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Pletsch-Borba, L.* ; Wernicke, C.* ; Machann, J. ; Meyer, N.M.T.* ; Huong Nguyen, T.* ; Pohrt, A.* ; Hornemann, S.* ; Gerbracht, C.* ; Pfeiffer, A.F.H.* ; Spranger, J.* ; Mai, K.*

Increase in PUFA and protein, and decrease in carbohydrate intake improves liver fat in 12 months and the role of weight loss as a mediator: A randomized controlled trial.

Clin. Nutr. 43, 361-369 (2024)

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BACKGROUND & AIMS: Recently, a beneficial effect of high intake of unsaturated fatty acids (UFA) and protein on intrahepatic lipids (IHL) was demonstrated over 12 months within a randomized controlled trial (the NutriAct trial). We now aimed to explore the specific macronutrient components driving this IHL improvement within this trial in middle-aged and elderly subjects (50-80 y) at risk for age-related diseases. METHODS: The NutriAct trial (n = 502) analyzed the effect of a high-protein and high-UFA diet on age related diseases including fatty liver disease. Individuals who completed 3-day food records with available IHL data both at baseline and at month 12 were included in this analysis. The impact of each macronutrient (E%) on IHL (measured by magnetic resonance spectroscopy) was analyzed by linear regression analyses and mediation analysis. Adherence in the intervention group was defined as intake at month 12 of ≥1 g protein/kg bodyweight or ≥25%E UFA intake; in the control group it was defined as intake of ≥15%E protein or ≥17%E UFA. RESULTS: 248 participants were included in the analyses (34 % male, median age 66 y). Although BMI changed similarly in both groups within 12 months (mean change -0.41 kg/m² in the control and -0.70 kg/m² in the intervention group, p within groups <0.001, p between groups = 0.09), IHL improved more strongly in the compliant intervention participants than in compliant controls (estimate of relative change 0.21 % (95 % CI 0.01, 0.40), p = 0.03). Participants with stronger increase in protein and PUFA intake and a greater decrease in carbohydrate intake showed a stronger improvement in IHL (estimate for linear relative change -0.04 % (95%CI -0.06, -0.02), estimate 4th quartile vs. 1st quartile -0.40 % (95%CI -0.65, -0.16), and 0.32 % (95%CI 0.05, 0.59), respectively). These associations were partially mediated by BMI changes. Increase in PUFA intake was also directly associated with IHL improvement independently of BMI changes (estimate for linear relative change -0.03 % (95%CI -0.05, -0.01)). CONCLUSIONS: Beneficial effects of increased protein and decreased carbohydrate intake on IHL are mediated by BMI changes in middle-aged and elderly subjects. The effect of high PUFA intake on IHL improvement was partly independent of weight loss. These results give insight into the understanding of a macronutrient specific effect on IHL changes in a long-term dietary intervention. CLINICAL TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.

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