What causes gout?March 2016
By Michael Smith MD
MS: The underlying cause of gout is hyperuricemia, the buildup of excess uric acid in the blood. Uric acid is produced during the metabolism of purines, which are compounds found in high amounts in certain foods and beverages such as meats, poultry, seafood, and beer.
There are two ways to get purines, one is from the diet and the other is from making it in the body. Purines are important for the synthesis of nucleic acids, the building blocks of DNA. However, your body doesn’t need dietary purines, it can produce them on its own. So just about all dietary purines are converted to uric acid.1
Hyperuricemia results either from excess production of uric acid, not enough excretion, or a combination of both. Underexcretion is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%.2
However, high blood levels of uric acid don’t necessarily mean you’ll develop gout. It only increases the risk based upon varying degrees of hyperuricemia. When blood levels are between 7 and 8.9 mg/dL, the risk of gout is less than 1% per year.3 But when uric acid levels are greater than 9 mg/dL, the risk of developing gout is 6 times higher.4-7
All of this is why the mainstay of gout treatment is preventing hyperuricemia. Unfortunately for a lot of us, this can be tough as gender, menopause, and genetics play a role. Men and post-menopausal women produce the most uric acid. If you fall into one of these two groups, you might consider taking preventative measures.
Research also shows that hyperuricemia is a genetic trait. Genetic studies have demonstrated a high degree of similarity (concordance) of hyperuricemia between pairs of twins, 53% for identical twins and 24% for fraternal twins.8
But there’s good news for those of us at increased risk. All of the studies indicate that environmental factors substantially influence whether or not a predisposition for hyperuricemia will actually result in gout. Or simply put…lifestyle is a driving force behind the development of hyperuricemia and gout.
Here are a few lifestyle tips for preventing hyperuricemia:
- Avoid excessive alcohol. Drinking too much can interfere with the removal of uric acid from the body. Remember, underexcretion is the primary way it builds up.
- Limit dietary purines. This includes red meats, pork, lamb, and seafood.
- Maintain a healthy weight. Obesity increases the risk of gout. One theory is that excess body weight causes rapid turn-over of body tissues, increasing the need for purines and nucleic acids. The end result is more uric acid production.
- Optimize kidney health. Since underexcretion causes 90% of hyperuricemia cases, improving and maintaining kidney function is important.
- Optimize thyroid function. Hypothyroidism is associated with gout.
- Optimize blood pressure. Hypertension is associated with gout.
- Lower lead in your body. Chronic exposure has been linked to some cases of gout.
- Minimize use of prescription diuretics. Medications that increase urine flow are associated with gout. Talk to your doctor if you’re at an increased risk for gout and discuss alternatives for treating high blood pressure.
- Treat sleep apnea. A recent study in Arthritis & Rheuma-tology has found that sleep apnea is an independent risk factor of gout.
LE: How does gout increase my risk of heart disease?
MS: Gout is bad for your heart because it’s associated with diabetes and obesity, which are two independent risk factors of heart disease. For instance, the odds of developing gout are almost 4 times higher for diabetics than nondiabetics.9
However, in the last few years, reports indicate that the underlying cause of gout, hyperuricemia, may in fact be an independent risk factor of cardiovascular disease.10 And the likely culprit is chronic inflammation.
Uric acid’s crystalline structure appears to activate the immune system and trigger a robust inflammatory reaction. Detailed analysis of uric acid’s role in initiating inflammation reveals a complex and powerful interaction between uric acid crystals, immune cells, multiple chemical signals, and eventual production of a powerful inflammatory protein, interleukin-1-beta.11
Once released into circulation, interleukin-1-beta signals the activation of more and more immune cells and inflammatory proteins, resulting in a destructive inflammatory response.
Chronically elevated, inflammation can damage cells and tissues throughout the body, making it the common denominator of age-related disorders, including heart disease.
LE: Why is gout so painful?
MS: Gout is painful because needle-like crystals of uric acid are piercing joint tissues. And, as if that weren’t enough, the crystals also initiate a powerful inflammatory response that causes redness, swelling, and heat. This occurs within tight joint spaces with little ability to expand and relieve pressure.
It’s so painful that a 2010 Gout Attitudes Patient Survey reported 37% of people with the disease would trade a winning lottery ticket for an assurance of never suffering another flare-up of acute gout.12
The survey, developed by the Men’s Health Network and Takeda Pharmaceuticals North America Inc., also found that:
- 23% compare the pain to shattered glass piercing their skin, 28% to breaking a bone, 34% to a severe burn, and 37% to a stubbed toe.
- 69% describe the pain of an attack as “miserable.”
- 73% reported limited physical activity.
- 27% of gout patients say the disease causes them to take time off from work.
- 43% said they had canceled social plans because of a gout attack.
- 36% said they would leave their homes more often if they did not have gout.
This is why people suffering from acute gout are willing to ingest large quantities of prescription and over-the-counter pain medications. But the possibility of severe side effects has some patients searching for safer ways to control the pain.
Cherries can help. Several studies provide strong evidence that the anthocyanins from cherries relieve pain and reduce inflammation. An animal study conducted at Johns Hopkins Hospital found that tart cherry extracts provided relief from painful inflammation comparable to the nonsteroidal anti-inflammatory drug indomethacin.13
Korean angelica is another alternative to side-effect prone pain medications. Used in traditional herbal medicine as a pain reliever, Korean angelica fights pain through its effects on the brain. This makes it useful for many types of pain, including the painful inflammation characterizing gout.14
Curcumin and Boswellia are additional alternatives simply because they are so effective at inhibiting powerful inflammatory pathways that are activated during acute gout.
LE: How is gout diagnosed?
MS: Classically, hyperuricemia and podagra (swollen, red big toe) are enough to make the diagnosis of gout. However, clinicians will tell you that gout doesn’t only affect the big toe. Just about any joint can be involved.
So that leaves hyperuricemia (uric acid level greater than 8.6 mg/dL in men and 7.1 mg/dL in women) and severe pain in at least one joint as the criteria for most clinicians to call it gout. But keep in mind that gout occurs without hyperuricemia, and many people with raised uric acid levels never develop gout.
In cases with normal uric acid levels, synovial fluid analysis should be considered. Although some doctors might treat for gout without one, the presence of large needle-shaped crystals within the joint fluid confirms the diagnosis and can be used to differentiate gout from pseudogout or septic arthritis.
By the way, outside of ruling out a fracture, you probably can forgo the X-ray if your doctor orders one. It won’t help in diagnosing acute gout, and should only be used to evaluate bone and joint erosions in chronic gout.
LE: If I already have high uric acid levels during an acute attack, how can I bring my levels down quickly without using prescription drugs?
MS: During an acute attack, lowering uric acid isn’t beneficial. Instead, focus on quickly reducing inflammation. Start by icing and resting the affected joint. Talk with your doctor about conventional medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, and biologic agents that inhibit interleukin-1 beta. They might be appropriate for you, but they also have the potential for severe side effects.
Although not as effective in reducing inflammation from gout individually, natural extracts when taken together can be safe and effective at reducing acute inflammation. However, the quick progression and resolution of acute gout may make it less amenable to nutrient “interventions,” many of which have only been tested for their long-term effects oninflammation.
But there are specific nutrients that target joint inflammation and inflammatory signals, including interleukin-1-beta. Taking them together, at a slightly higher-than normal dose, for a short duration, may produce the wanted results. Curcumin, omega-3 fatty acids, and resveratrol may be especially suited for this purpose.
LE: I have chronically elevated uric acid. Luckily, I haven’t had gout, but I don’t want to keep pushing the odds. What are my top choices for reducing uric acid naturally?
MS: The immediate “natural” thing to do is change your diet. Limit red meat, eat more vegetable protein, and drink more water. Reduce alcohol intake and eliminate sugar-sweetened drinks from your diet as well. All of this will help to lower dietary purines involved in the excessive uric acid production.
Once dietary changes are in effect, your next choice could be an extract from the fruit of Terminalia bellerica. Used in Ayurveda medicine for many years, researchers have now shown that T. bellerica provides compounds that may inhibit xanthine oxidase, an enzyme involved in the production of uric acid.4
In subjects with elevated uric acid levels, 500 mg twice a day of Terminalia bellerica extract decreased uric acid by a little over 27%.4
Vitamin C is also a xanthine oxidase inhibitor and is a good second choice. In a comprehensive review of 13 clinical studies, using an average dose of 500 mg per day, uric acid was reduced on average by 0.35 mg/dL.15
I already mentioned tart cherries for reducing pain. Well, they also reduce uric acid levels. A small set of case studies in the 1950s documented decreased duration and severity of gout attacks in people on cherry-supplemented diets.16
A more recent investigation demonstrated that following a single dose of 280 grams of cherries, the blood urate levels in 10 healthy women dropped 14% after five hours. Additionally, markers of inflammation (like C-reactive protein, CRP) also decreased slightly.17
And rounding out the natural choices is coffee. A well-conducted large study says four cups a day of coffee will reduce the risk of gout.18 It’s believed caffeine is providing the benefit as a xanthine oxidase inhibitor. But interestingly, decaffeinated coffee also reduced the risk of gout. This implies that other compounds in coffee may also be important.
Because of the intense inflammatory response associated with hyperuricemia and gout, it’s important to recognize if you’re at risk and take appropriate steps to reduce inflammation and prevent the buildup of uric acid. Remember, gout is not just causing pain in your joints, it can negatively affect other parts of your body.
Dr. Smith, a graduate of the University of Texas Southwestern Medical School, is senior health scientist and online personality for Life Extension ®. Often described as “the country doctor with a city education,” Dr. Smith is an author, blogger, and lecturer who has created and conducted numerous health-related webinars, as well as scripted and hosted a variety of informative online videos.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Available at: http://www.ncbi.nlm.nih.gov/books/NBK273/. Accessed December 9, 2015.
- Richette P, Bardin T. Gout. Lancet. 2010;375(9711):318-28.
- Eggebeen AT. Gout: an update. Am Fam Physician. 2007;76(6):801-8.
- Rani U, Kishan P, Chandrasekhar N. A randomized, double blind, placebo controlled, parallel-group study to evaluate the effect of Terminalia chebula, Terminalia bellerica and Febuxostat in patients with hyperuricemia. Publication pending.
- Available at: http://www.apiindia.org/pdf/medicine_update_2012/rheumatology_08.pdf. Accessed December 8, 2015.
- Schlesinger N, Norquist JM, Watson DJ. Serum urate during acute gout. J Rheumatol. 2009;36(6):1287-9.
- Hall AP, Barry PE, Dawber TR, et al. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med. 1967;42(1):27-37.
- Krishnan E, Lessov-Schlaggar CN, Krasnow RE, et al. Nature versus nurture in gout: a twin study. Am J Med. 2012;125(5):499-504.
- Wandell P, Carlsson AC, Ljunggren G. Gout and its comorbidities in the total population of Stockholm. Prev Med. 2015;81:387-91.
- Volterrani M, Iellamo F, Sposato B, et al. Uric acid lowering therapy in cardiovascular diseases. Int J Cardiol. 2015.
- Shi Y, Mucsi AD, Ng G. Monosodium urate crystals in inflammation and immunity. Immunol Rev. 2010;233(1):203-17.
- Available at: http://www.webmd.com/arthritis/news/20100611/gout-survey-offers-peek-at-the-pain. Accessed December 9, 2015.
- Tall JM, Seeram NP, Zhao C, et al. Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat. Behav Brain Res. 2004;153(1):181-8.
- Choi SS, Han KJ, Lee JK, et al. Antinociceptive mechanisms of orally administered decursinol in the mouse. Life Sci. 2003;73(4):471-85.
- Juraschek SP, Miller ER, 3rd, Gelber AC. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken). 2011;63(9):1295-306.
- Blau LW. Cherry diet control for goutand arthritis. Tex Rep Biol Med. 1950;8(3):309-11.
- Jacob RA, Spinozzi GM, Simon VA, et al. Consumption of cherries lowers plasma urate in healthy women. J Nutr. 2003;133(6):1826-9.
- Choi HK, Curhan G. Coffee consumption and risk of incident gout in women: the Nurses’ Health Study. Am J Clin Nutr. 2010;92(4):922-7.