Objective To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. Design Three arm, parallel group, randomized, modified double blind, controlled trial. Setting Ambulatory, academic medical center in the United States over 16 weeks. Participants 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). Interventions Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)—increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)—increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)—maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care. Main outcome measures The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. Results In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (−1.6, −4.2 to 1.0, and −1.5, −4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (−1.7, −2.5 to −0.9, and −1.3, −2.1 to −0.5, respectively), moderate to severe headache hours per day (−0.8, −1.2 to −0.4, and −0.7, −1.1 to −0.3, respectively), and headache days per month (−4.0, −5.2 to −2.7, and −2.0, −3.3 to −0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (−2.0, −3.2 to −0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. Conclusions The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. Trial registration ClinicalTrials.gov [NCT02012790][1] Data sharing: The data and code are available from the corresponding author upon reasonable request. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02012790&atom=%2Fbmj%2F374%2Fbmj.n1448.atom

中文翻译：

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改变 n-3 和 n-6 脂肪酸的饮食可减少成人偏头痛患者的头痛：随机对照试验

目的 确定增加 n-3 脂肪酸同时或不减少 n-6 亚油酸的饮食干预是否可以改变与头痛发病机制有关的循环脂质介质，并减少成人偏头痛患者的头痛。设计三臂、平行组、随机、改良双盲、对照试验。在美国设置流动学术医疗中心超过 16 周。参与者 182 名参与者（88% 为女性，平均年龄 38 岁）每月有 5-20 天偏头痛（67% 符合慢性偏头痛标准）。干预措施 以二十碳五烯酸 (EPA)、二十二碳六烯酸 (DHA) 和亚油酸为控制变量，设计三种饮食： H3 饮食 (n=61) — 将 EPA+DHA 增加至 1.5 克/天，并将亚油酸维持在 7% 左右能量；H3-L6 饮食 (n=61) — 将 n-3 EPA+DHA 增加至 1。5克/天，并将亚油酸减少至能量的≤1.8%；控制饮食 (n=60)——将 EPA+DHA 维持在 <150 毫克/天，将亚油酸维持在能量的 7% 左右。所有参与者都接受了占每日食物能量三分之二的食物，并继续进行常规护理。主要结局指标 主要终点（第 16 周）是血液中的镇痛介质 17-羟基二十二碳六烯酸 (17-HDHA) 和头痛影响测试 (HIT-6)，这是一项评估头痛对生活质量影响的六项问卷。每天用电子日记评估头痛频率。结果 在意向治疗分析 (n=182) 中，与对照饮食相比，H3-L6 和 H3 饮食增加了循环 17-HDHA (log ng/mL)（基线调整平均差 0.6，95% 置信区间 0.2）分别为 0.9、0.7、0.4 至 1.1）。H3-L6 和 H3 组中观察到的 HIT-6 评分改善不具有统计学意义（分别为 -1.6、-4.2 至 1.0 和 -1.5、-4.2 至 1.2）。与对照饮食相比，H3-L6和H3饮食减少了每天总头痛时间（分别为-1.7、-2.5至-0.9和-1.3、-2.1至-0.5），每天中度至重度头痛时间（分别为-0.8、-1.2至-0.4和-0.7、-1.1至-0.3），以及每月头痛天数（分别为-4.0、-5.2至-2.7和-2.0、-3.3至-0.7）。H3-L6 饮食比 H3 饮食每月减少头痛天数更多（-2.0、-3.2 至 -0.8），这表明降低膳食亚油酸有额外的好处。H3-L6和H3饮食改变了血浆、血清、红细胞或免疫细胞中的n-3和n-6脂肪酸及其几种伤害性氧脂衍生物，但没有改变经典的头痛介质降钙素基因相关肽和前列腺素E2。结论 H3-L6 和 H3 干预措施改变了与头痛发病机制有关的生物活性介质，降低了头痛的频率和严重程度，但没有显着改善生活质量。试验注册 ClinicalTrials.gov [NCT02012790][1] 数据共享：根据合理要求，数据和代码可从通讯作者处获得。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02012790&atom=%2Fbmj%2F374%2Fbmj.n1448.atom 试验注册 ClinicalTrials.gov [NCT02012790][1] 数据共享：根据合理要求，数据和代码可从通讯作者处获得。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02012790&atom=%2Fbmj%2F374%2Fbmj.n1448.atom 试验注册 ClinicalTrials.gov [NCT02012790][1] 数据共享：根据合理要求，数据和代码可从通讯作者处获得。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02012790&atom=%2Fbmj%2F374%2Fbmj.n1448.atom