Gout and Our Starving Ancestors

You know how people are always telling you that something tasty you thought was also good for you may actually not be? Here’s another one: umami. Not the glutamate salt to which we are most sensitive, but some of its synergistic sidekicks. These chemicals are called 5′ (pronounced five-prime) ribonucleotides, three classes of which are found in meats, plants/mushrooms and seafood: inosonate, guanylate and adenosine monophosphate, respectively, plus a few less common ones. All of them are classed as purines. These are the chemicals that can increase uric acid in the blood. 

Depending on your genetic makeup, consumption of purines can cause gout—a problem I have seen frequently in the brewing industry, as beer and especially yeast can be contributors. But there also may be less painfully obvious consequences for our health: fatty liver, high blood pressure, diabetes, obesity and more. 

Why would this be? It’s a fascinating story. Most mammals have an enzyme called uricase (uric acid oxidase), capable of removing excess uric acid from the blood. Our primate ancestors, having boldly migrated out of Africa into Europe about 19 million years ago, got there at exactly the wrong time, in an extended period of global cooling. Then, as in the ‘when it rains (or snows), it pours’ adage, twin asteroids impacted the region that is now Southern Germany. The obvious fallout of all of this was a heaping helping of hardship, their fossilized teeth showing signs of starvation. 

A series of mutations eventually helped these proto-apes better conserve food resources, including storing fructose as fat. Unfortunately, this adaptation also deleted the uricase gene, leaving them—and us—unable to control uric acid levels. This unlucky group, by the way, toughed it out for a few more million years, then high-tailed it back to Africa and continued evolving into human beings and our ape cousins. With our abundant food resources, this mutation is now causing trouble.

I was curious about the well-documented connection between purines in foods, their intake and their role in gout and hyperuricemia, the elevated blood uric acid that causes it. It seemed to me that a lot of the charts out there on what to eat or avoid seemed oversimplified, so I found a relatively recent paper (Kaneko, below), that had more detail, plus fresh assays of dozens of food ingredients.

First, it should be pretty obvious to everyone that I am not a doctor, so if you’re going to make lifestyle changes, you should first contact yours.

Here are some quick toplines. Purines are not created equal when it comes to this issue. There are four major players, two of which are troublesome here: adenine and the worst offender, hypoxanthine. The other two, xanthine and guanine, have minimal effects. As the chemical terminology is confusing, we can cut to the chase; just know that meat, fish and shellfish score in the middle of the five-point scale used to categorize uricogenic foods. Organ meats like liver are always at the top. 

While scores in the 2–3 range may make purine levels appear high in some vegetables, mushrooms and grains, we don’t need to worry about them because their particular purines have little impact on blood uric acid levels. Since its purines are similar to those in vegetables, dairy not only gets a pass here as, but proteins like casein it contains can actually help with the excretion of uric acid. This is why high consumption of dairy is often recommended for those afflicted.

But here’s the heartbreaker: Beer is bad. How bad? One lager-style beer contains about 11.8 milligrams of hypoxanthine and adenine combined; make that a 7% a/v IPA, and the number goes to 18.5 mg, which has to count against your typical maximum 400 mg/day purine limit. That’s not the end of it. Yeast is extremely high in purines, although it’s unclear what kind of dosage one might get from drinking, say, a traditional yeasty hefeweizen, or an unfiltered IPA for that matter. Brewers need to taste a lot of yeasty tank beer before it’s clarified, an occupational hazard for some. Oh, and while alcohol doesn’t seem to be a cause of gout, it is an aggravating factor during attacks. 

The light at the end of this dark tunnel is that by carefully managing ingredients—especially mushrooms—in a dish, the potent synergistic effects of 5′-ribonucleotides can achieve high levels of umami taste without adding a ton of purines.

Reference for the evolutionary tale and a paper with extensive lists of foods and drinks and their purine levels:

Richard J. Johnson, “Umami: The Taste That Drives Purine Intake,” The Journal of Rheumatology 40, no. 11 (2013): 1794-1796, https://doi.org/10.3899/jrheum.130531.

Kiyoko Kaneko, “Total Purine and Purine Base Content of Common Foodstuffs for Facilitating Nutritional Therapy for Gout and Hyperuricemia,” Biological Pharmacology Bulletin 37, no. 5 (2014): 709-721, https://doi.org/10.1248/bpb.b13-00967.