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. 2020 Nov 19;50:101122. doi: 10.1016/j.molmet.2020.101122

Table 2.

Effects of dietary interventions in randomized controlled and randomized parallel group clinical trials demonstrating increases in intrahepatic fat content by magnetic resonance methods.

Diet Design, Ref.
Cohort
N total (males), % NAFLD
BMI (kg/m2)
Intervention
Duration
Δ body mass
vs BL
vs CTRL
Liver TAG Metabolic effects
Monounsaturated fat R/C, [71]
14 (14), 0%
22±1 d
Canola oil vs VCL
Once

Canola oil: ↑ by 33% from -120 min to 240 min (↔ vs -120 min)
VCL: ↑ by 7% from -120 min to 240 min (↔ vs -120 min+ BG)
↔ WB- IS (HEC)
Polyunsaturated fat R/P, [64]
37 (26), 0%
18–27
Habitual diet + high SFA vs high-n-6 PUFA muffins
7 w
SFA: +1.6 kg PUFA: +1.6 kg
SFA: ↑ 58% a
PUFA: ↑ 53% a,f
MRI
PUFA: ↑ 0.22 of HOMA-IR
SFA: ↑ 0.18 of HOMA-IR (↔BG)
NR vs BL
R/P, [65]
61 (21) , NR
PUFA: 30.3 ± 3.7
SFA: 31.3 ± 3.9
n-6 PUFA enriched (15% TE)
SFA enriched (15% TE)
10 w

n-6 PUFA: ↓ 0.9% b
SFA: ↑ 0.3% b,f
MRI/1H-MRS
Both: ↔ SAT + VAT mass (MRI)
BG + vs BL
Saturated fat R/P, [80]
38 (17), NR
31 ± 1
SFA (60% TE)
UFA (59% TE)
CARB (24% TE)
3 w
All: +1.4% e
↔ BG
SFA: ↑ 55%e,f
UFA: ↑ 15%e
CARB: ↑ 33%e
1H-MRS
SFA: ↓ IS e (HEC)
High fat/high protein diets R/C, [70]
10 (10), NR
22.4 ± 0.6
Hypercal+HF (+100% fat intake)
Hypercal+HFHP (+100% fat +>100% protein intake)
Isocal
4 d
HF: ↔
HFHP: +1.1 kg e
↔ BG
HF: ↑ 90% e
HFHP: ↑ 68% a,e,f
1H-MRS
↔ in the fEGP
↔EGP (2-step HEC)
High fat diet R/P, [78]
20 (20), NR
LF: 29.3 ± 0.6
HF: 28.3 ± 0.5
LF (20%TE)
HF (55% TE)
→ LF to HF after 3 w
6 w
NR LF: ↓ 13%
HF: ↑ 17% f
NR vs BL
1H-MRS
↔ IMCLC BG (histology)
↔ IS BG (HEC)
NR vs BL
R/C, [79]
10 (0), NR
33 ± 4
LF (16% TE)
HF (56% TE)
2 w

LF: ↓ 20% ± 9% e
HF: ↑ 35% ± 21% e,f
1H-MRS
↔ VAT + SAT mass (MRI)
BG + vs BL
Energy-dense diet R/P, [66]
36 (36), 0%
19.5–24.5
Habitual diet + 3 L/HF HS
Habitual diet + HS beverage, consumed 3x/d with meals or 2–3 h after meal
6 w
All: +2.5 kg c,e
↔ BG
↔ in groups consuming beverages with meals,
HF HS: ↑ 45%e
HS: ↑ 110%e when consumed between meals (↔ in between meals groups)
1H-MRS
↔ in WB-IS (2-step HEC)
BG+ vs BL
Fructose R/P, [67]
32 (32), NR
Fru 30 ± 1.4 d
Glu 28.9 ± 1.7 d
StdD + Glu (25% TE)
StdD + Fru (25% TE)
2 w
Fru: +1.0 kg e
Glu: +0.6 kg e
↔ BG
Fru: ↑ 24% a,e
Glu: ↑ 26% a,e (↔ BG)
1H-MRS
Fru: ↑ 0.8 f HOMA-IR
Glu: ↑ 0.1f HOMA-IR
R/C, [73]
10 (10), NR
19–25
StdD+Fru (3.5 g/kg/FFM)
StdD+Glu (3.5 g/kg/FFM)
7 d
Fru: +0.6 kga,e
Glu: +1 kga,e
Fru: ↑ 52% ± 13% e
Glu: ↑ 58% ± 23% a
↔ BG
1H-MRS
↔ FG + Ins
Glu: ↑IMCLC (1H-MRS) e,f
Fru: ↔IMCLC
R/C, [74]
9 (9), NR
22.6 ± 0.5
StdD + high Fru (3 g/kg)+PLC (6.6 g/day maltodextrin)
StdD + high Fru (3 g/kg) + AAs (20.3 g/day)
6 d

High-Fru + PLC: ↑
115% a,e
High-Fru+ AAs: ↑ 81% a,e,f
1H-MRS
↔ for glycemia 9 h after oral fructose loading
Beverages R/P, [68]
47 (17) , 0%
26–40
StdD + 1 L/d of cola, semi-skimmed milk, diet cola, or water
24 w
NR
↔ BG
Cola: ↑ 132%–143% vs other groups e
↔ milk, diet cola or water
1H-MRS
Cola: ↑ 24%–31% VAT (dxa) vs other groupse (Significant difference between regular cola + milk)
Cola: ↑ IMCLC (MRS) vs other groupse

Single group assignment studies and non-randomized parallel group studies were excluded.

Subject data presented as mean (±SEM) unless otherwise stated.

AAs: amino acids, ALA: alpha-linolenic acid, BW: body weight, BG: between groups, BL: baseline, BMI: body mass index, CARB: simple sugars, CTRL: control, d: day, DHA: docosahexaenoic acid, dxa: dual-energy X-ray absorptiometry, EA: eicosapentaenoic acid, EGP: endogenous glucose production, fEGP: fasting endogenous glucose production, FFM: free fat mass, FG: fasting glucose, Fru: fructose, g: grams, Glu: glucose, HbA1c: glycated hemoglobin, HEC: hyperinsulinemic euglycemic clamp, HF: high fat, HFHP: high fat high protein, HOMA-IR: homeostasis model assessment of insulin resistance, 1H-MRS: proton magnetic resonance spectroscopy, HS: high sugar, Hypercal: hypercaloric, IMCLC: intramyocellular lipid content, Ins: insulin, IS: insulin sensitivity, isocal: isocaloric, kg: kilograms, LF: low fat, min: minutes, MRI: magnetic resonance imaging, MD: Mediterranean diet, N: number, NA: not assessed, NAFLD: non-alcoholic fatty liver disease, NASH: non-alcoholic steatohepatitis, NEFA: non esterified fatty acids, NR: not reported, PLC: placebo, PUFAs: polyunsaturated fatty acids, Ref: references, R/C: randomized controlled, R/P: randomized parallel group, SAT: subcutaneous adipose tissue, SG: single group assignment study, SFA: saturated fatty acids, StdD: standard diet, TAG: triacylglycerol, T2DM: type 2 diabetes mellitus, TE: total energy, TG: triglycerides, VAT: visceral adipose tissue, UFA: unsaturated fatty acids, VCL: vehicle, vs: versus, w: weeks, WB: whole body.

a

Estimated from table/graph.

b

Median.

c

Pooled data.

d

mean ± SD.

e

Significant effect of intervention (p < 0.05) according to the manuscript.

f

Significant difference between groups (p < 0.05) according to the manuscript.