While a healthy level (on the high side) of uric acid might correlate with intelligence, elevated uric acid levels can be harmful.
What Is Uric Acid?
Uric acid (urate) is an end-product of purine degradation in humans. Purines are generated as a final product in the digestion of certain proteins and DNA in the diet, but some are synthesized in the body .
Uric acid has antioxidant properties but can be pro-oxidant depending on its chemical environment .
In normal conditions, uric acid is eliminated via urine . However, many factors affect the ability of the kidneys to eliminate it efficiently. This results in abnormal blood uric acid levels (too high or too low)
High uric acid levels have been linked to :
- Kidney stones
- High blood pressure
- Kidney disease
- Cognitive dysfunction
How Our Bodies Produce Uric Acid
Uric acid is the last step in the breakdown pathway of purines. Purines are converted to hypoxanthine, then to xanthine and finally, to uric acid.
For the last two steps in conversion, we need the enzyme xanthine oxidase (uricase). Humans have a mutation that prevents the production of the enzyme that destroys uric acid (uricase) .
Consequently, humans have higher urate levels (around 240 – 360 μM) compared to other mammals (around 30 – 50 μM in mice) .
How Uric Acid Is Eliminated from the Body
Uric acid is removed via the kidney and the gut: through urine (70%) and feces (30%) .
Uric Acid Tests
Uric Acid Blood Test
A uric acid blood test is the most common test used to monitor people who have :
- Likely problems with kidney functions, kidney disorders, or stones
- Undergoing chemotherapy or radiation treatment
Reference values for blood uric acid levels generally fall between 2.6 – 5.7 mg/dl for women and 3.5 – 7 mg/dl for men, although this may vary between laboratories .
Uric Acid Urine Test
For the test, 24 hours of urine is collected to measure the amount of uric acid in the urine and evaluate how the body produces and eliminates uric acid. The test is also used to detect gout or hyperuricemia [10, 11].
Normal results for this test are :
- Adults (normal diet): 250 – 800 mg/day
- Adults (purine-free diet): <420 mg/day
- Adults (low-purine diet) :
- Males: <480 mg/day
- Females: <400 mg/day
- Adults (high-purine diet): <1,000 mg/day
Pros and Cons of Uric Acid
There are pros and cons to having high uric acid.
High Levels of Uric Acid and Diseases Associated with It
An excess of uric acid in the body is known as hyperuricemia.
People with high uric acid without symptoms typically don’t need any medical treatment, but it presents several health risks, so the high uric acid levels should be addressed.
Gout is a form of inflammatory arthritis associated with hyperuricemia. It occurs when there are high levels of uric acid in the circulating blood, which causes urate crystals to settle in the tissues of the joints .
The symptoms appear suddenly, overnight. It comes with agonizing pain, redness, and swelling of the joint. The attack may be precipitated by too much food, alcohol, by starting a diuretic, or by dehydration .
Symptoms go away after 10 to 15 days but may keep recurring. Eventually, stone-like deposits known as tophi may build up in joints, ligaments, and tendons, which lead to possible joint deformation .
2) Kidney Stones
The most common risk factor for uric acid stones is acidic urine (pH<5.5) because uric acid stones precipitate in acidic environments. Therefore, patients should increase their alkaline load by eating more fruits and vegetables .
3) Metabolic Syndrome
Blood uric acid is significantly correlated with metabolic syndrome and its components, particularly blood triglycerides and waist circumference .
This may also be because the rise in uric acid after fructose intake induces insulin resistance (by lowering nitric oxide), a key factor involved in metabolic syndrome .
4) Type 2 Diabetes
High blood uric acid is associated with a higher risk of type 2 diabetes, independent of obesity, high cholesterol, and blood pressure .
It is thought that hyperuricemia raises the risk for diabetes by increasing oxidative stress and inflammation (by increasing tumor necrosis factor-α), both of which are related to the development of diabetes .
5) Hypertension and Chronic Kidney Diseases
Hyperuricemia may directly cause hypertension. In rats, hypertension associated with high uric acid was reversible with drugs that lower uric acid, including febuxostat and allopurinol .
These include hardening of the arteries, heart failure, stroke, type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease, and others .
Chronic hyperuricemia in patients with gout increases uric acid crystal build-up in kidney tissues, resulting in tissue injury and inflammation .
6) Lesch-Nyhan Syndrome
Lesch-Nyhan syndrome, an extremely rare genetic disorder, is associated with very high blood uric acid levels .
In Lesch–Nyhan syndrome, hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme involved in the recycling of purine nucleotides, is mutated. This leads to increased uric acid production because purine nucleotides cannot be reused, so they are subsequently degraded .
Muscle tightness, involuntary movement, self-injury, cognitive retardation, and gout formation are exhibited in cases of this syndrome .
7) Down Syndrome
Patients with down syndrome consistently have higher blood uric acid levels .
8) May Increase Bone Fracture Risk
Increased blood urate levels are associated with an increased risk of hip fractures in men .
9) Erectile Dysfunction
Erectile dysfunction is commonly observed in patients with gout. This is likely because high uric acid levels are strongly linked to poor blood vessel function, hypertension, and microvascular disease (disease of smaller blood vessels), all of which are risk factors for erectile dysfunction .
Blood uric acid levels were significantly higher in patients with psoriasis compared with controls .
However, uric acid levels did not increase or decrease the inflammation seen in these patients.
Health Benefits of High Levels of Uric Acid
Read this post to learn about the positive health benefits of having high uric acid.
Factors That Increase or Decrease Uric Acid Levels
Age: Uric acid levels start to rise after puberty. Men have slightly higher levels than women until female menopause .
These levels depend on the balance between purine production and the ingestion of dietary purines, as well as the elimination of urates by the kidney and intestine. Abnormal levels (too high or too low) are detrimental and lead to a variety of health conditions .
Causes of High Uric Acid
1) Kidney Problems
Higher levels of uric acid occur when your kidneys don’t eliminate it efficiently. This could be due to kidney dysfunction and/or influence by certain metabolites and medications .
2) High Protein Diets
Studies have shown that each additional intake of meat portion per day increases the risk of gout by 21% .
In a crossover study design, the effect of ingesting some purine-rich foods like beef liver, haddock fillets, and soybean was investigated. Results showed that the ingestion of all the test meals caused an increase in blood uric acid levels .
Fructose rapidly raises uric acid levels because it activates enzymes that break down ATP into AMP (fructokinase and adenosine deaminase), which leads to the increased production of inosines .
In addition, fructose stimulates uric acid synthesis from amino acid precursors, such as glycine .
Diuretics are one of the most important causes of secondary hyperuricemia. Drugs increase blood uric acid levels by an increase of uric acid reabsorption and/or a decrease of uric acid secretion .
According to a population-based cohort study, alcohol-related diseases were significantly associated with gout risk. Also, severe alcohol-dependent patients were associated with an increased risk of gout .
Alcohol may stimulate uric acid production by increasing lactic acid, which then reduces the excretion of uric acid in the kidneys .
Hyperuricemia and gout are frequently found in patients with hypothyroidism .
Thyroid hormones (T4 and T3) stimulate energy production processes, and heir deficiency affects purine metabolism, resulting in increases in uric acid levels and hyperuricemia .
Also, hypothyroidism may lead to a reduction in kidney blood flow and filtration rate, which elevates uric acid levels in the blood .
According to a population-based epidemiological study, obesity resulted in an increased risk of developing hyperuricemia. If you are overweight, your body produces more uric acid. As a result, the kidney has a more difficult time eliminating uric acid .
Blood uric acid levels correlate with leptin levels. Since obese individuals have higher leptin levels (due to leptin resistance), high leptin may be linked to the development of hyperuricemia in obesity .
The gene UCP2 influences blood urate concentration and the risk of hyperuricemia. The degree of association varies with gender and BMI levels .
9) Male Gender and Sex Hormones
Men have higher blood uric acid levels than women and are more at risk for developing gout .
Estrogen is required for the normal elimination of urate through the kidneys. During the post-menopausal period, women have the same content of uric acid as men of similar age, suggesting that low estrogen may have a role in hyperuricemia development .
10) Older Age
Blood uric acid content increases with age .
Also, the prevalence of gout increases by approximately four-fold to 4.1% by the age of 75 years .
11) Nutrient Deficiencies
Vitamin D deficiency is significantly correlated with hyperuricemia in post-menopausal women .
12) Ketogenic Diet and High Sodium Intake
A ketogenic diet reduces the ability of the kidney to excrete uric acid because of competition for transport between uric acid and ketones .
Higher intakes of sodium are associated with increased blood uric acid levels .
13) Parathyroid Hormones
Elevated blood parathyroid hormone levels are associated with higher blood uric acid levels in the general population. Although exact mechanisms are unclear, it is thought that parathyroid hormone increases blood uric acid by reducing kidney urate excretion [64, 65].
14) Cancer Treatment and Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that occur during cancer treatment. When large amounts of tumor cells are killed at the same time, they release their cellular contents into the bloodstream. When nucleic acids from the DNA and RNA of these cells are released into the bloodstream, it generates high concentrations of uric acid .
15) Chronic Lead Poisoning Leads to Hyperuricemia
Lead exposure is associated with impaired kidney function and increased blood uric acid levels .
High levels of lead damage the kidneys, causing inflammation and inhibiting urate excretion, which results in urate build-up and eventually, saturnine gout (i.e., lead gout) .
How to Lower Uric Acid Naturally
1) Weight Loss
Weight loss may help reduce high uric acid levels in overweight and obese people .
2) Purine-Restricted Diet
Avoid alcohol, red meat, seafood, and sugary beverages. Avoid/ limit refined carbs if you have high uric acid levels. The foods lowest in purine content include eggs, fruit, cheese, nuts, and vegetables other than legumes .
Dehydration leads to elevated uric acid levels .
4) Vitamin C
Vitamin C increases the excretion of uric acid in the urine and thereby lowers blood uric acid levels .
Caffeine is a methylxanthine and may be a competitive inhibitor of xanthine oxidase .
However, one study comparing the effects of coffee, tea, and caffeine intake on uric acid levels found that coffee consumption was associated with lower uric acid levels due to components in coffee other than caffeine, suggesting that coffee itself (regular or decaf), not caffeine, is responsible for the inverse association .
6) Dairy Products
Milk proteins (i.e., casein and lactalbumin) promote the excretion of uric acid in the urine .
7) Cherry Juice
Medical Treatments to Lower Uric Acid
1) Non-Steroidal Anti-Inflammatory Drugs
2) Uricosuric Drugs
These drugs increase the secretion of uric acid in urine: probenecid, sulfinpyrazone, and benzbromarone .
3) Xanthine Oxidase Inhibitors
Allopurinol is recommended because it prevents gout, but it is also taken when patients have a certain form of leukemia or lymphoma, to prevent a complication of chemotherapy or tumor lysis syndrome.
Also, due to its adverse effect, allopurinol is currently not indicated in asymptomatic hyperuricemia and its related heart disease, or in the diseases other than gout .
Febuxostat is a selective xanthine oxidase/xanthine dehydrogenase inhibitor .
It has several advantages over allopurinol including tolerability in allopurinol-hypersensitive patients, more effectiveness in kidney failure, and faster dissolution of tophi .
Febuxostat works quickly and treatment usually begins with doses of 40 mg/day. If blood uric acid level is not reduced to 6.0 mg/dL by two weeks, the dose can be increased to 80 mg/day. The average reduction in blood uric acid level is 40% and 56% at 40 mg/day and 80 mg/day respectively, and is similar in individuals with and without kidney failure, in contrast to allopurinol .
Irregular Uric Acid Levels?
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