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Background Several studies have employed dried blood spot (DBS) analysis to measure omega-3 levels in whole blood and investigate their associations with cardiovascular risk. Our study evaluated the effectiveness of using DBS as a marker for dietary intake, specifically focusing on omega-3 fatty acids, over both short- and long-term periods. As a novel approach, this study aims to determine whether the fatty acid (FA) profile of DBS can be useful to accurately reflect nutritional habits and monitor changes in fish intake over different consumption periods. Methods A within-subject nutritional intervention study was conducted with 18 healthy volunteers (both males and females aged 18–65 years). Their FA profiles were determined by GC-FID in DBS before the intervention began, and changes in their blood FA profiles were monitored at five different time-points across different periods of oily fish consumption. Dietary information was recorded daily through questionnaires. For statistical analysis, hierarchical clustering and principal component analysis were performed to detect patterns of FA profiles in DBS. Differences among groups were tested by Student´s t test or by Wilcoxon test, and changes across visits were analysed via linear mixed models. Results The results revealed three main patterns of the DBS profile, which could be explained by the participants’ dietary habits. Furthermore, the changes during the intervention indicated that eicosapentaenoic acid (20:5n-3) levels were highly affected by the diet of the previous day, whereas docosapentaenoic acid (22:5n-3) and docosahexaenoic acid (22:6n-3) required at least one or two weeks to show changes, with little difference depending on the FA levels of the participants before they started the intervention. Conclusion The use of DBS to examine blood FA composition is a promising, reliable and convenient way to assess dietary habits and monitor responses to food intake, which could help advance personalised nutritional strategies. Trial registration The study was registered at the ISRCTN (registration number ISRCTN47135203) the 22nd October 2024.

Background/Objectives: Hereditary fructose intolerance (HFI) is an inherited metabolic disorder caused by a deficiency of the enzyme fructose-1,6-bisphosphate aldolase. Treatment consists of a lifelong diet restricted in fructose, sucrose, and sorbitol (FSS). The aim of this study was to determine dietary intake of FSS and to analyze the consumption patterns of vegetables, fruit, legumes, pulses, and dried fruit in a nationwide cohort of HFI patients. Methods: Overall, 36 HFI patients and 28 age-, sex- and BMI-matched healthy control subjects participated in this study. A self-administered three-day dietary record and an adapted quantitative food frequency questionnaire (FFQ) including frequency and portion sizes were collected. FSS intake was calculated using the DIAL Nutritional Calculation Program (ALCE INGENIERÍA). Total fructose intake was calculated as the sum of free fructose, 50% of sucrose, and sorbitol. Results: Protein intake was significantly higher in HFI patients compared to the controls (92.43 g/day [65.1–165.03] vs. 70.39 g/day [35.21–133.83]; p = 0.001). In most patients, total fructose intake was within the recommended limits (9.79 mg/kg bw/day [0.29–59.09]), with no significant differences between children and adults (p = 0.325). Although the established dietary recommendations did not always match the actual intake observed in a real-life setting, in general, foods with higher fructose content were consumed less frequently and in smaller quantities. Conclusions: Further research on the fructose content of various foods, particularly fruits and vegetables, and updated dietary recommendations for HFI patients are warranted to provide the best tools for the nutritional management of the disease.

Liver fibrosis must be evaluated in patients with hepatitis C virus (HCV) after liver transplantation because its severity affects their prognosis and the recurrence of HCV. Since invasive biopsy is still the gold standard to identify patients at risk of graft loss from rapid fibrosis progression, it becomes crucial the development of new accurate, non-invasive methods that allow repetitive examination of the patients. Therefore, we have developed a non-invasive, accurate model to distinguish those patients with different liver fibrosis stages. Two hundred and three patients with HCV were histologically classified (METAVIR) into five categories of fibrosis one year after liver transplantation. In this cross-sectional study, patients at fibrosis stages F0-F1 (n = 134) were categorised as “slow fibrosers” and F2-F4 (n = 69) as “rapid fibrosers”. Chloroform/methanol serum extracts were analysed by reverse ultra-high performance liquid chromatography coupled to mass spectrometry. A diagnostic model was built through linear discriminant analyses. An algorithm consisting of two sphingomyelins and two phosphatidylcholines accurately classifies rapid and slow fibrosers after transplantation. The proposed model yielded an AUROC of 0.92, 71% sensitivity, 85% specificity, and 84% accuracy. Moreover, specific bile acids and sphingomyelins increased notably along with liver fibrosis severity, differentiating between rapid and slow fibrosers.

Background Hyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy) metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD) in rats were investigated. Methods and results After feeding rats a standard low fat diet (control) or a high fat diet (57% metabolisable energy as fat) for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGS), the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group. Conclusions These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

Low serum folate levels are inversely related to metabolic associated fatty liver disease (MAFLD). The role of the folate transporter gene (SLC19A1) was assessed to clarify its involvement in lipid accumulation during the onset of MAFLD in humans and in liver cells by genomic, transcriptomic, and metabolomic techniques. Genotypes of 3 SNPs in a case-control cohort were initially correlated to clinical and serum MAFLD markers. Subsequently, the expression of 84 key genes in response to the loss of SLC19A1 was evaluated with the aid of an RT2 profiler-array. After shRNA-silencing of SLC19A1 in THLE2 cells, folate and lipid levels were measured by ELISA and staining techniques, respectively. In addition, up to 482 amino acids and lipid metabolites were semi-quantified in SLC19A1-knockdown (KD) cells through ultra-high-performance liquid chromatography coupled with mass spectrometry. SNPs, rs1051266 and rs3788200, were significantly associated with the development of fatty liver for the single-marker allelic test. The minor alleles of these SNPs were associated with a 0.6/−1.67-fold decreased risk of developing MAFLD. When SLC19A1 was KD in THLE2 cells, intracellular folate content was four times lower than in wild-type cells. The lack of functional SLC19A1 provoked significant changes in the regulation of genes associated with lipid droplet accumulation within the cell and the onset of NAFLD. Metabolomic analyses showed a highly altered profile, where most of the species that accumulated in SLC19A1-KD-cells belong to the chemical groups of triacylglycerols, diacylglycerols, polyunsaturated fatty acids, and long chain, highly unsaturated cholesterol esters. In conclusion, the lack of SLC19A1 gene expression in hepatocytes affects the regulation of key genes for normal liver function, reduces intracellular folate levels, and impairs lipid metabolism, which entails lipid droplet accumulation in hepatocytes.

Classic infantile Pompe disease (IPD) is a rare lysosomal storage disorder characterized by severe hypertrophic cardiomyopathy and profound muscle weakness. Without treatment, death occurs within the first 2 years of life. Although enzyme replacement therapy (ERT) with alglucosidase alfa has improved survival, treatment outcome is not good in many cases and is largely dependent on age at initiation. The objective of the study was (a) to analyse the different stages in the diagnosis and specific treatment initiation procedure in IPD patients, and (b) to compare clinical and biochemical outcomes depending on age at ERT initiation (<1 month of age vs. <3 months of age). Here, we show satisfactory clinical and biochemical outcomes in two IPD patients after early treatment initiation before 3 months of life with immunomodulatory therapy in the ERT-naïve setting, with a high ERT dose from the beginning. Despite the overall good evolution, the patient who initiated treatment <1 month of life presented even better outcomes than the patient who started treatment <3 months of life, with an earlier normalization of hypertrophic cardiomyopathy, along with CK normalization, highlighting the importance of early treatment initiation in this progressive disease before irreversible muscle damage has occurred.

Several etiologies result in chronic liver diseases including chronic hepatitis C virus infection (HCV). Despite its high incidence and the severe economic and medical consequences, liver disease is still commonly overlooked due to the lack of efficient non-invasive diagnostic methods. While several techniques have been tested for the detection of fibrosis, the available biomarkers still present severe limitations that preclude their use in clinical diagnostics. Liver diseases have also been the subject of metabolomic analysis. Here, we demonstrate the suitability of 1H NMR spectroscopy for characterizing the metabolism of liver fibrosis induced by HCV. Serum samples from HCV patients without fibrosis or with liver cirrhosis were analyzed by NMR spectroscopy and the results were submitted to multivariate and univariate statistical analysis. PLS-DA test was able to discriminate between advanced fibrotic and non-fibrotic patients and several metabolites were found to be up or downregulated in patients with cirrhosis. The suitability of the most significantly regulated metabolites was validated by ROC analysis. Our study reveals that choline, acetoacetate and low-density lipoproteins are the most informative biomarkers for predicting cirrhosis in HCV patients. Our results demonstrate that statistical analysis of 1H-NMR spectra is able to distinguish between fibrotic and non-fibrotic patients suffering from HCV, representing a novel diagnostic application for NMR spectroscopy.

Background The ITTHACA project is a collaborative initiative involving six research institutions from the Basque Country including Universities, Health, Technology and Basic Research Institutions. It builds upon the ongoing CITA GO‐ON) CITA Go‐On study, ClinicalTrials.gov, NCT04840030) cohort study, which adapts the Finnish FINGER [Ngandu, T., et al. 2015] model to the local context. ITTHACA focuses on enhancing healthy aging by identifying markers, prediction models and sensors for in vivo monitoring that allow the establishment and implementation of combined intervention strategies in the population. Method This one‐year randomized‐controlled trial (total n = 250; 125 control and 125 intervention), focused on 60‐85‐year‐old males and females at risk of dementia, adopts a multimodal approach. Biomarker identification includes proteomics and metabolomics in biological fluids (blood) and 16S metagenomics and lipidomics in the gut microbiome (stool), as well as employing a FINGER‐like mice model. Biosensor technology under development includes multi‐channel bioimpedance spectroscopy for tissue analysis and electrochemical sensors for real‐time detection of aging markers in biofluids. Predictive modeling integrates data from these analyses and multiple domains—cognition, cardiovascular health, voice, food texture perception and habits—to generate diagnostic tools that monitor biological aging and inform early interventions. A proof‐of‐concept study in an older population sample, with special attention to user experience, will evaluate the potential benefits of these findings in improving the quality of life for older adults. Result Not applicable. The ITTHACA project is ongoing, with outcomes expected to include validated biomarkers, novel biosensors, and predictive models that facilitate early interventions. Conclusion ITTHACA demonstrates the power of interdisciplinary collaboration in tackling the complex multidomain challenge of aging. By leveraging the expertise of complementary Basque Country Research Centers, this initiative is poised to produce innovative resources for prolonging healthy and autonomous living. The project's outcomes are expected to support new therapeutic strategies and socio‐healthcare interventions that address the rising prevalence of aging‐related conditions, including cognitive decline.

BackgroundHereditary fructose intolerance (HFI) is a rare inborn error of fructose metabolism caused by the deficiency of aldolase B. Since treatment consists of a fructose-, sucrose- and sorbitol-restrictive diet for life, patients are at risk of presenting vitamin deficiencies. Although there is no published data on the status of these vitamins in HFI patients, supplementation with vitamin C and folic acid is common. Therefore, the aim of this study was to assess vitamin C and folate status and supplementation practices in a nationwide cohort of HFI patients.MethodsVitamin C and folic acid dietary intake, supplementation and circulating levels were assessed in 32 HFI patients and 32 age- and sex-matched healthy controls.ResultsMost of the HFI participants presented vitamin C (96.7%) and folate (90%) dietary intake below the recommended population reference intake. Up to 69% received vitamin C and 50% folic acid supplementation. Among HFI patients, 15.6% presented vitamin C and 3.1% folate deficiency. The amount of vitamin C supplementation and plasma levels correlated positively (R = 0.443; p = 0.011). Interestingly, a higher percentage of non-supplemented HFI patients were vitamin C deficient when compared to healthy controls (30% vs. 3.1%; p = 0.036).ConclusionsOur results provide evidence for the first time supporting vitamin C supplementation in HFI. There is great heterogeneity in vitamin supplementation practices and, despite follow-up at specialised centres, vitamin C deficiency is common. Further research is warranted to establish optimal doses of vitamin C and the need for folic acid supplementation in HFI.