21st Century Gout

Welcome to the Nutrition Facts podcast.  I’m your host Dr. Michael Greger.  I am thrilled that you have decided to join me today.  Because the more I learn about latest nutrition research – the more convinced I am that this information can make a real difference in all of our lives.  And I like nothing better – than sharing it with you. 

Today we look at a disease that many associate with English kings from the 17^th century – called Gout. But anyone who has it today can tell you it’s a very real and painful condition.  It occurs when there is a buildup of uric acid in the blood – and is often caused by the food we eat.

If the uric acid crystals that trigger gout come from the breakdown of purines, should gout patients avoid even healthy, purine-rich foods, such as beans, mushrooms, and cauliflower?  That will be our first story that I cover here.

Over 2,000 years ago, Hippocrates described gout as a “disease of kings,” primarily because it was the wealthy who could afford the rich foods which seemed to precipitate gouty attacks. But now, we can all eat like kings and acquire some diseases of royalty ourselves.

Gout is caused by needle sharp crystals of uric acid in our joints, and uric acid comes from the breakdown of purines. And purines are the breakdown product of genetic material, DNA, the foundation of all life. So, there is no such thing as a purine-free diet, but foods do vary in their purine content, and it was long thought that people with gout just needed to stay away from all high-purine foods, whether from animals, like organ meats, or plants like beans, but this strategy proved ineffective. Yes, all uric acid comes from the breakdown of purines, and so limiting meat makes sense, but that means all kinds of meat, and plant sources have now largely been exonerated.

The association of gout with both alcohol intake and increased dietary purine consumption has been known since ancient times, but there were no prospective trials to back it up… until just a decade ago. The Harvard Health Professional’s Follow-Up Study, about 50,000 men followed for a dozen years, and alcohol intake was strongly associated with an increased risk of gout, and in terms of food, they found an increased risk of gout with higher meat and fish consumption, but not with higher consumption purine-rich plant foods, maybe because the purines in plants are less bioavailable? So, though it’s been suggested that gout sufferers should moderate both purine rich animal and plant foods, their results suggest that this type of dietary restriction may be only applicable to purines of animal origin.

Although it was not surprising that meat and seafood had significant associations with the incidence of gout, this lack of effect of purine-rich plant foods was new. There don’t appear to be any long-term studies showing purine rich, plant foods increase risk, though there are still some guidelines continuing to disseminate outdated recommendations.

Not only has the intake of purine-rich plants not been associated with high uric acid levels, but the vegetables gout sufferers are specifically told to stay away from –  mushrooms, peas, beans, lentils, and cauliflower – were actually found to be protective. This may be because foods rich in fiber, folate, and vitamin C appear to protect against uric acid buildup and gout. For example, fiber has been recognized as having a potential role in binding uric acid in the gut for excretion.

 Lack of association between purine-rich vegetables and urate could be due to the co-packaging of these beneficial plant components (such as vitamin C, dietary fiber, or some phytochemicals), which may have masked an effect of purine on uric acid. Vegetable intake, regardless of purine content, may also be protective as it may increase uric acid excretion.

 By changing the pH of our urine, we can change uric acid clearance. Eating an alkaline diet, a vegetarian diet in this case, was found effective for removing uric acid from the body. Those eating the alkaline diet excreted significantly more uric acid than those eating the acidic diet. As such, uric acid levels in the blood of those eating the acid-forming diet rose within days.

So, one would assume uric acid levels are lower in vegetarians. And indeed, those eating vegetarian long term were found to have significantly lower levels in their blood. To prove cause and effect, though, you need to do an interventional trial, where you take people, change their diets, and see what happens. So, they took ten guys for a study of the build-up of uric acid in the kidneys, kept them on a standard Western diet for five days, and measured their relative supersaturation for uric acid. Then, they tried a vegetarian diet for five days  The intake of the vegetarian diet led to a 93% decline in the risk of uric acid crystallization, within days.

Or, you can do it the other way: take a bunch of people with gout, feed them a big meal of meat and see if you can trigger an attack. Seven patients were put in a hospital, stabilized on a low-purine diet, and then challenged with a meat-laden dinner. In response, uric acid levels shot up, and they started getting gout attacks. Then, they added alcohol and uric acid levels shot up even further. In all, just with single meals, they were able to trigger gout attacks in six out of seven patients.

Now, some meat has less purines than others. Superworms have particularly low purine levels, super, because they’re like two to three inches long.

Not all animal foods increase gout risk, though. Low-fat dairy products were found to be protective. If that’s the case, we would predict vegans would be at a disadvantage, which is indeed what was found, though these all were within the normal range, which is like 3.5 to 7.

Should gout patients add milk to their diets? Well, although drinking the equivalent of ten cups of skim milk at a time appears to have an acute lowering effect on uric acid levels, in the long term over months, at the equivalent of two cups a day, there was no significant lowering effect. They gave skim milk powder to gout patients for three months, and it did not appear to help. Though soy milk has also been associated with a lower risk of uric acid buildup, there are no interventional trials to back that up.

The bottom line is that we now have good research on how to reduce the risk of gout without the use of drug treatments, through modification of diet. That’s important, because allopurinol is the drug of choice. It’s considered generally safe. What does it mean when doctors talk about a relatively safe drug? Well, about 2% of patients develop hypersensitivity reactions, which can sometimes be severe and fatal with a mortality rate of up to 20%–and that’s the safe drug. The other leading drug, colchicine, has no clear-cut distinction between the nontoxic, toxic, and lethal dose.

In our next story we explore how sweet cherries compare to the drug allopurinol and a low-purine diet for the treatment of the painful inflammatory arthritis gout?

The Fruit Commission of Washington state, our largest cherry producer, can fund reviews cherry-picking studies on the anti-inflammatory effects of cherries in a petri dish and animal models. But, what we need are human studies. For example, if you stuff the human equivalent of up to a thousand cups of cherries down the throats of rats, it appears to have an anti-inflammatory effect. But, we couldn’t eat that many. And, in fact, if we tried, it could end up badly.

But, we didn’t have many human studies, until now. Men and women were asked to eat about 45 cherries a day for a month. I wouldn’t mind being part of that study. 25% drop in C-reactive protein levels, as well as an inflammatory protein with an inelegant acronym: Regulated on, Activation, Normal, T cell, Expressed, and Secreted.” That’s actually the name.  Even a month after the study ended, there appeared to be residual anti-inflammatory benefit from the cherry fest.

Now, these were all healthy people, with low levels of inflammation to begin with. But, the same was found in a follow-up study on folks with higher levels: a solid 20% drop in CRP, and a number of other markers for chronic inflammatory diseases. But, how about trying out cherries on people who actually have a chronic inflammatory disease—to see if they actually work?

Well, back in 1950, in an obscure Texas medical journal, “observations made by responsible physicians” suggested that in a dozen patients with gout, “eating [half a pound] of fresh or canned cherries” helped prevent flares of gout. But, it had never seriously been tested, until now. “Gout is an excruciatingly painful inflammatory arthritis caused by the crystallization of uric acid [in our] joints,” affecting eight million Americans. “Such attacks cause tremendous pain.”

Hundreds of gout sufferers studied, and cherry intake…was associated with a 35% lower risk of gout attacks,” with over half the risk gone at three servings, measured over a two-day period—which comes out to be about 16 cherries a day. That’s the kind of efficacy they saw with a low-purine diet; uric acid is a breakdown product of purines.

This same research group found that “purine intake of animal origin increased the odds for recurrent] gout attacks by nearly fivefold.” Heavy alcohol consumption isn’t a good idea, either. Now, there are some high-purine non-animal foods, like mushrooms and asparagus, but they found no significant link to plant sources of purines. So, they recommended eliminating meat and seafood from the diet.

That may decrease risk, and adding cherries on top may decrease risk of gout attacks even further. Same thing with the leading drug; allopurinol works, but pills and produce appear to work even better.

And, dietary changes and cherries may be all many patients have, as doctors are hesitant to prescribe uric acid-lowering drugs, like allopurinol, “due to rare but serious side effects”—including the most feared of all drug side effects: Stevens-Johnson syndrome, which can detach our skin from our body. I will spare you the photos.

In addition to fighting inflammation, cherries may actually help lower uric acid levels, as well. Within five hours of eating a big bowl of cherries, uric acid levels in the blood significantly drop. At the same time, antioxidant levels in the blood go up, as vitamin C levels start to rise. So, it is just an antioxidant effect? Would other fruit work just as well? No. They tried grapes, strawberries, and kiwi fruit, and none significantly lowered uric acid levels, supporting a specific “anti-gout effect of cherries.”

There are some new gout drugs out now, costing up to $2,000 per dose, and, also carries “a risk of toxicity that may be avoided by using nonpharmacologic treatments or [prevention]” in the first place. Given the potential harms and high costs, “attention ought to be directed to dietary modification”—reducing alcohol and meat intake, particularly sardines and organ meats. And, hey, “if life serves up a bowl of cherries consumed on a regular basis, the risk of a recurrent gout attack may be meaningfully reduced.”

Cherry consumption has been shown to successfully prevent gout arthritis attacks, but what about cherry juice concentrate?

Over the last 40 years, the burden of gout, a painful inflammatory arthritis, has risen considerably, now affecting millions of Americans. Gout is now the most common inflammatory arthritis in men and older women.

In my video, Gout Treatment with a Cherry on Top, I profiled new research, suggesting that even as little as a half a cup of cherries a day may significantly lower the risk of gout attacks. Fresh cherries aren’t always in season, though, so I listed a few alternatives, and frozen appeared second-best, with cherry juice concentrate the runner-up. But does concentrated cherry juice actually help prevent attacks of gout? We didn’t know, until now.

The first pilot study was a randomized controlled trial cherry juice concentrate with pomegranate juice concentrate as a control for the prevention of attacks in gout sufferers who were having as many as four attacks a month. The cherry group got a tablespoon of cherry juice concentrate twice a day for four months, and the control group got a tablespoon of pomegranate juice concentrate twice a day for four months.

The number of gout flares in the cherry group dropped from an average of 5 down to 2, better than the pomegranate group, which only dropped from about 5 to 4. And about half of those in the cherry group who were on prescription anti-inflammatory drugs were able to stop their medications within two months after starting the cherry juice, as opposed to none of the patients in the pomegranate group.

The second study was a retrospective investigation over the longer term. 24 gout patients went from having about seven attacks a year, down to two. The researchers conclude that cherry juice concentrate is efficacious for the prevention of gout flares.

So large long-term randomized controlled trials are needed to further evaluate the usefulness of cherries and cherry juice concentrate for gout flare prophylaxis.

But in the meanwhile, so, are cherries now ripe for use as a complementary therapeutic in gout?  I understand how the pharmaceutical industry can get nervous seeing studies where half of patients were able to stop taking their gout drugs, given the billions of dollars at stake, but what’s the downside of eating a half cup of cherries a day, or worst comes to worst a few spoonfuls of cherry juice a day?

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Thanks for listening to Nutrition Facts.  I’m your host, Dr. Michael Greger.