The intestinal bone morphogenetic protein (BMP) pathway counteracts the Wnt pathway, which is overactivated in 90% of colorectal cancers (CRC) due to mutations in the adenomatous polyposis coli ( APC) gene. Our study aimed to identify a polyphenol that acts on the colonic BMP pathway and to evaluate its ability to mitigate the harmful effects of 4-hydroxynonenal (HNE), a dietary genotoxic molecule, on normal colonocytes. We first evaluated the effect of 10 polyphenols on the expression of BMP pathway actors using a normal mouse colonocyte and fibroblast culture model. Apigenin (Apig) and resveratrol (Res) increased the production of BMP4 ligand and reduced expression of the Gremlin1 (Grem1) antagonist in fibroblasts. Apig also enhanced the expression of the bone morphogenetic protein receptor type 2 ( Bmpr2) in fibroblasts and that of the Smad1 effector in colonocytes. Finally, Apig inhibited the phenotypic transformation of colonocytes induced by HNE through a mechanism that involved the BMP pathway in both fibroblasts and colonocytes. Our findings suggest that targeting the colonic BMP signaling pathway through dietary factors could contribute to the prevention of CRC. Apig-rich foods or supplements may play a role in this preventive nutrition, although further in vivo experiments are needed to confirm this potential.
Obesity, characterized by chronic low-grade inflammation, promotes cardiac structural and functional abnormalities. This study evaluated the therapeutic potential of lycopene in attenuating obesity-induced cardiac remodeling, based on its antioxidant and anti-inflammatory properties and its ability to inhibit matrix metalloproteinase-2 (MMP-2) activation, thereby preserving myocardial collagen integrity. Male Wistar rats were fed a high-sugar, high-fat (HSF) diet to induce obesity and cardiac remodeling. After the onset of cardiac dysfunction, animals received lycopene supplementation (10 mg/kg/day) for 10 weeks. The HSF diet caused metabolic disturbances, including hypertension, increased adiposity, and insulin resistance, accompanied by myocardial remodeling, inflammation, and elevated MMP-2 activity. Lycopene supplementation reversed insulin resistance, mitigated myocardial remodeling, and improved both systolic and diastolic cardiac function. It also reduced inflammatory markers (TNF-α, IL-6, NF-κB, TLR-4), decreased MMP-2 activation, and enhanced TIMP-2 and type I collagen expression. Lycopene demonstrated cardioprotective and anti-inflammatory effects in obesity-induced cardiac remodeling. By targeting inflammation and extracellular matrix degradation, lycopene may serve as an effective adjunctive therapeutic approach for preventing or treating obesity-related cardiac disorders.
Gut microbiota dysbiosis is closely linked to depression and can be modulated by dietary polysaccharides. This study aimed to characterize three polysaccharide fractions from Pericarpium Citri Reticulatae "Chachiensis" (PCRCP)-PCRCPI, PCRCPII, and PCRCPIII-and evaluate their antidepressant effects in a high-fat diet-induced mouse model. Their average molecular weights were approximately 48.9 kDa (PCRCPI), 13.7 kDa (PCRCPII), and 34.8 kDa (PCRCPIII), with a composition primarily of galacturonic acid, arabinose, galactose, and rhamnose. PCRCPI most effectively mitigated depression-like behaviors, as indicated by improved behavioral performance and neurotransmitter levels and reduced neuronal damage. The antidepressant effect of PCRCPI was contingent upon the gut microbiota, as demonstrated by the fact that fecal microbiota transplantation (FMT) from donors treated with PCRCPI conferred behavioral improvements. Mechanistically, PCRCPI treatment selectively increased the abundance of Lactobacillus species and elevated fecal levels of metabolites associated with retrograde endocannabinoid signaling, particularly 2-arachidonoylglycerol (2-AG). Subsequent colonization experiments with specific Lactobacillus strains, either alone or in combination with PCRCPI, activated hippocampal retrograde endocannabinoid signaling as revealed by transcriptomic analysis, and ameliorated depression-like phenotypes. These findings demonstrate the potential of PCRCPI as a prebiotic for alleviating diet-associated depression, through a novel microbiota-gut-brain axis mechanism targeting the endocannabinoid system.
This study examined the metabolic effects of wheat flour intake on body weight regulation in mice. Male and female C57BL/6 mice were given free access to standard chow and wheat-based foods, including bread and baked wheat flour, and food preference, energy expenditure, hepatic gene expression, and blood metabolite profiles were analyzed. Mice showed a strong preference for wheat-based foods, leading to significant body weight gain despite comparable caloric intake. Wheat flour consumption was associated with reduced energy expenditure, increased adiposity, and elevated circulating insulin and leptin levels. Blood metabolomic analysis revealed increased fatty acid levels and reduced essential amino acids, suggesting enhanced lipogenesis and a potential imbalance in amino acid intake. Consistently, hepatic expression of genes involved in fatty acid synthesis and lipid transport was upregulated. Importantly, withdrawal of wheat flour rapidly attenuated body weight gain and reversed the associated metabolic alterations. These findings demonstrate that wheat flour intake promotes obesity in mice primarily by decreasing energy expenditure and altering metabolic pathways independent of excess calorie consumption, highlighting wheat flour as a dietary factor that strongly influences energy homeostasis and body weight regulation.
This study aimed to investigate the effects of maternal supplementation with fish oil, flaxseed oil, and walnut oil rich in omega-3 fatty acids during lactation on mammary tissue structure and milk quality. Rats were randomly assigned to negative control, control, fish oil, walnut oil, and flaxseed oil groups. The supplements were administered by oral gavage from parturition (Day 0) to the end of lactation (Day 21). Mammary tissues were evaluated immunohistochemically, and blood samples were analyzed biochemically. The docosahexaenoic acid (DHA) level in the fish oil group was significantly higher than in other groups (p < 0.05). Fatty Acid Desaturase-2 (FADS2) levels also differed significantly between the negative control and all other groups (p < 0.05), while no significant change was observed in the walnut oil group (p > 0.05). Immunostaining intensities for insulin-like growth factor 1 (IGF-1), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) varied significantly among all groups (p < 0.05). These findings suggest that maternal fish oil supplementation during lactation more effectively enhances milk quality and mammary tissue function than flaxseed or walnut oil, indicating its potential as a dietary strategy to improve milk composition and support offspring nutrition. Trial Registration: Registered on the Clinical Trial Registry (www.clinicaltrials.gov; Clinical Trials identifier: NCT06111378 (26/10/2023).
Chemotherapy-induced senescence-associated tumor microenvironment (S-TME) facilitates colorectal cancer (CRC) progression. This study elucidates the mechanism by which Tianma granule (TMG), a traditional Chinese medicine formula, remodels the S-TME and inhibits CRC, specifically investigating the role of the miR-29a-5p/P53 axis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 18 bioactive components in TMG, and network pharmacology highlighted P53 as a core target. Functional assays, including Cell Counting Kit-8 (CCK-8), β-galactosidase staining, flow cytometry, wound-healing, and Transwell migration tests, were conducted using doxorubicin (DOX)-induced senescent human umbilical vein endothelial cells (HUVECs) and CRC lines. TMG suppressed CRC cell proliferation, motility, and invasiveness while promoting apoptosis. TMG reduced P53/cyclin-dependent kinase inhibitor 1A (P21) and senescence-associated secretory phenotype (SASP) factors (IL-6, IL-8, CCL20), while upregulating miR-29a-5p in senescent HUVECs. miR-29a-5p inhibition enhanced senescence and increased P53/P21/SASP, whereas P53 silencing lowered P21 and decreased miR-29a-5p, indicating mutual regulation. In azoxymethane/dextran sulfate sodium (AOM/DSS)-CRC mice, TMG reduced tumor burden and improved survival, accompanied by lower P53/P21 and restored miR-29a-5p in tissues. TMG remodels the chemotherapy-induced S-TME and suppresses CRC progression by modulating the miR-29a-5p/P53 axis, enhancing apoptosis in senescent cells, and counteracting S-TME-mediated tumor growth and metastasis. This highlights TMG's therapeutic potential.
To investigate whether early-life docosahexaenoic acid (DHA) consumption mitigated the effects of a high-fat diet (HFD) on body composition, endocrine hormones, immune function, inflammatory biomarkers, and identify sex differences. Wistar rats were fed (PND 0-70) diets differing only in fat composition: control low-fat (10% fat, 0% arachidonic acid [ARA], 0% DHA), control high-fat (HF, 20% fat, 0% ARA, 0% DHA), or DHA HF (20% fat, 1% ARA, 2% DHA) (n = 16/group, males/females = 8/8). Plasma hormones (ELISA), inflammatory biomarkers (electrochemiluminescence), splenocytes phenotype (immunofluorescence), and ex vivo cytokine production (ELISA) after mitogen stimulation were measured. HFD did not alter body weight/composition or inflammatory profile but increased plasma glucagon-like peptide 1 (GLP-1, males, p = 0.02). In the spleen, HFD lowered transforming growth factor-beta (TGF-β) and increased interleukin (IL)-10 (females) and IL-2 production (p < 0.03). It also lowered % of regulatory T cells (Treg), B cells (males), conventional type 1dendritic cells (cDC1), and MHC-II and CD86 expression (males) (p < 0.03). DHA mitigated HFD-related changes in plasma GLP-1 (males) andTGF-β, IL-10 (females), and IL-2 production (p ≤ 0.03) and increased % of B cells (males), cDC1, MHC-II, and CD86 expression (males) (p < 0.03). DHA mitigated HFD-induced impaired Treg response and compromised adaptive immunity and antigen-presenting function in a sex-specific manner.
The gut microbiota is a key determinant of metabolic health in adolescence, a critical period for the onset of obesity. Understanding its associations with body mass index (BMI), diet, and socioeconomic status (SES) helps identify early determinants of metabolic risk. We analyzed stool samples from 95 Mexican adolescents (11-15 years) using 16S rRNA V3-V4 sequencing. The main phyla were Bacteroidetes, Firmicutes, and Proteobacteria, with. At the genus level Azobacteroides Candidatus, Parabacteroides, Bacteroides, and Prevotella being the most abundant. Overweight and obese adolescents showed lower diversity and more Bacteroidetes, while normal-weight peers had more Firmicutes and beneficial taxa. Lactobacillus was enriched in normal-weight individuals, while Parabacteroides and Prevotella were more abundant in adolescents with low SES. A diet high in sugar-sweetened beverages and low in whole grains was associated with a predominance of Bacteroides and lower diversity. Low SES was also associated with potential pathogens, including Escherichia and Salmonella, and gastrointestinal symptoms. In particular, Vibrio and Salmonella were inversely associated with cholesterol and triglycerides, while Clostridiodes was positively correlated with triglycerides. Diet and SES influenced the adolescent gut microbiome, by shaping diversity, potentially pathogenic taxa, and their associations with metabolic health indicators.
Iron deficiency anemia may affect carbohydrates and lipid metabolism. This study aimed to evaluate the iron bioavailability from biofortified cowpeas in the context of a high-fat/high-sugar diet and its relationship with carbohydrate and lipid metabolism. Forty-eight Wistar rats were induced to anemia for 21 days, and during the repletion phase (35 days), the animals received diets containing 12 ppm of iron from ferrous sulfate or biofortified (BRS Aracê and BRS Tumucumaque) and a conventional (BRS Pajeú) cowpeas. The biofortified cowpea Aracê showed a hemoglobin gain similar to ferrous sulfate, improved crypt size in the colon, lowered insulin levels and area under the curve in the glucose tolerance test compared to ferrous sulfate (p < 0.05). Hepcidin levels were similar between the groups. The biofortified cowpeas increased the production of short-chain fatty acids compared to ferrous sulfate (p < 0.05). Both biofortified and conventional cowpeas increased HDL-c concentrations, reduced the total cholesterol/HDL-c ratio, and decreased fecal triglyceride excretion (p < 0.05). The biofortification process favors beneficial metabolic changes in the iron, glucose, and lipid metabolism.
Based on Traditional Chinese Medicine (TCM) theory, the efficacy and mechanism of Ginger juice processed Ziziphi Spinosae Semen (GJPZSS) for treating insomnia, particularly stress-related types, were investigated to provide empirical evidence. An insomnia model was induced in mice by DL-4-chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC-Q-TOF-MS/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels, decrease hypothalamic-pituitary-adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep-improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP/PKA/CREB/BDNF signaling pathway.
Several studies demonstrated curative responses of combined radio-immunotherapy, although not standard-of-care for most cancers. Increased fiber intake has been associated with improved radiotherapy and immunotherapy outcomes, but fiber compositions’ impact remains unclear. This study aimed to explore whether dietary fiber composition influences the therapeutic outcome of combined radio-immunotherapy in a preclinical cancer model. A syngeneic mouse model of colon cancer (CT26) (female BALB/cOla Hsd) was used. Mice were randomized into three groups ( n = 12) of iso-caloric diets with different fiber compositions. Five instances of local radiotherapy on tumors, combined with injections of anti-PD-L1, were administered over 5 and 10 days. Diets’ impact was assessed on progression-free survival, SCFA levels in fecal and cecal samples, gut microbiome composition, and immunological profile. Progression-free survival was different between compositions, as well as their gut microbiota community structure, at all measured time-points. Therapeutic outcome (cure) was negatively associated with the relative abundance of Bacteroides and positively with Atopobiaceae Family . There was no association with SCFA levels. Cured mice displayed smaller spleens containing increased proportions of CD8+ T-cells and decreased proportions of myeloid-derived suppressor cells. Our data suggest that fiber composition may influence therapeutic outcome of combined radio-immunotherapy treatment in vivo.
Pancreatic cancer treatment typically involves surgery, chemotherapy, and radiotherapy. However, recent studies are investigating alternative therapeutic strategies, including targeted therapies, immunotherapy, and the adjunctive use of compounds like vitamin B6. PLP functions as a cofactor in over 100 enzymatic reactions crucial for amino acid metabolism, neurotransmitter production, and heme synthesis. Previous studies demonstrated PLP's anti-cancer properties in human lymphoma cells, demonstrating its anti-proliferative and anti-migratory effects, as well as its influence on cytokine levels and checkpoint marker expression. Herein, we further investigated PLP's anti-cancer effects on human pancreatic cancer cells, showing a reduction in cell growth, disruption of the mitochondrial membranes, increased superoxide production, and the induction of apoptosis. In addition, PLP treatment in BxPC3 cells affects transcripts related to key pathways like E2F, G2M Checkpoint, mTOR, and KRAS, enhancing functional protein networks that may improve anti-cancer effects. In PANC1 cells, PLP reduces KRAS-related transcripts and increases those involved in Tumor Necrosis Factor signaling and the unfolded protein response, suggesting a regulatory role that may enhance cellular stress responses. Overall, the findings from this study indicate that PLP may pave the way for more effective therapeutic adjunctive options in the management of pancreatic cancer.
Childhood malnutrition, including undernutrition, obesity, and micronutrient deficiencies, remains a major global health burden. Emerging evidence points to the gut microbiome as a critical mediator linking maternal, prenatal, and early-life nutrition to long-term offspring health outcomes. From conception and through the first years of life, maternal diet, metabolic state, and environmental exposures shape offspring microbial colonization and maturation. Breastfeeding and consumption of fiber-rich and fermented foods (maternal and post-weaning) support beneficial microbiota, while high-fat, high-sugar diets, xenobiotics, and artificial additives may promote dysbiosis. The composition and diversity of the infant microbiome influence immune, metabolic, and neurodevelopmental processes and may also contribute to the intergenerational transmission of malnutrition. While commercial formulas increasingly include "biotics" to mimic human milk, exclusive breastfeeding remains the gold standard. Complementary feeding practices, including timing and diet quality, are known to modulate microbial maturation. Diet-based interventions in pregnancy show promise in improving microbiome function and preventing disease in offspring. Because the microbiome is highly plastic in the first years of life, this window offers unique opportunities for preventive strategies targeting maternal and child nutrition. Integrating microbiome science into public health and dietary guidelines could enhance current approaches to breaking the cycle of malnutrition and promoting lifelong health.
Chronic obstructive pulmonary disease (COPD) is primarily induced by chronic cigarette smoke (CS) exposure, which triggers irreversible airway inflammation and remodeling. Although Canarium album L. (CA) has been historically utilized to alleviate respiratory symptoms, its efficacy and mechanisms against COPD remain poorly characterized. This study aimed to investigate the anti-COPD potential of CA and further explore its crucial bioactive constituents. In this work, the phytochemicals and 15 phenolic compounds of eight varieties of CA were determined. Network pharmacology was used to search COPD targets and related pathways. The active constituents were screened, and the efficacy and mechanism of CA against COPD were uncovered based on the CS-induced Beas-2B cell model combined with spectrum-effect analyses and molecular docking. The results suggested that CA could reduce the release of inflammatory mediators and the expressions of COX-2 and iNOS via downregulating MAPK signaling pathway to mitigate COPD. Among them, (+)-catechin, epicatechin and (-)-epigallocatechin showed stronger correlations and better interactions with the core targets of COPD, they might be the effective components. This study lays foundation for understanding the potential of CA in COPD treatment and provides guidance for subsequent functional food development.
Purple red rice bran, a nutrient-rich byproduct of rice processing, contains abundant anthocyanins that distinguish it from ordinary bran and may offer metabolic benefits, while previous in vitro work has revealed that anthocyanins can form V-shaped inclusion complexes with rice starch (S-A), thereby enhancing resistant starch content and stimulating the growth of beneficial gut bacteria. However, the in vivo effects remain unclear. Therefore, using a high-fat diet/streptozotocin-induced T2DM mouse model to assess the metabolic impact of S-A, the results showed that dietary supplementation with S-A regulated glucose-lipid homeostasis, significantly reducing serum total cholesterol (5.98 ± 1.02→3.21 ± 1.07 mmol/L) and low-density lipoprotein cholesterol (3.25 ± 0.67→1.15 ± 0.74 mmol/L), with histopathological analysis revealing alleviated hepatic steatosis, renal fibrosis, and adipocyte hypertrophy; moreover, S-A reshaped the gut microbiota by enriching beneficial taxa, suppressing pathogens, and elevating short-chain fatty acids, while predictive functional analysis indicated restoration of microbial pathways involved in energy and amino acid metabolism. Overall, S-A exerts multifaceted regulation of lipid-glucose metabolism and gut microbiota, mitigating metabolic dysfunction in diabetic mice, and these findings underscore its potential as a novel functional dietary intervention while promoting the value-added utilization of purple red rice bran in managing metabolic disorders.
2'-Fucosyllactose (2'FL) is an abundant human milk oligosaccharide and is recognized for its diverse biological benefits. The aim of this study was to investigate the effects of 2'FL supplementation on small intestinal remodeling and the associated enhancement of nutrient absorption capabilities. Mice were orally supplemented with 2'FL daily for 20 d. This supplementation significantly increased the length of the small intestine and the density of villi, with no adverse effects on intestinal barrier function. Mice treated with 2'FL exhibited an enhanced absorption of triglycerides containing docosahexaenoic acid in lipid tolerance tests. Additionally, the absorption of CL316,243 and curcumin was significantly increased in the co-administration groups. This was accompanied by elevated uncoupling protein 1 levels in inguinal adipose tissue. Our study showed that 2'FL enhances nutrient and functional compound absorption by promoting intestinal remodeling. This highlights the novel role of 2'FL-a non-nutritive compound-in supporting intestinal health. Our findings suggest potential applications of 2'FL in growth promotion, lifestyle-related disease prevention, and frailty reduction, thereby advancing research on the nutritional functions of food-derived compounds.
The oxidative balance score (OBS) integrates dietary and lifestyle factors to reflect oxidative stress. OBS has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the modifying roles of genetic predisposition and gut microbiota remain unclear. This study evaluated the prospective association between OBS and MASLD and potential modification by genetic and microbial factors. We analyzed 182 601 UK Biobank participants free of MASLD at baseline. OBS was calculated from 16 dietary and 4 lifestyle components. Incident MASLD cases were identified from hospital and death records. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). During a median 10.5 years of follow-up, 1500 participants developed MASLD. Compared with the lowest OBS quartile, adjusted HRs (95% CIs) were 0.82 (0.71-0.94), 0.71 (0.61-0.83), and 0.68 (0.58-0.81) for the second, third, and fourth quartiles (p-trend < 0.001). MASLD genetic risk score (GRS) and microbial GRSs for Ruminococcus torques and Sutterella were associated with MASLD risk but did not modify the OBS-MASLD association (all p-interaction > 0.05). Higher OBS was associated with lower MASLD risk, independent of genetic and microbial GRSs. These findings provide prospective association evidence that may inform future intervention studies.
Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin, which occurs in broccoli. Several human health-promoting effects are attributed to the consumption of cruciferous vegetables or food supplements containing SFN. Its described cancer-preventive, chemoprotective, and antioxidant properties made SFN an increasingly important research topic. The antioxidant properties have previously been connected to stimulation of the Nuclear factor erythroid-2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling pathway. However, the global effects of SFN on the primary metabolic pathways have yet to be fully unraveled. Therefore metabolic profiling was used to elucidate the effects of SFN on the cellular metabolome. For this purpose, human hepatoblastoma cells (HepG2) were incubated with SFN and the changes of primary metabolite levels were determined by targeted hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) analysis. Metabolic profiling revealed that SFN affects the tricarboxylic acid cycle, the urea cycle and their related amino acids. Furthermore, effects on glycolysis, pentose phosphate pathway and glutathione (GSH) levels were observed. This profound impact on nearly all primary metabolic pathways indicates a high bioactive potential of this natural compound. Especially elevated GSH levels underline the commonly described antioxidant potential of SFN.
Galactose, a component of lactose, has nutritional programming power in mice. Lactose-free formulae contain maltodextrin, but no galactose. Here, partly replacing maltodextrin with galactose in the post-weaning diet was investigated for its metabolic and nutritional programming effects. Female and male mice were fed 39 energy% (en%) maltodextrin and 8 en% glucose (CON), or 31 en% maltodextrin with 16 en% galactose (GAL), or 15 en% maltodextrin and 16 en% galactose plus 16 en% glucose (lactose-mimic, LM) from postnatal week (PW) 3 to PW6. Body weight, fat mass, lean mass, energy expenditure (EE), and respiratory exchange ratio (RER) were lower at PW6 in female GAL and LM mice (p < 0.05). After receiving 9 weeks of the same obesogenic high-fat diet, the expression of hepatic insulin-like growth factor 1 (Igf1) appeared lower in both galactose-fed groups in females (p < 0.05). Partly replacing maltodextrin with galactose or galactose plus glucose in a post-weaning diet in mice resulted in significantly lower body weight, fat and lean mass, EE, and RER in early-life, and had no obvious nutritional programming effects except on liver Igf1 mRNA in females in later-life. The implications of this programming effect remain to be investigated further.
Fish is rich in nutrients; however, concerns persist regarding its potential role in delaying aging due to the possible accumulation of cadmium. This study aimed to assess the association between fish consumption, dietary ω-3 polyunsaturated fatty acids (PUFAs), and Phenotypic Age Acceleration (PhenoAgeAccel) in the presence of cadmium exposure. The study used data from National Health and Nutrition Examination Survey (NHANES) 2011-2018. Multiple linear regression, restricted cubic splines (RCS), and subgroup analysis were used to assess potential associations. Mediation analysis further examined whether blood cadmium levels mediated the association between fish consumption and PhenoAgeAccel. Results showed that higher fish consumption and ω-3 PUFAs intake were significantly associated with lower PhenoAgeAccel. This association persisted even in the presence of cadmium exposure. Furthermore, the association between fish consumption or ω-3 PUFAs and PhenoAgeAccel was more pronounced in people with low cadmium exposure levels. RCS analysis revealed a non-linear relationship between fish consumption and dietary ω-3 PUFAs and PhenoAgeAccel. Blood cadmium levels partially mediated the association between fish consumption and PhenoAgeAccel. Our results support dietary recommendations to consume fish to slow biological aging. Even in the presence of cadmium exposure, fish consumption was negatively associated with PhenoAgeAccel.
