URIC ACID: Much Bigger Than A Big Toe Problem!

A Malady Of Kings 

Uric acid is probably most famous for causing gout, an extremely painful, acute arthritis typically in the big toe but occasionally in other joints. However, new research over the last 10 years has exposed this circulating purine breakdown product as a metabolite that warrants our attention and concern, and not just for the health of our toes! There is accumulating evidence that uric acid directly causes fat accumulation, predicts the development of diabetes, and plays a major role in the appearance of metabolic syndrome (hypertension, diabetes, high lipids, abdominal fat deposits). All this can happen with or without a red-hot toe. 

Many of us are familiar with how to nurse a gouty toe: elevation of the foot, Indocin (anti-inflammatory), tart cherry juice, and avoiding high purine foods such as scallops, beer, lentils, etc. and those maneuvers will usually calm this painful condition. But after a few attacks, the gout tends to “settle in” and become more frequent, even chronic, requiring medication to keep the uric acid levels lower. 

What Is Uric Acid?

But let’s dig a little deeper and discuss how the uric acid bucket gets full in the first place – filled enough so that 2 beers and a small steak will put things over the top and send us to bed with painkillers. Are we seeing the tip of an iceberg, dealing with the obvious problem, while ignoring the danger signals we are getting from our body? And is the uric acid that is quietly circulating in our bloodstream, when above the “lab upper limit of normal”, driving a fat accumulation in our internal organs, especially the liver?

Basically, too much fructose, typically from added sugars in the diet, alcohol, or from fruit juices or high-fructose corn syrup, or from higher fructose fruit, will metabolize down a pathway that turns on our “winter” metabolism, depleting phosphate in our cells and sending a clear message to our body that winter is coming and it is time to store extra fat and water to prepare. The uric acid is simply a by-product of this metabolic state, but the uric acid itself amplifies the signal. One tablespoon of Heinz ketchup contains 4 grams of high fructose corn syrup. Other common sources are fruit preserves, ice cream, salad dressings, breakfast cereals, fruit juices, and of course packaged sweets and candy. It is very important to read ingredient labels carefully. 

Uric Acid As A Predictor Of More Serious Issues

We have all heard that the simple solution to excess fat is to eat less and move more, and “a calorie is a calorie” instructions from doctors, nutritionists, weight watchers, friends, and apps like Noom. Richard J. Johnson, MD in Colorado, has focused his career on how diet (in particular fructose) as well as serum uric acid, may have participated in the epidemics of overweight, diabetes, hypertension, and chronic kidney disease. 

In the case of fructose, in a background of excess intake, the fructose will divert to enhance triglyceride (fat) accumulation, especially in the liver, leading to NAFLD (non-alcoholic fatty liver disease), a metabolic epidemic at this point. The same amount in calories, of glucose, a similar 1-ring sugar, does not have as potent an effect. The uric acid rises after a significant fructose intake (anything over about 10 grams or 40 calories) and occurs within 30-60 minutes and remains elevated up to 24 hours. Dr. Johnson published that a persistent elevated uric acid independently predicts the onset of fatty liver, diabetes, obesity, and elevations in C-reactive protein. He points out that although high insulin levels will impede the excretion of uric acid, uric acid clearly predates the development of hyperinsulinemia. 

Managing Symptoms vs. Addressing Cause

The jury is still out on allopurinol, a medication to lower uric acid. It will lower gout frequency, but it may not change the overall metabolic state, a condition of high insulin resistance. Allopurinol may be a case of symptom management without root cause correction, something we care about in functional medicine. Some of the same issues occur with many of our medications, even effective ones. The medication alleviates a problem we can see or feel or measure but doesn’t course-correct our health trajectory. Metformin or insulin is another clear example of this short-term approach. It’s not that the medications aren’t indicated- they are- but they don’t repair or heal, just cover up a discomfort or lab issue. With current medical care alleviating our symptoms, we continue down the wrong road with an unhealthy future in front of us, wondering why we get macular degeneration, fatty liver, or other problems later in life.

HVLM: Looking Forward Towards Prevention

We now understand that too much sitting along with too many carbs and fructose sets us on this shaky path that can date back to our teens and 20s. Detailed studies on college students tell us that 82% of young, thin adults, if not engaged in significant exercise most days, are metabolically unhealthy. This means they have lab values that show they are “on the road” to diabetes, with poor regulation of blood sugar. It also means it is likely that less than 12% of us older adults have healthy glucose disposal with that estimate having been validated by several large studies. 

Most primary care providers do not consistently check Hemoglobin A1c, Fasting insulin, Fructosamine, waist and visceral fat measurements, 24-hour urine albumin, and uric acid, nor do they think 10 years down the road to your “future self”. In our patient evaluations here at HVLM we do a detailed look for the earliest signs of metabolic dysfunction, and many of our patients wear a continuous glucose monitor for 14 days to get a more accurate reading on real-time glucose excursions after meals. We are always looking forward and working upstream, which is what true preventative medicine and smart care are all about. 

Resources

Uric Acid as a Cause of the Metabolic Syndrome [Christopher King, Miguel A Lanaspa, Thomas Jensen, Dean R Tolan, L Gabriela Sánchez-Lozada, Richard J Johnson]: https://pubmed.ncbi.nlm.nih.gov/29393133/ 

An Integrated Plan for Lowering Uric Acid [David Perlmutter, MD, FACN]: https://www.drperlmutter.com/an-integrated-plan-for-lowering-uric-acid/

Exposing The Deadly Truth About Uric Acid [David Perlmutter, MD, FACN]: https://www.drperlmutter.com/books/drop-acid/

Rick Johnson, Md: Fructose—The Common Link In Hypertension, Insulin Resistance, T2d, & Obesity? [Peter Attia MD podcast]: https://www.youtube.com/watch?v=LbSic4Oo8ME

Prevalence of Optimal Metabolic Health in U.S. Adolescents, NHANES 2007–2016 [Young Sammy Choi, Thomas Anthony Beltran, and John Stanislaus Klaric]: https://www.liebertpub.com/doi/10.1089/met.2020.0099