1.18-3.10) for renal dysfunction and 2.72(95% CI: 1.64-4.52) for hyperuricemia. MixedCauses of hyperuricemia that are of mixed type have a dual action, both increasingproduction and decreasing excretion of uric acid.High intake of alcohol (ethanol), a significant cause of hyperuricemia, has a dual action thatis compounded by multiple mechanisms. Ethanol increases production of uric acid byincreasing production of lactic acid, hence lactic acidosis. Ethanol also increases the plasmaconcentrations of hypoxanthine and xanthine via the acceleration of adenine nucleotidedegradation, and is a possible weak inhibitor of xanthine dehydrogenase. As a byproduct ofits fermentation process, beer additionally contributes purines. Ethanol decreases excretion ofuric acid by promoting dehydration and (rarely) clinical ketoacidosis.High dietary intake of fructose contributes significantly to hyperuricemia. In a largestudy in the United States, consumption of four or more sugar-sweetened soft drinks per daygave an odds ratio of 1.82 for hyperuricemia. Increased production of uric acid is the resultof interference, by a product of fructose metabolism, in purine metabolism. This interferencehas a dual action, both increasing the conversion of ATP to inosine and hence uric acid andincreasing the synthesis of purine. Fructose also inhibits the excretion of uric acid,apparently by competing with uric acid for access to the transport protein SLC2A9. Theeffect of fructose in reducing excretion of uric acid is increased in people with a hereditary(genetic) predisposition toward hyperuricemia and/or gout.Starvation causes the body to metabolize its own (purine-rich) tissues for energy. Thus, like ahigh purine diet, starvation increases the amount of purine converted to uric acid. A very low
calorie diet without carbohydrate can induce extreme hyperuricemia; including somecarbohydrate (and reducing the protein) reduces the level of hyperuricemia. Starvation alsoimpairs the ability of the kidney to excrete uric acid, due to competition for transport betweenuric acid and ketones. Unclassified Phosphofructokinase deficiency TreatmentPrecipitation of uric acid crystals, and conversely their dissolution, is known to be dependenton the concentration of uric acid in solution, pH, sodium concentration, and temperature.Established treatments address these parameters. ConcentrationFollowing Le Chateliers principle, lowering the blood concentration of uric acid may permitany existing crystals of uric acid to be gradually dissolved into the blood, from whence thedissolved uric acid can be excreted. Maintaining a lower blood concentration of uric acidsimilarly should reduce the formation of new crystals. If the person has chronic gout orknown tophi, then large quantities of uric acid crystals may have accumulated in joints andother tissues, and aggressive and/or long duration use of medications may be needed.Medications most often used to treat hyperuricemia are of two kinds: xanthine oxidaseinhibitors and uricosurics. Xanthine oxidase inhibitors decrease the production of uric acid,by interfering with xanthine oxidase. Uricosurics increase the excretion of uric acid, byreducing the reabsorption of uric acid once the kidneys have filtered it out of the blood. Someof these medications are used as indicated, others are used off-label. Several other kinds ofmedications have potential for use in treating hyperuricemia. In people receivinghemodialysis, sevelamer can significantly reduce serum uric acid, apparently byadsorbing urate in the gut. In women, use of combined oral contraceptive pills issignificantly associated with lower serum uric acid.Non-medication treatments for hyperuricemia include a low purine diet (see Gout) and avariety of dietary supplements. These treatments are regarded by many physicians as havinglittle or no efficacy. Treatment with lithium salts has been used as lithium improves uric acidsolubility. pHSerum pH is neither safely or easily altered. Therapies that alter pH principally alter the pHof urine, to discourage a possible complication of uricosuric therapy: formation of uric acidkidney stones due to increased uric acid in the urine (see Nephrolithiasis). Dietarysupplements that can be used to make the urine more alkaline include sodium bicarbonate,potassium citrate, magnesium citrate, and Shohls Solution (now replaced by Bicitra).Medications that have a similar effect include acetazolamide. Temperature
Low temperature is a commonly reported trigger of acute gout: an example would be a dayspent standing in cold water, followed by an attack of gout the next morning. This is believedto be due to temperature-dependent precipitation of uric acid crystals in tissues at belownormal temperature. Thus, one aim of prevention is to keep the hands and feet warm, andsoaking in hot water may be therapeutic. PrognosisIncreased levels predispose for gout and, if very high, renal failure. The metabolic syndromeoften presents with hyperuricemia.Persons with gout, and by inference hyperuricemia, are significantly less likely to developParkinsons disease, unless they also require diuretics. Dalmatian dogsIn Dalmatian dogs, a lack of uricase (a genetic trait fixed in this breed) contributes tohyperuricemia and corresponding hyperuricosuria. GeneticsHyperuricemiacosegregating with osteogenesisimperfecta has been shown to be associatedwith a mutation in GPATCH8 using exomesequencingHypouricemiaFrom Wikipedia, the free encyclopediaJump to: navigation, searchNot to be confused with Hyperuricemia. Hypouricemia Classification and external resources Uric acid
DiseasesDB 21432Hypouricemia is a level of uric acid in blood serum that is below normal. In humans, thenormal range of this blood component has a lower threshold set variously in the range of2 mg/dL to 4 mg/dL, while the upper threshold is 530 micromol/L (6 mg/dL) for women and619 micromol/L (7 mg/dL) for men.Hypouricemia usually is benign and sometimes is asign of a medical condition.Contents[hide] 1 Causes o 1.1 Medication o 1.2 Diet o 1.3 Genetics o 1.4 Medical conditions 2 Prevalence 3 Diagnosis 4 Treatment o 4.1 Drugs and dietary supplements that may be helpful 5 Complications 6 See also 7 References CausesHypouricemia is not a medical condition itself (i.e., it is benign), but it is a useful medicalsign. Usually hypouricemia is due to drugs and toxic agents, sometimes it is due to diet orgenetics, and rarely it is due to an underlying medical condition. When one of these causalmedical conditions is present, hypouricemia is a common sign. MedicationThe majority of drugs that contribute to hypouricemia are uricosurics (drugs that increase theexcretion of uric acid from the blood into the urine). Others include drugs that reduce theproduction of uric acid: xanthine oxidase inhibitors, urate oxidase (rasburicase), andsevelamer. DietHypouricemia is common in vegetarians due to the low purine content of most vegetariandiets. Vegetarian diet has been found to result in mean serum uric acid values as low as 239µmol/L (2.7 mg/dL). While a vegetarian diet is typically seen as beneficial with respect to
conditions such as gout, care should be taken to avoid associated health conditions.[citationneeded]Transient hypouricemia sometimes is produced by total parenteral nutrition. Paradoxically,total parenteral nutrition may produce hypouricemia followed shortly by acute gout, acondition normally associated with hyperuricemia. The reasons for this are unclear. GeneticsGenetic mutations known to cause hypouricemia are of two kinds: mutations causingxanthine oxidase deficiency, which reduces the production of uric acid; and mutationscausing abnormal kidney function that increases the excretion of uric acid. Collectivelyknown as familial renal hypouricemia, these latter mutations are of two types, involvingdefects of presecretory and postsecretory reabsorption.A genetic mutation in Dalmatian dogs causes hypouricemia due to a kidney defect thatinterferes with reabsorption of uric acid. A similar mutation has been reported in a humanbrother and sister.In humans, loss-of-function mutations in the gene URAT1 are associated with presecretoryreabsorption defects. Medical conditionsMedical conditions that can cause hypouricemia include: Fanconi syndrome Hyperthyroidism Multiple Sclerosis Myeloma Nephritis Wilsons disease PrevalenceIn one study, hypouricemia was found in 4.8% of hospitalized women and 6.5% ofhospitalized men. (The definition was less than 0.14 mmol l-1 for women and less than0.20 mmol l-1 in men.)  DiagnosisUric acid clearance should also be performed, increase in clearance points to proximal tubulardefects in the kidney, normal or reduced clearance points to a defect in xanthine oxidase. TreatmentIdiopathichypouricemia usually requires no treatment. In some cases, hypouricemia is amedical sign of an underlying condition that does require treatment. For example, if
hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria) with its riskof uric acid nephrolithiasis, the hyperuricosuria may require treatment. Drugs and dietary supplements that may be helpful Inositol Antiuricosurics ComplicationsAlthough normally benign, idiopathic renal hypouricemia may increase the risk of exercise-induced acute renal failure.What diet is recommended for high uric acid?Wednesday, 30 June 2010Answered by: Ms. Puja GandhiNutrition ConsultantDubai192Share Q. My 58 years old husband has high homocystine levels and the uric acid is 6.9 and bloodpressure is 130/90 mmHg. He takes Tozzar 50 and Metilda plus. Please suggest which fruits andvegetables he should avoid and which oil is safe for him?A. Purines are organic compounds, which create uric acid [photo gallery] on breakdown in the body.While your body needs uric acid for blood vessel health and other processes, a buildup of excess uricacid can lead to gout, diabetes and even cardiovascular disease. Purines consumed in the dietaccount for about 50 percent of the uric acid produced in the body. Therefore, avoiding foods high inpurines or following a modified purine diet may help improve uric acid levels.General guidelines are -Restrict meat/fish/poultry intakeAvoid alcohol and processed foods
Lose weight if overweightExercise regularlyDrink 8-10 glasses of water a dayEat plenty of fruits & vegetablesRestrict foods high in purines -Organ meats such as liver, kidney, heartSelected fish and shellfishMeat & yeast extracts brewers and bakers yeastMeat soups & stock cubesRecommended foods to eat -Fresh cherries, strawberries, blueberries and other red-blue berriesBananasCeleryTomatoesVegetables including cabbage and parsleyFoods high in bromelain (pineapple)Foods high in vitamin C (red cabbage, red bell peppers, tangerines, mandarins, oranges, potatoes)Low-fat dairy productsComplex carbohydrates (breads, cereals)Chocolate, cocoaCoffee, tea
Since purines are found in so many foods, it’s important to understand that not all purine-sourcefoods affect the body in the same way. For instance, although purines are found in vegetablesources, these purines dont cause the same amount of uric acid buildup in the body that meatsources do. In fact, fresh fruits and vegetables reduce acid levels in the body and it is often advisedto avoid red meats, organ meats and highly processed foods. Fresh fruits and vegetables areencouraged so the patient can increase alkalinity in the blood. Therefore, rather than attempting tofind foods that are free of purines and uric acid, its important to know how to increase the body’salkalinity, which naturally reduces the body’s acidity. Fresh, non-processed foods, such as fruits andvegetables, are the way to go.Being overweight appears to be the most common determining factor for excess uric acidproduction. Therefore, it is very important to maintain a healthy weight. Consider the calorific valueof the foods that do not contain purines and aim to eat a healthy well-balanced diet. Fatty foodssuch as butter and cream should be avoided. When you begin to lose weight, the kidneys are moreable to eliminate uric acid and in some cases, the production of uric acid by the liver is also reduced.Read more at:http://doctor.ndtv.com/faq/ndtv/fid/13620/What_diet_is_recommended_for_high_uric_acid.html?cpWhat Causes High Uric Acid?X Marcie FitzmauriceMarcie Fitzmaurice is a copywriter, editor and proofreader from Chicago,Illinois with 10 years experience. Her work has appeared in newspapers, web sites, catalogs, printadvertisements, direct mail pieces and more. Fitzmaurice has a Bachelor of Arts degree in Englishfrom Augustana College in Rock Island, Illinois.By Marcie Fitzmaurice, eHow ContributorPrint this articleHyperuricemia results when excessive amounts of uric acid are present in a personsbloodstream. In healthy individuals, uric acid flows through the liver and into the bloodstream,where it is either excreted in urine, or passed through the intestines to regulate levels.Hyperuricemia may result from either poor lifestyle habits or because of other medical ailments ortreatments for such conditions. Gout and kidney stones are two medical ailments that can result
from high uric acid levels. Normal uric acid levels for women should be between 2.4 and 6.0 mg/dL,while mens levels should be between 3.4 and 7.0 mg/dL.Related Searches:Causes of Acid RefluxHigh Blood Glucose Levels Dehydration and Kidney FunctionWhen water and other fluids arent consumed in adequate amounts, the kidneys wont functionproperly. Uric acid wont be removed from the blood through excretion, and will build up inabnormally high amounts. To prevent dehydration and keep the kidneys working as they should, youought to drink water throughout the day, and particularly when exercising or if temperatures are hot.Purine-Rich FoodPurines, which are nitrogen-containing compounds, are either made inside the cells of the body, orbrought into the body with food. Excess purines can cause elevated levels of uric acid, which mayaccumulate in tissues and form crystals, thus causing high uric acid levels in the blood. Foods high inpurines, including organ and red meats, and some seafood, should be eaten in moderation, oreliminated completely, to keep uric acid levels in balance.Excessive Alcohol ConsumptionAlcohol, and especially beer and wine, can increase uric acid levels. In order to stabilize uric acid inthe bloodstream, you may need to eliminate alcohol.MedicationsCertain medications, such as those used to treat high blood pressure, as well as aspirin, vitamin Cand niacin among others, can produce high levels of uric acid. Chemotherapy for the treatment ofcancer can also be a cause.CancerCertain cancers like non-Hodgkins lymphoma, Hodgkins lymphoma, leukemia and other medicalconditions, like sickle cell anemia and heart failure can cause increased breakdown of body cells andresult in hyperuricemia.Obesity
Obesity can cause excessive amounts of weight to fall on the kidneys, and prevent them fromfunctioning properly. Losing excess weight and maintaining a healthy weight can preventhyperuricemia.Read more: What Causes High Uric Acid? | eHow.comhttp://www.ehow.com/about_5195926_causes-high-uric-acid_.html#ixzz1jE3FrhQoUric Acid Diet - 9 SecretsTo Treat Gout NaturallyGout is one of the most painful things you can have in your life. It affects mainly the distal ends ofyour joints like the fingers, foot, knee and toes. Some of the symptoms of gout are swelling, unableto put all your weight on your leg, burning pain, redness, stiffness and plenty other nasty things.Gout is caused by the accumulation of crystals of monosodium urate (MSU) and/or uric acid withinthe surrounding tendons, tissues and cartilage of the joint. In order to control and prevent gout fromoccurring, you need to have a uric acid diet.If there is too much uric acid in the joint, it will cause acute inflammation of the joint. If you don’ttreat it fast enough, the gout can become chronic and can cause severe and permanent damage tothe surrounding tissues.The uric acid is a by-product of purine metabolism. That is, purines are formed due to thebreakdown of particular type of foods in your body. Furthermore, it is evident that two thirds ofpurine production occurs in the kidneys and the rest are formed by the liver. Everyone have purinesin the body but people will gout has an excess amount of them. As a result, a uric acid diet is focusedon reducing the amount of purines within the body.Here are several things you need to eat or avoid if you on a uric acid diet:1. Proteins contain bucket loads of purines in them. They are most abundant in dark meat such asvenison, beef and seafood. According to a large and respected study, it states that if you have a highconsumption of seafood and/or meat, the changes of having gout is 41% and 50%. Furthermore,shellfish like scallop, lobster, oyster, clam, and shrimp will have more purine levels than normal fish.Any offals like liver or brain should also be avoided.
2. Vegetables that is high in protein. The above study also implicated that vegetable that has highprotein level and/or is dark green leafy vegetable have more purine concentration than any othervegetables. These can include cauliflower, spinach, mushrooms and asparagus.3. Eat more dairy products like milk or yogurt. Not only these are good for your bones, they have lowamounts of purine levels. In fact, studies have suggested that eating more dairy products reducesthe chances of you having gout by 44%!4. Drink less soft drinks or anything with high sugar content. This is one of the major causes of goutand if you drink two or more soft drink a day, you will have an 85% risk of getting gout than a personwho drinks just once a month. We are always hearing about how bad soft drinks are for your teethbut it can also cause other problems such as gout and obesity.5. Drink less beer and spirits. I know it’s hard to hear this, but drinking beer causes a significant riskin getting gout. If you drink a normal can of beer every day (around about 345ml or 12 oz), you willhave a 49% increase of risk.6. Any sweets that have high fructose level like candy, jelly and jam.7. Drink plenty of water. Drinking more water will help your body filtrate the purines out of yourbody. However, do not drink energy drinks like Gatorade as these have high fructose and thereforehigh purine levels.8. Any food that contains celery extracts or you can get them in a form of a capsule from your healthfood shop. Celery is a natural anti-inflammatory. It also reduces the uric acid levels in the body.9. New studies have suggested that tart cherries can be beneficial in preventing and treating gout. Itworks by dissolving sharp edgy urine crystals within the joints.Gout Diet - Foods to AvoidWhich Items Should You Scratch from Your Grocery List?By Carol Eustice, About.com GuideUpdated June 27, 2011
About.com Healths Disease and Condition content is reviewed by the Medical Review Board.See More About:goutdietgout foods to eatgoutpreventiongouttreatmentsgoutAdsCongress on AutoimmunitySpain | 9-13 May, 2012 Register Now and Save up to €175!www.kenes.com/autoimmunityHow to Treat a Sore KneeSafe simple solution you can wear comfortable, washable SoothingTherapySocks.com/knee-pain.htmlJapan No1 slimming secret3 days lose 3 kg, Fast, Natural & Effective. Made in Japani-slim.netArthritis & Joint Conditions Ads•Arthritis•Gout Treatment•Uric Acid Gout•Gout Diet•Gout Foods to AvoidAdsHypno-Counselling KLHypnotherapy &Counselling for all ailments.Fast cure.012 3300413.www.asiahypnosis.comDo You Suffer From Gout?
Stop the pain and prevent outbreaks fast with this effective method.AttackGout.comDiets that are high in purines and high in protein have long been suspected of causing an increasedrisk of gout -- a type of arthritis caused by high levels of uric acid in the body. Excessive uric acid canform crystals in the joints, causing pain and inflammation). Results from a study led by Dr. Hyon K.Choi, reported in the March 11, 2004 issue of The New England Journal of Medicine, offer aninteresting twist.About the StudyChois research team followed 47,150 men with no prior history of gout over a 12-year period.During that time, 730 men were diagnosed with gout. Study participants who consumed the highestamount of meat were 40 percent more likely to have gout than those who ate the least amount ofmeat. Study participants who ate the most seafood were 50 percent more likely to have gout.In this specific study, though, not all purine-rich foods were associated with an increased risk of gout.There was no increased risk associated with a diet that included:•peas•beans•mushrooms•cauliflower•spinachThese foods are considered high in purines. Chois team also found that low-fat dairy productsdecrease the risk of gout, and overall protein intake had no effect. Ultimately, diets shown to beconnected to gout are the same kinds of diet linked to cardiovascular disease.•The Gout Diet QuizRecommendations for Seafood Should Be IndividualizedAt this point, it may seem things are getting confusing. Isnt seafood typically recommended as partof a diet which is healthy for the heart? Yet research has revealed that there is a strong, undeniablelink between seafood and gout. How does Choi reconcile what seems like conflicting information?He believes "recommendations for seafood should be individualized."Sorting Out the Myths
More importantly, how does a person begin to sort the myths from the facts and decide what to buyat the grocery store? According to the University of Washington, Department of Orthopedics:•Obesity can be linked to high uric acid levels in the blood. People who are overweight shouldconsult with their doctor to decide on a reasonable weight-loss program. Fasting or severe dietingcan actually raise uric acid levels and cause gout to worsen.•Usually people can eat what they like within limits. People who have kidney stones due to uric acidmay need to actually eliminate purine-rich foods from their diet because those foods can raise theiruric acid level.•Consuming coffee and tea is not a problem, but alcohol can raise uric acid levels and provoke anepisode of gout. Drinking at least 10 to 12 eight-ounce glasses of non-alcoholic fluids every day isrecommended, especially for people with kidney stones, to help flush the uric acid crystals from thebody.Foods Higher in PurinesJohns Hopkins lists foods that are higher in purines:•hearts•herring•mussels•yeast•smelt•sardines•sweetbreadsFoods moderately high in purines include:•anchovies•grouse•mutton•veal•bacon•liver•salmon
•turkey•kidneys•partridge•trout•goose•haddock•pheasant•scallopsGout MedicationsMayo Clinic experts suggest that medications for gout have reduced the need for dietary restrictions,but some modifications can decrease the severity or frequency of gout attacks. Dietary modificationmay also be preferred by people who cannot tolerate gout medicationsGoutFrom Wikipedia, the free encyclopediaJump to: navigation, search "Podagra" redirects here. For the moth genus, see Podagra (moth). Gout Classification and external resources Gout, a 1799 caricature by James Gillray ICD-10 M10 ICD-9 274.00274.1274.8274.9
OMIM 138900300323 DiseasesDB 29031 MedlinePlus 000422 eMedicine emerg/221med/924med/1112oph/506orthoped/124radio/313 MeSH D006073Gout (also known as podagra when it involves the big toe) is a medical conditionusually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender,hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the mostcommonly affected (approximately 50% of cases). However, it may also present as tophi,kidney stones, or urate nephropathy. It is caused by elevated levels of uric acid in theblood which crystallizes and the crystals are deposited in joints, tendons, and surroundingtissues.Diagnosis is confirmed clinically by the visualization of the characteristic crystals in jointfluid. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, orcolchicine improves symptoms. Once the acute attack has subsided, levels of uric acid areusually lowered via lifestyle changes, and in those with frequent attacks allopurinol orprobenecid provide long-term prevention.Gout has increased in frequency in recent decades affecting approximately one to twopercent of the Western population at some point in their lives. The increase is believed tobe due to increasing risk factors in the population, such as metabolic syndrome, longerlife expectancy and changes in diet. Gout was historically known as "the disease ofkings" or "rich mans disease".Contents[hide] 1 Signs and symptoms 2 Cause o 2.1 Lifestyle o 2.2 Genetics o 2.3 Medical conditions o 2.4 Medication 3 Pathophysiology 4 Diagnosis o 4.1 Synovial fluid o 4.2 Blood tests
o 4.3 Differential diagnosis 5 Prevention 6 Treatment o 6.1 NSAIDs o 6.2 Colchicine o 6.3 Steroids o 6.4 Pegloticase o 6.5 Prophylaxis 7 Prognosis 8 Epidemiology 9 History 10 In other animals 11 Research 12 References 13 External links Signs and symptomsGout presenting in the metatarsal-phalangeal joint of the big toe. Note the slight rednessof the skin overlying the joint.Gout can present in a number of ways, although the most usual is a recurrent attack ofacute inflammatory arthritis (a red, tender, hot, swollen joint). The metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half ofcases. Other joints, such as the heels, knees, wrists and fingers, may also be affected.Joint pain usually begins over 2–4 hours and during the night. The reason for onset atnight is due to the lower body temperature then. Other symptoms that may occur alongwith the joint pain include fatigue and a high fever.Long-standing elevated uric acid levels (hyperuricemia) may result in othersymptomatology, including hard, painless deposits of uric acid crystals known as tophi.Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels ofuric acid may also lead to crystals precipitating in the kidneys, resulting in stoneformation and subsequent urate nephropathy. Cause
Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons,including diet, genetic predisposition, or underexcretion of urate, the salts of uric acid.Renal underexcretion of uric acid is the primary cause of hyperuricemia in about 90% ofcases, while overproduction is the cause in less than 10%. About 10% of people withhyperuricemia develop gout at some point in their lifetimes. The risk, however, variesdepending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L(7 and 8.9 mg/dL), the risk is 0.5% per year, while in those with a level greater than535 μmol/L (9 mg/dL), the risk is 4.5% per year. LifestyleDietary causes account for about 12% of gout, and include a strong association with theconsumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other triggersinclude physical trauma and surgery. Recent studies have found dietary factors oncebelieved to be associated are, in fact, not; including the intake of purine-rich vegetables(e.g., beans, peas, lentils, and spinach) and total protein. The consumption of coffee,vitamin C and dairy products as well as physical fitness appear to decrease therisk. This is believed to be partly due to their effect in reducing insulinresistance. GeneticsThe occurrence of gout is partly genetic, contributing to about 60% of variability in uricacid level. Two genes called SLC2A9 and ABCG2 have been found to commonly beassociated with gout and variations in them can approximately double the risk. A fewrare genetic disorders, including familial juvenile hyperuricemic nephropathy, medullarycystic kidney disease, phosphoribosylpyrophosphatesynthetasesuperactivity, andhypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhansyndrome, are complicated by gout. Medical conditionsGout frequently occurs in combination with other medical problems. Metabolic syndrome,a combination of abdominal obesity, hypertension, insulin resistance and abnormal lipidlevels occurs in nearly 75% of cases. Other conditions that are commonly complicatedby gout include: polycythemia, lead poisoning, renal failure, hemolytic anemia, psoriasis,and solid organ transplants. A body mass index greater than or equal to 35 increasesa males risk of gout threefold. Chronic lead exposure and lead-contaminated alcoholare risk factors for gout due to the harmful effect of lead on kidney function.Lesch-Nyhan syndrome is often associated with gouty arthritis. MedicationDiuretics have been associated with attacks of gout. However, a low dose ofhydrochlorothiazide does not seem to increase the risk. Other medicines that have beenassociated include niacin and aspirin (acetylsalicylic acid). The immunosuppressivedrugsciclosporin and tacrolimus are also associated with gout, the former particularlywhen used in combination with hydrochlorothiazide.
 PathophysiologyUric acidGout is a disorder of purine metabolism, and occurs when its final metabolite, uric acid,crystallizes in the form of monosodium urate, precipitating in joints, on tendons, and inthe surrounding tissues. These crystals then trigger a local immune-mediatedinflammatory reaction with one of the key proteins in the inflammatory cascade beinginterleukin 1β. An evolutionary loss of uricase, which breaks down uric acid, in humansand higher primates is what has made this condition so common.The triggers for precipitation of uric acid are not well understood. While it maycrystallize at normal levels, it is more likely to do so as levels increase. Other factorsbelieved to be important in triggering an acute episode of arthritis include cooltemperatures, rapid changes in uric acid levels, acidosis, articular hydration, andextracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate.The increased precipitation at low temperatures partly explains why the joints in the feetare most commonly affected. Rapid changes in uric acid may occur due to a number offactors, including trauma, surgery, chemotherapy, diuretics, and stopping or startingallopurinol. DiagnosisGout on X-rays of a left foot.Typical location at the big toe joint. Note also the soft tissueswelling at the lateral border of the foot.
Spiked rods of uric acid (MSU) crystals from a synovial fluid sample photographed undera microscope with polarized light. Formation of uric acid crystals in the joints isassociated with gout.Gout may be diagnosed and treated without further investigations in someone withhyperuricemia and the classic podagra. Synovial fluid analysis should be done, however,if the diagnosis is in doubt.X-rays, while useful for identifying chronic gout, have littleutility in acute attacks. Synovial fluidA definitive diagnosis of gout is based upon the identification of monosodium urate(MSU) crystals in synovial fluid or a tophus. All synovial fluid samples obtained fromundiagnosed inflamed joints should be examined for these crystals. Under polarizedlight microscopy, they have a needle-like morphology and strong negative birefringence.This test is difficult to perform, and often requires a trained observer. The fluid mustalso be examined relatively quickly after aspiration, as temperature and pH affect theirsolubility. Blood testsHyperuricemia is a classic feature of gout; gout occurs, however, nearly half of the timewithout hyperuricemia, and most people with raised uric acid levels never developgout. Thus, the diagnostic utility of measuring uric acid level islimited.Hyperuricemia is defined as a plasmaurate level greater than 420 μmol/L(7.0 mg/dL) in males and 360 μmol/L (6.0 mg/dL) in females. Other blood testscommonly performed are white blood cell count, electrolytes, renal function, anderythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR maybe elevated due to gout in the absence of infection. A white blood cell count as highas 40.0×109/L (40,000/mm3) has been documented. Differential diagnosisThe most important differential diagnosis in gout is septic arthritis. This should beconsidered in those with signs of infection or those who do not improve with treatment.To help with diagnosis, a synovial fluid Gram stain and culture may be performed.Other conditions which present similarly include pseudogout and rheumatoid arthritis.Gouty tophi, in particular when not located in a joint, can be mistaken for basal cellcarcinoma, or other neoplasms.
 PreventionBoth lifestyle changes and medications can decrease uric acid levels. Dietary and lifestylechoices that are effective include reducing intake of food such as meat and seafood,consuming adequate vitamin C, limiting alcohol and fructose consumption, and avoidingobesity. A low-calorie diet in obese men decreased uric acid levels by 100 µmol/L(1.7 mg/dL). Vitamin C intake of 1,500 mg per day decreases the risk of gout by45%. Coffee, but not tea, consumption is associated with a lower risk of gout. Goutmay be secondary to sleep apnea via the release of purines from oxygen-starved cells.Treatment of apnea can lessen the occurrence of attacks. TreatmentThe initial aim of treatment is to settle the symptoms of an acute attack. Repeatedattacks can be prevented by different drugs used to reduce the serum uric acid levels.Ice applied for 20 to 30 minutes several times a day decreases pain. Options foracute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine andsteroids, while options for prevention include allopurinol, febuxostat and probenecid.Lowering uric acid levels can cure the disease. Treatment of comorbidities is alsoimportant. NSAIDsNSAIDs are the usual first-line treatment for gout, and no specific agent is significantlymore or less effective than any other. Improvement may be seen within 4 hours, andtreatment is recommended for 1–2 weeks. They are not recommended, however inthose with certain other health problems, such as gastrointestinal bleeding, renal failure,or heart failure. While indomethacin has historically been the most commonly usedNSAID, an alternative, such as ibuprofen, may be preferred due to its better side effectprofile in the absence of superior effectiveness. For those at risk of gastric side effectsfrom NSAIDs, an additional proton pump inhibitor may be given. ColchicineColchicine is an alternative for those unable to tolerate NSAIDs. Its side effects(primarily gastrointestinal upset) limit its usage. Gastrointestinal upset, however,depends on the dose, and the risk can be decreased by using smaller yet still effectivedoses. Colchicine may interact with other commonly prescribed drugs, such asatorvastatin and erythromycin, among others. SteroidsGlucocorticoids have been found to be as effective as NSAIDs and may be used ifcontraindications exist for NSAIDs. They also lead to improvement when injected intothe joint; the risk of a joint infection must be excluded, however, as they worsen thiscondition. Pegloticase
Pegloticase (Krystexxa) was approved in the USA to treat gout in 2010. It will be anoption for the 3% of people who are intolerant to other medications.Pegloticase isadministered as an intravenous infusion every two weeks and has been found to reduceuric acid levels in this population. ProphylaxisA number of medications are useful for preventing further episodes of gout, includingxanthine oxidase inhibitor (including allopurinol and febuxostat) and uricosurics(including probenecid and sulfinpyrazone). They are not usually commenced until one totwo weeks after an acute attack has resolved, due to theoretical concerns of worsening theattack, and are often used in combination with either an NSAID or colchicine for thefirst 3–6 months. They are not recommended until a person has suffered two attacks ofgout, unless destructive joint changes, tophi, or urate nephropathy exist, as it is notuntil this point that medications have been found to be cost effective.Urate-loweringmeasures should be increased until serum uric acid levels are below 300–360 µmol/L(5.0-6.0 mg/dL) and are continued indefinitely. If these medications are being usedchronically at the time of an attack, it is recommended they be continued.As a rule of thumb, uricosuric drugs are preferred if there is undersecretion of uric acid,in turn indicated if a 24-hour collection of urine results in a uric acid amount of less than800mg.  They are, however, contraindicated if the person has a history of renalstones. In contrast, a 24-hour urine excretion of more than 800mg indicatesoverproduction, and xanthine oxidase inhibitors are preferred. Overall, probenecidappears to be less effective than allopurinol.Xanthine oxidase inhibitors (including allopurinol and febuxostat) block uric acidproduction, and long term therapy is safe and well tolerated, and can be used in peoplewith renal impairment or urate stones, although allopurinol has caused hypersensitivity ina small number of individuals. In such cases, the alternative drug febuxostat has beenrecommended. PrognosisWithout treatment, an acute attack of gout will usually resolve in 5 to 7 days. However,60% of people will have a second attack within one year. Those with gout are atincreased risk of hypertension, diabetes mellitus, metabolic syndrome, and renal andcardiovascular disease and thus at increased risk of death. This may be partly due toits association with insulin resistance and obesity, but some of the increased risk appearsto be independent.Without treatment, episodes of acute gout may develop into chronic gout with destructionof joint surfaces, joint deformity, and painless tophi. These tophi occur in 30% of thosewho are untreated for five years, often in the helix of the ear, over the olecranonprocesses, or on the Achilles tendons. With aggressive treatment, they may dissolve.Kidney stones also frequently complicate gout, affecting between 10 and 40% of people,and occur due to low urine pH promoting the precipitation of uric acid. Other forms ofchronic renal dysfunction may occur.
Nodules of the finger and helix of the ear representing gouty tophi Tophus of the knee Tophus of the toe, and over the external maleolus Gout complicated by ruptured tophi (exudate tested positive for uric acid crystals) EpidemiologyGout affects around 1–2% of the Western population at some point in their lifetimes, andis becoming more common. Rates of gout have approximately doubled between 1990and 2010. This rise is believed to be due to increasing life expectancy, changes in diet,and an increase in diseases associated with gout, such as metabolic syndrome and highblood pressure. A number of factors have been found to influence rates of gout,including age, race, and the season of the year. In men over the age of 30 and womenover the age of 50, prevalence is 2%.In the United States, gout is twice as likely in African American males as it is inEuropean Americans. Rates are high among the peoples of the Pacific Islands and theMāori of New Zealand, but rare in Australian aborigines, despite a higher meanconcentration of serum uric acid in the latter group. It has become common in China,Polynesia, and urban sub-Saharan Africa. Some studies have found attacks of gout
occur more frequently in the spring. This has been attributed to seasonal changes in diet, alcohol consumption, physical activity, and temperature.  History Antonie van Leeuwenhoek described the microscopic appearance of uric acid crystals in 1679. The word gout was initially used by Randolphus of Bocking, around 1200 AD. It is derived from the Latin word gutta, meaning "a drop" (of liquid). According to the Oxford English Dictionary, this is derived from humorism and "the notion of the dropping of a morbid material from the blood in and around the joints".Gout has, however, been known since antiquity. Historically, it has been referred to as "theking of diseases and the disease of kings" or "rich mans disease". The firstdocumentation of the disease is from Egypt in 2,600 BC in a description of arthritis of the bigtoe. The Greek physician Hippocrates around 400 BC commented on it in his Aphorisms,noting its absence in eunuchs and premenopausal women.Aulus Cornelius Celsus (30AD) described the linkage with alcohol, later onset in women, and associated kidneyproblems:Again thick urine, the sediment from which is white, indicates that pain and disease are to beapprehended in the region of joints or viscera... Joint troubles in the hands and feet are veryfrequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attackeunuchs or boys before coition with a woman, or women except those in whom the menseshave become suppressed... some have obtained lifelong security by refraining from wine,mead and venery.While in 1683, Thomas Sydenham, an English physician, described its occurrence in theearly hours of the morning, and its predilection for older males:Gouty patients are, generally, either old men, or men who have so worn themselves out inyouth as to have brought on a premature old age - of such dissolute habits none being morecommon than the premature and excessive indulgence in venery, and the like exhaustingpassions. The victim goes to bed and sleeps in good health. About two oclock in the morning
he is awakened by a severe pain in the great toe; more rarely in the heel, ankle or instep. Thepain is like that of a dislocation, and yet parts feel as if cold water were poured over them.Then follows chills and shivers, and a little fever... The night is passed in torture,sleeplessness, turning the part affected, and perpetual change of posture; the tossing about ofbody being as incessant as the pain of the tortured joint, and being worse as the fit comeson.The Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance ofurate crystals in 1679. In 1848 English physician Alfred Baring Garrod realized that thisexcess uric acid in the blood was the cause of gout.Diet For Uric Acid And Gout PreventionBy Pat | December 5, 2008Food For Gout Patient And Diet For Uric Acid Kidney StonesIn order to control your uric acid levels, you need to cut down your intake of foods that are high inpurines. Purine is a substance that is obtained from many food sources and is also generated by thebody as a by product of natural processes. In turn, purines are processed by the body and brokendown into uric acid. In some cases, a problem with this process of metabolizing purine may causeexcessive levels of uric acid in the body. This cannot always be controlled, but monitoring andcontrolling your intake of purine rich food is possible and is one of the best ways to control uric acidlevels.There are many food sources of purine, but meat sources seem to have the most impact on uric acidlevels. It is therefore important that you cut down your intake of meat, especially red meat. Themuch sought after “spare parts” – liver, kidney, heart etc – are unfortunately particularly high inpurine content, and should be completely avoided. Duck and goose meat also tends to be high inpurine, and should be avoided as far as possible. Sea food is usually considered extremely healthyfor almost any condition, but unfortunately for people with high uric acid levels, sea food intakeneeds to be cut down as well. Fish tends to be very rich in purine, especially anchovies, salmon,sardines, mackerel, and shell fish such as mussels.Recommended Diet For Gout TreatmentAs far as meat goes, chicken and pork, as well as most sea food other than the ones mentioned, arequite safe. However, make sure that you do not consume an excess as compensation for the meatsthat you are avoiding, or your diet will not be very useful. Certain vegetables are also high in purine,but these somehow do not affect uric acid levels much. You can therefore eat pretty much anyvegetables you like, preferably maintaining as wide a variety as possible.
If you are concerned about your protein intake being too low due to the drastic cutting out of meatfrom your diet, you can supplement it with eggs, milk, and milk products. This too should of coursebe done within reasonable limits – eggs and milk products will not affect your uric acid levels, but anexcess could cause other problems. Finally, you should control your intake of alcohol, particularlybeer. If your uric acid levels are particularly high, you should completely cut out alcohol for a fewmonths, and then limit consumption to rare occasions.Uric Acid DietThe foods we eat play a very significant role in the quality of life that we lead. While theconsumption of a hamburger on a regular basis may not really seem like you are doing too muchwrong, apart from a little self indulgence, the impact that it will have in a few months time issomething that you will usually not consider while munching on that lovely snack. If ignored thosefew months down the line, the condition can spiral out of control into a full blown case of obesity.While the most obvious effect that obesity has on an individual is the fact that it affects the aestheticappeal of the person considerably, the other problems that it causes – such as heart failure, chronicrespiratory illnesses and blood pressure as well as cholesterol levels can have a significant impact onthe individuals quality of life. Just as with obesity, there are a number of other conditions that willusually develop as a direct result of the kinds of foods you consume. For instance, gout is a verycommon condition that is particularly influenced by the foods you consume.Before getting into the details of exactly what gout is, it is important to understand exactly what uricacid is. Uric acid is a chemical substance that is created within the body as a result o the breakdownof substances known as purines. Under normal circumstances, this uric acid is dissolved into theblood and is flushed out of the body through the kidneys. However, some cases will see a buildup ofuric acid within the body – giving rise to serious medical ailments such as gout and kidney disease.Medical research has shown that the intake of foods that are high in uric acid content play asubstantial role in the development as well as aggravation of certain conditions that can have asignificant impact on the workings of the human body. The uric acid condition in the body is a verypainful and common condition – especially in older men, although it is also known to affect somewomen. Understanding the various symptoms as well as causes of gout will help you understandbetter the best methods of gout prevention, diet and beneficial foods, herbs and medication. Thereare also a number of gout prevention tips that can be found on a number of websites on the Internetthat will share information on how you can deal with the condition better and also ensure that thecondition does not affect you significantly.One of the most common causes of the development of gout is the lack of adequate consumption ofliquids. This will occasionally cause the kidneys to malfunction and the uric acid will not be removedfrom the blood through the normal process of excretion. Another very common cause of the buildupof uric acid in the human body is the excessive consumption of purine rich foods. Essentially nitrogencontaining compounds, these foods will cause elevated levels of uric acid – causing it to accumulate
in the tissues of the body and form crystals. Some of the more popularly consumed foods thatcontain high levels of purines include red meat, certain types of seafood and organs. Excessivealcohol consumption is also known to be a very significant factor in the development of uric acidbuildup within the body. Most cases of treatment will require the individual to almost completelycease any intake of alcohol until the acid levels have been returned to normal.Before getting into the details of how to control uric acid in the blood and human body, it helps tounderstand the most prominent symptoms of the condition – thereby helping you diagnose thecondition much earlier in the chain of its development. Probably the first symptom of thedevelopment of the condition is the swelling at the base of the big toe. However, there are a fewcases in which the first swelling can occur in some other joint in the legs. The individual is likely toexperience a significant amount of pain as soon as any kind of pressure is applied to the affectedarea.Because of the fact that gout prevention is very sought after, there are a number of uric acid dietsthat have been developed all over the world to help deal with the condition. Exercise is one of themost important, while also being one of the most overlooked, aspects of gout prevention and aregular period of between 20 to 30 minutes every day will help significantly in helping the bodyreduce the amount of uric acid it contains. The best uric acid is to consume foods that are low insugar and salt content. Basil is known to be a very effective substitute for salt in the event that youare looking for something to help season the food. Increasing your intake of foods like brown rice,whole wheat bread, fruits and vegetables will also go a long way into preventing the development ofgout in your body. Another aspect of dealing with gout that one should point out is the fact thatthere is no medical cure as yet for the condition. This means that, as of yet, no chemically basedmedication has been developed that can help with the condition. Any gout prevention will alwaysrequire a readjusting of the individual’s lifestyle and habits to ensure that the uric acid content in thebody is reduced substantially. Obesity is also known to play a significant role in the development ofgout because of the fact that the additional weight will, more often than not, press down on thekidneys and cause them to malfunction – thereby causing the condition to develop further.Exercising when one has gout can be a little painful and so it is best to include in your exerciseschedule those exercises that do not place undue stress on affected joints. Simple yoga poses andexercises for the upper body can be very useful in remaininglimber despite suffering from gout.Foods High in Uric Acid – a Surprising MythPurines from food are a source of uric acid. The foods high in uric acid table below is now replacedby the Purine Rich Foods chart.Foods High In Uric Acid IntroductionDietitians and nutritionists commonly measure foods high in uricacid by measuring the total purine content of food.
The table below lists foods high in uric acid first with purine concentration reducing as you movedown the list. Many advisers tell gout sufferers to avoid anything over 400mg and restrict foods inthe 100-400mg range, but you should treat this advice with caution.Firstly, you must realize that typical portion sizes vary enormously.Be sure to calculate the amount that applies to your typical serving size from the value shown for100 grams.Secondly, the effect of foods high in uric acid depends on direct absorption through the digestivetract. Most uric acid derives from the breakdown of your cells as part of normal metabolism. Theoverall contribution of foods high in uric acid is debatable – figures of between 5% and 15% arecommon.Purines WarningPlease be careful about getting obsessed with the purine content of food. Thoughpurines in food can have a slight effect on uric acid, there are many other factors to consider. Readmore about the main food factors that can affect gout in the Gout Diet section.Foods High In Uric Acid TableYou should use the information in the table below only as a guideline.Many other factors, besides foods high in uric acid, affect the risk of gout attacks.If you do feel that it is important to manage foods high in uric acid, then you should measure yourtotal intake. Multiply the weight of your food (in grams) by the value from the table and divide thisby 100 to give your uric acid intake in milligrams. In this way you can calculate a total intake from thelist of foods high in uric acid for every meal. You need to find the level that you can tolerate best bytrial and error.Foods High in Uric AcidTo find a particular food quickly, use your browser Find function (usually Ctrl-F).Food Purines(Uric Acidmg/100g)Theobromine 2300Yeast, Brewer’s 1810Neck sweet bread, Calf’s 1260
Kidney, Calf’s 218Fish, Herring, Atlantic 210Horse meat 200Bean, Soya, seed, dry 190Fish, Herring roe 190Lamb (muscles only) 182Fish, Halibut 178Chicken (breast with skin) 175Veal, muscles only 172Fish, salmon 170Poppy seed, seed, dry 170Pork muscles only 166Goose 165Sausage, liver (liverwurst) 165Fish, Saithe (coalfish) 163Fish, Carp 160Ox tongue 160Pork leg (hind leg) 160Chicken, boiling fowl, average 159Pork fillet 150Pork shoulder with skin (blade of shoulder) 150Turkey, young animal, average, with skin 150Veal knuckle with bone 150Veal, leg of veal with bone 150Veal, neck with bone 150Lungs, Calf’s 147Shrimp, brown 147
Fish, Mackerel 145Pork chop with bone 145Caviar (real) 144Sunflower seed, dry 143Pike 140Pork chuck 140Veal chop, cutlet with bone 140Veal fillet 140Veal, shoulder 140Fish, Haddock 139Duck, average 138Venison haunch (leg) 138Pig’s tongue 136Scallop 136Beef, muscles only 133Rabbit meat, average with bone 132Fish, Sole 131Ham, cooked 131Bean, seed, white, dry 128Lentil, seed, dry 127Pork belly, raw, smoked dried 127Beef, chuck 120Beef, fore rib, entrecote 120Pork hip bone (hind leg) 120Lobster 118Chicken (chicken for roasting), average 115Mussel 112
Sausage “Jagdwurst” 112Beef, fillet 110Beef, roast beef, sirloin 110Beef, shoulder 110Chicken, leg with skin, without bone 110Fish, Pike-perch 110Fish, Cod 109Peas, chick (garbanzo), seed, dry 109Grape, dried, raisin, sultana 107Linseed 105Rabbit/Hare (average) 105Venison back 105Sausage salami, German 104Sausages, frying, from pork 101Pork belly 100Barley without husk, whole grain 96Sausage “Mortadella” 96Pea, seed, dry 95Oats, without husk, whole grain 94Plaice 93Brain, Calf’s 92Mushroom, flat, edible Boletus, cep 92Sausages, frying, from veal 91Oyster 90Frankfurter sausages 89Sausage “Bierschincken” 85Pea, pod and seed, green 84
Cheese, edam, 30% fat content in dry matter 7.1Cheese, edam, 40% fat content in dry matter 7.1Cheese, edam, 45% fat content in dry matter 7.1Cherry, sweet 7.1Cheese, Cheddar/Cheshire cheese, 50% fat content in dry matter 6Search BooksShowing 1 - 3 of 7 resultsFood Composition and Nutrition Tables, 7th …Siegfried W. Souci, W Fachmann, Heinrich Kraut (…$164.18Food Composition and Nutrition Tables, Sixt…Siegfried W. Souci, W Fachmann, Heinrich Kraut (…$265.96Phytosterols as Functional Food Component…(Hardcover - Dec 2, 2003)$206.85123>PrivacyI took the data in this table from Food Composition and Nutrition Tables bySouci, Fachmann, Kraut [see box on right]. Their notes for the purine data statesPurinesThe total of free and bound compounds is given for each component. The “total purines” columncontains the total of all individual components calculated as uric acid.The exact calculation of this is beyond the scope of this article, but you can easily see the relativepurine count in the table. Remember, the table of foods high in uric acid shows the number ofmilligrams per 100 grams, so intake will depend on portion size.GoutPal warns against taking these types of analysis too seriously. Firstly, gout food researchindicates that vegetable purines do not increase the risk of gout, and dairy foods can actually reduceit. More importantly, people digest foods differently – a food that causes gout in one person mightbe tolerated by another, and different food combinations have significantly different effects. Thereis more information about dealing with foods high in uric acid in my Gout Diet section.
Various food types and their purine content. Total Nutr. Purines in Density 224 Foods (alphabetically) mg uric Min Max in acid/100 g mg/MJ (Average) HIGHEST IN PURINES (400 mg. uric acid/100 g and higher)Fish, sardines in oil 480 399 560 519.5Liver, Calfs 460 837.5Mushroom, flat, edible Boletus, dried 488 932.8Neck sweet bread, Calfs 1260 3012.9Ox liver 554 1013.3Ox spleen 444 1052.6Pigs heart 530 1382Pigs liver 515 937.9Pigs lungs (lights) 434 911.2Pigs spleen 516 1208.2Sheeps spleen 773 1702.6Sprat, smoked 804 795.6Theobromine 2300 1611.3Yeast, Bakers 680 2071.3Yeast, Brewers 1810 1866.6 MODERATELY HIGH IN PURINES (100 to 400 mg. uric acid/100g)Bean, seed, white, dry 128 127.1Bean, Soya, seed, dry 190 139.1Beef, chuck 120 192Beef, fillet 110 216.4Beef, fore rib, entrecote 120 185.4Beef, muscles only 133 292.1Beef, roast beef, sirloin 110 110 120 201.4Beef, shoulder 110 203.9Black gram (mungo bean), seed, dry 222 194.3Caviar (real) 144 141.6Chicken (breast with skin) 175 288.4Chicken (chicken for roasting), average 115 165.8Chicken, boiling fowl, average 159 149.2Chicken, leg with skin, without bone 110 152.2Duck, average 138 146.2