High Fructose Corn Syrup Intake Research Articles

Effects of Excessive High-fructose Corn Syrup Drink Intake in Middle-aged Mice.

The global prevalence of type 2 diabetes (T2D) continues to increase, necessitating the need for understanding the causes of its development. The widespread use of high-fructose corn syrup (HFCS) in drinks and diets is suspected to play a role in metabolic disorders. Although many studies have reported on the effects of excessive HFCS and excessive energy intakes in middle-aged individuals, few have focused on energy restriction. This study aimed to investigate the effects of excessive HFCS drink intake under energy restriction on developing T2D in early middle-aged mice. Early middle-aged mice were divided in HFCS and control groups; they were provided either 10% HFCS water or deionized water ad libitum for 12 weeks, respectively. Total energy intake was controlled using a standard rodent diet. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), tissue weight measurements, serum parameter analyses, and mRNA expression assessments were performed. No increase in body and adipose tissue weight was observed with excessive HFCS intake under energy restriction. Moreover, serum lipid parameters did not differ from those of controls. However, in the OGTT and ITT, the HFCS group showed higher blood glucose levels than the control group. Moreover, the pancreatic weight and insulin II mRNA expression were reduced. The excessive HFCS drink intake under energy restriction did not induce obesity; however, it induced impaired glucose tolerance, indicating its negative effects on the pancreas in early middle-aged mice. When translated in human physiology, our results show that even if one does not become obese, excessive HFCS may affect the overall metabolic mechanism; these effects may vary depending on age.

Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease

AimsThe developmental origin of health and disease (DOHaD) theory postulates that poor nutrition during fetal life increases the risk of disease later in life. Excessive fructose intake has been associated with obesity, diabetes, and nonalcoholic fatty liver disease, and maternal fructose intake during pregnancy has been shown to affect offspring health. In this study, we investigated the effects of high maternal fructose intake on the liver stem/progenitor cells of offspring. Main methodA fructose-based DOHaD model was established using Sprague-Dawley rats. Small hepatocytes (SHs), which play an important role in liver development and regeneration, were isolated from the offspring of dams that were fed a high-fructose corn syrup (HFCS) diet. The gene expression and DNA methylation patterns were analyzed on postnatal day (PD) 21 and 60. Key findingsMaternal HFCS intake did not affect body weight or caloric intake, but differences in gene expression and DNA methylation patterns were observed in the SHs of offspring. Functional analysis revealed an association between metabolic processes and ion transport. SignificanceThese results suggest that maternal fructose intake affects DNA methylation and gene expression in the liver stem/progenitor cells of offspring. Furthermore, the prolonged retention of these changes in gene expression and DNA methylation in adulthood (PD 60) suggests that maternal fructose intake may exert lifelong effects. These findings provide insights into the DOHaD for liver-related disorders and highlight the importance of maternal nutrition for the health of the next generation.

High-fructose corn syrup intake increases hepatic mitochondrial DNA copy number and methylation in adolescent rats

High-fructose corn syrup (HFCS) is consumed worldwide. However, it has been demonstrated that an increased intake of sweetened beverages, including those sweetened using fructose, is associated with the development of childhood obesity. It is unknown why the negative effects of fructose are stronger in young persons than in elderly individuals. In recent years, mitochondria have been identified as 1 of the targets of the negative effects of fructose; they possess their own genome called mitochondrial DNA (mtDNA), which encodes genes involved in metabolic functions. We hypothesized that HFCS intake affects mtDNA in the livers of rats, and that the intensity of these effects is age-dependent. The experimental period was divided into 3 parts: childhood and adolescence (postnatal day [PD] 21-60), young adulthood (PD61-100), and adulthood (PD101-140). Rats in the different age groups were assigned to receive either water (control group [CONT]) or a 20% HFCS solution (HFCS). The hepatic mtDNA copy number of the HFCS group was higher than that of the CONT group in childhood and adolescence. In addition, the mtDNA methylation level was increased in the HFCS group in the same experimental period. No significant differences were observed between the CONT and HFCS groups during the other experimental periods. We demonstrated that HFCS has the strongest effect on mtDNA during childhood and adolescence, suggesting a need to analyze the HFCS intake of young people.

Effects of High-Fructose Corn Syrup Intake on Glucocorticoid Metabolism in Rats During Childhood, Adolescence and Adulthood.

The consumption of high-fructose corn syrup (HFCS) has been increasing in recent decades, especially among children. Some reports suggest that children and adolescents are more sensitive to the adverse effects of fructose intake than adults. However, the underlying mechanism of the difference in vulnerability between adolescence and adulthood have not yet been elucidated. In this study, we attempted to elucidate the different effects of HFCS intake at different growth stages in rats: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and adulthood (PD100-140). Since alterations in hepatic glucocorticoid (GC) metabolism can cause diseases including insulin resistance, we focused on GC metabolizing enzymes such as 11 beta-hydroxysteroid dehydrogenase 1 and 2 (Hsd11b1 and Hsd11b2) and steroid 5 alpha-reductase 1 (Srd5a1). Western blotting showed an increase in Hsd11b1 expression and a decrease in Hsd11b2 expression in childhood and adolescence but not in adulthood. We also observed changes in Hsd11b1 and Hsd11b2 activities only in childhood and adolescence, consistent with the results of mRNA and protein expression analysis. The effect of high-fructose intake with regards to GC metabolism may therefore vary with developmental stage. This study provides insight into the adverse effects of fructose on GC metabolism in children in the context of increasing rates of HFCS consumption.

Relationship between irritable bowel syndrome, psychological comorbidities and the consumption of high-fructose corn syrup in a low-income community in a food desert area

<h2>Summary</h2><h3>Background & aim</h3> Hypersensitivity to fructose-containing foods including those containing high fructose corn syrup (HFCS) contributes to the worsening of irritable bowel syndrome (IBS) symptoms. There is scarcity of healthy food options in food desert areas. This may result in increased HFCS consumption in its residents. Thus there is a critical need to evaluate HFCS consumption of IBS patients, especially in socioeconomically challenged communities. The aim of this study was to explore the extent and origins of HFCS consumption in IBS patients that will help in the management of this disease. <h3>Methods</h3> We carried out a retrospective chart review of 969 IBS patients for demographics and medical and psychiatric comorbidities. We then collected information about dietary HFCS intake from a subset of IBS patients and control subjects using USDA-database-driven-surveys that included 398 HFCS-rich food items. Control subjects lacked history of gastrointestinal symptoms/disorders. <h3>Results</h3> 84% and 78% of IBS patients were female and Caucasian, respectively. 82% IBS patients were >40 years old. All IBS patients had at least one psychological comorbidity: depression, anxiety, bipolar, PTSD or psychosis; depression (66%) and anxiety (54%) being the most common. Overall HFCS intake was significantly higher in IBS patients compared to control subjects (<i>p</i> > 0.0001), which occurred <i>via</i> beverages, breakfast foods, jams, jellies, syrup, and desserts. Beverages contributed (76%) to the highest HFCS consumption observed in the IBS-diarrhea patients. <h3>Conclusion</h3> Our study is first to show a significantly high consumption of HFCS in IBS patients suffering from socioeconomic challenges and underscores the urgent need for provider-driven patient education regarding dietary interventions. This intervention is pivotal to avoid exacerbation of gastrointestinal symptoms as well as that of co-existing psychological comorbidities.

Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.

Consumption of fructose-containing beverages such as high-fructose corn syrup (HFCS) is increasing, raising concerns about the negative effects of excessive fructose intake. A recent report indicated that excess HFCS intake impairs hippocampal function. In this study, we focused on neurotrophic factors (NFs) in the hippocampus from the viewpoint of epigenetics to clarify the adverse effects of fructose. We analyzed the effects of HFCS intake on hippocampal function in three age categories: childhood and adolescence (postnatal day (PD) 21–60), young adulthood (PD60-100), and late adulthood (PD100-140). For the experiments, male Sprague-Dawley rats were divided into three age categories, the control group was received distilled water and the HFCS group was received 20% HFCS solution for 40 days in each period. We analyzed mRNA and protein levels for qPCR and western blotting, respectively, of a hippocampal NF, brain-derived neurotrophic factor (Bdnf). HFCS consumption reduced hippocampal Bdnf mRNA and protein expressions in childhood and adolescence. Moreover, pyrosequencing assays revealed increased DNA methylation at the Bdnf promoter in childhood and adolescence. This Bdnf levels reduction may be due to hypermethylation of the promoter regions. It should be noted that this phenomenon was observed only in childhood and adolescence fructose consumption. Our results indicate that the sensitivity of the hippocampus to fructose may vary with age. This study provides insight into the adverse effects of excessive HFCS consumption on the hippocampus in children.

High-fructose corn syrup intake has stronger effects on the transcription level of hepatic lipid metabolism-related genes, via DNA methylation modification, in childhood and adolescence than in other generations

AimsThis study aimed to analyze differences in sensitivity to hepatic lipid metabolism at different ages, through DNA methylation, using an experimental rat model of high-fructose corn syrup (HFCS) intake. Main methodsThe experimental was divided into three periods: childhood and adolescence (postnatal day (PD) 21–60), young adulthood (PD61–100), and adulthood (PD101–140). Rats in the different age groups were assigned to receive either water (C: control group) or 20% HFCS solution (H: HFCS-fed group). We measured hepatic mRNA levels of peroxisome proliferator-activated receptor alpha (Ppara), carnitine palmitoyltransferase 1A (Cpt1a), fatty acid synthase (Fasn), and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a) using real-time PCR. Additionally, we examined the DNA methylation levels of Ppara, Cpt1a, Fasn, and Pgc1a using pyrosequencing. Key findingsGene expressions of Cpt1a and Ppara in childhood and adolescence were significantly lower in the H group than in the C group. Conversely, Fasn and Pgc1a expressions were significantly higher in the H group than in the C group. Additionally, there was hypermethylation of Cpt1a and Ppara and hypomethylation of Fasn and Pgc1a in the H groups of childhood and adolescence. However, only one gene expression and methylation change was observed in young adulthood and adulthood groups. We found that HFCS intake in rats had stronger lipid metabolic effects in childhood and adolescence than in other generations, and that its mechanism involved epigenetic regulation. SignificanceWe anticipate that these research findings will be a breakthrough for elucidating the varying effects of growth stage in the future.

Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the Pparα promoter region

There are concerns about the negative effects of fructose intake during pregnancy on the next generation. We have previously reported that offspring from dams fed with fructose during gestation and lactation demonstrate abnormal lipid metabolism in the liver. In this study, we aimed to elucidate the molecular mechanism of the effects of maternal high-fructose corn syrup (HFCS) consumption on offspring. Pregnant Sprague-Dawley rats were fed with 20% HFCS water solution during gestation and lactation. Offspring were put on a normal diet after weaning, and the serum parameters and gene expression patterns were studied at predetermined intervals. Offsprings from pregnant rats fed with 20% HFCS (HFCS group) developed insulin resistance and hyperlipidemia at 60 d of age. RNA-seq analysis demonstrated that peroxisome proliferator-activated receptor α (PPARα) expression is downregulated by maternal HFCS intake. Hepatic Pparα expression in the HFCS group appeared to be suppressed by the enhanced DNA methylation of its promoter region. It is suggested that the development of insulin resistance and hyperlipidemia in the HFCS group may be attributable to aberrant Pparα methylation in the offspring liver. Pparα hypermethylation may be one of molecular mechanism underlying the toxicity of maternal fructose intake.

Acute Consumption of a Caffeinated Soft Drink Sweetened with High Fructose Corn Syrup Does Not Modify the Cutaneous Microvascular Response to Ischemia‐Reperfusion Injury

Background Copious intake of soft drinks sweetened with high fructose corn syrup (HFCS) is associated with a heightened risk of cardiovascular disease, which is likely contributed to by chronic HFCS mediated endothelial dysfunction occurring secondary to decreased nitric oxide (NO) bioactivity. Acute consumption of a soft drink sweetened with HFCS does not affect cutaneous vasodilation during local heating, a functional test of NO bioactivity in the cutaneous microvasculature. However, this study was undertaken in the absence of a basal reduction in NO bioactivity, such as is speculated to occur with chronic intake of HFCS. Therefore, the present study tested the hypothesis that the cutaneous vasodilatory response to local skin heating following ischemia-reperfusion injury, which acutely reduces NO bioactivity, is attenuated following acute consumption of a caffeinated soft drink sweetened with HFCS compared to water. Methods In a randomized, counter-balanced crossover design, fourteen healthy young adults (six women) consumed 500 mL of either tap water (H2O) or a caffeinated soft drink sweetened with HFCS (Mtn. Dew®, DEW). 30 min following consumption, participants underwent 20 min of forearm ischemia and 20 min of reperfusion. Local skin heating at the forearm to 39⁰C was performed for 40 min and increased to 44⁰C for 20 min. Skin blood flow (SkBF) was measured on the dorsal forearm using laser Doppler flowmetry, blood pressure was measured using the Penaz method, and heart rate was measured via 3-lead electrocardiogram. Cutaneous vascular conductance (CVC) was calculated as the quotient of SkBF and mean arterial pressure (MAP). SkBF and CVC data during local heating to 39⁰C, which is mostly a NO mediated response, were normalized as a percentage of maximal values obtained during local skin heating to 44⁰C. Data are presented as mean ± SD. Results During local skin heating at 44⁰C, there were no differences observed between H20 and DEW trials for SkBF (H2O: 252 ± 37 PU; DEW: 240 ± 35 PU, p = 0.317), CVC (H2O: 2.6 ± 0.4 PU/mmHg; DEW: 2.4 ± 0.5 PU/mmHg, p =0.215), MAP (H2O: 96 ± 6 mmHg; DEW: 101 ± 10 mmHg, p = 0 .162), and heart rate (H2O: 59 ± 7 bpm; DEW 60 ± 10 bpm, p = 0.654). During local skin heating to 39°C, no differences were observed in absolute SkBF (H2O: 154 ± 44 PU; DEW: 152 ± 44 PU, p = 0.879), percent of maximal SkBF (H20: 60.6 ± 12.2%; DEW 62.4 ± 12.7% p = 0.272), absolute CVC (H2O: 2 ± 0.5 PU/mmHg; DEW: 1.5 ± 0.5 PU/mmHg, p = 0.368), or percent of maximal CVC (H2O): 63.8 ± 13.9%; DEW 62.6 ± 13.7% p = 0.787) in the DEW and H2O trials. However, during local heating at 39°C DEW did result in a higher MAP (H2O: 92 ± 7 mmHg; DEW: 100 ± 12 mmHg, p = 0.022) and heart rate (H2O: 56 ± 7 bpm; DEW 59 ± 8 bpm, p = 0.032) compared to H2O. Conclusion Under conditions of ischemia-reperfusion injury, these data indicate that, compared to an equivalent volume of water, consumption of 500 mL of a caffeinated soft drink sweetened with HFCS does not affect the cutaneous vasodilatory response to local heating, a mostly nitric oxide mediated response.

Exposure to high fructose corn syrup during adolescence in the mouse alters hepatic metabolism and the microbiome in a sex-specific manner.

The prevalence of obesity and non-alcoholic fatty liver disease in children is dramatically increasing at the same time as consumption of foods with a high sugar content. Intake of high fructose corn syrup (HFCS) is a possible aetiology as it is thought to be more lipogenic than glucose. In a mouse model, HFCS intake during adolescence increased fat mass and hepatic lipid levels in male and female mice. However, only males showed impaired glucose tolerance. Multiple metabolites including lipids, bile acids, carbohydrates and amino acids were altered in liver in a sex-specific manner at 6weeks of age. Some of these changes were also present in adulthood even though HFCS exposure ended at 6weeks. HFCS significantly altered the gut microbiome, which was associated with changes in key microbial metabolites. These results suggest that HFCS intake during adolescence has profound metabolic changes that are linked to changes in the microbiome and these changes are sex-specific. The rapid increase in obesity, diabetes and fatty liver disease in children over the past 20years has been linked to increased consumption of high fructose corn syrup (HFCS), making it essential to determine the short- and long-term effects of HFCS during this vulnerable developmental window. We hypothesized that HFCS exposure during adolescence significantly impairs hepatic metabolic signalling pathways and alters gut microbial composition, contributing to changes in energy metabolism with sex-specific effects. C57bl/6J mice with free access to HFCS during adolescence (3-6weeks of age) underwent glucose tolerance and body composition testing and hepatic metabolomics, gene expression and triglyceride content analysis at 6 and 30weeks of age (n=6-8 per sex). At 6weeks HFCS-exposed mice had significant increases in fat mass, glucose intolerance, hepatic triglycerides (females) and de novo lipogenesis gene expression (ACC, DGAT, FAS, ChREBP, SCD, SREBP, CPT and PPARα) with sex-specific effects. At 30weeks, HFCS-exposed mice also had abnormalities in glucose tolerance (males) and fat mass (females). HFCS exposure enriched carbohydrate, amino acid, long chain fatty acid and secondary bile acid metabolism at 6weeks with changes in secondary bile metabolism at 6 and 30weeks. Microbiome studies performed immediately before and after HFCS exposure identified profound shifts of microbial species in male mice only. In summary, short-term HFCS exposure during adolescence induces fatty liver, alters important metabolic pathways, some of which continue to be altered in adulthood, and changes the microbiome in a sex-specific manner.

High fructose corn syrup, excess-free-fructose, and risk of coronary heart disease among African Americans\u2013 the Jackson Heart Study

BackgroundResearchers have sought to explain the black-white coronary heart disease (CHD) mortality disparity that increased from near parity to ~ 30% between 1980 and 2010. Contributing factors include cardiovascular disease prevention and treatment disparities attributable to disparities in insurance coverage. Recent research suggests that dietary/environmental factors may be contributors to the disparity. Unabsorbed/luminal fructose alters gut bacterial load, composition and diversity. There is evidence that such microbiome disruptions promote hypertension and atherosclerosis. The heart-gut axis may, in part, explain the black-white CHD disparity, as fructose malabsorption prevalence is higher among African Americans. Between 1980 and 2010, consumption of excess-free-fructose–the fructose type that triggers malabsorption-exceeded dosages associated with fructose malabsorption (~ 5 g–10 g), as extrapolated from food availability data before subjective, retroactively-applied loss adjustments. This occurred due to an industrial preference shift from sucrose to high-fructose-corn-syrup (HFCS) that began ~ 1980. During this period, HFCS became the main sweetener in US soda. Importantly, there has been more fructose in HFCS than thought, as the fructose-to-glucose ratio in popular sodas (1.9-to-1 and 1.5-to-1) has exceeded generally-recognized-as-safe levels (1.2-to-1). Most natural foods contain a ~ 1-to-1 ratio. In one recent study, ≥5 times/wk. consumers of HFCS sweetened soda/fruit drinks/and apple juice-high excess-free-fructose beverages–were more likely to have CHD, than seldom/never consumers.MethodsJackson-Heart-Study data of African Americans was used to test the hypothesis that regular relative to low/infrequent intake of HFCS sweetened soda/fruit drinks increases CHD risk, but not orange juice-a low excess-free-fructose juice. Cox proportional hazards models were used to calculate hazard ratios using prospective data of 3407–3621 participants, aged 21–93 y (mean 55 y).ResultsAfrican Americans who consumed HFCS sweetend soda 5-6x/wk. or any combination of HFCS sweetened soda and/or fruit drinks ≥3 times/day had ~ 2 (HR 2.08, 95% CI 1.03–4.20, P = 0.041) and 2.5–3 times higher CHD risk (HR 2.98, 95% CI 1.15–7.76; P = 0.025), respectively, than never/seldom consumers, independent of confounders. There were no associations with diet-soda or 100% orange-juice, which has a similar glycemic profile as HFCS sweetened soda, but contains a ~ 1:1 fructose-to-glucose ratio.ConclusionThe ubiquitous presence of HFCS in the food supply may pre-dispose African Americans to increased CHD risk.

S0489 Correlation Between Irritable Bowel Syndrome and Consumption of High-Fructose Corn Syrup in a Low-Income Community

INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic and debilitating disease. It is predominant in female patients. Due to its complicated treatment, clinical research is focused to improve symptomatology through dietary modifications. Hypersensitivity to certain fructose-containing foods plays a role in the development of IBS. High fructose corn syrup (HFCS) is a widely used, cost-effective sweetener. Our hospital system is committed to service to medically underserved, low-income, and minority populations. More than 37% of our city population lives in poverty. Our city is considered a ‘food desert’ with limited dietary choices due to the lack of access to healthy foods. This may increase consumption of readily available, cheaper, processed HFCS-rich foods. We investigated if HFCS consumption is higher in our IBS patients. Identifying and eliminating these food triggers will aid in the management of this disease. METHODS: We completed a retrospective chart review of 969 IBS patients for demographics, social history and psychiatric comorbidities. We also obtained 122 patient and 50 control surveys with additional information on HFCS consumption. USDA database was used to identify foods particularly high in HFCS. HFCS was quantified by Glinsmann's coefficient. Student's t-tests were used to compare means of quantitative data. Chi-square was used for categorical proportions. Spearman's rank-order correlation was used to assess strength of correlation between IBS and psychiatric comorbidities. RESULTS: 83% and 78% IBS patients were female and Caucasian, respectively; 39% were obese. Significant number of IBS patients showed one or more psychiatric comorbidities, such as depression (567), anxiety (325), bipolar (93), PTSD (87), and psychosis (21). Notably, IBS patients had significantly higher consumption of HFCS per capita as compared to the control group (P > 0.0001) (Table 1 and Figure 1). Specific foods contributing to HFCS consumption are also schematically presented in Figure 2. This will be useful to design a personalized dietary plan to reduce HFCS intake, e.g. HFCS consumption is highest in the IBS-diarrhea patients and majority of that is contributed by beverages. CONCLUSION: Our data shows a strong correlation between IBS and certain psychiatric comorbidities as well as IBS and HFCS consumption. Our data will help to create a personalized management plan for IBS patients in areas where access to healthy food options is difficult.Table 1Figure 1Figure 2

145-OR: GLP-1 Analogue Effects on Neural Responses to High-Fructose Corn Syrup and Eating Behavior in Obesity

GLP-1 analogues (GLP-1a) may change sweet food preferences but the neural mechanisms are not fully understood. We studied the effect of GLP-1a on neural responses to drinking high fructose corn syrup (HFCS) using fMRI in 5 lean (LN, BMI 21kg/m2, mean age 21, A1c 5.3%) and 7 obese (OB, BMI 38, age 26, A1c 5.5%) subjects. The OB group had a second fMRI after 3-mos treatment with liraglutide 3.0 mg daily. Food intake was evaluated by dietary recall. At baseline, OB group had increased cerebral blood flow (CBF) in regions implicated in reward/motivation (putamen) and taste perception (insula) vs. LN (p=.05). However, the OB group’s responses to HFCS changed markedly after 3-mos GLP-1a treatment. As shown in the Figure, CBF in OB group increased in regions related to impulse control (anterior cingulate cortex/ventromedial prefrontal cortex), taste perception (insula), and thalamus. It is also noteworthy that CBF did not increase in the reward/motivation region (putamen) during liraglutide treatment. Changes in neural responses to HFCS intake during GLP-1a treatment were accompanied by a 1080 kcal/d decrease in food intake (p&amp;lt;.006), as well as a &amp;gt;50% decrease in daily sugar intake. These preliminary data suggest decreased food and sugar intake induced by GLP-1a may be related to neural mechanisms that promote impulse control while simultaneously suppressing dysregulated reward responses following sugar intake. Disclosure K. Joseph: None. J. Leventhal: None. S. Hwang: None. M. Knight: None. D. Seo: None. C. Lacadie: None. M.A. Van Name: None. S. Caprio: None. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Cecelia Health. Consultant; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi, T1D Exchange. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi US. Other Relationship; Self; Eisai Inc., MannKind Corporation. R. Sinha: None. A.M. Jastreboff: Consultant; Self; Novo Nordisk Inc., Rhythm Pharmaceuticals. Funding American Diabetes Association (1-18-JDF-003 to A.M.J.)

2976 Risk of Developing Non-Alcoholic Fatty Liver Disease (NAFLD) With Increased Intake of High Fructose Corn Syrup (HFCS): A Systematic Review

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) encompasses the spectrum of fatty liver disease without significant alcohol consumption. The pathogenesis of NAFLD is complex and according to the “multiple parallel hits hypothesis,” a number of different processes may contribute to liver inflammation. High fructose corn syrup (HFCS, a mixture of fructose and glucose monosaccharides) appears to have a major role in inducing fatty liver by both stimulating de novo lipogenesis and blocking β-fatty acid oxidation. We performed a systematic review to demonstrate the association of HFCS in NAFLD. METHODS: Two independent authors performed a thorough literature search of English language studies in PubMed, Embase, Medline, Google Scholar, and Science Citation Index to identify relevant studies between January 2010 to January 2018. Keywords used were “high fructose corn syrup,” “nonalcoholic fatty liver disease,” “nonalcoholic steatohepatitis,” “high fructose diet,” “fatty liver,” “hepatic metabolism,” “hepatic triglycerides,” “hepatic de novo lipogenesis” and “liver enzymes.” Effects of HFCS on changes in liver enzymes, hepatic metabolism, and risk of NAFLD were assessed. The strength of evidence was evaluated by considering precision, the risk of bias and consistency. RESULTS: Based on our search criteria 6 animal studies were identified and 3 were excluded after careful review. 3 animal (rat/mice) studies were included for our final analysis. We found a significant evidence from all three studies that consumption of HFCS diet increased de novo lipogenesis in association with up-regulation of fatty acid synthase, sterol regulatory element binding protein (SREBP)-1c and decreased β-oxidation with down-regulation of Peroxisome proliferator-activated receptor (PPARα) in the liver of rats. In addition, ALT (Alanine Aminotransferase) elevation and increased liver triglycerides content were observed in all the three studies. CONCLUSION: Our systematic review shows that HFCS intake is associated with increased risk of developing NAFLD. However, we need more trials looking at the association between HFCS intake and liver metabolism in the future.

The effects of high-fructose corn syrup consumption on testis physiopathology-The ameliorative role of melatonin.

This study investigated the ameliorative role of melatonin (MLT) and the effects of a long-term intake of high-fructose corn syrup (HFCS) on the male reproductive system. Thirty-six male Sprague Dawley rats were randomly divided into 3 groups as follows: Control, HFCS and HFCS+MLT. Testis and epididymal weights were measured. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, total testosterone levels, testicular histopathological damage scores were evaluated, and immunohistochemical analyses were performed on testicular tissue. Epididymal weights were significantly lower in the HFCS+MLT group than those of the control and HFCS groups. MDA was significantly increased, while SOD and CAT activities were reduced in the HFCS group compared with the control group. Administration of melatonin significantly increased SOD and CAT activities in the HFCS+MLT group. Histopathological evaluation revealed slight hyperaemia and oedema in the stromal tissue of rat testes in the HFCS group. Sperm count and Johnsen's testicular biopsy score (JTBS) were significantly decreased in the HFCS group. Immunohistochemical analysis revealed that HSP, iNOS, MDA, OPN and VEGF values were significantly increased in the HFCS group. However, melatonin ameliorated the immunohistochemical scoring. Our results showed that a long-term intake of HFCS caused testicular damage. Melatonin may be a promising pharmacological agent against testicular toxicity induced by HFCS.

Fructose Contents of Various Popular Sweetened Beverages based on Milk Using by HPLC

The global consumption of fructose in the form of high-fructose corn syrup (HFCS) has increased considerably over the past several decades. The current intake of HFCS exceeds that of other major caloric sweeteners such as sucrose. Fructose has potentially adverse effects on human metabolism. Therefore, the objective of this study was to analyze the monosaccharide contents of 13 sweetened milk-based beverages by using high-performance liquid chromatography (HPLC). The total monosaccharide (fructose and glucose) contents of various sweetened milk-based beverages ranged from 0.60 g/100 mL (cheese) to 26.03 g/100 mL (maple caramel snack), while milk showed only 0 g/100 mL monosaccharides. The fructose-to-glucose ratio of various popular sweetened milk-based beverages ranged from not-detected (ND) to 2.24 g/100 mL, but the content of glucose was higher than that of fructose in only three samples, namely, strawberry flavored milk, shrimp chips, and maple caramel snack. The analyzed results revealed important basic information about monosaccharides in various milk-based sweetened beverages, presenting ideas for future fructose research.

Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20-30 years.

Objective:There is a link between joint and gut inflammation of unknown etiology in arthritis. Existing research indicates that regular consumption of high-fructose corn syrup sweetened (HFCS) soft drinks, but not diet soft drinks, may be associated with increased risk of seropositive rheumatoid arthritis (RA) in women, independent of other dietary and lifestyle factors. One unexplored hypothesis for this association is that fructose malabsorption, due to regular consumption of excess free fructose (EFF) and HFCS, contributes to fructose reactivity in the gastrointestinal tract and intestinal in situ formation of enFruAGEs, which once absorbed, travel beyond the intestinal boundaries to other tissues and promote inflammation. In separate studies, the accumulation of advanced glycation end-products has been associated with joint inflammation in RA. Objective of this study was to assess the association between EFF beverages intake and non-age, non-wear and tear-associated arthritis in US young adults.Methods:In this cross sectional study of 1209 adults aged 20–30y, (Nutrition and Health Examination Surveys 2003–2006) exposure variables were high EFF beverages, including HFCS sweetened soft drinks, and any combination of HFCS sweetened soft drinks, fruit drinks (FD) and apple juice, referred to as tEFF. Analyses of diet soda and diet FD were included for comparison. The outcome was self-reported arthritis. Rao Scott Ҳ2 was used for prevalence differences and logistic regression for associations, adjusted for confounders.Results:Young adults consuming any combination of high EFF beverages (tEFF) ⩾5 times/week (but not diet soda) were three times as likely to have arthritis as non/low consumers (odds ratios=3.01; p⩽0.021; 95% confidence intervals=1.20–7.59), independent of all covariates, including physical activity, other dietary factors, blood glucose and smoking.Conclusion:EFF beverage intake is significantly associated with arthritis in US adults aged 20–30 years, possibly due to the intestinal in situ formation of enFruAGEs.

Effects of dietary high fructose corn syrup on regulation of energy intake and leptin gene expression in rats

OBJECTIVE: To evaluate in Wistar rats the effect of chronic use of high fructose corn syrup on serum lipids, body weight, energy intake regulation, and expression of associated genes. METHODS: For 11 weeks, male rats were fed a standard diet with either water (control) or 15% high fructose corn syrup solution, or fed a high-fat diet. The rats' food intake and body weight were measured weekly. Expression of leptin and fatty acid synthase genes was quantified in their brain and adipose tissue upon sacrifice at age 119 days using real-time polymerase chain reaction. RESULTS: The intake of 15% high fructose corn syrup did not affect the rats' weight, only the rats on the high-fat diet gained significant weight. The rats in both diets had lower levels of leptin expression and high levels of fatty acid synthase in the brain, which were associated with high serum triglycerides. CONCLUSION: Fifteen percent high fructose corn syrup intake and the high-fat diet reduced leptin gene expression in the brain of Wistar rats, with differential effects on weight gain.

Fructose-containing sugars do not raise blood pressure or uric acid at normal levels of human consumption.

The impact of fructose, commonly consumed with sugars by humans, on blood pressure and uric acid has yet to be defined. A total of 267 weight-stable participants drank sugar-sweetened milk every day for 10 weeks as part of their usual, mixed-nutrient diet. Groups 1 and 2 had 9% estimated caloric intake from fructose or glucose, respectively, added to milk. Groups 3 and 4 had 18% of estimated caloric intake from high fructose corn syrup or sucrose, respectively, added to the milk. Blood pressure and uric acid were determined prior to and after the 10-week intervention. There was no effect of sugar type on either blood pressure or uric acid (interaction P>.05), and a significant time effect for blood pressure was noted (P<.05). The authors conclude that 10 weeks of consumption of fructose at the 50th percentile level, whether consumed as pure fructose or with fructose-glucose-containing sugars, does not promote hyperuricemia or increase blood pressure.

High-fructose corn syrup-induced hepatic dysfunction in rats: improving effect of resveratrol.

The increased consumption of high-fructose corn syrup (HFCS) may contribute to the worldwide epidemic of fatty liver. In this study, we have investigated whether HFCS intake (20% beverages) influences lipid synthesis and accumulation in conjunction with insulin receptor substrate-1/2 (IRS-1; IRS-2), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and inducible NOS (iNOS) expressions in liver of rats. Resveratrol was tested for its potential efficacy on changes induced by HFCS. Animals were randomly divided into four groups as control, resveratrol, HFCS and resveratrol plus HFCS (resveratrol + HFCS). HFCS was given as 20% solutions in drinking water. Feeding of all rats was maintained by a standard diet that enriched with or without resveratrol for 12 weeks. Dietary HFCS increased triglyceride content and caused mild microvesicular steatosis in association with up-regulation of fatty acid synthase and sterol regulatory element binding protein (SREBP)-1c in liver of rats. Moreover, HFCS feeding impaired hepatic expression levels of IRS-1, eNOS and SIRT1 mRNA/proteins, but did not change iNOS level. Resveratrol promoted IRS, eNOS and SIRT1, whereas suppressed SREBP-1c expression in rats fed with HFCS. Resveratrol supplementation considerably restored hepatic changes induced by HFCS. The improvement of hepatic insulin signaling and activation of SIRT1 by resveratrol may be associated with decreased triglyceride content and expression levels of the lipogenic genes of the liver.