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. 2023 Feb 1;14(3):475–499. doi: 10.1016/j.advnut.2023.01.001

TABLE 3.

Data extracted from studies included for the updated systematic review investigating the effects of randomized controlled dietary intervention(s) and/or cointervention on inflammatory markers in adults with nonalcoholic fatty liver disease for the intervention effects of cytokines

High-sensitivity C-reactive protein
Reference Diet Unit Preintervention serum concentration Postintervention serum concentration P value Computed change Mean change conc. (95% CI), mg/mL
Dietary intervention alone
Baldry et al. (2017) [46] Very-low energy diet; food-based diet mg/L 8.2 (42.8) 5.1 (21.7) 0.007 −37.8%
Very-low energy diet; meal-replacement plan 9.6 (29.1) 6.4 (21.8) 0.004 −33.3%
Kani et al. (2014) [45] Low calorie mg/L nd nd nd −1.0 ± 0.6b
Low calorie, low carbohydrate nd nd nd −1.1 ± 0.6b
Low calorie, low carbohydrate, soy containing nd nd 0.01 −8.0 ± 1.0b
Marin-Alejandre et al. (2019) [42] Hypocaloric diet (AHA) mg/L 6.5 + 1.9 3.2 + 0.4 0.250 −51.0%
Hypocaloric Mediterranean diet (FLIO) 4.0 + 0.60 1.8 + 0.20 0.001 −55.0%
Marina et al. (2014) [83] Low-fat diet mg/L 3.3 ± 2.8 2.8 ± 2.5 ns −15.1%
High-fat diet 2.3 ± 1.9 2.2 ± 1.2 ns −4.3%
Razavi Zade et al. (2016) [55] Hypocaloric diet mg/L 4.9 ± 3.4 4.6 ± 2.8 0.08 −6.1%
DASH diet 4.8 ± 3.3 3.6 ± 2.7 0.004 −25.0%
Ristic-Medic et al. (2020) [44] Hypocaloric (NIHFN) mg/L 2.10 (0.98,3.20)a 0.77 (0.54,1.27)a 0.008 −63.0%
Hypocaloric Mediterranean diet (NIHFN) 1.02 (0.75,2,23)a 0.81 (0.34,1.40)a 0.000 −21.0%
Dietary intervention plus cointervention
Chan et al. (2010) [51] Hypocaloric diet, Low fat mg/L 2.2 ± 1.3 2.4 ± 1.6 nd 9.1%
Hypocaloric diet, Low fat + cholesterol-lowering agent 3.9 ± 3.8 2.2 ± 2.7 <0.05∗ −43.6%
Kaliora et al. (2016) [81] Isocaloric diet mg/L 2.4 ± 3.0 0.84 ± 1.1 0.023 −65.0%
Isocaloric diet + Corinthian currants 2.1 ± 1.8 0.82 ± 0.7 0.002 −60.9%
Malaguarnera et al. (2010) [69] NCEP-ATPIII mg/L 8.7 ± 3.4 7.4 ± 3.2 ≥ 0.05 −14.9%
NCEP-ATPIII + L-carnitine 9.1 ± 3.2 5.2 ± 3.1 <0.001∗ −42.9%
Dietary intervention plus supplementation
Abedi et al. (2018) [48] Energy-restricted diet plus Vitamin E supplement mg/L 4.1 + 4.6 3.4 + 4.1 0.008 −17.0%
Energy-restricted diet plus CLA and Vitamin E supplement 3.6 + 4.6 2.6 + 3.8 0.001 −28.0%
Abhari et al. (2020) [73] Energy-balanced (NHLBI-EB) plus placebo mg/L 5797.3 ± 3497.5 6049.7 ± 4740.0 0.459 259.67 ± 1274.55b
Energy-balanced (NHLBI-EB) plus synbiotic (B. coagulans) 5183.9 ± 3497.1 4397.5 ± 3616.0 0.119 −793.38 ± 2174.87b
Behrouz et al. (2020) [56] Energy-balanced diet (NHLBI-EB) plus placebo pg/ml 9.2 + 4.5 6.9 + 3.7 0.03 −25.0%
Energy-balanced diet (NHLBI-EB) plus probiotic and prebiotic placebo 9.3 + 4.3 6.3 + 4.9 0.001 −32.0%
Energy-balanced diet (NHLBI-EB) plus prebiotic and probiotic placebo 9.9 + 5.8 6.1 + 5.0 0.001 −38.0%
Cerletti et al. (2020) [57] Mediterranean diet mg/L 2.97 (0.36, 4.67)a 2.52 (1.39, 4.30)a 0.420 −15.0%
Mediterranean diet plus nutraceutical 2.20 (1.40, 4.00)a 17.1 (1.80, 3.20)a 0.120 −19.0%
Darand et al. (2019) [58] Energy balanced diet (NHLBI-EB) plus placebo. mg/L 5057.53 + 3,291.26 4509.86 + 3,288.4 0.480 −11.0%
Energy balanced diet (NHLBI-EB) plus Nigella sativa seed powder supplement 4959.63 + 3,391.89 3514.22 + 3982.89 0.000 −29.0%
Eslami et al. (2019) [40] Hypocaloric diet mg/L 3.51 + 1.3 3.14 + 1.4 0.18 −11.0%
Hypocaloric diet plus soy milk 3.68 + 1.82 2.34 + 1.59 <0.001∗ −36.0%
Eslamparast et al. (2014) [68] Energy-balanced diet (NHLBI-EB) mg/L nd nd −1.04 (−1.5 to −0.6)
Energy-balanced diet (NHLBI-EB) + synbiotic supplement nd nd −2.30 (−3.0 to −1.5)
Faghihzadeh et al. (2014) [60] Energy-balanced diet (NHLBI-EB) mg/L 3.20 + 1.85 3.4 + 2.13 0.861 6.0%
Energy balanced diet (NHLBI-EB) plus trans-resveratrol supplement 3.02 + 1.04 2.11 + 0.96 0.011 −30.0%
Haidari et al. (2020) [61] Energy-restricted normal-protein diet mg/L 4.9 + 1.5 3.5 + 0.1 <0.001∗∗ −29.0%
Energy-restricted normal-protein diet plus BCX 5.0 + 1.9 3.2 + 0.1 <0.001∗∗ −36.0%
Energy-restricted High Protein Diet 4.7 + 1.5 2.6 + 0.1 <0.001∗∗ −45.0%
Energy-restricted High Protein Diet plus BCX 4.8 + 1.9 2.4 + 0.1 <0.001∗∗ −50.0%
Kavyani et al. (2021) [75] Low calorie diet plus placebo ng/mL -1 11.66 ± 2.90 10.23 ± 2.37 nd −12.0%
Low calorie diet plus Camelina Sativa oil & prebiotic 10.49 ± 1.58 8.81 ± 2.29 <0.05 −16.0%
Malaguarnera et al. (2012) [49] Hypocaloric (NCEP-ATPIII) diet mg/L 6.7 + 3.1 6.0 + 3.0 ≥ 0.05 −10.0%
Hypocaloric diet (NCEP-ATPIII) plus probiotic and prebiotic supplement 7.0 + 3.4 4.1 + 3.1 <0.001∗ −41.0%
Mofidi et al. (2017) [70] NHLBI-EB Diet mg/L nd nd −0.42 ± 0.1b
NHLBI-EB Diet plus synbiotic supplement nd nd −1.16 ± 0.4b
Moradi et al. (2021) [76] Energy-restricted diet (AHA) plus placebo mg/L 5.20 ± 2.73 4.75 ± 1.04 0.425 −9.0%
Energy-restricted diet (AHA) plus Chromium Picolinate supplement 4.32 ± 1.42 3.61 ± 1.36 0.004 −16.0%
Nomi-Golzar et al. (2021) [52] Low-calorie diet ng/mL 5.0 ± nd 5.1 ± nd >0.05 2.0%
Low-calorie diet plus Hydroxy-citric acid supplement 4.9 ± nd 5.1 ± nd >0.05 4.0%
Pour et al. (2020) [77] Healthy diet plus placebo ng/mL 5.48 ± 5.17 4.37 ± 3.90 0.248 −20.0%
Healthy diet plus saffron supplement 5.30 ± 4.48 2.49 ± 2.25 <0.01 −53.0%
Rahimlou et al. (2016) [71] NHLBI-EB Diet mg/L 4.8 ± 0.2 2.8 ± 0.2 0.005 −41.7%
NHLBI-EB Diet plus ginger supplement 4.6 ± 0.1 3.4 ± 0.1 0.007 −26.1%
Rafie et al. (2020) [62] NHLBI-EB Diet mg/L 2.26 (1.16,3.98)a 2.12 (0.98,3.78)a 0.128 −-6.0%
NHLBI-EB Diet plus ginger supplement 2.40 (1.14,3.58)a 1.82 (0.88,3.18)a 0.001 −24.0%
Shahmoham-madi et al. (2017) [72] NHLBI-EB Diet mg/L 1.5 (0.4, 2.7)a 1.5 (0.4, 3.0)a 0.846 0.0%
NHLBI-EB Diet plus GCBE supplement 1.4 (0.4, 3.4)a 1.1 (0.5, 2.3)a <0.001∗ −21.4%
Yari et al. (2016) [82] NHLBI-EB Diet mg/L nd nd −1.02 (−1.6 to −0.5)
NHLBI-EB Diet plus flaxseed supplement nd nd −2.05 (−2.6 to 1.5)
Yari et al. (2021) [79] Hypocaloric diet mg/L 3.81 + 3.30 3.04 + 2.67 0.388 −20.0%
Hypocaloric diet plus hesperidin 4.17+ 2.62 2.98 + 2.34 0.005 −28.0%
Hypocaloric diet plus flaxseed 4.68 + 2.04 4.80 + 6.72 0.992 2.0%
Hypocaloric diet plus hesperidin and flaxseed 6.19 + 5.50 4.62 + 4.93 <0.001∗ −25.0%
Interleukin-6
Reference Diet Unit Pre- Post- P value Computed change Mean change (95%CI), mg/mL
Dietary intervention alone
Baldry et al. (2017) [46] Very-low energy diet; food-based diet pg/mL 3.7 (10.4)c 3.7 (25.4)c 0.175 0.0%
Very-low energy diet; meal-replacement plan 4.5 (42.6)c 3.7 (25.4)c 0.04 −17.8%
Marina et al. (2014) [83] Low-fat diet pg/mL 1.08 (1.09)c 1.01 (1.14)c ≥ 0.05 −6.5%
High-fat diet 0.91 (1.4)c 0.83 (2.4)c ≥ 0.05 −8.8%
Markova et al. (2016) [80] Plant-protein isocaloric diet pg/mL 1.4 ± 1.4 1.4 ± 1.5 0.816 −1.4%
Animal protein isocaloric 1.1 ± 1.1 0.9 ± 0.7 0.166 21.7%
Dietary intervention plus cointervention
Chan et al. (2010) [51] Hypocaloric diet, Low fat pg/mL 0.8 ± 0.2 0.9 ± 0.4 ≥0.05 12.5%
Hypocaloric diet, low fat + cholesterol-lowering agent 1.1 ± 0.4 0.9 ± 0.5 <0.05∗ −18.2%
Kaliora et al. (2016) [81] Isocaloric diet pg/mL 1.7 ± 3.2 1.3 ± 1.4 0.322 −23.5%
Isocaloric diet + Corinthian currants 1.6 ± 1.4 0.9 ± 0.5 0.009 −43.7%
Dietary intervention plus supplementation
Abedi et al. (2018) [48] Energy-restricted diet plus Vitamin E pg/mL 23.11 + 16.80 22.10 + 15.78 0.610 −4.0%
Energy-restricted diet plus CLA and Vitamin E 16.18 + 5.95 15.27 + 5.5 0.042 −6.0%
Amanat et al. (2017) [66] Weight-management diet pg/mL 18.2 ± 3.4 18.1 ± 1.8 0.8 0.5%
Weight management + soy isoflavone 18.8 ± 3.1 16.6 ± 2.5 0.01 −11.7%
Duseja et al. (2019) [59] Hypocaloric diet pg/mL 112.8 + 83.7 141.4 + 107.3 0.507 25.0%
Hypocaloric diet plus multistrain probiotic 125.6 + 95.3 100.6 + 74.7 0.041 −20.0%
Faghihzadeh et al. (2014) [60] NHLB-EBI Diet pg/dL 7.22 + 4.73 6.65 + 4.23 0.677 −8.0%
NHLBI-EB Diet plus trans-resveratrol supplement 5.49 + 2.64 3.96 + 1.91 0.034 −28.0%
Ferro et al. (2020) [74] Mediterranean diet plus placebo pg/mL 1.68 ± 0.8 2.57 ± 1.3 <0.001 53.0%
Mediterranean diet plus BPF and CYC 1.92 ± 0.9 3.03 ± 1.3 <0.001 58.0%
Haidari et al. (2020) [61] Energy-restricted normal-protein diet pg/mL 6.1 + 2.2 4.8 + 0.3 <0.001∗∗ −21.0%
Energy-restricted normal-protein diet plus BCX 5.9 + 2.2 4.0 + 0.3 −32.0%
Energy-restricted High Protein Diet 6.6 + 2.2 3.5 + 0.3 −47.0%
Energy-restricted High Protein Diet plus BCX 6.4 + 1.9 3.1 + 0.3 −51.0%
Moradi et al. (2021) [76] Energy-restricted diet plus placebo pg/mL 39.23 ± 16.29 39.57 ± 15.25 0.902 1.0%
Energy-restricted diet plus Chromium Picolinate supplement 36.69 ± 17.70 28.76 ± 14.20 0.002 −22.0%
Rezaei et al. (2019) [64] Hypocaloric diet plus sunflower oil pg/mL 8.5 + 4.5 8.3 + 3.3 0.400 −2.0%
Hypocaloric diet plus olive oil 7.5 + 1.6 7.7 + 1.8 0.400 −3.0%
Rezaei et al. (2020) [65] Hypocaloric diet plus sunflower oil pg/mL 8.4 + 4.5 8.29 + 3.27 0.430 −1.0%
Hypocaloric diet plus flaxseed oil 7.63 + 1.29 7.35 + 0.89 0.100 −4.0%
Tumor necrosis factor-alpha
Reference Diet Unit Pre- Post- P value Computed change Mean change (95% CI), mg/mL
Dietary intervention alone
Markova et al. (2016) [80] Plant-protein isocaloric diet ng/mL 4.5 ± 2.6 3.8 ± 2.4 0.016 −15.6%
Animal protein isocaloric diet 4.3 ± 2.8 4.4 ± 2.2 0.925 2.3%
Dietary intervention plus cointervention
Chan et al. (2010) [51] Hypocaloric, low-fat diet ng/mL 5.4 ± 1.6 5.4 ± 1.9 ≥ 0.05 0.0%
Hypocaloric, low-fat diet + cholesterol-lowering agent 6.3 ± 1.9 5.4 ± 2.3 <0.05∗ −14.3%
Kaliora et al. (2016) [81] Isocaloric diet ng/mL 1.3 ± 1.0 0.8 ± 0.5 0.004 −38.5%
Isocaloric diet + Corinthian currants 0.9 ± 1.0 1.3 ± 0.5 0.063 44.4%
Malguarnera et al. (2010) [69] NCEP-ATPIII diet ng/mL 1.38 ± 0.22 1.30 ± 0.21 ≥ 0.05 −5.8%
NCEP-ATPIII diet + L-carnitine 1.44 ± 0.28 1.08 ± 0.15 <0.001∗ −25.0%
Dietary intervention plus supplementation
Abedi et al. (2018) [48] Energy-restricted diet plus Vitamin E supplement pg/mL 26.59 + 23.28 25.57 + 22.83 0.020 −3.0%
Energy-restricted diet plus CLA and Vitamin E supplement 64.25 + 94.18 37.53 + 51.13 0.010 −41.0%
Abhari et al. (2020) [73] NHLB-EB Diet plus placebo pg/mL 18.4 ± 1.79 16.95 ± 2.37 0.054 −1.68 ± 2.82b
NHLB-EB Diet plus synbiotic (B. coagulans) 17.35 ± 4.89 14.0 ± 1.29 0.010 −3.35 ± 5.24b
Amanat et al. (2017) [66] Weight-management diet ng/mL 1.8 ± 2.6 1.8 ± 2.6 0.990 0.0%
Weight-management diet + soy isoflavone 1.8 ± 2.5 1.6 ± 2.4 0.010 −11.1%
Darand et al. (2019) [58] NHLBI-EB Diet pg/mL 18.68 + 2.18 17.44 + 1.77 0.010 −6.0%
NHLBI-EB Diet plus Nigella sativa seed powder 17.71 + 6.47 14.02 + 1.91 0.010 −21.0%
Duseja et al. (2019) [59] Hypocaloric diet pg/mL 190.00 + 131.10 243.15 + 167.10 0.917 28.0%
Hypocaloric diet plus multistrain probiotic preparation 207.9 + 102.2 107.8 + 94.4 0.911 −48.0%
Eslamparast et al. (2014) [68] NHLBI-EB Diet ng/mL nd nd −0.59 (−0.8 to −0.3)
NHLBI-EB Diet plus synbiotic supplement nd nd −1.4 (−1.7 to −1.1)
Faghihzadeh et al. (2014) [60] NHLBI-EB Diet plus placebo pg/mL 16.55 + 4.79 20.62 + 10.88 0.094 25.0%
NHLBI-EB Diet plus trans-resveratrol supplement 19.96 + 18.80 16.25 + 5.47 0.317 −19.0%
Ferro et al. (2020) [74] Mediterranean diet plus placebo pg/mL 3.08 ± 0.6 1.53 ± 0.8 <0.001 −50.0%
Mediterranean diet plus BPF and CYC 3.56 ± 3.9 2.04 ± 2.4 0.002 −43.0%
Malaguarnera et al. (2012) [49] Hypocaloric (NCEP-ATPIII) diet plus placebo ng/mL 1.24 + 0.26 1.12 + 0.31 ≥ 0.05 −10.0%
Hypocaloric diet (NCEP-ATPIII) plus probiotic and prebiotic supplement 1.28 + 0.28 0.83 + 0.36 <0.001∗ −35.0%
Mofidi et al. (2017) [70] NHLBI-EB Diet ng/mL −0.3 ± 0.2c
NHLBI-EB Diet plus flaxseed supplement −1.22 ± 0.8c
Moradi et al. (2021) [76] Energy-restricted diet plus placebo pg/mL 72.6 ± 34.2 77.2 ± 37.4 0.367 6.0%
Energy-restricted diet plus Chromium Picolinate supplement 89.8 ± 40.8 70.2 ± 39.4 0.501 −22.0%
Pour et al. (2020) [77] Healthy diet plus placebo pg/mL 194.44 ± 99.45 181.60 ± 96.29 0.026 −7.0%
Healthy diet plus saffron supplement 207.31 ± 102.61 193.15 ± 95.10 0.019 −7.0%
Rafie et al. (2020) [62] NHLBI-EB Diet plus placebo pg/mL 11.63 + 1.77 11.57 + 1.23 0.880 0.0%
NHLBI-EB Diet plus ginger supplement 11.71 + 1.02 11.40 + 1.40 0.308 −3.0%
Rahimlou et al. (2016) [71] NHLBI-EB Diet ng/mL 3.0 ± 0.2 2.8 ± 0.2 0.003 −6.7%
NHLBI-EB Diet plus ginger supplement 4.7 ± 0.4 3.5 ± 0.4 0.00 −25.5%
Shahmoham-madi et al. (2017) [72] NHLBI-EB Diet ng/mL 8.2 ± 3.2 8.8 ± 4.1 0.279 7.3%
NHLBI-EB Diet plus GCBE supplement 9.6 ± 3.9 8.6 ± 5.0 0.161 −10.4%
Spadaro et al. (2008) [47] AHA diet ng/mL 3.1 ± 0.4 3.0 ± 0.7 ≥ 0.05 −3.2%
AHA diet + n-3 PUFA supplement 3.3 ± 0.5 2.7 ± 0.5 <0.05 −18.2%
Yari et al. (2016) [82] NHLBI-EB Diet ng/mL −0.14 (−0.07 to −0.2)
NHLBI-EB Diet plus flaxseed supplement −1.30 (−0.4 to 2.2)
Yari et al. (2021) [79] Hypocaloric diet (NHLBI-EB) pg/mL 22.36 + 5.61 20.16 + 5.93 0.037 −10.0%
Hypocaloric diet plus hesperidin 27.87 + 12.69 21.31 + 6.95 0.001 −23.0%
Hypocaloric diet plus flaxseed 19.46 + 5.41 18.97 + 5.64 0.383 −2.0%
Hypocaloric diet plus hesperidin and flaxseed 26.18 + 6.39 19.87 + 4.66 <0.001∗ −24.0%

1Values are mean ± SD or % change (calculated from means) unless otherwise indicated.

2 a Mean (minimum, maximum);

bMean change + SEM.

3∗Statistically significant. P<0.05 significant; ∗∗ Multivariable adjusted.

4AHA, American Heart Association; BCX, β-Cryptoxanthin; CLA, conjugated linoleic acid; FLIO, Fatty Liver in Obesity; NCEP-ATPIII, National Cholesterol Education Program Adult Treatment Panel III; NHLBI-EB, National Heart Lung and Blood Institute-Energy Balanced; NIHFN, National Institute of Health & Food & Nutrition; ns, nonsignificant.