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High dietary sugar (HDS), a contemporary dietary concern due to excessive intake of added sugars and carbohydrates, escalates the risk of metabolic disorders and concomitant cancers. However, the molecular mechanisms underlying HDS-induced cancer progression are not completely understood. We found that phosphoenolpyruvate carboxykinase 1 (PEPCK1), a pivotal enzyme in gluconeogenesis, is paradoxically upregulated in tumors by HDS, but not by normal dietary sugar (NDS), during tumor progression. Targeted knockdown of pepck1, but not pepck2, specifically in tumor tissue in Drosophila in vivo, not only attenuates HDS-induced tumor growth but also significantly improves the survival of Ras/Src tumor-bearing animals fed HDS. Interestingly, HP1a-mediated heterochromatin interacts directly with the pepck1 gene and downregulates pepck1 gene expression in wild-type Drosophila. Mechanistically, we demonstrated that, under HDS conditions, pepck1 knockdown reduces both wingless and TOR signaling, decreases evasion of apoptosis, reduces genome instability, and suppresses glucose uptake and trehalose levels in tumor cells in vivo. Moreover, rational pharmacological inhibition of PEPCK1, using hydrazinium sulfate, greatly improves the survival of tumor-bearing animals with pepck1 knockdown under HDS. This study is the first to show that elevated levels of dietary sugar induce aberrant upregulation of PEPCK1, which promotes tumor progression through altered cell signaling, evasion of apoptosis, genome instability, and reprogramming of carbohydrate metabolism. These findings contribute to our understanding of the complex relationship between diet and cancer at the molecular, cellular, and organismal levels and reveal PEPCK1 as a potential target for the prevention and treatment of cancers associated with metabolic disorders., (© 2024. The Author(s).)

The effects and underlying mechanisms of metformin which can improve glucose homeostasis of fish have rarely been explored. This experiment aimed to explore the influence of metformin on growth performance, body composition, liver health, hepatic glucolipid metabolic capacity and IR/PI 3 K/AKT pathway in grass carp (Ctenopharyngodon idella) fed high-carbohydrate diets. A normal diet (Control) and high carbohydrate diets with metformin supplementation (0.00 %, 0.20 %, 0.40 %, 0.60 % and 0.80 %) were configured. Six groups of healthy fish were fed with the experimental diet for eight weeks. The results showed that the growth performance of grass carp was impaired in high carbohydrate diet. Impairment of IR/PI 3 K/AKT signalling pathway reduced insulin sensitivity, while hepatic oxidative stress damage and decreased immunity affected liver metabolic function. The glycolysis and lipolysis decrease while the gluconeogenesis and fat synthesis increase, which triggers hyperglycaemia and lipid deposition in the body. Metformin supplementation restored the growth performance of grass carp. Metformin improved IR/PI 3 K/AKT pathway signalling and alleviated insulin resistance, while liver antioxidant capacity and immunity were enhanced resulting in the restoration of liver health. The elevation of glycolysis and lipolysis maintains glycaemic homeostasis and reduces lipid deposition, respectively. These results suggest that metformin supplementation restores liver health and activates the IR/PI 3 K/AKT signalling pathway, ameliorating insulin resistance and glucose-lipid metabolism disorders caused by a high-carbohydrate diet. As judged by HOMA-IR, the optimum supplementation level of metformin in grass carp (C. idella) fed a high-carbohydrate diet is 0.67 %., Competing Interests: Declaration of competing interest We confirmed there is no conflict of interested to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to investigate the associations between carbohydrate intake and gout risk, along with interactions between genetic susceptibility and carbohydrates, and the mediating roles of biomarkers. We included 187,387 participants who were free of gout at baseline and completed at least one dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between carbohydrate intake and gout risk. Over a median follow-up of 11.69 years, 2548 incident cases of gout were recorded. Total carbohydrate intake was associated with a reduced gout risk (Q4 vs. Q1: HR 0.67, 95% CI 0.60-0.74), as were total sugars (0.89, 0.80-0.99), non-free sugars (0.70, 0.63-0.78), total starch (0.70, 0.63-0.78), refined grain starch (0.85, 0.76-0.95), wholegrain starch (0.73, 0.65-0.82), and fiber (0.72, 0.64-0.80), whereas free sugars (1.15, 1.04-1.28) were associated with an increased risk. Significant additive interactions were found between total carbohydrates and genetic risk, as well as between total starch and genetic risk. Serum urate was identified as a significant mediator in all associations between carbohydrate intake (total, different types, and sources) and gout risk. In conclusion, total carbohydrate and different types and sources of carbohydrate (excluding free sugars) intake were associated with a reduced risk of gout.

Both maternal obesity and postnatal consumption of obesogenic diets contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). However, there is no consensus as to whether diets that are high in fat or carbohydrates/sugars differentially influence the development of HCC. Moreover, the long-term effects of prenatal HF exposure on HCC and whether this is influenced by postnatal diet has not yet been evaluated. C57BL/6 dams were fed either a low-fat, high-carbohydrate control (C) or low-carbohydrate, high-fat (HF) diet. At weaning, male and female offspring were fed the C or HF diet, generating four diet groups: C/C, C/HF, HF/C and HF/HF. Tissues were collected at 16 months of age and livers were assessed for MASLD and HCC. Glucose regulation and pancreatic morphology were also evaluated. Liver tissues were assessed for markers of glycolysis and fatty acid metabolism and validated using a human HCC bioinformatic database. Both C/HF and HF/HF mice developed obesity, hyperinsulinemia and a greater degree of MASLD than C/C and HF/C offspring. However, despite significant liver and pancreas pathology, C/HF mice had the lowest incidence of HCC while tumour burden was highest in HF/C male offspring. The molecular profile of HCC mouse samples suggested an upregulation of the pentose phosphate pathway and a downregulation of fatty acid synthesis and oxidation, which was largely validated in the human dataset. Both pre-weaning HF diet exposure and post-weaning consumption of a high-carbohydrate diet increased the risk of developing spontaneous HCC in aged mice. However, the influence of pre-weaning HF feeding on HCC development appeared to be stronger in the context of post-weaning obesity. As rates of maternal obesity continue to rise, this has implications for the future incidence of HCC and possible dietary manipulation of offspring carbohydrate intake to counteract this risk.

In Korea and other Asian countries, traditional high-carbohydrate diets are increasingly associated with metabolic syndrome (MetS) and its complications. As dietary patterns shift, there is a growing need to assess the effect of these changes on health outcomes related to MetS. This study aimed to investigate the prospective relationship between carbohydrate consumption and the risk of MetS and its components. We analyzed data from 7902 participants from the Korean Association Resource, part of the Korean Genome and Epidemiology Study Dietary intakes, including carbohydrates and fiber, were assessed using a validated semi-quantitative food frequency questionnaire, allowing for the calculation of the proportion of total energy from carbohydrates (P_CARB) and the carbohydrate-to-fiber ratio to assess carbohydrate quality. Blood samples were collected after at least eight hours of fasting for laboratory analysis. We employed Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals, focusing on the relationship between the P_CARB and the risk of developing MetS and its individual components, while adjusting for carbohydrate quality. In the fully adjusted model, which accounted for carbohydrate quality as a covariate, individuals in the highest percentile of the P_CARB showed a significantly increased risk of MetS, hypertriglyceridemia, hypo-high density lipoprotein cholesterolemia, dyslipidemia, and high blood pressure, compared to those in the lowest P_CARB group. Spline curve analyses indicated that the risks for MetS and its components consistently escalated with increasing P_CARB, with all p -values for nonlinearity exceeding 0.05. The findings suggest that higher levels of P_CARB are associated with an increased risk of MetS and related conditions, except for high fasting glucose. These results highlight the importance of dietary awareness and potential adjustments for populations consuming high-carbohydrate diets.

Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre-mediated deletion of TGF-β receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.

Background: Regarding the role of insulin and insulin-inducing dietary factors in some cancers' etiology, we hypothesized that the risk of colorectal cancer may be lessened by following a lower carbohydrate and insulinogenic diet. Therefore, we performed this study to explore the association between a low-carbohydrate diet and insulin indices and the odds of colorectal cancer., Method: This hospital-based case-control study was conducted on 150 newly diagnosed colorectal cancer patients and 300 healthy age- and sex-matched hospitalized controls. A valid and reliable food frequency questionnaire was used to calculate the insulin indices and low-carbohydrate diet score. Multivariate logistic regression was used to estimate the association between insulin indices and low-carbohydrate diet and the odds of colorectal cancer., Result: After adjusting for potential confounders, individuals in the highest tertile of insulin indices had a higher risk of colorectal cancer (OR insulin index  = 3.46; 95% CI, 2.00-5.96; OR insulin load  = 2; 95% CI, 1.17-3.41). No association was found between a low-carbohydrate diet and colorectal cancer (OR = 1.55; 95% CI, 0.85-2.84)., Conclusion: Current results demonstrated that a high insulinemic diet was associated with a higher risk of colorectal cancer., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

People are living longer and rates of age-related diseases such as age-related macular degeneration (AMD) are accelerating, placing enormous burdens on patients and health care systems. The quality of carbohydrate foods consumed by an individual impacts health. The glycemic index (GI) is a kinetic measure of the rate at which glucose arrives in the blood stream after consuming various carbohydrates. Consuming diets that favor slowly digested carbohydrates releases sugar into the bloodstream gradually after consuming a meal (low glycemic index). This is associated with reduced risk for major age-related diseases including AMD, cardiovascular disease, and diabetes. In comparison, consuming the same amounts of different carbohydrates in higher GI diets, releases glucose into the blood rapidly, causing glycative stress as well as accumulation of advanced glycation end products (AGEs). Such AGEs are cytotoxic by virtue of their forming abnormal proteins and protein aggregates, as well as inhibiting proteolytic and other protective pathways that might otherwise selectively recognize and remove toxic species. Using in vitro and animal models of glycative stress, we observed that consuming higher GI diets perturbs metabolism and the microbiome, resulting in a shift to more lipid-rich metabolomic profiles. Interactions between aging, diet, eye phenotypes and physiology were observed. A large body of laboratory animal and human clinical epidemiologic data indicates that consuming lower GI diets, or lower glycemia diets, is protective against features of early AMD (AMDf) in mice and AMD prevalence or AMD progression in humans. Drugs may be optimized to diminish the ravages of higher glycemic diets. Human trials are indicated to determine if AMD progression can be retarded using lower GI diets. Here we summarized the current knowledge regarding the pathological role of glycative stress in retinal dysfunction and how dietary strategies might diminish retinal disease., Competing Interests: Declaration of competing interest The authors declare that the manuscript was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

To date, although the high-carbohydrate (HC) feed has been extensively adopted in the aquaculture industry, its effects on the intestinal function and development of aquatic animals still remain unclear. In addition, the corresponding nutritional intervention is still barely reported. This study aimed to evaluate the influence of xylooligosaccharides (XOS) on the intestinal health of Megalobrama amblycephala subjected to a HC feeding. Fish (average weight: 44.55 ± 0.15 g) were randomly offered 3 diets, including a control one (29 % carbohydrate), a HC one (41 % carbohydrate), and a XOS supplemented one (HC + 1.0 % XOS, HCX) respectively for 12 weeks. The HC feeding caused morphological abnormalities of intestine, an increased intestinal permeability, and the intestinal immunosuppression, all of which were markedly reversed by XOS administration. In addition, compared with the HC group, HCX feeding remarkably promoted the intestinal activities of digestive and brush border enzymes, and the expressions of cell proliferation-related proteins (Wnt10b and Cyclin D1). The 16s rDNA sequencing also revealed that XOS administration increased the abundance of beneficial bacteria, and decreased that of pathogenic ones. In conclusion, dietary supplementation of XOS improved the intestinal histomorphology, barrier function, cell proliferation and bacterial communities of carbohydrate-overloaded fish Megalobrama amblycephala., Competing Interests: Declaration of competing interest The authors declare no financial interest with any individual or organization that may affect the results of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stearoyl-CoA desaturase-1 (SCD1) is a pivotal enzyme in lipogenesis, which catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids, whose ablation downregulates lipid synthesis, preventing steatosis and obesity. Yet deletion of SCD1 promotes hepatic inflammation and endoplasmic reticulum stress, raising the question of whether hepatic SCD1 deficiency promotes further liver damage, including fibrosis. To delineate whether SCD1 deficiency predisposes the liver to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), we employed in vivo SCD1 deficient global and liver-specific mouse models fed a high carbohydrate low-fat diet and in vitro established AML12 mouse cells. The absence of liver SCD1 remarkably increased the saturation of liver lipid species, as indicated by lipidomic analysis, and led to hepatic fibrosis. Consistently, SCD1 deficiency promoted hepatic gene expression related to fibrosis, cirrhosis, and HCC. Deletion of SCD1 increased the circulating levels of Osteopontin, known to be increased in fibrosis, and alpha-fetoprotein, often used as an early marker and a prognostic marker for patients with HCC. De novo lipogenesis or dietary supplementation of oleate, an SCD1-generated MUFA, restored the gene expression related to fibrosis, cirrhosis, and HCC. Although SCD1 deficient mice are protected against obesity and fatty liver, our results show that MUFA deprivation results in liver injury, including fibrosis, thus providing novel insights between MUFA insufficiency and pathways leading to fibrosis, cirrhosis, and HCC under lean non-steatotic conditions., Competing Interests: Declaration of competing interest The authors who participated in this study declare no conflicts of interest regarding this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the potential interplay between a carbohydrate diet and inflammation in atherosclerotic cardiovascular disease (ASCVD) development. ATTICA is a prospective observational study of 3042 adults free of cardiovascular disease (CVD) who were recruited in 2002 and followed for 20 years. Baseline data on carbohydrate intake and inflammatory biomarker levels were collected. Participants were stratified by carbohydrate intake (low vs. high: 190 g/day) and carbohydrate quality. At the 20-year follow-up in 2022, 1988 participants had complete data for CVD assessment. The overall quantity and quality of carbohydrate intake did not show a significant association with CVD incidence; inflammatory markers were positively correlated with an increased risk of CVD ( p -values < 0.05). Chronic systemic inflammation seems to affect the CVD risk of participants who had a higher carbohydrate intake more substantially, as compared to those with low intake. Additionally, individuals with higher high carbohydrate/low fiber intake experienced a higher risk of inflammation-related CVD, compared to those with high carbohydrate/high fiber intake. The presented findings revealed that the effect of inflammation markers on the CVD risk is influenced both by the amount and quality of carbohydrate intake, irrespective of overall dietary habits and clinical and lifestyle characteristics.

Background: Mounting evidence links glucose intolerance and diabetes as aspects of metabolic dysregulation that are associated with an increased risk of developing dementia. Inflammation and inflammasome activation have emerged as a potential link between these disparate pathologies. As diet is a key factor in both the development of metabolic disorders and inflammation, we hypothesize that long term changes in dietary factors can influence nervous system function by regulating inflammasome activity and that this phenotype would be sex-dependent, as sex hormones are known to regulate metabolism and immune processes., Methods: 5-week-old male and female transgenic mice expressing a caspase-1 bioluminescent reporter underwent cranial window surgeries and were fed control (65% complex carbohydrates, 15% fat), high glycemic index (65% carbohydrates from sucrose, 15% fat), or ketogenic (1% complex carbohydrates, 79% fat) diet from 6 to 26 weeks of age. Glucose regulation was assessed with a glucose tolerance test following a 4-h morning fast. Bioluminescence in the brain was quantified using IVIS in vivo imaging. Blood cytokine levels were measured using cytokine bead array. 16S ribosomal RNA gene amplicon sequencing of mouse feces was performed to assess alterations in the gut microbiome. Behavior associated with these dietary changes was also evaluated., Results: The ketogenic diet caused weight gain and glucose intolerance in both male and female mice. In male mice, the high glycemic diet led to increased caspase-1 biosensor activation over the course of the study, while in females the ketogenic diet drove an increase in biosensor activation compared to their respective controls. These changes correlated with an increase in inflammatory cytokines present in the serum of test mice and the emergence of anxiety-like behavior. The microbiome composition differed significantly between diets; however no significant link between diet, glucose tolerance, or caspase-1 signal was established., Conclusions: Our findings suggest that diet composition, specifically the source and quantity of carbohydrates, has sex-specific effects on inflammasome activation in the central nervous system and behavior. This phenotype manifested as increased anxiety in male mice, and future studies are needed to determine if this phenotype is linked to alterations in microbiome composition., (© 2024. The Author(s).)

Aims: Numerous studies report positive associations between total carbohydrate (CHO) intake and incident metabolic syndrome (MetS), but few differentiate quality or type of CHO relative to MetS. We examined source of CHO intake, including added sugar (AS), AS-rich CHO foods, and sugar-sweetened beverages (SSBs) associated with incident MetS in adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study., Methods and Results: Among 3154 Black American and White American women and men aged 18-30 years at baseline, dietary intake was assessed by diet history three times over 20 years. Sources of AS-rich CHO foods and beverages include sugar-rich refined grain products, candy, sugar products, and SSBs. Incident MetS was created according to standard criteria. Time-dependent Cox proportional hazards regression analysis evaluated the associations of incident MetS across quintiles of cumulative intakes of AS-rich CHO foods and beverages, AS, and SSBs adjusted for potential confounding factors over 30 years of follow-up. The associations of AS-rich CHO foods and beverages, AS, and SSB intakes with incident MetS were consistent. Compared with the lowest intake, the greatest intakes of AS-rich CHOs, AS, and SSBs were associated with 59% (Ptrend < 0.001), 44% (Ptrend = 0.01), and 34% (Ptrend = 0.03) higher risk of developing MetS, respectively. As expected, diet quality was lower across increasing quintiles of AS-rich CHO foods and beverages, AS, and SSBs (all Ptrend < 0.001)., Conclusion: Our study findings are consistent with an elevated risk of developing MetS with greater consumption of AS, AS-rich CHO foods, and SSBs, which support consuming fewer AS-rich CHO foods and SSBs., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The study aimed to compare the effects of a diet rich in fat, carbohydrates and protein on rat kidneys. The study was conducted on 40 Wistar albino rats bred at İnönü University Faculty of Medicine after the approval of the ethics committee. Rats were randomly divided into 4 groups: Control group, and the groups where the animals were fed with high carbohydrate, fat and protein rich feed. After the applications, the rat kidney tissues were removed by laparoscopy under anesthesia and blood samples were collected. 13 weeks long fat-rich and carbohydrate feed application had negative effects on oxidant-antioxidant balance, oxidative stress index, inflammation markers, kidney functions tests, histopathology and immunohistochemistry caspase-3 findings in rat kidney tissues, especially in the carbohydrate group when compared to the controls. Protein-rich feed, there were no significant difference in biochemical and histopathology compared to the control group. Fat and carbohydrate rich feed led to an increase in oxidative stress in rat kidney tissues. Oxidative stress led to nephrotoxicity, which in turn led to chronic kidney tissue damages. A more balanced and protein-rich diet instead of excessive sugar and fatty food intake could be suggested to prevent chronic kidney damage., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: High FODMAP (fermentable oligo-, di, monosaccharides and polyols) foods have been linked with worsening symptoms of IBS patients. The aim was to compare gastrointestinal symptoms and dietary intake of patients with irritable bowel syndrome following a low FODMAP diet, with or without individual nutrition therapy., Materials and Methods: A total of 54 patients that met Rome IV criteria for IBS were randomized into two groups, guided group (individual nutrition therapy, n=28) and self-management group (learned about low FODMAP diet online, n=26). Both groups followed low FODMAP diet for 4 weeks. Four-day food records were used to assess dietary intake. Symptoms were assessed by the IBS-severity scoring system (ISB-SSS)., Results: The number of subjects who did not complete the study was 13, thereof five in the nutrition therapy and eight in the self-management group, leaving 23 and 18 subjects available for analysis, respectively. Symptoms declined from baseline to endpoint in both groups, by 183±101 points on average in the group receiving nutrition therapy (p< 0.001) and 132±110 points in the self-management group (p< 0.001), with no difference between groups. At baseline, about 80% of meals in both groups contained food high in FODMAP's. The corresponding proportion was 9% and 36% in week 3 in the nutrition therapy and self-management group, respectively (p< 0.001)., Conclusion: Both groups experienced relieve of symptoms, but compliance to the low FODMAP diet was better in the group receiving individual nutrition therapy compared with the group who only received instructions on how to learn about low FODMAP diet online.

The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic host immune responses including host defense against pathogens. Disease-associated gut dysbiosis has been characterized by blooms of pathobionts, which are bacterial species that can drive disease under certain conditions. Pathobionts like Enterobacteriaceae often bloom during flares of inflammatory bowel disease (IBD) and are causally linked with IBD in murine models. In this issue of the JCI, Hecht and colleagues investigated how simple carbohydrates are causally linked to the bloom of the gut pathobiont Klebsiella pneumoniae, which belong to the Enterobacteriaceae family. Notably, the presence of fiber reduced the dissemination of K. pneumoniae into the blood and liver in a colitis model. Their findings provide a diet-related mechanism for gut dysbiosis, which has implications in the management of IBD and other conditions in which gut dysbiosis is an underlying factor.

Background: The association between macronutrient intake and diabetes is unclear. We used data from the China Health and Nutrition Survey to explore the association between macronutrient intake trajectories and diabetes risk in this study., Methods: We included 6755 participants who did not have diabetes at baseline and participated in at least three surveys. The energy supply ratio of carbohydrate, protein, and fat was further calculated from dietary data; different macronutrient trajectories were determined using multitrajectory models; and multiple Cox regression models were used to evaluate the association between these trajectories and diabetes., Results: We found three multitrajectories: decreased low carbohydrate-increased moderate protein-increased high fat (DLC-IMP-IHF), decreased high carbohydrate-moderate protein-increased low fat (DHC-MP-ILF), and balanced-macronutrients (BM). Compared to the BM trajectory, DHC-MP-ILF trajectories were significantly associated with increased risk of diabetes (hazard ratio [HR]: 3.228, 95% confidence interval [CI]: 1.571-6.632), whereas no association between DLC-IMP-IHF trajectories and diabetes was found in our study (HR: 0.699, 95% CI: 0.351-1.392)., Conclusions: The downward trend of high carbohydrate and the increasing trend of low fat increased the risk of diabetes in Chinese adults., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Several studies have demonstrated the protective effects of melatonin against metabolic diseases, such as liver steatosis. However, its therapeutic effects have received less scrutiny. The present study aimed to explore melatonin's therapeutic effectiveness in treating non-alcoholic fatty liver disease (NAFLD) induced by a high-carbohydrate high-fat (HCHF) diet in rats. The NAFLD was developed in male Wistar rats using an HCHF diet for 8 weeks. Afterward, they were given melatonin orally for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, along with the HCHF diet. In addition, six age-matched healthy rats received the highest dose of melatonin (30 mg/kg) for the same duration. Rats on the HCHF diet exhibited obesity, dyslipidemia, hyperglycemia, glucose intolerance, insulin resistance, inflammation, oxidative stress, and liver injury (steatosis). Melatonin treatment at 10 mg/kg and 30 mg/kg reduced body weight, adiposity index, oxidative damage, and inflammation but did not affect impaired glucose metabolism induced by the HCHF diet. Meanwhile, the highest dose of melatonin (30 mg/kg) reduced the liver steatosis index in HCHF rats but caused mild liver damage in healthy rats. In conclusion, using melatonin demonstrated positive outcomes in treating NAFLD induced by the HCHF diet in rats, with no noteworthy effects observed in healthy rats. A moderate dosage of 10 mg/kg of melatonin proved to be a safer and more efficient method for reducing HCHF diet-induced NAFLD in rats. Higher melatonin doses should be cautiously administered due to potential disruptions in lipid metabolism and the risk of liver complications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: The association between glycemic index (GI), glycemic load (GL), total carbohydrate intake, and risk of cardiovascular diseases has been controversial. Premature coronary artery disease (PCAD) is characterized by the age of onset lower than 55 and 65 respectively in men and women. The aim of the current study is to investigate the relationship between GI, GL and carbohydrate levels and the risk of PCAD in Iran., Methods and Results: In total, 419 healthy people and 553 patients struggling with PCAD have participated in this case-control study. Dietary GI and GL were calculated using a validated food frequency questionnaire at the baseline. Crude and multivariable logistic regression were used to assess the relationship between GI, GL, and total carbohydrate intake and risk of PCAD. The mean age of participants was 51.13 ± 6.90 and 46 % of them were women. A significant direct relationship was observed between higher carbohydrate intake (OR: 1.74, 95%CI: 1.27-2.38) and GL levels (OR: 1.56, 95 % CI:1.14-2.14) and risk of PCAD. These associations were not significant after adjusting for potential variables. No significant association has been observed between GI and odds of PCAD even after controlling for all covariates., Conclusion: We found no significant association between GI, GL, and total carbohydrate intake and risk of premature coronary heart disease. Further observational and clinical trials are required to assess this relationship., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

This study aimed to explore the association of carbohydrate to fiber ratio (CFR) with metabolic dysfunction-associated fatty liver disease (MAFLD) in adults. In this study, data from the 2 cycles (2017-2018 and 2019-2020) of the NHANES were used. Univariate and multivariate weighted logistic regression analyses were applied to evaluate the association between CFR and MAFLD. Odds ratios (ORs) and 95% confidence levels (CIs) were estimated. Subgroup analysis was further performed in terms of gender, age and comorbidity (diabetes, hypertension). A total of 3180 individuals were included, with 1408 (44.28%) in the non-MAFLD group and 1772 (55.72%) in the MAFLD group. After adjusting different variables, a dietary fiber intake of 11.15-18.40 g was associated with significantly lower odds of MAFLD compared with a fiber intake < 11.15 g (OR = 0.71, 95% CI 0.54-0.93). In contrast to a dietary CFR < 12.58, a CFR > 19.91 was associated with significantly higher odds of MAFLD (OR = 1.57, 95% CI 1.09-2.27). Compared with females with a dietary CFR < 12.58, those with a CFR > 19.91 had significantly increased odds of MAFLD (OR = 1.87, 95% CI 1.29-2.73). Among individuals aged < 65 years, a dietary CFR > 19.91 was associated with higher odds of MAFLD than a dietary CFR < 12.58 (OR = 1.52, 95% CI 1.02-2.25). For participants without diabetes (OR = 1.79, 95% CI 1.26-2.54) or hypertension (OR = 1.93, 95% CI 1.02-3.65), a dietary CFR > 19.91 was associated with elevated odds of MAFLD than a CFR < 12.58. In summary, a higher CFR was associated with significantly greater odds of MAFLD, indicating the negative association between carbohydrate quality and MAFLD. The research would be conducive to metabolic dysfunction-associated fatty liver disease treatment., (© 2024. The Author(s).)

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

The beneficial effects of high-fat low-carbohydrate (HFLC) diets on glucose metabolism have been questioned and their effects on liver metabolism are not totally clear. The aim of this work was to investigate the effects of an HFLC diet under different energy conditions on glucose homeostasis, fatty liver development, and hepatic gluconeogenesis using the isolated perfused rat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) was administered to rats for 4 weeks under three conditions: ad libitum (hypercaloric), isocaloric, and hypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liver were higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric and hypercaloric groups, although insulin sensitivity was not altered. HFLC diet also caused marked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reduced capacity to metabolize alanine, the latter effect being more intense in the hypocaloric condition. Thus, even when HFLC diets are used for weight loss, our data imply that they can potentially cause harmful consequences for the liver., Competing Interests: There are no competing interests.

Improper glycemic carbohydrates (GCs) consumption can be a potential risk factor for metabolic diseases such as obesity and diabetes, which may lead to cognitive impairment. Although several potential mechanisms have been studied, the biological relationship between carbohydrate consumption and neurocognitive impairment is still uncertain. In this review, the main effects and mechanisms of GCs' digestive characteristics on cognitive functions are comprehensively elucidated. Additionally, healthier carbohydrate selection, a reliable research model, and future directions are discussed. Individuals in their early and late lives and patients with metabolic diseases are highly susceptible to dietary-induced cognitive impairment. It is well known that gut function is closely related to dietary patterns. Unhealthy carbohydrate diet-induced gut microenvironment disorders negatively impact cognitive functions through the gut-brain axis. Moreover, severe glycemic fluctuations, due to rapidly digestible carbohydrate consumption or metabolic diseases, can impair neurocognitive functions by disrupting glucose metabolism, dysregulating calcium homeostasis, oxidative stress, inflammatory responses, and accumulating advanced glycation end products. Unstable glycemic status can lead to more severe neurological impairment than persistent hyperglycemia. Slow-digested or resistant carbohydrates might contribute to better neurocognitive functions due to stable glycemic response and healthier gut functions than fully gelatinized starch and nutritive sugars.

Background: Higher intake of total sugar has been linked with coronary heart disease (CHD) risk, but the role of individual sugars, particularly fructose, is uncertain., Objectives: This study aimed to investigate the associations of individual dietary sugars with CHD risk., Methods: In prospective cohort studies, we followed 76,815 women (Nurses' Health Study, 1980-2020) and 38,878 men (Health Professionals Follow-up Study, 1986-2016). Sugar and carbohydrate intake, including total fructose equivalents ([TFE] from fructose monosaccharides and sucrose), total glucose equivalents ([TGE] from glucose monosaccharides, disaccharides, and starch), and other sugar types, was measured every 2 to 4 y by semiquantitative food frequency questionnaires., Results: We documented 9,723 incident CHD cases over 40 years. In isocaloric substitution models with total fat as a comparison nutrient, comparing extreme quintiles of intake, hazard ratios (HRs), 95% confidence interval [CI]) for CHD risk were 1.31 (1.20 to 1.42; P trend < 0.001) for TGE and 1.03 (0.94 to 1.11; P trend = 0.25) for TFE. TFE from fruits and vegetables was not associated with CHD risk (P trend = 0.70), but TFE from added sugar and juice was associated with CHD risk (HR: 1.12, 95% CI: 1.04 to 1.20; P trend < 0.01). Intakes of total sugars and added sugar were positively associated with CHD risk (HRs: 1.16, 95% CI: 1.07 to 1.26, P trend < 0.001; 1.08, 95% CI: 0.99 to 1.16, P trend = 0.04)., Conclusions: Intakes of TGE, total sugar, added sugar, and fructose from added sugar and juice were associated with higher CHD risk, but TFE and fructose from fruits and vegetables were not., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Aims: Adopting a low- or very low-carbohydrate (LCD or VLCD) diet in type 1 diabetes mellitus (T1D) is a controversial intervention. The main fear is that these diets may increase the risk of diabetic ketoacidosis. However, there is little data about the ketoacidosis risk and the level of physiological nutritional ketosis in individuals following these diets. We aimed to define the level of ketosis in those with T1D following carbohydrate restricted diets in a real-world observational study., Methods: Patients with T1D who had self-selected dietary carbohydrate restriction were enrolled from local clinics and were compared to those following an unrestricted regular carbohydrate control diet (RCCD). Participants completed a 3-day diary, documenting food intake, ketones, and blood/interstitial glucose concentrations., Results: Participants were divided into three groups according to mean carbohydrate intake: VLCD (<50 g carbohydrates/day) n = 6, LCD (50-130 g carbohydrates/day) n = 6, and RCCD (>130 g carbohydrates/day) n = 3. Mean beta-hydroxybutyrate (BOHB) concentrations were 1.2 mmol/l (SD 0.14), 0.3 mmol/l (SD 0.12) and 0.1mmol/l (SD 0.05) in the VLCD, LCD and RCCD groups, respectively (p = 0.02). Post hoc Dunn test demonstrated this reached statistical significance between the VLCD and RCCD groups (p = 0.02)., Conclusion: Carbohydrate restricted diets, in particular VLCDs, are associated with a higher BOHB level. However, the degree of ketosis seen is much lower than we expected, and significantly lower than the level typically associated with diabetic ketoacidosis. This may suggest the risk of ketoacidosis is lower than feared, although safety will need to be evaluated further in large scale randomised trials., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Competing Interests: Competing interests: None declared.

Objectives: One of the leading causes of obesity is the consumption of excess nutrients. Obesity is characterized by adipose tissue expansion, chronic low-grade inflammation, and metabolic alterations. Although consumption of a high-fat diet has been demonstrated to be a diet-induced obesity model associated with gut disorders, the same effect is not well explored in a mild-obesity model induced by high-refined carbohydrate (HC) diet intake. The intestinal tract barrier comprises mucus, epithelial cells, tight junctions, immune cells, and gut microbiota. This system is susceptible to dysfunction by excess dietary components that could increase intestinal permeability and bacterial translocation. The aim of this study was to evaluate whether an HC diet and the alterations resulting from its intake are linked to small intestine changes., Methods: Male BALB/c mice were fed a chow or an HC diet for 8 wk., Results: Although differences in body weight gain were not observed between the groups, mice fed the HC diet showed increased adiposity associated with metabolic alterations. The interferon-γ expression and myeloperoxidase levels were increased in the small intestine in mice fed an HC diet. However, the intestinal villi length, the expression of tight junctions (zonula occludens-1 and claudin-4) and tumor necrosis factor-α cytokine, and the percentage of intraepithelial lymphocytes did not differ in the jejunum or ileum between the groups. We did not observe differences in intestinal permeability and bacterial translocation., Conclusion: Metabolic alterations caused by consumption of an HC diet lead to a mild obesity state that does not necessarily involve significant changes in intestinal integrity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hormone-related cancers, namely breast, endometrial, cervical, prostate, testicular, and thyroid, constitute a specific group of cancers dependent on hormone levels that play an essential role in cancer growth. In addition to the traditional risk factors, diet seems to be an important environmental factor that partially explains the steadily increased prevalence of this group of cancer. The composition of food, the dietary patterns, the endocrine-disrupting chemicals, and the way of food processing and preparation related to dietary advanced glycation end-product formation are all related to cancer. However, it remains unclear which specific dietary components mediate this relationship. Carbohydrates seem to be a risk factor for cancer in general and hormone-related cancers, in particular, with a difference between simple and complex carbohydrates. Glycemic index and glycemic load estimates reflect the effect of dietary carbohydrates on postprandial glucose concentrations. Several studies have investigated the relationship between the dietary glycemic index and glycemic load estimates with the natural course of cancer and, more specifically, hormone-related cancers. High glycemic index and glycemic load diets are associated with cancer development and worse prognosis, partially explained by the adverse effects on insulin metabolism, causing hyperinsulinemia and insulin resistance, and also by inflammation and oxidative stress induction. Herein, we review the existing data on the effect of diets focusing on the glycemic index and glycemic load estimates on hormone-related cancers.

Background: Metabolic syndrome (MetS), as a cluster of cardiometabolic risk factors, is a global public health concern due to its increasing prevalence. Considering the previous evidence of the association between carbohydrate quality and cardiometabolic risk factors, our study was aimed to evaluate any possible association between carbohydrate quality index (CQI) and cardiometabolic risk factors among obese adults., Methods: In this cross-sectional study, 336 apparently healthy individuals with obesity were participated. Dietary intake was assessed by a semi-quantitative Food Frequency Questionnaire (FFQ), including 168 food items validated for the Iranian population. CQI was calculated with three components of solid carbohydrates to total carbohydrates ratio, dietary fiber intake, and dietary glycemic index (GI). Body composition was determined by bioelectrical impedance analysis (BIA). Blood pressure was measured by sphygmomanometer and enzymatic methods were used to evaluate serum lipid, glucose, and insulin concentrations., Results: Subjects in the third quartile of CQI had significantly lower systolic blood pressure (SBP) (P = 0.03) and diastolic blood pressure (DBP) (P = 0.01). Participants in the higher quartiles of CQI had more intake of energy, carbohydrates, fat, saturated fatty acid (SFA), and mono-saturated fatty acid (MUFA) (P < 0.05). Moreover, the homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the second quartile of CQI [odds ratio (OR) = 0.146, P = 0.01) after adjustment for age, body mass index (BMI), sex, physical activity, socioeconomic status (SES) and energy intake., Conclusion: According to our findings, a higher quality of dietary carbohydrates, determined by CQI, could be associated with a lower risk of hypertension., (© 2023. The Author(s).)

Background: The role of carbohydrate quantity and quality in weight gain remains unsolved, and research on carbohydrate subcategories is scarce. We examined total carbohydrates, dietary fiber, total sugar, and sucrose intake in relation to the risk of weight gain in Finnish adults., Methods: Our data comprised 8327 adults aged 25-70 years in three population-based prospective cohorts. Diet was assessed by a validated food frequency questionnaire and nutrient intakes were calculated utilizing the Finnish Food Composition Database. Anthropometric measurements were collected according to standard protocols. Two-staged pooling was applied to derive relative risks across cohorts for weight gain of at least 5% by exposure variable intake quintiles in a 7-year follow-up. Linear trends were examined based on a Wald test., Results: No association was observed between intakes of total carbohydrate, dietary fiber, total sugar or sucrose and the risk of weight gain of at least 5%. Yet, total sugar intake had a borderline protective association with the risk of weight gain in participants with obesity (RR 0.63; 95% CI 0.40-1.00 for highest vs. lowest quintile) and sucrose intake in participants with ≥10% decrease in carbohydrate intake during the follow-up (RR 0.78; 95% CI 0.61-1.00) after adjustments for sex, age, baseline weight, education, smoking, physical activity, and energy intake. Further adjustment for fruit consumption strengthened the associations., Conclusions: Our findings do not support an association between carbohydrate intake and weight gain. However, the results suggested that concurrent changes in carbohydrate intake might be an important determinant of weight change and should be further examined in future studies., (© 2023. The Author(s).)

Background: More than one-third of adults in the United States have metabolic syndrome, and dietary carbohydrate intake may modify the likelihood of developing this condition. Currently, there is a lack of consistent evidence demonstrating the relationship between carbohydrate intake that falls below recommendations and metabolic syndrome. Not accounting for the differences in fatty acid classes of these dietary patterns may be a reason for inconsistent findings., Objective: This study evaluated the association between a carbohydrate intake below recommendations and metabolic syndrome stratified by fat quantity and fatty acid classes in a nationally representative sample of US adults., Design: This cross-sectional study acquired data on food and nutrient intake and markers of metabolic syndrome from respondents in the National Health and Nutrition Examination Survey 1999-2018., Participants/setting: This study included 19,078 respondents who were aged 20 years or older, had reliable and complete data on food and nutrient intake and markers of metabolic syndrome, and were not pregnant or breastfeeding., Main Outcome Measures: The main outcome was prevalence of metabolic syndrome., Statistical Analyses Performed: Usual dietary intake was estimated using the National Cancer Institute's usual intake methodology. Multivariable logistic regression models assessed the relative odds of prevalent metabolic syndrome between those who had a carbohydrate intake below recommendations and those who met carbohydrate recommendations., Results: Those who had a carbohydrate intake below recommendations had 1.067 (95% CI 1.063 to 1.071) times greater odds of having metabolic syndrome compared with those who met carbohydrate recommendations (P < 0.001). High intake of fat of any class was associated with higher odds of metabolic syndrome (total fat: 1.271, 95% CI 1.256 to 1.286; saturated fatty acid: 1.072, 95% CI 1.060 to 1.085; monounsaturated fatty acid: 1.317, 95% CI 1.300 to 1.333; polyunsaturated fatty acid: 1.056, 95% CI 1.047 to 1.066; P < 0.001 for all comparisons) in those who had a carbohydrate intake below recommendations., Conclusions: The odds of prevalent metabolic syndrome were higher among individuals who had a carbohydrate intake below recommendations compared with individuals who met carbohydrate recommendations., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

South Asians, comprising almost one fourth of the world population, are at higher risk of type 2 diabetes mellitus, hypertension, cardiovascular disease, and CKD compared with other ethnic groups. This has major public health implications in South Asia and in other parts of the world to where South Asians have immigrated. The interplay of various modifiable and nonmodifiable risk factors confers this risk. Traditional models of cardiometabolic disease progression and CKD evaluation may not be applicable in this population with a unique genetic predisposition and phenotype. A wider understanding of dietary and lifestyle influences, genetic and metabolic risk factors, and the pitfalls of conventional equations estimating kidney function in this population are required in providing care for kidney diseases. Targeted screening of this population for metabolic and vascular risk factors and individualized management plan for disease management may be necessary. Addressing unhealthy dietary patterns, promoting physical activity, and medication management that adheres to cultural factors are crucial steps to mitigate the risk of cardiovascular disease and CKD in this population. In South Asian countries, a large rural and urban community-based multipronged approach using polypills and community health workers to decrease the incidence of these diseases may be cost-effective., (Copyright © 2023 by the American Society of Nephrology.)

Purpose: Metabolic syndrome (MetS) is a major public health concern that increases the risk of cardiovascular disease and mortality. In previous studies of MetS management, low-carbohydrate diets have been strongly emphasized, despite the fact that many apparently healthy individuals have difficulties adhering to these diets on a long-term basis. The purpose of the present study was to elucidate the effects of a moderately restricted carbohydrate diet (MRCD) on cardiometabolic risk factors in women with MetS., Methods: This parallel 3-month, single-blind randomized controlled trial was conducted in Tehran, Iran, among 70 women with overweight or obesity aged 20 to 50 years with MetS. Patients were randomly allocated to receive either MRCD (42%-45% carbohydrates and 35%-40% fats) (n = 35) or a normal weight loss diet (NWLD) (52%-55% carbohydrates and 25%-30% fats) (n = 35). Both diets contained the same quantity of protein, which accounted for 15% to 17% of total energy. Anthropometric measurements, blood pressure, lipid profile, and glycemic indices were all assessed before and after the intervention., Findings: Compared with the NWLD group, following an MRCD significantly decreased weight (-4.82 vs -2.40 kg; P = 0.01), body mass index (-1.88 vs -0.94 kg/m 2 ; P = 0.01), waist circumference (-5.34 vs -2.75 cm; P = 0.01), hip circumference (-2.58 vs -1.11 cm; P = 0.01), serum triglyceride (-26.8 vs -7.19 mg/dL; P = 0.01), and increased serum HDL-C levels (1.89 vs. 0.24 mg/dL; P = 0.01). There was no significant difference between the 2 diets in waist-to-hip ratio, serum total cholesterol, serum LDL-C, systolic and diastolic blood pressure, fasting blood glucose, insulin levels, or the homeostasis model assessment for insulin resistance., Implications: Moderate carbohydrate replacement with dietary fats significantly improved weight, body mass index, waist circumference, hip circumference, serum triglyceride, and HDL-C levels among women with MetS. Iranian Registry of Clinical Trials identifier: IRCT20210307050621N1., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recent studies have reported that the associations between dietary carbohydrates and cardiovascular disease (CVD) may depend on the quality, rather than the quantity, of carbohydrates consumed. This study aimed to assess the associations between types and sources of dietary carbohydrates and CVD incidence. A secondary aim was to examine the associations of carbohydrate intakes with triglycerides within lipoprotein subclasses., Methods: A total of 110,497 UK Biobank participants with ≥ two (maximum five) 24-h dietary assessments who were free from CVD and diabetes at baseline were included. Multivariable-adjusted Cox regressions were used to estimate risks of incident total CVD (4188 cases), ischaemic heart disease (IHD; 3138) and stroke (1124) by carbohydrate intakes over a median follow-up time of 9.4 years, and the effect of modelled dietary substitutions. The associations of carbohydrate intakes with plasma triglycerides within lipoprotein subclasses as measured by nuclear magnetic resonance (NMR) spectroscopy were examined in 26,095 participants with baseline NMR spectroscopy measurements., Results: Total carbohydrate intake was not associated with CVD outcomes. Free sugar intake was positively associated with total CVD (HR; 95% CI per 5% of energy, 1.07;1.03-1.10), IHD (1.06;1.02-1.10), and stroke (1.10;1.04-1.17). Fibre intake was inversely associated with total CVD (HR; 95% CI per 5 g/d, 0.96;0.93-0.99). Modelled isoenergetic substitution of 5% of energy from refined grain starch with wholegrain starch was inversely associated with total CVD (0.94;0.91-0.98) and IHD (0.94;0.90-0.98), and substitution of free sugars with non-free sugars was inversely associated with total CVD (0.95;0.92-0.98) and stroke (0.91;0.86-0.97). Free sugar intake was positively associated with triglycerides within all lipoproteins., Conclusions: Higher free sugar intake was associated with higher CVD incidence and higher triglyceride concentrations within all lipoproteins. Higher fibre intake and replacement of refined grain starch and free sugars with wholegrain starch and non-free sugars, respectively, may be protective for incident CVD., (© 2023. The Author(s).)

Aims: Type 1 diabetes (T1D) is tied to an increased risk of cardiovascular morbidity and mortality. Dietary treatment would be an elective therapeutic strategy to fight this risk. However, it is not known what the best dietary approach is. We revisited the currently available literature on the nutritional treatment of T1D in the light of their potential comprehensive effects on the management of cardio-metabolic risk factors (body weight, fasting and postprandial glucose and lipid metabolism)., Data Synthesis: Nutritional research in T1D is mainly focused on blood glucose control, with most of the trials aiming at evaluating the acute effects of nutrients on postprandial glycemic response. The effects of the quantity and quality of nutrients and some specific foods on other metabolic risk factors have been explored mainly in cross-sectional analysis. Very few well-designed nutritional trials evaluated the best dietary approach to comprehensively manage cardiovascular risk by targeting along with blood glucose control, overweight, fasting and postprandial dyslipidemia. Therefore, the current best practice guidance for the dietary management of cardiovascular risk in T1D is generally based on evidence from patients with type 2 diabetes., Conclusions: Well-conducted nutritional trials specifically designed for T1D are needed to identify the best dietary treatment to fight cardiovascular risk in these patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Evidence remains conflicted on the association between dietary carbohydrate quantity and quality and risk of cardiovascular disease, all-cause, cardiovascular and cancer mortality, and such meta-analyses are lacking. The study aimed to conduct a systematic review and meta-analysis to synthesize the knowledge about their associations and to explore the dose-response relations., Methods: We comprehensively searched PubMed, EMBASE, and Web of Science up to March 2022 for observational studies investigating the associations in adults. Random effect model was used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs) and the dose-response association was explored by restricted cubic splines., Results: We obtained the data from 41 eligible studies. Compared with participants with lowest dietary carbohydrate intake, those with highest intake had an RR of 1.10 (95% CI 1.03-1.17, I 2  = 52.8%) for cardiovascular disease, 1.10 (0.98-1.24, I 2  = 65.5%) for coronary heart disease (CHD), 1.20 (1.08-1.34, I 2  = 0) for stroke, 1.07 (1.00-1.14, I 2  = 61.9%) for all-cause mortality, 1.02 (0.92-1.14, I 2  = 51.3%) for cardiovascular mortality, and 1.01 (0.89-1.13, I 2  = 56.7%) for cancer mortality. For each 5 %E increase in dietary carbohydrate intake, the summary RR was 1.02 (1.00-1.04, I 2  = 66.8%) for cardiovascular disease, 1.04 (1.01-1.06, I 2  = 0) for stroke but not significant for other outcomes. Restricted cubic splines showed linear associations with risk of cardiovascular disease (P non-linearity  = 0.143), CHD (P non-linearity  = 0.508), stroke (P non-linearity  = 0.654) and non-linear associations with all-cause mortality (P non-linearity  = 0.008) and cardiovascular mortality (P non-linearity  = 0.055). Limited studies were found on the association of cardiovascular disease and mortality with dietary carbohydrate quality using a multidimensional and integrated indicator., Conclusions: Increased consumption of dietary carbohydrate intake is associated with increased risk of cardiovascular disease, stroke, and all-cause mortality. Linear relation was found for cardiovascular disease and stroke but non-linear relation for all-cause mortality. More studies are warranted to investigate the association of dietary carbohydrate quality using a combined indicator and cardiovascular disease and mortality., Competing Interests: Conflict of Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI ( RR  = 1.11, 95% CI  = 0.80-1.53), GL ( RR  = 1.09, 95% CI  = 0.76-1.55), and daily carbohydrates intake ( RR  = 1.09, 95% CI =  0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC ( RR  = 0.65, 95% CI  = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC ( RR  = 1.52, 95% CI  = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI ( RR  = 1.23, 95% CI  = 0.88-1.70) and GL ( RR  = 1.17, 95% CI  = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.

Background: High consumption of carbohydrates can trigger metabolic and inflammatory disorders in the body. Thus, the aim of this study was to evaluate the effect of fiber supplementation on inflammation and hepatic steatosis in mice fed high-carbohydrate diets. Methods: Swiss male mice were distributed into two control groups and two experimental groups that received isocaloric diet rich in starch (55%) or rich in fructose (55%). In the last 4 weeks of the experiment, the animals received 5% fructo-oligosaccharide (FOS) supplementation via gavage, or water in the control groups. After 16 weeks, biochemical analyses, inflammatory cytokines, and histology of the liver of the animals were performed. Results: The animals that received fructose had higher weight at the end of the experiment as well as liver weight, consumed more feed, had higher levels of tumor necrosis factor (TNF) and monocyte chemoattractant protein-1 (MCP-1), and a higher degree of hepatic steatosis when compared with the animals that received starch. However, the animals that received starch showed a higher inflammatory process. FOS supplementation was efficient in reducing liver weight and hepatic steatosis degree in animals fed with fructose diet but showed more degeneration of liver tissue and high levels of inflammatory cytokines. FOS reduced the levels of urea and total cholesterol in the starch-fed animals. Conclusions: Diets rich in carbohydrates such as starch and fructose cause deleterious effects in animals, and fiber supplementation can bring beneficial effects.

The human oral microbiome is associated with chronic diseases including cancer. However, our understanding of its relationship with diet is limited. We assessed the associations between carbohydrate and glycemic index (GI) with oral microbiome composition in 834 non-diabetic subjects from the NCI-PLCO and ACS-CPSII cohorts. The oral microbiome was characterized using 16Sv3-4 rRNA-sequencing from oral mouthwash samples. Daily carbohydrate and GI were assessed from food frequency questionnaires. We used linear regression, permutational MANOVA, and negative binomial Generalized Linear Models (GLM) to test associations of diet with α- and β-diversity and taxon abundance (adjusting for age, sex, cohort, BMI, smoking, caloric intake, and alcohol). A q-value (FDR-adjusted P-value) of <0.05 was considered significant. Oral bacterial α-diversity trended higher in participants in the highest quintiles of carbohydrate intake, with marginally increased richness and Shannon diversity (p-trend=0.06 and 0.07). Greater carbohydrate intake was associated with greater abundance of class Fusobacteriia (q=0.02) and genus Leptotrichia (q=0.01) and with lesser abundance of an Actinomyces OTU (q=4.7E-04). Higher GI was significantly related to greater abundance of genus Gemella (q=0.001). This large, nationwide study provides evidence that diets high in carbohydrates and GI may influence the oral microbiome., Competing Interests: Competing interests: The authors declare no competing financial interests

Postpartum depression (PPD) is possibly caused by indoor air pollution and may be modified by maternal diet during pregnancy. Using the data from a prospective cohort study, we examined the interaction between indoor air quality and maternal dietary patterns on PPD development. A perceived indoor air quality (PIAQ) score was used to assess indoor air pollution. A higher PIAQ score indicated a worse indoor air quality. Women with higher PIAQ scores were at increased risk for PPD (tertile 3 vs. tertile 1, odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.37-3.29). Compared with a lower adherence to a "sweet foods pattern" (OR = 1.20, 95% CI = 0.66-2.18), a higher adherence to a "sweet foods pattern" enhanced the hazardous associations of the PIAQ on PPD (OR = 3.09, 95% CI = 1.81-5.27, adjusted p for interaction = 0.044). Higher adherence to a "whole grain-seafood pattern" and lower adherence to a "traditional pattern" also increased the risk for PPD, although the p values for the interaction were not significant. Our findings provide further evidence of the link between diet during pregnancy, air pollution, and PPD, and it can be used to develop PPD prevention strategies., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Polysaccharide from Polygonatum sibiricum (PSP) possesses antioxidant, antiaging, and neuroprotective activities. However, whether and how the steaming process influences the biological activities of PSP, especially against aging-related memory impairment, is not yet known. In this study, Polygonatum sibiricum rhizome was subjected to a "nine steaming and nine drying" process, then PSPs with different steaming times were abstracted. Thereafter, the physicochemical properties were qualified; the antioxidant activities of PSPs were evaluated in a D-gal-induced HT-22 cell model, and the effects of PSPs (PSP0, PSP5 and PSP9) on memory was evaluated using D-gal-injured mice. Our results showed that while the steamed PSPs had a low pH value and a large negative charge, they shared similar main chains and substituents. Cellular experiments showed that the antioxidant activity of steamed PSPs increased. PSP0, PSP5, and PSP9 could significantly ameliorate the memory impairment of D-gal-injured mice, with PSP5 showing the optimal effect. Meanwhile, PSP5 demonstrated the best effect in terms of preventing cell death and synaptic injury in D-gal-injured mice. Additionally, the steamed PSPs increased anti-oxidative stress-related protein expression and decreased inflammation-related protein expression in D-gal-injured mice. Collectively, the steaming process improves the effects of PSPs against D-gal-induced memory impairment in mice, likely by increasing the antioxidant activity of PSPs.

Diet is a critical risk factor for gastric cancer, and Koreans consume significantly high amounts of carbohydrates. This study examined the association between carbohydrate intake, glycemic index, and glycemic load and the risk of gastric cancer and whether the association varied based on the general risk factors for gastric cancer. We hypothesized that carbohydrate intake, glycemic index, and glycemic load elevated gastric cancer risk and the relationship differed by the gastric cancer risk factors. This was a case-control study with a total of 307 matched pairs aged 20 to 79 years. Data collection was completed at two hospitals from December 2002 to September 2006. A food frequency questionnaire was applied for dietary assessment. Carbohydrate intake was not related to gastric cancer risk. However, a high glycemic index (odds ratio [OR], 1.88; 95% confidence interval (95% CI), 1.18-2.97) and glycemic load (OR, 2.51; 95% CI, 1.53-4.12) were significantly associated with the elevated risk of gastric cancer. When the relationship between glycemic load and gastric cancer risk was stratified by risk factors for gastric cancer, the gastric cancer risk especially increased among men, ≥65 years, smokers, drinkers, and people with Helicobacter pylori infection. Although there was no association between carbohydrate consumption and gastric cancer, high glycemic index and glycemic load were associated with the increased gastric cancer risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetS) is a common feature in obesity, comprising a cluster of abnormalities including abdominal fat accumulation, hyperglycemia, hyperinsulinemia, dyslipidemia, and hypertension, leading to diabetes and cardiovascular diseases (CVD). Intake of carbohydrates (CHO), particularly a sugary diet that rapidly increases blood glucose, triglycerides, and blood pressure levels is the predominant determining factor of MetS. Complex CHO, on the other hand, are a stable source of energy taking a longer time to digest. In particular, resistant starch (RS) or soluble fiber is an excellent source of prebiotics, which alter the gut microbial composition, which in turn improves metabolic control. Altering maternal CHO intake during pregnancy may result in the child developing MetS. Furthermore, lifestyle factors such as physical inactivity in combination with dietary habits may synergistically influence gene expression by modulating genetic and epigenetic regulators transforming childhood obesity into adolescent metabolic disorders. This review summarizes the common pathophysiology of MetS in connection with the nature of CHO, intrauterine nutrition, genetic predisposition, lifestyle factors, and advanced treatment approaches; it also emphasizes how dietary CHO may act as a key element in the pathogenesis and future therapeutic targets of obesity and MetS., (© 2022 International Union of Biochemistry and Molecular Biology.)

Dietary patterns based on rich-carbohydrate foods were associated with breast cancer (BC) in Córdoba (Argentina). Nevertheless, the effect of dietary indicators of postprandial blood glucose or insulinemia on this cancer has not been studied. Thus, we hypothesize that higher dietary glycemic and insulinemic indices increase the risk of BC occurrence, with differential effects according to the presence/absence of overweight. A case-control study was conducted for BC (346/596 cases/controls) in Córdoba, Argentina, from 2008 to 2016. Multiple logistic regression models were used to assess the effect of glycemic index (GI), glycemic load, insulin index, and insulin load (IL) and the intake of high-GI foods (HGIF) on BC occurrence, adjusted by specific confounders and stratified by body mass index (BMI, <25 or ≥25 kg/m 2 ). The odds ratio (OR) for BC occurrence comparing the highest versus the lowest tertile of dietary GI was 1.77 (95% confidence interval [CI], 1.19-2.64). Additionally, a positive association between the weekly intake of HGIF and the dietary IL was found (OR, 1.71; 95% CI, 1.14-2.55 and OR, 1.50; 95% CI, 1.03-2.19, respectively). In normal-weight women, dietary GI and IL were associated with cancer occurrence, whereas in overweight women, only weekly intake of HGIF was associated. Our findings suggest that the BC risk related to hyperglycemic and hyperinsulinemic diet changed according to BMI. Furthermore, frequent exposure to HGIF has a relevant role in BC occurrence and its promoting effect is even higher in the presence of overweight., Competing Interests: Conflict of Interest None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Epidemiological studies on the relationship between dietary glycemic index (GI), glycemic load (GL) and all-cause and cause-specific mortality yielded conflict results. We aimed to assess these associations in Chinese., Methods: We conducted this study based on two prospective cohort studies in Shanghai. Dietary information was collected using validated cohort-specific food frequency questionnaires. We used Cox regression model to estimate the hazard ratios (HR) for mortality associated with GI and GL., Results: After median follow-up periods of 12.8 years for 59,770 men and 18.2 years for 74,735 women, 8,711 deaths in men and 10,501 deaths in women were documented. After we controlled the potential confounders, dietary GI, GL, and carbohydrate intake were associated with a higher risk of cardiovascular disease (CVD) mortality (P values for trend = 0.025, 0.001, and 0.001). Dietary GI was associated with lower risk of total and cause-specific mortality in men in the second quartile (Q) (all-cause mortality: HR Q2 vs. Q1  = 0.89, 95%CI: 0.84, 0.95). Dietary GL was associated with lower risk of cancer mortality but higher risk of CVD mortality in men. In women, dietary GI was associated with mortality due to all-cause (HR Max Q4 vs. Q1  = 1.10, 95%CI: 1.04, 1.06), cancer (HR Max Q4 vs. Q1  = 1.12, 95%CI: 1.02, 1.23), and CVD (HR Max Q4 vs. Q1  = 1.10, 95%CI: 1.00, 1.22)., Conclusions: The present study indicates that diet with higher GI and GL was associated with an increased risk of CVD mortality in Chinese adults. The association may vary for men and women, which need further investigating in other Asian populations., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

This meta-analysis evaluated the relationship between dietary glycemic index (GI), glycemic load (GL), and lung cancer risk, which has been controversial in previous studies. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for relevant studies from inception to October 2021 in English only. We included case-control and cohort studies that reported relative risks (RRs) and 95% confidence intervals (CI) between dietary GI or GL intake and lung cancer risk. Either a fixed- or random-effects model was used to estimate pooled RRs. Subgroup analysis, sensitivity analysis, meta-regression, publication bias test, and dose-response meta-analysis were performed. We identified nine studies eligible for meta-analysis with 32810 cases and 351013 controls. The pooled RR for highest versus lowest intake was 1.14 (95% CI: 1.03-1.26, I 2 =64.8%, P=0.002) for GI and 0.93 (95% CI: 0.84-1.02, I 2 =42.3%, P=0.076) for GL. Subgroup analysis showed that the associations between GI or GL and lung cancer were similar between groups. Sensitivity analysis revealed reduced heterogeneity among GL-related studies when one particular study was excluded. There was no evidence of publication bias. A linear association between GI intake and lung cancer risk was observed. The present meta-analysis suggests that high dietary GI intake is associated with a significantly increased risk of lung cancer in a linear fashion. However, no significant association was observed between GL and lung cancer risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: There is considerable inconsistency in results regarding the association of dietary glycemic index (GI) and glycemic load (GL) with cancer risk. We therefore conducted this systematic review and dose-response meta-analysis of prospective cohort studies to evaluate the relationship between dietary GI/GL and cancer risk., Methods: We searched PubMed and Web of Science for prospective cohort studies of dietary GI/GL in relation to risks of all types of cancer up to 31 March 2021. We used a random-effect model to calculate summary relative risks (RR) and 95% confidence intervals (CI). The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. This study was registered at PROSPERO (CRD42020215338)., Results: Overall, 55 cohorts were included in the meta-analysis. We assessed the relationship between dietary GI or GL and risks of 23 cancer types, including hormone-related cancers, cancers from digestive system, respiratory system, urinary system and other cancer sites. High GI diet increased overall risk of cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.04, 95% CI 1.01-1.07). For site-specific cancers, high GI diet increased risks of lung cancer (highest vs lowest categories, n = 5, RR 1.08, 95% CI 1.01-1.18) and breast cancer (highest vs lowest categories, n = 14, RR 1.05, 95% CI 1.01-1.09), especially for postmenopausal breast cancer (highest vs lowest categories, n = 10, RR 1.06, 95% CI 1.00-1.13), all with low certainty of evidence. Additionally, dietary GI was positively related to risk of bladder cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.23, 95% CI 1.09-1.40), as well as negatively related to ovarian cancer risk with very low certainty of evidence (highest vs lowest categories, n = 4, RR 0.83, 95% CI 0.69-1.00) and lymphoma risk with low certainty of evidence (highest vs lowest categories, n = 2, RR 0.84, 95% CI 0.72-0.98). Besides, we found an inverse association of dietary GL with lung cancer risk with low certainty of evidence (highest vs lowest categories, n = 5, RR 0.87, 95% CI 0.80-0.94)., Conclusion: High dietary GI increased overall cancer risk with low certainty of evidence. For site-specific cancers, high GI diet increased the risks of breast cancer with low certainty of evidence and lung cancer with low certainty of evidence. Dietary GL was inversely associated with lung cancer risk with low certainty of evidence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Aims: Accurate estimation of the glycemic index (GI) and glycemic load (GL) of diets is essential when assessing health implications of dietary GI and GL. The present study aimed to estimate dietary GI and GL utilizing the updated GI tables with a large number of new, reliable GI values and assess their associations with metabolic syndrome among Korean adults., Methods and Results: We analyzed data from 3317 men and 6191 women for this cross-sectional study. Dietary intake was assessed with a validated food frequency questionnaire. Metabolic syndrome and its components were defined based on the harmonized criteria with Korean-specific cutoffs for waist circumference. Multivariate logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with women in the lowest quintiles of energy-adjusted dietary GI and GL, women in the highest quintiles had significantly greater risks of metabolic syndrome (GI, OR = 1.56, 95% CI = 1.18-2.06; GL, OR = 1.80, 95% CI = 1.27-2.57), elevated blood pressure, reduced high-density lipoprotein cholesterol (HDL-C, both GI and GL), elevated triglycerides (GI only), elevated waist circumference, and elevated fasting glucose (GL only). Among men, no significant association was noted except for a higher risk of reduced HDL-C (OR = 1.59, 95% CI = 1.01-2.29) in the highest quintile of energy-adjusted dietary GI than in the lowest quintile., Conclusion: Our findings suggest that dietary GI and GL are positively associated with metabolic syndrome risk among women, but not men, in Korea., Competing Interests: Declaration of competing interest All authors have nothing to disclose., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)