No Difference Between High-Fructose and High-Glucose Diets on Liver Triacylglycerol or Biochemistry in Healthy Overweight Men (original) (raw)
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Different acute effects of fructose and glucose administration on hepatic fat content
The American Journal of Clinical Nutrition, 2018
Background: Diets rich in fat and added sugars (especially fructose) play an important role in the pathogenesis of nonalcoholic liver disease (NAFLD), but there is only limited information on the acute effects of these nutrients on hepatic fat content (HFC). Objectives: We therefore explored how the administration of highfat load, glucose, fructose, and combinations thereof affects HFC measured in vivo using proton magnetic resonance spectroscopy (1 H-MRS) in healthy subjects. Methods: Ten healthy nonsteatotic male volunteers (age 38.5 ± 9.6 y, body mass index [BMI, kg/m 2 ] 26.9 ± 2.7) underwent, in random order, 6 experiments, each lasting 8 h, that included: 1) fasting; 2) a high-fat load (150 g of fat [dairy cream] at time 0); 3) glucose (3 doses of 50 g at 0, 2, and 4 h); 4) a high-fat load with glucose; 5) fructose (3 doses of 50 g at 0, 2, and 4 h); and 6) a high-fat load with fructose. HFC was measured using 1 H-MRS prior to test meal administration (before time 0) and at 3 and 6 h. Plasma concentrations of triglycerides, nonesterified fatty acids, glucose, and insulin were monitored throughout each experiment. Results: HFC increased to 119 ± 19% (P < 0.05) and 117 ± 17% (P < 0.01) of baseline when subjects consumed a high-fat load alone or a high-fat load with fructose, respectively, but was not affected when glucose was coadministered with a high-fat load. HFC was not affected when subjects had fasted or had consumed repeated doses of fructose. When subjects were administered 3 doses of glucose, HFC dropped to 85 ± 13% (P < 0.05) of baseline. Conclusions: Our results demonstrate that fructose and glucose have a different immediate impact on HFC in humans in vivo. Clinical trial registry: The study was registered at clinicaltrials.gov and obtained clinicaltrials.gov identifier: NCT03680248.
Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat
The Journal of clinical endocrinology and metabolism, 2015
Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear if these effects occur independent of positive energy balance and weight gain. We compared the effects of a high-fructose (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose. Eight healthy men were studied as inpatients for consecutive nine-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy. Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average 18.6±1.4% vs. 11.0±1.4% for CCHO, P=0.001) and higher liver fat (median +137% of ...
Diabetes & Metabolism, 2010
The present study aimed to assess the effects of excess fat, fructose and fat-plus-fructose intakes on intrahepatocellular lipid (IHCL). Healthy male subjects were studied after an isocaloric diet or a 7-day high-fructose (Fru: +3.5 g fructose/kg fat-free mass/day, +35% energy), high-fat (Fat: +30% energy as saturated-fat) or high-fructose, high-fat diet (FruFat: +3.5 g fructose/kg fat-free mass/day, +30% energy as fat, +65% total energy). IHCL was measured by (1)H magnetic resonance spectroscopy. All hypercaloric diets increased IHCL (Fru: +16%; Fat: +86%; FruFat: +133%; P<0.05). Very low-density lipoprotein (VLDL) triacylglycerols increased after Fru (+58%; P<0.05), but decreased after Fat (-22%; P<0.05), while no change was observed after FruFat. Fat and fructose both increased IHCL, but fructose increased, while fat decreased, VLDL triacylglycerols. However, excess fat and fructose combined had additive effects on IHCL and neutralizing effects on VLDL triglycerides. This suggests that fructose stimulates, while fat inhibits, hepatic VLDL triacylglycerol secretion.
Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects
The American Journal of Clinical Nutrition, 2019
Background Increased fructose intake has been associated with metabolic consequences such as impaired hepatic lipid metabolism and development of nonalcoholic fatty liver disease (NAFLD). Objectives The aim of this study was to investigate the role of fructose in glucose and lipid metabolism in the liver, heart, skeletal muscle, and adipose tissue. Methods Ten healthy subjects (age: 28 ± 19 y; BMI: 22.2 ± 0.7 kg/m2) underwent comprehensive metabolic phenotyping prior to and 8 wk following a high-fructose diet (150 g daily). Eleven patients with NAFLD (age: 39.4 ± 3.95 y; BMI: 28.4 ± 1.25) were characterized as “positive controls.” Insulin sensitivity was analyzed by a 2-step hyperinsulinemic euglycemic clamp, and postprandial interorgan crosstalk of lipid and glucose metabolism was evaluated, by determining postprandial hepatic and intra-myocellular lipid and glycogen accumulation, employing magnetic resonance spectroscopy (MRS) at 7 T. Myocardial lipid content and myocardial functi...
Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review
Nutrients, 2022
Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease and it is considered the hepatic manifestation of metabolic syndrome (MetS). Diet represents the key element in NAFLD and MetS treatment, but some nutrients could play a role in their pathophysiology. Among these, fructose added to foods via high fructose corn syrup (HFCS) and sucrose might participate in NAFLD and MetS onset and progression. Fructose induces de novo lipogenesis (DNL), endoplasmic reticulum stress and liver inflammation, promoting insulin resistance and dyslipidemia. Fructose also reduces fatty acids oxidation through the overproduction of malonyl CoA, favoring steatosis. Furthermore, recent studies suggest changes in intestinal permeability associated with fructose consumption that contribute to the risk of NAFLD and MetS. Finally, alterations in the hunger–satiety mechanism and in the synthesis of uric acid link the fructose intake to weight gain and hypertension, respective...
European Journal of Clinical Nutrition, 2014
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 X7 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 (þ 21-35% energy) from high-dose fructose (þ 104-220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD ¼ 0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD ¼ 4.94 U/l (95% CI: 0.03, 9.85)). LIMITATIONS: Few trials were available for inclusion, most of which were small, short (p4 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.
Comparison of free fructose and glucose to sucrose in the ability to cause fatty liver
European Journal of Nutrition, 2010
Background-There is evidence that disaccharide sucrose produce a greater increase in serum fructose and triglycerides (TGs) than the effect produced by their equivalent monosaccharides, suggesting that long-term exposure to sucrose or fructose + glucose could potentially result in different effects. Aim of the study-We studied the chronic effects of a combination of free fructose and glucose relative to sucrose on rat liver. Methods-Rats were fed either a combination of 30% fructose and 30% glucose (FG) or 60% sucrose (S). Control rats were fed normal rat chow (C). All rats were pair fed and were followed for 4 months. After killing, blood chemistries and liver tissue were examined. Results-Both FG-fed-and S-fed rats developed early features of metabolic syndrome when compared with C. In addition, both diets induced hepatic alterations, including variable increases in hepatic TG accumulation and fatty liver, an increase in uric acid content in the liver, as well as an increase in hepatic levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factoralpha (TNF-α) measured in liver homogenates. Conclusions-Diets containing 30% of fructose either as free fructose and glucose, or as sucrose, induce metabolic syndrome, intrahepatic accumulation of uric acid and TGs, increased MCP-1 and TNF-α as well as fatty liver in rats. It will be relevant to determine clinically whether pharmacological reduction in uric acid levels might have a therapeutic advantage in the treatment of non-alcoholic fatty liver disease.
Hepatology, 2012
Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP depletion after an intravenous (IV) fructose challenge test in low-versus high-fructose consumers was assessed. We evaluated diabetic adults enrolled in the Action for Health in Diabetes Fatty Liver Ancillary Study (n 5 244) for whom dietary fructose consumption estimated by a 130-item food frequency questionnaire and hepatic ATP measured by phosphorus magnetic resonance spectroscopy and uric acid (UA) levels were performed (n 5 105). In a subset of participants (n 5 25), an IV fructose challenge was utilized to assess change in hepatic ATP content. The relationships between dietary fructose, UA, and hepatic ATP depletion at baseline and after IV fructose challenge were evaluated in low-(<15 g/day) versus high-fructose (!15 g/day) consumers. High dietary fructose consumers had slightly lower baseline hepatic ATP levels and a greater absolute change in hepatic a-ATP/ inorganic phosphate (Pi) ratio (0.08 versus 0.03; P 5 0.05) and c-ATP /Pi ratio after an IV fructose challenge (0.03 versus 0.06; P 5 0.06). Patients with high UA (!5.5 mg/dL) showed a lower minimum liver ATP/Pi ratio postfructose challenge (4.5 versus 7.0; P 5 0.04). Conclusions: High-fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion after an IV fructose challenge. Subjects with high UA show a greater nadir in hepatic ATP in response to fructose. Both high dietary fructose intake and elevated UA level may predict more severe hepatic ATP depletion in response to fructose and hence may be risk factors for the development and progression of NAFLD. (HEPATOLOGY 2012;56:952-960) T he increasing prevalence of nonalcoholic fatty liver disease (NAFLD) parallels the rise in obesity and type 2 diabetes mellitus (T2DM). Patients with obesity and T2DM have not only a higher prevalence, but also more severe forms of NAFLD (i.e., steatohepatitis, hepatic fibrosis, or cirrhosis). 1 The rapid rise in NAFLD supports the role for environmental factors, which, in tandem with predisposing genetic factors, likely contribute to the pathogenesis and epidemic of NAFLD. In recent
Hepatology, 2010
The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency 3 amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (!7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (P < 0.0001), male sex (P < 0.0001), hypertriglyceridemia (P < 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (P < 0.001), increased calorie intake (P < 0.0001), and hyperuricemia (P < 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (P < 0.05 for each). In older adults (age ! 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P 5 0.05). Conclusion: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD. (HEPATOLOGY 2010;51:1961-1971 Abbreviations: AMP, adenosine monophosphate; AMPK, adenosine monophosphate kinase; ATP, adenosine triphosphate; BMI, body mass index; CI, confidence interval; HDL, high-density lipoprotein; HFCS, high-fructose corn syrup; HOMA-IR, homeostasis model assessment of insulin resistance; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; OR, odds ratio.
AJP: Endocrinology and Metabolism, 2010
The objective of this study was to assess the response of a large animal model to high dietary fat and fructose (HFFD). Three different metabolic assessments were performed during 13 wk of feeding an HFFD ( n = 10) or chow control (CTR, n = 4) diet: oral glucose tolerance tests (OGTTs; baseline, 4 and 8 wk), hyperinsulinemic-euglycemic clamps (HIEGs; baseline and 10 wk) and hyperinsulinemic-hyperglycemic clamps (HIHGs, 13 wk). The ΔAUC for glucose during the OGTTs more than doubled after 4 and 8 wk of HFFD feeding, and the average glucose infusion rate required to maintain euglycemia during the HIEG clamps decreased by ≈30% after 10 wk of HFFD feeding. These changes did not occur in the CTR group. The HIHG clamps included experimental periods 1 (P1, 0–90 min) and 2 (P2, 90–180 min). During P1, somatostatin, basal intraportal glucagon, 4 × basal intraportal insulin, and peripheral glucose (to double the hepatic glucose load) were infused; during P2, glucose was also infused intraport...