The strong prevalence of both non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction has led to the pairing of both syndromes to create the more accurately descriptive MAFLD; a severe liver injury established as a major global health problem.
Modifiable lifestyle factors are key to targeting its multi-factor pathogenesis, with dietary interventions presenting a strong potential for treatment and prevention. Specifically, the key role of oxidative stress in disease development allows for potential hypothesis’ to be made about the beneficial abilities of dietary antioxidants such as flavonoids.
It has previously been reported that intake of these compounds, with sub-classes including isoflavones and anthocyanins, have been associated with a lower prevalence of metabolic disease. Thus, the present cross-sectional study sought to assess the relationship between flavonoid intake and MAFLD prevalence in US adults.
To the researchers' knowledge, this is the first national population based study to evaluate the relationship between flavonoid and subclasses (especially anthocyanins and isoflavones) intake and the risk of MAFLD.
They conclude: "MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD."
The researchers utilised data from 4,341 participants gained from the National Health and Nutrition Examination Survey (NHANES), with flavonoid and subclasses intake calculated using the Food and Nutrient Database for Dietary Studies (FNDDS) of 2017-2018.
Dietary intakes had been assessed by NHANES using two 24 hour dietary recalls, one collected at an initial interview and the second by telephone interview up to 10 days later.
Healthy eating index (HEI)-2015 scores were used to indicate individual dietary quality to enable analysis of the effect of flavonoid intake, utilising multivariate logistic regression to establish associations following adjustment for cofounders.
The overall prevalence of MAFLD was observed to be 41.83%, with diagnosis definitions previously agreed by consensus. Whilst it was observed that there was no association between MAFLD and total flavonoid intake, such associations were observed in the subclasses of anthocyanins and isoflavones.
Higher intakes of anthocyanins were found to be associated with a lower incidence of MAFLD, with significant relationships established in male, non-Hispanic White, and non-Hispanic Asia participants. Furthermore, when compared with the lower quartile of intake, higher isoflavone intake was found to have a protective effect against the disease in those of young age (age < 50), non-Hispanic black, non-Hispanic Asia and higher HEI-2015 scores.
Diet against disease
The study findings suggest that increased consumption of the flavonoid subclasses of anthocyanins and isoflavones may provide protection against MAFLD.
The researchers describe the characterisation of toxic liver accumulation in those with the disease, explaining that “The dysfunction in lipid metabolism leads to the activation of oxidative stress, stimulation of ROS, the release of pro-inflammatory cytokines and apoptotic cell death, and subsequent stimulation of inflammation and fibrogenesis”.
Previous in vitro and animal studies have supported the findings observed here, with the researchers attributing the observations to the anti-inflammatory and antioxidant mechanisms flavonoids exhibit, with anthocyanins reported to increase insulin secretion and decrease plasma LDL, as well as modulating the gut microbiota.
Similarly, Isoflavones have been shown “to modulate oxidative stress, lipid synthesis, fatty acid β-oxidation, peroxisome proliferator-activated receptor α (PPARα) activity, and aldose reductase/polyol production”.
The study exhibits promising data in support of a modifiable lifestyle factor for the prevention of a highly prevalent disease, highlighting a need to focus on flavonoid subclass and their differing mechanisms of action.
In addition, the variation of effects by established risk factor such as gender, age and obesity have further emphasised the need for personalisation in future prevention and treatment interventions.
Whilst the study provides reliable data due to the large, representative sample size used, cause and effect cannot be established due to the study design. Therefore, further RCTs would be required to prove the protective effect.
“Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017–2018”
Junlu Tong, Yingjuan Zeng, Jianhui Xie, Kecen Xiao, Man Li, and Li Cong.