Gout Dr. Heidi Fritz 4 July 2013 Gout - a Natural Approach By: Heidi Fritz MA, ND Bolton Naturopathic Clinic 64 King St W, Bolton, ON L7E1C7 www.boltonnaturopathic.ca firstname.lastname@example.org Jump to: Part 1 Part 2 Part 3Part 4 Part I: What is Gout? Gout is a severely painful inflammatory joint condition that most commonly affects the large toe, and (more rarely) the knee. Up to 4% of western populations are affected, making this the most common inflammatory arthritis.(1) Gout attacks are acutely painful, and although they resolve rapidly on treatment with anti-inflammatory drugs, they may recur frequently; up to 60% of patients with gout will have recurrent attacks within one year or suffer from chronic gout.(2) Clearly, such outcomes are less than ideal, and considerably limit patients’ quality of life. In addition, gout signals an underlying metabolic disturbance that may impact the risk of other chronic diseases. This series will discuss the implications of gout and natural approaches to management. Gout is caused by deposits of urate crystals within the joint space.(3) When blood levels of uric acid become elevated, urate crystals precipitate and deposit in joints as well as soft tissues, where they produce masses called tophi. Urate crystal may also deposit in the kidney, causing kidney stones and urate nephropathy.(2) Elevated levels of uric acid in the blood, also called hyperuricemia, are defined as serum uric acid greater than or equal to 7.0 mg/dl in males and greater than or equal to 6.0 mg/dl in females.(4) Drugs such as allopurinol, which is the mainstay of gout management, act to inhibit the synthesis of uric acid.(2) Gout has traditionally been regarded as a simple disorder of purine metabolism in which purines (found in certain foods) are converted in the body to excess uric acid. As a result, the mainstay of gout treatment is the drug allopurinol in combination with a low purine diet. A low purine diet entails avoidance of meat and seafood, yeast and yeast containing foods such as beer and alcohol, as well as select purine-rich vegetables including beans, peas, lentils, oatmeal, spinach, asparagus, cauliflower, and mushrooms.(5) Despite these well established treatment strategies, there is a growing recognition that gout is not simply a disorder of purine metabolism, but may represent a more pervasive metabolic problem with long term health implications. Most recently, research has linked gout to a condition called metabolic syndrome, which leads to elevated risk of cardiovascular disease and pre-diabetes. In light of this new knowledge, therefore, the underlying factors contributing to gout deserve re-examination and careful management. The link between gout and metabolic syndrome will be further discussed in Part II of this series. References 1. Singh JA. Emerging therapies for gout. Expert OpinEmerg Drugs. 2012;17(4):511-8. 2. Eggebeen AT. Gout: an update. AmFam Physician. 2007;76(6):801-8. 3. Smith HS, Bracken D, Smith JM. Gout: current insights and future perspectives. J Pain. 2011;12(11):1113-29. 4. Pascual E, Sivera F. Therapeutic advances in gout. CurrOpinRheumatol. 2007;19(2):122-7. 5. Emmerson BT. The management of gout. N Engl J Med. 1996;334(7):445-51. Gout - a Natural Approach Part II: Gout and Metabolic Syndrome by: Heidy Fritz MA, ND Bolton Naturopathic Clinic 64 King St W, Bolton, ON L7E1C7 www.boltonnaturopathic.ca email@example.com In Part I we discussed the fact that gout is usually viewed as a benign condition without repercussions for long-term health. In this section we show that, on the contrary, gout is strongly associated with a number of chronic diseases that also have metabolic components, most notably, metabolic syndrome and its components; hypertension; and cardiovascular disease.(1) These conditions appear to share common underlying metabolic links that can be addressed in concert to reduce symptoms of gout as well as future disease risk. In particular, the researchers Saag and Choi have proposed that obesity and insulin resistance, which are the driving factors behind metabolic syndrome, are also key factors in contributing to elevated uric acid (hyperuricemia) and gout.(1) Obesity is defined as a body mass index (BMI) over 30. BMI is calculated based on height and weight using the formula below, and quick calculators can easily be found online, such as this one: http://www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm. BMI= (Weight in Kilograms) (Height in Meters)2 Insulin resistance refers to a state in which the body no longer responds appropriately to the hormone insulin. Insulin is responsible for telling the cells to take up sugar, called glucose, from the blood. This prevents blood sugar from rising too high, and drives the storage of sugar inside the cells. In people with insulin resistance, the cells stop responding to insulin properly, and in response the body starts producing more and more insulin. This state is also considered pre-diabetes. Two important factors contribute to insulin resistance. One is a diet high in sugar or refined carbohydrates. The second is being overweight or obese. Metabolic syndrome is a constellation of three or more of the following: overweight, borderline elevated blood sugar; borderline low levels of good cholesterol, called HDL; borderline elevated triglycerides, which is part of a cholesterol blood test; and borderline elevated blood pressure. The concept of metabolic syndrome is important because it tells us that even if these markers are not actually “abnormal,” even slight increases very powerfully predict elevated risk of cardiovascular disease down the road. With respect to gout, research indicates that there is significant overlap between gout and metabolic syndrome. People who are overweight or who have metabolic syndrome are much more likely to also have elevated levels of uric acid or gout, compared to people of normal weight, and vice versa.(2,3) Even among young, healthy people, those with higher BMI, insulin levels, triglyceride, or lower good cholesterol had higher blood levels of uric acid.(4) In fact, in one study, being overweight was the single most powerful predictor of having elevated uric acid levels.(5) On the other hand, even moderate weight reduction reduces serum uric acid.(6-8) Obesity can increase production and decrease renal excretion of urate while weight loss decreases uric acid by increasing excretion through the kidneys.(8) One study found that among very obese patients, even a 5% reduction in body weight was associated with reduced serum uric acid, such that uric acid decreased 5.7% with weight loss of between 5%-9.9% of initial body weight, and decreased 16.6% with weight loss of 20% of body weight or greater.(9) Again, another study found that among 53 moderately overweight women, caloric restriction (1200 kcal/d) resulting in between 5-8 kg weight loss led to significant reductions of serum uric acid.(10) These studies suggest that the most appropriate way to manage gout is through diet and lifestyle strategies that promote healthy weight loss and addressing the metabolic factors identified by metabolic syndrome. This will be discussed in detail in Part III. References 1. Saag KG, Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther. 2006;8Suppl 1:S2. 2. Chen JH, Pan WH, Hsu CC, Yeh WT, Chuang SY, Chen PY, et al. Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: a prospective study. Arthritis Care Res (Hoboken). 2013;65(1):133-40. 3. Zhang ML, Gao YX, Wang X, Chang H, Huang GW. Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults. J ClinBiochemNutr. 2013;52(1):38-42. 4. Rathmann W, Haastert B, Icks A, Giani G, Roseman JM. Ten-year change in serum uric acid and its relation to changes in other metabolic risk factors in young black and white adults: the CARDIA study. Eur J Epidemiol. 2007;22(7):439-45. 5. Bonora E, Targher G, Zenere MB, Saggiani F, Cacciatori V, Tosi F, et al.Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Atherosclerosis Risk Factors Study. Int J Obes Relat Metab Disord. 1996;20(11):975-80. 6. Krzystek-Korpacka M, Patryn E, Kustrzeba-Wojcicka I, Chrzanowska J, Gamian A, Noczynska A. The effect of a one-year weight reduction program on serum uric acidin overweight/obese children and adolescents.ClinChem Lab Med. 2011;49(5):915-21. 7. Madero M, Arriaga JC, Jalal D, Rivard C, McFann K, Pérez-Méndez O, et al. The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome parameters: a randomized controlled trial. Metabolism. 2011;60(11):1551-9. 8. Yamashita S, Matsuzawa Y, Tokunaga K, Fujioka S, Tarui S. Studies on the impaired metabolism of uric acid in obese subjects: marked reduction of renal urate excretion and its improvement by a low-calorie diet. Int J Obes. 1986;10(4):255-64. 9. Johnson WD, Brashear MM, Gupta AK, Rood JC, Ryan DH. Incremental weight loss improves cardiometabolic risk in extremely obese adults. Am J Med. 2011;124(10):931-8. 10. Birketvedt GS, Aaseth J, Florholmen JR, Ryttig K. Long-term effect of fibre supplement and reduced energy intake on body weight and blood lipids in overweight subjects. ActaMedica (Hradec Kralove). 2000;43(4):129-32. Gout - a Natural Approach Part III: The Gout Pyramid by: Heidy Fritz MA, ND Bolton Naturopathic Clinic 64 King St W, Bolton, ON L7E1C7 www.boltonnaturopathic.ca firstname.lastname@example.org In Part II we showed that management for gout should focus on healthy weight loss and reduction of cardiovascular risk factors as identified by metabolic syndrome. Gout researchers Saag and Choi have created a “food pyramid” to outline dietary recommendations for patients with gout, taking into consideration not only high purine foods, but also foods that exacerbate insulin resistance and contribute to metabolic syndrome. Saag and Choi have pointed out that following a “rigid purine restricted diet” (1) must be weighed against the fact that a low-purine diet is often high in refined carbohydrates and saturated fat, which may actually aggravate the underlying metabolic factors. In the long run, following a diet that promotes weight loss, improves insulin sensitivity and lipid levels, and lowers uric acid is also crucial in controlling gout symptoms as well as in managing cardiovascular risk. The resulting “food pyramid” incorporates both moderate restriction of purine intake, as well as strategies to improve insulin resistance that are characteristic of the diet used to control metabolic syndrome.(2) An adaptation of this pyramid is shown in Figure 1. There are some notable inclusions in this dietary plan, namely, moderate amounts of purine rich legumes and vegetables, as well as fish and poultry. Choi states that plant source purines do not increase risk of gout.(2) In a large observational study of over 47 thousand men, consumption of meat and seafood increased risk of gout by 40-50%, but intake of purine-rich vegetables and legumes did not.(3) Another inclusion is low fat dairy products; in the same study, intake of dairy products was associated with approximately 50% reduced risk of gout.(3) Fish is another inclusion that is recommended in moderate amounts considering its cardiovascular benefits,(2) however, given the high-purine content of fish, a fish oil supplement (no protein content) seems an even better strategy for patients with gout. Soft drinks and sweetened juices are discouraged since they contribute to insulin resistance and obesity, however regular consumption of coffee in moderate amounts is allowable. Caffeine is a natural xanthine oxidase inhibitor; this means that it slows down the conversion of purines to uric acid. Therefore as long as intake is consistent on a day-to-day basis, coffee may help lower uric acid levels.(4) If intake is variable, however, coffee may in theory worsen gout, since this pattern results in unstable changes in serum uric acid which may actually precipitate an attack.(2) Of course adequate water intake is necessary to ensure uric acid excretion. Finally, it is crucial to note that the base of the pyramid (the most important recommendation) is daily exercise.(2) This benefits metabolic parameters independently of weight loss, and when added to moderate weight loss and appropriate dietary strategies, the effect is even more powerful. We advise readers to consult a licensed naturopathic doctor for guidance on how to safely and effectively implement these diet and lifestyle changes. Figure 1. Food Pyramid for Gout (See attached file;Please adapt so we don’t infringe copyright) References 1. Saag KG, Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther. 2006;8Suppl 1:S2. 2. Choi HK. A prescription for lifestyle change in patients with hyperuricemia and gout.CurrOpinRheumatol. 2010;22(2):165-72. 3. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004;350(11):1093-103. 4. Choi HK, Willett W, Curhan G. Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum. 2007;56(6):2049-55. Gout - a Natural Approach Part IV: Use of Natural Health Products (NHPs) and “Prescription Foods” by: Heidy Fritz MA, ND Bolton Naturopathic Clinic 64 King St W, Bolton, ON L7E1C7 www.boltonnaturopathic.ca email@example.com In Part III we discussed dietary guidelines for the management of gout and associated metabolic risk factors. In Part IV we discuss how use of select natural health products (NHPs) and/or “prescription foods” can further augment the benefit attained through these diet strategies. We consider “prescription foods” to be those foods that we specifically ask our patients (in a clinical setting) to consume regularly at a specific dose because they possess unique therapeutic properties. Dairy foods A randomized controlled trial compared the effects of dairy milk and soy milk on blood urate levels.(1) Dairy milk contains high concentrations of orotic acid, a naturally occurring agent that increases uric acid excretion. Soy milk increased urate approximately 10%, while the other three dairy milks decreased urate by approximately 10%. To promote cardiovascular health, low-fat diary (2%) such as milk or yogurt is recommended. Cherries Astudy investigated the effect of cherry consumption in 10 healthy women.(2) The women consumed two servings (280g) of sweet cherries after an overnight fast, followed by periodic blood and urine testing. Five hours after cherry consumption, blood urate levels decreased from 214 to 183 micromol/L. Urinary excretion of urate also increased by approximately 50% following consumption of cherries. Black tea/ Coffee In a randomized controlled trial, three cups of black tea per day resulted in a significant 7-9% decrease in blood uric acid.(3) Coffee has been associated with an approximate 60% decreased risk of gout, as is expected based on its inhibition of xanthine oxidase. However since coffee is a diuretic and diuretic agents are known to aggravate gout, coffee drinkers should be careful to increase in water in order to support adequate kidney clearance. Eicosapentanoic acid (EPA from fish oil) Although no human trials have investigated the effects of fish oils on uric acid or risk of gout, there is good rationale for supplementing with EPA in gout patients since fish oil has well established anti-inflammatory and heart-protective effects.(4) Studies in animals have shown that a combination of EPA and gamma linolenic acid (GLA) was able to reduce urate crystal-induced inflammation.(5) Citrate A randomized controlled trial found that the addition of a large dose of a citrate containing formula (3g) was able to increase the excretion of uric acid in patients who were already on allopurinol.(6) Citrate alkalinizes the urine to prevent urate deposits from forming in the kidney, thereby facilitating excretion. Citrate can be obtained as part of a magnesium citrate supplement. Vitamin C Vitamin C is a relatively well recognized uricosuric agent, meaning that it promotes urinary excretion of uric acid. A recent meta analysis of 13 randomized controlled trialsfound that there was a significant reduction in blood levels of uric acid (-0.35 mg/dl)associated with use of vitamin C 500mg.(7) Conclusion Gout strongly impacts quality of life in affected patients. Because hyperuricemia is associated with the metabolic syndrome and cardiovascular risk factors, dietary strategies for gout need to be balanced in order to reduce purine intake but also reduce risk of cardiovascular disease. Weight loss is key in lowering uric acid levels. Therapeutic foods and nutritional supplements for gout include low fat dairy, black tea/ coffee, cherries, EPA, citrate, and vitamin C. References 1. Dalbeth N, Wong S, Gamble GD, Horne A, Mason B, Pool B, et al. Acute effect of milk on serum urate concentrations: a randomised controlled crossover trial. Ann Rheum Dis. 2010;69(9):1677-82. 2. Jacob RA, Spinozzi GM, Simon VA, Kelley DS, Prior RL, Hess-Pierce B, et al. Consumption of cherries lowers plasma urate in healthy women. J Nutr. 2003;133(6):1826-9. 3. Bahorun T, Luximon-Ramma A, Gunness TK, Sookar D, Bhoyroo S, Jugessur R, et al. Black tea reduces uric acid and C-reactive protein levels in humans susceptible to cardiovascular diseases. Toxicology. 2010;278(1):68-74. 4. Choi HK. A prescription for lifestyle change in patients with hyperuricemia and gout.CurrOpinRheumatol. 2010;22(2):165-72. 5. Tate GA, Mandell BF, Karmali RA, Laposata M, Baker DG, Schumacher HR Jr, et al. Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid. Arthritis Rheum. 1988;31(12):1543-51. 6. Saito J, Matsuzawa Y, Ito H, Omura M, Ito Y, Yoshimura K, et al. The alkalizer citrate reduces serum uric Acid levels and improves renal function in hyperuricemic patients treated with the xanthine oxidaseinhibitor allopurinol. Endocr Res. 2010;35(4):145-54. 7. 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.