Obesity is a global health issue characterized by the excessive fat accumulation, leading to an increased risk of chronic noncommunicable diseases (NCDs), including metabolic dysfunction-associated fatty liver disease (MAFLD), which can progress from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, there are no approved pharmacological protocols for prevention/treatment of MAFLD, and due the complexity lying beneath these mechanisms, monotherapies are unlikely to be efficacious. This review article analyzes the possibility that NCDs can be prevented or attenuated by the combination of bioactive substances, as they could promote higher response rates, maximum reaction results, additive or synergistic effects due to compounds having similar or different mechanisms of action and/or refraining possible side effects, related to the use of lower doses and exposures times than monotherapies. Accordingly, prevention of mouse MAFLD is observed with the combination of the omega-3 docosahexaenoic acid with the antioxidant hydroxytyrosol, whereas attenuation of mild cognitive impairment is attained by folic acid plus cobalamin in elderly patients. The existence of several drawbacks underlying published monotherapies or combined trials, opens space for adequate and stricter experimental and clinical tryouts to achieve meaningful outcomes with human applicability.

中文翻译：

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预防 N(M)AFLD 和其他非传染性疾病的联合方案的相关方面

肥胖是一个全球性的健康问题，其特征是脂肪过度积累，导致慢性非传染性疾病（NCD）的风险增加，包括代谢功能障碍相关的脂肪肝病（MAFLD），它可以从单纯性脂肪变性发展为脂肪性肝炎、纤维化、肝硬化和肝细胞癌。目前，尚无批准的预防/治疗 MAFLD 的药理学方案，并且由于这些机制的复杂性，单一疗法不太可能有效。这篇综述文章分析了生物活性物质组合可以预防或减弱非传染性疾病的可能性，因为它们可以促进更高的反应率、最大的反应结果、由于化合物具有相似或不同的作用机制和/或抑制作用而产生相加或协同效应可能的副作用，与使用比单一疗法更低的剂量和暴露时间有关。因此，观察到将omega-3二十二碳六烯酸与抗氧化剂羟基酪醇联合使用可预防小鼠MAFLD，而叶酸加钴胺素可减轻老年患者的轻度认知障碍。已发表的单一疗法或联合试验存在一些缺点，为充分且更严格的实验和临床试验提供了空间，以实现具有人类适用性的有意义的结果。