The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial

Abstract

Background: Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT).

Methods: In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues.

Results: Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m²; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models).

Conclusions: A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.

Trial registration: ClinicalTrials.gov , NCT03020186.

Keywords: Mediterranean; Obesity; Plant-based diet; Polyphenols; Visceral adipose tissue.

Fig. 1

Eighteen-month changes in abdominal adipose tissues (mean (SE)) between the intervention groups (n = 286). After 18 months of intervention, all groups reduced all three abdominal adipose tissues significantly. Significant differences in VAT% change between the green-MED group and MED, as well as HDG groups, were observed after adjustment for age, sex, and waist circumference change. Deep SAT, deep subcutaneous; superficial SAT, superficial subcutaneous; HDG, healthy dietary guidelines; MED, Mediterranean; VAT, visceral adipose tissue. *Significant within-group change vs. baseline at the 0.05 level. **Significant differences between the groups at the 0.05 level

Fig. 2

Multivariate linear regression models were adjusted for age, sex, weight changes, and the three intervention groups. We aimed to identify the independent associations between the changes in abdominal fat depots and biomarkers in multivariate models, adjusted for age, sex, intervention group, and weight loss. While VAT loss was independently associated with an improved lipid profile, the deep SAT loss was independently and significantly associated with beneficial glycemic biomarkers during the intervention (p < 0.05 for all). The association between changes in blood biomarkers and reduction in abdominal fat subdepots is presented by the β standardized coefficient. *p < 0.05 considered statistically significant. HDL-c, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model of insulin resistance; LDL-c, low-density lipoprotein cholesterol

Fig. 3

Multivariate models for the assessment of the associations between nutritional components of the green-MED diet with changes in VAT% adjusted for age and sex. Mankai consumption was adjusted for age and referred to the green-MED group only. Mankai consumption categories (18 months): low/non: ≤ 1/week, medium: 2–3/week, and high: > 3/week; walnut consumption categories (18 months): low/non: 0 to 1–3 times/month, medium: 1–2/week to 3–4/week, and high: more than 5–6/week; serum folate tertiles (of 18-month change in serum folate, ng/dL): lower ≤ − 0.41, medium − 0.40 to 1.46, and top ≥ 1.47; fiber consumption tertiles (18-month change, g): lower ≤ − 6.73, medium − 6.72 to − 0.17, and top ≥ − 0.16; plasma polyphenol tertiles (18 months, mg/L): lower ≤ 0.23, medium 0.24 to 0.47, and top ≥ 0.48; specific polyphenols (urine and plasma) and VAT change after 18 months of intervention adjusted for age and sex: urine urolithin-A delta 18 months compared to baseline (log2) tertiles: T1 ≤ 0, T2 = 0 to 4.92, and T3 = 4.92+. r = − 0.241, p < 0.001, q = 0.00036 (MC -139 metabolites). Plasma Hippuric-acid tertiles (time18, mg/L): T1 ≤ 0.21, T2 = 0.21 to 0.44, and T3 = 0.44+. *Significant differences between the groups at the 0.05 level. VAT, visceral adipose tissue