Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA.
Am J Clin Nutr. 2020 May 1;111(5):1068-1078. doi: 10.1093/ajcn/nqaa023.
Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of ɣ-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-ɣ-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively.
The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleotide polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA, and ARA.
Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Merr.; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention.
SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03, 2.85) in TT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA.
The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils. This trial was registered at clinicaltrials.gov as NCT02337231.
临床试验中未解释的异质性导致人们对含 γ-亚麻酸（GLA）的植物性油补充剂的有效性产生了疑问。这种异质性可能是由脂肪酸去饱和酶（FADS）基因簇内的遗传变异引起的，该基因簇与花生四烯酸（ARA）和二高-γ-亚麻酸（DGLA）的循环和组织浓度有关，这两种酸都可以从 GLA 合成，并分别产生促炎和抗炎代谢物。
本研究的目的是前瞻性比较非西班牙裔白人群体在关键单核苷酸多态性（SNP）rs174537 处的 FADS 基因型分层后，将琉璃苣油（BO）和大豆油（SO）中的 18 碳 ω-6（n-6）多不饱和脂肪酸转化为 GLA、DGLA 和 ARA 的能力。
健康成年人（n=64）参加了一项随机、双盲、交叉干预研究。个体接受了封装的 BO（琉璃苣 L.；37% LA 和 23% GLA）或 SO[ Glycine max（L.）Merr.；50% LA 和 0% GLA]，为期 4 周，然后在 8 周的洗脱期后，再服用相反的油 4 周。在基线和干预第 2 和第 4 周时，对两种油的血清脂质和炎症标志物（C 反应蛋白）进行评估。
SO 补充剂未能改变任何 n-6 长链多不饱和脂肪酸的循环浓度。相比之下，每日适量的 BO 以依赖 rs174537 基因型的方式升高了血清 GLA 和 DGLA 浓度。特别是，GG 基因型个体的 DGLA 增加了 57%（95%CI：0.38，0.79），而 TT 个体增加了 141%（95%CI：1.03，2.85）。对于 ARA，基线浓度因基因型而异，且随 BO 补充而适度增加，表明 FADS 变异在 DGLA 和 ARA 的平衡中起着关键作用。
本研究的结果清楚地表明，考虑 FADS 遗传变异的个性化和基于人群的方法可能对于优化含 GLA 油的未来临床研究的设计是必要的。该试验在 clinicaltrials.gov 上注册为 NCT02337231。
