Known as “the disease of kings and the king of diseases”, gout has been studied by physicians and has caused suffering in countless humans since at least the days of Hippocrates. Formerly a leading cause of painful and disabling chronic arthritis, gout has been all but conquered by advances in research. Unfortunately, many people with gout continue to suffer because knowledge of effective treatments has been slow to spread to patients and their physicians.
The inflammatory process in gout is unrelated to infection. Rather, it is incited by the deposition in the joint of uric acid crystals usually due to an excess of uric acid in the bloodstream. This can be caused by an increase in production by the body, by under-elimination of uric acid by the kidneys or by increased intake of foods containing purines which are metabolized to uric acid in the body. Certain meats, seafood, dried peas and beans are particularly high in purines. Alcoholic beverages may also significantly increase uric acid levels and precipitate gout attacks. Gout is strongly associated with obesity, hypertension, hyperlipidemia, diabetes and dehydration. A familial pattern is observed in 5-15% of cases.
The four phases of gout include elevated uric acid levels without symptoms, acute gouty arthritis, multiple attacks with intervals between attacks, and chronic tophaceous (nodular masses of uric acid crystals (tophi) deposited in different soft tissue areas of the body) gout. Patients with asymptomatic hyperuricemia do not require treatment, but efforts should be made to lower their urate levels by encouraging them to make changes in diet or lifestyle.
Uric acid is a product of the chemical breakdown of the purine bases that compose the genetic material, DNA. As cells die and release DNA from their chromosomes, purines are converted into uric acid which is excreted in the urine and, to a lesser extent, the intestinal tract. The level of uric acid dissolved in the bloodstream is directly related to this delicate balance between uric acid production and excretion. The normal level is approximately 2-7mg/dl.
In most cases, an under-excretion of uric acid by the kidneys is responsible. Among the more common predisposing factors are kidney failure from any cause, diuretics, dehydration, hormonal diseases, alcohol consumption and using low doses of aspirin. About 10% of people with hyperuricemia are overproducers of uric acid. For some of these patients, diseases of the blood and bone marrow or inherited enzyme abnormalities can be implicated. Some are associated with metabolic alterations due to obesity, but for most the exact cause is indeterminable.
An attack of acute gouty arthritis is caused by the body’s inflammatory reaction to intermittent deposition of needle-like uric acid crystals. When these crystals are ingested by white blood cells, the cells release enzymes that evoke inflammation. Attacks are usually marked by intermittent joint pain, swelling, redness and warmth. In some individuals, it is a progressive, crippling chronic disease that also damages the kidneys. Gout is from 5 to 20 times more common in men than in women and afflicts an estimated 840 out of 100,000 people. Gout and its complications occur more commonly and at a younger age in males.
Signs and Symptoms
- Rapid onset of severe joint pain, swelling and redness, often beginning at night after ingestion of alcoholic beverages, uric acid-elevating medications or high-purine foods.
- In 90% of initial episodes a single joint is involved – especially the joint at the base of the big toe. Gouty arthritis of the big toe afflicts some 90% of patients some time during the course of their disease. The foot, heel, ankle, knee, hands, wrists and elbows are some of the other joints that are frequently involved.
- Attacks tend to last a few days to a few weeks.
- Attacks respond well to medications.
- The frequency of subsequent attacks is variable. 5-10% of patients will never be bothered again, but most relapse within a year.
Untreated cases may develop chronic gouty arthritis in which multiple joints are involved by a long-term destructive process. Tophi, small nodules consisting of uric acid and inflammatory tissues, may be seen on the ear cartilage and along tendons.
Diagnosis
Since several other kinds of arthritis can mimic a gout attack, and since treatment is specific to gout, proper diagnosis is essential. The definitive diagnosis of gout is dependent on finding uric acid crystals in the joint fluid during an acute attack. However, uric acid levels in the blood alone are often misleading and may be transiently normal or even low. Additionally, uric acid levels are often elevated in individuals without gout. While sudden swelling and pain in a joint, especially the big toe, suggests the diagnosis of gout, many other arthritic conditions and some infections present themselves in a similar manner. Gout is the diagnosis if gout medications resolve the symptoms. Uric acid levels are usually elevated around an attack, and reduced when treated successfully.
Gout in women occurs nearly always after menopause. Women develop gout at an older age than men and have twice the prevalence of hypertension, renal insufficiency and exposure to diuretics. The onset of gout before age 30 in men or before menopause in women is unusual and raises concern about an associated inherited enzyme defect or renal disease.
Comparison with 220 male patients with gout showed that female patients developed gout significantly later, more frequently had associated diseases, and more often were receiving diuretics, whereas significantly more male than female patients had alcoholism. The articular features of gout were similar in both groups. However, the prevalence of tophi was higher and its localization different in female than in male patients. Female patients with gout had a higher mean serum urate concentration and a lower mean urinary uric acid excretion than did male patients with gout. These differences were significant and independent of the effects of age, renal insufficiency, alcoholism, or previous diuretic intake. Renal underexcretion of uric acid appears to be more severe in female than in male patients with gout.
Treatment
Aside from those mentioned below, also avoid purine-rich foods: anchovies, asparagus, crab, fish roe, herring, kidney, liver, meat gravies and broth, mushrooms, mussels, peas & beans, and sardines.
Conditions that suggest Gout / Hyperuricemia
Multiple Sclerosis / Risk
It has been reported that MS (possibly associated with low uric acid) and gout (associated with high uric acid) are mutually exclusive. A study of 20 million Medicare and Medicaid records found no overlap between MS and gout.
Hypertension
Gout is strongly associated with obesity, hypertension, hyperlipidemia and diabetes.
Elevated Total Cholesterol
Gout is strongly associated with obesity, hypertension, hyperlipidemia and diabetes.
Risk factors for Gout / Hyperuricemia
Dehydration
Gout can be caused by dehydration and the use of diuretics such as coffee or alcohol.
Elevated Insulin Levels
Preliminary research suggests that insulin resistance may play a role in the development of gout. Gout is strongly associated with the consequences of insulin resistance i.e. obesity, hypertension, hyperlipidemia and diabetes.
Problem Caused By Being Overweight
Gout is strongly associated with obesity, hypertension, hyperlipidemia and diabetes.
Kidney Failure
Patients with impaired renal function filter and excrete less uric acid and therefore become hyperuricemic. Interestingly, patients with renal failure do not develop gout as frequently as expected, despite their high plasma urate levels. The explanation for this phenomenon may be that they have not incurred sustained hyperuricemia levels long enough to develop gout. Only 1% of renal failure patients develop gout but nearly 30% of patients with adult polycystic kidney disease do.
Kidney Weakness / Disease
Hyperuricemia is caused by a variety of means, one of which is abnormal kidney function.
Kidney Stones (Urolithiasis)
Gout (excess uric acid) is a common cause of kidney stones.
Moderate/high alcohol consumption
Alcohol inhibits uric acid secretion by the kidneys.
History of gout
Gout / Hyperuricemia suggests the following may be present
Hypertension
Gout is strongly associated with obesity, hypertension, hyperlipidemia and diabetes.
Elevated Insulin Levels
Preliminary research suggests that insulin resistance may play a role in the development of gout. Gout is strongly associated with the consequences of insulin resistance i.e. obesity, hypertension, hyperlipidemia and diabetes.
Elevated Total Cholesterol
Gout is strongly associated with obesity, hypertension, hyperlipidemia and diabetes.
Kidney Weakness / Disease
Hyperuricemia is caused by a variety of means, one of which is abnormal kidney function.
Kidney Failure
Patients with impaired renal function filter and excrete less uric acid and therefore become hyperuricemic. Interestingly, patients with renal failure do not develop gout as frequently as expected, despite their high plasma urate levels. The explanation for this phenomenon may be that they have not incurred sustained hyperuricemia levels long enough to develop gout. Only 1% of renal failure patients develop gout but nearly 30% of patients with adult polycystic kidney disease do.
Gout / Hyperuricemia can lead to
Increased Risk of Coronary Disease / Heart Attack
Elevated uric acid levels, as seen in gout, may be associated with a higher incidence of coronary heart disease amongst alcohol abstainers, but has not been seen to occur in those who were light, moderate or heavy drinkers. [ Journal of Clinical Epidemiology,1996;49(6) pp.673-678]
In evaluating 5,926 subjects who were between 25 and 74 years of age, after 16.4 years of follow-up, there were 1,593 deaths of which 45.9% were attributed to cardiovascular disease. It was found that increased serum uric acid levels were independently and significantly associated with the risk of cardiovascular mortality. [JAMA, May 10, 2000;283(18): pp.2404-2410]
Gout / Hyperuricemia could instead be
Lyme Disease
Lyme disease is similar to gout and is sometimes misdiagnosed as such.
Recommendations for Gout / Hyperuricemia
Alcohol Avoidance
The evidence linking alcohol and gout is not extensive, but is persuasive, especially when allied with several hundred years’ of experience. Men with gout are probably best advised to refrain from alcohol.
Low Purine Diet
A low-purine diet is commonly used to treat gout. Some people need to follow the diet more closely than others to prevent symptoms.
Fructose Avoidance/reduction
In the United States, levels of gout have doubled over the last few decades, which coincided with a substantial increase in the consumption of soft drinks and fructose (a simple sugar and the only carbohydrate known to increase uric acid levels). The authors point out that sugary soft drinks are the largest single food source of calories in the US diet, and that the per capita intake of commercial high fructose corn syrup in the United States is now up to a whopping 29 kilograms (over 60 pounds) per year!
It is also known exactly how fructose spikes uric acid levels acutely. Fructose, like alcohol, increases blood levels of uric acid within minutes by using the high energy phosphate ATP in the liver for its own metabolism. This process converts ATP to AMP, which is a chemical forerunner to uric acid.
Conventional dietary recommendations for gout have focused on the restriction of purines (found in high levels in meat and meat products, especially liver and kidney) and alcohol but with no restriction of sugar sweetened soft drinks.
So researchers in the US and Canada examined the relation between intake of sugar sweetened soft drinks and fructose and the risk of gout.
They followed over 46,000 men aged 40 years and over with no history of gout. The men completed regular questionnaires on their intake of more than 130 foods and beverages, including sugar sweetened soft drinks and diet soft drinks, over a period of 12 years. Different types of fruits and fruit juices (high in natural fructose) were also assessed.
At the start of the study, and every two years thereafter, information on weight, regular use of medications and medical conditions were also recorded. Gout was diagnosed according to American College of Rheumatology criteria.
During 12 years of follow-up, the researchers documented 755 newly diagnosed cases of gout.
The risk of gout increased with increasing intake of sugar sweetened soft drinks. The risk was significantly increased with an intake level of 5-6 servings per week and the risk was 85% higher among men who consumed two or more servings of sugar-sweetened soft drinks per day compared to those who consumed less than one serving per month.
These associations were independent of other risk factors for gout such as body mass index, age, diuretic use, high blood pressure, alcohol intake, and dietary factors.
Diet soft drinks were not associated with the risk of gout.
Fruit juice and fructose-rich fruits (apples and oranges) were also associated with a higher risk of gout. However, the authors stress that this finding needs to be balanced against the benefit of fruit and vegetable intake to prevent other chronic disorders like high blood pressure, coronary heart disease, stroke and certain types of cancer.
In conclusion, the findings provide prospective evidence that consumption of fructose sweetened soft drinks and fructose is strongly associated with an increased risk of gout, say the authors. Furthermore, fructose rich fruits and fruit juices may also increase the risk. In contrast, diet soft drinks were not associated with the risk of gout.
Caffeine/Coffee Avoidance
Intake of diuretics (chiefly coffee and alcohol) should be reduced/avoided as far as possible.
Soy Isoflavones (genistein, daidzein)
Tofu, which is made from soybeans, may be a better choice than meats, when it comes to providing protein in those who have gout.
Increased Fruit/Vegetable Consumption
Dark berries may contain chemicals that lower uric acid and reduce inflammation. Especially recommended are cherries. Liberal amounts (up to 1 pound per day) of cherries, blueberries, and other anthocyanoside-rich (i.e. red-blue) berries or extracts should be consumed. Consuming fresh or canned cherries has been shown to be very effective in lowering uric acid levels and preventing attacks of gout. Cherries, hawthorn berries, blueberries, and other dark red-blue berries are rich sources of anthocyanidins and proanthocyanidins. These compounds are flavonoid molecules that give these fruits their deep red-blue color, and are remarkable in their ability to prevent collagen destruction.
Vegetarian/Vegan Diet
Preferably no meat should be eaten as it is rich in uric acid forming components. Raw fruit, vegetables, grains, seeds and nuts are highly recommended.
Weight Loss
Achieve normal body weight but avoid rapid weight loss diets, which may result in increased uric acid levels in the blood.
Sugars Avoidance / Reduction
Men who drink two or more sugary soft drinks a day have an 85% higher risk of gout than those who drink less than one a month, according to U.S. and Canadian researchers. Gout has been increasing steadily in the UK in recent years, and the researchers believe it is linked to a rise in soft drink consumption over the same period.
During the 12-year study, 46,000 men aged 40 and over were asked questions about their diet. The risk of developing gout significantly increased among men who drank five to six servings of sugary soft drinks a week. Fruit juice and fructose-rich fruits such as oranges and apples also increased the risk. Fructose is known to inhibit the excretion of uric acid, which may help to explain the study’s findings.
Conventional Drugs / Information
Medications such as NSAIDs, corticosteroids and allopurinol are commonly used against gout.
Since the 1800s, colchicine has been the standard treatment for acute gout. While colchicine is very effective, it often causes nausea, vomiting and diarrhea. These side-effects are uncommon when this drug is given intravenously, but because of their unpleasant nature, non-steroidal anti-inflammatory drugs (NSAIDs) have become the treatment of choice for most acute attacks of gout. The NSAID that is most widely used to treat acute gout is indomethacin. NSAIDs may also have significant toxicity, but if used for the short-term, are generally well tolerated. Aspirin and aspirin-containing products should be avoided during acute attacks because they will further elevate uric acid levels.
Therapy directed at normalizing uric acid levels in the blood should be considered for patients who have had multiple gout attacks or have developed tophi or kidney stones. Several drugs that help the kidneys eliminate uric acid are available, such as probenecid, and a drug that blocks production of uric acid by the body, such as allopurinol. The choice between these two types of drugs depends on the amount of uric acid in the urine. With correct treatment, gout should be well controlled in almost all cases.
Aspirin
Among the more common predisposing factors to hyperuricemia are kidney failure from any cause, diuretic use, dehydration, hormonal diseases, alcohol consumption and using low doses of aspirin. Aspirin, which normally reduces pain, raises uric acid levels and makes gout pain worse!
Lithium (low dose)
A JAMA article from the 1880s noted that uric acid could be made more soluble (less likely to crystallize) if lithium were added to the solution containing uric acid. Therefore some doctors recommend lithium orotate at a dose of 5-10mg TID, along with vitamin C at 1-2gm TID, which often prevents the recurrence of symptoms.
MSM (Methyl Sulfonyl Methane)
According to Dr. Stanley Jacobs, MD, MSM can be helpful in most musculoskeletal pain and inflammation, including gout.
Molybdenum
Molybdenum is known to raise uric acid levels which is why people with gout (a condition of elevated uric acid levels) are told to avoid molybdenum supplements.
Vitamin C (Ascorbic Acid)
Researchers found in the 1970’s that high doses of vitamin C prompt the kidneys to excrete more uric acid into the urine.
For people suffering from gout, the use of vitamin C (1-2gm TID) can help bring the condition under control.
A study of 20 years involved about 47,000 men, 1,317 of whom developed gout. Those who took 1,000mg to 1,499mg of vitamin C per day had a 34% lower risk of developing gout, while those who took 1,500mg per day had a 45% lower risk. This was irrespective of other gout risk factors such as diet and alcohol use.
“Vitamin C may reduce the frequency of attacks and provide a degree of protection,” said Rheumatologist Dr Michael Snaith of the UK Gout Society, adding as a warning, “But that does not mean to say that taking whacking great amounts of vitamin C is going to eliminate gout.” [Arch Intern Med. 2009;169(5):502-507]
Vitamin B3 (Niacin)
The vitamin niacin, also called nicotinic acid, can raise uric acid levels, so should not be used by people who have gout.
Key
| Weak or unproven link |
| Strong or generally accepted link |
| Very strongly or absolutely counter-indicative |
| May do some good |
| Likely to help |
| Highly recommended |
| May have adverse consequences |
| Reasonably likely to cause problems |
| Avoid absolutely |
Glossary
Gout
A disease characterized by an increased blood uric acid level and sudden onset of episodes of acute arthritis.
Chronic
Usually Chronic illness: Illness extending over a long period of time.
Arthritis
Inflammation of a joint, usually accompanied by pain, swelling, and stiffness, and resulting from infection, trauma, degenerative changes, metabolic disturbances, or other causes. It occurs in various forms, such as bacterial arthritis, osteoarthritis, or rheumatoid arthritis. Osteoarthritis, the most common form, is characterized by a gradual loss of cartilage and often an overgrowth of bone at the joints.
Hypertension
High blood pressure. Hypertension increases the risk of heart attack, stroke, and kidney failure because it adds to the workload of the heart, causing it to enlarge and, over time, to weaken; in addition, it may damage the walls of the arteries.
Hyperlipidemia
Increased cholesterol level.
Diabetes Mellitus
A disease with increased blood glucose levels due to lack or ineffectiveness of insulin. Diabetes is found in two forms; insulin-dependent diabetes (juvenile-onset) and non-insulin-dependent (adult-onset). Symptoms include increased thirst; increased urination; weight loss in spite of increased appetite; fatigue; nausea; vomiting; frequent infections including bladder, vaginal, and skin; blurred vision; impotence in men; bad breath; cessation of menses; diminished skin fullness. Other symptoms include bleeding gums; ear noise/buzzing; diarrhea; depression; confusion.
Acute
An illness or symptom of sudden onset, which generally has a short duration.
Asymptomatic
Not showing symptoms.
DNA
Deoxyribonucleic acid, the large molecule that is the main carrier of genetic information in cells. DNA is found mainly in the chromosomes of cells.
Milligram
(mg): 1/1,000 of a gram by weight.
Chronic Renal Failure
(CRF) Irreversible, progressive impaired kidney function. The early stage, when the kidneys no longer function properly but do not yet require dialysis, is known as Chronic Renal Insufficiency (CRI). CRI can be difficult to diagnose, as symptoms are not usually apparent until kidney disease has progressed significantly. Common symptoms include a frequent need to urinate and swelling, as well as possible anemia, fatigue, weakness, headaches and loss of appetite. As the disease progresses, other symptoms such as nausea, vomiting, bad breath and itchy skin may develop as toxic metabolites, normally filtered out of the blood by the kidneys, build up to harmful levels. Over time (up to 10 or 20 years), CRF generally progresses from CRI to End-Stage Renal Disease (ESRD, also known as Kidney Failure). Patients with ESRD no longer have kidney function adequate to sustain life and require dialysis or kidney transplantation. Without proper treatment, ESRD is fatal.
Diuretic
An agent increasing urine flow, causing the kidneys to excrete more than the usual amount of sodium, potassium and water.
Enzymes
Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.
Metabolism
The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.
White Blood Cell
(WBC): A blood cell that does not contain hemoglobin: a blood corpuscle responsible for maintaining the body's immune surveillance system against invasion by foreign substances such as viruses or bacteria. White cells become specifically programmed against foreign invaders and work to inactivate and rid the body of a foreign substance. Also known as a leukocyte.
Cartilage
Specialized fibrous connective tissue that forms the skeleton of an embryo and much of the skeleton in an infant. As the child grows, the cartilage becomes bone. In adults, cartilage is present in and around joints and makes up the primary skeletal structure in some parts of the body, such as the ears and the tip of the nose.
Menopause
The cessation of menstruation (usually not official until 12 months have passed without periods), occurring at the average age of 52. As commonly used, the word denotes the time of a woman's life, usually between the ages of 45 and 54, when periods cease and any symptoms of low estrogen levels persist, including hot flashes, insomnia, anxiety, mood swings, loss of libido and vaginal dryness. When these early menopausal symptoms subside, a woman becomes postmenopausal.
Serum
The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
Bursitis
The bursa is a fluid-filled pad that allows your muscles to easily slide over other muscles and bones. Bursitis occurs when this pad becomes inflamed. It usually occurs when you overuse or injure a specific joint, but it can also be caused by a bacterial infection. Symptoms include pain and inflammation around joints such as the elbow, hip, shoulder, big toe, ankle or knee.
Insulin
A hormone secreted by the pancreas in response to elevated blood glucose levels. Insulin stimulates the liver, muscles, and fat cells to remove glucose from the blood for use or storage.
Kidney Stone
A stone (concretion) in the kidney. If the stone is large enough to block the tube (ureter) and stop the flow of urine from the kidney, it must be removed by surgery or other methods. Also called Renal Calculus. Symptoms usually begin with intense waves of pain as a stone moves in the urinary tract. Typically, a person feels a sharp, cramping pain in the back and side in the area of the kidney or in the lower abdomen. Sometimes nausea and vomiting occur. Later, pain may spread to the groin. The pain may continue if the stone is too large to pass; blood may appear in the urine and there may be the need to urinate more often or a burning sensation during urination. If fever and chills accompany any of these symptoms, an infection may be present and a doctor should be seen immediately.
Epidemiology
The study of the causes and distribution of disease in human populations.
Cardiovascular
Pertaining to the heart and blood vessels.