Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality.

BACKGROUND: Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population. METHODS: This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause. RESULTS: In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease. CONCLUSIONS: In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death. (Funded by the Population Health Research Institute and others.).

Association between dietary sugar intake and depression in US adults: a cross-sectional study using data from the National Health and Nutrition Examination Survey 2011-2018.

BACKGROUND: Studies examining whether diet sugar intake increases the risk of depression have produced inconsistent results. Therefore, we investigated this relationship, using the US' National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study included 18,439 adults (aged ≥ 20 years) from NHANES (2011-2018). Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9). Covariates, including age, sex, race/ethnicity, poverty-income ratio, education, marital status, hypertension, diabetes mellitus, cardiovascular disease, alcohol intake, smoking status, physical activity, and dietary energy intake, were adjusted in multivariate logistic regression models. Subgroup and threshold saturation effect analyses were performed. RESULTS: After adjusting for potential confounders, we found that a 100 g/day increase in dietary sugar intake correlated with a 28% higher prevalence of depression (odds ratio = 1.28, 95% confidence interval = 1.17-1.40, P < 0.001). CONCLUSION: Dietary sugar intake is positively associated with depression in US adults.

Sugar intake and colorectal cancer risk: A prospective Japanese cohort study.

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle-aged adults in a Japanese large-scale population-based cohort study. The participants (42,405 men and 48,600 women) who were 45-74 years old and answered the questionnaire in 1995-1999 in the Japan Public Health Center-based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147-item food frequency questionnaire and divided into quintiles (Q1-Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow-up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07-2.87] for Q1 vs. Q5; p linear trend  = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle-aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded.

Maternal high-sugar diet results in NMDA receptors abnormalities and cognitive impairment in rat offspring.

Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Considering the prevalence of obesity in developed countries, it seems important to examine the effects of diet on the behavior and physiology of future generations. We hypothesized that exposure to sugar excess in a maternal diet during pregnancy and lactation would affect memory as the NMDA receptor-related processes. Through the manipulation of the sugar amount in the maternal diet in rats, we assessed its effect on offspring's memory. Then, we evaluated if memory alterations were paralleled by molecular changes in NMDA receptors and related modulatory pathways in the prefrontal cortex and the hippocampus of adolescent and young adult female and male offspring. Behavioral studies have shown sex-related changes like impaired recognition memory in adolescent males and spatial memory in females. Molecular results confirmed an NMDA receptor hypofunction along with subunit composition abnormalities in the medial prefrontal cortex of adolescent offspring. In young adults, GluN2A-containing receptors were dominant in the medial prefrontal cortex, while in the hippocampus the GluN2B subunit contribution was elevated. In conclusion, we demonstrated that a maternal high-sugar diet can affect the memory processes in the offspring by disrupting the NMDA receptor composition and regulation in the medial prefrontal cortex and the hippocampus.

Dietary sugar intake and risk of Alzheimer's disease in older women.

BACKGROUND: Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. AIM: The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. METHODS: A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative - Dietary Modification Trial (WHI-DM) in 1993-2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates. RESULTS: During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3-6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8-6.6), 6.4 (6.0-6.8), 6.6 (6.3-7.0), and 6.9 (6.5-7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p < 0.001). Individuals in Q4 of total sugar intake had a 1.19 higher risk of incident AD than those in Q1 (hazard ratio [HR] = 1.19, 95% CI: 1.05-1.34, p = 0.01). An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased AD risk by 1.3-1.4%. Of six subtypes of sugar intake, lactose was significantly associated with AD risk. CONCLUSIONS: Our study indicates that excessive total sugar intake was significantly associated with AD risk in women. Of six subtypes of sugar intake, lactose had a stronger impact on AD risk.

Dietary sugars and subclinical vascular damage in moderate-to-high cardiovascular risk adults.

BACKGROUND AND AIMS: The association between dietary sugars and vascular damage has been scarcely examined out of the context of established cardiovascular disease. We aimed to investigate the association between different types of sugars with subclinical atheromatosis and arteriosclerosis, in individuals free of cardiovascular disease being, however, at moderate-to-high cardiovascular risk. METHODS AND RESULTS: Two 24-h dietary recalls were conducted to estimate sugars intake. Subclinical atheromatosis was assessed by B-mode ultrasonography and arteriosclerosis (arterial stiffness) via tonometry (carotid-to-femoral pulse wave velocity). Multiple logistic regression analysis was performed to determine the relationship of quartiles of total sugars, monosaccharides and disaccharides with atheromatosis and arteriosclerosis, adjusting for potential confounders [Odds Ratio (95%Confidence Interval)]. In 901 participants (52.4 ± 13.8 years, 45.2% males), total sugars intake was not associated with any type of subclinical vascular damage. Subjects at 4th quartile of lactose intake (15.3 ± 5.5 g/day) had lower probability to present atheromatosis compared to those at 1st quartile (0.00 ± 0.01 g/day) even in the fully adjusted model [0.586 (0.353-0.974)]. Subjects at 3rd quartile of total disaccharides intake and particularly sucrose (15.1 ± 2.2 g/day) had higher probability to present arteriosclerosis compared to those at 1st quartile (3.0 ± 1.9 g/day) even after adjustment for all potential confounders [2.213 (1.110-4.409)]. CONCLUSIONS: Overall, the present data suggest a distinct role of each type of sugars on vascular damage. These observations highlight the need for further studies investigating not only foods rich in sugars, but sugars as separate components of food as they probably contribute via different ways on the development of arterial pathologies.

High versus low-added sugar consumption for the primary prevention of cardiovascular disease.

BACKGROUND: High intake of added sugar have been suggested to impact the risk for cardiovascular disease (CVD). Knowledge on the subject can contribute to preventing CVD. OBJECTIVES: To assess the effects of a high versus low-added sugar consumption for primary prevention of CVD in the general population. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) on 2 July 2021. We also conducted a search of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) Search Portal for ongoing or unpublished trials. The search was performed together with reference checking, citation searching and contact with study authors to identify additional studies. We imposed no restriction on language of publication or publication status. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cross-over trials, that compared different levels of added sugar intake. Exclusion criteria were: participants aged below 18 years; diabetes mellitus (type 1 and 2); and previous CVD. Primary outcomes were incident cardiovascular events (coronary, carotid, cerebral and peripheral arterial disease) and all-cause mortality. Secondary outcomes were changes in systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose and adverse events (gastrointestinal symptoms and impaired dental health). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 21 RCTs (1110 participants completing the interventions) examining the effects of different levels of added sugar intake with a mean duration of 14 weeks. The study participants were generally described as healthy and the mean age ranged from 22 to 57 years. No studies reported on cardiovascular events or all-cause mortality. There was minimal effect of low intake of added sugar on total cholesterol levels (MD 0.11, 95% CI 0.01 to 0.21; I² = 0%; 16 studies; 763 participants; low certainty of evidence) and triglycerides (MD 0.10, 95% CI 0.03 to 0.17; I² = 3%; 14 studies; 725 participants) but no evidence of effect on LDL-cholesterol and HDL-cholesterol. There was minimal effect on diastolic blood pressure (MD 1.52, 95% CI 0.67 to 2.37; I² = 0%; 13 studies; 873 participants) and on systolic blood pressure (MD 1.44, 95% 0.08 to 2.80; I² = 27%, 14 studies; 873 participants; low certainty of evidence), but no evidence of effect on fasting plasma glucose. Only one study reported on dental health, with no events. No other trials reported adverse events (impaired dental health or gastrointestinal symptoms). All results were judged as low-quality evidence according to GRADE. The risk of bias was generally unclear, five studies were classified at an overall low risk of bias (low risk in at least four domains, not including other bias). AUTHORS' CONCLUSIONS: No trials investigating the effect of added sugar on cardiovascular events or all-cause mortality were identified in our searches. Evidence is uncertain whether low intake of added sugar has an effect on risk factors for CVD; the effect was small and the clinical relevance is, therefore, uncertain. Practical ways to achieve reductions in dietary added sugar includes following current dietary recommendations. Future trials should have longer follow-up time and report on all-cause mortality and cardiovascular events in order to clarify the effect of added sugar on these outcomes. Future trials should also aim for more direct interventions and preferably be more independent of industry funding.

Pathways in the association between added sugar consumption, obesity in mother-child dyads, and chronic oral disease burden in early childhood.

In this study, we modeled the pathways in the association of socioeconomic status, frequency of added sugar consumption, and obesity in mother-child dyads with chronic oral disease burden in early childhood using structural equation modeling. A population-based study was conducted on preschoolers from public daycare centers in São Luís, Brazil (n = 674) and their mothers. Chronic oral disease burden in early childhood was a latent variable, representing the shared variance of the following indicators: visible plaque index, gingivitis, and dental caries. A higher consumption frequency of added sugars by children [standardized regression coefficient (SC) = 0.219] explained the chronic oral disease burden. A higher consumption frequency of added sugars by mothers was associated with greater consumption of sugar by children (SC = 0.236), and indirectly with a greater chronic oral disease burden (SC = 0.052). Maternal obesity was associated with obesity in the offspring (SC = 0.130). The chronic oral disease burden is already present in early childhood and can be explained by the higher consumption of added sugars by the mother-child dyad. Approaches to preventing chronic oral diseases should focus on common risk factors, start early in life, and promote family involvement in this process.

AMPK in the gut-liver-brain axis and its influence on OP rats in an HSHF intake and WTD rat model.

Obesogenic diets (ODs) can affect AMPK activation in several sites as the colon, liver, and hypothalamus. OD intake can impair the hypothalamic AMPK regulation of energy homeostasis. Despite consuming ODs, not all subjects have the propensity to develop or progress to obesity. The obesity propensity is more associated with energy intake than expenditure dysregulations and may have a link with AMPK activity. While the effects of ODs are studied widely, few evaluate the short-term effects of terminating OD intake. Withdrawing from OD (WTD) is thought to improve or reverse the damages caused by the intake. Therefore, here we applied an OD intake and WTD protocol aiming to evaluate AMPK protein content and phosphorylation in the colon, liver, and hypothalamus and their relationship with obesity propensity. To this end, male Wistar rats (60 days) received control or high-sugar/high-fat (HSHF) OD for 30 days. Half of the animals were OD-withdrawn and fed the control diet for 48 h. After intake, we found a reduction in AMPK phosphorylation in the hypothalamus and colon, and after WTD, we found an increase in its hepatic and hypothalamic phosphorylation. The decrease in colon pAMPK/AMPK could be linked with hypothalamic pAMPK/AMPK after HSHF intake, while the increase in hepatic pAMPK/AMPK could have prevented the increase in hypothalamic pAMPK/AMPK. In the obesity-prone rats, we found higher levels of hypothalamic and colon pAMPK/AMPK despite the higher body mass gain. Our results highlight the relevance in multi-organ investigations and animal phenotype evaluation when studying the energy metabolism regulations.

GLUT5 is a determinant of dietary fructose-mediated exacerbation of experimental colitis.

The Western diet has been suggested to contribute to the rising incidence of inflammatory bowel diseases. This has led to the hypothesis that fructose, a component of the Western diet, could play a role in the pathogenesis of inflammatory bowel diseases. A high-fructose diet is known to exacerbate experimental colitis. This study tested whether the expression of GLUT5, the fructose transporter, is a determinant of the severity of experimental colitis during elevated fructose consumption and whether ileal inflammation is associated with altered GLUT5 expression in Crohn's disease. Studies in genetically engineered mice showed that in comparison to Glut5+/+ mice, feeding a 15 kcal% fructose diet to Glut5-/- mice led to worse dextran sodium sulfate (DSS)-induced colitis. This effect was associated with elevated levels of colonic fructose and a shift in the fecal microbiota in Glut5-/- mice. Importantly, treatment with broad-spectrum antibiotics protected against the worsening of colitis mediated by dietary fructose in Glut5-/- mice. Gene expression analysis revealed that GLUT5 levels are reduced in the intestines of patients with ileal Crohn's disease. Moreover, levels of GLUT5 negatively correlated with expression of proinflammatory mediators in these samples. Collectively, these results demonstrate that dietary constituent (fructose)-host gene (GLUT5) interactions can shape the colonic microbiota, thereby impacting the severity of colitis.NEW & NOTEWORTHY This study provides the first evidence that reduced levels of GLUT5, the fructose transporter, worsen experimental colitis upon fructose feeding, an effect mediated by changes in the gut microbiota. Moreover, GLUT5 expression is reduced in Crohn's ileitis. Overall, these findings demonstrate the importance of interactions between dietary fructose and host GLUT5 as determinants of both the composition of colonic microbiota and severity of experimental colitis.

Susceptibility of Rat Steatotic Liver to Ischemia-Reperfusion Is Treatable With Liver-Selective Matrix Metalloproteinase Inhibition.

BACKGROUND AND AIMS: This study examined whether enhanced susceptibility of steatotic liver to ischemia-reperfusion (I/R) injury is due to impaired recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (LSECs, also called sinusoidal endothelial cell progenitor cells [sprocs]) with diminished repair of injured LSECs and whether restoring signaling to recruit BM sprocs reduces I/R injury. APPROACH AND RESULTS: Hepatic vessels were clamped for 1 hour in rats fed a high-fat, high-fructose (HFHF) diet for 5, 10, or 15 weeks. Matrix metalloproteinase 9 (MMP-9) antisense oligonucleotides (ASO) or an MMP inhibitor were used to induce liver-selective MMP-9 inhibition. HFHF rats had mild, moderate, and severe steatosis, respectively, at 5, 10, and 15 weeks. I/R injury was enhanced in HFHF rats; this was accompanied by complete absence of hepatic vascular endothelial growth factor (VEGF)-stromal cell-derived factor 1 (sdf1) signaling, leading to lack of BM sproc recruitment. Liver-selective MMP-9 inhibition to protect against proteolytic cleavage of hepatic VEGF using either MMP-9 ASO or intraportal MMP inhibitor in 5-week and 10-week HFHF rats enhanced hepatic VEGF-sdf1 signaling, increased BM sproc recruitment, and reduced alanine aminotransferase (ALT) by 92% and 77% at 5 weeks and by 80% and 64% at 10 weeks of the HFHF diet, respectively. After I/R injury in 15-week HFHF rats, the MMP inhibitor reduced active MMP-9 expression by 97%, ameliorated histologic evidence of injury, and reduced ALT by 58%, which is comparable to control rats sustaining I/R injury. Rescue therapy with intraportal MMP inhibitor, given after ischemia, in the 5-week HFHF rat reduced ALT by 71% and reduced necrosis. CONCLUSIONS: Lack of signaling to recruit BM sprocs that repair injured LSECs renders steatotic liver more susceptible to I/R injury. Liver-selective MMP-9 inhibition enhances VEGF-sdf1 signaling and recruitment of BM sprocs, which markedly protects against I/R injury, even in severely steatotic rats.

Association between per capita sugar consumption and diabetes prevalence mediated by the body mass index: results of a global mediation analysis.

PURPOSE: The aim of this study was to examine the mediation of body mass index (BMI) on the association between per capita sugar consumption and diabetes prevalence using country-related data. RESEARCH DESIGN AND METHODS: In this ecological study, based on 192 countries, data on per capita sugar consumption were obtained from the Food and Agriculture Organization of the United Nations (FAO), on BMI from the World Health Organization and on diabetes prevalence from the International Diabetes Federation. Data on demography and economic factors were obtained from the Central Intelligence Agency, the United Nations and the FAO. Multiple linear regression analysis was performed to investigate the association between per capita sugar consumption and diabetes prevalence, and mediation analysis to detect the mediated percentage of BMI on this association. RESULTS: Each increase of 100 kcal/day per capita sugar consumption was associated with a 1.62% higher diabetes prevalence [adjusted ß-estimator (95% CI): 1.62 (0.71, 2.53)]. Mediation analysis using BMI as the mediator demonstrated an adjusted direct association of 0.55 (95% CI: - 0.22, 1.32) and an adjusted indirect association of 1.07 (95% CI: 0.54, 1.68). Accordingly, the BMI explained 66% (95% CI: 34%, 100%) of the association between per capita sugar consumption on diabetes prevalence. CONCLUSIONS: These findings indicate that the association between dietary sugar intake and the occurrence of diabetes is mediated by BMI to a large proportion. However, it seems that other mechanisms may explain the association between sugar consumption and development of type 2 diabetes.

Dairy consumption and subclinical atherosclerosis: A cross-sectional study among middle-aged Mexican women.

BACKGROUND AND AIMS: Many dietary guidelines encourage low-fat dairy products; however, recent studies have found null and inverse associations between high-fat dairy intake and cardiovascular disease (CVD) risk. We examined the association between the intake of total dairy and different types of dairy and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in Mexican women. METHODS AND RESULTS: Dairy consumption was assessed using a validated food-frequency questionnaire (FFQ) in 1759 women in the Mexican Teachers' Cohort (MTC) study who were free of CVD or cancer. We categorized participants according to total dairy intake and consumption of four mutually exclusive dairy groups: high-fat, low-fat, yogurt, and dairy with added sugars. IMT and atherosclerotic plaque were measured by B-mode ultrasonography. Subclinical atherosclerosis was defined as an IMT ≥0.8 mm and/or the presence of plaque. Multivariable linear regression and logistic regression models were used to respectively assess the mean percentage difference of mean IMT and odds ratios (OR) for subclinical atherosclerosis across quantiles of dairy consumption. Mean (±SD) age was 45.4 ± 5.0 years and the median (interquartile range: IQR) total dairy consumption was 11.0 (6.6, 17.1) servings/week. After adjusting for lifestyle, clinical, and dietary factors, comparing the highest category of consumption, to the lowest, total dairy was associated with increased IMT (2.6%, 95% confidence interval (CI): 0.6, 4.3; p-trend<0.01). Moreover, yogurt consumption was associated with lower odds of subclinical atherosclerosis (OR = 0.65, 95% CI: 0.47, 0.91; p-trend = 0.01). CONCLUSIONS: While total dairy consumption was associated with carotid wall thickening, yogurt consumption was related to lower subclinical atherosclerosis.

The effects of different types of aquatic exercise training interventions on a high-fructose diet-fed mice.

Gradual weight gain in modern people and a lowering onset age of metabolic disease are highly correlated with the intake of sugary drinks and sweets. Long-term excessive fructose consumption can lead to hyperglycemia, hyperlipidemia and accumulation of visceral fat. Abdominal obesity is more severe in females than in males. In this study, we used a high-fructose-diet-induced model of obesity in female mice. We investigated the effects of aquatic exercise training on body weight and body composition. After 1 week of acclimatization, female ICR mice were randomly divided into two groups: a normal group (n=8) fed standard diet (control), and a high-fructose diet (HFD) group (n=24) fed a HFD. After 4 weeks of induction followed by 4 weeks of aquatic exercise training, the 24 obese mice were divided into 3 groups (n=8 per group): HFD with sedentary control (HFD), HFD with aquatic strength exercise training (HFD+SE), and HFD with aquatic aerobic exercise training (HFD+AE). We conducted serum biochemical profile analysis, weighed the white adipose tissue, and performed organ histopathology. After 4 weeks of induction and 4 weeks of aquatic exercise training, there was no significant difference in body weight among the HFD, HFD+SE and HFD+AE groups. Serum triglyceride (TG), AST, ALT, and uric acid level were significantly lower in the HFD+SE and HFD+AE groups than in the HFD group. The weight of the perirenal fat pad was significantly lower in the HFD+AE group than in the HFD group. Hepatic TG and total cholesterol (TC) were significantly lower in the HFD+AE group than in the other groups. Long-term intake of a high-fructose diet can lead to obesity and increase the risk of metabolic disease. Based on our findings, we speculate that aquatic exercise training can effectively promote health and fitness. However, aquatic aerobic exercise training appears to have greater benefits than aquatic strength exercise training.

Fructose-mediated effects on gene expression and epigenetic mechanisms associated with NAFLD pathogenesis.

Nonalcoholic fatty liver disease (NAFLD) is a chronic, frequently progressive condition that develops in response to excessive hepatocyte fat accumulation (i.e., steatosis) in the absence of significant alcohol consumption. Liver steatosis develops as a result of imbalanced lipid metabolism, driven largely by increased rates of de novo lipogenesis and hepatic fatty acid uptake and reduced fatty acid oxidation and/or disposal to the circulation. Fructose is a naturally occurring simple sugar, which is most commonly consumed in modern diets in the form of sucrose, a disaccharide comprised of one molecule of fructose covalently bonded with one molecule of glucose. A number of observational and experimental studies have demonstrated detrimental effects of dietary fructose consumption not only on diverse metabolic outcomes such as insulin resistance and obesity, but also on hepatic steatosis and NAFLD-related fibrosis. Despite the compelling evidence that excessive fructose consumption is associated with the presence of NAFLD and may even promote the development and progression of NAFLD to more clinically severe phenotypes, the molecular mechanisms by which fructose elicits effects on dysregulated liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. The aim of this review is to summarize the current research supporting a role for dietary fructose intake in the modulation of transcriptomic and epigenetic mechanisms underlying the pathogenesis of NAFLD.

Association between sleep duration and sleep quality with sugar and sugar-sweetened beverages intake among university students.

BACKGROUND AND AIM: Both short sleep duration and intake of sugar or sugar-sweetened beverages (SSBs) are associated with weight gain; but the linkage between sleep characteristics and sugar or SSBs intake was less studied. We aimed to evaluate the associations of sleep duration and sleep quality with sugar and SSBs intake among Iranian adults. METHOD: This cross-sectional study consisted of 395 adults chosen among students of Isfahan University of Medical Sciences, based on a multistage cluster random sampling method. Sleep characteristics and dietary intakes and were assessed using the Pittsburgh Sleep Quality Index (PSQI) and a 147-item validated food frequency questionnaire, respectively. RESULTS: Mean age and percentage of women in the study population were 22.79 (year) and 51.8%, respectively. No significant difference was observed between sleep duration and sugar intake, but short sleepers (< 6 h/d) had higher consumption of SSBs intake (86.54 vs. 65.73 g/day; P = 0.05) in comparison with those who had more than 8 h/d of sleep. Poor quality sleepers had significantly higher intake of SSBs compared with those with good quality of sleeping (87.09 vs. 56.73 g/day; P = 0.004). No significant correlation was found between sleep duration and SSBs intake. However, sleep quality score was positively correlated with SSBs intake (rp:0.14, P = 0.007) in whole population, such that higher quality score (defined as poor sleep quality) was correlated with greater consumption of SSBs. Similar results were found in younger individuals (rp:0.27, P = 0.002) and non-obese participants (rp:0.14, P = 0.006). CONCLUSION: We found that sleep duration was not associated with sugar or SSBs intake in Iranian adults. Poor sleep quality was correlated with high consumption of SSBs, especially in younger and non-obese individuals. More prospective investigations are required to confirm these findings.

Early-Life Patterns of Sugar Consumption and Dental Caries in the Permanent Teeth: A Birth Cohort Study.

Early-life family conditions may presage caries development in childhood. The aim of this study was to evaluate associations between patterns of sugar consumption in early childhood and permanent dentition caries at age 6 years. A cohort enrolled women accessing prenatal care at public health clinics in Porto Alegre, Brazil. Sociodemographic, anthropometric, and dietary data were collected during pregnancy and 6-month, 12-month, and 3-year follow-ups. Calibrated dental examinations occurred at ages 3 and 6 years. Multivariable logistic regression analysis was performed in series to quantify associations between early-life variables and permanent dentition caries. At age 6 years, 7.9% of children (21/266) had ≥1 caries lesion on permanent teeth (first molars). In unadjusted models, gestational weight gain, sweet food introduction (age 6 months), household sugar purchases (age 3 years), and caries (age 3 years) were positively associated with permanent dentition caries (age 6 years). In multivariable models, each 1-kg increase in gestational weight gain (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.01, 1.16) and each 1-item increase in sweet food consumption at age 6 months (OR: 1.27; 95% CI: 1.02, 1.59) remained statistically significantly associated with permanent molar caries. Findings from this cohort study suggest family and child factors that long predate the permanent dentition, including sugar-related behaviors, predict future dental status, and may inform prevention strategies.

Fructose Production and Metabolism in the Kidney.

Understanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.

Recommendations from paediatric dentistry associations of the Americas on breastfeeding and sugar consumption and oral hygiene in infants for the prevention of dental caries: A bibliometric review.

BACKGROUND: The Internet provides a plethora of information on health issues related to children's oral health. AIM: Identify online recommendations of paediatric dentistry associations of the Americas (PDAAs) regarding breastfeeding practices, weaning, sugar introduction and initiating oral hygiene. DESIGN: Websites of PDAAs were accessed to record recommendations/questions (Q) relevant to early childhood that specifically covered issues about exclusive breastfeeding-Q1, indications of bottle feeding-Q2, when and how to start weaning-Q3 and Q4, respectively, association of breast milk and dental caries-Q5, when to start oral hygiene and how to introduce it-Q6 and Q7, respectively, and guidance on the introduction of sugar-Q8. Similarity/dissimilarity frequencies between the associations (Euclidean distances) were calculated. RESULTS: From 35 countries on the two American continents, 21 associations were affiliated with the International Association of Paediatric Dentistry and/or the Latin American Pediatric Dentistry Association, whereas eight did not have websites. Higher (P < .05) dissimilarities for Q6 (68.2%), Q7 (72.7%), and Q8 (62.1%) were observed. Results were similar for Q1 and Q5 (P > .05). No association mentioned Q2, Q3 or Q4 responses, whereas Q7 was the most frequently discussed issue. CONCLUSION: Not all of the investigated issues are mentioned on websites of PDAAs, potentially stymieing efforts by both the layperson and health professional to gather information.

Exploring the risk factors for early-life sugar consumption: A birth cohort study.

BACKGROUND: Sugar consumption in early childhood is the primary cause of negative health outcomes, including early childhood caries. AIM: To investigate risk factors associated with early-life sugar consumption. DESIGN: Explanatory variables were collected at baseline of a birth cohort in Porto Alegre, Southern Brazil. At six months of age, data were collected on child feeding practices, including the number of foods and beverages containing sugar. Multivariate Poisson regression analysis with robust variance was performed. RESULTS: Virtually all children (98.3%) had consumed sugar by the age of 6 months. Multivariable analysis showed that the number of sweet items was significantly larger in children whose mothers were less than 20 years of age (MR = 1.19; 95% CI: 1.05-1.36), those from non-nuclear families (MR = 1.12; 95% CI: 1.04-1.20), those whose mothers had less than eight years of schooling (MR = 1.34; 95% CI: 1.20-1.50) and those whose mothers smoked (MR = 1.23; 95% CI: 1.13-1.35). Moreover, the number of sweet items was significantly lower among children who breastfed in the first hour of life (MR = 0.85; 95% CI: 0.76-0.95). CONCLUSION: Sugar consumption begins very early, especially in children with no access to breastfeeding in the first hours of life and those from younger, less educated, and smoking mothers.