高尿酸血症不等於痛風. 可以看另一篇筆記 急性痛風發作與血中尿酸值
參考資料 uptodate-Gout: Nonpharmacologic strategies for prevention and treatment
9. 攝取高果糖玉米糖漿和含糖飲料(柳橙汁、含糖飲料、蘋果、葡萄乾和柳橙等等), 會增加血清尿酸水平，並增加痛風發作的風險
10. 無糖軟性飲料不會增加痛風發病風險
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根據美國的研究報告，62%的痛風患者會在第1年復發，78%在2年內復發，維持10年未復發者僅占7%。 台灣痛風盛行率,2010 年 6.24%， 原住民
11.7%. |
飲食調整概述 － 某些食物會增加血清尿酸水平或痛風發作的風險。對於患有痛風或痛風高風險的患者，通常應盡量減少食用此類食物（最好避免食用）。此外，採取某些飲食習慣，例如健康的全飲食方法，可能有助於降低痛風或痛風發作的風險。
對於大多數高尿酸血症或痛風患者，我們會建議他們考慮對以下成分進行可能的調整：
●減少食用可能誘發痛風發作的食物，包括：
•高嘌呤食物（如紅肉、貝類）
•各種類型的酒精飲料
•高果糖玉米糖漿和含糖飲料
●考慮採用整體飲食方法，例如「停止高血壓的飲食方法」（DASH飲食）和地中海飲食。
●從植物性食物和/或低脂乳製品中獲得足夠的膳食蛋白質
我們的方法與 2020 年美國風濕病學會 (ACR) 痛風治療指南 [ 47 ] 中概述的方法基本一致。
如果患者的身體質量指數（BMI；18.5 至 24.9 mg/kg²）正常，我們會討論維持健康體重的重要性。如果患者超重或肥胖，他們可能需要採取額外的減重措施。
在向患者建議飲食改變對痛風或痛風發作風險的潛在影響時，需要考慮一些限制。飲食在降低血清尿酸水平方面的作用總體有限，因此應僅作為痛風綜合管理方案的一部分。這可能與大眾對痛風的普遍認知相悖，後者通常將痛風描述為不良飲食選擇的結果。此外，支持大多數飲食改變的證據有限，因為大多數研究是觀察性的，而隨機對照試驗很少。研究特定飲食成分的影響本身就具有挑戰性，因為食物的來源、製備方法和整體環境（例如，生植物蛋白在素食飲食中的作用）可能會影響其效果。過度關注飲食和酒精限制可能會加劇痛風患者的社會歧視。我們鼓勵與患者進行公開對話並提供個別化的指導，因為對於接受穩定降尿酸治療且血清尿酸水平達到或低於目標值的患者而言，富含嘌呤的食物和少量酒精不太可能誘發痛風發作。
減少嘌呤攝取 － 對於已確診痛風或有痛風風險的患者，我們建議減少飲食嘌呤攝入，尤其是來自動物來源的嘌呤（例如紅肉）。美國風濕病學會（ACR）痛風治療指引[ 47 ]也支持減少飲食嘌呤攝取。此外，我們還會指導患者如何在減少嘌呤攝取的同時確保每日攝取足夠的蛋白質，因為一些常見的富含嘌呤的食物也富含蛋白質（例如紅肉、海鮮）。對於接受穩定降尿酸治療且血清尿酸水平達到或低於目標值的痛風患者，富含嘌呤的食物可能不會誘發痛風發作或促進疾病進展。
嘌呤是芳香族、含氮雜環分子，包括腺嘌呤和鳥嘌呤。嘌呤代謝產生尿酸。某些食物嘌呤含量較高，如紅肉、動物內臟、某些海鮮（如沙丁魚、貝類）和某些蔬菜（如青豆、菠菜、蘆筍）。然而，蔬菜中的嘌呤含量遠低於動物性食物。
攝取富含嘌呤食物（包括高嘌呤蛋白質）的患者患痛風的風險增加。蛋白質攝取本身與痛風風險增加無關[ 54 ]。嘌呤或蛋白質的來源不同，對血清尿酸水平和痛風風險的影響也可能不同：
●一項前瞻性隊列研究納入了 633 名痛風患者，比較了痛風發作前兩天的嘌呤攝取量。結果顯示，嘌呤攝取量處於最高五分位的患者，其痛風發作風險幾乎是最低五分位患者的五倍（比值比 [OR] 4.76）[ 55 ]。此外，動物來源的嘌呤比植物來源的嘌呤更容易導致痛風發作。
●多項研究發現，肉類和/或海鮮攝取量較高與血清尿酸濃度升高和/或痛風發生率增加有關[ 15,56,57 ]。例如，一項針對47150名無痛風的男性醫務人員的前瞻性觀察研究發現，肉類攝入量最高五分之一人群的痛風發病風險高於肉類攝入量最低五分之一人群（調整後風險比[HR] 1.41，95% CI 1.07-1.86）[ 15 ]。同樣，魚類攝取量最高五分之一族群的痛風發病風險也高於魚類攝取量最低五分之一族群（HR 1.51，95% CI 1.17-1.95）。
●一項針對健康專業人員的前瞻性研究並未發現攝取大量富含嘌呤蔬菜的患者發生痛風的風險增加[ 54 ]。
對於高尿酸血症患者，限制嘌呤的飲食可以適度降低血清尿酸水平。在降尿酸藥物出現之前，嚴格限制嘌呤的飲食曾被用於治療痛風，可使每日尿尿酸排泄量減少 200 至 400 毫克。然而，平均血清尿酸濃度僅下降約 1 毫克/分升（59 微摩爾/公升）[ 58 ]。嚴格限制嘌呤的飲食可能難以接受且難以實施，因此通常僅適用於治療選擇有限的患者（例如，無法耐受藥物治療的患者）。
對於已透過其他方法達到目標血清尿酸水平的患者，減少嘌呤攝取量的作用可能有限。一項小型試驗將痛風患者隨機分配到對照幹預組或以減少嘌呤攝取量為重點的教育幹預組[ 59 ]。所有患者均接受降尿酸治療，且血清尿酸濃度在目標範圍內。幹預措施提高了患者的相關知識水平並改善了他們的飲食習慣，但並未改變血清尿酸水平。
限製酒精攝取 － 對於已確診痛風或有痛風風險的患者，我們建議限製酒精攝取。如果痛風患者在接受穩定的降尿酸治療後，血清尿酸水平達到或低於目標值，那麼少量飲酒不太可能誘發痛風發作或促進病情進展。如果患者報告有不健康或危險的飲酒行為，我們會告知患者飲酒對健康的危害，並建議他們尋求專業協助。
飲酒會增加痛風的風險[ 60,61 ]。例如，一項針對無痛風的男性醫護人員的大型前瞻性隊列研究發現，與不飲酒者相比，飲用啤酒或烈酒者發生痛風的風險增加（每日每12盎司啤酒的相對風險[RR]為1.49，95% CI 1.32-1.70；每日每杯酒的RR為1.15，95% CI 1.32-1.70；每日每杯酒的RR為1.15，95% CI 1.4-16.04-16 ]。適量飲用葡萄酒（兩杯或兩杯以上，每杯4盎司）者發生痛風的風險沒有差異；這可能是由於混雜因素造成的，因為飲用葡萄酒通常與健康的生活方式相關。
對於痛風患者而言，飲酒會增加痛風發作的風險，而戒酒則會增加發作風險[ 62,63 ]。一項針對痛風患者的病例交叉研究表明，與不飲酒者相比，所有形式的酒精（啤酒、烈酒和葡萄酒）均與24小時內痛風發作風險增加相關[ 63 ]。酒精攝取量與痛風發作之間的關係呈現劑量依賴性：與24小時內未飲酒者相比，飲酒超過1-2杯者痛風發作的OR值為1.36（95% CI 1.00-1.88），而飲酒超過2-4杯者痛風發作的OR值為1.51（1.09-2.09）。同時飲酒且嘌呤攝取量高和/或使用利尿劑的患者痛風發作風險也較高。相較之下，服用別嘌醇時飲酒的人風險降低，服用秋水仙鹼時風險也有所降低（程度較輕）。
痛風石也與飲酒有關。一項針對痛風患者的隊列研究發現，飲酒過量（>70 克/週）、飲酒史較長（≥10 年）、飲用烈酒和飲用啤酒的患者，透過超音波檢查發現痛風石的風險較高（OR 分別為 1.79，95% CI 1.16 至 2.78；1.96，95% 至 15% CI 1.15% CI 15%； 2.95；以及 1.66，95% CI 1.03 至 2.68）[ 64 ]。
飲酒對健康的其他影響將在其他章節中單獨討論。
減少高果糖玉米糖漿和含糖飲料的攝取 — 攝取高果糖玉米糖漿和含糖飲料會增加血清尿酸水平，並增加痛風發作的風險。我們建議患者減少此類食物的攝取。這與包括美國風濕病學會 (ACR) 和歐洲風濕病協會聯盟 (EULAR，前身為歐洲抗風濕病聯盟) 在內的多個醫學組織的建議一致[ 6-11,47 ]。高果糖玉米糖漿和含糖飲料的其他負面健康影響將在其他章節中討論。
攝取果糖等單醣可升高血清尿酸濃度。一項研究發現，給予患者每公斤體重1克果糖後，兩小時血清尿酸濃度升高1至2毫克/分升[ 65 ]。這種效果可能是由於尿酸生成增加[ 66 ]和腎臟尿酸排泄減少所致。此外，腎臟尿酸/葡萄糖/果糖轉運蛋白（SLC2A9）存在基因變異，此變異會使痛風患者在攝取蔗糖後出現高尿酸血症反應[ 67 ]。較高的身體質量指數（BMI）可能介導含糖飲料攝取量與血清尿酸水平之間的關係；與BMI正常的患者相比，BMI較高的患者在攝取果糖後尿酸排泄減少[ 68 ]。
多項研究探討了高攝取量單醣（果糖、蔗糖）與痛風發生率之間的關係[ 66-72 ]。例如，兩項大型前瞻性隊列研究分別納入了46,393名男性醫護人員[ 69 ]和78,906名女性護理師[ 70 ]，這些受試者均無痛風病史，並分別進行了12年和22年的追蹤。對這些研究的系統性回顧發現，果糖攝取量最高五分位組的痛風發病風險高於最低五分位組（風險比1.62，95% CI 1.28-2.03）[ 71 ]。在男性醫護人員的研究中，果糖的主要飲食來源是柳橙汁、含糖飲料、蘋果、葡萄乾和柳橙[ 69 ]。兩項研究均未發現飲用無糖軟性飲料與痛風發病風險增加有關。
採用整體飲食方案 － 我們與高尿酸血症或痛風患者探討整體飲食方案，以及此類改變改善血清尿酸水平的潛力。整體飲食方案的例子包括DASH飲食和地中海飲食。這兩種飲食都強調攝取水果和蔬菜；DASH飲食也注重低脂乳製品，而地中海飲食則優先考慮全穀物、豆類、堅果和種子。這些飲食方案在其他章節中有詳細討論。
一些有限的證據表明，整體飲食療法可能降低血清尿酸水平和痛風發病風險。痛風及相關疾病（如代謝症候群）的盛行率在全球範圍內存在差異，這可能與飲食有部分關係[ 73 ]。支持特定飲食療法的證據包括：
●DASH飲食－DASH試驗的證據表明，該飲食可以降低血清尿酸水平和痛風發病風險；然而，它尚未在痛風患者中進行廣泛研究。最初的試驗比較了DASH飲食與對照飲食對無痛風的高血壓前期或1期高血壓患者的影響。一項小型輔助分析指出，與對照飲食相比，DASH飲食可降低血清尿酸水平；在8名基線尿酸水平較高（≥7 mg/dL）的患者中，這種效果更為顯著（平均降低1.3 mg/dL，95% CI -2.5至-0.08）[ 74 ]。同樣，一項大型縱向隊列研究發現，DASH 飲食模式評分較高的人患痛風的風險較低，而西方飲食模式評分較高的人患痛風的風險較高（極端五分位數的調整 RR 分別為 0.68，95% CI 0.57-0.80；和 1.42，95% CI 1.16-173 ]。
●地中海飲食－兩項試驗的二次分析表明，地中海飲食與高尿酸血症發生率降低和平均血清尿酸水平降低有關[ 75,76 ]。例如，一項對照試驗將中度肥胖且血清尿酸水平升高（≥416 μmol/L）的患者隨機分配到三種飲食組之一：低熱量地中海飲食、低熱量低脂飲食或不限制熱量低碳水化合物飲食[ 75 ]。研究發現，所有患者在6個月和24個月時血清尿酸水平均降低，各組之間無顯著差異（6個月時的平均變化分別為-119、-113和-143 μmol/L）。
對於患有痛風且合併高血壓和代謝症候群等常見疾病的患者，整體飲食療法也可能是有益的。
額外的飲食調整，但證據有限 —— 有限的數據表明，額外的飲食調整可能會降低血清尿酸水平、痛風發病風險和/或痛風發作風險。
●可能增加痛風風險和/或加重痛風症狀的食物－高脂肪食物與誘發痛風發作有關[ 77 ]，這可能與長鏈脂肪酸啟動NLRP3發炎小體活化所需的「第一訊號」和「第二訊號」有關，從而導致痛風發作的發炎表現[ 78 ]。 「促發炎飲食」也與增加痛風風險有關[ 79 ]。
●可能降低痛風發作風險的食物
•低脂乳製品－攝取低脂乳製品可能對痛風患者或有痛風風險的人有益。 2020 年美國風濕病學會 (ACR) 痛風治療指南由於證據有限，並未對低脂乳製品提出意見[ 12 ]，儘管先前發布的指南曾建議增加低脂乳製品的攝取量[ 4,6,7,10,11 ]。對於痛風患者，建議其攝取低脂乳製品以獲得整體健康益處，這些益處將在其他章節中討論。
低脂乳製品的攝取與痛風風險降低和血清尿酸水平降低有關。一項針對男性健康專業人員的大型觀察性研究發現，乳製品攝取量最高五分之一人群與最低五分之一人群相比，痛風發病風險降低了近50%（RR 0.56，95% CI 0.42-0.74）[ 54 ]。每日額外攝取一份乳製品，痛風發病風險的調整後比值為0.82（95% CI 0.75-0.90）；此益處主要侷限於低脂乳製品的攝取。另一項大型觀察性研究也發現，乳製品攝取與痛風發病率降低有關，尤其是在具有痛風高遺傳風險的患者中；這些發現是在觀察到更豐富、更多樣化的飲食與痛風風險降低相關的背景下得出的[ 80 ]。此外，多項針對非痛風患者的橫斷面研究表明，乳製品攝取與較低的血清尿酸水平相關[ 56,81,82 ]。一項針對健康男性的小型隨機試驗發現，與大豆補充劑相比，牛奶補充劑能更顯著地降低血清尿酸水平；兩種補充劑的蛋白質含量都非常高（80克/天）[ 82 ]。
對於已確診痛風的患者，目前尚無強有力的證據顯示攝取低脂乳製品可以減少痛風發作。在一項試驗中，復發性痛風發作（即過去四個月內發作≥2次）的患者被隨機分配到三種膳食補充劑組（含乳糖的對照補充劑、標準脫脂奶粉[SMP，相當於每天增加兩份低脂乳製品]或富含“抗炎”乳成分的強化SMP）中，持續三個月強化。結果顯示，標準SMP補充劑組與乳糖對照組在痛風發作次數的變化上並無顯著差異[ 83 ]。與乳糖對照組相比，強化SMP補充劑組痛風發作次數顯著減少，尿酸排泄分數和患者自述疼痛程度也有所改善。
•櫻桃－有限的證據表明，飲食補充櫻桃可能降低痛風發作的風險[ 84-86 ]。如果痛風患者有興趣且情況合適（例如，無糖尿病），我們會與他們討論櫻桃的攝取量。由於證據有限，美國風濕病學會（ACR）痛風治療指引未包含補充櫻桃的意見[ 12 ]。
支持櫻桃對痛風有益的證據有限[ 84-86 ]。一項針對痛風患者的病例交叉研究發現，在兩天內食用櫻桃或櫻桃萃取物的患者，與未食用櫻桃的患者相比，痛風發作的可能性更低（調整後的OR值分別為0.65，95% CI 0.50-0.85；以及0.55，95% CI 0.30-0.98）[ 85 ]。這種益處似乎在兩天內食用最多三份櫻桃即可獲得；增加食用量並未帶來進一步的益處。然而，在一項為期四週的試驗中，50 名患有痛風和高尿酸血症（血清尿酸 >0.36 微摩爾/公升）的患者隨機分配到酸櫻桃汁濃縮液組的參與者，與接受安慰劑的參與者相比，其血清尿酸水平沒有顯著降低，尿尿酸排泄量沒有顯著升高，28 天痛風發作風險也沒有顯著降低 [ 86 ]。
•維生素C補充劑－我們不建議痛風患者補充維生素C ，除非他們已從飲食中攝取了足夠的維生素C。美國風濕病學會（ACR）痛風治療指引並未就補充維生素C提出具體建議，因為維生素C對痛風患者的血清尿酸濃度影響甚微[ 12 ]。維生素C的每日需求量、主要來源和毒性已在其他文獻中詳細討論，但值得注意的是，男性服用維生素C會增加草酸鈣腎結石的風險。
維生素C可能降低無痛風族群的血清尿酸水平，並降低痛風的發生風險。在一項雙盲試驗中，受試者均為無痛風患者，隨機分配至維生素C補充劑組（500毫克/天）或安慰劑組。結果顯示，兩個月後，維生素C補充劑組的血清尿酸水平顯著降低，而安慰劑組則無此效果（平均變化分別為-0.5毫克/分升[95%置信區間-0.6至-0.3]和0.09毫克/分升[95%置信區間-0.05至0.2]）[ 87 ]。一項隨機對照試驗的統合分析也發現，維生素C補充劑可降低血清尿酸水平較高的無痛風患者的血清尿酸水平[ 87,88 ]。維生素C的劑量可能很重要；在一項針對無痛風男性的前瞻性隊列研究中，與每日總維生素 C 攝取量較低（≤250 毫克）相比，每日維生素 C 劑量較高（≥500 毫克）的男性患痛風的相對風險較低（每日維生素 C 補充劑量每增加 500 毫克，相對風險為 0.83，95% 置信區間為 0.907-907-90073，為 0.83，95% 置信區間。
然而，對於痛風患者而言，支持使用維生素C的證據非常有限。在一項針對痛風合併高尿酸血症患者的隨機試驗中，每日補充維生素C（500毫克）8週的參與者與服用別嘌醇治療的患者相比，血清尿酸水平並未顯著降低[ 89 ]。
•咖啡－由於證據不足且高咖啡因攝取可能產生不良反應，我們不建議患有痛風或有痛風風險的患者增加咖啡攝取量。含咖啡因飲料的各種風險和益處已在其他文獻中詳細闡述。
對於有痛風風險的患者，與不喝咖啡相比，大量攝取咖啡（例如，每天四到五杯）與痛風發病相對風險降低相關（RR 0.60，95% CI 0.41-0.87）[ 90 ]。無咖啡因咖啡降低風險的效果略弱，而經常喝茶則未觀察到這種效果。然而，在痛風患者中，與不喝咖啡相比，大量攝取咖啡（每天超過4杯）僅與血清尿酸水平的較小降低相關（平均差異為-0.42 mg/dL，95% CI -1.01至0.17）[ 91 ]。
•魚類和ω-3脂肪酸－對於痛風患者而言，增加ω-3多元不飽和脂肪酸（n-3 PUFA）的攝取量可能是有益的。有限的證據表明，n-3 PUFA可能降低痛風發作的風險。在一項痛風患者的病例交叉研究中，與未食用富含n-3 PUFA魚類的患者相比，報告在前兩天食用過此類魚類的患者痛風發作的風險較低[ 92 ]。相較之下，服用n-3 PUFA補充劑並未降低痛風發作的風險，這可能是因為補充劑中n-3 PUFA的含量通常低於魚類。在一項小型試驗可行性試驗中，痛風成年患者被隨機分配服用ω-3脂肪酸或安慰劑（橄欖油膠囊），同時開始接受降尿酸治療，結果顯示，在28週內，兩組患者的痛風發作次數沒有差異；這可能是因為該研究樣本量不足以檢測出病情發作次數的差異[ 93 ]。關於ω-3脂肪酸的膳食攝取量，其他文獻有詳細討論。
•植物性飲食－關於植物性飲食如何影響痛風發病率和痛風發作風險的數據非常有限。在一項大型隊列研究中，植物性飲食指數（PDI）與痛風無關[ 72 ]；然而，報告健康PDI（例如，食用全穀物、水果、蔬菜、堅果、豆類）較高的人群痛風發病風險較低，而不健康PDI（即，食用精製穀物、果汁、含糖飲料）較高的人群痛風發病風險。全穀物和某些膳食木脂素（一種在植物性食物中含量豐富的主要植物雌激素）也與較低的痛風發病風險相關[ 94 ]。
•其他建議的補充劑－有限的數據表明，膳食纖維和葉酸也可能降低痛風的發生風險[ 95 ]。然而，目前尚無充分證據推薦膳食補充劑。關於膳食纖維和葉酸的其他適應症，請參考其他文獻。
Overview of dietary modification — Certain foods can increase serum urate or the risk of gout flares. Such foods generally should be minimized (or even avoided when possible) for patients who have or are at high risk for developing gout. In addition, adopting certain dietary practices, such as healthy whole-diet approaches, may be beneficial in reducing the risk of gout or gout flares.
In most patients with hyperuricemia or gout, we counsel them about potential modification of the following components:
●Reducing consumption of foods that potentially trigger gout flares, including:
•High-purine foods (eg, red meat, shellfish) (see 'Reduce purine intake' below)
•Alcoholic beverages of all types
•High-fructose corn syrup and sugar-sweetened beverages
●Considering whole-diet approaches such as the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets
●Obtaining adequate dietary protein from plant-based and/or low-fat dairy sources
Our approach is largely consistent with that outlined by the 2020 American College of Rheumatology (ACR) gout treatment guideline [47].
If patients have a normal body mass index (BMI; 18.5 to 24.9 mg/kg2), we discuss the importance of maintaining a healthy weight. If patients have overweight or obesity, they may benefit from additional modifications directed at weight reduction.
There are several limitations to consider when advising patients about the potential impact of dietary changes on the risk of gout or gout flares. Diet plays a limited role overall in reducing serum urate levels and therefore should be just one component of a comprehensive plan to manage gout. This may be a contrast to common public perceptions of gout, which often portray gout as the result of poor dietary choices. In addition, evidence to support most dietary changes is limited, since most studies are observational and randomized controlled trials are rare. It is inherently challenging to study the impact of a specific dietary component, as the effect may be modified by the source, preparation, and overall context of the food (eg, the role of raw plant-based protein as part of a vegetarian diet). Excessive focus on dietary and alcohol restrictions can contribute to stigma in people with gout. We encourage open dialogue with patients and individualized guidance, as purine-rich foods and small amounts of alcohol may be unlikely to trigger flares in patients with serum urate at or below goal on stable urate-lowering therapy.
Reduce purine intake — For patients who have established gout or are at risk of developing gout, we suggest reducing dietary purine intake, especially purines derived from animal sources (eg, red meat). Reduction of dietary purine intake is supported by recommendations in the ACR gout treatment guideline [47]. We additionally counsel patients on ways to ensure they obtain adequate daily protein when reducing purine intake, since some common high-purine foods are also rich in proteins (eg, red meat, seafood). In patients with gout who have a serum urate at or below their goal level on stable urate-lowering therapy, purine-rich foods may not trigger flares or promote disease progression.
Purines are aromatic, nitrogen-containing, heterocyclic molecules and include adenine and guanine. Purine metabolism produces urate. Certain foods have higher concentrations of purines, including red meat, organ meats, certain types of seafood (eg, sardines, shellfish), and certain vegetables (eg, green peas, spinach, asparagus). However, the purine content in vegetables is much lower than in animal sources.
There is an increased risk of gout among patients with higher intake of purine-rich foods, including proteins that contain high levels of purines. Protein intake itself is not associated with an increased risk of gout [54]. The effect on serum urate and gout risk may vary depending on the source of purines or protein:
●In a prospective cohort study of 633 patients with gout that compared the level of purine intake in the two days preceding a gout flare, the risk of gout flare was increased almost fivefold for patients who scored in the highest quintile of purine intake compared with those in the lowest quintile (odds ratio [OR] 4.76) [55]. The risk of gout flare was higher when purines were derived from animal versus vegetable sources.
●Several studies have found a relationship between higher levels of meat and/or seafood consumption and increased levels of serum urate and/or incident gout [15,56,57]. As an example, in a prospective observational study of 47,150 male health professionals without gout, patients in the highest quintile of meat consumption had an increased risk of incident gout compared with those in the lowest quintile (adjusted hazard ratio [HR] 1.41, 95% CI 1.07-1.86) [15]. Likewise, those in the highest quintile of fish consumption had an increased risk of gout compared with those in the lowest quintile (HR 1.51, 95% CI 1.17-1.95).
●A prospective study of health professionals did not identify an increased risk of incident gout among patients with high intake of purine-rich vegetables [54].
In people with hyperuricemia, purine-restricted diets can modestly reduce serum urate levels. Prior to the availability of urate-lowering pharmacotherapy, severely purine-restricted diets were used to treat gout and could reduce daily urinary urate excretion by 200 to 400 mg/day. However, mean serum urate concentrations decrease only approximately 1 mg/dL (59 micromol/L) [58]. Diets that severely restrict purines may be unpalatable and impractical to implement and are therefore usually reserved for patients who have limited therapeutic options (eg, patients who do not tolerate pharmacotherapy).
Reducing purine intake may have a limited role in patients who have achieved goal serum urate through other means. A small trial randomly assigned patients with gout to a control intervention or an educational intervention that focused on reducing purine intake [59]. All patients were on urate-lowering therapy and had a serum urate within the goal range. The intervention resulted in better knowledge and dietary modification but did not change serum urate levels.
Limit alcohol intake — For patients with established gout or who are at risk for developing gout, we suggest limiting alcohol intake. If patients with gout have a serum urate at or below their goal level on stable urate-lowering therapy, small amounts of alcohol may be unlikely to trigger flares or promote disease progression for most patients. If patients report unhealthy or risky use of alcohol beverages, we counsel the patient about the risks of alcohol intake to their health and refer them for professional assistance.
Alcohol intake can increase the risk of developing gout [60,61]. As an example, a large, prospective cohort study of health professional males without gout found an increased risk of incident gout among those consuming beer or hard liquor compared with those not consuming alcohol (relative risk [RR] per 12 ounce serving of beer per day 1.49, 95% CI 1.32-1.70, and RR per drink or shot per day 1.15, 95% CI 1.04-1.28) [60]. The risk of incident gout was not different for those consuming moderate amounts of wine (two or more four-ounce glasses); this may be because of confounding since wine consumption is often associated with healthy lifestyle behaviors.
For patients with gout, drinking alcohol increases the risk of flare compared with abstaining from alcohol [62,63]. In a case-crossover study of people with gout, all forms of alcohol (beer, liquor, and wine) were associated with an increased risk of flare within 24 hours when compared with no alcohol consumption [63]. The relationship between alcohol intake and gout flare was dose-dependent: when compared with people who did not drink within 24 hours, those reporting more than one to two drinks had an OR of gout flare of 1.36 (95% CI 1.00-1.88), while those reporting more than two to four drinks had an OR of 1.51 (1.09-2.09). People who reported alcohol use together with high purine consumption and/or diuretic use also had a higher risk of flares. By contrast, the risk was attenuated for people who drank alcohol while taking allopurinol and, to a lesser degree, colchicine.
Tophaceous gout is also associated with alcohol intake. A cohort study of patients with gout found that the risk of having tophi detected by ultrasound was greater among patients with excessive alcohol intake (>70 g/week), longer history of alcohol exposure (≥10 years), consumption of hard liquor, and consumption of beer (OR 1.79, 95% CI 1.16 to 2.78; 1.96, 95% CI 1.22 to 3.15; 1.81, 95% CI 1.11 to 2.95; and 1.66, 95% CI 1.03 to 2.68, respectively) [64].
Other health effects of alcohol intake are discussed separately. Reduce intake of high-fructose corn syrup and sugar-sweetened beverages — Intake of high-fructose corn syrup and sugar-sweetened beverages can increase serum urate and the risk of incident gout. We counsel patients about reducing the intake of such foods. This is consistent with recommendations from multiple medical organizations, including the ACR and the European Alliance of Associations for Rheumatology (EULAR, formerly known as the European League Against Rheumatism) [6-11,47]. Other negative health effects of high-fructose corn syrup and sugar-sweetened beverages are discussed elsewhere.
Intake of simple sugars like fructose can increase serum urate. A study that gave patients 1 g of fructose per kg of body weight found that the serum urate level increased by 1 to 2 mg/dL after two hours [65]. This effect may be due to increased urate production [66] and reduced renal urate excretion. There is also a genetic variant in the renal urate/glucose/fructose transporter (SLC2A9) that favors a hyperuricemic response to sucrose intake among individuals with gout [67]. Elevated BMI may mediate the relationship between intake of sugar-sweetened beverages and serum urate; urate excretion was reduced after a fructose load in patients who had a high BMI compared with those who had a normal BMI [68].
Several studies have examined the relationship between high intake of simple sugars (fructose, sucrose) and incident gout [66-72]. As an example, two large prospective cohort studies included 46,393 male health professionals [69] and 78,906 female nurses [70] without gout and had 12 and 22 years of follow-up, respectively. A systematic review of these studies found that the risk of incident gout was higher for those in the highest versus lowest quintiles of fructose intake (risk ratio 1.62, 95% CI 1.28-2.03) [71]. In the male health professionals study, the main dietary sources of fructose were orange juice, sugar-sweetened beverages, apples, raisins, and oranges [69]. Drinking diet soft drinks was not associated with an increased risk for incident gout in either study.
Use whole-diet approaches — We discuss whole-diet approaches with patients with hyperuricemia or gout and the potential for such changes to improve serum urate. Examples of whole-diet approaches include the DASH and Mediterranean diets. Both of these diets emphasize intake of fruits and vegetables; the DASH diet additionally focuses on low-fat dairy, while the Mediterranean diet prioritizes whole grains, beans, nuts, and seeds. These diets are discussed in detail elsewhere.
There is some limited evidence to suggest that whole diet approaches may reduce serum urate and the risk of incident gout. The prevalence of gout and related conditions, such as metabolic syndrome, differ worldwide and may be partially related to diet [73]. Supportive evidence for specific diets includes the following:
●DASH diet – Evidence from the DASH trials has suggested that the diet can lower serum urate levels and the risk of incident gout; however, it has not been studied extensively in patients with gout. The original trial compared the DASH diet with a control diet in prehypertensive or stage 1 hypertensive persons without gout. A small ancillary analysis noted that the DASH diet led to lower serum urate levels when compared with the control diet; the effect was more pronounced in eight patients with high baseline urate (≥7 mg/dL) (mean reduction of 1.3 mg/dL, 95% CI -2.5 to -0.08) [74]. Similarly, a large longitudinal cohort study found that people who had higher DASH dietary pattern scores had a lower risk of incident gout, whereas people with higher Western dietary pattern scores had a higher risk of incident gout (adjusted RR for extreme fifths 0.68, 95% CI 0.57-0.80; and 1.42, 95% CI 1.16-1.74], respectively) [73].
●Mediterranean diet – The Mediterranean diet has been associated with lower likelihood of hyperuricemia and lower mean serum urate in secondary analyses of two trials [75,76]. As an example, a controlled trial randomly assigned patients with moderate obesity and elevated serum urate (≥416 micromol/L) to one of three diets: a low-calorie Mediterranean diet, a low-calorie and low-fat diet, or an unrestricted calorie, low-carbohydrate diet [75]. It found that serum urate was reduced at 6 and 24 months for all patients, without significant differences between the groups (mean change at six months of -119, -113, and -143 micromol/L, respectively).
Whole-diet approaches may also be beneficial for patients with gout who have common comorbid conditions, such as hypertension and metabolic syndrome.
Additional dietary modifications with limited evidence — Limited data suggest that additional dietary modifications may reduce serum urate levels, the risk of incident gout, and/or the risk of gout flares.
●Foods that may increase risk of gout and/or worsen gout symptoms – Fatty meals have been implicated in precipitating flares [77], which may be related to long-chain fatty acids priming the "first signal" and "second signal" required for NLRP3 inflammasome activation, which leads to the inflammatory manifestations of gout flares [78]. "Proinflammatory diets" have also been implicated in increasing the risk of gout [79].
●Foods that may decrease risk of incident gout and/or gout flares
•Low-fat dairy products – Intake of low-fat dairy products may be beneficial for patients with gout or who are at risk of developing gout. The 2020 ACR gout treatment guideline does not include opinions on low-fat dairy products because of limited evidence [12], although previously published guidelines had recommended increasing intake of low-fat dairy foods [4,6,7,10,11]. Dietary intake of low-fat dairy products can be recommended to patients with gout for overall health benefits, which are discussed elsewhere.
Consumption of low-fat dairy products has been associated with a decreased risk of developing gout and lower serum urate levels. In a large observational study of male health professionals, the risk of incident gout was nearly 50 percent lower when comparing people in the highest and lowest quintiles of dairy product consumption (RR 0.56, 95% CI 0.42-0.74) [54]. The adjusted risk ratio of incident gout per additional daily serving of dairy products was 0.82, 95% CI 0.75-0.90; this benefit was primarily restricted to intake of low-fat dairy products. Another large observational study likewise found that dairy consumption was associated with a decreased incidence of gout, especially among patients with high genetic risk for gout; these findings were in the context of observing that a richer, more diverse diet was associated with lower risk of gout [80]. In addition, several cross-sectional studies in people without gout have shown that dairy product intake is associated with lower serum urate levels [56,81,82]. One small randomized trial in healthy males found that milk-based supplements acutely lowered serum urate levels to a greater extent than soy-based supplements; each supplement was very high in protein (80 g/day) [82].
For patients with established gout, there is no strong evidence to suggest that intake of low-fat dairy products reduces gout flares. In a trial in which patients with recurrent gout flares (ie, ≥2 flares in the preceding four months) were randomly assigned to one of three dietary supplements (control supplement with lactose, standard skim milk powder [SMP, equivalent increase of two servings of low-fat dairy per day], or enriched SMP containing "anti-inflammatory" milk fractions) for three months, there was no significant difference in the change in gout flares between standard SMP supplementation and the lactose control [83]. Enriched SMP supplementation led to a greater reduction in gout flares as well as improvements in fractional excretion of urate and self-reported pain when compared with the lactose control.
•Cherries – Limited evidence suggests that dietary supplementation with cherries may reduce the risk of gout flares [84-86]. We discuss cherry intake with patients with gout if they are interested and if it is otherwise appropriate (eg, no diabetes). The ACR gout treatment guideline does not include opinions on cherry supplementation because of limited evidence [12].
Supportive evidence for cherries in gout is limited [84-86]. A case-crossover study of patients with gout found that patients who reported eating cherries or cherry extract over a two-day period were less likely to have a gout flare when compared with patients who did not eat cherries (adjusted OR 0.65, 95% CI 0.50-0.85; and 0.55, 95% CI 0.30-0.98, respectively) [85]. This benefit appeared to occur with up to three servings of cherries in a two-day period; additional servings were not associated with further benefit. However, in a four-week trial of 50 patients with gout and hyperuricemia (serum urate >0.36 micromol/L), participants randomly assigned to tart cherry juice concentrate did not have significantly lower serum urate, higher urinary urate excretion, or lower gout 28-day flare risk compared with participants receiving placebo [86].
•Vitamin C supplementation – We do not encourage vitamin C supplementation for patients with gout who otherwise have adequate dietary intake of vitamin C. The ACR gout treatment guideline does not make a specific recommendation regarding vitamin C supplementation due to clinically insignificant effects on serum urate among people with gout [12]. The daily requirements, main sources, and toxicities of vitamin C are discussed in detail elsewhere, but notably include risk of oxalate kidney stones in males.
Vitamin C may lower serum urate among people without gout and reduce the risk of incident gout. In a double-blinded trial of participants without gout who were randomly assigned to receive vitamin C supplementation (500 mg/day) or placebo, serum urate levels at two months were reduced with vitamin C supplementation but not with placebo (mean change -0.5 mg/dL [95% CI -0.6 to -0.3] versus 0.09 mg/dL [95% CI -0.05 to 0.2]) [87]. A meta-analysis of randomized controlled trials also found that vitamin C supplementation reduced serum urate in participants without gout who had high serum urate [87,88]. The dose of vitamin C may matter; in a prospective cohort study of males without gout, the RR of incident gout was lower with higher daily doses of vitamin C (≥500 mg) compared with lower total daily vitamin C intake (≤250 mg) (RR per 500 mg increase in total daily vitamin C supplementation of 0.83, 95% CI 0.77-0.90) [89].
However, for patients with gout, evidence to support use of vitamin C is very limited. In a randomized trial in people with gout and hyperuricemia, participants taking daily vitamin C supplementation (500 mg) for eight weeks did not have a significant reduction in serum urate when compared with those taking allopurinol therapy [89].
•Coffee – We do not counsel patients who have or are at risk of developing gout to increase coffee intake due to insufficient evidence and potential adverse effects of high caffeine consumption. The various risks and benefits of caffeinated beverages are detailed elsewhere.
For patients at risk of developing gout, high coffee intake (eg, four to five cups daily) has been associated with a lower relative risk of incident gout compared with no coffee intake (RR 0.60, 95% CI 0.41-0.87) [90]. The reduction in risk was slightly less with decaffeinated coffee and was not observed with frequent tea intake. However, in patients with gout, high coffee intake (>4 cups daily) was only associated with a relatively small reduction in serum urate when compared with no coffee intake (mean difference of -0.42 mg/dL, 95% CI -1.01 to 0.17) [91].
•Fish and omega-3 fatty acids – For patients who have gout, increasing intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) may be beneficial. Limited evidence suggests that n-3 PUFA may reduce the risk of gout flares. In a case-crossover study of patients with gout, the risk of a gout flare was lower for patients who reported eating fish with high levels of n-3 PUFA during the preceding two days compared with patients who did not eat such fish [92]. By contrast, taking n-3 PUFA supplements did not reduce the risk of gout flare, potentially because supplements typically have lower amounts of n-3 PUFA than fish. A small pilot feasibility trial in which adults with gout were randomly assigned to take omega-3 fatty acids or placebo (olive oil capsules) while initiating urate-lowering therapy did not demonstrate a difference in flares over 28 weeks; this could be because the study was not powered to detect a difference in flares [93]. Dietary intake of omega-3 fatty acids is discussed in detail elsewhere.
•Plant-based diets – There are very limited data about how plant-based diets affect the incidence of gout and risk of gout flare. In a large cohort study, the plant-based diet index (PDI) was not associated with gout [72]; however, the risk of incident gout was lower among people who reported a higher healthy PDI (eg, consumption of whole grains, fruits, vegetables, nuts, legumes) and higher among those who reported a higher unhealthy PDI (ie, consumption of refined grains, fruit juice, sugar-sweetened beverages). A lower risk of incident gout has also been observed with whole-grain cereals and certain dietary lignans, a major group of phytoestrogens abundant in plant foods [94]. More information on health benefits of plant-based and vegetarian diets is provided separately.
•Other proposed supplements – Limited data suggest that dietary fiber and folate may also reduce the risk of incident gout [95]. However, evidence is insufficient to recommend dietary supplementation. Information on other indications for dietary fiber and folate are described elsewhere.
