Fish oil supplementation and risk of dementia among diabetic patients: a prospective study of 16,061 older patients.

BACKGROUND: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes. METHOD: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60-0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers. CONCLUSION: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients.

Effect of probiotic supplementation on cognition and depressive symptoms in patients with depression: A systematic review and meta-analysis.

BACKGROUND: Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating depressive symptoms in major depressive disorder patients. METHODS: Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Population, Intervention, Comparator, Outcome, and Study design framework, we systematically reviewed randomized controlled trials examining probiotic effects on cognition and depressive symptoms. Searches spanned 7 databases from January 2010 to May 2022. Risk of bias was assessed using Revised Cochrane Risk of Bias 2.0, and meta-analysis was conducted with RevMan 5.4.1. Publication bias was evaluated via Egger test. RESULTS: In a systematic review on the effects of probiotic supplementation on cognition and depressive symptoms in depression patients, 635 records were initially identified, with 4 studies ultimately included. These randomized controlled trials were conducted across diverse regions, primarily involving females, with assessment periods ranging from 1 to 2 months. Concerning cognitive outcomes, a statistically significant moderate improvement was found with probiotic supplementation, based on the mean difference and its 95% confidence interval. However, for depressive symptoms, the overall effect was negligible and not statistically significant. A heterogeneity test indicated consistent findings across studies for both cognitive and depressive outcomes (I²â€…= 0% for both). The potential for publication bias was evaluated using the Egger linear regression test, suggesting no significant bias, though caution is advised due to the limited number of studies. CONCLUSION: Probiotics may enhance cognitive domains and mitigate depressive symptoms, emphasizing the gut-brain axis role. However, methodological variations and brief intervention durations call for more standardized, extensive research.

Healthy dietary patterns and risk of cardiovascular disease in diabetic patients: a prospective cohort study.

Purpose: Evidence is limited regarding the associations of different dietary patterns with cardiovascular disease (CVD) risk among the population with diabetes. Thus, we aimed to explore the associations between three dietary patterns and CVD incidence among the population with diabetes. Materials and methods: We prospectively followed 22 473 diabetic patients from the UK Biobank at the baseline. The healthy dietary pattern was derived from a food frequency questionnaire; meanwhile, the Alternate Mediterranean Diet (AMED) and the Dietary Approaches to Stop Hypertension (DASH) diet were assessed based on the Oxford WebQ online 24 h dietary questionnaire. Results: During an average of 10.8 years of follow-up, 5209 incident CVD cases, including 3552 coronary heart disease (CHD) events and 881 strokes, were documented. After multivariate adjustment, a higher healthy diet score was negatively associated with CVD, CHD, and stroke incidence. The hazard ratios and 95% confidence intervals across increasing quintiles of healthy diet score were 0.86 (0.79-0.95), 0.83 (0.75-0.93), and 0.71 (0.57-0.88) for CVD, CHD, and stroke, respectively. A similar protective association with CVD incidence was found for the AMED but not the DASH diet. Conclusions: Adherence to healthy dietary patterns is related to a lower risk of developing CVD among diabetic patients. Our findings further provide vigorous evidence for formulating dietary adherence guidelines for diabetic patients to reduce the burden of CVD complications.

Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study.

The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.

Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Potato consumption, polygenic scores, and incident type 2 diabetes: An observational study.

Whether the consumption of different processed potatoes is detrimental to type 2 diabetes (T2D) is highly debated. This study aimed to assess the relations between potato consumption and the risk of T2D and whether the relationship was modified by the genetic predisposition to T2D. We included 174,665 participants from the UK Biobank at baseline. Potato consumption was evaluated using the 24-hour dietary questionnaire. The genetic risk score (GRS) was calculated based on 424 variants associated with T2D. After adjustment for demographic, lifestyle, and dietary factors, the consumption of total potatoes was significantly and positively associated with T2D risk [hazard ratio (HR) comparing two or more servings/day with non-consumers was 1.28 (95% CI: 1.13-1.45)]. HRs (95% CIs) of T2D for each 1-SD increment in boiled/baked potatoes, mashed potatoes, and fried potatoes were 1.02 (0.99-1.05), 1.05 (1.02-1.08), and 1.05 (1.02-1.09), respectively. There were no significant interactions between the consumption of total or different processed potatoes and overall GRS on T2D risk. Theoretically, replacing one serving/day of total potatoes with the same amount of non-starchy vegetables was related to a 12% (95% CI: 0.84-0.91) lower T2D risk. These results showed the positive associations of the consumption of total potatoes, mashed potatoes or fried potatoes and genetic risk with higher incident T2D. An unhealthy potato-based diet is associated with higher diabetes risk regardless of genetic risk.

The sulfur microbial diet and increased risk of obesity: Findings from a population-based prospective cohort study.

BACKGROUND & AIMS: Gut-produced hydrogen sulfide (H2S) has been associated with increased gut permeability and inflammation, which may be related to higher obesity risk. We investigated the association of sulfur microbial diet, a dietary index associated with 43 sulfur-metabolizing bacteria, with the incident obesity and whether the relationship was modified by the genetic predisposition to obesity. METHODS: We included 27,429 participants with available body mass index (BMI) data from the UK Biobank. The sulfur microbial diet score was assessed using the 24-h dietary assessment method. Obesity and abdominal obesity were defined according to the World Health Organization criteria. Body fat percentage was assessed using a body composition analyzer. The genetic risk score (GRS) was calculated by 940 BMI-related variants. RESULTS: We documented 1472 and 2893 cases of obesity and abdominal obesity during a mean follow-up of 8.1 years. After multivariable adjustment, the sulfur microbial diet score was positively associated with obesity (HRQ4vsQ1 = 1.63; 95% CI = 1.40-1.89, P-trend = 0.001) and abdominal obesity risk (HRQ4vsQ1 = 1.17; 95% CI = 1.05-1.30, P-trend = 0.002). We also observed that increased sulfur microbial diet score was positively related to several adiposity indicators, including a 5% increase in BMI, WC, and body fat percentage. Moreover, the sulfur microbial diet had no significant interactions with genetic risk on obesity incidence. CONCLUSIONS: Our results emphasized the significance of avoiding the sulfur microbial diet for obesity prevention across all levels of genetic risk.

Physiologically-based toxicokinetic model for the prediction of perchlorate distribution and its application.

Perchlorate is a stable and readily transportable thyroid hormone disruptor, and prevalent exposure to perchlorate through food and drinking water has raised public concern about its health effects. The physiologically based toxicokinetic (PBTK) model as a dose prediction method is effective to predict the toxicant exposure dose of an organism and helps quantitatively assess the dose-dependent relationship with toxic effects. The current study aimed to establish a multi-compartment PBTK model based on updated time-course datasets of single oral exposure to perchlorate in rats. With adjustment of the kinetic parameters, the model fitted well the toxicokinetic characteristics of perchlorate in urine, blood, and thyroid from our experiments and the literature, and the coefficient of determination (R2) between the fitting values and the experimental data in regression analysis was greater than 0.91, indicating the robustness of the current model. The results of sensitivity analysis and daily repeated exposure simulations together confirmed its effective renal clearance. According to the distribution characteristic of perchlorate, a correlation study of internal and external exposure was conducted using urinary perchlorate as a bioassay indicator. The developed multi-compartment model for perchlorate updates important toxicokinetic data and kinetic parameters, providing analytical and modeling tools for deriving total exposure levels in the short term.

Development of physiologically based toxicokinetic models for 3-monochloropropane-1,2-diol and glycidol.

3-Monochloropropane-1,2-diol (3-MCPD), glycidol, together with their fatty acid esters are commonly presented in various food and have shown carcinogenicity in various laboratory animals. Public health risk assessment of 3-MPCD and glycidol exposure relies on quantitative tools that represent their in vivo toxicokinetics. In order to better understand the absorption, distribution, metabolism, and excretion profiles of 3-MCPD and glycidol in male rats, a physiologically based pharmacokinetic (PBTK) model was developed. The model's predictive power was evaluated by comparing in silico simulations to in vivo time course data obtained from experimental studies. Results indicate that our PBTK model successfully captured the toxicokinetics of both free chemicals in key organs, and their metabolites in accessible biological fluids. With the validated PBTK model, we then gave an animal-free example on how to extrapolate the toxicological knowledge acquired from a single gavage to a realistic dietary intake scenario. Three biomarkers, free compound in serum, urinary metabolite DHPMA, and glycidol-hemoglobin adduct (diHOPrVal) were selected for in silico simulation following constant dietary intakes, and their internal levels were correlated with proposed external daily exposure via reverse dosimetry approaches. Taken together, our model provides a computational approach for extrapolating animal toxicokinetic experiments to biomonitoring measurement and risk assessment.

Metabolomics strategy comprehensively unveils the effect of catechins intervention on the biomarkers of exposure to acrylamide and biomarkers of cardiometabolic risk.

Polyphenolic antioxidants have been suggested to control the generation of acrylamide during thermal reactions. However, their role in protecting against the toxicity of acrylamide and the mechanism of action regarding profile alteration of biomarkers and metabolome remains unclear. A total of 65 adults were randomized into tea polyphenols (TP) and control groups and served with potato chips, which corresponded to an intake level of 12.6 µg/kg·bw of acrylamide, followed by capsules containing 200 mg, 100 mg or 50 mg TP, or equivalent placebo. Moreover, nontargeted urinary metabolomics analysis in acrylamide exposed rats was conducted using ultra-high performance liquid chromatography linked with a quadrupole-orbitrap high-resolution mass spectrometry. Our results showed that supplementation with catechins promoted the excretion of N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine in both humans and rats. We also found that epigallocatechin gallate (EGCG) or epicatechin (EC) intervention attenuated the ratio of hemoglobin adduct of glycidamide to hemoglobin adduct of acrylamide in rat blood. Metabolomics analysis revealed that EGCG/EC intervention regulated the differential expressed metabolites, including l-glutamic acid, 2-oxoglutarate, citric acid, and cysteinylglycine. Kyoto Encyclopedia of Genes and Genomes pathway analysis further showed acrylamide-induced metabolic disorders were improved after EGCG/EC supplementation by glycolipid metabolism (alanine, aspartate and glutamate metabolism, and d-Glutamine and d-glutamate metabolism) and energy metabolism (tricarboxylic acid cycle). Notably, the supplement use of EGCG prevented the cardiometabolic risk after exposure to acrylamide by mediating the phenylalanine and hippuric acid in phenylalanine metabolism. Here we showed the beneficial effect of catechins as major polyphenolic antioxidant ingredients on the toxicity of acrylamide by the changes in biomarkers from metabolic profile analysis based on human and animal studies. These findings shed light into the catechins as natural polyphenolic antioxidants that could be a therapeutic ingredient for preventing acrylamide-induced cardiometabolic toxicity.

Rapid Simultaneous Determination of Three Synthetic Cannabinoids in Urine and Plasma of Rats Using Ultra-High Performance Liquid Chromatography Tandem Mass Spectrometry.

Synthetic cannabinoids, a class of psychoactive compounds, are controlled as new psychoactive substances (NPSs) identified by the early warning system (EWS) of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). At present, several new synthetic cannabinoids have appeared in the illegal drug market, including 4-methylnaphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-122), methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L-valinate (5F-AMB), and methyl 2-(1-(4-fluorobenzyl)-1Hindazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA). A convenient, rapid, and highly sensitive analytical method was developed to determine three synthetic cannabinoids in rat plasma and urine. The liquid chromatography tandem mass spectrometry (LC-MS/MS) method was optimized and validated to analyze the three synthetic cannabinoids in rat plasma and urine. The method identified intra-assay precision (1.3-9.0% and 2.8-6.7%), inter-assay precision (3.0-8.6% and 3.9-8.8%), limits of detection (0.003-0.004 ng/mL and 0.00125-0.002 ng/mL) and quantification (0.012-0.016 ng/mL and 0.003-0.005 ng/mL), recovery (95.4-106.8% and 92.0-106.8%) for rat plasma and urine, and the matrix effect (93.4-118.0%) for rat urine, and the correlation coefficients were above 0.99 in the linear range. The established LC-MS/MS method was successfully used to simultaneously detect the JWH-122 and 5F-AMB in rat plasma and JWH-122, 5F-AMB, and AMB-FUBINACA in rat urine. The present study provides methodological support for internal exposure assessment of three synthetic cannabinoids and promotes the quantitative analysis and technical supervision of synthetic cannabinoids.

Associations of Hemoglobin Adducts of Acrylamide and Glycidamide with Prevalent Metabolic Syndrome in a Nationwide Population-Based Study.

Environmental and dietary exposures to acrylamide (AA) have been linked with various metabolic-related outcomes, but the results are mixed. However, the association between long-term exposure to AA and the prevalence of metabolic syndrome (MetS) remains unknown. In this study, we aimed to assess the relationship between hemoglobin adducts of AA, biomarkers of internal exposure to AA, and MetS prevalence among a U.S. nationwide population. MetS patients were defined by meeting three or more of the following five characteristics: elevated blood pressure, high fasting glucose, abdominal obesity, hypertriglyceridemia, and lower high-density lipoprotein cholesterol (HDL-C). Multivariate-adjusted logistic regression models and restricted cubic spline models were used to analyze the associations between AA hemoglobin biomarkers and MetS prevalence. A total of 1552 MetS cases were documented. After adjustment for the potential confounders, the odds ratios (95% confidence intervals) of MetS prevalence in the highest quartile of AA hemoglobin biomarkers were 0.60 (0.40-0.89), 1.26 (0.84-1.89), 0.93 (0.71-1.21), and 1.61 (1.18-2.20) for HbAA, HbGA, the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA to HbAA (HbGA/HbAA), compared with the lowest quartile, respectively. HbAA was significantly and inversely associated with blood pressure, fasting glucose, abdominal obesity, hypertriglyceridemia, and low HDL-C, while the HbGA/HbAA ratio was also positively associated with abdominal obesity, hypertriglyceridemia, and low HDL-C. The restricted cubic spline models revealed a positive relationship between the HbGA/HbAA ratio and the prevalence of MetS, while the HbAA level was inversely associated with MetS prevalence. Our current findings provided epidemiological evidence that HbAA and the HbGA/HbAA ratio were significantly associated with MetS prevalence among general U.S. adults. Further studies should be conducted to examine the association between internal exposure to AA and MetS prevalence.

Circulating Fatty Acids and Genetic Predisposition to Type 2 Diabetes: Gene-Nutrient Interaction Analysis.

OBJECTIVE: To assess the relationship of circulating fatty acids (FA) with risk of type 2 diabetes (T2D) and potential interactions with genetic risk. RESEARCH DESIGN AND METHODS: A total of 95,854 participants with complete data on plasma FA from the UK Biobank were enrolled between 2006 and 2010 and were followed up to the end of 2020. Plasma concentrations of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were analyzed by a high-throughput nuclear magnetic resonance-based biomarker profiling platform. The genetic risk scores (GRS) were calculated on the basis of 424 variants associated with T2D. Pathway-specific GRS were calculated based on robust clusters of T2D loci. RESULTS: There were 3,052 instances of T2D documented after an average follow-up of 11.6 years. Plasma concentrations of SFA and MUFA were positively associated with T2D risk, while plasma PUFA were inversely associated. After adjustment for major risk factors, hazard ratios (95% CI) of T2D for 1-SD increment were 1.03 (1.02-1.04) for SFA, 1.03 (1.02-1.05) for MUFA, 0.62 (0.56-0.68) for PUFA, 0.67 (0.61-0.73) for n-6 PUFA, 0.90 (0.85-0.95) for n-3 PUFA, and 1.01 (0.98-1.04) for n-6-to-n-3 ratio. Plasma MUFA had significant interactions with the overall GRS and GRS for proinsulin and liver/lipid clusters on T2D risk. The protective associations of n-3 PUFA with T2D risk were weaker among individuals with higher obesity GRS (P interaction = 0.040) and liver/lipid GRS (P interaction = 0.012). Additionally, increased plasma n-3 PUFA concentration was associated with more reductions in T2D risk among participants carrying more docosapentaenoic acid-associated alleles (P interaction = 0.007). CONCLUSIONS: Plasma concentrations of SFA and MUFA were associated with a higher T2D risk, whereas plasma PUFA and n-6 and n-3 PUFA were related to a lower risk. Circulating MUFA and n-3 PUFA had significant interactions with genetic predisposition to T2D and FA-associated variants.

Triterpenes from Poria cocos are revealed as potential retinoid X receptor selective agonists based on cell and in silico evidence.

Poria cocos is an edible and medicinal fungus that is widely used in Traditional Chinese Medicines as well as in modern applications. Retinoid X receptor (RXR) occupies a central place in nuclear receptor signaling, and a pharmacological RXR-dependent pathway is involved in myeloid cell function. Here, structural information for 82 triterpenes from P. cocos and 17 known RXR agonists was collected in a compound library and retrieved for a molecular docking study. Three triterpenes, 16α-hydroxytrametenolic acid (HTA), pachymic acid (PA), and polyporenic acid C (PPAC), were identified as novel RXR-specific agonists based on luciferase reporter assays and in silico evidence. Treatment with HTA, PA, and PPAC significantly induced differentiation of the human promyelocytic leukemia cell line HL-60 with EC50 values of 21.0 ± 0.52, 6.7 ± 0.37, and 9.4 ± 0.65 µM, respectively. These effects were partly blocked by the RXR antagonist UVI3003, suggesting that an RXR-dependent pathway may play an important role in their anti-acute promyelocytic leukemia (APL) effects. Taken together, triterpenes from P. cocos are revealed as naturally occurring RXR selective agonists with the potential for anti-cancer activity. These results suggest a novel approach to the treatment or prevention of APL.

Group boundary permeability moderates the effect of a dependency meta-stereotype on help-seeking behaviour.

Previous studies have found that when low-status group members are aware that their in-group is stereotyped as dependent by a specific out-group (i.e. a dependency meta-stereotype is salient), they are reluctant to seek help from the high-status out-group to avoid confirming the negative meta-stereotype. However, it is unclear whether low-status group members would seek more help in the context of a salient dependency meta-stereotype when there is low (vs. high) group boundary permeability. Therefore, we conducted two experiments to examine the moderating effect of permeability on meta-stereotype confirmation with a real group. In study 1, we manipulated the salience of the dependency meta-stereotype, measured participants' perceived permeability and examined their help-seeking behaviour in a real-world task. Participants who perceived low permeability sought more help when the meta-stereotype was salient (vs. not salient), whereas participants who perceived high permeability sought the same amount of help across conditions. In study 2, we manipulated the permeability levels and measured the dependency meta-stereotype. Participants who endorsed a high-dependency meta-stereotype sought more help than participants who endorsed a low-dependency meta-stereotype; this effect was particularly strong in the low-permeability condition. The implications of these results for social mobility and intergroup helping are discussed.