Mediterranean diet for NAFLD: ‘Greener’ is better

A Mediterranean (MED) diet enriched with polyphenols from Mankai, green tea, and walnuts, plus restricted red and processed meat intake, is a better strategy to treat nonalcoholic fatty liver disease (NAFLD), as suggested in the DIRECT-PLUS study. This ‘greener’ protocol is said to amplify the beneficial effect of the classic MED diet on hepatic fat, beyond weight loss.

In a cohort of individuals with abdominal obesity and dyslipidaemia, adopting a green-MED diet doubled intrahepatic fat (IHF) loss percentage and halved the prevalence of NAFLD, as reflected by increased plasma polyphenols and serum folate, the investigators pointed out. [Gut 2021;doi:10.1136/gutjnl-2020-323106]

Polyphenols help shed excess fat buildup in the liver through several possible mechanisms, including reducing de novo lipogenesis, increasing fatty acid oxidation, and reducing oxidative stress. Folate, on the other hand, is an essential vitamin of the B vitamins family and is involved in the expression of genes that might contribute to the accumulation of lipids in the liver. These micronutrients are naturally present in a wide variety of foods, including vegetables and fruits. [Proc Nutr Soc 2016;75:47-60; Biofactors 2014;40:277-283]

The MED eating pattern, based mainly on consuming olive oil and plant-based foods, is already a good source of polyphenols and folate. And the results of DIRECT-PLUS confirmed the hypothesis that the additional green component could promote further effectiveness in treating NAFLD, beyond the expected beneficial effects of the MED diet, the investigators stated.

“[W]e found an independent association between 18-month IHF percentage reduction and beneficial changes in cardiometabolic, inflammatory parameters, specific gut bacteria, and global microbiota composition, which was also found to have a mediatory role in the association between lifestyle intervention and liver fat reduction,” they continued.

In the 18-month DIRECT-PLUS trial, participants in the green-MED arm were instructed to consume 3–4 cups/day of green tea rich in epigallocatechin gallate (EGCG) and a daily Mankai green shake, made using 100-g frozen cubes of the Wolffia globosa aquatic plant strain, to replace dinner. They also received a 28-g/day serving of walnuts. Altogether, these foods contributed to additional daily polyphenol intake of 800 mg.

Meanwhile, the others were assigned to dietary arms that received standard nutritional counselling to promote a healthy diet (healthy dietary guidelines [HDG] arm) or asked to follow a classic MED eating pattern rich in vegetables, with poultry and fish replacing beef and lamb (MED arm). The latter also included 28 g/day of walnuts (containing 440-mg polyphenols/day; gallic acid equivalents) in their diet. All interventions accompanied a moderate-intensity physical activity component.

There were 294 participants (mean age, 51 years; 88 percent male) in total. At baseline, body mass index was 31.3 kg/m² and the median IHF was 6.6 percent. NAFLD prevalence decreased from 62 percent in the entire population at baseline to 54.8 percent with HDG, 47.9 percent with MED, and 31.5 percent with green-MED after 18 months (p=0.012 between groups).

Both MED arms achieved similar moderate weight loss, but participants in the green-MED arm exhibited an IHF loss that was almost twice that seen in the other arm (−38.9 percent vs −19.6 percent, p=0.035 weight loss adjusted; −12.2 percent in the HDG arm, p<0.001 vs green-MED).

Compared with HDG, both MED arms had significantly higher total plasma polyphenol levels, with higher concentrations of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all).

“Following our previous trials suggesting that the MED diet is favourable to a low-fat diet in terms of cardiometabolic risk and IHF loss, this clinical trial may suggest an effective nutritional tool for the treatment of NAFLD beyond weight loss, a predicament that very little, if any effect, pharmacological treatment exists for,” the investigators said. [N Engl J Med 2008;359:229-241; N Engl J Med 2012;367:1373-1374; Circulation 2018;137:1143-1157]