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二十二碳六烯酸治疗类风湿关节炎:以微藻和葵花籽油进行双盲、安慰剂对照、随机交叉研究。

Docosahexaenoic acid in the treatment of rheumatoid arthritis: A double-blind, placebo-controlled, randomized cross-over study with microalgae vs. sunflower oil.

机构信息

Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany; Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Dornburger Str. 25, 07743 Jena, Germany.

Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University of Jena, Dornburger Str. 25, 07743 Jena, Germany.

出版信息

Clin Nutr. 2018 Apr;37(2):494-504. doi: 10.1016/j.clnu.2017.02.021. Epub 2017 Mar 6.

DOI:10.1016/j.clnu.2017.02.021
PMID:28302406
Abstract

UNLABELLED

The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited.

STUDY DESIGN

In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study.

RESULTS

In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation.

CONCLUSION

The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.

摘要

未加说明

人们对鱼类或鱼油作为二十碳五烯酸 (EPA,C20:5n3) 和二十二碳六烯酸 (DHA,C22:6n3) 的潜在供应源进行了深入研究,以降低心血管风险因素并支持慢性炎症性疾病的治疗,但我们对 EPA 和 DHA 这两种单一化合物的生理作用的了解是有限的。

研究设计

在这项双盲先导研究中,将 38 名确诊的类风湿关节炎患者分配为食用富含裂殖壶菌的微藻油(2.1gDHA/d)或葵花籽油(安慰剂),共 10 周(交叉),在研究期间维持常规类风湿关节炎药物治疗。

结果

与安慰剂相比,每天摄入 DHA 可使压痛关节和肿胀关节的总数(68/66)从 13.9±7.4 降至 9.9±7.0(p=0.010),总 DAS28 从 4.3±1.0 降至 3.9±1.2(p=0.072),超声评分(US-7)从 15.1±9.5 降至 12.4±7.0(p=0.160)。食用安慰剂产品会导致红细胞脂质(EL)中 n-6PUFA 亚油酸和花生四烯酸(AA)增加(p<0.05)。DHA 补充患者的 EL 中 DHA 量增加了一倍,AA/EPA 和 AA/DHA 的比值显著下降。我们推测,与抗炎/促愈合的 DHA 和 EPA 衍生脂质介质相关的促炎/非愈合 AA 衍生类二十烷酸的产生可能会减少。事实上,由于 DHA 补充,血浆中 AA 衍生的血栓素 B 和血液将 AA 转化为促炎 5-脂氧合酶产物 5-羟二十碳四烯酸的能力显著降低,而 DHA 衍生的maresin/resolvin 前体 14-/17-羟基二十二碳六烯酸的水平显著增加。

结论

该研究首次表明,补充微藻 DHA 可改善类风湿关节炎患者的疾病活动度,并使 AA 和 DHA 衍生的脂质介质之间的平衡向抗炎/促愈合状态转变。

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