Why uric acid increases in blood

The human diet is very poor in urate, which is produced mainly in the liver and to a less extent in the small intestine. It is recommended that individuals with hyperuricemia should not ingest a large amount of purine-rich food for instance, veal, bacon, kid meat, mutton, turkey, pork, duck, goose, etc.

During fructose metabolism, the phosphorylation of such monosaccharide into fructose 1-phosphate occurs by means of enzyme fructokinase. When high fructose intake occurs, fructose phosphorylation into fructose 1-phosphate is fast, but the reaction with aldolase is slow. Hence, fructose 1-phosphate accumulates, and inorganic concentrations of intracellular phosphate also decrease.

There are other ways to increase urate concentrations, such as the intake of sorbitol, sucrose, lactate and methylxanthines [ 38 ]. After absorption, sorbitol is converted into fructose by the liver, and thus, it can increase UA production [ 39 , 40 ]. Fruit and vegetables, in addition to flavonoids, can contain other nutrients that can affect the plasma total antioxidant capacity TAC.

The mechanism for such elevation would be the degradation of purine nucleotides or UA excretion reduction [ 41 - 43 ]. High vitamin-C intake shows an inverse relation with UA [ 44 ] as such vitamin has a uricosuric effect due to competition of UA renal resorption through a change in the anion transportation system in the proximal tubule [ 45 , 46 ].

Beer intake is an independent factor from UA increase [ 32 ] both due to its alcoholic content and high-quality purine [ 47 ]. Beer intake has a stronger power to increase UA than liqueur, but moderate wine intake does not increase UA [ 36 , 48 ]. Alcohol intake increases UA concentrations by reducing excretion [ 49 , 50 ] and increasing urate production [ 51 ].

Dairy product intake has an inverse relation with UA [ 32 , 36 , 52 ]. Probably, the mechanism for such association is due to milk-forming proteins lactalbumin and casein , which have a uricosuric effect [ 53 ].

There is an inverse relation between coffee intake and UA concentrations [ 48 ], but such association seems to be due to other substances, as it does not seem to result from caffeine. Decreased UA concentrations would result from the improved insulin resistance observed with increased coffee intake, which occurs mainly due to chlorogenic acid, an antioxidant found in that drink [ 54 , 55 ].

Tsunoda et al. This type of diet indirectly decreased UA serum concentrations because it improved insulin sensitivity in these individuals, and this occurred regardless of changes in body weight or blood pressure.

Gout is caused by articulation deposition of monosodium urate crystals after chronic hyperuricemia [ 2 ]. Uric acid values higher than 7. Renal calculi are formed by calcium salts deposited on an organic matrix of oxalate or urate. Their formation occurs in the glomerular filtrate in acid oxalate or urate or alkaline carbonates and phosphates pH in the presence of high calciuria hyperparathyroidism or bone demineralization.

They are usually formed and then dissolved, but under abnormal pH variation or filtrate concentration conditions, they may remain until excretion [ 30 ]. The contribution of UA to renal stone formation has an important role in progressive renal failure [ 57 ]. Meta-analysis has recently shown that UA elevation is related to an increase in coronary artery disease infarction and mortality events [ 1 ], and epidemiological studies showed that UA is an independent risk factor for cardiovascular diseases [ 5 , 10 ], particularly in hypertensive and diabetic individuals [ 21 ].

It is also speculated that UA is one of the determinants of the metabolic syndrome [ 22 ]. Individuals with high UA levels have an odds ratio of 1. UA is associated with Metabolic Syndrome [ 59 ] and its components [ 60 ], obesity, dyslipidemia, hypertension [ 18 ], insulin resistance metabolic syndrome , increased C-reactive protein PCR concentration [ 23 ] and endothelial dysfunction [ 20 ], or even, to risk factors for cardiovascular diseases [ 7 , 17 , 19 ].

UA increase is observed in individuals with insulin resistance, probably because hyperisulinemia would cause lower renal UA excretion [ 61 ]. Additionally, insulin could indirectly act on UA, since there is an association between hyperinsulinemia and hypertriglyceridemia. Some studies show that high concentrations of plasma triglycerides are related to hyperuricemia [ 58 , 62 - 64 ].

There are some explanations for such relation, and one of them is that during triglycerides TG synthesis there would be a greater need for NADPH [ 62 ].

The synthesis of fatty acids in the liver is associated with the de novo synthesis of purine, thus accelerating UA production [ 65 ].

Chen et al. The likely mechanism is the relationship between decreased HDL-C and insulin resistance [ 66 ]. Confirming this hypothesis, our research group showed that when adjusted for the other MS components, the relation between UA and HDL-c is lost [ 67 ]. In the adipose tissue, there is adipokine production, including that of leptin. One possible explanation for the association between higher waist circumference and hyperuricemia were suggested by Bedir et al.

Some authors report UA to be responsible for blood pressure increase, and others show arterial hypertension AH to be a risk factor for hiperuricemia. UA inhibits the bioavailability of nitric oxide, which is a vasodilator [ 70 ], and, on the other hand, AH would lead to vascular disease and increase renal vascular resistance. Both of these processes reduce renal flow, thus increasing urate resorption [ 71 ]. A recent study showed an inverse relation between muscle mass MM and UA in healthy individuals older than 40 years [ 72 ].

Chronic elevation of UA concentrations would be a causal factor for sarcopenia, especially through increased inflammation and oxidative stress [ 72 , 73 ].

The activation of the xanthine oxidase metabolic pathway, which increases UA production and the superoxide radical [ 74 ] could elevate the reactive oxygen species ROS and it could be the main mechanism for the reduction of MM. Furthermore, UA exerts a pro-inflammatory effect, thus stimulating the production of interleukin-1, interleukin-6 the tumor necrosis factor which also can influence the muscle mass [ 75 ]. It is not known whether UA would be a causal factor or an antioxidant protective response against oxidative stress [ 76 ].

While chronic high UA concentrations are associated to increased risk for CAD, acute elevations seem to provide antioxidant protection [ 77 ]. Furthermore, the UA has a protective action in vitamins C and E [ 79 ] with the stabilizing activities in these vitamins [ 79 , 80 ] and the presence of ascorbic acid in plasma is required for the antioxidant effect of UA [ 80 ].

Also, it has a direct effect on the inhibition of free radicals such as peroxyl radical and peroxynitrite, protecting the cell membrane and DNA [ 81 , 82 ]. Most authors do not consider UA as a detrimental factor to the body health, because of its antioxidant function [ 8 , 83 ]. The antioxidant activity of UA also occurs in the brain [ 84 ], being a protector for several disease such as multiple sclerosis and neurodegenerative disease.

Higher concentration of UA is associated with lower risk of development of Parksons disease and a favorable effect at the disease progression mainly [ 85 ]. Several factors are associated as cause and consequences of high UA concentration.

Higher waist circumference and BMI are associated with higher insulin resistance and leptin production, and both reduce renal uric acid excretion, thus increasing its concentration. HDL-c concentration is negatively associated to insulin resistance, what can influence its negative correlation to uric acid.

Determinants of hyperuricemia. Additionally, obesity and muscle mass MM reduction are associated with low-intensity chronic inflammation, and uric acid levels can increase in order to protect the organism against the moderate oxidative stress resulting from this situation.

Low muscle mass sarcopenia is negatively associated with uric acid, However, it has not yet been clarified what the cause or effect is. Probably, oxidative stress produced by excessive uric acid can influence muscle mass reduction. Furthermore, there is still no consensus if UA is a protective or a risk factor, however, it seems that the quantity and the duration of the concentration of the uric acid in the blood is essential for this answer.

Acute elevation seems to be a protective factor, whereas chronic elevation a risk factor. All authors read and approved. National Center for Biotechnology Information , U. Journal List Diabetol Metab Syndr v. Diabetol Metab Syndr. Published online Apr 4. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Erick Prado de Oliveira: rb. Received Jan 17; Accepted Apr 4. This article has been cited by other articles in PMC.

Abstract High plasma uric acid UA is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. Introduction High plasma uric acid UA is a prerequisite for gout and is also associated with the Metabolic Syndrome and risk factors for cardiovascular diseases [ 1 - 4 ].

Chemical characterization and biological importance Uric acid 2,6,8 trioxypurine-C5H4N4O3 is an organic compound that is endogenously produced by animals as a purine metabolite.

Uricemia homeostasis Physiologically, uric acid plasma concentrations increases with age; they are smaller in women of childbearing age and, in post menopause women, it increase to similar values to those found in males [ 2 , 3 ]. Excretion control In the kidney, uric acid and urate are initially filtered and additionally secreted. Production control Purine bases and their nucleotides are rapidly captured by the liver [ 27 ] and converted into xanthines, metabolized by uric acid or recycled by salvage pathways or de novo synthesis, and the latter requires a higher energetic cost ATP consumption [ 28 ].

Diet The relation between diet and UA has not yet been fully clarified since most studies have not estimated basal urate concentrations, have not excluded confounding factors or have not even correctly evaluated ingested nutrients [ 32 ]. Uricemia as a risk factor Gouty arthritis Gout is caused by articulation deposition of monosodium urate crystals after chronic hyperuricemia [ 2 ]. Renal calculi Renal calculi are formed by calcium salts deposited on an organic matrix of oxalate or urate.

Metabolic syndrome and body composition Meta-analysis has recently shown that UA elevation is related to an increase in coronary artery disease infarction and mortality events [ 1 ], and epidemiological studies showed that UA is an independent risk factor for cardiovascular diseases [ 5 , 10 ], particularly in hypertensive and diabetic individuals [ 21 ]. Uricemia as a protective factor It is not known whether UA would be a causal factor or an antioxidant protective response against oxidative stress [ 76 ].

Conclusions Several factors are associated as cause and consequences of high UA concentration. Open in a separate window. Figure 1. Competing interests The authors declare that they have no competing interests. Hyperuricemia and risk of stroke: a systematic review and meta-analysis.

High levels can also be caused by a low-salt diet. The test is done with a blood sample. A needle is used to draw blood from a vein in your arm or hand. Having a blood test with a needle carries some risks. These include bleeding, infection, bruising, and feeling lightheaded. When the needle pricks your arm or hand, you may feel a slight sting or pain. Afterward, the site may be sore. Foods high in purines, including organ meats, mushrooms, some types of fish and seafood, and dried peas and beans.

Ask your healthcare provider if you should avoid any foods, beverages, or medicines before the test. Be sure your provider knows about all medicines, herbs, vitamins, and supplements you are taking. This includes medicines that don't need a prescription and any illegal drugs you may use. Search Encyclopedia. Uric Acid Blood Does this test have other names? Serum uric acid What is this test? This test measures the amount of uric acid in your blood.

Why do I need this test? Symptoms of gout include: Joint pain or soreness Swelling and pain in a joint, such as the big toe, ankle, or knee, or red skin around a joint Joints that are hot to the touch Swelling and pain that affects only 1 joint in the body Skin that looks shiny and is red or purple You may also need this test if you have symptoms of kidney stones.

Symptoms include: Severe pain along your lower back. Nausea Vomiting Urgent need to urinate Blood in your urine What other tests might I have along with this test? Symptoms High uric acid level. Sections Basics Definition Causes When to see a doctor. Definition Causes When to see a doctor. Products and services. Thank you for Subscribing Our Housecall e-newsletter will keep you up-to-date on the latest health information. Please try again. Something went wrong on our side, please try again. Show references Uric acid.

Lab Tests Online. Accessed Oct. Questions and answers about gout. Kim SY, et al. Hyperuricemia and coronary heart disease: A systematic review and meta-analysis. Ohno, I. Relationship between hyperuricemia and chronic kidney disease. Nucleosides, Nucleotides and Nucleic Acids. Kanbay M, et al. Uric acid in hypertension and renal disease: The chicken or the egg?