Uric Acid: A New Metric for Heart Health

Explore the contents of this article:

⋅ Understanding Uric Acid
⋅ Metabolic Syndrome and the Brain
⋅ The Trouble With Fructose
⋅ How to Lower Uric Acid

Before she passed away in a memory-care unit at age 93, my friend George’s mother had been suffering for years from a combination of gout, diabetes, high blood pressure, and dementia. On the surface, these conditions may not seem related, but a growing body of evidence suggests they may share a common underlying mechanism: high levels of uric acid.

“Globally, we’re being devastated by chronic degenerative conditions: type 2 diabetes, obesity, heart disease, various forms of cancer, and Alzheimer’s. These are metabolic issues — problems with how our bodies use fuel to create energy,” says David Perlmutter, MD, neurologist and author of Drop Acid: The Surprising New Science of Uric Acid.

Traditionally, metabolic health markers have included fasting blood sugar, insulin levels, blood lipids, body mass index, and blood pressure. But some physicians are now paying close attention to uric acid as well.

“We’ve known for a long time that there’s a correlation between high uric acid and obesity, hypertension, and diabetes. Now we know that it’s not just an innocent bystander but is playing a central role in causing them,” says Perlmutter.

Understanding Uric Acid

One of the body’s waste products, uric acid is generated when the body metabolizes purines. These organic compounds are abundant in an array of food and drink, with the highest concentration found in red meat, beer and spirits, and in certain seafoods. Our bodies also create their own purines (and subsequently uric acid) when we metabolize fructose and alcohol.

Because our bodies can’t break down uric acid, we need to excrete it. “We have two ways to get rid of it. About a third of it goes through the gut, and the other two-thirds go through the kidneys,” explains University of Colorado professor of medicine Richard Johnson, MD, author of Nature Wants Us to Be Fat.

When uric-acid levels are under control, this process works nicely. But when they rise past a certain threshold, excess uric acid can overwhelm our ability to excrete it, forming crystals in the kidneys that can develop into kidney stones. These crystals can also accumulate in joints, leading to the painful swelling and inflammation known as gout.

“Traditionally, we’ve looked at uric acid in the context of only two things: kidney stones and gout,” Perlmutter says. “To this day, that’s how it’s being taught in medical schools.”

“In the last few decades, uric acid has been linked with heart attacks, heart disease, and systemic inflammation.”

New research suggests the risks of excess uric acid don’t end there. “Now there’s data showing that maybe 80 percent of people with gout also have crystals in their aorta or in their coronary arteries,” says Johnson.

That means these crystals also have the potential to damage the heart. “In the last few decades, uric acid has been linked with heart attacks, heart disease, and systemic inflammation,” he adds.

While many doctors still check uric-acid levels only in patients with gout, that’s changing. Cardiologist Mimi Guarneri, MD, founder and president of the Academy of Integrative Health and Medicine in La Jolla, Calif., routinely checks her patients’ levels. “The reason I test it is because of the links with cardiovascular disease,” she explains.

Gout and kidney stones become more likely when uric-acid levels ­exceed 7 milligrams/deciliter, which is why the standard “normal” lab value range tops out around 7.2 mg/dL. But some physicians suspect cardiovascular risks occur at lower levels, even in the absence of ­other symptoms.

“Uric acid’s effects on the heart are sort of hidden,” Guarneri notes. “It can act as a potent oxidant, causing oxidative stress and damaging the lining of the blood vessels.”

Ideally, levels should be below 5.5 mg/dL, says Perlmutter. “The literature is clear that cardiometabolic risk begins at that level in men, women, and children, so our target goal is 5.5 mg/dL or less.”

The Survival Switch

Why would our bodies generate a potentially harmful compound? The answer lies in the differences between our modern environment and the one in which our ancestors evolved millions of years ago. It turns out that uric acid isn’t merely a waste product; in certain circumstances, it can help keep us alive.

“Uric acid is a central player in regulating our metabolism. It’s an alarm system telling our bodies to prepare for times of food scarcity,” Perlmutter explains.

Around 14 million years ago, the earth’s temperature dropped sharply, initiating an ice age. “The cooling eventually became a powerful environmental pressure, favoring survival among those who were able to sustain significant periods of caloric scarcity,” he writes in Drop Acid.

Among the adaptations our ancestors developed was a deactivation of the gene that codes for uricase, a liver enzyme that breaks down uric acid. Without that enzyme, uric acid can accumulate in our system.

Why would this be adaptive? Uric acid causes oxidative stress inside the body’s cells, suppressing mitochondria’s ability to produce energy. “When you drop the cells’ active energy, it’s like the low fuel warning on the dashboard. It stimulates hunger,” Johnson explains.

Not only does that process encour­age additional calorie consumption, but it also reduces fat burning, increases fat storage, and raises blood pressure and blood sugar.

These effects are useful when facing starvation. Consuming more energy and storing it away can get a person through lean times: When blood sugar runs high over an extended period, insulin becomes less effective at moving glucose into muscle and liver cells — what’s known as insulin resistance. In the short term, this helps ensure that all that glucose remains available to fuel the brain as it searches for more food to pad the stores.

We can witness this energy-­conserving process in nature. “Animals in the wild that ingest large amounts of fructose present in honey and fruit activate a series of survival responses that include foraging for food, lowering their metabolism, becoming insulin resistant, and increasing fat storage,” explains Johnson.

This strategy is used by hibernating animals as well as by birds preparing for long-distance travel; it helps them survive periods of food shortage. “Our studies suggest that uric acid produced from the metabolism of fructose activates this whole process.”

The difference between modern humans and our Ice Age ancestors, as well as between modern humans and wild animals, is that we don’t have hibernation, long migrations, or long periods of food scarcity to help us use up all that stored energy. Yet when there’s insulin resistance, the “survival switch” mechanism stays on. This sets off a domino effect, known in humans as metabolic syndrome.

Metabolic Syndrome and the Brain

Insulin resistance, high blood sugar, and high blood pressure aren’t only dangerous for the heart; they’ve also been linked to a higher risk of dementia and Alzheimer’s disease. “Everything bad for the heart is also bad for the brain because it affects the blood vessels,” notes Guarneri.

A study that followed 1,598 seniors for a decade discovered that those with the highest baseline levels of uric acid were 1.8 times more likely to develop dementia than those with the lowest levels. Another study, of 228 elderly people in Japan, published in 2016, found that subjects with the highest levels of uric acid were more than four times as likely to be cognitively impaired than those with lower numbers (specifically, levels below 5.5 mg/dL for men and 4.2 mg/dL for women).

Uric acid inhibits the production of nitric oxide, a chemical that relaxes blood vessels and facilitates blood flow.

While these studies don’t prove uric acid causes cognitive decline, there are a couple of possible mechanisms for how elevated uric acid might hurt the brain. First, while insulin resistance can boost the brain in the short run by giving it more glucose, long-term insulin resistance compromises the brain’s ability to function.

Second, uric acid inhibits the produc­tion of nitric oxide, a chemical that relaxes blood vessels and facilitates blood flow. “We certainly don’t want to compromise blood flow to the brain, which is what happens when nitric oxide is unavailable,” ­Perlmutter notes.

The Trouble With Fructose

Modest amounts of fructose are found in fruit, honey, and vegetables such as broccoli, asparagus, artichokes, and okra. Still, whole foods are not where most Americans are getting the bulk of their fructose.

Some estimates suggest that in the early 20th century, the average American ate around 15 grams of fructose a day — roughly an orange plus a cup of blueberries. Today, we consume an average of more than 55 grams. Most of that comes from soft drinks, desserts, sauces, condiments, and processed foods. Fructose, along with glucose, is also found in table sugar.

This trend is leading to unexpected health problems in certain populations.

Gout was once known as the disease of kings, because only the wealthy could afford to consume great quantities of purine-rich red meat, organ meats, shellfish, sardines, anchovies, and beer and spirits. Yet “shellfish and beer” doesn’t exactly describe the diet of American teens, many of whom are now showing elevated uric-acid levels.

A small study of adolescents diagnosed with hypertension found a strong correlation between uric-acid levels over 5.5 mg/dL and high blood pressure. The randomized, double-blind, placebo-controlled trial found that taking measures to reduce uric acid successfully lowered the teens’ blood pressure, demonstrating that uric acid may have been initiating their hypertension.

“Why would uric acid be high in a 14-year-old?” Johnson asks. “These were teens who were drinking a lot of soda. We realized that sugar could do it.”

“Why would uric acid be high in a 14-year-old?” Johnson asks. “These were teens who were drinking a lot of soda. We realized that sugar could do it.” Specifically, high-fructose corn syrup, the most common sweetener for conventional sodas and snacks.

“Fructose is substantially sweeter than glucose, and making high-fructose corn syrup is very, very cheap,” Perlmutter notes.

Our uric-acid levels have risen in tandem with our fructose consumption. “The average Ameri­can had a uric-acid level of 3.5 mg/dL in the 1920s, and today it’s north of 6,” Perlmutter says. “High-purine foods aren’t the biggest culprits. It’s the fructose.”

Alcohol is another trigger, Johnson says. It lowers adenosine triphosphate, a key source of cellular energy. “It does it both indepen­dently and by stimulating fructose production.”

While glucose from refined carbohydrates doesn’t lead directly to uric-acid production, it can transform into fructose in the body.

And animal studies suggest that excess salt may also trigger the body to convert glucose into fructose.

Uric Acid: Chicken or Egg?

If elevated uric acid is associated with a range of metabolic problems, lowering uric acid should help reverse them, right? The frustrating answer so far is that we don’t know.

Uric acid may trigger metabolic syndrome, Johnson explains, but then other processes take over and perpetuate it. “We see small, partial effects of lowering uric acid on ­obesity, insulin resistance, fatty liver, and high blood pressure,” he says. “We discovered that what initiates something and what continues to drive it can be different.”

For instance, uric acid can raise blood pressure by constricting blood vessels. Over time, the kidneys ­develop a low-grade injury in response to reduced blood flow, and that can continue to drive high blood pressure even if uric-acid levels come down.

Likewise, uric acid can harm mitochondria, the cellular power plants that generate energy. When that goes on long enough, the mitochondria can start to deteriorate.

At that point, lowering uric acid may not have much of an effect on symptoms of metabolic syndrome.

“There’s strong clinical evi­dence that high uric acid increases your risk of heart disease, type 2 diabetes, hyper­tension, and kidney disease. What’s not proven is whether lowering uric acid reduces the risk,” Johnson says. “But I’m pretty convinced that if you can lower uric acid before you get metabolic syndrome, there’s going to be benefits.”

How to Lower Uric Acid

If you’re concerned about your uric-acid level, the first step is to measure it, Perlmutter says. You can ask your physician to order a uric-acid test as part of routine labs at your annual physical, or use a home testing kit. (Several brands are available online. Typical cost is about $80.)

If you discover you’re above 5.5 mg/dL, Perlmutter recommends testing once a week while you implement a program of dietary and lifestyle changes, then once every two weeks thereafter until reaching levels of 5.5 mg/dL or below.

“The top three things to reduce your uric-acid level are [to] ­reduce your fructose consumption, reduce your fructose consumption, and reduce your ­fructose consumption.”

Aim to test first thing in the morning, before meals or exercise. Levels tend to fluctuate in response to food, alcohol, purines, heat stress, and intense exercise.

The following are some other steps you can take.

1) Address Diet

Dietary changes to lower uric acid are pretty straightforward.

“The top three things to reduce your uric-acid level are [to] ­reduce your fructose consumption, reduce your fructose consumption, and reduce your ­fructose consumption,” ­Perlmutter says. “That’s the biggest issue, far and away.”

You may also want to reduce your salt consumption if you eat a lot of starchy, high-glycemic foods, such as rice, bread, and potatoes, because salt may activate pathways that convert glucose into fructose.

Increasing hydration can also help, because dehydration concentrates the blood and can lead to elevated uric acid.

Guarneri recommends limiting high-purine foods and alcohol, and drinking tart cherry juice, which research finds can lower serum levels of uric acid.

2) Try Supplements

In scientific studies, several supplements have shown promise for reducing high levels:

Quercetin, a compound found in onions, apples, and capers, inhibits the actions of an enzyme called xanthine oxidase, which is crucial in generating uric acid. A study published in 2016 found that adults taking 500 mg of quercetin per day significantly lowered their levels of uric acid. (For more on quercetin, visit “What Are the Health Benefits of Quercetin?“)

Luteolin, a flavonoid found in many vegetables and fruits, may have uric-acid-lowering abilities comparable with those of the most commonly used medication to treat gout. Perlmutter recommends 100 mg per day.

Vitamin C has been shown in multiple studies to lower uric acid and protect against gout. A meta-analysis at Johns Hopkins University concluded that vitamin C supplementation significantly lowers serum levels of uric acid. Johnson recommends 500 mg twice daily. (For more about this essential nutrient, see “What You Need to Know About Vitamin C.”)

3) Right-Size Exercise

Both too little and too much exercise can increase uric-acid production.

When we push too hard, too often, without taking time for recovery, the breakdown of muscle tissues increases the supply of purines for the body to metabolize, leading to spikes in uric acid.

Meanwhile, a study conducted by researchers in South Korea found that subjects who were sedentary for more than 10 hours a day were more likely to have high uric acid than those who were inactive for fewer than five hours per day. The researchers calculated that low- and moderate-intensity physical activity reduced the subjects’ risk of elevated uric-acid levels by 12 percent, and a routine including some vigorous physical activity reduced the risk by 29 percent.

Perlmutter prefers to err on the side of vigorous exercise. “Strength training is best for your metabolism and improving insulin sensitivity. Uric acid might tick up a bit after breaking down muscle cells, but the net effect long-term is beneficial,” he says.

Just be sure to build in time for recovery between workouts.

4) Experiment With Intermittent Fasting

Research suggests that limiting food intake to an eight-to-12-hour window can improve insulin sensitivity, blood pressure, fat metabolism, gut function, and immune function. It can also lower inflammation and help regulate uric acid.

Note that some medications, like diuretics, proton pump inhibitors, beta-blockers, and blood pressure medicines, are associated with elevated uric acid. Work with your healthcare provider to test and address your level to ensure you’re taking a holistic view of possible contributing factors.

As with any measure of health, no single marker can tell you everything. But as the new kid on the block when it comes to cardiometabolic health, uric acid may provide another important metric for keeping the body in balance before disease sets in. It may not be mainstream yet, Johnson notes, but he expects it will be.

“I think there will be a time when people realize that treating uric acid early has a chance to really show benefit.”

Fruit vs. Fructose

Lowering your overall fructose intake does not mean ditching all fruit. “The small amount of fructose you eat with natural fruit is actually good,” says clinician and researcher Richard Johnson, MD, who has conducted multiple clinical trials on fructose metabolism.

Whole fruits contain nutrients — such as vitamin C, flavonoids, potassium, and fiber — that tend to block the harmful effects of fructose. Most fruit juices, though, lack many of these beneficial substances and concentrate fructose at much higher levels. Likewise, dried fruit is higher in fructose than its fresh counterparts.

Johnson suggests sticking to modest portions of fresh, whole fruit, and consuming 8 grams or less of fructose at a time; this is a little more than you’d find in a cup or two of berries or in a single orange or banana.

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This article originally appeared as “A Surprising Metabolic Marker.”