Tirosh Oren, Verman Michal, Ivancovsky-Wajcman Dana, Grinshpan Laura Sol, Fliss-Isakov Naomi, Webb Muriel, Shibolet Oren, Kariv Revital, Zelber-Sagi Shira
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
JHEP Rep. 2024 Aug 22;6(11):101194. doi: 10.1016/j.jhepr.2024.101194. eCollection 2024 Nov.
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly related to nutrition. However, only a few human and animal studies have tested the association between MASLD and dairy consumption and the effect of milk fat on liver damage. Therefore, we aimed at testing the association between consumption of dairy product and the incidence of MASLD and fibrosis markers in humans, and the effect of milk fat other fats on MASLD in animal studies.
A prospective 7-year follow-up cohort study was performed including baseline and follow-up fasting blood tests, liver evaluation and a face-to-face interview on health status and behaviour using structured questionnaires. MASLD was determined by ultrasonography or by controlled attenuation parameter (CAP), and liver fibrosis by FibroTest™ or FibroScan®. An animal study was performed in which 6-week-old C57BL/6j male mice were fed a high-fat diet (HFD) consisting of lard, soybean oil, and milk fat for 12 weeks. Metabolic impairment was assessed during the animal experiment, and serum advanced glycation end-products (AGEs) and liver damage were evaluated.
A total of 316 patients were included in the prospective cohort. In multivariable analysis, high consumption of low-medium fat low-sugar dairy products (g/day above the baseline sex-specific median) was associated with a lower risk for MASLD incidence (OR 0.42, 95% CI 0.18-0.95, 0.037) or incidence/persistence at follow-up (OR 0.58, 0.34-0.97, 0.039). Constantly high consumption of high-fat low-sugar dairy products was associated with greater odds for new onset/persistence of MASLD. Neither low-medium nor high-fat dairy consumption was related to fibrosis markers. In mice, all HFDs induced similar weight gain and steatosis and did not affect liver enzymes. Milk fat increases serum cholesterol and AGEs levels more than lard or soybean oil.
Low-medium fat low-sugar dairy products may be protective and should be preferred over high-fat dairy to prevent MASLD. HFDs from different fat sources with a wide spectrum of fatty acid saturation content are equally deleterious.
MASLD is related to nutrition, but evidence of an association between high-fat and low-fat dairy products is lacking, therefore, we evaluated this association by performing experimental studies in mice and an observational human study. For MASLD prevention, a differential effect based on the type of dairy products should be considered: low-medium fat low-sugar dairy products were found to be protective, in contrast high-fat dairy and generally high-fat diets may be harmful. It would be advisable to prefer low-fat low-sugar dairy products and minimise intake of high-fat dairy products; however, additional evidence is needed to allow generalisability of our findings.
代谢功能障碍相关脂肪性肝病（MASLD）与营养密切相关。然而，仅有少数人体和动物研究检验了MASLD与乳制品消费之间的关联以及乳脂肪对肝损伤的影响。因此，我们旨在检验人类乳制品消费与MASLD发病率及纤维化标志物之间的关联，以及在动物研究中乳脂肪和其他脂肪对MASLD的影响。
进行了一项为期7年的前瞻性队列研究，包括基线和随访时的空腹血液检测、肝脏评估，以及使用结构化问卷对健康状况和行为进行面对面访谈。通过超声检查或受控衰减参数（CAP）确定MASLD，通过FibroTest™或FibroScan®确定肝纤维化。进行了一项动物研究，给6周龄的C57BL/6j雄性小鼠喂食由猪油、大豆油和乳脂肪组成的高脂饮食（HFD），持续12周。在动物实验期间评估代谢损害，并评估血清晚期糖基化终产物（AGEs）和肝损伤情况。
前瞻性队列共纳入316例患者。在多变量分析中，高消费中低脂肪低糖乳制品（高于基线性别特异性中位数的克/天）与较低的MASLD发病风险相关（OR 0.42，95%CI 0.18 - 0.95，P = 0.037）或随访时的发病率/持续存在率相关（OR 0.58，0.34 - 0.97，P = 0.039）。持续高消费高脂肪低糖乳制品与MASLD新发/持续存在的几率更高相关。中低脂肪或高脂肪乳制品消费均与纤维化标志物无关。在小鼠中，所有高脂饮食均导致相似的体重增加和脂肪变性，且不影响肝酶。乳脂肪比猪油或大豆油更能增加血清胆固醇和AGEs水平。
中低脂肪低糖乳制品可能具有保护作用，在预防MASLD方面应优于高脂肪乳制品。来自不同脂肪来源、脂肪酸饱和度含量范围广泛的高脂饮食同样有害。
MASLD与营养相关，但缺乏高脂肪和低脂肪乳制品之间关联的证据，因此，我们通过在小鼠中进行实验研究和一项观察性人体研究来评估这种关联。对于MASLD的预防，应考虑基于乳制品类型的差异效应：发现中低脂肪低糖乳制品具有保护作用，相反，高脂肪乳制品和一般高脂饮食可能有害。建议优先选择低脂低糖乳制品并尽量减少高脂肪乳制品的摄入；然而，需要更多证据才能使我们的研究结果具有普遍性。
