Modified Mediterranean diet halves NAFLD risk

A modification of the Mediterranean diet (MED), otherwise called green-MED, may reduce the risk of developing NALFD*, the DIRECT PLUS** trial suggests.

 

“[Several studies] have proven … that MED is the healthiest [diet regimen],” said lead researcher Professor Iris Shai from the Ben-Gurion University of the Negev, Beer-Sheva, Israel. “Now, we have refined that diet and discovered elements that can make dramatic changes to hepatic fat and other key health factors.”

 

Left untreated, NAFLD may progress to steatohepatitis, cancer, and cirrhosis. [J Hepatol 2015;62:S47-S64; Endocr Rev 2008;29:939-960] With no specific drug for NALFD, lifestyle interventions (ie, diet, physical activity) are key for its treatment or prevention. [Therap Adv Gastroenterol 2016;9:392-407] The current findings may improve current dietary protocols for mitigating NAFLD risk, said Shai and colleagues.

 

Apart from the usual plant food sources abundant in MED, green-MED is augmented with specific plant-based, polyphenol-rich elements such as walnuts (28 g daily), green tea (3–4 cups daily), and a Mankai*** green shake (100 grams frozen cubes, as dinner replacement). Consumption of red and processed meat is also restricted.

 

A total of 294 participants (mean age 51 years, 88 percent male) with abdominal obesity and/or dyslipidaemia (BMI 31.3 kg/m2, 62 percent with NAFLD) were randomized 1:1:1 to adhere to healthy dietary guidelines (HDG), MED^#, or green-MED, on top of moderate-intensity physical activity, for 18 months. The trial was conducted in an isolated workplace to facilitate monitored lunches and measurements. [Gut 2021;doi:10.1136/gutjnl-2020-323106]

 

With green-MED, NAFLD prevalence dropped dramatically from 62 percent at baseline to 32 percent at 18 months. With HDG and MED, NAFLD prevalence dropped to 55 percent and 48 percent, respectively (p=0.012 between groups).

 

Compared with baseline, median relative intrahepatic fat (IHF)% loss at 18 months was significantly greater with green-MED (−39 percent) vs HDG and MED (−12 percent and −20 percent, respectively). The comparisons were significant after adjusting for age, sex, and baseline IHF (p=0.023 [green-MED vs MED] and p<0.001 [green-MED vs HDG]).

 

Evidence shows that a low folate level is an independent risk factor for NAFLD. [Clin Nutr 2018;37:1752-1758] In this study, green-MED increased baseline serum folate levels by 1.1 ng/dL at 18 months (p<0.001), which was greater than that seen with HDG (0.4 ng/dL; p=0.01 between groups). IHF% changes were inversely associated with serum folate change (r=−0.16; p=0.02). The greatest IHF reductions were observed among participants in the top serum folate change tertile (p<0.05).

 

Compared with HDG, both MED regimens similarly led to higher levels of total polyphenols (0.47 mg/L vs 0.35 mg/L; p<0.05 for both). Of note was the higher detection of Naringenin – a polyphenol apparently beneficial against liver disease – in the green-MED (65 percent) vs the HDG and MED arms (4 percent and 30 percent, respectively; p=0.001 for both).

 

“Polyphenols might play a role in reducing liver steatosis by preventing hepatocellular damage through several possible mechanisms^##,” said the researchers. “[As such, our] results suggest that a higher intake of specific polyphenol-serum folate-rich components, in addition to a decrease in red/processed meat, might mediate … liver fat [reduction].”

 

“We further report a novel observation linking IHF% change with a compositional shift in the microbiome over 18 months,” they added. IHF reduction was positively correlated with changes in Ruminococcaceae_UCG-014 and Ruminococcaceae_UCG-009 and negatively correlated with change in Ruminococcaceae_UCG-008.

 

Although the shift partially mediated the effect of lifestyle interventions on IHF%, the association was not significant as per mediation analysis. Further exploration is thus warranted to ascertain the role of the Ruminococcaceae genera, as well as other gut microbiome components, in NAFLD pathogenesis and resolution, the researchers noted. “[The] mediatory effect of gut microbiome composition on IHF reduction constitutes an advancement of observations made by others, establishing the association between gut microbiome composition and NAFLD susceptibility.”

 

Conducting the study in a specific workplace enabled close monitoring of the provided lunches, and provided access to free polyphenols and immediate onsite assistance, the researchers noted. Also, the population was relatively large, retention rate was high (~90 percent at 18 months), and IHF% was quantified using noninvasive imaging (H-MRS^###) with high reproducibility and accuracy.

 

However, the predominantly male population may limit extrapolation of the results to women. The findings may also not be generalizable to persons without abdominal obesity and/or dyslipidaemia. “[Also,] only a few phenolic acids derived from dietary polyphenol metabolism will be present in overnight, fasted blood samples [despite having polyphenol measurements],” they said.

 

“[Nonetheless, our findings] may suggest an effective nutritional tool for [NAFLD] treatment … beyond weight loss, a predicament that very little, if any, pharmacological treatment exists for,” they concluded.