营养失调与治疗杂志

抽象的

营养与健康 2017：共轭亚油酸对转诊至 Shariati 医院风湿病研究中心的活动性类风湿性关节炎患者某些骨标志物的影响：一项双盲临床对照试验 - Aryaeian Naheed - 德黑兰医科大学

雅利安·纳希德

背景与目的：类风湿关节炎 (RA) 是一种慢性复发性炎症性多系统疾病，伴有滑膜增生和关节软骨破坏。它是最常见的炎症性关节炎，影响全球约 0.5-1% 的普通人群。RA 已成为研究许多炎症和免疫介导疾病的有用模型。RA 的确切解释尚不清楚。最近，一些研究表明活性氧 (ROS) 可能在 RA 的发病机制中发挥作用。抗氧化剂可以改善 ROS 的破坏性反应。抗氧化剂对抑制与中性粒细胞功能相关的炎症具有​​有益作用，维生素 E 作为一种有效的抗氧化剂具有调节宿主免疫功能的能力，因此它可能对患有 RA 的患者产生积极影响。

共轭亚油酸 (CLA) 是亚油酸的天然异构体，存在于食草动物的肉和奶中。研究表明，它们的抗炎作用可以保护骨骼免受损伤。CLA 的生物活性因其抗癌、抗动脉粥样硬化和抗糖尿病作用以及增加骨量的作用而备受关注。人们已经研究了 CLA 作为抗氧化剂在氧化应激中的作用，以阐明其有益的生理作用。在之前的文章中，我们通过一项随机、双盲安慰剂对照试验报告了 CLA 对 RA 的影响。与服用安慰剂的组相比，服用 CLA 或 CLA 加维生素 E 的组在补充 12 周后疼痛和晨僵明显减少。我们得出结论，CLA 可以改善临床结果；降低脂质过氧化，而不会对 RA 患者的血脂谱和空腹血糖产生负面影响。

Materials & Methods: The present study may be a randomized double-blind clinical test. Subjects included 46 patients with active atrophic arthritis who were divided into two groups. Group I established normal behaviour plus 2 daily 1.25 gram capsules (containing about 2 grams of 9-cis 11-tans isomer and 10-cis 12-tans isomer in ratio of 50-50 CLAs in glycerinated form), Group II received standard treatment plus 2 placebo 1.25 gram capsules containing sunflower-seed oil with high monounsaturated fatty acid . PGE2 was done by competitive enzymatic immunoassay method, IGF-1 was analyzed by IRMA method supported the sandwich method and ALK-P of bone. Before and after intervention the questionnaires about general information and medical record were filled. Nutrition calculation with 24-hour greatest questionnaire about three day’s diet was done. The results were analyzed using SPSS version 18 software.

Biochemical analysis

Blood sample collection: A sample of 15 ml blood was obtained from each patient before the trial and at the top of it. The patients were fast for 12–14 h. Ethylene diamine tetra ethanoic acid as anticoagulant was used for plasma isolation. Plasma α-tocopherol was measured by high-performance liquid chromatography (Cuesta–Sanz method) with a C15 column and ultraviolet–visible detector. Measurement of plasma inflammatory and immunity reactants: Plasma cytokines were done by ELISA method and by human high sensitivity ELISA kits from eBioscience Company [USA] (sensitivities for interleukin-2 (IL-2), IL-4, IL-1, tumor necrosis factor-α (TNF-α) were 0.4, 0.1, 0.05, 0.13 pg/ml, respectively). Matrix metalloproteinase 3 (MMP-3) was measured by human ELISA Platinum kits from Ebioscience Company; sensitivity was 0.008 ng/ml. Citrullinated antibody (CPP-A) was measured by ELISA method for IgG Antibody citrullinated protein and kits produced by Genesis (England) company, and clinical sensitivity was 80%. Hematological values were determined by an automatic blood counter (Beckman Coulter, Miami, USA). Nutrients intakes were estimated using 24 h dietary recall questionnaire before and at the top of the trial for 3 days analyzed by Nutrition IV(San Bruno, CA, USA, Firsty Data Bank) software. the themes were asked to not change their usual diets and physical activities throughout the study, and any changes in their medications were avoided if possible. Compliance with the supplement intake was assessed by counting number of the capsules used and determining changes within the plasma α-tocopherol. Statistics methods:

Differences between the four groups were determined by ANOVA (one-way analysis of variance) for continuous data and therefore the Chi-square test for group data. Log transformation was wont to normalize the abnormal distributions. Differences between before and after data in each group were determined with paired-sample t-test. If the distribution of a variable wasn't normal, Mann–Whitney U-test was wont to compare the differences between two groups and Wilcoxon signed-rank test was performed for every group to match mean values before and after intervention. ANOCVA were wont to adjust the effect of confounding factors. Correlation decided by Pearson test. P < 0.05 was considered as statistically significant. (Version 18; SPSS Inc., Chicago, Il, USA) was used for data analysis. Quantitative values are reported as mean ± variance.

 

Findings: Totally 102 subjects entered to the study, and 87 of them completed the study. Fifteen patients were excluded from the study thanks to either incomplete consumption of prescription drugs (6 patients: 1 in each groups C [CLA] and CE [CLA + Vitamin E], 2 in each groups E [Vitamin E] and P [Placebo]), changing the dose of their antiinflammatory drugs (8 patients: 2 in each groups), or side-effects (1 patient in group C).

There were no significant differences among the four groups at the start of the study regarding age, sex, BMI, daily intake of vitamin E , disease duration and diseases activity score (P > 0.05). Also, the differences between drugs intake (NSAIDS, glucocorticoid and other disease-modifying antirheumatic drugs) weren’t significant between groups (P > 0.05). The Plasma level of α-tocopherol increased significantly in groups E and CE in contrast to the placebo group (P ≤ 0.017, P < 0.023 respectively).

There were no significant differences between groups at the baseline in cytokines IL-2, IL-4, TNF-α, IL-1β, IL-2/IL-4 and citrullinated antibody variables also as white blood corpuscle (WBC). during this study, significant changes weren't seen in neutrophils, lymphocyte, monocytes, eosinophil numbers and BMI after treatment between groups. Decrease in WBC count was significant in group CLA plus vitamin E , and therefore the lymphocytes increased in group P (P ≤ 0.05).

虽然在研究过程中所有组别的TNF-α都有所降低，但仅CE组降低显著（P < 0.05）。IL1β在P组和E组均显著增加，但在CE组降低（P > 0.05），E组IL-1β的增加幅度小于安慰剂组。IL-4在C组、E组、CE组均降低（分别为P = 0.03、P = 0.07和P = 0.003），但在P组无显著变化。所有组别的血浆IL-2水平均无显著变化，但在P组升高，而在其余各组降低（P > 0.05）。IL-2/IL-4在所有组别中均升高，分别为P组、CLA组、E组和CE组P = 0.005、P = 0.016、P = 0.005、P = 0.006，但组间差异均不显著。 P组CCP-A显著升高，CE组显著降低（P≤0.05），E组CCP-A升高幅度小于安慰剂组。P组MMP-3升高，CE组降低（P≤0.05），P组与CE组间差异显著（P=0.018）。除CCP-A和MMP-3外，其余数据组间差异均不显著。

未观察到显著的副作用。有 3 例报告出现胀气（C 组 2 例，CE 组 1 例）。2 例患者通过在用餐期间（而非用餐前）服用药片缓解了胀气，但 C 组中有 1 例患者需要排除。

结论：CLA 可能对萎缩性关节炎患者的骨标志物产生有益作用。因此，为了研究 CLA 对减少 RA 患者以及所有自身免疫和骨病患者的骨密度降低的影响，需要进行更多更长时间的研究，同时评估骨密度。

该研究部分在2017 年 2 月 20 日至 21 日于德国柏林举行的第九届^国际 营养与健康大会上发表。