I've heard of uric acid before. What the heck is it?

January 24, 2021 Chris Trejbal

I decided to take a dive into the science behind uric acid, its metabolism, and its relation to disease states.

What are purines, and what is uric acid? How are they metabolized?
Hyperuricemia vs. normal uric acid levels.
Uric acid and disease.
Uric acid in children.

An introduction to purines and uric acid

This is a purine. A purine is a double-ringed molecule that looks simple but is important for human life.

DNA is made up of two kinds of building blocks: purines and pyrimidines. These blocks join together to form the strands of DNA, which carry the instructions for our cells to make the proteins that keep us alive.

Adenine (A) and guanine (G) are two examples of purines. They link up with pyrimidines to create the "rungs" of the DNA "ladder." This pairing is essential for forming the DNA structure. The order of these base pairs encodes the genetic information that tells our cells how to make proteins.

In the image below, you can see how adenine and guanine (the purines) connect with their matching pyrimidines to build the DNA strands.

DNA!

To recap: Purines are molecules that form DNA. DNA is the blueprint for making proteins, which are crucial for life. Adenine and guanine are both purines.

Metabolism

Purine metabolism

Now that we understand what purines are and why they’re important, let's look at how they break down in the body into uric acid.

Purines are made within the body, but we also consume them through diet. Some foods that are high in purines include:

Meats (venison, turkey, veal, liver, bacon)
Seafood, some fish (anchovies, sardines, herring, mussels, codfish, scallops, trout, and haddock)
Some alcohol
Some legumes

After food is eaten, it’s then broken down into its constituents, such as protein, carbohydrates, fats, vitamins, and minerals. Purines get converted to a compound in the liver called xanthine. Next, it gets oxidized by xanthine oxidase to form uric acid. Finally!

To recap: Purines (adenine and guanine) ---> uric acid

Uric acid metabolism

What happens to uric acid once it's formed within the body? After uric acid is created in the liver, it’s then converted into urea. 60-70% is processed in the kidneys and excreted in urine, and 30-40% through the intestines.

To recap: Uric acid ---> urea, out in urine

Ur-ine for a treat. Keep reading!

Normal uric acid levels & hyperuricemia

What is hyperuricemia, and what are the clinical guidelines for elevated uric acid levels in the blood?

Hyperuricemia is elevated uric acid in the blood, which is considered anything over 7 mg/dL. The following may contribute to elevated uric acid levels:

Purine-rich diet
Error of purine metabolism: hypoxanthine phosphoribosyltransferase (HPRT) deficiency, phosphoribosylpyrophosphate (PRPP) synthetase overactivity
Cell breakdown or turnover: lymphoproliferative diseases, myeloproliferative disease, polycythemia vera, Paget disease, psoriasis, tumor lysis, hemolysis, rhabdomyolysis, exercise

Uric acid and disease

Now that we know what uric acid is and the levels considered too high, let's address whether it causes inflammation. This topic can be a bit confusing.

Think of it like this: Is uric acid the spark that ignites the fire, or is it the dry wood that keeps it burning? Uric acid is a molecule produced from natural breakdown reactions in the body. However, just because it’s a natural by-product doesn’t mean it’s always safe, especially when present at high levels in the blood.

Inherently, uric acid does not cause inflammation. In fact, it's quite the opposite. Uric acid is an essential molecule that acts as an antioxidant and may account for up to two-thirds of the blood’s antioxidant capacity. However, like some antioxidants, if present in excessive amounts, it can become a pro-oxidant, leading to oxidative stress.

A PubMed search of systematic reviews reveals a significant number of studies showing a close relationship between high uric acid levels and kidney and cardiovascular diseases. There appears to be a dose-response relationship between blood uric acid levels and these diseases. Additionally, higher body mass index (BMI) and waist circumference are also associated with increased uric acid levels.

The kidneys play a crucial role in removing certain substances from the body, including uric acid, through urine. One of the best ways to assess kidney health is through a test called estimated Glomerular Filtration Rate (eGFR). Diseases that impair kidney function, such as kidney disease, can decrease the filtration rate, allowing more uric acid to remain in the body, which contributes to higher levels of uric acid in diseased states.

Additionally, a study published in the Journal of Diabetology and Metabolic Syndrome suggests that uric acid levels may be elevated in conditions of insulin resistance, often accompanied by kidney impairment.

When it comes to cardiovascular disease, understanding the role of uric acid is more complex. Researchers are still investigating why uric acid levels rise during disease states, but a definitive conclusion has yet to be reached.

What foods help reduce uric acid levels?

A review published in the International Journal of Rheumatoid Diseases suggests that certain dietary factors like vitamin C, coffee, certain wines, milk, and yogurt have the potential to lower levels of uric acid in the blood. Other sources support these findings, and in the case of coffee, it's believed that compounds other than caffeine may play a role.

When blood uric acid levels are elevated (a condition called hyperuricemia), dietary antioxidants might counteract the pro-oxidant effects of uric acid. It's worth noting that wine, vitamin C, and coffee are rich in antioxidants, which could explain their potential to help lower uric acid levels.

Dairy products present an intriguing aspect in this discussion. A cross-sectional analysis comparing various dietary patterns—meat eaters, fish eaters, vegetarians, and vegans—found that vegans had the highest levels of serum uric acid. This could be attributed to certain plant-based foods like soy and specific legumes, which are high in purines and lack the uric acid-lowering effect of dairy.

But why does dairy have this effect? According to one review, dairy proteins such as casein and lactalbumin may play a role in reducing serum uric acid levels. These proteins are commonly found in dairy products such as milk, cheese, and yogurt. Another study demonstrated that consuming 80 grams of casein, lactalbumin, and soybean isolates was effective in lowering uric acid levels. Foods rich in casein include dairy products like milk and cheese, while lactalbumin is found primarily in whey protein supplements and dairy products.

Yum.

Uric acid levels in children

A child consuming a balanced diet, and without any diseases that impact uric acid breakdown or excretion, should not expect any issue handling uric acid.

If you’re interested, here’s a list of diseases and/or disorders:

1. Gout

2. Chronic diseases (a) Metabolic disease Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency (complete, Lesch–Nyhan syndrome; partial, Kelly–Seegmiller syndrome) Adenine phosphoribosyl transferase (APRT) deficiency Phosphoribosylpyrophosphate (PRPP) synthetase overactivity Myoadenylate deaminase deficiency Glycogen storage diseases (types I, III, V, and VII) Acyl-coenzyme A dehydrogenase deficiency (b) Down syndrome (c) Congenital heart disease (especially cyanotic diseases) (d) Genetic diseases Familial juvenile hyperuricemic nephropathy (FJHN)

3. Acute diseases (a) Gastroenteritis (especially Rotavirus infection) (b) Bronchial asthma (especially on attacks) (c) Malignant disorders (tumor lysis syndrome) (d) Hemolytic anemia (e) Drugs Diuretics (thiazide) Theophylline Anticonvulsants (valproate and phenobarbital) Cyclosporine Pyrazinamide

4. Lifestyle-related disorders (a) Obesity (b) Metabolic syndrome

Regarding high-purine foods, I don’t see any reason for children to avoid them. Actually, foods like legumes and meat are good sources of protein and other nutrients, and removing them may negatively impact overall health.

What we know, and what we don’t

More information is always needed to strengthen a hypothesis, but there seems to be some evidence to support the following:

Having higher serum uric acid levels is strongly correlated with disease states.
Does uric acid exacerbate disease states, or is it generally a by-product of them? We don’t know yet.
Eating a balanced diet that is high in antioxidants, as well as dairy and dairy protein may be beneficial in attenuating serum uric acid levels.
In my research, I did not find any reason for children to avoid foods high in purines, as long as they are consuming a balanced diet.

In conclusion

Eating a balanced diet high in antioxidants and including dairy seems to be important in regulating uric acid levels in healthy adults and potentially improving uric acid levels in those with certain diseases. It seems like elevated uric acid levels may not be a result of diet per se but are much more related to disease progression, but more information is needed.

References

Which Foods are Safe for Gout? (purine diet)

Deoxyribonucleic Acid (DNA) Play Audio

Uric Acid, Hyperuricemia and Vascular Diseases (purine metabolism)

High plasma uric acid concentration: causes and consequences (AO status information)

Biochemistry, Xanthine Oxidase - StatPearls (xanthine oxidase)

Renal Transport of Uric Acid: Evolving Concepts and Uncertainties (Uric acid metabolism)

High plasma uric acid concentration: causes and consequences (Uric acid metabolism)

https://www.ncbi.nlm.nih.gov/books/NBK459218/#:~:text=Hyperuricemia%20is%20an%20elevated%20uric,a%20combination%20of%20both%20processes (Hyperuricemia)

Intake of purine‐rich foods, protein, and dairy products and relationship to serum levels of uric acid: The Third National Health and Nutrition Examination Survey (Dairy intake)

Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males | British Journal of Nutrition (Coffee)

Coffee, tea, and caffeine consumption and serum uric acid level: The third national health and nutrition examination survey (Coffee)