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Once considered a “waste product” and only discussed in terms of gout or kidney stones, uric acid is proving to be a powerful indicator to assess your risk factors for metabolic syndrome, hypertension, obesity and other imbalances in metabolism and cardiac health. Sometimes, uric acid levels rise even before symptoms develop, suggesting that it could become an important screening tool in medicine.
In today’s article, we will discuss these details and answer these questions:
Let’s get started!
What Is Uric acid?
Uric acid, or urate, is the end product of compounds metabolized through the purine pathway. These include fructose (a type of sugar found in fruit) and nucleotides (part of the building blocks of DNA and RNA). When these are metabolized, mainly in the liver, uric acid is released, and concentrations can be measured in the blood. Then, uric acid undergoes excretion by the kidneys, as do other compounds like creatinine.
Uric acid can be an antioxidant or pro-oxidant, contributing to oxidative stress, depending upon its microenvironment in the body. (Source 1)
Interestingly, most animals make an enzyme called uricase, that breaks down uric acid, keeping serum uric acid levels low. Humans have lost the ability to make their own uricase and have higher uric acid levels in the blood compared to other mammals, typically over 3 mg/dl. (Source 2)
This may have been a beneficial adaptation earlier in human evolution, allowing us to store more body fat. However, it may not be so beneficial in modern times, as we will discuss.
Health Risks of Elevated Uric Acid
Elevated serum uric acid, or hyperuricemia, is associated with a range of metabolic and cardiovascular diseases. These include:
Metabolic syndrome is the collection of several known cardiovascular risk factors associated with insulin resistance. For diagnosis, three of the five characteristics need to be met:
Mechanistically, the metabolism of purines stimulates fat storage and insulin resistance. (Source 2)
Over time, metabolic syndrome progresses to type 2 diabetes, which increases risk for heart disease and heart failure. The cardiometabolic factors are all connected.
Elevated uric acid concentration is an independent predictor for the development of high blood pressure. In addition, lowering uric acid has also been shown to lower blood pressure in hypertensive patients. (Source 2)
When uric acids are elevated over time, uric acid creates both inflammation in the kidney and changes to the microvascular system in the kidney. While the uric acid initiates hypertension, it’s the damage to the kidney that perpetuates it, making one more sensitive to salt and damaging renal function. (Source 2)
Several mechanisms are at play here. Elevated uric acid:
The result is hypertension. So, while medication like diuretics or nutrition interventions like a low sodium diet helps manage the symptom, they don’t address the root cause.
Pre-diabetes and Type 2 DiabetesHigh uric acid is not a consequence of insulin resistance but a driver. In fact, uric acid levels are an independent risk factor for insulin resistance, which leads to pre-diabetes, diabetes and associated complications, including heart disease. Epidemiological studies suggest high serum uric acid levels predict insulin resistance and diabetes, even before diagnosis is made. In addition, allopurinol, a uric acid-lowering medication, may improve insulin resistance. (Source 2)
In insulin resistance, blood sugar levels are high. Insulin, the hormone required to move glucose from the bloodstream and into cells where it can enter the citric acid cycle and create energy, becomes required in greater amounts to address the blood sugar levels. Eventually, the cells are overwhelmed and insulin signaling becomes impaired.Mechanistically, too much uric acid plays a causal role in insulin resistance because it:
With obesity, we are talking about not simply body mass index, but the accumulation of visceral, midsection fat which is associated with insulin resistance. Like the other condition, epidemiology shows elevated uric acid in the blood predicts the incidence of obesity and the development of fatty liver disease.
(Source 2)This is because uric acid directs fat storage to adipose tissue (fat tissue) as well as the liver. Underlying factors include:
The association between heart health and uric acid has been known for decades in cardiology, but the role of uric acid doesn’t seem to directly cause or contribute to heart disease, like the other conditions above. Instead, uric acid contributes to hypertension, insulin resistance, obesity and kidney disease. These are all risk factors for heart disease. (Source 2)
In addition, uric acid promotes inflammation, oxidative stress and endothelial dysfunction, which may influence atherosclerosis and the development of coronary heart disease. (Source 2)
On the other hand, lowering uric acid improves markers of heart health and metabolic syndrome as well as decreases cardiovascular events (heart attack and stroke), especially in those without renal disease. (Source 2)
As you can see, the metabolic conditions we’ve discussed today are modern chronic disease related to lifestyle factors, including diet.
What Causes High Uric Acid?Uric acid plays an important role in determining metabolic health. Because of this, it may not be surprising to learn that the main factor contributing to hyperuricemia is diet, specifically a highly processed standard American or Western diet. This type of diet already puts someone in a high-risk category for chronic disease.
Certain foods are higher in purines than others, and lowering purines in the diet is the main nutrition intervention in those with gout, a type of arthritis where uric acid crystals form in the big toe and other joints. These foods include:
Sucrose is a naturally occurring sugar found in fruit and some other plant foods, that contains one molecule of glucose and one molecule of fructose. Adding sugar to food increases its fructose content. Fructose is also concentrated in sweeteners like agave syrup and high fructose corn syrup. Soda, juice and other sweetened beverages deliver extremely high amounts of fructose rapidly into the body and result in high uric acid levels.
Now, let’s talk about how to reduce uric acid levels, naturally and safely to decrease health risk and mortality.
Action Steps to Maintain Healthy Uric Acid LevelsThere is an association of serum uric acid levels and diet, which in turn either directly or indirectly contribute to cardiometabolic disease. To manage this, we can start with diet and add in other supportive measures. Here’s how:
When you go to the doctor, they might look at blood pressure or other biomarkers of heart and metabolic health. Uric acid is a lab to add to the list, because it may increase risk of cardiovascular disease and all-cause mortality. If uric acid levels are high, in addition to diet lifestyle changes to support overall health, certain supplements, including Liposomal Vitamin C are incredibly helpful.