Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials.

BACKGROUND/OBJECTIVES: In the absence of consistent clinical evidence, there are concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD). To determine the effect of fructose on markers of NAFLD, we conducted a systematic review and meta-analysis of controlled feeding trials. SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 3 September 2013). We included relevant trials that involved a follow-up of ≥ 7 days. Two reviewers independently extracted relevant data. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) for intrahepatocellular lipids (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). RESULTS: Eligibility criteria were met by eight reports containing 13 trials in 260 healthy participants: seven isocaloric trials, in which fructose was exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in which the diet was supplemented with excess energy (+21-35% energy) from high-dose fructose (+104-220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03, 9.85)). LIMITATIONS: Few trials were available for inclusion, most of which were small, short (≤ 4 weeks), and of poor quality. CONCLUSIONS: Isocaloric exchange of fructose for other carbohydrates does not induce NAFLD changes in healthy participants. Fructose providing excess energy at extreme doses, however, does raise IHCL and ALT, an effect that may be more attributable to excess energy than fructose. Larger, longer and higher-quality trials of the effect of fructose on histopathological NAFLD changes are required.

Total sulfur amino acid requirement in young men as determined by indicator amino acid oxidation with L-[1-13C]phenylalanine.

BACKGROUND: Determining the sulfur amino acid (SAA) requirements of humans has remained elusive because of the complex nature of SAA metabolism. Current recommendations are based on nitrogen balance studies. OBJECTIVE: The goal of the present study was to determine the methionine requirement of men fed a diet devoid of cysteine (total SAA requirement). DESIGN: Six men were randomly assigned to receive 6 graded intakes of methionine: 0, 6.5, 13.0, 19.5, 26.0, and 32.0 mg x kg(-1) x d(-1). The total SAA requirement was determined by measuring the oxidation of L-[1-13C]phenylalanine to 13CO2 (F(13)CO2)). The mean total SAA requirement was estimated with use of a linear regression crossover analysis, which identified a breakpoint of the F(13)CO2 response to methionine intake. RESULTS: On the basis of the mean measures of F(13)CO2, the mean requirement and population-safe intake (upper limit of the 95% CI) of total SAAs were found to be 12.6 and 21 mg x kg(-1) x d(-1), respectively. CONCLUSION: Although the mean SAA requirement is consistent with current guidelines for the total SAA intake, the population-safe intake is substantially higher than the currently recommended total SAA intake.

Dietary cysteine reduces the methionine requirement in men.

BACKGROUND: Despite early evidence suggesting that dietary cysteine has a sparing effect on methionine requirements, some recent reports question the existence of a measurable sparing capacity. OBJECTIVE: The goal of the present study was to determine whether dietary cysteine could reduce the requirement for methionine in men consuming diets with and without cysteine. DESIGN: Six men were randomly assigned to receive graded intakes of methionine while fed a diet containing either no exogenous cysteine or an excess of cysteine (21 mg x kg(-1) x d(-1)). The methionine requirement was determined by measuring the oxidation of L-[1-13C]phenylalanine to 13CO2 and estimated by using a linear regression crossover analysis. RESULTS: The mean and population-safe (upper limit of the 95% CI) methionine requirements in the absence of exogenous cysteine were found to be 12.6 and 21 mg x kg(-1) x d(-1), respectively. The mean and population-safe methionine requirements in the presence of excess dietary cysteine were found to be 4.5 and 10.1 mg x kg(-1) x d(-1), respectively, representing a cysteine sparing effect of 64% in a comparison of mean methionine requirements and of 52% in a comparison of population-safe methionine intakes. Furthermore, the difference between population-safe intakes with and without dietary cysteine establishes a safe cysteine intake of 10.9 mg x kg(-1) x d(-1) in the presence of adequate methionine intakes. CONCLUSION: Our data suggest that dietary cysteine can reduce the exogenous requirement for methionine in men. These results strongly support the existence of a cysteine sparing effect in humans.

Comparison of deuterium incorporation and mass isotopomer distribution analysis for measurement of human cholesterol biosynthesis.

To compare endogenous cholesterol biosynthesis measured by deuterium incorporation (DI) and mass isotopomer distribution analysis (MIDA), cholesterol fractional and absolute synthetic rates were measured simultaneously by both techniques under identical physiological conditions. Twelve subjects (22 to 39 years of age) underwent a dual stable isotope protocol, involving oral deuterium oxide administration and measurement of incorporation of deuterium into cholesterol coincident with constant infusion of sodium [1-(13)C]acetate and measurement of the mass isotopomer distribution pattern of newly synthesized cholesterol. Synthesis was determined over 24 h with a 7-h feeding period. Both methods yielded similar measurements of fractional cholesterol synthesis (7.8 +/- 2.5% day(-)(1) for DI vs. 6.9 +/- 2.2% day(-)(1) for MIDA). Correlation of fractional synthesis across techniques was strong (r = 0.84, P = 0.0007). Absolute synthesis rates were also not different at 24 h (13.4 +/- 4.3 mg kg(-)(1) day(-)(1) for DI vs. 11.9 +/- 3.6 mg kg(-)(1) day(-)(1) for MIDA, r = 0.79, P < 0.002). We conclude that despite different assumptions and analytical requirements, deuterium incorporation and MIDA yield similar rates of cholesterogenesis in humans when measurements are made over 24 h. The decision as to which method to adopt depends on available clinical and analytical facilities

Weight loss due to energy restriction suppresses cholesterol biosynthesis in overweight, mildly hypercholesterolemic men.

Mechanisms explaining the decrease in circulatory cholesterol levels after weight loss remain ill defined. The objective was to examine effects of weight loss as achieved through energy restriction upon human in vivo cholesterol biosynthesis. Six subjects (64-77 y, body mass index, 30.3 +/- 3.8 kg/m(2)) were recruited into a two-phase prospective clinical trial. In the first phase, subjects complied with American Heart Association (AHA) Step I diets for 3 mo with no change in their usual energy intake. After this weight-stable phase, subjects consumed an AHA Step I diet with a targeted reduction in energy intake of approximately 1000 kJ/d for 6 mo to achieve negative energy balance leading to weight loss. The incorporation rate of deuterium from body water into erythrocyte membrane free cholesterol over 24 h was utilized as an index of cholesterogenesis at the end of both phases. Subjects' mean weights decreased (P < 0.05) from 89.3 +/- 12.5 kg to 83.2 +/- 11.5 kg (6.8 +/- 2.6% of initial body weight) across phases. Circulating concentrations of total and LDL-cholesterol, and triglycerides also decreased (P < 0. 05) across phases. HDL-cholesterol concentrations were unchanged (P > 0.05). Cholesterol fractional synthetic rate (FSR) after phase 2 (3.04 +/- 1.90%/d) was lower (P < 0.05) than that after phase 1 (8. 42 +/- 3.90%/d). Absolute synthesis rate (ASR) after phase 2 [0.59 +/- 0.38 g/(kg. d)] also was lower (P < 0.05) than that after phase 1 [1.66 +/- 0.84 g/(kg. d)]. These data suggest that, in obese men, energy restriction resulting in even modest weight loss suppresses endogenous cholesterol synthesis, which contributes to a decline in circulating lipid concentrations.