Department of Psychiatry, University of Rochester Medical Center/Strong Memorial Hospital, Laboratory for Mood Disorders in Children and Adolescents, Rochester, NY 14642, USA.
Bipolar Disord. 2010 Mar;12(2):142-54. doi: 10.1111/j.1399-5618.2010.00799.x.
This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid alpha-linolenic acid (alpha-LNA), safely reduced symptom severity in youth with bipolar disorder.
Children and adolescents aged 6-17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg alpha-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions-Bipolar ratings using Kaplan-Meier survival analyses.
There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician-rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: %alpha-LNA (r = -0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = -0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for alpha-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for alpha-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms.
Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and/or decreased AA and DPA n-6 levels, individual variations in conversion of alpha-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone.
本临床试验旨在评估富含ω-3 脂肪酸 α-亚麻酸（α-LNA）的亚麻籽油补充剂是否能安全减轻双相障碍青少年的症状严重程度。
年龄在 6-17 岁之间、患有症状性双相 I 或双相 II 障碍的儿童和青少年（n=51），表现为躁狂、轻躁狂、混合或抑郁，随机分为亚麻籽油胶囊组（每 1 克含 550 毫克 α-LNA）或橄榄油安慰剂辅助治疗或单药治疗。在 16 周内，根据耐受情况将剂量滴定至每天 12 粒胶囊。主要结局指标包括使用 Kaplan-Meier 生存分析评估青年躁狂量表、儿童抑郁评定量表修订版和双相临床总体印象量表的变化。
按治疗分配比较时，主要结局指标无显著差异。然而，临床医生评定的总体症状严重程度与最终血清 ω-3 脂肪酸组成呈负相关：%α-LNA（r=-0.45，p<0.007）、%二十碳五烯酸（EPA）（r=-0.47，p<0.005）；与最终花生四烯酸（AA）（r=0.36，p<0.05）和二十二碳六烯酸（DPA）n-6（r=0.48，p<0.004）呈正相关。α-LNA 的平均治疗持续时间为 11.8 周，安慰剂为 8 周；然而，在控制基线变量后，α-LNA 的较长治疗持续时间并不显著。研究对象因持续抑郁症状而停止研究。
必需脂肪酸补充研究在儿科人群中是可行且耐受良好的。尽管亚麻籽油可能会降低患有双相障碍的儿童和青少年的疾病严重程度，这些患者的血清 EPA 百分比水平显著增加，AA 和 DPA n-6 水平降低，但 α-LNA 向 EPA 和二十二碳六烯酸转化的个体差异以及剂量负担均有利于鱼油用于临床试验和临床实践。此外，未来的研究应侧重于依从性，并根据必需脂肪酸组织成分的变化而非单纯的分组随机化来分析结果。
