Gout is caused by a buildup of uric acid in the blood, which eventually forms sharp crystals inside your joints. When blood uric acid rises above 6.8 mg/dL, it crosses a saturation threshold where crystals can start to form. But the story behind why uric acid climbs that high, and why crystals form in some people but not others, involves your diet, your kidneys, your genes, and sometimes your medications working against you at the same time.
How Uric Acid Builds Up in Your Body
Uric acid is a waste product your body creates when it breaks down substances called purines. Purines come from two sources: foods you eat (especially certain meats and seafood) and the natural turnover of your own cells. Your liver processes these purines through a series of steps, ultimately converting them into uric acid with the help of an enzyme called xanthine oxidase. In most mammals, another enzyme breaks uric acid down further into a harmless compound. Humans lost that enzyme through evolution, so uric acid is our end product, and the only way to get rid of it is through the kidneys and, to a lesser extent, the gut.
Under normal conditions, your kidneys filter uric acid out of the blood and excrete it in urine. The system stays in balance. Gout develops when that balance tips, either because your body produces too much uric acid or because your kidneys aren’t clearing enough of it. In roughly 90% of cases, the problem is underexcretion rather than overproduction.
Why Crystals Form in Your Joints
High uric acid alone doesn’t guarantee gout. Only about 36% of people with elevated uric acid levels ever develop symptoms, and even among those with levels at or above 10 mg/dL, only about half develop gout over a 15-year period. Something else has to trigger crystal formation.
Temperature plays a surprisingly important role. Uric acid crystallizes more easily in cooler environments. A drop of just 2°C (about 3.6°F) lowers the concentration at which crystals form from 6.8 mg/dL to 6.0 mg/dL. This is one reason gout so often strikes the big toe: it’s the coolest joint in the body, farthest from your core. Feet, ankles, and knees are all more vulnerable than warmer joints closer to the trunk.
Acidity also matters. A more acidic environment in the joint fluid promotes crystal formation through a separate mechanism involving calcium. When pH drops, calcium ions that were bound to proteins in the fluid get released, and those free calcium ions lower the solubility of uric acid even further. The combination of cool temperature and slight acidity creates ideal conditions for crystals to nucleate and grow.
Foods That Raise Uric Acid
Certain foods deliver a heavy load of purines directly into your system. Organ meats like liver, kidney, and sweetbreads are the most concentrated sources. Red meat (beef, lamb, and pork) contributes meaningfully, as do specific types of seafood: anchovies, sardines, shellfish, and codfish rank among the highest.
Fructose deserves special attention because it raises uric acid through an entirely different pathway than purine-rich foods. When your liver processes fructose, the first step burns through your cells’ energy currency (ATP) rapidly. That energy depletion triggers a cascade: the leftover molecular fragments get funneled into uric acid production. Worse, the drop in cellular energy stimulates your body to manufacture more purines to compensate, which generates even more uric acid when additional fructose arrives. This is why sugary drinks sweetened with high-fructose corn syrup are a significant gout risk factor, along with foods like sweetened cereals, baked goods, and even some salad dressings and canned soups.
How Alcohol Contributes
Alcohol raises uric acid through multiple mechanisms at once. The metabolism of ethanol accelerates the breakdown of ATP into uric acid precursors, increasing production. At the same time, alcohol causes lactic acid to accumulate in the blood, which competes with uric acid for excretion through the kidneys. The result is a one-two punch: more uric acid being made and less being removed.
Not all alcohol is equal here. Beer carries the highest risk because it contains both ethanol and high levels of guanosine, a purine that your body absorbs readily. So beer hits you with the alcohol effect and the purine effect simultaneously. Distilled spirits raise risk through the ethanol pathway alone. Wine appears to carry a lower risk than either beer or spirits, though it’s not completely neutral in large amounts.
When Your Kidneys Can’t Keep Up
Your kidneys handle uric acid through a complex filtering and reabsorption process in tiny tubes called proximal tubules. Specialized transporter proteins on these tubes decide how much uric acid gets pulled back into the blood versus how much passes into urine. Two transporters are especially important: one (URAT1) sits on the inner surface of the tube and pulls uric acid back in, while another (GLUT9) moves it across the tube wall and back into circulation.
Anything that increases reabsorption or decreases the kidney’s filtering rate can tip the balance toward gout. Chronic kidney disease reduces the overall filtering capacity. Insulin resistance, common in people with type 2 diabetes or metabolic syndrome, directly affects these transporter proteins: it ramps up the reabsorption transporter and dials down the excretion transporter, trapping more uric acid in the blood. This connection helps explain why gout, obesity, and diabetes so often cluster together.
Medications That Raise Risk
Diuretics (water pills), commonly prescribed for high blood pressure and heart failure, are one of the most frequent medication-related triggers for gout. They work by increasing urine output, which concentrates the remaining body fluid and makes crystal formation more likely. Some types also directly interfere with the kidney’s ability to excrete uric acid. If you’re taking a diuretic and developing joint symptoms, the medication may be a contributing factor worth discussing with your prescriber.
Low-dose aspirin, the kind often taken daily for heart protection, also reduces uric acid excretion through the kidneys. Other medications that can raise uric acid levels include certain immune-suppressing drugs used after organ transplants and some tuberculosis treatments.
Genetic Factors
Your genes have a meaningful influence on how your body handles uric acid, which is why gout tends to run in families. Two genes matter most. The SLC2A9 gene controls the GLUT9 transporter protein in the kidneys. Variants of this gene can increase how aggressively your kidneys reabsorb uric acid back into the blood instead of letting it pass into urine. The ABCG2 gene controls a separate transporter that actively pumps uric acid out through both the kidneys and the intestines. Common variants of ABCG2 reduce this pumping action, leaving more uric acid circulating.
These genetic differences explain why some people develop gout despite a relatively healthy diet, while others eat large amounts of red meat and beer without ever having an attack. Genetics sets the baseline, and lifestyle factors push you toward or away from the threshold where crystals form.
Why Gout Attacks Come and Go
One of the more confusing aspects of gout is its episodic nature. Uric acid crystals can sit in joint tissue for long periods without causing symptoms. An attack occurs when your immune system suddenly recognizes the crystals as foreign invaders and mounts an intense inflammatory response. This is what produces the dramatic redness, swelling, heat, and pain that can make even the weight of a bedsheet unbearable.
Triggers for this immune activation include sudden changes in uric acid levels in either direction, which is why attacks sometimes happen after starting uric acid-lowering medication or after a heavy meal followed by fasting. Dehydration, physical trauma to a joint, illness, and surgery can also set off an attack. The joint already has crystals lying in wait; it just takes a nudge for the immune system to react.