Effect of Dietary Intervention, with or without Cointerventions, on Inflammatory Markers in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to nonalcoholic steatohepatitis, with inflammatory cytokines and adipokines identified as drivers of disease progression. Poor dietary patterns are known to promote an inflammatory milieu, although the effects of specific diets remain largely unknown. This review aimed to gather and summarize new and existing evidence on the effect of dietary intervention on inflammatory markers in patients with NAFLD. The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane were searched for clinical trials which investigated outcomes of inflammatory cytokines and adipokines. Eligible studies included adults >18 y with NAFLD, which compared a dietary intervention with an alternative diet or control (no intervention) group or were accompanied by supplementation or other lifestyle interventions. Outcomes for inflammatory markers were grouped and pooled for meta-analysis where heterogeneity was allowed. Methodological quality and risk of bias were assessed using the Academy of Nutrition and Dietetics Criteria. Overall, 44 studies with a total of 2579 participants were included. Meta-analyses indicated intervention with an isocaloric diet plus supplement was more effective in reducing C-reactive protein (CRP) [standard mean difference (SMD): 0.44; 95% CI: 0.20, 0.68; P = 0.0003] and tumor necrosis factor-alpha (TNF-α) (SMD: 0.74; 95% CI: 0.02, 1.46; P = 0.03) than an isocaloric diet alone. No significant weighting was shown between a hypocaloric diet with or without supplementation for CRP (SMD: 0.30; 95% CI: -0.84, 1.44; P = 0.60) and TNF-α (SMD: 0.01; 95% CI: -0.43, 0.45; P = 0.97). In conclusion, hypocaloric and energy-restricted diets alone or with supplementation, and isocaloric diets with supplementation were shown to be most effective in improving the inflammatory profile of patients with NAFLD. To better determine the effectiveness of dietary intervention alone on a NAFLD population, further investigations of longer durations, with larger sample sizes are required.

Keywords: adipokines; cytokines; diet; dietary patterns; inflammation; inflammatory markers; nonalcoholic fatty liver disease; nutrition.

FIGURE 1

PRISMA flow chart for study selection.

FIGURE 2

Meta-analyses for subgroup of selected studies assessing the effect of an isocaloric diet and isocaloric diet plus supplementation (A) and hypocaloric diet and hypo caloric diet plus supplement (B) on hs-CRP.

FIGURE 3

Meta-analysis by subgroup of selected studies on the effect of an isocaloric diet (A) or hypocaloric diet (B) on TNF-α when used alone or in conjunction with a supplement.

FIGURE 4

Individual quality assessment of studies according to Academy of Nutrition and Dietetics Quality Criteria Checklist. ¹KEY: Category – Relevance: 1. Implementation; 2. Importance; 3. Common Concern; 4. Feasibility. Category – Validity: 1. Clarity of research question; 2. Selection bias; 3. Study groups comparable; 4. Attrition; 5. Blinding; 6. Transparent and parallel interventions; 7. Validity and reliability of outcomes; 8. Statistical analyses; 9. Conclusions, biases, and limitations adequately described; 10. Funding or sponsorship bias. ²Y, yes; N, no; Ø, unclear

FIGURE 4

Individual quality assessment of studies according to Academy of Nutrition and Dietetics Quality Criteria Checklist. ¹KEY: Category – Relevance: 1. Implementation; 2. Importance; 3. Common Concern; 4. Feasibility. Category – Validity: 1. Clarity of research question; 2. Selection bias; 3. Study groups comparable; 4. Attrition; 5. Blinding; 6. Transparent and parallel interventions; 7. Validity and reliability of outcomes; 8. Statistical analyses; 9. Conclusions, biases, and limitations adequately described; 10. Funding or sponsorship bias. ²Y, yes; N, no; Ø, unclear