If you or someone you know suffers from gout, then you know what a painful condition it can be. If you don’t know what it’s like, imagine having broken glass embedded in your big toe, turning something as simple as walking into an excruciating endeavor.
Joints in the big toes aren’t the only ones affected in gout, but they’re typically the most common. Gout results from an abnormal buildup in the blood of a compound called uric acid. When uric acid concentration is high, it may precipitate or solidify into crystals, which accumulate in soft tissues, and this is what’s responsible for the pain associated with the condition.
The Conventional Approach
Gout has long been believed to result from a high intake of alcohol or animal protein. This is because a major source of uric acid is the breakdown of purines — a nitrogen-containing compound found in high concentrations in seafood, muscle meats, and organ meats. (There’s also a moderate amount of purines in protein-containing plant foods, such as beans, oats, wheat and peas.)
For this reason, gout sufferers have traditionally been advised to avoid alcohol — especially beer — and follow a diet low in animal protein, particularly low in red meat. However, while some people experience relief by going this route, many others don’t, which suggests there’s something else behind this condition.
To see what that “something else” might be, it helps to look at things from an evolutionary perspective. If a high intake of animal protein caused gout — or was the primary cause, anyway — then our hunter-gatherer ancestors would have had too much joint pain to go chasing after yet more prey. So it makes sense to look for a different explanation for why so many people are afflicted with gout in the 21st Century. And what’s really the problem in this condition, anyway: do people with gout produce more uric acid, or is the problem with clearance of uric acid?
Incidence of gout has risen in concert with other disorders attributed to “Western” diets and lifestyles, such as type-2 diabetes and heart disease. Previous posts on the KetoDiet blog have explored chronically high insulin as a driving factor in PCOS, Alzheimer’s disease, and several other issues not typically associated with hyperinsulinemia, such as skin tags, erectile dysfunction, and migraines.
With this in mind, could gout be yet another condition driven by chronically elevated insulin?
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The Epidemiology of Elevated Uric Acid and Gout
Epidemiology is getting a bad rap in the low carb and keto communities lately. Epidemiology is the branch of medical research that studies the incidence and prevalence of diseases in large populations.
It’s primarily observational in nature, rather than interventional. What this means is, epidemiology is a good place to start for generating ideas and formulating hypothesis, especially with regard to associations and connections between particular dietary elements and certain diseases, but until those ideas are tested in clinical trials, we can’t know for sure whether any of those dietary factors cause the diseases.
Since epidemiological findings can help frame the discussion, though, let’s start there. We’ll look at some statistics regarding incidence of metabolic syndrome, elevated uric acid, and gout, and then dig deeper to see whether there are plausible mechanisms to explain some of the findings.
The Link Between Metabolic Syndrome and High Blood Uric Acid
There’s a strong correlation between metabolic syndrome and elevated blood levels of uric acid. Different sources list different cutoff points for defining a high blood uric acid level (called hyperuricemia), but 6.8 mg/dL is a common reference point (1). Other sources suggest ≥6 mg/dL for women and ≥7 mg/dL for men as defining hyperuricemia (2).
According to data from over 8000 people in the early 1990s, prevalence of metabolic syndrome was 18.9% for uric acid levels less than 6 mg/dL, 36.0% for uric acid levels from 6 to 6.9 mg/dL, 40.8% for uric acid levels from 7 to 7.9 mg/dL, 59.7% for uric acid levels from 8 to 8.9 mg/dL, 62.0% for levels from 9 to 9.9 mg/dL, and 70.7% for levels ≥ 10 mg/dL.
In other words, the higher the uric acid level, the greater the prevalence of metabolic syndrome. Stated more clearly, the higher someone’s uric acid level, the more likely they were to have metabolic syndrome (3).
What is Metabolic Syndrome?
The stereotypical metabolic syndrome patient is overweight or obese, but excess weight is definitely not required to be diagnosed with metabolic syndrome or gout. Metabolic syndrome — which is rooted in chronic hyperinsulinemia — may be driving gout even in people with a “normal” body weight.
Among people with a normal body mass index (BMI), those with a uric acid level < 6 mg/dL had a prevalence of metabolic syndrome of just 5.9%, compared to a whopping 59.0% among those with a uric acid level ≥ 10 mg/dL — ten times as high! Another study estimates that up to 76% of patients with gout have metabolic syndrome (3, 4).
How Many People Are Affected by Hyperuricemia?
According to data gathered from the National Health and Nutrition Examination Survey (NHANES), nearly one-third of the entire US population — about 49 million people — had a serum uric acid concentration > 6mg/dL, and nearly 12% (almost 20 million people) had a uric acid level > 7mg/dL.
Using the NHANES III definition of hyperuricemia (serum uric acid > 7.0 mg/dL for men and > 5.7 mg/dL for women), the prevalence of hyperuricemia is around 18%, which translates into 30.5 million people in the US. These aren’t small numbers. Clearly, elevated uric acid is a very common issue.
High Uric Acid Doesn’t Always Cause Gout
Before we go assuming there’s a gout epidemic, though, it should be noted that elevated uric acid isn’t always a problem. Not everyone with a high uric acid level will experience gout attacks. As many as two-thirds of people with elevated uric acid remain asymptomatic. It’s important to note, though, that they might not have any signs or symptoms of gout, but that doesn’t mean they’re free of other cardiometabolic diseases driven by hyperinsulinemia (5).
So even if someone doesn’t have gout, elevated uric acid levels can be considered a “warning sign” of metabolic trouble that could eventually manifest elsewhere in the body. And the truth is, there is a strong relationship between high uric acid and development of gout (6).
What Causes Elevated Uric Acid?
There are two possible causes of hyperuricemia:
- people over-produce uric acid
- uric acid excretion is impaired — that is, the body isn’t able to get rid of it properly
Only about 10% of cases of hyperuricemia are caused by overproduction of uric acid; the other 90% result from impaired excretion.
The kidneys are the primary players in uric acid excretion, so anything that affects healthy kidney function can interfere with clearance of uric acid. Older age tends to be a factor, and several commonly used medications impair uric acid clearance, such as low-dose aspirin, thiazides or loop diuretics, and cyclosporine A (an immunosuppressant used for rheumatoid arthritis, psoriasis, Crohn’s disease, and dry eyes).
Other than that, the major influence on renal uric acid excretion is insulin.
Elevated Insulin Inhibits Uric Acid Excretion
More and more research indicates gout is related to chronically high insulin levels. As discussed in the KetoDiet post on hyperinsulinemia, insulin is far more than just a “blood sugar hormone.” High insulin has powerful effects on kidney function (7). Hypertension is one result, coming from the kidneys retaining more sodium in the blood, and hyperuricemia is another, because the kidneys hold on to more uric acid, rather than filtering it out into the urine (8).
Gerald Reaven, MD, who coined the term “syndrome X” and was one of the first doctors to identify insulin as the underlying factor in metabolic syndrome, observed hyperuricemia and hypertension in insulin resistance and called the kidneys “an unwilling accomplice” in hyperinsulinemia more than 20 years ago (9). Perhaps this explains why hypertension and gout so often occur together (10). Some researchers speculate that one causes the other, but it’s more likely that a third factor — high insulin — causes both.
Bottom line: High insulin leads to high uric acid, and high uric acid often leads to gout.
This is likely why many people who reduce their intake of animal protein and alcohol often experience no relief from gout. Just as with sodium and blood pressure, it’s not the consumption of dietary purines that results in gout, but rather, the buildup of uric acid. And since elevated insulin is what causes the body to retain uric acid, the most effective long-term solution isn’t to decrease purine intake, but to decrease insulin.
Dietary Factors and Gout
Alcohol intake may contribute to gout, and it appears to do so in a dose-dependent manner — meaning, the higher the alcohol intake, the greater the risk for gout. Beer increases risk more than distilled spirits or hard liquor, likely because beer is higher in purines. Wine lovers rejoice: wine consumption hasn’t been shown to increase risk for gout (11).
Aside from alcohol, animal protein is believed to be the biggest dietary contributor to gout. In a study of over 47,000 male health professionals, risk of gout was 40-50% higher in those who consumed the most red meat or seafood compared to those who consumed the least of these. However, this association may very well have been eclipsed if the researchers had asked about intake of sugars and refined carbs.
Is it the animal protein leading to gout, or is it the carbs also present in the diet, and the insulin load they induce? A high protein intake in the absence of refined carbs might have a very different effect on uric acid levels and gout than a high or even moderate protein intake combined with a lot of carbs. We’ll explore this in detail, but first, let’s look at another contributing factor that’s a large part of the modern diet.
Increasing evidence indicates that gout may be related to consumption of large amounts of fructose (12). Fructose was long believed to be a “safe” sugar for diabetics because it doesn’t raise blood glucose or stimulate insulin to the same degree that glucose and sucrose (table sugar) do. In fact, decades ago, candies and snack foods that were formulated to contain more fructose than glucose were marketed as being helpful for diabetics specifically for this reason.
However, even though fructose doesn’t seem to have immediate effects on insulin, chronic exposure — that is, consuming a lot of it on a regular basis over a long period of time — may indirectly cause elevated insulin levels (13).
So while fructose doesn’t have the same acute effect that glucose has on insulin secretion, over time — decades, say, of consuming fruit juice, sugar-sweetened soft drinks, and high-sugar snack foods — fructose could play a role in the development of insulin resistance.
This is believed to result from the effects of fructose on the liver, which is second only to the pancreas in importance for maintaining healthy blood sugar levels. (Consuming too much fructose may, over time, result in the buildup of fat in the liver [“fatty liver”], which interferes with the liver’s ability to regulate blood sugar.) Fructose doesn’t stimulate insulin secretion in the short term, but animal studies show that long-term fructose feeding induces insulin resistance and obesity (14).
Ironically, people who adopt a vegetarian diet in hopes of alleviating gout may find that the opposite happens, at least if they consume a lot of fructose. Increasing fruit or fruit juice intake could exacerbate gout, especially when combined with a high-carb diet in general.
Protein, Gout, and Ketogenic Diets
Since protein-rich foods are the main source of purines, on the surface, it makes sense to reduce protein intake in order to reduce the severity of gout. Ketogenic and low carb diets aren’t “high” in protein, but because carbs are so low, for many people, going keto or low carb results in an increase in total protein intake compared to when they followed a higher carb diet.
It’s possible to do a vegetarian keto diet, but most people who go keto get the bulk of their protein from animal sources. Conventional wisdom would predict that this would result in more gout attacks. But is this what actually happens?
Do Low Carb Diets Increase Frequency of Gout Attacks?
On the contrary, higher protein diets that are a bit lower in carbs have been shown to reduce uric acid levels and gout attacks.
Epidemiological evidence suggests higher protein intakes — including animal protein — are not associated with increased risk of gout. According to a paper from The New England Journal of Medicine, “High-protein diets are associated with increased urinary uric acid excretion and may reduce the blood uric acid level.” (15)
Intake of meat and seafood did seem to have an association with incidence of gout, but purine-rich vegetables and dairy proteins had no such association. In fact, according to the researchers, “The level of consumption of purine-rich vegetables and the total protein intake were not associated with an increased risk of gout,” and “the incidence of gout decreased with increasing intake of dairy products.”
There’s a lot of noise here to sort through in order to find a signal, but one thing that comes through loud and clear is that protein intake, per se, doesn’t seem to increase risk for gout.
Low Carb Diets and Gout
There isn’t much research on strict ketogenic diets and gout, but studies have been done employing diets that are lower in carbs than a typical Western diet.
In a small study of overweight or obese subjects, a high-protein diet — actually referred to by name as the Atkins diet — resulted in dramatic decreases in serum uric acid (16). Beyond this result, participants also experienced a mean weight loss of about 7 kg (around 15 pounds), a 46 mg/dL drop in triglycerides, and a 7.7 µU/mL reduction in fasting insulin. The study authors noted, “the Atkins diet (i.e., a high protein diet without calorie restriction) can reduce SUA [serum uric acid] levels despite substantial purine loading.”
Another study involved 13 overweight men with gout (17). The intervention diet called for 1600 calories, made up of 40% carbohydrate (from complex carbs, while avoiding refined), and 30% each protein and fat.
A 40% carbohydrate diet isn’t ketogenic, and it’s not even really “low carb,” but it may have been a significant decrease in carbs compared to what the subjects were eating before, and 30% protein was likely a proportional increase, if not an absolute one.
After 16 weeks on the diet, the men lost weight, had increases in HDL and decreases in triglycerides, and most important, had reduced uric acid levels and reduced frequency of gout attacks. Before the study, mean gout attack frequency was 2.1 per month, which dropped to 0.6 at the end of the study — including a few subjects who had zero attacks. So, even just reducing carbs somewhat, without going fully keto, was beneficial for gout. (See image below.)
Following a 30% protein diet for 16 weeks resulted in decreased serum uric acid and frequency of gout attacks in 13 men who experienced at least two gout attacks during the four months prior to the study. (Source: Dessein P, et al, 2000.)
In noting that dietary advice for people with gout typically calls for limiting protein and encouraging “the unlimited use of several food substances high in carbohydrate,” the authors of this study concluded, “Current dietary recommendations for gout may need re-evaluation.” (18) (In the interest of full disclosure, subjects in this study were also instructed to substitute saturated fat with monounsaturated fat, and to consume fish [as a source of polyunsaturated fat] at least four times a week. So the dietary fat sources were changed too, not just the amount and type of carbohydrate.)
Take Home Message
Owing to the effects of insulin on uric acid retention, people suffering from gout may want to try a low carb or ketogenic diet.
Contrary to conventional advice for this condition, there’s no need to avoid animal protein. If anything, evidence indicates that increasing protein intake could be beneficial for gout — as long as people also cut way back on carbs. Beyond a low carb way of eating, other strategies that improve insulin sensitivity may also help, such as getting adequate physical activity and good quality and quantity of sleep.
A word of caution: In the early stages of a very low-carb diet, individuals prone to gout flares may experience an increase in attacks. This is because ketones compete with uric acid for excretion. As the body excretes excess ketones in the first few days and weeks on a ketogenic diet, uric acid may accumulate in the body, potentially resulting in a gout attack. However, this is only temporary. The likelihood of gout attacks decreases over time, as the body becomes more efficient at utilizing ketones and uric acid is excreted normally.
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