• Acute onset of intense joint pain, typically involving the first joint of the big toe (about 50% of cases)
• Elevated serum uric acid level
• Periods without symptoms between acute attacks
• Identification of urate crystals in joint fluid
• Aggregated deposits of urate crystals in and around the joints of the extremities, but also in subcutaneous tissue, bone, cartilage, and other tissues
• Uric acid kidney stones
Gout is a common type of arthritis caused by an increased concentration of uric acid (the final breakdown product of the metabolism of purine, one of the units of DNA and RNA) in biological fluids. In gout, uric acid crystals (monosodium urate) are deposited in joints, tendons, kidneys, and other tissues, where they cause considerable inflammation and damage.1,2 The uric acid deposits around the joints and tendons may lead to pain. Excessive uric acid deposits in the kidneys may result in kidney failure.
The first attack of gout is characterized by intense pain, usually involving only one joint. The first joint of the big toe is affected in nearly half of first attacks and is at some time involved in more than 90% of individuals with gout. If the attack progresses, fever and chills will appear. The first attacks usually occur at night and are usually preceded by a specific event, such as dietary excess, alcohol ingestion, trauma, certain drugs (mainly chemotherapy drugs, certain diuretics, and high doses of niacin), or surgery.
The classic description of gout was written by an English physician, Thomas Sydenham, who suffered from it in 1683.1 Little has changed in the clinical picture of gout in more than 300 years. This is Sydenham’s classic description:
The victim goes to bed and sleeps in good health. About two o’clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation, and yet parts feel as if cold water were poured over them. Then follows chills and shivers, and a little fever. The pain which at first was moderate, becomes more intense. With its intensity the chills and fever increase. After a time this comes to a height, accommodating itself to the bones and ligaments of the tarsus and metatarsus. Now it is a violent stretching and tearing of the ligaments, now it is a gnawing pain, and now a pressure and tightening. So exquisite and lively meanwhile is the feeling of the part affected, that it cannot bear the weight of bedclothes nor the jar of a person walking in the room. The night is passed in torture, sleeplessness, turning the part affected, and perpetual change of posture; the tossing about of the body being as incessant as the pain of the tortured joint, and being worse as the fit comes on. Hence the vain effort by change of posture, both in the body and the limb affected, to obtain an abatement of pain.
Subsequent attacks are common, with the majority of gout patients having another attack within one year. However, nearly 7% never have a second attack. Chronic gout is extremely rare these days, owing to the advent of dietary therapy and drugs that lower uric acid levels. Some degree of kidney dysfunction occurs in almost 90% of subjects with gout as a result of uric acid deposits, and there is a higher risk of kidney stones.
Causes
Gout is divided into two major categories: primary and secondary. Primary gout accounts for about 90% of all cases, while secondary gout accounts for only 10%. The cause of primary gout is usually unknown. There are, however, several genetic defects in which the exact cause of the elevated uric acid is known.
The increased serum uric acid level observed in primary gout can be divided into three categories:
1. Increased synthesis of uric acid, found in a majority of gout patients
2. Reduced ability to excrete uric acid, found in about 30% of gout patients
3. Overproduction and underexcretion of uric acid, found in a small minority of gout patients
Although the exact metabolic defect is not known in the majority of cases, gout is one of the most controllable metabolic diseases.
Secondary gout refers to those cases in which the elevated uric acid level is a result of some other disorder, such as excessive breakdown of cells or some form of kidney disease. Diuretic therapy for high blood pressure and low-dose aspirin therapy are also important causes of secondary gout, since they cause decreased uric acid excretion.
Causes of Gout
• Increased purine intake
• Increased production of purines (primary causes):
Idiopathic (unknown causes)
Due to specific enzyme defects
• Increased production of purines (secondary to another factor)
• Increased turnover of purines due to:
Cancer
Chronic hemolytic anemia
Chemotherapy drugs
Psoriasis
• Increased synthesis of purines
• Increased breakdown of purines due to:
High fructose intake
Exercise
• Impaired kidney function:
Decreased kidney clearance of uric acid (primary)
Intrinsic kidney disease
Decreased kidney clearance of uric acid (secondary)
Functional impairment of kidney function
– Drug-induced (e.g., thiazides, salicylates, etc.)
– Increased lactic acid (e.g., lactic acidosis, alcoholism, toxemia of pregnancy, etc.)
– Increased ketoacid levels (e.g., diabetic ketoacidosis)
– Chronic lead intoxication
About 200 to 600 mg uric acid is excreted per day in the urine of an adult male, and another 100 to 300 mg is excreted in the bile and other gastrointestinal tract secretions. The dietary contribution to the level of uric acid in the blood is usually only 10 to 20% of the total, but purines and uric acid obtained through the diet can increase crystal formation in tissues nonetheless.
Uric acid is a highly insoluble molecule, and at a blood pH of 7.4 and normal body temperature, the serum (blood minus the blood cells) is saturated with uric acid at 6.4 to 7.0 mg/100 ml. Although higher concentrations do not necessarily result in the deposit of uric acid crystals in tissues (some unknown factor in serum appears to inhibit crystal precipitation), the chance of an acute attack of gout is greater than 90% when the level is above 9 mg/100 ml.
Lower body temperatures decrease the saturation point of uric acid, and this may explain why uric acid deposits tend to form in areas such as the top of the ear, where the temperature is lower than the average body temperature. Uric acid is even less soluble when the blood pH is below 6.0; this condition can lead to kidney stones.
Therapeutic Considerations
The current standard medical treatment of acute gout is administration of colchicine, an anti-inflammatory drug originally isolated from the plant Colchicum autumnale (autumn crocus, meadow saffron). Colchicine has no effect on uric acid levels; rather, it stops the inflammatory process by inhibiting neutrophil migration into areas of inflammation.
More than 75% of patients with gout show major improvement in symptoms within the first 12 hours after receiving colchicine. However, up to 80% of patients are unable to tolerate an optimal dose because of gastrointestinal side effects.
Colchicine may also cause bone marrow suppression, hair loss, liver damage, depression, seizures, respiratory depression, and even death. Other anti-inflammatory agents used in acute gout include various nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, phenylbutazone, naproxen, and fenoprofen.
Once the acute episode has resolved, a number of measures are taken to reduce the likelihood of recurrence:
• Drugs such as allopurinol or febuxostat to keep uric acid levels within a normal range
• Controlled weight loss in obese individuals
• Avoidance of known precipitating factors such as heavy alcohol consumption or a diet rich in purines or refined carbohydrates
• Low doses of colchicine to prevent further acute attacks
Several dietary factors are known to lead to the development of gout or trigger an attack: alcohol, especially beer and hard liquor; high-purine foods (e.g., organ meats, meat, yeast, poultry); fats; refined carbohydrates, particularly high amounts of fructose; and overconsumption of calories. Individuals with gout are typically obese; prone to hypertension, metabolic syndrome,3 and diabetes;4 and at a greater risk for cardiovascular disease. Obesity is probably the most important factor. Thiazide and loop diuretics also are associated with a higher risk of incident gout and a higher rate of gout flares.5
The naturopathic approach to chronic gout focuses on dietary and herbal measures to keep uric acid levels within the normal range. The conventional medical treatment of gout often relies excessively on drugs that inhibit xanthine oxidase. The drug allopurinol, a structural isomer of hypoxanthine (a naturally occurring purine in the body), has been the mainstay treatment for decades. However, in February 2009 the FDA approved febuxostat (Uloric), another xanthine oxidase inhibitor, which is more effective at lowering and maintaining serum urate levels and is beginning to supplant allopurinol.6 Agents that increase uric acid excretion (probenecid, sulfinpyrazone, and benzbromarone) are used as second-line therapy for patients with underexcretion of uric acid.
A secondary type of gout, sometimes called saturnine gout, can result from lead toxicity. Historically, saturnine gout was caused by the consumption of alcoholic beverages stored in containers with lead in them. An unexpected and fairly common source of lead appears to be leaded crystal; port wine, for example, takes on lead when stored in a crystal decanter.7 Lead concentration increases with storage time, reaching toxic levels after several months. Even a few minutes in a crystal glass results in a measurable increase in the level of lead in wine. While lead levels in the general population have decreased substantially since it was banned from gasoline, those working with aviation fuel are still exposed. The mechanism of action is related to a decrease in excretion of uric acid by the kidneys.
The dietary treatment of gout involves the following guidelines:
• Decreasing purine intake
• Eliminating alcohol
• Achievement of ideal body weight
• Liberal consumption of complex carbohydrates
• Low fat intake
• Low protein intake
• Liberal fluid intake
Low-Purine Alkaline-Ash Diet
A low-purine diet has been the mainstay of the dietary therapy of gout for decades. Today, however, many physicians prefer to lower uric acid levels by prescribing potent drugs rather than subjecting the patient to the inconvenience and deprivation associated with a purine-free diet. However, dietary restriction of purines is still recommended to reduce metabolic stress. Foods with high purine levels should be entirely omitted. These include organ meats, yeast (brewer’s and baker’s), and smaller fish such as sardines, herring, and anchovies. Foods with moderate levels of purine should be curtailed as well. These include dried legumes, spinach, asparagus, fish, meat, poultry, shellfish, and mushrooms.
An alkaline-ash diet is recommended in the dietary treatment of gout because a more alkaline pH increases uric acid solubility. An alkaline-ash diet was shown to increase uric acid excretion from 302 mg per day at pH 5.9 to 413 mg per day at pH 6.5.8 For information on the acid-alkaline effect of common foods, see Appendix C.
High-Purine Foods
• Anchovies
• Consommé
• Meat extracts
• Organ meats (brain, kidney, liver, sweetbreads)
• Roe (fish eggs)
• Sardines (and other small fish such as herring and mackerel)
• Yeast
Moderate-Purine Foods
• Asparagus
• Fish (larger species)
• Legumes
• Meat
• Mushrooms
• Peas (dried)
• Poultry
• Shellfish
• Spinach
Low-Purine Foods
• Eggs
• Fruit
• Grains
• Milk
• Pasta
• Nuts
• Olives
Alcohol
Alcohol consumption increases uric acid production by accelerating purine nucleotide degradation and reduces uric acid excretion by increasing lactate production, which impairs kidney function. The net effect is a significant increase in serum uric acid levels. This explains why alcohol consumption is often a precipitating factor in acute attacks of gout. In many individuals, eliminating alcohol is all that is necessary to reduce uric acid levels and prevent gout.
Excess Weight
Excess weight is associated with an increased incidence of gout. Weight reduction in obese individuals significantly reduces serum uric acid levels.9 See the chapter “Obesity and Weight Management” for more information.
Carbohydrates, Fats, and Protein
Refined carbohydrates and saturated fats should be kept to a minimum, as the former increase uric acid production while the latter increase uric acid retention. In addition, one of the key dietary goals in the treatment of gout appears to be to enhance insulin sensitivity.9
Protein intake should not be excessive (i.e., more than 0.8 g/kg per day), as it has been shown that uric acid synthesis may be accelerated in both normal and gouty patients by a high protein intake.5
Fluid Intake
Liberal fluid intake keeps the urine dilute and promotes the excretion of uric acid. Furthermore, dilution of the urine reduces the risk of kidney stones.
Fish Oils
Fish oil supplementation may prove useful in the treatment of gout. The omega-3 fatty acids EPA and DHA limit the production of leukotrienes, which contribute to much of the inflammation and tissue damage observed in gout.
Folic Acid
Folic acid has been shown to inhibit xanthine oxidase, the enzyme responsible for producing uric acid.10 Research has demonstrated that a derivative of folic acid is an even greater inhibitor of xanthine oxidase than allopurinol, suggesting that folic acid at pharmacological doses may be an effective treatment in gout.11 Positive results in the treatment of gout have been reported, but the data are incomplete and uncontrolled.12
The bioflavonoid quercetin has demonstrated several effects in experimental studies that indicate its possible benefit to individuals with gout.13–15 Quercetin may offer significant protection by inhibiting the following:
• Xanthine oxidase in a fashion similar to the drug allopurinol
• Leukotriene synthesis and release
• White blood cell accumulation and enzyme release
However, since the absorption of quercetin is quite poor, we recommend using the highly bioavailable enzymatically modified form of isoquercitrin (EMIQ) instead.
Vitamin C
Megadoses of vitamin C should be avoided by individuals with gout, as vitamin C may increase uric acid levels in a small number of individuals.16
Niacin
High doses of niacin (i.e., above 100 mg per day) are probably contraindicated in the treatment of gout, as niacin competes with uric acid for excretion.17
Cherries and Other Dark Red and Blue Fruits
Consuming 1/2 lb fresh or canned cherries per day has been shown to be effective in lowering uric acid levels and preventing attacks of gout.18 One study measured plasma uric acid and antioxidant and inflammatory markers in 10 healthy women who consumed 280 g cherries after an overnight fast.19 Blood and urine samples were taken before the cherry dose and at 1.5, 3, and 5 hours afterward. Five hours after cherry consumption, plasma uric acid levels had decreased by an average of 30 mmol/l. This reduction correlated with increased urinary excretion of urate. Inflammatory markers (plasma C-reactive protein and nitric oxide concentrations) decreased slightly after the 1.5-hour mark.
Cherries, hawthorn berries, blueberries, and other dark red and blue fruits are rich sources of anthocyanidins and proanthocyanidins. These compounds are flavonoid molecules, which give these fruits their deep red-blue color and are remarkable in their ability to prevent collagen destruction. Anthocyanidins and other flavonoids affect collagen metabolism in many ways:
QUICK REVIEW
• Gout is caused by uric acid crystals deposited in joints.
• Several dietary factors are known to be causes of gout: alcohol, high-purine foods, fats, and refined carbohydrates.
• Elimination of alcohol consumption reduces uric acid levels and prevents gouty arthritis in many individuals.
• Liberal fluid intake dilutes the urine and promotes the excretion of uric acid.
• Consuming 1/2 lb fresh or canned cherries per day has been found effective in lowering uric acid levels and preventing attacks of gout.
• They have the unique ability to actually cross-link collagen fibers, resulting in reinforcement of the natural cross-linking of collagen that forms the collagen matrix of connective tissue.
• They prevent free radical damage through their potent antioxidant and free-radical-scavenging action.
• They inhibit enzymatic cleavage of collagen by enzymes secreted by leukocytes during inflammation.
• They prevent the release and synthesis of compounds that promote inflammation, such as histamine, serine proteases, prostaglandins, and leukotrienes.
Celery Seed Extract
The compound 3-n-butylphthalide (3nB) is unique to celery and is responsible for its characteristic flavor and odor. A celery seed extract standardized to contain 85% 3nB and other celery phthalides has shown benefit in the treatment of rheumatism—the general term used for arthritic and muscular aches and pain.20,21 In studies that included gout sufferers, subjects had for approximately 10 years been experiencing lack of joint mobility and intermittent or continual pain, interfering with household duties, hobbies, and job-related activities. Subjects noted significant pain relief after three weeks of use, with an average 68% reduction in pain scores and some subjects experiencing complete relief from pain. Most subjects achieved maximum benefit after six weeks of use, although some did notice improvements the longer the extract was used. Celery seed extract appears to be particularly helpful for sufferers of gout, as 3nB lowers the production of uric acid by inhibiting the enzyme xanthine oxidase.22
TREATMENT SUMMARY
The naturopathic approach to the prevention and treatment of gout involves the following:
• Dietary and herbal measures that maintain uric acid levels within the normal range
• Controlled weight loss in obese individuals
• Avoidance of known precipitating factors (such as heavy alcohol consumption and a high-purine diet)
• The use of nutritional substances to prevent further acute attacks
• The use of herbal and nutritional substances to inhibit the inflammatory process
Follow the general guidelines given in the chapter “A Health-Promoting Diet.” Eliminate alcohol intake, avoid high-purine foods, increase consumption of complex carbohydrates, decrease consumption of simple carbohydrates, maintain a low fat intake, optimize protein intake (under 0.8 g/kg per day), and consume liberal quantities of fluid.
In addition, liberal amounts (4 to 8 oz per day) of cherries, blueberries, and other anthocyanoside-rich red or blue berries should be consumed; their extracts can be substituted. See Appendix C, “Acid-Base Values of Selected Foods.”
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)
• Fish oils: 1,000 mg EPA + DHA per day
• One of the following:
Cherry fruit extract (10:1): 500 to 1,000 mg three times per day
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Enzymatically modified isoquercitrin (EMIQ): 100 mg twice per day
• Celery seed extract (85% 3nB content): 75 mg two to three times per day