By Richard J. Johnson, MD
Gout Education Society board member and
Professor of Medicine at the University of Colorado
The pain of an acute attack of gout is all too well known, especially for many of you who are reading this blog. And, there is good evidence that the risk of more attacks can be reduced if your serum uric acid is lowered to 6.0 mg/dL or lower, as recommended by the American College of Rheumatology. This can sometimes be done by changes to your diet, but it is difficult, and involves seriously reducing your intake of sugar, red meats, seafood, and alcohol. So, most people with gout have to take daily medications, such as allopurinol or febuxostat, and often we are told that the medicine needs to be taken for life.
Let’s face it: taking a medication for life is hard to do for a condition in which the frequency of an attack can be as low as once every few years. And while the pain of gout can be crippling, it responds pretty quickly to a variety of medications. Which means, it is understandable that the majority of patients with gout are either not on daily uric acid-lowering medications or are inadequately treated. In addition to that, many physicians also do not like giving medications, such as allopurinol, because of the risk of potential side effects. Additionally, if the treatment is effective and no more gout attacks occur, many physicians assume it should be fine to stop the medication completely.
But there is new data that suggests that we should not be so cavalier about not treating gout on an ongoing basis. New studies have found that the crystals of uric acid that cause such pain and inflammation do not just occur in the joints (to cause the gout attack) or in the skin (resulting in nodules called tophi), but that they can also occur in the blood vessels, including the coronary arteries, where they prefer to deposit in the blood vessel at areas where cholesterol and lipid-containing plaques occur. More and more evidence suggests that the uric acid crystals causing gout may be also contributing to heart attacks and sudden cardiac death, and also are strongly associated with high blood pressure, diabetes and obesity. Treating high uric acid levels may have a major potential in reducing the risk for death from heart disease.
However, there is an additional benefit to take gout medications that just might trump everything else. There is probably no disease more devastating than dementia. There are two major types of dementia. One is associated with high blood pressure, stroke and heart disease, called vascular dementia. Vascular dementia has been linked with both high uric acid and gout, and it probably should not surprise anyone that there has been increasing evidence that good control of blood pressure can reduce the risk for this disease. With the finding that uric acid crystals can deposit in blood vessels, it is a small leap to realize that controlling gout might be a way to reduce the risk for vascular dementia.
But, the bigger elephant in the room is Alzheimer’s disease. This is now the seventh most common cause of death and why and how it develops has been unknown. We know that at the end stages of the disease, the brain is shrunken and carries material called amyloid plaques—but treatments aimed at eliminating these plaques, while promising, seem to have only minimal success. This has led investigators to wonder if the disease might need to be treated earlier. In this way, studies focusing on the early changes in Alzheimer’s disease have identified problems with the brain showing low energy, the inability to metabolize nutrients such as glucose, and low-grade inflammation.
I worked with a group that recently published a paper showing evidence that these early changes may be due to the production in the brain of a particular sugar, known as fructose. This is the sugar present in high fructose corn syrup and table sugar, and it is a major cause of gout. When it is metabolized in the brain, fructose can produce uric acid locally, and there is evidence that in the early stages of Alzheimer’s disease, uric acid levels are high in the brain. Indeed, we have hypothesized that the uric acid effects in the brain may have a role in causing the biological deterioration that eventually can lead to the Alzheimer’s condition.
It is interesting, then, that when people are diagnosed with Alzheimer’s disease, many have low uric acid levels, even if they had suffered from gout in prior years. This is likely because as dementia develops, general food intake and nutrition suffer, and the serum uric acid level can also reflect nutritional status. This has confused people to think that a low uric acid might be protective.
However, a great way to know whether or not gout, or even a high uric acid level, can lead to dementia is to determine if there is a benefit to lowering serum uric acid levels despite the risk for developing dementia. Turns out, numerous research papers show that people with gout who are treated with uric acid-lowering therapy have a significantly lower risk for developing dementia (including both vascular and Alzheimer’s disease). In one remarkable study, the drug febuxostat was associated with an 80 percent reduction!
So, there is a “sweet surprise” with treating gout. There are some added benefits. Yes, it is true that once your uric acid level is controlled, you are less likely to have any more gout attacks. That should be a relief in itself. But, after a few years, you may say, “Why still take my medicine?” Think about it: What medicine do you know that can reduce risk for both heart attacks (the No. 1 cause of death in the United States) and dementia (the No. 1 cause of misery)? Indeed, you may be ahead of the game, for it is my hope that prospective clinical trials can be done for people who have high uric acid and do not have gout. This could help determine if lowering uric acid might provide health benefits to reduce heart and neurological disease.
So, if your doctor tries to stop your medication for gout, say, “No, thank you. I want to keep my serum uric acid at the target range of 6.0 mg/dL or lower.”
Richard J. Johnson, MD, is a board member of the Gout Education Society and Professor of Medicine at the University of Colorado who has studied the effects of fructose and uric acid on health for the last 20 years. He has written a book, Nature Wants Us to Be Fat (Benbella books, 2022), which discusses the role of fructose and uric acid in a wide variety of diseases from cancer to dementia.
