Fructose: Pure,White, and Deadly? Fructose,by Any Other Name,Is a Health Hazard

The worldwide consumption of sucrose, and thus fructose, has risen logarithmically since 1800. Many concerns about the health hazards of calorie-sweetened beverages, including soft drinks and fruit drinks and the fructose they provide, have been voiced over the past 10 years. These concerns are related to higher energy intake, risk of obesity, risk of diabetes, risk of cardiovascular disease, risk of gout in men, and risk of metabolic syndrome. Fructose appears to be responsible for most of the metabolic risks, including high production of lipids, increased thermogenesis, and higher blood pressure associated with sugar or high fructose corn syrup. Some claim that sugar is natural, but natural does not assure safety.     

Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance

Background and Objectives:

High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial.

Subjects/Methods:

We investigated the metabolic consequences of mice fed a (a) regular diet, (b) ‘Western'' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80⁺CD11c⁺ macrophages and anti-inflammatory F4/80⁺CD11c⁻ macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat.

Results:

We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing ‘Western'' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to ‘Western'' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis.

Conclusion:

Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion mitigates the effects of HFCS on adipose inflammation and insulin resistance, suggesting that GHS-R antagonists may represent a novel therapy for insulin resistance.     

Fructose and Risk of Cardiometabolic Disease

Fructose and glucose in soft drinks and fruit drinks account for just under 50?% of added sugars. Soft drinks intake has risen five-fold between 1950 and 2000, and this increase in intake of simple sugars has raised health concerns. The risks of cardiovascular disease, obesity and the metabolic syndrome have all been related to consumption of sugar-sweetened beverages in several, but not all meta-analyses. Fructose and sugar-sweetened beverages have also been related to the risk of gout in men, and to non-alcoholic fatty liver disease. Studies show that the calories in sugar-sweetened beverages do not produce an adequate reduction in the intake of other foods, leading to increased caloric intake. Plasma triglycerides are increased by sugar-sweetened beverages, and this increase appears to be due to fructose, rather than to glucose in sugar. Several 10-week to 26-week randomized trials of sugar-containing soft drinks show increases in triglycerides, body weight, and visceral adipose tissue; there were also increases in muscle fat and liver fat, which might lead to non-alcoholic-fatty liver disease.     

Alcohol consumption and fatty liver disease

Hamaguchi et al recently reported some interesting observations on alcohol consumption and risk of fatty liver disease from a large population. However, we feel that it might be necessary to discuss some concerns in this study. As the alcohol consumption categorization was defined by the same criteria in both men and women, which might affect their results. As another factor is soft drinks consumption. It has been proved that soft drinks, especially fructose, contributes to the development of obesity, diabetes, metabolic syndrome, and nonalcoholic fatty liver disease. However, this confounding factor was not adjusted or discussed in this article. The third is the genetic background, for some genetic factors are related with the development of fatty liver disease, which was also not considered yet.     

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 high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects

It is unclear whether high-fructose corn syrup (HFCS), which contains a higher amount of fructose and provides an immediate source of free fructose, induces greater systemic concentrations of fructose as compared with sucrose. It is also unclear whether exposure to higher levels of fructose leads to increased fructose-induced adverse effects. The objective was to prospectively compare the effects of HFCS- vs sucrose-sweetened soft drinks on acute metabolic and hemodynamic effects. Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened beverages in a randomized crossover design study. Blood and urine samples were collected over 6 hours. Blood pressure, heart rate, fructose, and a variety of other metabolic biomarkers were measured. Fructose area under the curve and maximum concentration, dose-normalized glucose area under the curve and maximum concentration, relative bioavailability of glucose, changes in postprandial concentrations of serum uric acid, and systolic blood pressure maximum levels were higher when HFCS-sweetened beverages were consumed as compared with sucrose-sweetened beverages. Compared with sucrose, HFCS leads to greater fructose systemic exposure and significantly different acute metabolic effects.     

Association between habitual coffee consumption and metabolic syndrome in type 1 diabetes

Background and aimsIn the general population, habitual coffee consumption is inversely associated with the metabolic syndrome, a syndrome that is rather common also in patients with type 1 diabetes. However, whether coffee intake is beneficially related to the metabolic syndrome also in type 1 diabetes, is not known. We, therefore, studied the potential association between coffee consumption and the metabolic syndrome in a large population of individuals with type 1 diabetes. Furthermore, we investigated whether coffee consumption is associated with insulin resistance (estimated glucose disposal rate, eGDR), kidney function (estimated glomerular filtration rate, eGFR), and low-grade chronic inflammation (high-sensitivity C-reactive protein, hsCRP).Methods and resultsData from 1040 participants in the Finnish Diabetic Nephropathy Study were included in these cross-sectional analyses. Metabolic syndrome was assumed if at least 3 of the following cardiovascular risk factors were present: central obesity, high blood pressure, low HDL-cholesterol concentration, high triglyceride concentration, and hyperglycaemia. Subjects were categorized based on self-reported daily coffee intake: non-consumers (<1 cup/d), low (≥1 cups/d < 3), moderate (≥3 cups/d < 5), and high coffee consumption (≥5 cups/d). In multivariable logistic regression analysis, moderate and high coffee consumption was associated with increased odds of the metabolic syndrome. Moreover, any level of coffee consumption was associated with increased risk of the blood pressure-component. An increasing trend was observed in the eGFR with increasing coffee consumption.ConclusionsIn type 1 diabetes, high coffee intake is associated with the metabolic syndrome, and especially its blood pressure-component.     

Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease

BACKGROUND & AIMS: Nonalcoholic fatty liver disease has been defined by the presence of hepatic steatosis in the absence of other chronic liver diseases. We sought to determine whether obesity, insulin resistance, and the metabolic syndrome, which are the main risk factors for nonalcoholic fatty liver disease, are associated with similar elevations in serum alanine aminotransferase activity in persons with and those without other causes of chronic liver disease. METHODS: Adult participants of the third National Health and Nutrition Examination Survey were divided into those with causes of chronic liver disease (n = 1037), defined as viral hepatitis, excessive alcohol consumption, or increased transferrin-iron saturation, and those without (n = 8004). RESULTS: Among persons with other causes of chronic liver disease, obesity (adjusted odds ratio, 4.9; 95% confidence interval, 2.5-9.4), insulin resistance (adjusted odds ratio, 6.8; 95% confidence interval, 3.0-15.5, comparing the highest and the lowest quartile), and the metabolic syndrome (adjusted odds ratio, 3.3; 95% confidence interval, 1.4-8.0) were all strongly associated with increased alanine aminotransferase activity (>43 IU/L). Among persons without other causes of chronic liver disease, statistically similar associations were identified. CONCLUSIONS: Obesity, insulin resistance, and the metabolic syndrome are strong predictors of increased alanine aminotransferase activity in the US population, both in persons with and in persons without other causes of chronic livers disease. We hypothesize that metabolic fatty liver disease related to these conditions is the cause of the increased alanine aminotransferase activity and may be underrecognized in persons with other causes of chronic liver disease.     

Alcohol consumption and metabolic syndrome

Drinking excessive amounts of alcohol regularly for years is toxic to almost every tissue of the body. On the other hand, epidemiological and clinical evidence shows that light‐to‐moderate drinking is associated with a reduced risk of coronary heart disease, total and ischemic stroke, and mortality. In the past two decades, metabolic syndrome, the combination of obesity, hypertension, dyslipidemia and hyperglycemia, are all also recognized as major cardiovascular risk factors, has given rise to much clinical and research attention, because of its high prevalence in the world. Therefore, it is of interest to evaluate the overall associations of alcohol consumption with the development of metabolic syndrome. Recently, the protective, detrimental or J‐shaped associations have been reported between alcohol consumption and metabolic syndrome. This controversy may be due to the complex mechanistic relation between alcohol consumption and each component of metabolic syndrome, and almost all studies have various limitations and problem points. Prospective studies are therefore needed to confirm the association between alcohol consumption and prevalence of metabolic syndrome, and to assess the influence of alcohol drinking patterns and other possible factors, such as smoking, physical activity, socioeconomic status, education, occupation, diet and exercise. This article reviews the relation of alcohol consumption and components of metabolic syndrome, and discusses the epidemiological evidence for alcohol's putative vascular protective effects and plausible underlying biological mechanisms.     

Genome-wide association studies of obesity and metabolic syndrome

Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years.     

Relation of habitual snoring with components of metabolic syndrome in Korean adults

AIMS: To examine the association between habitual snoring and components of the metabolic syndrome in Korean adults. Whether these associations are independent of obesity was also explored. METHODS: Four thousand five hundred and six men and 5041 women aged 40-69 years from the Korean Health and Genome Study were examined. Information of snoring frequency was obtained by a questionnaire and components of the metabolic syndrome were measured. RESULTS: There was a clear dose-response relationship between the increasing frequency of snoring and the higher prevalence of each component of the metabolic syndrome (P<0.001). After adjustment for age, abdominal obesity, and the other metabolic components, hypertension was significantly associated with a 1.2-fold excess of habitual snoring in both men (P<0.05) and women (P<0.05). The association of habitual snoring with hypertension was unaltered by obesity. Regardless of the presence or absence of abdominal obesity, there was an increase in the prevalence of habitual snoring as the number of metabolic abnormalities increased. CONCLUSIONS: Habitual snoring is associated with hypertension independent of obesity. While the relationship between habitual snoring and obesity is well recognized, characterization of the role of the other components of the metabolic syndrome as a cause or result of habitual snoring warrants a further study.     

Inflammation,insulin resistance,and obesity

Obesity, in particular visceral obesity, has strong associations with cardiovascular disease and is related to many factors that are constituents of the metabolic syndrome. Increasing evidence suggests that features of the metabolic syndrome, including visceral obesity, are associated with a low-grade inflammatory state. Indeed, visceral fat is a source of several molecules, such as leptin, adiponectin, tumor necrosis factor-α, and interleukin 6, that are collectively called adipokines. All of them may induce a proinflammatory state and oxidative damage, leading to initiation and progression of atherosclerosis. Reducedenergy diets might represent an effective and healthful approach for long-term weight loss in patients with metabolic syndrome by reducing the underlying inflammatory condition.     

Challenges in developing drugs for the metabolic syndrome

Metabolic syndrome refers to a clustering of established and emerging cardiovascular disease (CVD) risk factors within a single individual. The established risk factors—such as obesity, diabetes, dyslipidemia, hypertension—and other emerging risk factors are closely related to central obesity (especially intra-abdominal adiposity). Insulin resistance is also an important factor in this syndrome’s etiology. However, despite the potential use of having all the CVD risk factors under an umbrella diagnosis of metabolic syndrome, debate continues about the very existence of the metabolic syndrome. Despite the controversies, many existing therapies and new drugs in development are targeting the metabolic syndrome. To date, no drugs are approved specifically for treating the metabolic syndrome. This article discusses some of the challenges in developing therapies for the metabolic syndrome.     

Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population.

BACKGROUND & AIMS: Both alcohol and obesity are associated with hepatic steatosis. However, little is known about whether the toxicity of alcohol to the liver is influenced by adiposity. We examined the relationship of alcohol drinking and binge drinking with abnormal serum aminotransferase activity in normal weight, overweight, and obese persons in a national, population-based study. METHODS: Data were analyzed from 13,580 adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, after excluding participants with hepatitis B or C or iron overload. Abnormal aminotransferase levels were defined by using sex-specific cutoffs for ALT and AST. Analyses were adjusted for other liver injury risk factors. RESULTS: The prevalence of abnormal aminotransferase activity was elevated with consumption of >2 drinks per day or with overweight and obesity. In multivariate analysis, there was no association of alcohol intake with a higher prevalence of elevated aminotransferase levels among normal weight persons. In contrast, among overweight persons, consumption of >2 drinks per day increased the risk of elevated aminotransferase levels, and among the obese, > or = 1 drink per day was associated with a higher risk. Results were similar with elevated ALT alone as the outcome. With elevated AST alone as the outcome, intake of >2 drinks per day increased the risk, even among normal weight persons. Binge drinking was associated with aminotransferase elevation among obese consumers of 1-2 drinks per day. CONCLUSIONS: In this large, national, population-based study, overweight and obesity increased the risk of alcohol-related abnormal aminotransferase activity.     

脂肪细胞关联基因与老年肥胖代谢性疾病

肥胖及肥胖代谢综合征作为老年人常见病和合并症目前已不再足某些发达国家或地区的问题,它已经成为全球各个国家都将面l临的重大医学问题和健康问题。而且,肥胖可引发老年代谢性疾病、呼吸系统疾病、心血管系统疾病以及骨关节退行性变、性激素分泌失调、静脉淤滞、深静脉血栓形成及肿瘤的发生和发展等,其潜在的健康影响和生命威胁难以估量,给国家带来的社会问题和经济损失也无法计算。而某些脂肪细胞关联基因及肥胖基因与人类肥胖及肥胖代谢综合征密切相关,因此,对这些肥胖基因表达及关联因素实施有效调控,对控制人类肥胖及肥胖代谢综合征的发生、发展及转归具有重要临床意义。正是基于这些,本文通过对肥胖相关基因及其与相关临床疾病关系的文献进行综述,希望未来能够对以这些肥胖基因作为靶点的肥胖预防和治疗药物的设计提供某些依据并奠定一定基础。     

The diversity of sex steroid action: regulation of metabolism by estrogen signaling

The metabolic syndrome is a complex condition characterized by obesity, insulin resistance, decreased high-density lipoproteins, and hypertension associated with high risk of developing type 2 diabetes and cardiovascular disease. A major increase in the incidence of developing metabolic syndrome and related diseases is observed worldwide in association with a change toward a less active lifestyle and increased food consumption. Estrogen and the estrogen receptors (ERs) are well-known regulators of several aspects of metabolism, including glucose and lipid metabolism, and impaired estrogen signaling is associated with the development of metabolic diseases. This review will describe the key effects of estrogen signaling in metabolic and glucose sensing tissues, including the liver, pancreatic β cells, adipose tissue, and skeletal muscle. The impact on metabolic processes of impaired estrogen signaling and knock out of each ER subtype will also be discussed.     

Metabolic syndrome and progression of atherosclerosis among middle-aged US adults

Metabolic syndrome, indicated by insulin resistance/hyperinsulinemia, obesity, central obesity, atherogenic dyslipidemia, and hypertension, contributes to atherosclerotic cardiovascular disease. However, it is controversial whether the indicators of metabolic syndrome are related to subclinical atherosclerosis collectively or individually. Whether there is any gender-based difference in the mechanisms of metabolic syndrome-induced atherosclerosis progression is also unknown. Two models were compared in this study. Model 1 assumes that a latent factor, metabolic syndrome per se, impacts subclinical atherosclerosis (collective effects model); Model 2 assumes the effect of the syndrome is mediated through its indicators (individual effects model). Data were obtained from the Los Angeles Atherosclerosis Study. The cohort consists of 573 adults (age, 40-60 years) who were asymptomatic for cardiovascular disease. Subclinical atherosclerosis was assessed by measuring common carotid artery intima-media thickness (CCA-IMT) using B-mode ultrasound. Three examinations were completed at 1.5-year intervals from 1995-1999. The analyses were performed with SAS 8.2 and AMOS 4.0. The results showed that atherogenic effects of metabolic syndrome were mediated through its indicators; there were gender-based differences in the mechanisms of metabolic syndrome-induced atherosclerosis. Central obesity was significantly associated with the baseline IMT for men only, whereas triglycerides were significantly associated with the progression of IMT for women only. Systolic blood pressure was significantly associated with the baseline and progression for both men and women. However, fasting insulin was not found to be significantly associated with the baseline and progression of IMT in the multivariate model, although it was significantly associated with other components of metabolic syndrome.     

Perfil metabólico-inflamatorio en la transición obesidad,síndrome metabólico y diabetes mellitus en población mediterránea. Estudio DARIOS Inflamatorio

Introduction and objectivesThere is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus.MethodsWe performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus.ResultsA total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated.ConclusionsThere are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked.Full English text available from: www.revespcardiol.org/en     

Impact of body weight,diet and lifestyle on nonalcoholic fatty liver disease

Nonalcoholic steatohepatitis is part of the broader spectrum of nonalcoholic fatty liver disease, strongly associated with insulin resistance, obesity and the metabolic syndrome. Its increasing prevalence appears to be closely related to the increased frequency of overweight or obesity; which is associated with changes in dietary habits, including an increased consumption of hypercaloric food and saturated fat, often concurrent with decreased activity and energy expenditure. Weight loss through dieting and increasing energy expenditure through the practice of regular exercise has been shown to be effective in improving nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and is considered the mainstay of treatment. The effectiveness of these lifestyle interventions seems to rely chiefly on an improvement in insulin sensitivity. At present, disease management using a multidisciplinary team is probably pivotal for patient-centered quality of care.     

The effects of whey protein on cardiometabolic risk factors

Obesity has reached epidemic proportions worldwide. The health consequences of obesity are more dangerous when associated with the metabolic syndrome and its components. Studies show that whey protein and its bioactive components can promote greater benefits compared to other protein sources such as egg and casein. The aim of this paper is to review the effects of whey protein on cardiometabolic risk factors. Using PubMed as the database, a review was conducted to identify current scientific literature on whey protein and the components of the metabolic syndrome published between 1970 and 2012. Consumption of whey protein seems to play an anti‐obesity and muscle‐protective role during dieting by increasing thermogenesis and maintaining lean mass. In addition, whey protein has been shown to improve glucose levels and insulin response, promote a reduction in blood pressure and arterial stiffness, and improve lipid profile. The collective view of current scientific literature indicates that the consumption of whey protein may have beneficial effects on some symptoms of the metabolic syndrome as well as a reduction in cardiovascular risk factors.