Hyperuricemia is the term used to describe an abnormally high level of uric acid in the blood. In the pH chemistry of body fluid, uric acid exists mostly as urate, the ion form.
The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract.
The upper end of the normal range is 360 µmol/L (6 mg/dL) for women and 400 µmol/L (6.8 mg/dL) for men. Increased levels of uric acid predispose you for gout. If the levels are very high, kidney failure is a risk.
What Causes Hyperuricemia
Consumption of alcoholic beverages is the biggest cause, but many there are other aspects which contribute to hyperuricemia, including:
The causes of hyperuricemia can be sorted into three types. First of all, increased production of uric acid. Then, decreased excretion of uric acid, and finally, the mixed type.
Causes of increased production include high levels of purine in the diet and increased purine metabolism. Causes of decreased excretion include kidney disease, certain drugs, and competition for excretion between uric acid and other molecules.
Mixed causes include high levels of alcohol and/or fructose in the diet, and starvation.
Increased Uric Acid Production
A purine-rich diet is a minor but common cause of hyperuricemia. Diet alone normally is not enough to cause hyperuricemia. Purine content of foods varies.
Foods high in the purines adenine and hypoxanthine may be more potent in exacerbating hyperuricemia. Hyperuricemia of this type is a common complication of solid organ transplant.
Apart from normal variation (with a genetic component), tumor lysis syndrome produces extreme levels of uric acid, mainly leading to renal failure. The Lesch-Nyhan syndrome is also associated with extremely high levels of uric acid.
Decreased Excretion of Uric Acid
The main drugs that contribute to hyperuricemia by decreased excretion are the primary antiuricosurics.
Other drugs and agents include nicotinic acid, diuretics, salicylates, pyrazinamide, ethambutol, ciclosporin, 2-ethylamino-1,3,4-thiadiazole, and cytotoxic agents.
A ketogenic diet impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and ketones.
Elevated blood lead is significantly correlated with both impaired kidney function and hyperuricemia, but the causal relationship among these correlations is not known.
Causes of hyperuricemia that are of mixed type have a dual action, both increasing production and decreasing excretion of uric acid.
High intake of alcohol, a significant cause of hyperuricemia, has a dual action that is compounded by multiple mechanisms. Alcohol increases production of uric acid by increasing production of lactic acid, hence lactic acidosis.
Alcohol also increases the plasma concentrations of hypoxanthine and xanthine via the acceleration of adenine nucleotide degradation, and is a possible weak inhibitor of xanthine dehydrogenase.
As a byproduct of its fermentation process, beer additionally contributes purines. Ethanol decreases excretion of uric acid by promoting dehydration and (rarely) clinical ketoacidosis.
High dietary intake of fructose contributes considerably to hyperuricemia. In a large study in the United States, consumption of four or more sugar-sweetened soft drinks per day gave an odds ratio of 1.82 for hyperuricemia.
Increased production of uric acid is the result of interference, by a product of fructose metabolism, in purine metabolism. This interference has a dual action, both increasing the conversion of ATP to inosine and hence uric acid and increasing the synthesis of purine.
Starvation causes the body to metabolize its own purine-rich tissues for energy. Thus, like a high purine diet, starvation increases the amount of purine converted to uric acid.
A very low calorie diet without carbohydrate can induce extreme hyperuricemia; including some carbohydrate (and reducing the protein) reduces the level of hyperuricemia. Starvation also impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and ketones
Medications most often used to treat hyperuricemia are of two kinds: xanthine oxidase inhibitors and uricosurics.
Xanthine oxidase inhibitors decrease the production of uric acid, by interfering with xanthine oxidase.
Uricosurics increase the excretion of uric acid, by reducing the reabsorption of uric acid once the kidneys have filtered it out of the blood.
Some of these medications are used as indicated, others are used off-label. Several other kinds of medications have potential for use in treating hyperuricemia.
In people receiving hemodialysis, sevelamer can significantly reduce serum uric acid, apparently by adsorbing urate in the gut. In women, use of combined oral contraceptive pills is significantly associated with lower serum uric acid.
Non-medication treatments for hyperuricemia include a low purine diet and a variety of dietary supplements. Treatment with lithium salts has been used as lithium improves uric acid solubility.
For More Information:
Al-Ashkar, Feyrouz (2010). “Gout and pseudogout” Disease Management Project. Cleveland Clinic
Brulé D, Sarwar G, Savoie L (1992). “Changes in serum and urinary uric acid levels in normal human subjects fed purine-rich foods containing different amounts of adenine and hypoxanthine”. J Am Coll Nutr 11 (3): 353–8. doi:10.1080/07315724.1992.10718238
Choi JW, Ford ES, Gao X, Choi HK (January 2008). “Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey”. Arthritis Rheum. 59 (1): 109–16. doi:10.1002/art.23245