Nutrients

Background: During adolescence, the brain is undergoing anatomical and physiological maturation processes with changes to cognitive development. However, in adolescents with phenylketonuria (PKU), executive function and mental health are adversely affected by high blood phenylalanine (Phe) levels. Objectives: We aim to describe clinical outcomes in adolescents with PKU. Methods: Cross-sectional questionnaires were performed on quality of life (EuroQol “EQ-5D-5L” questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale- HADS) and food neophobia in a single PKU centre. Retrospective data on metabolic control (previous 12 months) and medical history, and current data on anthropometry, dietary treatment, and comorbidities were collected. Results: In total, 33 adolescents with PKU participated with a mean age of 13.5 ± 1.3 y (16 boys, 17 girls). All were on a Phe restricted diet, with 3 also prescribed sapropterin. Questionnaires were self-completed by n = 25/33 (76%) adolescents. A mean of 36 ± 26 blood Phe spots were performed over 12 months. There was a mean of 83% of blood Phe < 600 µmol/L and 49% < 360 µmol/L. In total, 39% (n = 13/33) of adolescents were overweight/obese, 18% (n = 6/33) overweight and 21% (n = 7/33) obese. Medical history documented mental health disorders (anxiety/depression) in 7 cases, low mood, suicidal thoughts and self-harming in 5, and neuro diversity in 4 (autism and/or attention-deficit hyperactivity disorder (ADHD). In the HADS questionnaire, 12% (n = 3/25) of adolescents scored borderline abnormal for anxiety and 12% (n = 3/25) abnormal for depression. Mean anxiety scores for females were almost twice as high compared to males. No significant correlation was found between blood Phe and anxiety/depression scores. However, higher Phe levels showed a trend towards reduced enjoyment and emotional responsiveness, including lower scores on measures of pleasure, cheerfulness, and emotional reactivity. Although not statistically significant, these findings suggest a potential subtle association between poorer metabolic control and mood disturbances in adolescents with PKU. No food neophobia was identified in our study. Conclusions: Adolescents with PKU presented with high levels of depression and anxiety. Long term studies focusing on quality of life and neurocognition even when achieving the PKU European guidelines are necessary. Different therapeutic options are needed to improve the outcome of patients with PKU.

Background: Flaxseed (Linum usitatissimum L.) represents a unique source of bioactive compounds with demonstrated health benefits. The main aim of the research was to investigate the chemical composition, content of bioactive compounds and biological activities of various types of flaxseed and their defatted forms. Methods: Proximate composition (crude fat, protein, ash, digestible carbohydrates, fiber) was determined, and fatty acid profiles were analyzed via GC-MS (gas chromatography–mass spectrometry). Mineral content was measured by atomic absorption spectrometry, while total and individual polyphenols were quantified spectrophotometrically and by HPLC (high-performance liquid chromatography). Antioxidant activity was assessed using three assays. In vitro functional assays evaluated the effects of flaxseed extracts on lactic acid bacteria adhesion in two cellular models, nitric oxide production in liposaccharide (LPS)-stimulated RAW 264.7 macrophages, proliferation and apoptosis of MCF-7 breast cancer cells. Results: Significant differences (p ≤ 0.05) were observed in the proximate composition: brown flaxseed exhibited the highest crude fat content, whereas defatted seeds had higher levels of digestible carbohydrates and ash. α-Linolenic acid was the dominant fatty acid, with the highest concentration in defatted golden flaxseed. Defatted forms generally displayed increased mineral concentrations, particularly calcium, magnesium, potassium, and iron. The polyphenolic content and antioxidant activity were highest in defatted brown flaxseed, which also exhibited the greatest diversity of individual polyphenols. Flaxseed extracts modulated the adhesion of lactic acid bacteria, reduced the production of nitric oxide in RAW 264.7 macrophages, inhibited the proliferation of MCF-7 breast cancer cells in a dose- and time-dependent manner, and induced apoptosis of the mentioned cells. Conclusions: Flaxseed, especially the brown type, could be a promising source of bioactive compounds with antioxidant, anti-inflammatory and anticancer potential, supporting its use in nutritional and functional applications.

Background: Central adiposity is a modifiable risk factor for age-related cognitive decline and has been linked to lipid dysregulation. However, the mechanisms underlying this relationship, particularly the role of plasma lipids at the species level, remain poorly understood. This study investigates whether lipids mediate the relationship between central adiposity and cognition in cognitively unimpaired older adults. Methods: Ninety-four cognitively normal older adults (n = 94, mean age 69.0 ± 5.0 years, 54% female) were included in this study. Cognitive composite scores were derived from z-standardised neuropsychological assessments, and central adiposity was measured using the waist–hip ratio (WHR). Lipidomic profiling identified 918 lipid species, which were clustered into modules of highly correlated lipids using a Weighted Gene Co-Expression Network Analysis (WGCNA). Modules associated with the WHR and cognition were identified via partial Spearman’s correlation analysis, followed by a mediation analysis. Results: Of the 39 lipid modules identified, 1 enriched with phosphatidylglycerol (PG) lipids containing an arachidic acid (20:0) sidechain was positively correlated with cognition (ρ = 0.32, FDR p < 0.05) and negatively correlated with the WHR (ρ = −0.43, FDR p < 0.001). Mediation analysis revealed that this arachidic acid-carrying PG lipid-enriched module mediated the WHR–cognition relationship, with individual species PG (20:0_16:1), PG (20:0_18:1), and PG (20:0_18:2) also contributing individually. Conclusions: Arachidic acid-carrying PG lipids statistically mediate the WHR–cognition relationship in cognitively unimpaired older adults. These findings suggest that adiposity-related lipid pathways are detectable in cognitively unimpaired older adults and may represent targets for early intervention to preserve cognitive health.