Five Studies Highlight Uric Acid Link to Metabolism


The connection between uric acid (UA) and metabolism has recently emerged in scientific literature. David Perlmutter, MD, FACN, addressed this subject in a breakout session at the 2023 Integrative Healthcare Symposium in New York City.

In his presentation, Perlmutter discussed the significance of UA, an enzymatic end-product of purine metabolism, on human health, noting elevated UAlevels could be the root of many pervasive health conditions, such as diabetes, obesity, and cardiovascular disease. He said zeroing in on UA states can be considered “a new tool in a practitioner's toolbox” for understanding human metabolism.

Perlmutter, who recently authored a new book, Drop Acid: The Surprising New Science of Uric Acid, cited five studies, which we’ve rounded up as required reading for integrative healthcare professionals.

Association Between Metabolic Syndrome and Uric Acid

The systemic review and meta-analysis investigated the relationship between serum uric acid (UA) levels, metabolic syndrome (MetS), and carotid atherosclerosis. The researchers analyzed data from 12,038 participants and found that higher serum UA levels were independently associated with an increased risk of carotid atherosclerosis, particularly in individuals with MetS.

The study demonstrated that MetS and elevated UA levels increased the risk of developing carotid atherosclerosis more than either factor alone. According to researchers, this suggests UA plays a significant role in the development of atherosclerosis and highlights the importance of considering both MetS and UA levels in assessing cardiovascular risk.

Click here to read the study. 

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders

The review explored the connection between fructose consumption, uric acid (UA) production, and the development of cardiometabolic disorders. Elevated UA levels have been associated with hypertension, metabolic syndrome, cardiovascular disease, chronic kidney disease, type 2 diabetes, and cognitive decline.

The increase in UA levels is partly attributed to the rise in fructose consumption in the Western diet, the researchers said. The enzyme xanthine oxidase (XO) plays a significant role in UA production, and xanthine-oxidase inhibitors (XOI) have been proposed as a potential treatment to reduce UA levels and mitigate adverse effects on vascular health. The review highlights recent research on UA's role in cardiometabolic disorders and its link to fructose intake and associated diseases, particularly cardiovascular disease.

Click here to read the study. 

Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

For this study, researchers investigated the connection between uric acid (UA) and renal impairment, focusing on emerging hypotheses linking UA to pro-inflammatory status, endothelial dysfunction, and excessive activation of the renin-angiotensin-aldosterone system (RAAS). The study also explored the role of hyperuricemia-associated oxidative stress in DNA damage, inflammation, and cell apoptosis.

The researchers provided insight into the growing body of evidence that associates hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus.

Click here to read the study. 

Serum Uric Acid Level as an Independent Risk Factor for All-Cause, Cardiovascular, and Ischemic Stroke Mortality

This study examined the relationship between serum uric acid (UA) levels, hyperuricemia, and cardiovascular mortality in the Taiwanese population. The researchers conducted a prospective cohort study with 41,879 men and 48,514 women aged 35 years and older, using data from the MJ Health Screening Centers in Taiwan. They compared mortality rates from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease across increasing serum UA levels.

The results revealed that hyperuricemia (serum UA level >7 mg/dl) was an independent risk factor for all-cause mortality, total CVD, and ischemic stroke. This association remained significant in patients with hypertension and diabetes, the researchers said.

The study found that even in a low metabolic risk subgroup, hyperuricemia was associated with increased all-cause mortality and total cardiovascular morbidity.

Click here to read the study. 

Could Alzheimer’s Disease Be a Maladaptation of an Evolutionary Survival Pathway Mediated by Intracerebral Fructose and Uric Acid Metabolism?

The article explores a hypothesis that Alzheimer's disease (AD) may be linked to a maladaptation of an evolutionary survival pathway involving fructose metabolism and its metabolite, uric acid (UA). This survival response, triggered by fructose, aims to conserve resources during times of scarcity and results in a range of metabolic changes, including insulin resistance, fat and glycogen storage, and reduced resting metabolism. UA, a byproduct of fructose metabolism, plays a crucial role in this process.

In the study, the authors said this survival mechanism, once beneficial for our ancestors, now predisposes individuals to obesity, diabetes, and AD in today's environment. The pathway can be activated by diets high in sugar, high glycemic carbohydrates, and salt, elevating UA levels, the researchers said. 

Click here to read the study.