The Connection Between Fructose, Uric Acid and the effects of gout

The Connection Between Fructose and Uric Acid

By Dr. George Gillson, MD, PhD

Alexander Haig, MD was so far ahead of his time that everyone ignored him for about 132 years…

You more than likely have heard of gout, the recurrent, painful arthritis afflicting many body parts but especially the main joint in our big toes. And, you may also know it is caused by formation of uric acid crystals in the joints and precipitated by “rich” foods and too much drink. Gout was recognized as far back as 2500 BC and it’s interesting that some of the remedies discovered in antiquity are still in use today (e.g., colchicine derived from a species of crocus flowers).

This is all very interesting but why do we care? We care, because in the last twenty years, researchers have woken up to the fact that elevated blood uric acid is associated not only with gout but with just about every serious condition you can think of: cancer, cardiovascular disease, dementia, diabetes, fatty liver, high blood pressure, stroke and line-dancing.  Sadly, in the late 1890’s an astute Scottish physician, Alexander Haig, came to the same conclusions but no one listened.  Happily, it took us a while, but we now understand the mechanisms behind uric acid’s negative effects and how to mitigate them: except for the line-dancing which is basically incurable.

If you’re reading this post you probably have heard of the hallmark lifestyle and diet changes most folks need to do to address all the health conditions listed above: how to lower inflammation and blood pressure, how to decrease insulin resistance and lower blood sugar, how to reverse fatty liver and how to clean up your diet.  You’re probably doing many of those things already but learning about the role that uric acid plays in all this will help you to better understand the WHY of what you’re doing and perhaps improve long term compliance.  Many of you, in concert with your health care providers, are now routinely tracking blood markers such as hemoglobin A1c, fasting insulin, GGT and homocysteine as you seek better health and a better quality of life. Serum uric acid is another marker that needs to be on your list.

Uric Acid & Fructose

I first learned about the connection between uric acid and Metabolic Syndrome/Insulin Resistance about fifteen years ago but never really understood why they were connected.  Similarly, I also knew fructose as a food additive was basically deadly, back then but again, didn’t really know why. Reading this book certainly educated me and I know you will benefit from reading it too:

Uric Acid & Fructose the connection between uric acid and Metabolic Syndrome/Insulin Resistance

To continue the discussion, let’s look at how someone winds up with too much uric acid. For some, it is a genetic predisposition. There are quite a few drugs that cause increased production or decreased ability to excrete uric acid. They include some blood pressure medications, proton pump inhibitors for heartburn, L-dopa, seizure medications and rarely used drugs such as Viagra (A complete list can be found in Chapter Five of Dr. Perlmutter’s book). The following diagram captures the major drivers of increased uric acid.

Diagram captures the major drivers of increased uric acid.

[Note: Purines are ring-shaped molecules containing carbon and nitrogen.  Purine-rich foods include liver, kidney, thymus, beef tongue, herring, anchovy, scallops]

The main offender is fructose, which itself could be the topic of an entire book.  Fructose is a sugar that comes from fruit but eating whole fruits, unless they are inordinately sweet, they don’t raise uric acid.  Fructose consumption has increased astronomically in the last 20 years and the incidence of diabetes/Metabolic Syndrome/Insulin resistance has risen right along with it.  Sugar in general and highly concentrated fructose in particular, in the form of high fructose corn syrup, is in many, many processed foods.

In chapter seven of Drop Acid, Dr. Perlmutter lists more than 70 names of the various sugars found in processed food. The easier-said-than-done way to avoid them all is to stop eating and drinking processed foods. When I say drinking, I don’t just mean fruit juice.  Alcohol does the same job as fructose and beer is a particularly bad actor. More on that in a minute.  Thankfully, red wine, in moderation doesn’t have the same negative impact!

So, what’s the deal with eating too much fructose?

When fructose is broken down, instead of generating ATP or adenosine triphosphate, our cellular energy “currency”, it leaves us with AMP or adenosine monophosphate. Turns out AMP is an ancient metabolic “railroad switch”.  When food is scarce, we convert AMP to signals telling us to store fat, and when food is abundant, signals telling us to burn fat are generated.  High uric acid levels act to keep the switch flipped over to fat storage as shown in the diagram. That fat not only appears externally but also accumulates in the liver, damaging it.

The role of uric acid in driving fat storage is key to survival and almost all mammals have a built-in safety valve enzyme that starts to break down uric acid when it gets too high for too long. This works great for the bears who lay down fat for hibernation by gobbling prodigious amounts of fructose-laden berries but we humans lost that enzyme eons ago. Sugar-laden foods load us with too much energy and fructose-generated uric acid says, “Put it in the bank.” Elevated uric also plays a role in animals, helping them to survive drought: uric acid raises blood pressure, promoting retention of sodium and water. Sodium can also trigger conversion of endogenous (homegrown) glucose to fructose, aiding the fat storage response.

I know you’re all riveted to your seats at this point, but I learned something else from Dr. Perlmutter that is even more fascinating: too much uric acid inhibits the formation and function of nitric oxide or NO.  NO is a natural vasodilator: it keeps the blood flowing into every nook and cranny of our body, allows glucose to be consumed by muscle cells, lowers our blood pressure, facilitates blood flow to male and female erectile tissues and generally acts to keep our arteries healthy.  It has many other signaling roles that are beneficial.  Did I mention that it facilitates erections? In any event, low NO/impaired NO signaling is at the heart of insulin resistance, high blood pressure and cardiovascular disease.

As if that weren’t enough, when uric acid is broken down, reactive, electron-hungry free radicals are formed, leading to tissue damage in many tissues including blood vessels, fat cells and brain. We knew that all the major chronic diseases are associated with inflammation but now we know one of its root causes.

While fructose overconsumption is the main culprit driving high uric acid, beer also deserves special mention in the story.  As discussed, the body sees any alcohol as a sugar and forms AMP as it breaks it down.  Beer brewed via yeast is also high in DNA, which is also metabolized to uric acid.  Clearly, beer punches above its weight (pun intended) in its ability to drive up uric acid.  The other main driver is certain purine-rich foods, as discussed.  Note that some foods have relatively high purine content but do not raise uric acid, such as legumes.

What uric acid level should you aim to stay below?

This is a good question.  The upper limits of the urate (the form in which uric acid is measured) ranges listed by conventional laboratories are geared more toward avoidance of gout.  They are too high.  We want to nip trouble in the bud and so the action threshold for urate is approximately 330 umol/L or 5.5 mg/dL. You may not have any worrisome symptoms at this level but you don’t want your urate going higher, especially for preservation of cognitive function.

I have relied heavily on the Drop Acid book in writing this post.  Half the book is devoted to how you can “drop acid” (i.e., lower uric acid through dietary and lifestyle changes).  Dr. Perlmutter outlines a detailed three-week program on how to effect the needed changes which include getting enough sleep, enough exercise (including line-dancing), removing concentrated fructose and other sugars from your diet, and beer.  Lose the sardines and the thymus glands while you’re at it. I know that elimination of these last two items will be challenging for you. There are also specific foods you should add which will inhibit or decrease formation of uric acid, including tart cherries, pomegranates, walnuts and celery. Rest assured, this is all written down for you, courtesy the good Dr. P.

There are certain supplements and medications that can also lower uric acid and these include quercetin, Vitamin C, luteolin and DHA (from fish oil). The prescription medication allopurinol blocks formation of uric acid. Addition of supplements, changes to existing uric acid-raising prescription drugs and institution of prescription uric-acid blocking agents should be done in concert with your health care provider knowledgeable in Functional Medicine.

Don’t be shy in encouraging your Family Doctor to read Drop Acid.  Even today, many physicians are still not up to speed on uric acid.  I guess 130 years is barely long enough for good news to spread.

George Gillson MD PhD

Author: Dr. George Gillson, MD, PHD, CCFP
EvolveWell Medical Director