Dietary Fructose Intake Research Articles

Simulation and Local Parametric Sensitivity Analysis of a Computational Model of Fructose Metabolism

This research utilized a mathematical model of fructose metabolism within the CellDesigner software package to investigate the effects of varying dietary fructose intake on fat metabolism. By simulating different meal patterns with varying levels of fructose, the model provided valuable insights into the relationship between fructose consumption and hepatic triglyceride accumulation. The results demonstrated a clear correlation between increased fructose intake and elevated hepatic triglycerides. Additionally, a local parametric sensitivity analysis identified glyceraldehyde-3-phosphate and pyruvate as key regulatory factors in this process. Importantly, the model accurately simulated changes in fructose concentration and its metabolites, validating its predictive capabilities. These findings underscore the importance of systems biology in elucidating the complex mechanisms underlying nutrition-related diseases. By integrating computational modeling with experimental data, researchers can gain a deeper understanding of how dietary factors influence metabolic pathways and contribute to health outcomes. Ultimately, systems biology holds the promise of enabling personalized nutrition recommendations tailored to individual needs and genetic predispositions.

Dietary Fructose: A Literature Review of Current Evidence and Implications on Metabolic Health.

With the increasing intake of dietary fructose, primarily from sucrose and sweetened beverages, metabolic illnesses such as type 2 diabetes mellitus, hypertension, fatty liver disease, dyslipidemia, and hyperuricemia have become more prevalent worldwide, and there is also growing concern about the development of malignancies. These negative health impacts have been validated in various meta-analyses and randomized controlled trials. In contrast, the naturally occurring fructose found in fruits and vegetables contains only a minimal amount of fructose and, when consumed in moderation, may be a healthier choice. This review focuses on the biology of fructose, including its dietary sources, the physiology of its metabolism, and the pathological basis of various disorders related to high dietary fructose intake.

Association of uric acid and fructose levels in polycystic ovary syndrome.

Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A.

Fructose shields human colorectal cancer cells from hypoxia-induced necroptosis

Recent studies have shown that high dietary fructose intake enhances intestinal tumor growth in mice. Our previous work indicated that glucose enables hypoxic colorectal cancer (CRC) cells to resist receptor-interacting protein (RIP)-dependent necroptosis. Despite having the same chemical formula, glucose and fructose are absorbed through different transporters yet both can enter the glycolytic metabolic pathway. The excessive intake of dietary fructose, leading to its overflow into the colon, allows colonic cells to absorb fructose apically. This study explores the mechanisms behind apical fructose-mediated death resistance in CRC cells under hypoxic stress. Utilizing three CRC cell lines (Caco-2, HT29, and T84) under normoxic and hypoxic conditions with varying fructose concentrations, we assessed lactate dehydrogenase (LDH) activity, RIP1/3 complex formation (a necroptosis marker), and cell integrity. We investigated the role of fructose in glycolytic-mediated death resistance using glycolytic inhibitors iodoacetate (IA, a glycolytic inhibitor to glyceraldehyde 3-phosphate dehydrogenase), and UK5099 (UK, an inhibitor to mitochondrial pyruvate carrier). Our findings reveal that apical fructose prevents the hypoxia-induced RIP-dependent necroptosis in Caco-2 and HT29 cells. Fructose exposure under hypoxia also preserved epithelial integrity. IA, but not UK, blocked fructose-mediated glycolytic metabolite production and necrosis, indicating that anaerobic glycolytic metabolites facilitate death resistance. Notably, fructose treatment upregulated pyruvate kinase (PK)-M1 mRNA in hypoxic Caco-2 and HT29 cells, while PKM2 upregulation was exclusive to HT29 cells. In conclusion, apical fructose utilization through glycolysis effectively inhibits hypoxia-induced RIP-dependent necroptosis in CRC cells, shedding light on potential metabolic adaptation mechanisms in the tumor microenvironment and suggesting novel targets for therapeutic intervention.

Association between different dietary carbohydrates and risk of gallstone: a case-control study in Iranian adults

PurposeDietary components have been mentioned as modifiable risk factors in the development of gallstone disease (GSD), but it has been less addressed. The present study aimed to investigate the potential association between different types of dietary carbohydrate and the risk of gallstone.Design/methodology/approachIn this case-control study 189 patients diagnosed with GSD as a case group and 342 people as a control group were enrolled. Dietary intake of the participants was collected through a 168-item semi-quantitative food frequency questionnaire. Total intakes of calories, macronutrients and different types of carbohydrate were estimated. Crude and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between carbohydrate intake and GSD.FindingsPatients with gallstone consumed significantly more fructose and sucrose and less fiber. After fully adjustment, the logistic regression indicated significant association between GSD with dietary intake of total carbohydrate (OR = 1.65, 95% CI: 1.1–2.4, p = 0.009), sugar (OR = 1.23, 95% CI: 0.8–1.7, p = 0.014), fructose (OR = 2.5, 95% CI: 1.7–3.9, p < 0.001), glucose (OR = 1.9, 95% CI: 1.3–2.9, p = 0.002) and sucrose (OR = 1.37, 95% CI: 0.9–1.6, p = 0.042). Also, increasing intakes of lactose, galactose and maltose were associated with a decrease in the risk of GSD, but not statistically significant, although lactose was close to significance (OR = 0.71, 95% CI: 0.48–1, p = 0.051).Originality/valueThere is a positive and significant relationship between total carbohydrate, sugar, fructose, glucose and sucrose intake and the occurrence of gallstone.

Different concentrations of high fructose corn syrup in broiler diet cause different effects on selected hematological parameters

This study was aimed to explore how the consumption of high fructose corn syrup (HFCS) affects blood parameters of broilers. Total 120 chickens were divided into three groups including 4 subgroups in each with free access to food and water for 42 days. The control group received no additional treatment, while the second and third groups were fed diets containing 5% or 10% HFCS, respectively. On the last day, broilers were euthanized, and 5 mL blood samples were collected for hematological analyses. Results indicated no significant differences in red blood cell (RBC) or hemoglobin (HGB) levels between the control and 5% or 10% HFCS- treated groups. However, 10% HFCS treatment significantly increased packed cell volume (PCV) and mean corpuscular volume (MCV), while 5%-HFCS increased mean corpuscular hemoglobin (MCH) and decreased mean corpuscular hemoglobin concentration (MCHC) compared to the control group. Total leukocyte counts (TLC) and monocyte values remained unaffected by HFCS treatments. Notably, 5% HFCS treatment increased basophil, heterophil, and heterophil/lymphocyte ratio while decreasing lymphocyte. Conversely, 10% HFCS treatment reduced eosinophil and heterophil, increasing lymphocyte counts. In conclusion, our study suggests that dietary fructose intake can modify certain hematological parameters, potentially serving as early indicators of future systemic or metabolic issues.

Impact of Renin Angiotensin System Inhibition on Renal Function in Fructose-induced Salt Sensitive Blood Pressure

Combined dietary intake of fructose with high salt at levels comparable to that in the upper quintile of western population increases blood pressure, decreases glomerular filtration rate, and results in albuminuria and insulin resistance. We tested the hypothesis that chronic treatment with either an angiotensin converting enzyme inhibitor (enalapril) or angiotensin receptor blocker (losartan) will preserve glomerular filtration rate (GFR) and reduce albuminuria. Sprague Dawley rats of both sexes were instrumented with telemetry. After a baseline period on glucose+0.4% NaCl, rats were assigned to the following groups: 20% glucose+0.4%NaCl treated with vehicle (GNS+V) or 20% fructose+4% NaCl and treated with either vehicle (FHS+V), losartan 0.42 mg/kg/hr by osmotic minipump (FHS+L) or enalapril 0.21 mg/kg/hr (FHS+E). The doses of losartan and enalapril were chosen to achieve MAP similar to the control GNS+V group. Body weights did not differ among the groups upon entry into the protocol and increased similarly among the groups. Non-fasting blood glucose was elevated in all groups in both male and female rats. Mean arterial pressure (MAP) was 108±2 mmHg in GNS+V but was elevated in the FHS+V male rats, 118±2 mmHg ( P&lt;0.01). FHS+L and FHS+E displayed MAP similar GNS+V rats: 104±2 and 106±2 mmHg, respectively. GFR assessed by transdermal FITC-sinistrin elimination was similar across all groups: 0.85±0.04 (GNS+V), 0.86±0.08 (FHS+V), 0.94±0.10 (FHS+L), 1.13±0.12 ml/min/100 g bw (FHS+E). Female rats did not display elevated MAP: 108±1 mmHg (FHS+V) vs 105±2 mmHg (GNS+V). Losartan and enalapril did not change MAP, but GFR was higher in female FHS+L rats, 1.14± 0.05, vs GNS+V 0.75±0.06 ( P &lt; 0.05). Thus, male but not female fructose-fed rats on high salt diet display significantly higher blood pressure. Short-term fructose high salt feeding did not change GFR in either male or female rats. RAS inhibition did not impact GFR in male rats, but losartan increased GFR in female rats on high fructose plus high salt diet compared with glucose-fed female rats on normal salt diet. R01 HL163844. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

Fructose intake and its association with relative telomere length: an exploratory study among healthy Lebanese adults.

Shorter relative telomere length (RTL) has been associated with increased incidence of morbidity. Although still disputed, available evidence suggests that dietary factors, including sugar-sweetened beverages (SSB) may be linked with shorter RTL. It was argued that the link between SSB and RTL may be explained by the sugar content of these beverages, and specifically fructose given its impact on oxidative stress and the inflammatory response. However, none of the existing studies have examined the specific link between fructose intake and RTL. This exploratory study aimed at (1) assessing the intake of dietary fructose (total, added and natural) in Lebanese healthy adults and (2) examining dietary fructose as a predictor of short telomere length. Following a cross-sectional design (n = 282), anthropometric and biochemical data were collected. RTL was assessed by utilizing real-time polymerase chain reaction (RT-qPCR) to amplify both telomere and single-copy gene segments. Dietary intake was evaluated using a culture-specific food frequency questionnaire (FFQ). Intakes of added fructose, naturally-occurring fructose, and total fructose were estimated. Mean intakes of added and natural fructose were of 39.03 ± 34.12 and 12.28 ± 8.59 g/day, respectively, representing 4.80 ± 3.56 and 1.78 ± 1.41% of total energy intake (EI). Mean total fructose intake was of 51.31 ± 35.55 g/day, contributing 6.58 ± 3.71% EI. Higher intakes of total and added fructose were significantly associated with shorter RTL 2nd RTL tertile as compared to the 3rd RTL tertile; relative risk ratio (RRR) = 3.10 [95% confidence interval (CI): 1.38, 6.94] and RRR = 2.33 (95% CI: 1.02, 5.36), respectively after adjustment for confounders identified using a directed acyclic graph (DAG). In conclusion, although we could not observe a dose-dependent relation between fructose intakes and RTL shortening and although the study is limited by its small sample size, the findings suggest that total and added dietary fructose intakes may be associated with shorter RTL. Larger studies, of longitudinal nature, are needed to further confirm the study findings.

Association between higher duodenal levels of the fructose carrier glucose transporter-5 and nonalcoholic fatty liver disease and liver fibrosis.

An increased dietary fructose intake has been shown to exert several detrimental metabolic effects and contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). An augmented intestinal abundance of the fructose carriers glucose transporter-5 (GLUT-5) and glucose transporter-2 (GLUT-2) has been found in subjects with obesity and type 2 diabetes. Herein, we investigated whether elevated intestinal levels of GLUT-5 and GLUT-2, resulting in a higher dietary fructose uptake, are associated with NAFLD and its severity. GLUT-5 and GLUT-2 protein levels were assessed on duodenal mucosa biopsies of 31 subjects divided into 2 groups based on ultrasound-defined NAFLD presence who underwent an upper gastrointestinal endoscopy. Individuals with NAFLD exhibited increased duodenal GLUT-5 protein levels in comparison to those without NAFLD, independently of demographic and anthropometric confounders. Conversely, no difference in duodenal GLUT-2 abundance was observed amongst the two groups. Univariate correlation analyses showed that GLUT-5 protein levels were positively related with body mass index, waist circumference, fasting and 2h post-load insulin concentrations, and insulin resistance (IR) degree estimated by homeostatic model assessment of IR (r=0.44; p=0.02) and liver IR (r=0.46; p=0.03) indexes. Furthermore, a positive relationship was observed between duodenal GLUT-5 abundance and serum uric acid concentrations (r=0.40; p=0.05), a product of fructose metabolism implicated in NAFLD progression. Importantly, duodenal levels of GLUT-5 were positively associated with liver fibrosis risk estimated by NAFLD fibrosis score. Increased duodenal GLUT-5 levels are associated with NAFLD and liver fibrosis. Inhibition of intestinal GLUT-5-mediated fructose uptake may represent a strategy for prevention and treatment of NAFLD.

Associations of Dietary Fructose and Sucrose Intake with HbA1c and Anthropometric Measurements in Patients with Type 2 Diabetes Mellitus

Aim. This study aimed to evaluate the associations of daily dietary intake of fructose and sucrose with HbA1c levels and anthropometric measurements in patients with Type 2 diabetes mellitus.&#x0D; Methods. A total of 64 individuals were included in the study. Demographic characteristics, eating habits, frequency of fructose and sucrose source consumption, and dietary intakes were assessed through questioning. Anthropometric measurements, including body weight, height circumference (HtC), waist circumference (WC), hip circumference (HC), neck circumference (NC), wrist circumference (WrC), and mid-upper arm circumference (MUAC), were evaluated. The HbA1c level was categorized into two groups: good glycemic control (HbA1c≤ 7%) and poor (HbA1c&gt; 7%) glycemic control.&#x0D; Results. The mean daily fructose and sucrose intakes were 10.57 ± 8.28 g (2.38 ± 1.96%), and 29.21 ± 24.78 g (6.29 ± 5.35%), respectively. All the anthropometric measurements assessed were lower in the group with good glycemic control; however, only in case of BMI, MUAC, NC, and WrC, these differences were significant. Patients with good glycemic control were found to consume more fruit. Anthropometric measurements were not related to daily fructose intake, but positively associated with sucrose intake and HbA1c levels. Specifically, HbA1c levels were negatively associated with fiber intake and positively associated with sucrose intake. Moreover, HbA1c levels were positively affected by NC and consumption of non-alcoholic carbonated drinks, and negatively affected by WC and consumption of sugar-containing instant coffee.&#x0D; Conclusions. The mean daily fructose intake among diabetics was found to be moderate and sucrose intake was consistent with the recommended range. The level of HbA1c was shown to be associated with all the anthropometric parameters assessed, and it was found that sugar-sweetened beverages could affect the level of HbA1c. However, further studies with larger sample sizes are needed to investigate these relationships more comprehensively.

Abstract 107: Longitudinal Associations Of Dietary Fructose And Psychological Stress With Vascular Aging Index And Incident Cardiovascular Disease Among Us Black And White Adults In The CARDIA Study

Background: Cardiovascular diseases (CVD) is the leading cause of death and disability worldwide. CVD risk increases exponentially with age, largely due to pathophysiological changes within the vasculature. As per AHA’s Life’s Essential 8, modifiable lifestyle factors such as diet and psychological stress are important predictors of CVD. We designed this study to assess how dietary behaviors, specifically sucrose, fructose and sodium, and endured psychological stress in young adult men and women impact the vascular aging index (VAI) and CVD risk by mid-life. Methods: All data were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We used the data from black and white men and women (n=2656) who had undergone carotid artery ultrasound Doppler scans at visit 7 (year 20 of follow-up) and used these measures to calculate the VAI, as shown previously. Baseline demographics, dietary data and stress/depression measures (CES-D scores) were obtained from visits 1 (at enrollment, year 0) and 7 and compared (men vs. women) with Kruskal-Wallis and Pearson’s chi-square tests. Regression analyses were used to assess the predictive value of these variables on VAI. Cox regression analyses were conducted to assess the risk of fatal and non-fatal CVD, hypertensive CVD, and stroke. Results: Significant associations were found for fructose intake (expressed as percent total calories, P=0.042) and BP &gt;30/80 mmHg (P=0.025) at baseline with VAI in men but not women. Conversely, CES-D scores at baseline were significantly associated with VAI in women (P=0.014) but not men. On Cox regression analyses, baseline BMI was significantly associated with the incidence of any CVD (HR=1.065, P &lt;0.001), hypertensive CVD (HR=1.083, P&lt;0.001) and stroke (HR=1.068, P=0.002) 30 years later. Dietary fructose intake recorded in mid-life was significantly associated with the incidence of any CVD (HR=1.041, P=0.044), and having BP &gt;130/80 mmHg at baseline was associated with stroke (HR=1.996, P=0.029). No sex differences were noted in the Cox regression analyses. Conclusion: Our results suggest that in young adult black and white men but not women BMI and fructose consumption, but not sodium are associated with increased VAI and incidence of CVD by mid-life.

Dietary intake of fructose increases purine de novo synthesis: A crucial mechanism for hyperuricemia.

Fructose consumption is a potential risk factor for hyperuricemia because uric acid (UA) is a byproduct of fructose metabolism caused by the rapid consumption of adenosine triphosphate and accumulation of adenosine monophosphate (AMP) and other purine nucleotides. Additionally, a clinical experiment with four gout patients demonstrated that intravenous infusion of fructose increased the purine de novo synthesis rate, which implied fructose-induced hyperuricemia might be related to purine nucleotide synthesis. Moreover, the mechanistic (mammalian) target of rapamycin (mTOR) is a key protein both involved in fructose metabolism and purine de novo synthesis. The present study was conducted to elucidate how fructose influences mTOR and purine de novo synthesis in a hepatic cell line and livers of mice. RNA-sequencing in NCTC 1469 cells treated with 0- and 25-mM fructose for 24 h and metabolomics analysis on the livers of mice fed with 0- and 30-g/kg fructose for 2 weeks were assessed. Gene and protein expression of phosphoribosyl pyrophosphate synthase (PRPSAP1), Glutamine PRPP aminotransferase (PPAT), adenyl succinate lyase (ADSL), adenyl succinate synthetase isozyme-1 (Adss1), inosine-5'-monophosphate dehydrogenase (IMPDH), and guanine monophosphate synthetase (GMPS) was measured. The location of PRPSAP1 and PPAT in the liver was assessed by an immunofluorescence assay. Metabolite profiling showed that the level of AMP, adenine, adenosine, hypoxanthine, and guanine was increased significantly. RNA-sequencing showed that gene expression of phosphoribosyl pyrophosphate synthase (PRPS2), phosphoribosyl glycinamide formyl transferase (GART), AICAR transformylase (ATIC), ADSL, Adss1, and IMPDH were raised, and gene expression of adenosine monophosphate deaminase 3 (AMPD3), adenosine deaminase (ADA), 5',3'-nucleotidase, cytosolic (NT5C), and xanthine oxidoreductase (XOR) was also increased significantly. Fructose increased the gene expression, protein expression, and fluorescence intensity of PRPSAP1 and PPAT in mice livers by increasing mTOR expression. Fructose increased the expression and activity of XOR, decreased the expression of uricase, and increased the serum level of UA. This study demonstrated that the increased purine de novo synthesis may be a crucial mechanism for fructose-induced hyperuricemia.

Skeletal muscle insulin resistance and adipose tissue hypertrophy persist beyond the reshaping of gut microbiota in young rats fed a fructose-rich diet

To investigate whether short term fructose-rich diet induces changes in the gut microbiota as well as in skeletal muscle and adipose tissue physiology and verify whether they persist even after fructose withdrawal, young rats of 30 d of age were fed for 3 weeks a fructose-rich or control diet. At the end of the 3-weeks period, half of the rats from each group were maintained for further 3 weeks on a control diet. Metagenomic analysis of gut microbiota and short chain fatty acids levels (faeces and plasma) were investigated. Insulin response was evaluated at the whole-body level and both in skeletal muscle and epididymal adipose tissue, together with skeletal muscle mitochondrial function, oxidative stress, and lipid composition. In parallel, morphology and physiological status of epididymal adipose tissue was also evaluated. Reshaping of gut microbiota and increased content of short chain fatty acids was elicited by the fructose diet and abolished by switching back to control diet. On the other hand, most metabolic changes elicited by fructose-rich diet in skeletal muscle and epididymal adipose tissue persisted after switching to control diet. Increased dietary fructose intake even on a short-time basis elicits persistent changes in the physiology of metabolically relevant tissues, such as adipose tissue and skeletal muscle, through mechanisms that go well beyond the reshaping of gut microbiota. This picture delineates a harmful situation, in particular for the young populations, posed at risk of metabolic modifications that may persist in their adulthood.

Fructose, a trigger of metabolic diseases?—a narrative review

Worldwide the number of individuals being overweight or obese has dramatically increased during the last decades, which is also associated with a similar dramatic increase of individuals afflicted with metabolic disorders like dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD). Genetic predisposition may account for some of the increases in body weight and the development of metabolic disorders; however, much is probably also related to the changes in physical activity and dietary pattern. Indeed, results of epidemiological studies suggest that a ‘western-type dietary pattern’ composed of highly processed foods, sweetened foods, and beverages, all adding to a low fiber but high sugar and saturated fat intake, may increase the odd of developing overweight and metabolic disorders. Consumption of sugar, and especially, fructose has repeatedly been discussed to be a key contributor to the development of health disturbances including hypertension, dyslipidemia, insulin resistance as well as NAFLD. However, despite intense research effort, the question if and how (high) dietary fructose intake interferes with human health has not yet been fully answered also as findings are sometimes contradictory. In the present narrative review, results of recent studies assessing the effect of fructose consumption on the development of metabolic disorders including hypertension, dyslipidemia, cardiovascular diseases (CVDs), hyperinsulinemia, and NAFLD as well as underlying molecular mechanisms are reviewed, thereby, aiming to further address the question if (high) fructose intake is a trigger of metabolic diseases.

Dietary fructose as a metabolic risk factor

Over the past decades, the role of the intestinal microbiota in metabolic diseases has come forward. In this regard, both composition and function of our intestinal microbiota is highly variable and influenced by multiple factors, of which diet is one of the major elements. Between 1970 and 1990, diet composition has changed and consumption of dietary sugars has increased, of which fructose intake rose by more than 10-fold. This increased intake of sugars and fructose is considered as one of the major risk factors in the developments of obesity and several metabolic disturbances. In this review, we describe the association of dietary fructose intake with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and lipid metabolism. Moreover, we will focus on the potential causality of this altered gut microbiota using fecal transplantation studies in human metabolic disease and whether fecal microbial transplant can reverse this phenotype.

The Association Between Different Types of Dietary Carbohydrates and Colorectal Cancer: A Case-Control Study.

BackgroundSeveral factors such as genetics and dietary intake are involved in the development of colorectal cancer (CRC). Higher intake of dietary carbohydrates may be associated with an increased risk of CRC. This study aimed to investigate the association between different types of dietary carbohydrates and CRC.MethodsThis hospital-based case–control study was carried out from June 2020 to May 2021 on 480 randomly selected participants including 160 CRC patients and 320 healthy controls aged 35–70 years in Firoozgar hospital, Tehran, Iran. Dietary intake was assessed using Food Frequency Questionnaire (FFQ). Nutritionist IV software was used to determine the intake of calorie and various forms of dietary carbohydrates including total carbohydrate, simple sugar, glucose, fructose, galactose, sucrose, lactose, and maltose.ResultsThe average daily intake of calorie, carbohydrates, sugar, glucose, fructose, sucrose, and maltose were significantly higher among CRC cases compared to the controls (All P < 0.05). The logistic regression found significant associations between CRC with dietary intake of carbohydrates (OR = 1.009, CI 95%: 1.003–1.01, P = 0.002), sugar (OR = 1.02, CI 95%: 1.01–1.03, P < 0.001), glucose (OR = 1.06, CI 95%: 1.01–1.11, P = 0.009), fructose (OR = 1.31, CI 95%: 1.19–1.43, P < 0.001), sucrose (OR = 1.19, CI 95%: 1.12.−1.25, P < 0.001), maltose (OR = 9.03, CI 95%: 3.93–20.78, P < 0.001), galactose (OR = 1.31, CI 95%: 1.07–1.6, P = 0.008), and lactose (OR = 1.009, CI 95%: 1.01–1.18, P = 0.02). This association remained significant after adjustment for sex and age (except for galactose and lactose), and additional adjustment for sleep, tobacco, and alcohol level, and further adjustment for calorie intake and body mass index (BMI) (except for glucose).ConclusionsA positive association was found between CRC and dietary intake of carbohydrates, sugar, fructose, sucrose, and maltose. Following a low-carbohydrate, low-sugar diet may help prevent CRC. Future longitudinal studies are warranted to confirm these findings.

Maternal High-Fructose Intake Activates Myogenic Program in Fetal Brown Fat and Predisposes Offspring to Diet-Induced Metabolic Dysfunctions in Adulthood.

Excess dietary fructose intake is a major public health concern due to its deleterious effect to cause various metabolic and cardiovascular diseases. However, little is known about the effects of high-fructose consumption during pregnancy on offspring metabolic health in adulthood. Here, we show that maternal consumption of 20% (w/v) fructose water during pregnancy does not alter the metabolic balance of offspring with a chow diet, but predisposes them to obesity, fatty liver, and insulin resistance when challenged by a high-fat diet. Mechanistically, diet-induced brown fat reprogramming and global energy expenditure in offspring of fructose-fed dams are impaired. RNA-seq analysis of the fetal brown fat tissue reveals that the myogenic pathway is predominantly upregulated in the fructose-treated group. Meanwhile, circulating fructose level is found to be significantly elevated in both fructose-fed dams and their fetuses. Importantly fructose gavage also acutely activates the myogenic program in mice brown fat. Together, our data suggest that maternal high-fructose intake impairs fetal brown fat development, resultantly attenuates diet-induced thermogenesis and causes metabolic disorders in adult offspring probably through inducing myogenic signature in brown fat at the fetal stage.

Dietary fructose and its association with the metabolic syndrome in Lebanese healthy adults: a cross-sectional study

BackgroundEpidemiological studies investigating the association between dietary fructose intake and the metabolic syndrome (MetS) are scarce and have produced controversial findings. This study aimed at (1) assessing total dietary fructose intake in a sample of Lebanese healthy adults, and determining the intake levels of natural vs. added fructose; (2) investigating the association of dietary fructose with MetS; and (3) identifying the socioeconomic and lifestyle factors associated with high fructose intake.MethodsA cross-sectional survey was conducted on a representative sample of adults living in Beirut, Lebanon (n = 283). Anthropometric and biochemical data were collected, and dietary intake was assessed using a food frequency questionnaire. Intakes of naturally-occurring fructose from fructose-containing food sources, such as fruits, vegetables, honey, were considered as “natural fructose”. Acknowledging that the most common form of added sugar in commodities is sucrose or High Fructose Corn Syrup (HFCS), 50% of added sugar in food products was considered as added fructose. Total dietary fructose intake was calculated by summing up natural and added fructose intakes. Logistic regression analyses were conducted to investigate the association of total, added and natural fructose intakes with the MetS and to identify the socioeconomic predictors of high fructose intake.ResultsMean intake of total fructose was estimated at 51.42 ± 35.54 g/day, representing 6.58 ± 3.71% of energy intakes (EI). Natural and added fructose intakes were estimated at 12.29 ± 8.57 and 39.12 ± 34.10 g/day (1.78 ± 1.41% EI and 4.80 ± 3.56% EI), respectively. Participants in the highest quartile of total and added fructose intakes had higher odds of MetS (OR = 2.84, 95%CI: 1.01, 7.94 and OR = 3.18, 95%CI: 1.06, 9.49, respectively). In contrast, natural fructose intake was not associated with MetS. Age, gender and crowding index were identified as factors that may modulate dietary fructose intakes.ConclusionsThe observed association between high added fructose intake and the MetS highlights the need for public health strategies aimed at limiting sugar intake from industrialized foods and promoting healthier dietary patterns in Lebanon.

Fructose ingestion modifies NMDA receptors and exacerbates the seizures induced by kainic acid

Fructose ingestion elicits a diversity of brain alterations, but it is unknown how it affects N-methyl-D-Aspartate receptors (NMDAr). Here, we analyzed the expression of NMDAr subunits and protein kinases after the long-term dietary fructose intake. Since NMDAr are related to epileptogenesis, we also examined whether fructose increases the susceptibility to seizures after the microinjection of kainic acid (KA) in the rat hippocampus. Wistar rats were randomly divided into water (control) and fructose groups. For twelve weeks, groups had ad libitum access to water or fructose solution (10% w/v). After treatment, hippocampal protein expression of NMDAr subunits and protein kinases involved in NMDAr regulation were analyzed. Additionally, electroencephalographic and behavioral changes related to seizures were evaluated after the microinjection of a sub-convulsive dose of KA in the hippocampus. Fructose induced the decrease of NR1 and, conversely, the increase of NR2A subunits expression in the hippocampus. Also, the phosphorylation of protein kinase C alpha (PKCα) and c-Src increased significantly. No electroencephalographic or behavioral patterns related to convulsive motor seizures were observed in the control group. However, all the rats that ingested fructose showed stage 3 seizures (forelimb clonus) and a significant increase in the number of wet-dog shakes. Moreover, electroencephalographic recordings revealed pronounced epileptiform activity and increased total spectral power at 30 and 60 min after the microinjection of KA. This study shows for the first time that fructose intake exacerbates the seizures induced by KA. Therefore, we propose that this proconvulsant effect could be mediated by changes in NMDAr subunits expression and increased activation of kinases modulating NMDAr function.