Understanding Gout: A Multifaceted Condition

  

Understanding Gout: A Multifaceted Condition

by:  ju-boo lim

Before I write, let me wish all readers a very blessed Christmas today, and a bountiful New Year 2025 ahead.   

Christmas Day on 25 December is just an arbitrary date for the birth of Jesus. The exact date of His birth is not known. See explanation on the Birth Star of Jesus here:

The Mystery of The Star in the East

https://scientificlogic.blogspot.com/search?q=star+in+the+east

On this note, I also like to wish my first-born son Benjamin Lim Chong Minn a very Blessed Birthday. He was born on Christmas Eve under an exceptionally clear sky with Orion overhead and the Morning Star Venus rising in the East. I took note of this as astronomy is one of my fields of interest where I have some formal training.

This article on gout was written in July 1999 as a concise lecture note given out during a lecture for doctors delivered by me. It was never meant for this blog. However, at a request of a doctor friend of mine who recently asked me a question of uric acid, I decided to have this article posted here for interested readers as well.

Let’s now go into uric acid and gout.

A 45-year-old male patient who was a vegetarian once came to consult me about his gout that kept occurring despite seeking repeated treatment elsewhere. He was puzzled how he could develop gout when he hardly consumed meat.

Let me straight away clarify this.  It is not necessary to be a meat eater to suffer from gout. Neither is it true that vegans and vegetarians are immune to gout.
This condition arises from elevated levels of uric acid in the body. Unlike urea, which is highly soluble in water and easily excreted through the kidneys, uric acid is only sparingly soluble. When its levels rise beyond the body's capacity to excrete it, uric acid can crystallize in the blood, kidneys, and particularly in the joints. This results in inflammatory arthritis that manifests in painful flares.

Gout is historically known as the "disease of kings" It was once associated with the wealthy due to their access to rich diets. Today, it serves as a reminder that both dietary and metabolic factors contribute to its development.

Gout is a complex form of inflammatory arthritis characterized by sudden, severe attacks of pain, redness, and tenderness in joints, often the joint at the base of the big toe. It results from elevated levels of uric acid in the blood, leading to the formation of urate crystals in joints. While traditionally associated with a diet rich in meat and alcohol, gout can also affect vegetarians, vegans and individuals with various dietary habits.

Understanding Uric Acid and Purines:

Uric acid is a waste product formed from the breakdown of purines, substances found naturally in the body and in certain foods. Normally, uric acid dissolves in the blood and passes through the kidneys into the urine. However, if the body produces too much uric acid or the kidneys excrete too little, uric acid can accumulate, forming sharp, needle-like urate crystals in a joint or surrounding tissue, causing pain and inflammation.

Dietary Considerations:

Meat and seafood like salmon, trout, and tuna can increase uric acid levels. However, their heart benefits may outweigh the gout risk.  Shellfish like crab, lobster, oysters, and shrimp too is high in purines. So are anchovies (ikan bilis), sardines, mackerel, herring, scallops. These seafoods have higher levels of purines than other types. However, this does not mean they cause gout when consumed occasionally in small amounts.

Purine-Rich Vegetable Foods:

Some vegetables, despite their health benefits, are high in purines. These include, asparagus, cauliflower, dried lentils, beans, and peas, green peas, mushrooms, spinach, whole grains like oats and wheat bran. Certain vegetables like asparagus, cauliflower, spinach, and mushrooms also contain significant purine levels. However, studies suggest that these vegetable sources do not increase the risk of gout and can be included in a balanced diet. Conversely, alcohol (especially beer) and beverages sweetened with high-fructose corn syrup can raise uric acid levels and should be limited. These foods should be eaten in moderation. 

However, studies suggest that these vegetable sources do not increase the risk of gout and can be included in a balanced diet. Conversely, alcohol (especially beer) and beverages sweetened with high-fructose corn syrup can raise uric acid levels and should be limited. These foods should be eaten in moderation.

On the other hand, purine-rich meats like anchovies, bacon, organ meats, red meats, sardines, scallops, and tuna need to be curtailed for individuals with gout. A diet emphasizing vegetables low in purines and incorporating low-fat or non-fat dairy products is often advised to help manage uric acid levels.

Sources of Uric Acid:

According to the Arthritis Foundation, approximately two-thirds of uric acid is produced endogenously as a by product of cellular metabolism, while the remaining one-third comes from dietary sources. Uric acid is formed during the breakdown of purines—compounds found in certain foods. While it is widely known that purine-rich meats contribute to gout, it is less well-known that certain vegetables and grains can also significantly increase purine intake.

Role of Salicylic Acid:

A lesser-known contributor to gout is salicylic acid (aspirin) found naturally in fruits and vegetables as a protective compound against diseases and pests. Studies have shown that salicylic acid can reduce the excretion of uric acid by the kidneys, exacerbating hyperuricemia. Vegetables particularly rich in salicylic acid include, broccoli, cauliflower, mushrooms, cucumber, eggplant (brinjal), okra (lady’s fingers), peppers, radishes, spinach, squash and zucchini
The dual challenge of certain vegetables being high in both purines and salicylates highlights the complexity of dietary management in gout.
There are also other risk factors beyond diet. Other factors that contribute to the development of gout are:

1. Genetics: Family history can predispose individuals to gout.

2. Age and Gender: Men aged 30 to 50 are more susceptible, though postmenopausal women also face increased risk.

3. Obesity: Excess body weight increases uric acid production and reduces its excretion.

4. Kidney Function: Impaired renal function diminishes the body’s ability to excrete uric acid.

5. Medications: Certain medications, such as low-dose aspirin and diuretics, can increase uric acid levels.

Hydration and Lifestyle Modifications:

Adequate hydration helps maintain urine flow and reduces the risk of uric acid crystal formation. A daily water intake of at least 2 to 3 litres is recommended, unless contraindicated by other health conditions. Gradual weight loss, regular physical activity, and stress management techniques like yoga or meditation can also help manage gout.

Pathophysiology and Diagnosis:

Gout is diagnosed based on clinical criteria, including the identification of monosodium urate crystals in synovial fluid of the affected joint. This condition is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint.

Clinical Manifestations of Gout:

When uric acid or its salts (monosodium urate) accumulate and crystallize in the joints, they trigger intense pain and inflammation known as a gout attack. The condition typically affects the first metatarsophalangeal joint (the base of the big toe), although other joints may also be involved.
The diagnosis of gout is usually based on clinical criteria from the American College of Rheumatology. It can be confirmed by identifying monosodium urate crystals in synovial fluid aspirated from the affected joint.

Management and Prevention:

Acute gout attacks may be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine. To reduce the likelihood of recurrent flares, patients should limit their consumption of purine-rich foods and avoid alcoholic drinks and beverages sweetened with high-fructose corn syrup. Medications like allopurinol and febuxostat are first-line options for preventing recurrent gout, while colchicine and probenecid are reserved for patients who cannot tolerate first-line agents.

To prevent recurrences, patients are advised to:

1. Limit purine-rich foods (e.g., organ meats, shellfish)

2. Avoid alcohol, especially beer

3. Avoid beverages sweetened with high-fructose corn syrup

4. Maintain adequate hydration to promote uric acid excretion

Certain medications also play a role. For example:

1. Low-dose aspirin (commonly used for cardiovascular protection) can reduce uric acid excretion and contribute to hyperuricemia.

2. Loop and thiazide diuretics can increase uric acid levels.

3. Losartan, an angiotensin receptor blocker, enhances uric acid excretion and may be beneficial for patients with gout.

Long-term management involves reducing uric acid levels using medications like allopurinol or febuxostat. For patients who are intolerant to these drugs, colchicine or probenecid may be used. Uric acid levels should be reduced to target levels (below 6 mg/dL) and maintained for at least three months in patients without tophi or six months in those with a history of tophi.

Emerging Treatments and Research:

Recent studies have explored biological therapies, such as pegloticase, for severe or refractory cases of gout. Additionally, research into the gut microbiome's role in uric acid metabolism may open new avenues for treatment. Natural supplements like cherry extract or vitamin C are also being studied for their potential to lower uric acid levels.

Gout and Comorbidities:

Gout often coexists with other conditions, including hypertension, obesity, dyslipidemia, type 2 diabetes mellitus, hypertension, and chronic kidney disease. This underscores the importance of comprehensive health management in patients with gout. It is a multifactorial condition influenced by diet, genetics, and lifestyle. A comprehensive management strategy that includes dietary modifications, lifestyle changes, and appropriate medical treatment can help control and prevent gout flares.

This underscores the importance of adopting a holistic approach to managing gout, emphasizing proper nutrition, medication adherence, and addressing underlying comorbidities.

Gout serves as a reminder of how interconnected our diet, metabolism, and health truly are. While it is traditionally associated with meat consumption, gout can affect vegetarians and omnivores alike. A careful balance of nutrition, lifestyle modifications, and medical management is key to controlling this complex condition.

Risk Factors Beyond Diet:

Although diet plays a significant role in gout, it is not the sole factor. Other risk factors include, genetics and  family history of gout can predispose individuals to the condition. Men are more likely to develop gout, especially between the ages of 30 and 50, although postmenopausal women also face increased risk. Excess body weight increases uric acid production and reduces its excretion. Impaired renal function diminishes the body's ability to excrete the uric acid.
In addition to dietary adjustments, certain lifestyle changes can significantly reduce the risk and severity of gout flares:

Weight management to gradually reduce uric acid levels without triggering a flare. Rapid weight loss, however, should be avoided as it can increase uric acid temporarily. Regular physical activity helps improve overall metabolic health and reduces comorbid conditions like obesity and hypertension.
Chronic stress can increase inflammation and worsen gout symptoms. Relaxation techniques such as yoga, meditation or other stress management may be beneficial.
 

Hydration and Its Role in Uric Acid Excretion:

Emphasizing the importance of hydration could be useful. Drinking sufficient water helps maintain urine flow and reduces the risk of uric acid crystal formation in the kidneys and joints. Recommending a daily water intake of at least 2 to 3 litres, unless contraindicated by other health conditions, can reinforce this point.

Emerging Treatments and Research:

Discussing emerging therapies or ongoing research into gout management could be insightful. For example:

Biological Therapies:

Medications like pegloticase, an enzyme that breaks down uric acid, are used in severe or refractory cases of gout. Studies suggest that the gut microbiome may play a role in uric acid metabolism, opening new avenues for treatment.  Natural supplements like cherry extract or vitamin C are being studied for their potential to lower uric acid levels.
Preventing gout in individuals at risk could be another valuable addition. Preventive measures might include routine  monitoring uric acid levels in individuals with risk factors.

Prophylactic medications may be considered in certain high-risk patients, starting medications like allopurinol even before the onset of symptoms.

Conclusion:

Gout is one of the lifestyle diseases. As such, it must be managed holistically by considering all the causative factors already explained, and not merely treat it with colchicine or allopurinol.

References:
 

General Overview and Pathophysiology:

1. Richette, P., & Bardin, T. (2010). Gout. The Lancet, 375(9711), 318-328.
This article provides a comprehensive review of the pathophysiology, diagnosis, and management of gout, including the role of uric acid in the disease process.

2. Dalbeth, N., & Stamp, L. K. (2014). Gout: Pathophysiology and management. Nature Reviews Rheumatology, 10(12), 667-677.
A detailed review of gout's pathophysiology and the latest advances in its management

Diagnostic Criteria:

3. American College of Rheumatology. (2015). 2015 American College of Rheumatology/European League Against Rheumatism classification criteria for gout. Arthritis & Rheumatology, 67(5), 1307-1314.
This provides updated classification criteria for gout diagnosis, based on clinical and laboratory findings.

Management and Treatment:

4. Schlesinger, N., & Stojanovic, A. (2017). Acute gout: Diagnosis and management. Journal of Clinical Rheumatology, 23(6), 343-349.
This article reviews the diagnostic and treatment strategies for managing acute gout attacks.

5. Terkeltaub, R. A. (2003). Clinical practice. Gout. The New England Journal of Medicine, 349(17), 1647-1655.

A classic paper on the clinical management of gout, including both acute and chronic phases of the disease.
DOI: 10.1056/NEJMcp035643

6. Yang, T., & Li, W. (2020). Colchicine for the treatment of gout: A review of current evidence. American Journal of Therapeutics, 27(3), e253-e259.
A review of the evidence regarding the use of colchicine in managing acute gout.
DOI: 10.1097/MJT.0000000000000990

Dietary Considerations:

7. Choi, H. K., & Curhan, G. (2008). Beer, liquor, and wine consumption and risk of gout in men. The New England Journal of Medicine, 359(6), 585-591.

This study investigates the relationship between alcohol consumption and the risk of developing gout, providing important insights into dietary management.

8. Gaffo, A. L., & Saag, K. G. (2015). Management of gout: Current evidence and clinical guidelines. Current Rheumatology Reports, 17(7), 1-10.
A review on managing gout through both pharmacologic and lifestyle interventions, including diet.

These references cover the major aspects of gout, from pathophysiology to diagnosis, treatment, and lifestyle factors