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For many practitioners, elevated uric acid is not typically a marker that sets off alarm bells. Most write it off as an indication of over-indulgence, and send their patients home with a minor prescription and some sober advice about their lifestyle.

Gout, the most well-known consequence of elevated uric acid, is painful but easily treatable and usually benign. Uric acid kidney stones are more serious, but most pass without requiring surgery or intensive intervention. Recent research suggests, however, that these blood-borne crystals are harbingers of significant health decline.

Uric acid is a byproduct of the metabolism of fructose, purines and alcohol consumed in the diet. Beer, high fructose corn syrup (found in processed pastries, fast foods, cooldrinks and sweets) and alcoholic beverages – the staples of our deranged modern diet – are key contributors. The kidneys clear two thirds of uric acid from the bloodstream and the bowel one third, but when levels exceed our clearance capacity, this toxin can initiate a cascade of disease processes.

Mitochondrial Dysfunction and Uric Acid

The mitochondria are the powerhouses of the cell, which convert carbohydrate, fat and protein fuels into energy-rich ATP (adenosine triphosphate) molecules. Every cell in the body depends on ATP to energise the processes of life. Most carbohydrates are broken down into their component monosaccharides in the digestive tract, most common of which is glucose. As glucose is absorbed into the bloodstream, it triggers an insulin response that prompts cells to take it up and regulate blood sugar levels. Fructose is also a dietary monosaccharide, but unlike glucose, it does not stimulate an insulin response. Instead, it goes straight to the liver to be metabolised.

The fructokinase enzyme in the liver processes fructose into ADP (the deenergised sister molecule of ATP). The process costs precious cellular energy, with little nutritional reward. It can deplete ATP concentrations in the liver by up to 50%, stealing vital energy from crucial detoxification processes. The excessive breakdown of ATP elevates the production of byproduct AMP (Adenosine monophosphate), which in turn is converted to uric acid for excretion. High uric acid levels upregulate fructokinase enzyme activity, creating a positive feedback loop that perpetuates the drain of ATP and aggravates many other deleterious effects of fructose metabolism.

Obesity and Uric Acid

Recent studies found that elevated serum uric acid levels are associated with increases in both BMI and waist circumference. Fructose consumption increases hunger and thirst by inhibiting the release of leptin, the fullness hormone. Leptin normally suppresses ghrelin, the hunger hormone, after food is consumed. Without it hunger rages on unabated, leading to overeating. The body converts the excess calories to fat, encouraging obesity. Fructose also drives fat-formation, or lipogenesis, in the liver, promoting fatty liver disease. Because of its stimulatory effect on the fructokinase enzyme, uric acid accelerates the metabolism of fructose, and amplifies its lipogenic effects. Excess fructose-induced triglyceride accumulation for extended periods may promote leptin resistance, locking in the cycle of endless overeating and weight gain.

Cardiovascular Disease and Uric Acid

Elevated triglycerides usher in another danger: free radical damage to the blood vessels. Damaged triglycerides can trigger oxidative stress that may injure blood vessels, encouraging heart attacks, coronary artery disease and high blood pressure. Elevated uric acid further encourages inflammation and oxidative stress, while inhibiting the formation of vessel-protective nitric oxide. This pathological trifecta leaves the cardiovascular system vulnerable.

Insulin resistance and Uric Acid

Insulin resistance and metabolic syndrome are encouraged by uric acid in three ways. Firstly, the damaged triglycerides described above fuel inflammation that blocks insulin receptors. Secondly, uric acid  metabolism increases oxidative stress to the Islets of Langerhans, damaging their ability to produce insulin. Lastly the breakdown of fructose in the liver encourages glucose production, raising blood sugar levels which with sustained consumption promote insulin resistance.

Cognitive Decline and Uric Acid

Uric acid is absorbed into the hippocampus where it reduces mitochondrial function, impairing learning ability and memory recall. The risk of stroke is also increased with hyperuricemia. Studies have demonstrated that uric acid can decrease nitric oxide production, which in turn may inhibit the signalling of messages in the brain and memory formation. The brain requires nitric oxide to stimulate the uptake of glucose for optimal function. Alongside chronic inflammation, hyperuricemia may play a significant role in the cognitive decline frequently associated with metabolic syndrome.

The evidence implicating uric acid in the decline of multiple systems of the body is mounting. With effects ranging from aggravating mitochondrial dysfunction at the cellular level to metabolic syndrome, insulin resistance, obesity, cardiovascular disease and even cognitive decline on the systemic level, this metabolic by-product is far from benign. Its presence sounds the alarm that detrimental dietary habits are initiating disease processes, and provides a target for remediation. Its time that we stop laughing off this insidious urinary metabolite.

By Dr. Robin Kohler, MTech (Hom), Dip(Irid)

From an early age, Dr Robin Kohler knew that he wanted to help people. Like his specialist physician father, Dr Kohler was always intrigued by what made people ill. He completed a Masters in Homeopathy at the University of Johannesburg but found his true calling when he discovered Functional Medicine.

Functional Medicine’s systematic, science-based approach to finding and treating root causes was a perfect fit, and Dr Kohler has spent hundreds of hours growing and deepening his functional health knowledge.

He started the Perfect Health Practice with his wife, Bronwyn Kohler, in 2010. Together, they have striven to make it a haven of both healing and learning, where patients can learn how to not only restore their health, but also optimise and preserve it far into the future.