Food & Nutrition Research

Association of dietary acid load with diabetes and glucose metabolism index in Chinese adults: a cross-sectional study

2026-03-20T14:44:37+00:00

Background: Dietary acid load (DAL) has been proven to be associated with hypertension, chronic kidney disease, gout, and the prevalence of type 2 diabetes in several countries. However, its relationship with the prevalence of prediabetes and diabetes in the Chinese population, as well as with fasting blood glucose, fasting insulin levels, and insulin resistance-related indicators, remains unclear.

Method: This is a cross-sectional study based on the China Health and Nutrition Survey (CHNS), which uses Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) to assess DAL. Logistic regression was employed to analyze the relationship between DAL and prediabetes as well as diabetes. Linear regression was used to examine the associations between DAL and fasting blood glucose, fasting insulin levels, estimated glucose disposal rate (eGDR), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and the TyG index in the affected population. Restricted cubic spline (RCS) curves were utilized to explore potential nonlinear relationships, and mediation analysis was conducted to investigate the mediating role of insulin resistance in the effects of DAL on fasting blood glucose and insulin. Finally, the findings were validated and compared using data from the National Health and Nutrition Examination Survey (NHANES).

Results: Higher PRAL (odds ratio [OR]: 1.004, 95% confidence interval [CI]: 1.002–1.006) and NEAP (OR: 1.009, 95% CI: 1.005–1.012) were associated with an increased prevalence of diabetes and prediabetes. Elevated levels of PRAL and NEAP were also correlated with higher fasting blood glucose levels and a lower eGDR. Moreover, eGDR played a significant mediating role in the effect of DAL on fasting blood glucose (PRAL: 69.74%, P = 0.048; NEAP: 65.75%, P = 0.004). However, this phenomenon was not significant in the US population, indicating differences between Chinese and American populations.

Conclusion: High DAL is significantly associated with an increased prevalence of diabetes and prediabetes in the Chinese population, and it influences fasting blood glucose levels in affected individuals by reducing the eGDR. These findings highlight the clinical importance of regulating acid-producing diets to help manage blood glucose levels in individuals with diabetes.

SFTA2 reduced colorectal cancer ferroptosis promoting metastasis through regulating EMT transition by degradation of Nrf2

2026-03-20T15:02:41+00:00

Colon cancer is a common malignancy of the digestive system, tumor disease, and its prevalence in China shows a consistently increasing trend. This study aimed to investigate the role of surfactant associated 2 (SFTA2) in colorectal cancer (CRC) and its molecular mechanism involving ferroptosis.

Colon cancer tissues were obtained from patients and normal volunteers from our hospital, and a mouse model of CRC was established using azoxymethane (AOM)/dextran sulfate sodium (DSS) induction.

SFTA2 expression was significantly up-regulated at both the messenger RNA (mRNA) and protein levels in CRC tissues and cell lines. Patients with high SFTA2 expression exhibited a shorter survival time compared to those with low SFTA2 expression. SFTA2 was found to be expressed in cancer cells of CRC patients, associated with key signaling molecules.

Sh-SFTA2 reduced cancer proliferation in the mice model of CRC. SFTA2 up-regulation promoted cell proliferation of CRC. SFTA2 down-regulation promoted cell proliferation of CRC. SFTA2 up-regulation reduced oxidative stress and ferroptosis of CRC. SFTA2 up-regulation reduced ferroptosis of CRC through mitochondrial damage-tricarboxylic acid cycle (TAC). SFTA2 down-regulation suppressed nuclear factor erythroid 2-related factor 2 (Nrf2) expression in the model of CRC. SFTA2 up-regulation reduced Nrf2 ubiquitination in the model of CRC. Nrf2 reversed the effects of si-SFTA2 on ferroptosis of CRC. Furthermore, SFTA2 down-regulation suppressed Nrf2 expression, while SFTA2 up-regulation decreased Nrf2 ubiquitination in the CRC model. Nrf2 was shown to reverse the pro-ferroptotic effects of si-SFTA2, indicating that SFTA2 activates the Nrf2 pathway by inhibiting its ubiquitination, thereby reducing mitochondrial damage and TCA cycle disruption in CRC.

SFTA2 induced the Nrf2 pathway to reduce mitochondrial damage-TAC of the CRC model through the inhibition of Nrf2 ubiquitination. SFTA2 is thus a potentiallyeffective therapeutic strategy for patients with CRC or other cancers.

The Educational Gradient in the Adherence to the Healthy Nordic Food Index Among Adult Men and Women in Tromsø: The Tromsø study 2015–2016

2026-03-04T10:27:12+00:00

Background: There is a well-established relation between socioeconomic position (SEP) and diet. People with lower SEPs tend to eat high-calorie, low-nutrient foods, while those with a higher SEP tend to consume foods associated with better health. However, the underlying mechanisms are yet to be understood.

Objective: To examine the association between education and the Healthy Nordic Food Index (HNFI) in men and women in Tromsø, and investigate the role of three intermediate variables: household income, subjective occupational social status, and self-rated health.

Design: Dietary information from Food Frequency Questionnaires were used to construct the HNFI based on six food items and categorised as low, medium, and high adherence. Education and intermediate variables were self-reported. Multinomial logistic regression models stratified by sex were performed to assess the association between education and the HNFI among 8,610 women and 6,896 men aged 40–99 years.

Results: Median intake of all food items increased across categories of the HNFI for all participants. High adherers to the HNFI were slightly older, more educated, had higher household income, perceived their occupational social status as high, and rated their health as good/excellent. We observed an educational gradient in the adherence to the HNFI where men (odds ratios [OR] _TertiaryLong 1.92 [95% confidence intervals [CI] 1.47–2.5]) and women (OR _TertiaryLong 2.35 [1.94–2.85]) with higher education had higher odds of adhering to the HNFI compared to those with primary education. Household income partly attenuated this gradient in men only.

Conclusion: The association between education and adherence to the HNFI followed an educational gradient, which was partly attenuated by income in men but not in women. Our study highlights potential mechanisms underlying the relationship between education and diet. A deeper understanding of socioeconomic disparities in healthy eating is crucial for enhancing overall nutrition, especially among the socially disadvantaged.

Salubrious effects of Ficus carica L. leaves extract in inflammation, diabetes, and obesity: An in-vitro, in-silico, and in-vivo study

2026-02-20T02:02:39+00:00

Various traditional medicinal systems have utilized the plant-based remedies for addressing the diverse ailments worldwide. Hence, this study aimed to scientifically explore the biological and phytochemical potential of Ficus carica L. leaves. This investigation encompassed the assessments of flavonoids, total phenolic contents, as well as physicochemical and phytochemical properties. Antioxidant potential was evaluated through hydrogen peroxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays, while anti-inflammatory effects were determined via proteinase inhibition, bovine serum albumin (BSA) denaturation, and heat-induced hemolysis assays. Additionally, antiglycation potential was assessed through free carbonyl group estimation, fructosamine, and Congo-red assays. The impact on diabetes mellitus, obesity, and renal and hepatic functions was investigated using the high-fat high-sugar diet model. Advanced analytical techniques including Fourier-transform infrared, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry were employed to identify the active secondary metabolites present in the F. carica L. leaf extract. Molecular docking and absorption–distribution–metabolism–excretion–toxicity analyses were performed by different computational methods. Results revealed that substantial levels of total flavonoids (123 mg rutin equivalents/g) and phenolic content (333 mg gallic acid equivalent/g) along with promising antioxidant activity (IC₅₀: 0.58 mg/mL for DPPH assay, 35.6% inhibition for H₂O₂ assay, and FRAP value of 88.769 µg/g Fe₂SO₄ solution) were found. Notably, F. carica L. leaf extract exhibited the significant inhibition in heat-induced hemolysis (55 ± 0.03%), proteinase activity (28 ± 0.01%), and BSA denaturation (51.2 ± 0.05%). Furthermore, it exhibited the significant therapeutic effects on the biomarkers related to diabetes mellitus, obesity, liver, and kidney functions. Chemical analyses unveiled the presence of chlorogenic acid, ferulic acid, thymoquinone, rutin, coumarin, as well as terpenoids, alkaloids, coumarins, and flavonoids. The key findings suggest that F. carica L. leaf extract holds significant potential as an antioxidant, antidiabetic, and hypolipidemic agent.

Legumain level in patients with gestational diabetes to promote ferroptosis through liver gluconeogenesis by HSP90 and GPX4

2026-02-28T14:04:27+00:00

Background: The incidence of gestational diabetes mellitus (GDM) is the first diabetes in pregnancy and has gradually increased worldwide, increasing the burden of social healthcare systems. In GDM, oxidative stress induced by reactive oxygen species (ROS) can disrupt the integrity of the cell membrane through lipid peroxidation reactions and trigger ferroptosis, further exacerbating pancreatic islet β-cell dysfunction and insulin resistance. Lipid peroxidation products related to ferroptosis (such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)), along with the decrease in glutathione peroxidase 4 (GPX4) activity, may be involved in the placental oxidative damage and adverse fetal outcomes in GDM, suggesting that targeting the antioxidant pathway or regulating ferroptosis may serve as an intervention strategy. Legumain (LGMN) can serve as novel targets in diabetes mellitus genetic therapy.

Objective: This study investigated the mechanism and effects of LGMN in GDM.

Method: All blood samples of normal or patients with GDM were collected by Beijing Ditan Hospital Affiliated Capital Medical University. C57BL/6J female mice were intraperitoneally injected with streptozotocin. Sh-LGMN virus (20 μg of each) or control vector virus (20 μg of each) was injected into GDM mice. GDM mice randomly assigned to three groups (Number = 10). Sh-LGMN virus (20 μg of each) + HSP90 inhibitor or Sh-LGMN virus (20 μg of each) or control vector virus (20 μg of each) was injected into GDM mice. LGMN or si-LGMN Plasmids were transfected into HepG2 cells using Lipofectamine 2000. HepG2 cells were incubated by different insulin concentrations (100 nmol/L) treatment for 24 h. Microarray analysis, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, proliferation assay, ethynyl deoxyuridine staining, bioluminescence imaging, and Western blot were used in this study.

Results: Serum LGMN mRNA expression was significantly elevated in patients with GDM. LGMN mRNA and protein expression were also elicited in the liver tissue of GDM mice. LGMN mRNA expression exhibited a positive correlation with Body Mass Index (BMI), fasting plasma glucose, 1-h plasma glucose, or 2-h plasma glucose in patients. Sh-LGMN virus reduced blood glucose levels and body weight, inhibited fasting insulin (FINS) levels and Homeostatic Model Assessment of Beta-cell function (HOMA-β), enhanced Fasting Blood Glucose (FBG)/FINS/Total Cholesterol/Triglycerides levels, improved hepatic fibrosis (HE staining), and also upgraded HbAIc and HOMA-IR in mice of GDM. LGMN exacerbated ROS-induced oxidative stress in the in vitro model of GDM. LGMN promoted ferroptosis in vitro model of GDM. LGMN expanded ROS-induced mitochondrial damage in vitro model of GDM. LGMN inhibited the HSP90/GPX4 Signaling Pathway in the model of GDM. The inhibition of HSP90 reduced LGMN on GDM in the mice model or the in vitro model of GDM. LGMN interlinked with complex protein body of HSP90 and GPX4, which LGMN inhibited the HSP90/GPX4 Signaling Pathway.

Conclusions: The LGMN level in patients with GDM was upregulated, and LGMN facilitates ferroptosis by HSP90 and GPX4 in the mice model of GDM and may lead to therapeutic potential of ferroptosis or liver gluconeogenesis in the model of GDM.

Indole-3-carbinol ameliorates ER stress-mediated hyperleptinemia in western diet-fed apoE-/- mice

2026-02-11T10:46:23+00:00

Background: Endoplasmic reticulum (ER) stress during overnutrition causes leptin resistance in obese animals and humans. ER stress induces the activation of the unfolded protein response, which disrupts the leptin signaling pathway, accelerating atherosclerosis development and its complications.

Objective: Indole-3-carbinol (I3C) improves metabolic dysfunction in diet-induced obesity; however, its role in protecting against ER stress-induced hyperleptinemia remains unclear. Herein, we explored whether dietary I3C alleviates ER stress in apolipoprotein E-deficient (apoE^-/-) mice fed a western diet (WD).

Design: ApoE^-/- mice were fed either WD (60 kcal from fat, n = 10) or WD supplemented with 0.05% I3C (w/w, n = 10) for 12 weeks.

Results: I3C supplementation (0.05%) resulted in reduced adipose tissue weight and plasma leptin levels compared with those in WD-fed apoE^-/- mice after 12 weeks. I3C also significantly decreased the protein expression of ER stress markers, whereas increased the mRNA expression of genes related to cholesterol efflux and fatty acid β-oxidation in the liver, despite no changes in plasma cholesterol and triglyceride levels. Immunohistochemistry revealed reduced aortic localization of glucose-related protein 78 compared with the WD group, suggesting that I3C partially alleviated ER stress in atherosclerotic lesions of WD-fed apoE^-/- mice.

Conclusion: I3C may serve as a feasible compound for preventing atherosclerosis and its associated complications.

Investigation of the immunoregulatory mechanisms of total saponins from black ginseng

2026-02-06T00:33:06+00:00

Objective: This study aimed to elucidate the immune-regulating effects and underlying mechanisms of action of total saponins extracted from black ginseng in an immunosuppressed murine model.

Methods: The chemical composition of black ginseng total saponins (BGTS) was analyzed using high-performance liquid chromatography, which revealed a high content of rare ginsenosides, such as Rk1, Rg5, and Rg3. Immunosuppressed mice were administered BGTS, and key immunological parameters were assessed, including body weight, spleen and thymus indices, cytokine and immunoglobulin levels, and the expression of immune-related genes and proteins.

Results: BGTS treatment significantly improved body weight and immune organ indices and promoted the secretion of cytokines, including interleukin (IL) 2, IL-1β, tumor necrosis factor-alpha, immunoglobulin (Ig) A, IgG, and IgM. Mechanistically, BGTS significantly activated the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor-κB signaling pathway at the protein level and upregulated gene expression of TLR-4, TNF-α, IL-6, and IL-1β.

Conclusion: These findings suggest that BGTS exerts notable immunomodulatory effects by enhancing innate immune responses, primarily by activating the TLR4-mediated signaling pathway. Further studies are necessary to isolate the contribution of individual ginsenosides and evaluate the long-term safety and clinical potential of BGTS.

Melissa phospholipids improves sleep quality and mental well-being: concluding results from clinical study in adults with emotional distress

2026-01-31T12:50:50+00:00

Background: Melissa officinalis L. (lemon balm) is a botanical support widely used for its calming and sleep-promoting properties.

Objective: To evaluate the impact of daily supplementation with Melissa phospholipids (MOP) at 200 or 400 mg for 3 weeks on sleep quality and psychological well-being in adults with emotional distress and poor sleep quality.

Design: This prospective, open-label, dose-comparison clinical study enrolled 32 adults with poor sleep quality and/or clinically significant emotional distress. Participants received daily supplementation with either 200 or 400 mg/day MOP for 3 weeks. Sleep quality (primary endpoint) was assessed using the Pittsburgh Sleep Quality Index (PSQI) at baseline (T0), and week 3 (T1). Secondary endpoints included depression, anxiety, and stress, positive and negative affect, mental well-being, and quality of life. Safety was also assessed through adherence monitoring, documentation of side effects or adverse events, and by routine blood biochemistry parameters of liver and renal functions.

Results: PSQI scores significantly improved over time (P < 0.0001), with greater and earlier benefits at 400 mg/day (−30% vs. −15%; P < 0.05). The 400 mg dose also produced significant reductions in depression (−26%), anxiety (−18%), and stress (−22%) scores (all P < 0.001), together with increased positive and negative affect together with Warwick-Edinburgh Mental Well-Being Scale (+15%). Quality of life improved across total score (33%) and its four domains, with significant results in physical well-being (P < 0.05). No statistically significant changes in safety parameters were detected and no adverse effects were reported.

Discussion: MOP, particularly at 400 mg/day, confirmed to significantly improve sleep and life quality, mood, and overall mental well-being.

Conclusion: These findings support and extend the health benefits of MOP as a well-tolerated, safe natural approach in a dose-dependent frame to managing sleep quality and emotional distress. Future placebo-controlled trials are warranted to confirm these results and further elucidate the underlying mechanisms of action.

Energy drink consumption, sleep behavior, and food choices of Icelandic adolescents

2026-01-29T07:24:06+00:00

Background: The consumption of energy drinks has increased in the last decades, especially among adolescents. Caffeine and its effects on sleep are well known, but less is known about the timing of the consumption and its association with sleep and food choices.

Objective: The objective of this study was to evaluate the energy drink consumption, sleeping behavior, and food choices in Icelandic adolescents.

Design: A total of 171 participants (64 boys, 107 girls, aged 17–18 years) completed an online questionnaire on sleep, food choices, and energy drink consumption. Independent sample T-tests, Mann-Whitney U tests, and Chi-square tests were used to assess group differences.

Results: Overall, 57% reported drinking energy drinks, with higher rates among girls than boys (63 vs. 48%). Energy drink consumers were more likely to report sleeping 6 h or less. This was especially true for those drinking energy drinks after 3 PM, compared to those who avoided them after 3 PM. Participants who consumed energy drinks also ate fewer nutritious foods (fruits, vegetables, dairy, fish) and consumed more soft drinks, coffee, and alcohol compared to non-energy drink consumers.

Discussion: The results show that energy drink consumption is frequent among Icelandic 17-year-olds, particularly among girls. Consumers were more likely to report shorter sleep durations, especially when drinking after 3 PM, and had poorer dietary habits, including lower intake of nutritious foods and higher consumption of soft drinks, coffee, and alcohol.

Conclusion: Future research should explore the long-term effects of these behaviors and assess interventions to reduce energy drink use and promote healthier habits in adolescents.

Estrogen promotes the angiogenesis and osteogenesis of bone marrow stromal cells via regulating ESR1/RUNX2 axis

2026-01-16T09:15:02+00:00

Osteoporosis (OP) is a common bone disease characterized by decreased bone mass and microarchitectural deterioration. This study aimed to investigate the effects of estrogen on OP. Bilateral ovariectomy (OVX) surgery was performed to establish the OP mouse model. Histological analysis was performed using hema- toxylin and eosin (HE) staining and alizarin red S (ARS) staining. Angiogenetic factors were determined using enzyme-linked immunosorbent assay (ELISA). Messenger RNA (mRNA) levels were determined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Protein expression was determined using Western blot. Cellular functions were analyzed using Transwell, tube formation, alkaline phosphatase staining, and ARS staining assay. The co-localization of estrogen receptor alpha (ESR1) and runt-related transcription factor 2 (RUNX2) was determined using the fluorescence in situ hybridization (FISH) assay. The interaction between ESR1 and RUNX2 was determined using the co-immunoprecipi- tation (Co-IP) assay. We found that 17β-estradiol (E2) alleviated the decrease in bone intensity and mass induced by OVX. E2 promoted the angiogenesis and osteogenesis of bone marrow stromal cells (BMSCs). Mechanistically, E2 predominantly upregulated ESR1. Moreover, mediated nuclear-localization of ESR1 promoted the interaction between ESR1 and RUNX2. Furthermore, ESR1 overexpression promoted the angiogenesis and osteogenesis of BMSCs. Estrogen exerts a protective effect on OP. Estrogen mediates the angiogenesis and osteogenesis of BMSCs by regulating the ESR1/RUNX2 axis.

Enhanced bioavailability of a krill oil-based milk thistle extract formulation: in vitro and human studies

2026-01-08T02:08:35+00:00

Background/Objectives: The milk thistle plant (Silybum marianum) is known for its hepatoprotective properties. However, the poor water solubility of silymarin limits its dissolution in the intestinal tract and restricts its bioavailability following oral administration.

Methods: To improve bioavailability, special formulations, in particular micellar solubilization, are explored. In this study, we examined the transport rate of silymarin in a krill oil-based formulation across a Caco-2 epithelial barrier after upstream digestion simulation in vitro. Furthermore, in a randomized cross-over design study the bioavailability of the krill oil-based formulation was investigated after single dose intake in fasting conditions in healthy participants.

Results: We could demonstrate that the apparent transport coefficient of silybin, measured as lead substance of milk thistle extract, across the epithelium is efficiently boosted by a krill oil formulation, resulting in a 28% increase compared to silymarin powder. Consistent with these findings, a significant enhancement of bioavailability (P < 0.0001) was demonstrated for the krill oil-based formulation in comparison to the milk thistle extract resulting in an 8.59-fold higher AUC_0-8h and a 15.08-fold greater C_max of silybin and faster uptake kinetic after single dose intake.

Discussion and Conclusions: These findings suggest that phospholipid-based delivery systems offer a promising strategy for improving the efficacy of lipophilic bioactives. Furthermore, the combination of krill oil with milk thistle extracts efficiently provides silybin, PUFAs, and choline, which are important nutrients contributing to liver and heart health.