Fructose-Containing Sugars and Cardiovascular Disease

Cardiovascular disease (CVD) is the single largest cause of mortality in the United States and worldwide. Numerous risk factors have been identified for CVD, including a number of nutritional factors. Recently, attention has been focused on fructose-containing sugars and their putative link to risk factors for CVD. In this review, we focus on recent studies related to sugar consumption and cardiovascular risk factors including lipids, blood pressure, obesity, insulin resistance, diabetes, and the metabolic syndrome. We then examine the scientific basis for competing recommendations for sugar intake. We conclude that although it appears prudent to avoid excessive consumption of fructose-containing sugars, levels within the normal range of human consumption are not uniquely related to CVD risk factors with the exception of triglycerides, which may rise when simple sugars exceed 20% of energy per day, particularly in hypercaloric settings.     

Do Fructose-Containing Sugars Lead to Adverse Health Consequences? Results of Recent Systematic Reviews and Meta-analyses

Sugars have replaced fat as the dominant public health nutrition concern. A fructose-centric view of cardiometabolic disease has emerged whereby fructose-containing sugars are thought to have deleterious effects on body weight, fasting and postprandial blood lipids, glycemia, blood pressure, uric acid, and markers of nonalcoholic fatty liver disease. Long-term prospective cohort studies have not supported these associations when assessing the relation between total fructose-containing sugars at any amount of intake and incident cardiometabolic disease. Conversely, a consistent signal for harm has been reported for sugary beverages when comparing the highest with the lowest intakes. These associations, however, do not hold at moderate intakes, which are more reflective of real-world intakes, are subject to important collinearity effects, and have small risk estimates with modest population-attributable risk fractions. Higher-level evidence from controlled feeding trials shows that fructose-containing sugars in either liquid or solid form have adverse cardiometabolic effects only when they supplement diets with excess calories compared with the same diets without the excess calories. In the absence of harm when fructose-containing sugars are exchanged for other sources of carbohydrate under energy-matched conditions, excess calories appear to be the dominant consideration. Like with the earlier fat story, it is difficult to separate the contribution of fructose-containing sugars from that of other sources of excess calories in the epidemic of obesity and cardiometabolic disease. Attention needs to remain focused on reducing the overconsumption of all caloric foods associated with obesity and cardiometabolic disease, including sugary beverages and foods, and promoting greater physical activity.     

Frequency of Consumption of Whole Fruit,Not Fruit Juice,Is Associated with Reduced Prevalence of Obesity in Korean Adults

BackgroundFruit consumption is known to be beneficial to health. However, the health benefits of fruit juice are controversial due to its high sugar content.ObjectivesTo examine the associations of frequency of consumption of whole fruit and fruit juice with obesity and metabolic syndrome.DesignThis cross-sectional study used data from the 2012-2015 Korea National Health and Nutrition Examination Survey.ParticipantsA total of 10,460 adults (4,082 men and 6,378 women) aged 19 to 64 years were included in the study.Main outcome measuresFrequency of consumption of whole fruit and fruit juice was evaluated using a food frequency questionnaire, and dietary sugar intake was calculated using a 24-hour recall. Obesity and abdominal obesity were determined using body mass index and waist circumference, respectively. Metabolic syndrome was defined on the basis of the National Cholesterol Education Program Adult Treatment Panel III.Statistical analyses performedMultiple logistic regression analysis was performed to examine the associations between frequency of whole fruit or fruit juice consumption and obesity and metabolic syndrome abnormalities.ResultsThe percentage of participants who consumed whole fruit daily was 32.6%, whereas 52.3% consumed fruit juice rarely. The average intake of total sugars was 14.9% of total energy, which was within the recommend range (<20% of total energy) for Koreans. Consuming whole fruit ≥1 time/day was associated with reduced prevalence of obesity, abdominal obesity, and elevated blood pressure compared with consuming whole fruit ≤1 time/wk. However, frequency of fruit juice consumption showed no association with obesity, abdominal obesity, and metabolic syndrome.ConclusionsFrequency of whole fruit consumption was associated with reduced prevalence of obesity and metabolic syndrome abnormalities among Korean adults with average total sugar intake within the recommended range.     

Potential reductions in ultra-processed food consumption substantially improve population cardiometabolic-related dietary nutrient profiles in eight countries

Background and aimsThe negative effect on dietary nutrient profiles is the most obvious mechanism explaining the higher risk of cardiometabolic diseases associated with increased dietary share of UPF observed in large cohort studies.We estimate the proportion of diets with excessive energy density, excessive free sugars or saturated fat contents and insufficient fiber that could be avoided, if UPF consumption was reduced to levels among lowest consumers across eight countries, as well as the proportion of diets with multiple inadequacies.Methods and resultsUsing nationally-representative cross-sectional surveys from Brazil (2008–09), Chile (2010), Colombia (2005), Mexico (2012), Australia (2011–12), the UK (2008–16), Canada (2015), and the US (2015–16), inadequate energy density (≥2.25 kcal/g) or contents of free sugars (>10% of total energy intake), saturated fats (>10% of total energy intake) and fiber (<25 g/2000 kcal) population attributable fractions were quantified.Substantial reductions in nutrient inadequacies would be observed ranging from 50.4% in Chile to 76.8% in US for dietary energy density, from 15.5% in Colombia to 68.4% in Australia for free sugars, from 9.5% in Canada to 35.0% in Mexico for saturated fats, and from 10.3% in UK to 37.9% in Mexico for fiber. Higher reductions would be observed for diets with multiple nutrient inadequacies: from 27.3% in UK to 77.7% in Australia for ≥3 and from 69.4% in Canada to 92.1% in US, for 4 inadequacies.ConclusionsLowering dietary contribution of UPF to levels among country-specific lowest consumers is a way to improve population cardiometabolic-related dietary nutrient profiles.     

Association between Intake of Sugar-Sweetened Beverages and Circulating 25-Hydroxyvitamin D Concentration among Premenopausal Women

Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OH)D) concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OH)D concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OH)D were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OH)D concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OH)D levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1–3 and >3 servings/week, respectively; r = −0.11 (p = 0.004)). A correlation was observed between intake of other carbonated beverages and 25(OH)D concentrations but was not statistically significant (r = −0.06 (p = 0.10)). No association was observed between intake of sweet fruit drinks and 25(OH)D concentrations. This study suggests that high intake of colas may decrease 25(OH)D levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation.     

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

Background and aimsThe 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 resultsTwo 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)].ConclusionsOverall, 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.     

Galactosides in the rhizosphere: utilization by Sinorhizobium meliloti and development of a biosensor

Identifying the types and distributions of organic substrates that support microbial activities around plant roots is essential for a full understanding of plant-microbe interactions and rhizosphere ecology. We have constructed a strain of the soil bacterium Sinorhizobium meliloti containing a gfp gene fused to the melA promoter which is induced on exposure to galactose and galactosides. We used the fusion strain as a biosensor to determine that galactosides are released from the seeds of several different legume species during germination and are also released from roots of alfalfa seedlings growing on artificial medium. Galactoside presence in seed wash and sterile root washes was confirmed by HPLC. Experiments examining microbial growth on alpha-galactosides in seed wash suggested that alpha-galactoside utilization could play an important role in supporting growth of S. meliloti near germinating seeds of alfalfa. When inoculated into microcosms containing legumes or grasses, the biosensor allowed us to visualize the localized presence of galactosides on and around roots in unsterilized soil, as well as the grazing of fluorescent bacteria by protozoa. Galactosides were present in patches around zones of lateral root initiation and around roots hairs, but not around root tips. Such biosensors can reveal intriguing aspects of the environment and the physiology of the free-living soil S. meliloti before and during the establishment of nodulation, and they provide a nondestructive, spatially explicit method for examining rhizosphere soil chemical composition.     

Arabidopsis ROCK1 transports UDP-GlcNAc/UDP-GalNAc and regulates ER protein quality control and cytokinin activity

The formation of glycoconjugates depends on nucleotide sugars, which serve as donor substrates for glycosyltransferases in the lumen of Golgi vesicles and the endoplasmic reticulum (ER). Import of nucleotide sugars from the cytosol is an important prerequisite for these reactions and is mediated by nucleotide sugar transporters. Here, we report the identification of REPRESSOR OF CYTOKININ DEFICIENCY 1 (ROCK1, At5g65000) as an ER-localized facilitator of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) transport in Arabidopsis thaliana. Mutant alleles of ROCK1 suppress phenotypes inferred by a reduced concentration of the plant hormone cytokinin. This suppression is caused by the loss of activity of cytokinin-degrading enzymes, cytokinin oxidases/dehydrogenases (CKXs). Cytokinin plays an essential role in regulating shoot apical meristem (SAM) activity and shoot architecture. We show that rock1 enhances SAM activity and organ formation rate, demonstrating an important role of ROCK1 in regulating the cytokinin signal in the meristematic cells through modulating activity of CKX proteins. Intriguingly, genetic and molecular analysis indicated that N-glycosylation of CKX1 was not affected by the lack of ROCK1-mediated supply of UDP-GlcNAc. In contrast, we show that CKX1 stability is regulated in a proteasome-dependent manner and that ROCK1 regulates the CKX1 level. The increased unfolded protein response in rock1 plants and suppression of phenotypes caused by the defective brassinosteroid receptor bri1-9 strongly suggest that the ROCK1 activity is an important part of the ER quality control system, which determines the fate of aberrant proteins in the secretory pathway.The biosynthesis of glycans and glycoconjugates (e.g., glycoproteins or glycolipids) requires glycosyltransferases residing in the Golgi apparatus and endoplasmic reticulum (ER). Their activity depends on the presence of activated monosaccharide donor substrates, nucleotide sugars. About 30 different nucleotide sugars have been detected in plants, most of which are synthesized in the cytosol and required to be selectively transported over the compartmental membrane (1). This transport is mediated by nucleotide sugar transporters (NSTs), which generally function as antiporters transporting nucleotide sugars usually in exchange to the corresponding nucleoside monophosphate across the membranes of ER and Golgi (2). They belong to the NST/triose-phosphate translocator family consisting of 40 members in Arabidopsis (3). Transported substrates have been previously identified for 13 NSTs in Arabidopsis, which include UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal), GDP-mannose (GDP-Man), and CMP-sialic acid (4–8). However, molecular mechanisms underlying transport of other nucleotide sugars in plants are not understood. Interestingly, for some nucleotide sugars, like for example UDP-GalNAc, which was shown to accumulate in plant tissues (9), no target molecule carrying the corresponding sugar moiety has been identified. Hence, the cellular function of several nucleotide sugars is completely unknown in plants (1).Protein glycosylation can have an influence on protein folding and stability, interaction with proteins and ligands, or enzymatic activity (10–12). Protein N-glycosylation starts within the ER lumen with the transfer of a cytosol-derived core glycan on the nitrogen of an asparagine residue followed by its transformation into a high-mannose glycan (13). After protein transport into the Golgi apparatus, N-glycans can be further modified to hybrid, complex or paucimannosidic N-glycans. The initial committed step in this process is the addition of a GlcNAc residue to appropriately trimmed glycans by N-acetylglucosaminyltransferase I (GnT-I) (14). Whereas there are many examples for luminal protein O-glycosylation on serine and threonine residues of mammalian proteins (15), the only luminal O-glycosyltransferase described so far in plants adds glycans to hydroxyproline residues of proteins found in the cell wall (16).Glycosylation is essential for protein folding and maturation in the ER, which is equipped with a quality control (ERQC) system that safeguards correct folding and assembly of secretory and membrane proteins in eukaryotic cells and that eliminates improperly folded proteins (17). Under stress conditions, misfolded proteins can accumulate in the ER, which leads to ER stress. This triggers an unfolded protein response (UPR) that alleviates ER stress through enhanced expression of genes encoding components of the protein folding machinery or the ER-associated degradation (ERAD) system (18).Growth and development of plants is controlled by phytohormones. Among them, a group of N⁶-substituted adenine derivatives called cytokinins (CKs) play an important role in many developmental processes, like regulation of cell proliferation and differentiation in root and shoot apical meristems (SAM) (19–21). The catabolic degradation of CKs is mediated by CK oxidase/dehydrogenase (CKX) enzymes encoded by seven genes in Arabidopsis (22) and their overexpression causes a CK deficiency characterized by complex morphological changes such as a smaller SAM, a dwarfed shoot, and enhanced root growth (19). ckx3,5 Arabidopsis plants develop more active generative shoot meristems, larger flower organs, and more ovules (23). This demonstrates an important role of regulated CK degradation in defining the CK status of a given tissue. Most CKXs are probably N-glycoproteins (22, 24) and the role of glycosylation in fine tuning CKX activity has been discussed (25); however, the hypothesis has not been confirmed and no direct analysis of in planta glycosylation of individual CKX proteins has been reported.Here we describe a suppressor allele of CK deficiency named repressor of cytokinin deficiency 1 (rock1). Transport assays revealed ROCK1 to be the first transporter of UDP-GlcNAc and UDP-GalNAc identified in plants. We present data demonstrating that ROCK1 plays an important role in regulating CK responses and activity of the generative SAM through modulating the activity of CKX proteins. We provide evidence suggesting that the activity of ROCK1, in supplying the substrate(s) for a yet to be described protein modification, is important for ERQC in plants.