脂肪肝(专业版)
非酒精性脂肪肝(NAFLD)是一种与肥胖相关的慢性进展性肝脏疾病,通常是指不饮酒的人的脂肪堆积在肝脏中形成的一种疾病。NAFLD是一种很常见的健康状况,严重威胁着许多人的健康。
英文名称:Nonalcoholic Fatty Liver Disease,NAFLD;Nonalcoholic Steatohepatitis
定义
非酒精性脂肪肝(NAFLD)是一种与肥胖相关的慢性进展性肝脏疾病,通常是指不饮酒的人的脂肪堆积在肝脏中形成的一种疾病。NAFLD是一种很常见的健康状况,严重威胁着许多人的健康。轻度的NAFLD可能不会引起任何问题,但在某些情况下,脂肪肝可以引起肝脏炎症和纤维化/疤痕即肝硬化。如果控制不当,则可能导致肝衰竭或肝癌。病因
当肝脏不能分解脂肪时,它们就在肝组织中堆积起来形成脂肪肝。NAFLD是存在多个相互关联因素共同作用的结果,包括:- 肥胖导致胰岛素抵抗增加。
- 循环的脂肪酸(甘油三酯)过多。
- 晚期糖基化终产物(AGEs)等,引起氧化应激并长期存在,导致肝组织炎症、细胞死亡和纤维化即疤痕组织。
风险因素
NAFLD在男性中更易发生,并且随着年龄的增长而增加。其他可增加NAFLD几率的因素包括:
此外,NAFLD肝炎更可能在下列群体中发生:
- 老年人
- 糖尿病患者
- 腹部脂肪多的群体
症状
NAFLD通常不会引起症状,如果脂肪堆积导致肝功能异常即出现症状,可能包括:- 肝肿大
- 易疲劳
- 疼痛,腹部的右上侧隐痛
- 食欲不振
- 肌肉无力
- 皮肤发黄,眼白部分也发黄(黄疸症)
- 皮肤瘙痒
并发症
NAFLD主要并发症是肝硬化,这是肝脏后期的瘢痕形成(纤维化)造成的。肝硬化可导致:
- 腹部积液(肝腹水)。
- 食管静脉肿胀,可能会破裂并出血。
- 思维混乱、嗜睡和语言不清(肝性脑病)
- 肝癌
- 终末期肝衰竭,这意味着肝脏已停止运作。
疗法
第一线治疗是通过健康饮食和运动相结合来减轻体重。综合选项可包括如下:
调整饮食和生活方式
- 健康、均衡饮食,包括水果、蔬菜和全谷类食物
- 限制各种甜饮料,因为绝大部分都含果糖
- 不要饮酒过量
- 经常锻炼、保持健康体重
- 睡眠充足
- 学会和运用压力管理,压力大对肝脏不利
营养与草本综合干预
以下是基于循证医学和循证营养学有关文献综合的结果。
有助于防控NAFLD的营养和草本补充剂,主要包括如下:
1.维生素E:
维生素E通过防止脂质氧化有助于降低氧化应激,并因其对NAFLD和NASH(更严重的疾病形式)的可能益处而被广泛研究。一项对8项成人NAFLD随机对照试验的荟萃分析发现,维生素E比安慰剂更好地改善了肝脏病理,降低了肝酶水平。此外,补充维生素E降低了LDL胆固醇和空腹血糖,并提高了瘦素水平,一种在食欲和体重管理中发挥作用的代谢激素1。另一项荟萃分析包括五项针对患有NAFLD的成年人的随机对照试验,持续时间为三个月至四年,其中治疗组每天接受80–1000IU(53–670mg dα-生育酚当量)的维生素E,并结合其他疗法。分析发现,在治疗中加入维生素E改善了肝脏酶水平并减少了脂肪肝的症状2,包括基于活检的评估。
维生素E加吡格列酮(一种抗糖尿病药物)已在多项临床试验中被证明可以有效治疗NASH并减少纤维化3。与维生素E联合使用时显示出良好效果的其他药物包括己酮可可碱4、螺内酯(Aldactone)5。一些新出现的证据表明,携带某种变体的触珠蛋白(一种由肝脏产生的蛋白质)基因的人可能比携带其他变体的人更有可能从维生素E治疗中受益6。如果研究继续支持这种联系,基因检测可能有助于指导未来的治疗。
生育三烯酚是维生素E家族的成员之一,与更为所知的生育酚一起,也被研究了其对NAFLD的影响。在一项针对71名NAFLD患者的随机安慰剂对照试验中,每天两次300mg的δ-生育三烯酚、持续24周,可降低胰岛素抵抗和脂肪肝指数得分。此外,接受δ-生育三烯酚治疗的参与者在肝脏酶水平、炎症和氧化应激标志物以及肝脏脂肪变性的超声评估方面都有所改善7。在另一项试验中,87名NAFLD参与者接受了每天两次200mg混合生育三烯醇(包括61mgα-生育酚)或安慰剂治疗一年。服用生育三烯酚的患者在试验结束时更有可能进行正常的肝脏超声检查8。
2.益生菌:
益生菌是一种活的微生物,摄入足够的量可以促进健康。益生菌可以通过修复肠道屏障功能、缓解肠道微生物组中的微生态失调、减少内毒素诱导的肝损伤以及支持健康的代谢和免疫功能,使NAFLD患者受益9。益生菌在NAFLD或NASH患者的多项临床试验中显示出积极影响。一项对9项随机对照试验(共352名NAFLD受试者)的荟萃分析发现,益生菌治疗降低了肝酶和总胆固醇水平。持续至少三个月的试验表明,益生菌也降低了体重指数(BMI)10。
一项临床试验将52名NAFLD患者随机分配给安慰剂或“合生元”补充剂,每天两次,持续28周。合生元包括2亿CFU来自乳酸杆菌属、双歧杆菌属和链球菌属的7种细菌的组合,以及125mg低聚果糖(一种益生元)。安慰剂组和合生元组都被建议均衡饮食并定期进行体育活动。试验结束时,与服用安慰剂的人相比,合生元组表现出肝酶水平、炎症标志物水平和超声测量的纤维化方面表现出更大的下降11。一项针对50名正常体重NAFLD患者的类似试验发现,与安慰剂相比,同样的益生菌/益生元配方可显著减少肝脏脂肪和纤维化,改善炎症和代谢标志物12。
一项为期12周的随机对照试验,包括68名患有NAFLD和肥胖的参与者,比较了六种益生菌(嗜酸乳杆菌、鼠李糖乳杆菌、副干酪乳杆菌、戊糖球菌、乳双歧杆菌和啤酒双歧杆菌)与安慰剂的混合效果。发现益生菌治疗可减少肝脏脂肪和纤维化,这些影响似乎是由体重减轻介导的13。一项随机对照试验包括50名活检诊断为NASH的患者,该试验发现,用1亿CFU罗伊氏乳杆菌加4g益生元纤维(瓜尔胶和菊粉)治疗三个月,每天两次,可减少磁共振成像评估的肝脂肪变性,以及体重、BMI和腰围,但没有改善肠道通透性或血液内毒素水平14。在另一项试验中,58名NAFLD和2型糖尿病患者在8周内每天接受超过1万亿CFU的由双歧杆菌、乳酸杆菌、乳球菌、丙酸杆菌和醋杆菌菌株组成的14种益生菌的混合物或安慰剂治疗。接受益生菌治疗的患者肝脏酶和一些炎症标志物以及脂肪肝指数评分均下降15。
一项针对111名NAFLD参与者的为期12周的试验发现,与安慰剂相比,益生菌治疗每天两次,使用50亿CFU的五种乳酸杆菌和双歧杆菌菌株的组合,可以降低肝酶和甘油三酯水平16。在一项针对30名NAFLD患者的试验中,保加利亚乳杆菌和嗜热链球菌的5亿个CFU组合在三个月内每天比安慰剂更能降低肝酶水平17。
在一项为期12周的安慰剂对照试验中,一种每天提供10亿个孢子的另一种益生菌菌株凝结芽孢杆菌和菊粉的补充剂被发现可以降低肝脏脂肪(使用超声波技术进行评估)和炎症标志物水平,该试验包括53名NAFLD患者18。
然而,并不是所有的临床试验都发现了积极的效果。在一项针对39名NAFLD患者的为期六个月的试验中,含有300亿CFU的三种乳酸杆菌和三种双歧杆菌菌株的组合的多菌株益生菌不影响任何NAFLD或代谢参数,尽管它确实改善了肠道通透性的标志物19。另一项针对35名NAFLD患者的随机安慰剂对照试验没有发现乳酸杆菌、双歧杆菌和链球菌的八种益生菌菌株的混合物的有益效果,剂量为1.8万亿CFU,每天两次,关于10周后心血管或肝脏健康的标志物20。需要未来的研究来确定改善NAFLD疗效的最佳益生菌菌株和剂量。
3.水飞蓟:
水飞蓟在欧洲作为肝脏保护剂和解毒剂有着悠久的历史。水飞蓟素是从水飞蓟中提取的一种黄酮类复合抗氧化剂,是水飞蓟的主要活性成分21。2021年的一项荟萃分析包括八项随机安慰剂对照试验,共有622名参与者。这些试验持续了8至48个月,每天使用140mg至2100mg的水飞蓟素,大多数试验每天使用280mg的水飞蓟素。分析发现,在患有NAFLD的个体中,水飞蓟素比安慰剂更好地降低肝酶水平22。2017年的荟萃分析也支持了这一点23。在一项随机安慰剂对照试验中,包括99名NASH患者,肝活检显示,在接受700mg水飞蓟素治疗48周的患者中,22.4%的患者纤维化减轻,而接受安慰剂治疗的患者只有6%24。
水飞蓟素还与其他营养素联合应用于NAFLD患者。一项包括78名代谢综合征和NAFLD参与者的随机对照试验发现,每天提供250mg水飞蓟素和60IU维生素E的补充剂,以及饮食和锻炼计划,治疗90天,腰围、BMI、肝脏大小,以及与饮食和运动相比的NAFLD非侵入性测量的得分25。一项针对36名参与者的类似试验进一步指出,饮食和运动加上水飞蓟素/维生素E补充剂降低了γ-谷氨酰转移酶(GGT)的水平,而单纯的饮食和锻炼则不然26。
在一项有25名参与者参加的小型试验中,每天750mg水飞蓟素、200IU维生素E和1000mg L-肉碱的组合持续18周,比安慰剂更能降低血糖和胰岛素水平,改善胰岛素敏感性得分。参与者患有NAFLD、代谢综合征和肝酶水平升高27。在一项对81名受NAFLD影响的参与者的试验中,饮食和生活方式的改变,以及提供350mg乳蓟提取物(含280mg水飞蓟素)、120mg维生素C、40mg维生素E、20mg辅酶Q10的补充剂,83mcg硒持续90天,比单纯的饮食和生活方式更能改善肝脏酶和血脂水平。此外,根据超声成像,51.3%的服用补充剂参与者的肝脂肪变性显著减少,而只有15%的未补充补充剂的受试者的肝脏脂肪变性也有类似的减少28。一项单独的非对照试验对1700多名NAFLD患者进行了随访,发现维生素C、辅酶Q10、硒和硫辛酸的组合具有相似的益处29。
水飞蓟宾是水飞蓟素的主要活性成分之一,作为一种潜在的治疗NAFLD的药物,也受到了研究的关注。一项包括90名NAFLD受试者的对照试验发现,与未经治疗的受试者相比,接受303mg水飞蓟宾、10mcg(400IU)维生素D和15mg维生素E治疗的受测者在代谢标志物、氧化应激、内皮功能和NAFLD进展方面更有可能改善,每天两次,持续六个月。该补充剂对同样患有代谢综合征的参与者的效果更大30。在一项包括270名NAFLD和慢性乙型肝炎感染者的研究中,每天三次70mg水飞蓟宾以及饮食和生活方式计划在24周后比单独的饮食和生活方式改善了基于超声的脂肪肝评估31。
4.欧米伽3脂肪酸:
ω-3多不饱和脂肪酸,特别是来自深海高脂肪鱼类和鱼油的EPA和DHA,在体内被用来合成化合物以解决炎症免疫活性,并可能改善肝脏代谢,对NAFLD发挥保护作用32-34。
评估ω-3脂肪酸对NAFLD患者潜在益处的临床试验结果好坏参半。一项随机对照试验包括56名患有2型糖尿病和NAFLD的受试者,发现在12周内每天两次1000mg ω-3脂肪酸(包括180mg EPA和120mg DHA)改善了与NAFLD相关的血液化学和身体测量,导致用于评估NAFLD存在的三个指标降低,但似乎并没有降低心血管和代谢风险因素35,36。一项为期六个月的小型随机对照试验包括24名NAFLD患者,研究结果表明,通过基于超声波的技术评估,提供1509mg DHA和306mg EPA的鱼油可以改善肝纤维化37。然而,在一项针对104名NAFLD患者的随机对照试验中,每天两次的1250mg鱼油(提供425mg EPA和325mg DHA)在12周后并没有改善肝酶水平、身体成分或其他与心血管和代谢健康相关的因素38。
已经进行了多项荟萃分析,以更好地了解补充ω-3脂肪酸对NAFLD的影响。总的来说,这些荟萃分析包括持续2至24个月的随机对照试验的结果,这些试验使用的ω-3脂肪酸剂量范围为每天250–6000mg。分析发现,用ω-3脂肪酸治疗NAFLD可降低肝脏脂肪变性和肝酶水平,以及BMI、甘油三酯和葡萄糖水平和胰岛素抵抗,并改善代谢状态的其他标志物39-41。
有趣的是,所使用的ω-3的形式可能会影响对NAFLD发展和进展相关因素的影响。2022年一项对38篇学术论文的综述得出结论,临床前研究表明,与甘油三酯形式的ω-3相比,ω-3磷脂具有更显著的对抗肝细胞脂肪堆积的能力。海洋ω-3脂肪酸的替代来源,如磷虾油,通常以磷脂复合物的形式提供ω-3。该综述的作者呼吁进行临床试验,以检查ω-3磷脂对NAFLD发展和进展的影响42。鉴于已发表的证据支持在NAFLD中使用传统形式的ω-3,如乙酯(Ethyl esters)34,一个谨慎的选择可能是与传统形式一起食用ω-3磷脂。
衍生自ω-3脂肪酸并存在于鱼油中的专门的促分解介质(SPMs)也被认为在保护肝脏健康方面发挥着重要作用。SPM,如Resolvins、proteins和maresins,众所周知可以下调和解决炎症过程。某些SPM,包括来源于DHA的17-羟基二十二碳六烯酸(17-HDHA)和来源于EPA的18-羟基二十碳五烯酸(18-HEPE),在临床前研究中也被发现可以减少肝脏中甘油三酯的积累,改善纤维化机制,改善代谢参数32,33。然而,迄今为止,NAFLD的临床研究已经使用了ω-3脂肪酸,而不是直接使用SPM,因此直接SPM治疗的潜在益处需要进一步研究。
5.α硫辛酸:
α硫辛酸是一种抗氧化剂和抗氧化剂循环化合物,可减少代谢性疾病相关炎症并降低糖尿病并发症的风险43,44。在NAFLD参与者中使用硫辛酸作为单一疗法的试验产生了喜忧参半的结果45,46。然而,硫辛酸与胆汁酸结合熊去氧胆酸在一项试验中产生阳性结果。该试验包括120名被建议摄入低热量饮食的NAFLD参与者,他们被分配到四种干预措施中的一种,为期12个月:400mg α-硫辛酸、300mg熊去氧胆酸,400mg α-硫辛酸加300mg熊去氧胆酸,以及安慰剂。在为期12个月的试验结束时,与单独或安慰剂治疗的参与者相比,同时服用硫辛酸和熊去氧胆酸的参与者的肝酶水平、AST/ALT比率和肝纤维化评分下降幅度更大。坚持低热量饮食的人从补充剂组合中获得的好处更为明显47。
6.N乙酰半胱氨酸(NAC):
NAC是氨基酸半胱氨酸的一种,在肝脏中具有众所周知的清除自由基、抗炎和抗毒性作用。许多临床前研究表明,NAC有能力通过减少NAFLD动物模型中的氧化应激和炎症来限制脂肪积累并改善肝功能48。
在一项针对30名NAFLD参与者的临床试验中,三个月后,每天两次服用600mg NAC的参与者的ALT水平下降幅度大于每天两次摄入1000mg维生素C的参与者。NAC治疗也导致脾脏缩小,这可能表明脂肪浸润减少49。另一项针对53名NASH患者的临床试验发现,在二甲双胍治疗48周的基础上,每天添加1200mg NAC,可降低ALT水平、肝脏脂肪、肝细胞膨胀,以及与熊去氧胆酸或熊去氧胆酸加NAC相比用于评估NAFLD活性的评分50。一个研究小组比较了35名NASH患者每天600mg NAC与不治疗的效果,并在一封信中报告了他们的结果。四周后,接受NAC治疗的患者的三种肝酶(ALT、AST和GGT)水平下降,而在不治疗的情况下只有ALT水平下降51。
7.辅酶Q10:
CoQ10是一种遍布全身的化合物,参与线粒体能量的产生,中和自由基,并恢复维生素C和E等抗氧化剂。辅酶Q10因其对心血管疾病的治疗作用而被广泛研究,但它也被证明对退行性疾病和代谢紊乱有重要益处52。一项对318名患有代谢综合征(一种与NAFLD密切相关的疾病)的参与者进行的随机对照试验的荟萃分析发现,补充辅酶Q10增加了脂联素的水平,脂联素是一种由脂肪组织产生的代谢激素,使炎症和氧化应激标志物水平降低53。
临床前证据表明,辅酶Q10有助于调节脂质代谢并抑制肝脏中多余脂肪的积累。160辅酶Q10可以改善代谢并减缓NAFLD的进展,部分是通过改善线粒体功能障碍(NAFLD可能的促成因素),以及减少肝脏氧化应激和炎症54-56。在一项包括44名NAFLD参与者的随机对照试验中,100mg辅酶Q10仅对腰围有显著影响,而体重、代谢和肝脏健康的血液标志物与服用安慰剂的人在四周后没有显着差异,可能是由于试验持续时间短57。另一方面,在一项招募了41名NAFLD参与者的更长的随机对照试验中,补充辅酶Q10(100mg/天)12周后,肝脏酶和炎症标志物水平下降,代谢激素水平提高,NAFLD(基于超声评估)比安慰剂减少得更多58。
8.磷脂酰胆碱:
胆碱是一种在食物和身体中发现的基本营养素,主要作为磷脂磷脂酰胆碱(PC),对脂肪代谢和运输以及细胞结构、细胞信号传导、基因表达调节和神经递质乙酰胆碱的合成是必需的59。PC和其他磷脂对肝脏中的正常脂质代谢是必需的,人类和动物研究表明,饮食中胆碱缺乏会促进肝脏中脂肪的合成和积累,并增加NAFLD的风险59,60。观察证据表明,每天1.8g PC,结合标准护理,可能与肝脏脂肪减少、肝酶水平降低,并改善了同时存在心脏代谢紊乱的NAFLD患者的脂质状况61,62。一项包括29名NAFLD个体的随机对照试验发现,每天450mg PC联合7mg番茄红素(提高PC的生物利用度)治疗两个月,在减少超声检查中肝肿大方面比单独450mg PC更有效63。
9.类胡萝卜素:
类胡萝卜素是在许多水果和蔬菜中发现的黄色和橙色色素。在体内,类胡萝卜素可保护脂质免受氧化损伤,并已被研究其在NAFLD预防和治疗中的可能作用64。多项观察性研究表明,类胡萝卜素摄入量和血液水平的降低与NAFLD风险的增加有关65-68。
在一项对2687名NAFLD中老年受试者进行了为期6年的纵向研究中,较高的血液中类胡萝卜素(包括β-胡萝卜素、α-胡萝卜素、β-隐形黄质、番茄红素和叶黄素加玉米黄质的组合)水平升高,在研究开始时与NAFLD改善的可能性更大相关,而无需进行任何特定干预69。来自NAFLD动物模型的证据也表明,番茄红素、β-隐黄质、叶黄素、玉米黄质、虾青素、岩藻黄素和番红花素可能对肝脏脂肪代谢有有益影响66,70。
在一项包括40名NAFL或NASH参与者的随机安慰剂对照试验中,连续12周每天3mgβ-隐黄质降低了肝脏相关酶GGT的水平,改善了氧化应激和炎症的测量。研究作者还观察到,NASH患者的基线β-隐黄质水平低于NAFL患者71。
10.大蒜:
大蒜含有活性有机硫化合物,被认为是其抗炎、降胆固醇和降压作用的原因72。一个研究小组根据一项随机对照试验发表了三份报告,该试验招募了110名NAFLD受试者,并给他们服用400mg大蒜粉,每天两次,持续15周,或服用安慰剂。结果发现可以降低血压和hs-CRP(炎症标志物)的水平73,可以降低超声测量的肝脏脂肪变性,降低肝脏酶水平,改善与脂质和葡萄糖代谢相关的参数74,并与安慰剂相比减轻体重和体脂75。
一项涉及90名参与者的随机对照试验发现,每天1600mg大蒜粉可以改善NAFLD和代谢综合征的参数。大蒜治疗三个月后比安慰剂更能降低血压、腰围、GGT水平、甘油三酯水平、胰岛素水平、胰岛素抵抗和食欲。此外,大蒜显著降低了脂肪肝指数,该指数是根据BMI、腰围、GGT和甘油三酯计算的76。同一研究小组报告称,与安慰剂相比,每天1600mg大蒜,持续三个月,减少了肝脏脂肪(通过超声评估),改善了肝脏酶水平和脂质状况77。它还降低了腰围和体脂,以及改善氧化应激和葡萄糖代谢的标志物78。
11.黄连素:
黄连素(又称小檗碱)是一种生物碱化学物质,存在于许多药用植物中,包括伏牛、白毛茛和俄勒冈葡萄等,历史上一直用于治疗感染和肝脏疾病79。最近,一系列促进健康的作用被归因于小檗碱,包括减少氧化应激、调节免疫功能、减少炎症、调节碳水化合物和脂肪代谢、改善线粒体功能以及影响表观遗传学和微生物组因子79,80。临床前证据表明,黄连素可能是治疗NAFLD和NASH有希望的药物80。
一项荟萃分析包括六项对照试验的结果,共有501名参与者,其中将黄连素或黄连素加二甲双胍与生活方式干预或二甲双胍或其他单独的抗糖尿病药物进行了比较。试验时间为12至18周,每天三次,剂量为300或500mg黄连素。分析发现,黄连素比其他干预措施更能降低甘油三酯水平,并对血脂、葡萄糖和肝酶水平有积极影响81。
一项试验比较了小檗碱治疗联合生活方式干预与单独生活方式干预对80例2型糖尿病合并NAFLD患者NAFLD参数和循环脂质水平的影响。16周后,小檗碱治疗组的体重、BMI、腰围、肝脏脂肪含量、胆固醇和甘油三酯水平都有更大的下降,葡萄糖耐量也有更大的改善。此外,小檗碱治疗显著降低了神经酰胺水平,神经酰胺是一种脂质化合物,可由代谢功能失调的脂肪组织过量产生,并在肝脏中积聚,从而引发肝细胞损伤(尽管神经酰胺在皮肤中是安全的,且功能至关重要)82。
一种含有黄连素和熊去氧胆酸盐(Actigall)(一种用于治疗肝胆疾病的胆汁酸)的联合补充剂,在一项包括100名患有2型糖尿病、超重或肥胖以及NAFLD的受试者的试验中,发现每天两次1000mg的剂量比安慰剂更能降低肝脏脂肪含量、肝脏酶水平和体重,并在18周后改善血糖控制,这些受试者很有可能患NASH83。
尽管在人体临床试验中对黄连素进行了研究,并证明其具有多种代谢益处,但在某些临床前研究的基础上,人们对长期使用黄连素表示担忧84-86。一些证据表明,长期使用黄连素,尤其是高剂量使用,可能会损害特定类型细胞中细胞代谢的特定方面。因此,一般建议不宜长期服用黄连素。
12.姜黄素:
姜黄素具有公认的清除自由基和抗炎特性。越来越多的证据表明,姜黄素可以积极影响代谢健康,并在治疗代谢紊乱中发挥潜在作用,包括2型糖尿病、多囊卵巢综合征、心血管疾病、代谢综合征和NAFLD等87。
最近对随机对照试验结果的荟萃分析表明,姜黄素可以降低肝酶、总胆固醇和低密度脂蛋白胆固醇、葡萄糖、胰岛素和甘油三酯的水平,并改善NAFLD患者的胰岛素抵抗、腰围和BMI88-91。然而,两项安慰剂对照试验发现,在改变生活方式的基础上,每天服用1500mg姜黄素和其他类姜黄素,持续12周,与单独改变生活方式相比,NAFLD或炎症标志物或心血管风险没有统计学上的显著改善92,93。
一项随机对照试验检验了全姜黄粉对NAFLD的影响。该试验包括64名NAFLD患者,他们每天服用2g姜黄或安慰剂。八周后,姜黄比安慰剂更有效地降低肝酶,但根据超声波测量,不会影响肝脏脂肪变性94。尽管姜黄素作为未改性的姜黄粉末服用时生物利用度较差,研究表明,在与胃肠道健康相关的情况下(如NAFLD),在观察到的有益效果中可能存在肠道介导的机制95。
由于姜黄素的生物利用度差,人们使用了各种制备方法来增强姜黄素的吸收,例如添加胡椒碱,用各种类型的纳米脂质包膜将其包裹,或用纳米磷脂将其络合形成植物体96。在一项针对60名NAFLD患者的安慰剂对照研究中,500mg姜黄素和5mg胡椒碱持续12周,可降低腰围、空腹血糖、LDL胆固醇、总胆固醇和肝酶水平。然而,肝纤维化和脂肪变性并没有随着治疗而改变97。另一方面,一项针对70名NAFLD患者的随机对照试验发现,使用超声技术评估,每天500mg姜黄素和相关类姜黄素加上5mg胡椒碱,持续12周,可使肝脂肪变性的严重程度大大降低98。类似的试验也注意到,每天500mg姜黄素加5mg胡椒碱,持续两个月,比安慰剂更能降低NAFLD的严重程度99,100。
多项临床研究表明,每日剂量高达1500mg的姜黄素植物体对NAFLD患者有益101,102。姜黄素植物体,每日剂量250mg(相当于50mg姜黄素),持续两个月,在一项针对80名NAFLD患者的安慰剂对照试验中,发现可以降低肝脂肪和肝酶水平103。在一项包括80名超重和空腹血糖受损(糖尿病前期)患者的安慰剂控制试验中,一种类似的磷脂结合姜黄素制剂,每天提供200mg姜黄素、600mg磷脂和8mg胡椒碱,在56天后,发现其可降低肝脏酶水平,改善NAFLD指数以及葡萄糖和脂质代谢指标104。在一项随机对照试验中,84名患有NAFLD和超重或肥胖的参与者接受了40mg纳米胶囊姜黄素,每天两次或安慰剂;三个月后,服用姜黄素的患者通过超声检查发现,肝脏脂肪变性减少,腰围、炎症标志物、糖脂代谢也有所改善105。
13.绿茶:
绿茶及其主要活性多酚成分(EGCG)以其抗炎和减少氧化应激的特性而闻名。绿茶似乎还可以调节肠道微生物组,改善肠道屏障功能106。临床前证据表明,绿茶提取物可以缓解代谢功能障碍,减少纤维化,抑制癌症的发展,从而有助于减缓或逆转NAFLD的进展107。
一项随机对照试验,包括80名超声诊断为NAFLD且肝酶水平升高的参与者,发现在12周内,每天两次500mg绿茶提取物可使肝脂肪减少67.5%,而安慰剂可减少25%。此外,绿茶提取物可以改善体重、BMI和胰岛素抵抗,以及肝酶、总胆固醇、LDL胆固醇、高密度脂蛋白、甘油三酯和炎症标记物的水平108。另一项针对80名NAFLD患者的随机对照试验发现,在90天内,每天500mg绿茶提取物可以降低ALT和AST水平,而安慰剂则没有109。
在一项小型随机对照试验中,17名被诊断为NAFLD的参与者被发现,每天饮用富含儿茶素(EGCG)的绿茶,提供1080mg EGCG,有多种积极作用:12周后,与接受低儿茶素茶或安慰剂的人相比,接受高儿茶素茶的人在肝脂肪变性的间接测量中有所改善,体脂率较低,ALT(一种肝酶,高水平可以表明肝细胞损伤)和氧化应激标志物(尿8-异前列腺素)水平降低110。2018年对四项临床试验数据的荟萃分析共有234名参与者,发现绿茶或绿茶儿茶素治疗可降低NAFLD患者的肝酶、甘油三酯、总胆固醇和LDL胆固醇水平111。
14.褪黑素:
褪黑素是一种主要由大脑中的松果体产生的激素,是身体昼夜节律(睡眠-觉醒)周期的关键调节因子。它在减少氧化应激、抑制炎症信号传导、调节线粒体功能以及使细胞增殖和细胞死亡正常化方面也发挥着重要作用112,113。基于其已知的作用,研究了补充褪黑素作为NAFLD治疗药物的潜力。
两项荟萃分析表明,褪黑素治疗可改善肝酶水平,特别是在使用四周或更长时间时114,115。在一项45名参与者的随机对照试验中,每天睡前一小时6mg黑素,持续12周,在降低NAFLD严重程度、体重和腰围、肝酶水平、改善炎症和代谢标志物方面比安慰剂更有效116。在一项对42名活检诊断为NASH的患者进行的试验中,每天两次使用5mg褪黑素治疗12周,导致肝酶水平下降,在治疗12周后维持,但在停止褪黑素治疗12周后大部分消失117,118。一项为期14个月的随机对照试验,包括74名活检诊断为NAFLD的参与者,发现服用褪黑素5mg,每天两次,可降低炎症细胞因子水平,以及GGT,甘油三酯和LDL胆固醇水平;在9名自愿接受治疗的参与者中进行的治疗后活检显示,接受治疗的NASH患者肝损伤和炎症得到了缓解。有趣的是,在这项试验中,每天两次接受500mg色氨酸(褪黑素的氨基酸前体)治疗的参与者与接受褪黑素治疗的参与者有相似的改善119。
附注:胰岛素抵抗是导致肝脏脂质积聚的脂肪代谢异常的基本驱动因素。因此,建议还应参考本网站如下专文:
更多内容可点击其个性化的综合干预方案如下:
以及参阅本网如下专文的相关内容:
医疗干预
治疗的重点是针对引起脂肪肝的因素,以及避免损害肝脏。
- 医生可能推荐一些药物来控制引起NAFLD的情况,包括二甲双胍。
- 减肥控体重:体重减去10%,对治疗NAFLD明显有效。医生可能会建议如下方法:
- 健康饮食
- 运动、锻炼
- 行为疗法
- 注意用药
- 手术减肥,如果情况严重
预防
降低患上NAFLD的方法包括:- 通过饮食维持健康体重,主要是增加水果和蔬菜,全谷类和不饱和脂肪等。
- 每天至少30分钟中等程度锻炼、运动。
- 根据医生指导,管理好相关疾病。
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参考来源:
美国梅奥诊所
www.mayoclinic.org
美国肝脏基金会
http://www.liverfoundation.org
美国国立公众健康网
www.medlineplus.gov
美国胃肠病协会
http://www.gastro.org
加拿大胃肠病协会
https://www.cag-acg.org
加拿大肝脏基金会
http://www.liver.ca
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