A hypocaloric high-protein diet supplemented with β-cryptoxanthin improves non-alcoholic fatty liver disease: a randomized controlled trial

Abstract

Background Despite promising animal data, there is no randomized controlled trial (RCT) on the effects of high protein (HP)-diet and/or β-cryptoxanthin in non-alcoholic fatty liver disease (NAFLD). Aims: Safety and efficacy assessment of a hypocaloric HP-diet supplemented with β-cryptoxanthin in NAFLD. Methods Ninety-two Iranian NAFLD outpatients were recruited for this 12-week, single-center, parallel-group, double-blind RCT and randomized into 4 arms (n = 23): HP-diet and β-cryptoxanthin (hypocaloric HP-diet + β-cryptoxanthin), HP-diet (hypocaloric HP-diet + placebo), β-cryptoxanthin (standard hypocaloric diet + β-cryptoxanthin), and control (standard hypocaloric diet + placebo). Serum levels of liver enzymes and grade of hepatic steatosis were assessed at baseline and study endpoint as outcome measures. Results In the intention-to-treat population (N = 92), HP-diet and β-cryptoxanthin group experienced greater 12-week reductions in serum levels of liver enzymes than control group (mean difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase: − 27.2, − 7.2, − 39.2, and − 16.3 IU/L, respectively; all p < 0.010). Clinical remission rate (achieving grade 0 hepatic steatosis) in HP-diet and β-cryptoxanthin group (82.6%) was also higher than other groups (13.0%, 17.4%, and 0.0% in HP-diet, β-cryptoxanthin, and control groups, respectively; p < 0.001). Sixteen patients reported minor adverse events. Conclusion A hypocaloric HP-diet supplemented with β-cryptoxanthin safely and efficaciously improves NAFLD. Trial registration number This trial was registered at https://www.irct.ir as IRCT2017060210181N10.

Optimized strategy among diet, exercise, and pharmacological interventions for nonalcoholic fatty liver disease: A network meta‐analysis of randomized controlled trials

“…Among the 137 studies 13–145 reported the results of the BMI, serum metabolism profiles (TG, LDL‐C and IR) and liver injury markers were reported. In Figure 4, for BMI, there were 5,572 patients in total, 39 treatment schemes, and another 2,302 patients as the control group (the corresponding network plots are shown in Figure 5A).…”

Dietary Interventions in Liver Diseases: Focus on MAFLD and Cirrhosis

“…Several studies have examined the impact of high-protein diets, often in combination with a hypocaloric regimen and LCD, on hepatic health. In an Iranian study of 92 patients who underwent a hypocaloric high-protein diet (25% of energy intake) with or without the addition of antioxidant βcryptoxanthin, the high-protein groups showed a greater reduction in liver enzymes, but weight loss may have mediated this effect [16]. Among 19 bariatric patients, a hypocaloric high-protein diet (30% of energy intake) over 3 weeks prior to surgery led to a decrease of steatosis by 42.6% compared to no effect under identical energy but lower protein intake [67].…”

Safety, Tolerability, and Pharmacokinetics of β-Cryptoxanthin Supplementation in Healthy Women: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

“…The available human intervention trials examining the effect of β-cryptoxanthin supplementation on a variety of outcomes have reported oral doses ranging from 0.75 mg/day to 6 mg/day [ 14 , 18 , 19 , 20 , 21 ], with no major adverse reactions [ 18 , 20 ]. To date, only one study has involved supplemental ingestion of a β-cryptoxanthin in a purified form [ 18 ], whilst the remaining studies have used beverages or concentrates of tangerine enriched in β-cryptoxanthin [ 14 , 19 , 20 , 21 ]. These studies have reported on a range of endpoints, including the combined effect of β-cryptoxanthin supplements with a hypocaloric diet for 12 weeks on circulating liver enzyme status in NAFLD patients [ 18 ].…”

“…To date, only one study has involved supplemental ingestion of a β-cryptoxanthin in a purified form [ 18 ], whilst the remaining studies have used beverages or concentrates of tangerine enriched in β-cryptoxanthin [ 14 , 19 , 20 , 21 ]. These studies have reported on a range of endpoints, including the combined effect of β-cryptoxanthin supplements with a hypocaloric diet for 12 weeks on circulating liver enzyme status in NAFLD patients [ 18 ]. Further studies examining the actions of a Satsuma mandarin juice extract, containing β-cryptoxanthin, have demonstrated altered bone turnover markers in menopausal women [ 19 ].…”

“…Given the complexity of reported outcomes, the primary objective of this study was to evaluate the pharmacokinetics of a pure oily form of β-cryptoxanthin (15% FS), ingested at a dose of 3 mg/day and 6 mg/day in women of reproductive age for 8 weeks. The dosage for this study was chosen to be comparable with previous supplementation of partially purified and concentrated Satsuma mandarin extracts (3.3–6.0 mg/day) [ 14 , 18 , 19 , 21 ]. The duration of this study was chosen to be 8 weeks, which is comparable with previous supplementation of β-cryptoxanthin (3 to 12 weeks) [ 18 , 19 , 20 , 21 ].…”