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美国国家老龄化研究所Christopher E Ramsden团队研究了n-3和n-6脂肪酸饮食改变对偏头痛成人患者头痛缓解的影响。这一研究成果于2021年7月1日发表在《英国医学杂志》上。

为了确定增加n-3脂肪酸，同时减少或不减少n-6亚油酸的饮食干预是否能改变与头痛发病机制有关的循环脂质介质，并减少偏头痛患者的头痛症状，研究组在美国一家门诊学术医疗中心进行了一项为期16周的三臂、平行组、随机、改良双盲的对照试验。共招募了182名参与者，其中88%为女性，平均年龄为38岁，每月5-20天偏头痛发作，67%符合慢性偏头痛的标准。

研究组设计了二十碳五烯酸（EPA）、二十二碳六烯酸（DHA）和亚油酸为控制变量的三种饮食：61名患者接受H3饮食，将EPA+DHA增加到1.5 g/d，并将亚油酸维持在膳食能量的7%左右；61名接受H3-L6饮食，增加n-3 EPA+DHA至1.5 g/d，减少亚油酸至低于膳食能量的1.8%；60名接受对照饮食，将EPA+DHA维持在<150 mg/d，亚油酸维持在膳食能量的7%左右。所有参与者都接受了占每日膳食能量三分之二的食物，并继续进行日常护理。主要终点是第16周时血液中的镇痛介质17-羟基二十二碳六烯酸（17-HDHA）和头痛影响试验（HIT-6，评估头痛对生活质量影响的六项问卷）。每天通过电子日记评估头痛频率。

在意向治疗分析中，H3-L6组和H3组与对照组相比，循环17-HDHA（log ng/mL）显著增加。H3-L6组和H3组中观察到的HIT-6得分改善与对照组相比无统计学差异。与对照组相比，H3-L6组和H3组患者的每日头痛时间分别减少1.7和1.3小时，每日中重度头痛时间分别减少0.8和0.7小时，每月头痛天数分别减少4.0和2.0天。

H3-L6组比H3组每月减少头痛天数更多，表明降低饮食中的亚油酸有额外益处。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化脂质衍生物，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。

研究结果表明，H3-L6和H3饮食干预改变了与头痛发病有关的生物活性介质，降低了头痛的发生率和严重程度，但并未显著改善生活质量。

附：英文原文

Title: Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial

Author: Christopher E Ramsden, Daisy Zamora, Keturah R Faurot, Beth MacIntosh, Mark Horowitz, Gregory S Keyes, Zhi-Xin Yuan, Vanessa Miller, Chanee Lynch, Gilson Honvoh, Jinyoung Park, Russell Levy, Anthony F Domenichiello, Angela Johnston, Sharon Majchrzak-Hong, Joseph R Hibbeln, David A Barrow, James Loewke, John M Davis, Andrew Mannes, Olafur S Palsson, Chirayath M Suchindran, Susan A Gaylord, J Douglas Mann

Issue&Volume: 2021/07/01

Abstract:

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.

DOI: 10.1136/bmj.n1448

Source: https://www.bmj.com/content/374/bmj.n1448

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