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Beyond Gout: Why Lowering Uric Acid Matters

Article at a Glance
  • Uric acid is a waste product of protein and sugar metabolism that can accumulate to unhealthy levels in some people.
  • Uric acid acts as both an antioxidant as well as a pro-oxidant depending on how much is circulating in the blood.
  • What are considered to be healthy levels of uric acid have been increasing as doctors see populations with higher average levels of uric acid.
  • There is mounting concern that current lab ranges for acceptable uric acid may be out of touch with what is healthy for most people.
  • Genetics play a role in determing uric acid levels.
  • Despite the genetic link, there are multiple lifestyle adjustments people can make to bring uric acid under control.

Scientifically reviewed by Dr. Aaron Gardner

If you’ve arrived at this blog post chances are you’ve already scoured the mountain of identical posts out there that discuss uric acid in the context of gout.

The story goes a lot like this: eating a diet rich in sugar, alcohol and high purine meats and seafood leads to an accumulation in the blood of a waste product called uric acid. The uric acid forms crystals which attach to and irritate joints. The result are painful conditions like gout and arthritis.

And yes, all of this is true. Uric acid is a waste product of purine metabolism, which are essentially microscopic crystal compounds found in food. However, purines are similar to cholesterol in that we actually make the majority of purine circulating in the body, so they have both “endogenous” and “exogenous” sources. And food isn’t the whole story with uric acid. While different groups like to pin elevated uric acid on different lifestyle factors (usually sugar, alcohol and meat) some people just have a genetic predisposition to higher uric acid levels.

But that’s exactly what I want to focus on first in this post – what constitutes “higher” uric acid?

Looking at labs like Boston Heart Diagnostics (which provide the ranges we use in our custom nutrition plans), you see uric acid “in the green” if your levels sit anywhere beneath 7 mg/dl. However, a growing chorus of medical professionals agree that a uric acid level of 7 is way too high.

Side note: if you haven’t been to the doctor in awhile and are wondering what your uric acid levels are, there are at home test kits available for purchase on Amazon.

Are Most Labs Wrong About Healthy Uric Acid Ranges?

A conversation between two well known doctors in the nutrition world, Dr. Peter Attia and Dr. Robert Lustig on Peter Attia’s podcast a few weeks back is instructive. Both men argue that what is considered by most labs to be an acceptable uric acid level is out of touch with what is actually healthy.

Dr. Attia says his patients need to have uric acid below 5.0 mg/dl and that this is “non-negotiable.” Dr. Lustig gives a little more leeway with acceptable uric acid at 5.5 mg/dl or beneath. Both see uric acid as primarily driven by “fructose bio-toxicity,” rather than by eating too much meat.

When you start digging into some of the medical literature you start to see where these guys are coming from.

It seems that the problematic monosodium urate crystals formed by uric acid begin at a level of 6.8 mg/dl in the blood, which is less than ideal for health, but nevertheless listed as in the “green” on many of our most sophisticated labs.1  Monosodium urate crystals are thought to be the type responsible for gout, and are also thought to be bad for heart health.

Hyperuricemia (essentially a precursor state to gout) begins at 7.0 mg/dl for men and 6.0 mg/dl for women. So, you could be just barely on the yellow (beginning of the trouble zone on Boston Heart’s panel) and have hyperuricemia.1 In other words, your lab could be tacitly blessing the beginnings of a major metabolic problem.

The Jekyl vs. Hyde Nature of Uric Acid

While it’s likely that the current ranges for uric acid levels have creeped too high, we don’t want zero uric acid either.

Parkinson’s patients typically present with very low uric acid levels, and we do know that, at least at healthy levels, uric acid acts as an antioxidant in the body.2

When on its “best behavior,” uric acid operates as a free radical scavenger and metal chelator.3

However, when it rises to the level of hyperuricemia, it seems to take on a pro-oxidant role, increasing levels of oxidative stress in the heart, kidney and liver.

Health Conditions Associated With Elevated Uric Acid

Gout

The big one to mention right off the bat is gout. Gout is thought to be caused by the formation of uric acid crystals that damage the joints, commonly causing pain in areas like the big toe, elbows and feet (this is where you get the term “gouty arthritis”).

Kidney Stones

Uric acid stones are one of four types of kidney stone. Uric acid driven kidney stones can form when uric acid levels rise to unhealthy levels and urine PH remains too acidic.

Heart Disease

One of the big surprises for me when researching uric acid was the fact that uric acid, when elevated, can play a role in oxidizing LDL particles. The process of oxidized fats binding to LDL is one of the big accelerating risk factors for heart disease.

However, even though the pro-oxidant role of uric acid is fairly well established at this point, historically there have been conflicting views as far as uric acid and heart disease are concerned. It seems that the prevailing view had been that uric acid is a byproduct of other disease states, but it does not cause those states. That thinking is beginning to change now that we know uric acid is a nitric oxide inhibitor. For an example of the conflict over uric acid and heart health, the Framingham study found an association between serum uric acid and cardiovascular disease in women, but not in men.4 But then different studies came to the exact opposite conclusion for men when looking at the same data set.5

The overall modern trend line seems to agree uric acid is an independent risk factor for heart disease, especially as therapies aimed at lowering uric acid also tend to work in lowering high blood pressure.6

For a thorough review, take a look at Uric Acid and Cardiovascular Disease: an update.

Why would lower uric acid mean lower blood pressure?

Hypertension

This is a key point: more uric acid means less nitric oxide.

Uric acid is an inhibitor of nitric oxide synthesis (the creation of nitric oxide via genes like NOS3), which leads to hypertension as the heart needs to pump harder to get blood to the various regions of the body. Nitric oxide is a vasodilator, we need it to relax blood vessels so they can receive blood. At high levels, uric acid disrupts this process.7

Metabolic Syndrome

We can’t say for sure that it’s causative, but metabolic syndrome and high uric acid seem to go hand in hand.8

Strategies for Lowering Uric Acid

Ok, so we now know that even those of us who may have thought we had uric acid under control may have some work to do to bring our numbers into the Attia / Lustig range.

How can we make this happen?

Maintain an Alkaline Urine PH

I wrote about this recently in my blog post on urine PH and alkaline diets. There is good evidence to indicate that we excrete considerably more uric acid in our urine when the PH of our urine is alkaline. You can measure urine PH with at home test strips.

Avoid Sugar and Alcohol

I lump sugar and alcohol into the same boat here because they are metabolized in similar ways by the liver.

As I mention above, Dr. Lustig and Dr. Attia hammered home the point that high uric acid is, in their view, a “marker of fructose bio-toxicity.”

In the podcast interview, Dr. Lustig explains why fructose increases uric acid. To paraphrase, fructose can only be metabolized by the liver. Every time a fructose molecule enters a liver cell, it has the effect of converting ATP to ADP, and through a complex downstream process driven by fructose enzymes in the body, ADP eventually becomes uric acid on the other end. So, just as uric acid is a waste product of purine metabolism, it is also a waste product of sugar metabolism.

This is why many doctors see uric acid as a proxy for sugar consumption over time.

Limit High Purine Meats and Seafood

Although we make the majority of the purine in our bodies “endogenously,” we still get 1/3 of purine from food, and it’s clear that, in some cases, the addition of high purine food makes a difference on serum uric acid. Which foods are the highest in purine?

  • Organ meats
  • Beef
  • Pork
  • Beer and alcohol
  • Shellfish
  • Seafood
  • Duck

I should note here that I have seen the blood work of friends who eat a ton of meat and still maintain a uric acid level of 4.5 mg/dl (although his CRP is pretty high), so clearly dietary purine isn’t the whole story, but for some people, watching purine and avoiding the worst offenders like beef, pork, organ meats and poultry will offer benefit.

Since the studies are all over the map here (some find higher uric acid with higher protein, others don’t) the only way to know is to test your own numbers on various dietary protocols.

What About Grains?

To continue with the low purine theme, some would be surprised to learn that grains, especially whole grains like oats, are actually fairly high in purine. Having said that, it’s unlikely that eating whole grains will trigger gout flairs, or be the primary culprit behind higher than normal uric acid.

When whole grains are the driver of inflammation and joint pain, lectins are likely the culprit not purine, but many diet protocols for arthritis do prescribe a gluten free diet, so you be the judge after some self experimentation.

Vitamin C and Uric acid

Although not all studies agree, there is fairly extensive research to indicate that Vitamin C lowers uric acid.

For example, this study which found a 0.5 mg/dl average reduction in uric acid in subjects taking only 500 mg doses of Vitamin C for 2 months versus no change in the placebo group.

Tart Cherries

This is one you see on the internet with regularity and we even listed tart cherry extract as a good supplement for runners with the logic that it seems to reduce inflammation in the body. At first glance, you’d think that the fructose in the cherries would present a problem, especially under the Attia / Lustig thinking on uric acid, and in some cases it might, but there is also evidence of tart cherries being an effective tool in combatting gout attacks. To be clear, the studies don’t show that tart cherries lower uric acid, but they do show that tart cherries seem to be very effective at preventing and lessening the severity of gout flare ups.9

Sodium and Uric Acid

Some studies show a link between sodium in the diet and elevated uric acid.10

Candida, Mold and Uric Acid

We know that the yeast in beer is what gives it its purine content. Is it also possible that species of fungus that have taken up residence in the body could also be part of the equation when uric acid levels get out of range?

Does Coffee Lower Uric Acid?

Again, there is conflicting evidence here. Some sites recommend steering clear of caffeine as a means to avoiding gout flare ups, while others argue that coffee consumption helps lower uric acid. If coffee does act on uric acid, it’s not the caffeine that is driving the benefits. Large scale food frequency questionnaire studies have shown an inverse relationship between coffee consumption and uric acid, but not with tea and uric acid.11 Anecdotally, I have noticed that coffee and espresso have an alkalizing effect on my urine PH (which allows more uric acid to be excreted from the body) and that green tea is actually more acidic.

Do Vegans Have the Lowest Uric Acid Levels?

No, vegetarians and pescatarians have the lowest uric acid, not vegans.

If purine was the only factor in the uric acid equation, it would logically follow that Vegans have the lowest levels of uric acid. However, studies show the opposite is true. Vegans often have high uric acid levels, presumably because a Vegan diet is hard to follow without resorting to processed foods and foods with added sugar (which is everywhere).12

If you find the evidence for urine PH and excretion of uric acid compelling, as I do, you could also theorize that “unhealthy Vegans” who rely heavily on refined grains and processed carbs maintain an acidic urine PH which prevents them from excreting optimal amounts of uric acid. I was also interested to find this nutritionfacts.org page on uric acid describing reductions in uric acid after drinking milk and increases in uric acid after eating soy. Quite a concession from a site that is notoriously biased in favor of the plant based movement, but it goes to show that not all plant foods are healthy in every case.

While Paleo blogs have trotted out this “Vegans have high uric acid” study, they often fail to mention that Vegetarians and Pescatarians tend to have the lowest levels of uric acid, perhaps because they have the option of eggs and dairy products, which aren’t terrible in their purine count and are a low sugar option for a staple food.

Uric Acid and Genetics

For this section, I am bringing in Aaron to give us a run down of the genetic factors that contribute to the build up of uric acid to unhealthy levels in the body.

URAT1/SLC22A12

There are a couple of SNPs related to uric acid that are of interest. The first and potentially most interesting are located in the urate transporter 1 (URAT1) gene which is also called SLC22A12. This protein’s primary function is to regulate the re-absorption of uric acid in the kidneys, so you can see how any changes in function could dramatically alter uric acid levels. In this study, the authors identified three SNPs of real interest rs75786299, rs7929627 and rs3825017.

Of the three the first, rs75786299 (~30 times risk), had by far an away the strongest associated with elevated uric acid in the blood, which would be suggestive of reduced URAT1 activity, with the other two having a lesser but still significant effect on uric acid levels.

Most interestingly a particular combination of the three SNPs, known as a haplotype, showed a much larger (~90 times) risk than any one SNP alone. The individual risks and this haplotype are detailed in the table below. Importantly, whilst this single study showed a strong effect in a Korean population, other studies in Caucasian populations are less clear.13 14

GeneSNPRisk AlleleGout risk (per risk allele)Uric acid effect (per risk allele)
URAT1rs75786299AUnknownx32 risk for hyperuricaemia
rs7929627GUnknownx2 risk for hyperuricaemia
rs3825017TUnknownx2 risk for hyperuricaemia
Combination of aboveA,G,TUnknownx92 risk for hyperuricaemia
ABCG2rs2231142T1.7 xUnknown
rs72552713A2.8 xUnknown
GLUT9rs16890979C1.7 x+ 0.47 mg/dl
rs6449213T2 x+ 0.02 mMol/l
rs12498742A1.25 x (homozygote risk only)Unknown
SLC17A3rs1165205A0.15 xUnknown

ABCG2

There are a couple of other SNPs of interest as well. rs2231142 in the ABCG2 gene is probably the most well known and has a strong association with the development of gout, as does rs72552713 which is also in the ABCG2 gene. AS with URAT1, ABCG2 also functions in the kidney where it functions to export urate into the urine, allowing its excretion.15

The risk allele T of the rs2231142 SNP is very strongly associated with an increased risk of gout, with those homozygous for the risk allele having approximately 3.5 times the risk, and heterozygotes having roughly twice the risk16, an effect which several other studies have supported.17 18

A similar effect for the risk allele A of rs72552713 has also been reported, although there is less supporting evidence in multiple populations.19

GLUT9/SLC2A9

Finally, other SNPs in SLC2A9 rs16890979, rs6449213 and rs12498742 and SLC17A3 rs1165205 have also been associated with an increased risk of gout. SLC2A9, also known as GLUT9 is a major regulator of urate transfer in the kidneys, and so it is unsuprising that SNPs have been identified which increase risk.20 21 Of these, rs16890979 is perhaps the most widely investigated and the risk C allele was associated with approximately a 3.5x increased risk of developing gout, through having serum levels approximately 0.5 mg/dl higher for each copy of the risk allele carried.

Key Takeaways

When I look at my uric acid numbers these days, the points that jump out for me are:

  • Uric acid levels in the “green” from most labs might not mean much.
  • Sugar is to be avoided expect as a very occasional treat.
  • Proteins have waste products – use meat as a condiment not a main course.
  • I have a new respect for decaf coffee.
  • Supplements like Vitamin C have very little downside and may be valuable in keeping uric acid in range.
  • Alcohol is fun socially, but it’s bot good for you.
  • As crazy as it sounds, it may be valuable to keep an eye on what is driving the PH of your urine. The more alkaline the better.

John O'Connor

John O'Connor is the founder of Gene Food and an Integrative Health Coach, trained at Duke IM. He lives in Austin, Texas.

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