6 Things You Really Need to Know About Your Uric Acid Level: It’s Not Just About Gout…It’s About Inflammation

Uric acid levels have found a new level of significance in the role of health and disease. There are 6 things you need to know about your uric acid level…and it’s not just about its role in gout. Knowing how uric acid level influences inflammation and disease and what to do about it can provide you with insight into reducing your risk of disease.

1. What is uric acid? Uric acid is a chemical created when your body breaks down purines. Levels of uric acid can be measured in the blood. While most uric acid travels to the kidneys and is excreted, if the body accumulates too much, hyperuricemia or too much uric acid remains in your body and can cause many issues…and it’s not just about gout or kidney stones. High uric acid levels undermine the production of the body’s nitric oxide (NO) as well as how it functions. NO serves important functions in dilating blood vessels to support circulation and also supports insulin function. When NO is deficient heart disease, diabetes, or erectile dysfunction can result.

2. What are high uric acid levels? High levels of uric acid once were only associated with kidney stones and gout. Gout is a metabolic disease, where excess uric acid accumulates and erodes bone tissue and forms sharp, needle-like crystals of urate in the joints, which causes inflammation and pain and can be severe. Gout historically was associated with the rich and famous such as royalty and those who had access to and consumed diets high in sugar and alcohol. Over time, it was discovered that hyperuricemia was not limited to the development of gout or kidney stones. As a common inflammatory and immune system disease, gout has significantly increased, in parallel with obesity and metabolic syndrome. Interestingly, this increase is associated with increased dietary consumption of sugar-sweetened food and drinks including soda pop and fruit juices. High fructose corn syrup found in many processed foods, in particular, leads to insulin resistance and diabetes and predisposition to hyperuricemia.

While uric acid testing may be included in your annual physical, according to Dr. David Perlmutter, author of Drop Acid, The Surprising New Science of Uric Acid—The Key to Losing Weight, Controlling Blood Sugar, and Achieving Extraordinary Health, most physicians rarely pay attention to the result. However, asymptomatic hyperuricemia could be leading to biological processes that result in elevated blood sugar, elevated blood pressure, excess body fat, and inflammation that can lead to a number of chronic diseases.

As uric acid levels are associated with dysfunction and disease, they therefore should be managed. Per Dr. Perlmutter, your uric levels should ideally be below 5.5 mg/dL.¹  Even slight increases in blood levels can be an independent risk factor for death. A common denominator is inflammation. Elevated uric acid increases inflammation. Heart disease and cancer are two examples of different diseases related to inflammation. Current studies are looking at charting the parallels between uric acid levels and inflammation levels as measured by C-reactive protein in diseases like metabolic syndrome.²

3. Consequences of Elevated Uric Acid Levels-High levels of uric acid cause oxidative stress, which constrict blood vessels and increase blood pressure. Continued high levels of uric acid cause lasting inflammation and injury to the kidneys, which causes salt retention and water retention, increased blood pressure. What do elevated uric acid levels potentially predict?

• Gout-Gout is a common form of arthritis that can cause significant joint pain, especially in the big toe.
• Kidney Stones, Kidney Disease- There are differences among populations in kidney stones caused by high uric acid. In the U.S., 8-10 % of all kidney stones occur from uric acid nephrolithiasis, with increased prevalence in patients with type 2 diabetes mellitus and those with obesity.³
• High Blood Pressure (hypertension) and Cardiovascular Disease-Uric acid decreases NO and triggers hypertension and loss of ability of blood vessels to respond to changes in blood pressure.
• Risk of developing type 2 diabetes and insulin resistance. Metabolic syndrome, insulin resistance and correlation with elevated uric acid levels are seen even in obese children and linked to cardiovascular issues. ⁴
• Obesity and Metabolic Syndrome-uric acid triggers fat production even in those who are not obese. Metabolic Syndrome consists of 5 key characteristics, of which only 3 are required for diagnosis which are high blood pressure, elevated blood sugar, excess body waist circumference (greater than 40 inches in men, and greater that 35 inches in women), abnormal cholesterol levels (especially low HDL). Uric acid is becoming a new marker for metabolic syndrome.
• Diabetes- Hyperuricemia is closely related to the development of diabetes and its chronic complications.⁵

• Neurologic Disease-While uric acid is associated with diabetes and Alzheimer’s Disease (AD) is often referred to as Type III Diabetes, the relationship of uric acid to neurologic disease has been debated. While uric acid does have anti-oxidant properties, and can be neuroprotective according to some studies of AD and Parkinson’s Disease, it is known to be particularly toxic in the presence of vascular disease The relationship between uric acid and the cognitive system remains a debated issue.⁶
• Cancer- Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis.⁷ Hyperuricemia has been indicated promoting the progression of various cancers and reducing cancer-related overall survival, suggesting that uric acid might be a potential risk factor of cancer development.⁸
• Fatty Liver Disease-Hyperuricemia has been associates with higher risk of developing non-alcoholic fatty liver disease.⁹
• Erectile Dysfunction-This is due to decreased NO with hyperuricemia and effects on endothelial vascular causing penile erection dysfunction.¹⁰
• Decreased anti-inflammatory and immune function-Uric acid prevents your cells from clearing out waste and decreasing inflammation.
• Adverse changes to the gut microbiome-Hyperuricemia can lead to increase pro-inflammatory strains of gut bacteria, which can lead to leaky gut and leaky brain.  
• Reduced anti-aging-Reduces adenosine monophosphate-activated protein kinase, known as AMPK which signals the body that no more fat storage is needed. It can activate adenosine monophosphate deaminase, called, AMPD2 which silences AMPK and increases fat storage.

4. Things that Elevate uric acid levels:

• Highly processed, refined fructose-This is not the natural fructose found in fruit. Rather, it is found in many processed foods, such as baked goods, condiments, snacks, beverages, and energy bars. Fructose generates uric acid and today’s American diet is filled with fructose-laden products. Fructose when consumed in conditions of high uric acid levels, amplifies the negative effects of fructose. Fructose determines uric acid production and AMPH or AMPD2 activity.
• High purine foods-Purines are organic components of our genes, forming RNA and DNA. When broken down, they form uric acid. Purines are high in foods such as some seafoods (sardines, anchovies, mackerel, scallops, herring, haddock), meats, multigrain breads, beer, and even some legumes and vegetables such as cauliflower, spinach, and mushrooms. Purines are both produced naturally within the body as well as obtained through foods. Purines can affect blood flow, heart function, inflammatory and immune response, pain, digestive function and absorption of nutrients. Your total purine pool is the amount you produce plus the amount you obtain outside your body and when processed, the final end product of metabolism is uric acid. Purines are not harmful, but the excessive amount or uric acid and things that affect its elimination can cause higher levels of uric acid which adversely affect metabolism and multiple systems including the brain.

• Alcohol Consumption- Overall, alcohol while it can be a source of purines, it causes the body to excrete alcohol over uric acid, leaving more uric acid in circulation, and it increase the metabolism of nucleotides which are a source of purines. Alcohol has a direct correlation to increases in uric acid levels¹¹. Beer is higher in purines compared to liquor and wine is not considered to be a driver of uric acid levels when consumed in moderation.

5. How to decrease uric acid levels: Decreasing uric acid levels can be relatively simple as uric acid is only found in 3 sources which are fructose, alcohol, and purines. Refer to Dr. Permutter’s book, to learn about his LUV (lower uric acid values) diet:

• Eliminate processed fructose from the diet
• Avoid use of xylitol as a sweetener
• Eat a low-purine diet
• Take a high quality pro-biotic
• Eat pro-biotic rich, fermented foods such as kimchi, cultured yogurt
• Eat pre-biotics such as onions, garlic, leeks, asparagus.
• Increase fiber-Cruciferous vegetables, especially those high in sulforaphane, such as broccoli, broccoli sprouts, and brussel sprouts can decrease uric acid. Even vegetables high in purines do not raise uric acid.
• Consume uric acid-reducing foods such as tart cherries, blueberries, coffee, green tea, red onions, walnuts, green peppers, celery. Coffee, in addition to containing polyphenols, contains xanthine, which inhibits the enzyme xanthine oxidase required for uric acid production.
• Decrease consumption of seafood, red meat. Eliminate processed deli meat.
• Eliminate alcohol- Or if your drink, drink a small to moderate amount of red wine.
• Eat organic.
• Limit or restrict snacking.
• Consider intermittent fasting or time-restricted eating.
• Get quality sleep-Increased uric acid is a risk factor for sleep disorders. A study also showed that better sleep, around 7-8 hours per night was associated with lower uric acid levels. ¹²
• Moderate exercise-avoid excessive exercise which can increase uric acid levels temporarily.
• Decrease any uric acid-increasing drugs in consultation with your provider. Medications or supplements such as aspirin, replacement testosterone, Viagra, beta-blocker medications, diuretics, niacin supplementation, theophylline, levodopa,
• Take supplements such as vitamin C, quercetin.
• Eliminate toxin exposure-Consider testing for lead toxicity.
• Monitor your uric acid values.
• Monitor your blood glucose levels.
• Medications to lower uric acid levels-Your provider may consider uric acid-lowering medication to decrease inflammation and activate the AMPK pathway to reduce risk of or decrease disease. One example is the use of metformin in insulin resistant individuals.¹³ Another example, is use of uric-acid lowering medication in atherosclerosis and activation of the AMPK pathway.¹⁴

6. Get the Support of a Functional Practitioner-A functional practitioner can help support you with uric acid testing as well as other standard lab testing performed by traditional providers and functional lab testing that can help identify root causes of metabolic issues. For example, I support clients with general functional lab testing to help identify hidden causes of inflammation and also help clients with standard lab testing as indicated. When you test, and don’t guess, this can better help to pinpoint healing opportunities and root causes of issues that contribute to inflammation. Rebalancing your body with the appropriate personalized diet, good sleep hygiene, elimination of toxins, stress management, and appropriate exercise and supplementation can help to reduce hyperuricemia risk, reduce inflammation, and help to prevent and manage disease.

Summary-While you may not have been familiar with how uric acid plays a role beyond kidney stones and gout in health, it may be time to consider how you can actively monitor and control it to reduce inflammation, improve your health and prevent disease.

References:

1.          Perlmutter DM. Drop Acid: The Surprising New Science of Uric Acid–The Key to Losing Weight, Controlling Blood Sugar, and Achieving Extraordinary Health.

2.          Sah SK, Khatiwada S, Pandey S, et al. Association of high-sensitivity C-reactive protein and uric acid with the metabolic syndrome components. SpringerPlus. 2016;5(1). doi:10.1186/s40064-016-1933-y

3.          Sakhaee K. Epidemiology and clinical pathophysiology of uric acid kidney stones. Journal of Nephrology. 2014;27(3). doi:10.1007/s40620-013-0034-z

4.          Genoni G, Menegon V, Secco GG, et al. Insulin resistance, serum uric acid and metabolic syndrome are linked to cardiovascular dysfunction in pediatric obesity. International Journal of Cardiology. 2017;249. doi:10.1016/j.ijcard.2017.09.031

5.          Xiong Q, Liu J, Xu Y. Effects of Uric Acid on Diabetes Mellitus and Its Chronic Complications. International Journal of Endocrinology. 2019;2019. doi:10.1155/2019/9691345

6.          Tana C, Ticinesi A, Prati B, Nouvenne A, Meschi T. Uric acid and cognitive function in older individuals. Nutrients. 2018;10(8). doi:10.3390/nu10080975

7.          Yiu A, van Hemelrijck M, Garmo H, et al. Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: Findings from the AMORIS Study. Oncotarget. 2017;8(26). doi:10.18632/oncotarget.16198

8.          Mi S, Gong L, Sui Z. Friend or foe? An unrecognized role of uric acid in cancer development and the potential anticancer effects of uric acid-lowering drugs. Journal of Cancer. 2020;11(17). doi:10.7150/jca.46200

9.          Abbasi S, Haleem N, Jadoon S, Farooq A. Association Of Non-Alcoholic Fatty Liver Disease With Serum Uric Acid. Journal of Ayub Medical College, Abbottabad : JAMC. 2019;31(1).

10.        Barassi A, Corsi Romanelli MM, Pezzilli R, et al. Levels of uric acid in erectile dysfunction of different aetiology. Aging Male. 2018;21(3). doi:10.1080/13685538.2017.1420158

11.        BARTIMAEUS ES, ENO-ENO M. The Effect of Alcohol on Uric Acid Level in Consumers. Journal of Applied Sciences and Environmental Management. 2002;6(1). doi:10.4314/jasem.v6i1.17185

12.        Lee YC, Son DH, Kwon YJ. U-shaped association between sleep duration, c-reactive protein, and uric acid in korean women. International Journal of Environmental Research and Public Health. 2020;17(8). doi:10.3390/ijerph17082657

13.        Jiao Z, Chen Y, Xie Y, Li Y, Li Z. Metformin protects against insulin resistance induced by high uric acid in cardiomyocytes via AMPK signalling pathways in vitro and in vivo. Journal of Cellular and Molecular Medicine. 2021;25(14). doi:10.1111/jcmm.16677

14.        Kimura Y, Yanagida T, Onda A, Tsukui D, Hosoyamada M, Kono H. Soluble uric acid promotes atherosclerosis via AMPK (AMP-activated protein kinase)-mediated inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. Published online 2019. doi:10.1161/ATVBAHA.119.313224