Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the association between folic acid (FA) intake and CRC risk remains controversial. This study investigated the effects of varying dietary FA levels on colorectal carcinogenesis and the underlying mechanisms. Methods: BALB/c mice were fed diets containing FA at <0.1, 2.0, 6.0, 8.0, or 20.0 mg/kg for 14 weeks. After 4 weeks, colorectal tumorigenesis was induced using the azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Tumor multiplicity, maximum tumor diameter, tumor volume, colorectal length, histopathology, and cell proliferation were assessed. Mechanistic assessments included uracil misincorporation, thymidylate synthase (TS), telomere attrition, genome-wide DNA methylation, RAP1 signaling, immune-related markers, and inflammatory cytokines in colorectal tissues. Results: Both FA deficiency (<0.1 mg/kg) and excess (8.0/20.0 mg/kg) increased colorectal tumor burden, with increased tumor number, larger maximum diameter, greater tumor volume, shortened colorectal length, and enhanced cell proliferation, whereas the 6.0 mg/kg diet group showed the lowest tumor burden. FA deficiency reduced TS expression, elevated deoxyuridine monophosphate (dUMP) levels, decreased deoxythymidine monophosphate (dTMP) levels, increased uracil misincorporation, and exacerbated telomere attrition, as evidenced by shortened telomeres and increased damage. In contrast, excessive FA intake induced Rap1 GTPase-activating protein (RAP1GAP) hypermethylation, reduced Rap1GAP expression, enhanced RAP1 activity, and upregulated programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) expression. Conclusions: Dietary FA can exhibit a U-shaped association with colorectal carcinogenesis, with protective effects observed within an optimal range. FA deficiency and excess may drive tumor development through distinct molecular pathways involving uracil misincorporation-induced telomere attrition and DNA methylation-mediated immunosuppression, respectively.

Dementia is a growing global health challenge with limited pharmacological treatments. Emerging evidence from randomized controlled trials and prospective cohort studies suggests that healthy dietary patterns may contribute to the prevention or delay of cognitive decline. This review summarizes current evidence on the relations of overall dietary patterns and specific foods and nutrients to cognitive aging, with a particular focus on the potential role of gut microbiota, which is largely shaped by diet. Certain healthy dietary patterns, such as the Mediterranean and the Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND) diets, characterized by specific foods (e.g., vegetables and fruits) and dietary nutrients (e.g., n-3 fatty acids, B vitamins, and carotenoids) have shown potential benefits on cognitive health. However, inconsistencies across study findings necessitate further investigation. We review how the gut microbiota may mediate or moderate the diet-cognition association, or serve as a marker for cognitive health, particularly through mechanisms involving metabolic, immune, and neuroinflammatory pathways. Finally, we highlight key methodological challenges, including variability in exposure assessment, study design, and population heterogeneity, and propose a roadmap for future research, advocating for large-scale, multi-omics studies across diverse populations. These efforts are expected to facilitate the development of precision nutrition strategies for the prevention of cognitive decline and dementia.

Background:The myopia rate has increased rapidly worldwide, yet evidence regarding the association between dietary factors and myopia remains limited. This study assessed the association between dietary patterns and myopia among children and adolescents. Methods:This study used the Child and Adolescent Research of Eye data between August and October 2022. Myopia was defined based on uncorrected visual acuity and noncycloplegic refraction. Dietary assessment was parent-reported via a food frequency questionnaire (FFQ). Principal component analysis was used to extract dietary patterns. Binary logistic regression was used to evaluate the association between dietary patterns and myopia. Results:A total of 24,797 participants were included in the analysis. Controlling for confounders, the highest adherence to nuts-tubers vegetables pattern (characterized by high intake of nuts, tubers vegetables, legumes, whole grains, and aquatic products) was associated with a decreased risk of myopia compared with the lowest adherence (odds ratio [OR] = 0.933, 95% confidence interval [CI]: 0.872 to 0.999, p = 0.046). Conversely, the highest adherence to snacks pattern (characterized by high intake of fried and barbecued, fast foods and savoury snacks, sugar-sweetened beverages, desserts, and processed meats) was associated with an increased risk of myopia (OR = 1.083, 95% CI: 1.012 to 1.158, p = 0.021). Conclusions:These findings indicate a link between dietary patterns and myopia in children and adolescents. Dietary modification could be a potential public health measure for the primary prevention of childhood myopia.

BackgroundThis study investigated the association between dietary pattern and osteoporosis, exploring gut microbiota and plasma metabolites as potential mediators.MethodsThis case-control study included 90 osteoporosis patients and 90 healthy controls. All participants completed a validated semi-quantitative food frequency questionnaire (FFQ) to assess their dietary intake over the past year. Principal component analysis (PCA) was performed on the FFQ data to identify major dietary patterns. Gut microbiota composition was analyzed using metagenomic sequencing (Illumina HiSeq platform, PE150). Plasma metabolites were analyzed using untargeted metabolomics with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Binary logistic regression was employed to examine the association between dietary pattern and osteoporosis; Multivariate linear regression was used to investigate the association between dietary pattern and gut microbiota/metabolites. Additionally, mediation analysis was conducted to assess whether gut microbiota or plasma metabolites mediated the association between dietary patterns and osteoporosis, and the proportion of mediation was calculated.ResultsThe osteoporosis group showed significant differences in age (61.89 ± 7.86 vs. 56.10 ± 7.29 years), sex (72.2% vs. 36.7% female), and anthropometrics (all P < 0.05). Among six identified dietary patterns, “animal offal and seeds” was associated with higher osteoporosis risk (OR = 2.21, 1.21–4.06; P = 0.010). osteoporosis patients exhibited gut microbiota dysbiosis (enriched Enterobacteriaceae) and seven metabolites exerted mediating effects on the association between dietary pattern and osteoporosis.ConclusionIn high-altitude population, the “animal offal and seeds” dietary pattern elevates osteoporosis risk, partially mediated by metabolite. Gut microbiota composition also differs significantly between osteoporosis patients and controls.

BACKGROUND AND OBJECTIVES:Previous studies have linked famine exposure to the incidence of type 2 diabetes (T2D), yet its impact on diabetic microvascular complications (DMC) remains uncertain. This study aims to investigate the longitudinal association between early-life famine exposure and the risk of DMC in adult-hood among individuals with T2D. METHODS AND STUDY DESIGN:A retrospective cohort study was conducted among inpatients with T2D at Tianjin Medical University Chu Hsien-I Memorial Hospital from June 2014 to June 2022. The 2409 participants were divided into five famine exposure groups based on birth years: no exposure group (1962-1965), fetal period exposure group (1959-1961), early-childhood exposure group (1956-1958), mid-childhood exposure group (1953-1955), and late-childhood exposure group (1949-1952). RESULTS:Compared with those nonexposed, early-life famine exposure was associated with higher risks of incident overall DMC (HRtrend 1.134, 95% CI 1.052-1.223), diabetic retinopathy (DR) (HRtrend 1.193, 95% CI 1.100-1.293), and diabetic kidney disease (DKD) (HRtrend 1.262, 95% CI 1.117-1.425), but was not associated with diabetic neuropathy (p > 0.05). Notably, significant interactions were found between famine exposure and hypertension regarding the risk of DR, and between famine exposure and both and obesity patterns on the risk of DKD (all p for interaction < 0.05). CONCLUSIONS:Exposure to famine in early life was associated with increased risks of overall DMC, DR and DKD among patients with T2D. Specially, the association of DR was more pronounced in individuals with hypertension, while the association with DKD was stronger among those with hypertension or both general and abdominal obesity.

OBJECTIVE:To assess the efficacy of the reducing cardiometabolic disease risk (RCMDR) dietary pattern health education intervention on cardiometabolic disease (CMD) risk and carotid atherosclerosis in the Chinese older population. DESIGN:The cluster randomized clinical trial was conducted from April 2023 to December 2024. Participants according to residential areas were randomized to the intervention group (2 clusters) or control group (2 clusters). SETTING:Single-center in Tianjin, China. PARTICIPANTS:694 community older residents (61-80 years): intervention group (n = 349) and control group (n = 345). INTERVENTION:Participants in the intervention group received the RCMDR dietary pattern health education intervention, while those in the control group received general health education. The intervention period lasted 12 months. MEASUREMENTS:The primary outcome was clustered cardiometabolic risk score (CMRS). The secondary outcomes included common carotid artery ultrasound parameters and cardiometabolic risk indicators. Analysis was intention-to-treat principle. RESULTS:Of 694 participants, 411 (59.2%) were female; mean (SD) age was 68.2 (5.1) years. Compared with the control group, the RCMDR dietary pattern health education intervention resulted in a significantly lower CMRS (β = -0.25; 95% CI -0.31, -0.19); lower intima-media thickness (β = -0.05, 95% CI -0.08, -0.02); lower serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol; lower fasting blood glucose, fasting insulin, fasting C-peptide and HOMA-IR, higher HOMA-β; lower serum homocysteine; lower systolic blood pressure and diastolic blood pressure; lower weight, body mass index, waist circumference, waist-to-hip ratio, body fat percentage, body fat mass and Chinese visceral adiposity index, higher lean body mass (all P < 0.05). CONCLUSION:The RCMDR dietary pattern health education intervention could reduce the CMD risk, delayed the progression of carotid atherosclerosis and improved cardiometabolic factors among Chinese older population.

Age-related neurodegeneration is characterized by oxidative stress and iron-dependent cell death, yet the neuroprotective mechanisms of folic acid in modulating ferroptosis remain unclear. This study systematically investigated the role of folic acid in inhibiting ferroptosis and attenuating neuronal damage in aging, with a focus on the solute carrier family 7 member 11 (SLC7A11)-glutathione (GSH)-glutathione peroxidase 4 (GPX4) antioxidant pathway, using aged rats supplemented with folic acid (<0.1, 2.0, and 4.0 mg/kg·diet) for 22 months, with young adult rats as controls. Brain iron accumulation and ferroptosis-related proteins (SLC7A11, GPX4, Ferritin heavy chain 1 (FTH1)) were evaluated. In vitro, HT-22 hippocampal neuronal cells were pre-treated with folic acid (0, 10, 20 μmol/L) for 72 h before combining with Erastin (10 μmol/L)-induced ferroptosis for an additional 24 h. Intracellular Fe2+, lipid peroxidation (LPO), malondialdehyde (MDA), reactive oxygen species (ROS), along with cystine, GSH, and ferroptosis-related protein levels were quantified. Stable sh-SLC7A11 knockdown and control (sh-NC) cell lines were used to validate the dependency of folic acid’s protective effects on SLC7A11 expression. Folic acid supplementation in aged rats dose-dependently reduced aging-related brain iron accumulation and enhanced the expression of SLC7A11, GPX4, and FTH1. In Erastin-induced HT-22 cells, folic acid significantly mitigated ferroptosis hallmarks. Mechanistically, folic acid increased extracellular cystine uptake and intracellular GSH synthesis, thereby activating the SLC7A11-GSH-GPX4 antioxidant pathway. Notably, molecular docking technique suggested that compared to GPX4, folic acid stabilized SLC7A11’s active conformation. sh-SLC7A11 knockdown completely abolished folic acid-mediated protection against ferroptosis, as evidenced by restored loss of cystine, GSH and GPX4 production. This study innovatively emphasized the critical role of folic acid supplementation in inhibiting ferroptosis by up-regulating the SLC7A11-GSH-GPX4 antioxidant pathway, primarily through enhancing cystine availability and SLC7A11 expression. These findings established folic acid as a potential dietary intervention for aging-related neurodegenerative diseases characterized by neuronal ferroptosis, providing preclinical evidence for folic acid based neuroprotection.

Background and Objectives: The incidence of hypertension is higher in individuals with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype. Riboflavin serves as a coenzyme of MTHFR, but its role in hypertension prevalence is poorly understood. This study aimed to explore the relationship between riboflavin levels and hypertension and the impact of genotype on this relationship. Methods and Study Design: The case-control study used data from the Tianjin Elderly Nutrition and Cognition study, with 200 hypertensive patients and 200 matched non-hypertensive controls. It collected questionnaires, clinical data, and measured blood riboflavin levels using the dried blood spot technique. Conditional logistic regression analyzed variables related to hypertension prevalence, with effects assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Results: The hypertensive group had significantly lower riboflavin concentration than the non-hypertensive group (p<0.001). The regression analysis indicated that regardless of adjustment for sociodemographic characteristics, riboflavin concentration was negatively associated with the prevalence of hypertension. In the multivariable model, the OR was 0.607 [95%CI, 0.507-0.727], p<0.001. Additionally, we found an interaction between MTHFR genotype and riboflavin status. Compared with the combined TT genotype and below-median riboflavin levels as the reference category, the CC genotype and above-median riboflavin levels decreased the prevalence of hypertension (OR, 0.189 [95%CI, 0.071-0.501], p=0.001). Conclusions: In conclusion, riboflavin status impacts the development of hypertension. There is also interaction between the MTHFR genotype and riboflavin. Specifically, low riboflavin status increases the prevalence of hypertension when combined with the MTHFR 677TT genotype.

Adequate micronutrients play a crucial role in cognitive health. Identifying relevant micronutrients and constructing risk prediction models can guide the prevention of mild cognitive impairment (MCI) in older adults. This study aimed to assess the associations of MCI with whole blood micronutrient levels and develop a nomogram for personalized MCI risk prediction in older adults. In the matched case–control study, 100 MCI patients and 100 matched controls by age, sex and education from Baodi District, Tianjin, China were recruited. MCI was determined by a modified version of the Petersen criteria. Whole blood levels of 9 vitamins and 5 minerals were measured using the dried blood spot technique. Weighted quantile sum regression was employed to identify the most significant micronutrients associated with cognitive function. Receiver operating characteristic (ROC) curves were constructed, and a nomogram for predicting MCI risk was developed. High levels of vitamins (vitamin A, vitamin B2, vitamin B6, vitamin B9) and minerals (magnesium, selenium) were significantly associated with lower MCI prevalence, in which vitamin B2, vitamin B9 and selenium were ranked as the most significant contributors to cognitive function. The ROC curves for vitamin B2 and vitamin B9 (area under the curve = 0.855) have superior diagnostic accuracy compared to individual assessments (p < 0.05). Based on these findings, a nomogram was developed using these two micronutrients to predict MCI risk. The nomogram based on vitamin B2 and vitamin B9 can be effectively used to detect MCI early and guide preventive strategies in older adults.

Dietary patterns targeting cardiometabolic health, such as the Mediterranean diet, DASH diet, and the Chinese Healthy Heart (CHH) dietary pattern have demonstrated lipid-lowering effects, yet culturally adapted strategies for older adults in northern China remain understudied. This study developed a combined MeDi-DASH-CHH dietary pattern by integrating key components of Western evidence-based diets (Mediterranean and DASH) with local dietary preferences (e.g., whole grain consumption, seasonal vegetable intake) to evaluate its impact on blood lipid control in northern Chinese older adults with dyslipidemia. A total of 210 dyslipidemic adults aged 60–75 years were stratified by sex, then randomized (1:1) to a 6-month intervention group (MeDi-DASH-CHH diet, with emphasized intake of aquatic products, dairy, and whole grains) or a control group (conventional guidance per Dietary Guidelines for Chinese Residents (2024)). Both groups received monthly follow-up visits. The primary outcome was the changes from baseline to six months in lipoprotein cholesterol (LDL-C). Secondary outcomes included changes in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), dietary intake, and body composition indicators. After intervention, the intervention group showed improvements in lipid profiles compared to the control group (all P < 0.05). Dietary intake indicated increased consumption of whole grains, potatoes, vegetables, fruits, aquatic products, dairy products, and nuts, alongside reduced intake of livestock meat, poultry meat, and egg intake. The combined MeDi-DASH-CHH dietary effectively improves lipid profiles and promotes healthier eating behaviors in older adults with dyslipidemia in northern China.

BACKGROUND:Postpartum depression (PPD) affects numerous women globally, impairing maternal and infant health and contributing to substantial socioeconomic burdens on both families and society. This study aimed to investigate the association between the Dietary Inflammatory Index (DII) and PPD in Chinese women, and explore whether inflammatory cytokines mediate this association. METHODS:The study recruited 2038 participants and collected data from them. The Chinese version of the Self-Rating Depression Scale was used to assess postpartum depressive symptoms, and the DII scores were evaluated using semi-quantitative food frequency questionnaires (FFQ). To ensure balanced groups, researchers performed propensity score matching. From the matched participants, 126 blood samples were collected to determine serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Researchers used logistic regression to estimate the odds ratios (OR) and 95 % confidence intervals (CI) between the DII tertiles, inflammatory markers, and PPD. Finally, researchers conducted a mediation analysis using the bootstrap method to examine the relationship between DII, inflammation, and PPD. RESULTS:Among 2038 participants, 742 (36.4 %) participants were identified as having PPD symptoms. The higher DII scores were associated with PPD, and its significance still exists after a series of factors were adjusted (T2 vs T1: OR = 1.24, 95 % CI: 0.99, 1.55, P > 0.05; T3 vs T1: OR = 1.33, 95 % CI: 1.06, 1.66, P < 0.05). In addition, a higher level of CRP was associated with increased odds of PPD (OR = 1.34, 95 % CI: 1.13, 1.59, P < 0.05). The mediation analysis showed that a direct effect of DII on PPD persisted, and CRP mediated the relationship between DII and PPD. CONCLUSIONS:A higher DII was associated with an increased risk of PPD in Chinese women. The present finding reinforces the importance of limiting pro-inflammatory food consumed and adopting an anti-inflammatory diet to decrease the risk of PPD.

BACKGROUND:Medium-chain triglycerides (MCT) and docosahexaenoic acid (DHA) could affect cognitive function, but their combination effects remain unclear. This randomized, double-blind, placebo-controlled trial aimed to evaluate effects of MCT and DHA supplementation, alone or in combination, on mild cognitive impairment (MCI) patients. METHODS:A total of 280 MCI participants were randomly assigned to the placebo group, MCT group (14 g/d octanoic acid+10 g/d capric acid), DHA group (800 mg/d) and MCT + DHA (14 g/d octanoic acid, 10 g/d capric acid and 800 mg/d DHA) group, 70 individuals per group for 12 months. Cognitive function was assessed at baseline, 6 months and 12 months; blood indicators were analyzed at baseline and 12 months. This study is registered with Chinese Clinical Trial Registry (ChiCTR2200059641). RESULTS:After 12 months intervention, compared with the placebo group, MCT group, DHA group and MCT + DHA group had statistically significant improvements in full scale IQ (β: 0.107, 95 % CI: 0.006, 0.208; β: 0.135, 95 % CI: 0.034, 0.235; β: 0.136, 95 % CI: 0.035, 0.237), serum total ketone body levels (β: 10.540, 95 % CI: 9.550, 11.531; β: 5.884, 95 % CI: 4.894, 6.875; β: 13.186, 95 % CI: 12.196, 14.176), and decreases in mtDNA deletions (β: -0.370, 95 % CI: -0.648, -0.092; β: -0.335, 95 % CI: -0.613, -0.056; β: -0.427, 95 % CI: -0.705, -0.148) and plasma Aβ42 levels (β: -3.318, 95 % CI: -5.571, -1.064; β: -3.218, 95 % CI: -5.472, -0.965; β: -2.906, 95 % CI: -5.160, -0.653). CONCLUSIONS:Supplementation of MCT, DHA and their combination for 12 months can significantly improve cognitive function, mitochondria function and increase serum total ketone body levels in MCI individuals. Combined intervention was more beneficial than MCT or DHA alone.

BACKGROUND:The reference intervals (RIs) for venous whole blood micronutrients are instrumental in evaluating nutritional status within populations. However, research on establishing micronutrient RIs using the simple and efficient dried blood spot (DBS) technique remains scarce. Consequently, this study aims to establish RIs for venous whole blood micronutrients among healthy Chinese older individuals via DBS. METHODS:Participants were recruited from the general community of Baodi District, Tianjin, northern China. Healthy populations were identified based on the recommendations of the Clinical and Laboratory Standards Institute guidelines, physical signs (body mass index and waist circumference), and blood biochemical parameters (serum lipid status and hemoglobin). The micronutrient levels were measured via the DBS technique. For normally distributed data, the RI was calculated as the mean ± 2SD. For non-normally distributed data, the RI is calculated as the 2.5th to 97.5th percentiles. RESULTS:This study established RIs for 8 vitamins (vitamins A, D, E, B1, B2, B3, B6, B9) and 5 minerals (Mg, Cu, Fe, Zn, Se) in healthy older adults. For males, the RIs are as follows: VA (157.76-828.81 ng/mL); VD (8.89-58.32 ng/mL); VE (1.84-13.78 μg/mL); VB1 (0.19-5.36 ng/mL); VB2 (0.53-13.84 ng/mL); VB3 (4.43-13.70 μg/mL); VB6 (1.09-26.00 ng/mL); VB9 (1.02-9.48 ng/mL); Mg (27.54-52.99 mg/L); Cu (0.57-1.64 mg/L); Fe (287.00-708.60 mg/L); Zn (4.10-20.85 mg/L); Se (70.57-167.63 μg/L). For females: VA (142.62-755.78 ng/mL); VD (10.10-66.20 ng/mL); VE (1.87-13.43 ng/mL); VB1 (0.15-4.20 ng/mL); VB2 (0.61-12.81 ng/mL); VB3 (4.51-15.53 ng/mL); VB6 (1.82-24.05 ng/mL); VB9 (0.60-9.62 ng/mL); Mg (25.73-51.94 mg/L); Cu (0.58-1.41 mg/L); Fe (236.75-599.81 mg/L); Zn (3.93-22.22 mg/L); Se (70.57-167.63 μg/L). CONCLUSIONS:This study presents venous whole blood micronutrient parameters that can facilitate nutrition-related epidemiological research and inform personalized intervention strategies, thereby enhancing the quality of healthcare for elderly individuals in China.

Ocular trauma is a leading cause of vision impairment and blindness worldwide,significantly affecting quality of life[1].Each year,an estimated 55 million ocular injuries occur worldwide,with nearly 19 million resulting in vision loss or blindness and approx-imately 750,000 requiring hospitalization[2,3].Understanding the causes and trends of ocular trauma is essential for developing effective prevention strategies.However,most existing studies on the epidemiology and risk factors of ocular trauma have been con-ducted in Western countries,with limited population-based stud-ies available from China[1,4-6].To date,the United States is the only country to report national-level ocular trauma data,though this information is outdated,with data only available up to 2018.

Background: Phosphatidylserine (PS) and alpha-Linolenic acid (ALA), are positively associated with cognitive function, but their combination effects and possible mechanisms remain unclear. We aimed to explore the effects on cognition and potential mechanism of the supplements. Methods: This randomized, double-blind, placebo-controlled trial recruited 190 MCI patients in Tianjin, China, and randomly assigned in intervention group and placebo group. Each group consumed two capsules every day for 12 months. Each capsule for intervention group contains 144 mg ALA, 31.5 mg PS and 3.6 mg Ginkgo total flavonoids as main functional components, with 0.48 mg Vitamin B1 (as thiamine hydrochloride), 0.48 mg Vitamin B6 (as pyridoxine hydrochloride) and 90 mu g folic acid as supplement. Capsules for placebo group were identical but contain no active ingredients. Cognitive function, serum n-3 polyunsaturated fatty acids (PUFAs) and neurotransmitters were assessed at baseline and 12 months. Linear mixed effects model and causal mediation analysis were conducted to explore the effects and potential mechanism of the intervention. Results: A total of 190 participants (mean [SD] age, 67.95 [5.62] years; 70 (36.8 %) male and 120 (63.2 %) female) were randomized to the placebo group (n = 95) and intervention group (n = 95). Compared with placebo group, the intervention group had statistically significant improvements in arithmetic testing (/3, 0.688; 95 % CI, 0.103-1.274), the similarity test (/3, 1.070; 95 % CI, 0.472-1.667) and short-term memory (/3, 0.600; 95 % CI, 0.399-0.800). Besides, the intervention group had statistically significant increases in serum ALA (/3, 1.620; 95 % CI, 0.967-2.265), DHA (/3, 2.797; 95 % CI, 1.075-4.532), EPA (/3, 1.472; 95 % CI, 0.296-2.643), acetylcholine (/3, 0.441; 95 % CI, 0.415-0.468), GABA (/3, 0.009; 95 % CI, 0.001-0.016) and 5-HT (/3, 0.160; 95 % CI, 0.081-0.238) compared to the placebo group. And the intervention may improve short-term memory by increasing serum ALA levels (average causal mediation effect = 0.132, 95 % CI, 0.053-0.225) with 19.7 % mediation proportion. Conclusions: This food supplement containing phosphatidylserine could improve different cognitive functions of MCI patients, especially short-term memory, and increase serum n-3 PUFAs and neurotransmitters levels. Serum ALA level might play a mediation role.

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95% of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood.

Folic acid (FA) can modulate neurogenesis and neural cell death, including autophagy and apoptosis, crucial for maintaining neurological homeostasis. Previous studies on the relationship between autophagy and apoptosis were contradictory, and the study aimed to investigate FA's impact on these processes in neural cells and the mechanisms involved. Three-week-old Sprague Dawley (SD) rats were divided into four dietary groups based on FA intake: FA-deficient (<0.1 mg/kg), FA-normal (2 mg/kg), low FA-supplemented (4.0 mg/kg), and high FA-supplemented (8.0 mg/kg), with dietary treatments for 11 months. Neural cell apoptosis was quantified using TdT-mediated dUTP nick end labelling (TUNEL) assay, and autophagy-associated protein microtubule-associated light chain 3 (LC3)/Beclin-1 expression was detected by immunofluorescence (IF). HT-22 neurons were incubated with 1, 10, 20, and 40 µmol/L FA for 2, 4 and 8 d. Cell apoptosis was detected by flow cytometry, autophagic vacuoles were assessed by monodansyl cadaverine (MDC) assay, and the expression of autophagy-related proteins LC3/Beclin-1/p62 and p53/mammalian target of rapamycin (mTOR) pathway was analyzed by Western blotting (WB). In vivo, FA supplementation downregulated the autophagy-associated protein LC3/Beclin-1 expression in rat neural cells, further inhibiting apoptosis, whereas FA deficiency exhibited the opposite effect. In vitro study further revealed that FA supplementation reduced autophagy-dependent apoptosis in HT-22 neurons with decreased p53 expression and increased mTOR expression in a dose-dependent manner within the specific range. These results suggest that FA supplementation may inhibit autophagy-dependent apoptosis in neural cells via the p53/mTOR signaling pathway, whereas FA deficiency produced a significantly negative effect.

OBJECTIVES:To systematically summarise and evaluate the existing evidence of the associations between diverse folate exposures and the risk of colorectal cancer (CRC), while identifying evidence quality. DESIGN:Umbrella review of meta-analyses. DATA SOURCES:PubMed, Web of Science, Cochrane and Embase were searched from the database inception to March 2024, with an update to 12 October 2025. ELIGIBILITY CRITERIA:We included meta-analyses of randomised controlled trials or observational studies that investigated the associations between folate exposures and CRC or precancerous lesions (ie, adenoma and polyps). DATA EXTRACTION AND SYNTHESIS:For each association, we recalculated the summary effect size with 95% CI using the DerSimonian and Laird random-effects model, heterogeneity (I² statistic), 95% prediction interval, small-study effect (Egger's test) and excess significance bias (χ² test). RESULTS:This umbrella review included five meta-analyses describing 10 associations between folate exposures and CRC risk. In the general population, moderate-quality evidence supported an inverse association between total folate intake (from foods and supplements) and CRC risk (RR 0.84; 95% CI 0.80 to 0.90), while low-quality evidence suggested inverse associations of dietary folate intake (from foods alone) (RR 0.88; 95% CI 0.81 to 0.96) and folic acid supplement intake (RR 0.83; 95% CI 0.77 to 0.90) with CRC risk. Among patients with inflammatory bowel disease, low-quality evidence suggested an inverse association between folic acid supplement intake and CRC incidence (HR 0.71; 95% CI 0.53 to 0.96). Additionally, elevated circulating folate levels were observed to have a provoking effect on advanced-stage tumours (OR 1.95; 95% CI 1.18 to 3.22; Grading of Recommendations Assessment, Development and Evaluation (GRADE): very low). Sensitivity analysis revealed a potential increased risk of adenoma recurrence associated with folic acid supplement use among patients with a history of adenoma (RR 1.05; 95% CI 0.86 to 1.29; GRADE: high). CONCLUSIONS:These findings suggest that consuming dietary folate and total folate intake may be beneficial in CRC primary prevention. Specifically, folic acid supplements may inhibit colorectal carcinogenesis in normal tissues while promoting cancer in the established neoplastic foci. PROSPERO REGISTRATION NUMBER:CRD42024537550.

Concerns have been raised about potential hazards associated with folic acid fortification. This study aimed to explore associations between diverse folic acid fortification policies (mandatory vs. no mandatory fortification) and global late-onset colorectal cancer (LOCRC) incidence rates. The study systematically assessed (i) folic acid fortification policies in 193 member states of the World Health Organization, and (ii) age-standardized LOCRC incidence rates by country. We examined the associations between folic acid fortification types and LOCRC incidence using an ecological study design. Incidence trends before and after fortification were analyzed using a log-linear joinpoint regression model, and the annual percent change and average annual percent change with 95% confidence interval were determined for representative countries with mandatory fortification (the United States [U.S.] and Canada). By September 2024, 69 countries enacted mandatory folic acid fortification legislation, while 124 had no fortification. The overall LOCRC incidence rates per 100,000 were 70.8 and 84.0 with mandatory and no mandatory fortification, respectively. The decreasing trends after implementing folic acid fortification were more rapid than in the pre-fortification period in the U.S. and Canada. These findings suggested an association between mandatory folic acid fortification policies and reduced LOCRC incidence. These global data provide a scientific basis for transitioning fortification policies and inform strategies for cancer prevention through the fortification with folic acid.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is associated with Alzheimer's disease (AD). Both docosahexaenoic acid (DHA) and medium chain triglycerides (MCTs) play essential roles in lipid metabolism and the inhibition of amyloid-β (Aβ) accumulation. We aimed to explore the possible association between cerebral Aβ deposition and the development of NAFLD and to investigate the effect of DHA combined with MCTs on delaying NAFLD progression and Aβ accumulation. To this end, 40 three-month-old APP/PS1 male mice were randomly assigned to 4 groups. The mice were fed a control diet, a DHA (2.91 g/kg) diet, an MCTs (100 g/kg) diet, or a DHA + MCTs diet for 8 months. Ten C57BL/6J mice were fed a control diet and used as the wild-type (WT) group. The results indicated that APP/PS1 mice exhibited NAFLD and cerebral Aβ accumulation. DHA combined with MCTs decreased blood and liver lipids, relieved hepatic steatosis and fat accumulation, and decreased the level of Aβ in the brain and serum. Moreover, DHA combined with MCTs significantly upregulated the levels of Aβ clearance-related proteins in the liver, modulated the expression of key hepatic lipid metabolism enzymes and upstream hepatic lipid metabolism factors. In conclusion, compared with wild-type mice, APP/PS1 mice may be more sensitive to changes in lipid metabolism due to the accumulation of Aβ. DHA combined with MCTs alleviated NAFLD and decreased brain and serum Aβ levels in APP/PS1 mice compared with the control group. The possible mechanism may involve affecting hepatic fat and cholesterol metabolism and increasing hepatic Aβ clearance by modulating liver lipid metabolism enzymes.