The published data on the vitamin status of patients with phenylketonuria (PKU) is contradictory; therefore, this systematic review and meta-analysis evaluated the vitamin status of PKU patients. A comprehensive search of multiple databases (PubMed, Web of Sciences, Cochrane, and Scopus) was finished in March 2024. The included studies compared vitamin levels between individuals diagnosed with early-treated PKU and healthy controls while excluding pregnant and lactating women, untreated PKU or hyperphenylalaninemia cases, control groups receiving vitamin supplementation, PKU patients receiving tetrahydrobiopterin or pegvaliase, and conference abstracts. The risk of bias in the included studies was assessed by the Newcastle–Ottawa scale. The effect sizes were expressed as standardised mean differences. The calculation of effect sizes with 95% CI using fixed-effects models and random-effects models was performed. A p-value < 0.05 was considered statistically significant. The study protocol was registered in the PROSPERO database (CRD42024519589). Out of the initially identified 11,086 articles, 24 met the criteria. The total number of participants comprised 770 individuals with PKU and 2387 healthy controls. The meta-analyses of cross-sectional and case–control studies were conducted for vitamin B12, D, A, E, B6 and folate levels. PKU patients demonstrated significantly higher folate levels (random-effects model, SMD: 1.378, 95% CI: 0.436, 2.320, p = 0.004) and 1,25-dihydroxyvitamin D concentrations (random-effects model, SMD: 2.059, 95% CI: 0.250, 3.868, p = 0.026) compared to the controls. There were no significant differences in vitamin A, E, B6, B12 or 25-dihydroxyvitamin D levels. The main limitations of the evidence include a limited number of studies and their heterogeneity and variability in patients’ compliance. Our findings suggest that individuals with PKU under nutritional guidance can achieve a vitamin status comparable to that of healthy subjects. Our study provides valuable insights into the nutritional status of PKU patients, but further research is required to confirm these findings and explore additional factors influencing vitamin status in PKU.

Limited data suggested that inclusion of a strength component into endurance exercises might intensify the beneficial effect of training. However, the available data is limited. Therefore, we aimed to compare the effect of endurance and endurance-strength training on anthropometric parameters, endothelial function, arterial stiffness, antioxidant status, and inflammatory markers in abdominally obese women without serious comorbidities. A total of 101 women were recruited and randomly divided into endurance (n = 52) and endurance-strength (n = 49) groups. During the three-month intervention, both groups performed supervised sixty-minute training three times a week. All studied parameters were measured pre- and post-intervention period. In total, 85 women completed the study. Both training significantly decreased anthropometric parameters. Besides, endurance training decreased endothelial nitric oxide synthase, central aortic systolic pressure, pulse wave velocity, glutathione (GSH), total antioxidant status (TAS), interleukin (IL) 8, matrix metalloproteinase (MMP) 9, and tumor necrosis factor alpha, while endurance-strength training decreased MMP-2 concentrations, and increased IL-6, monocyte chemoattractant protein-1, and MMP-9 levels. We observed significant differences between groups for GSH, TAS, and MMP-9 levels. In summary, endurance and endurance-strength training did not differ in the impact on endothelial function and arterial stiffness. However, endurance training significantly depleted the antioxidant defense, simultaneously reducing MMP-9 levels. The study was retrospectively registered with the German Clinical Trials Register within the number DRKS00019832.

Background: Atherosclerosis (AT) is a chronic inflammatory process in which oxidative stress is the key event. Amaranth oil (AmO) has potential hypolipidemic and antiatherogenic effects. The aim of the study was to compare the effects of AmO and rapeseed oil (RaO) supplementation on expression of early markers of AT and lipid profile in obese or overweight subjects. Methods: A randomized, double-blinded cross-over study was conducted, in which participants took 20 mL of AmO in the first arm and 20 mL RaO in the second arm, switching after the washout period. Serum concentrations of adhesion molecules (sP-selectin, sVCAM-1), high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and lipid profile were assessed before and after nutritional interventions. In addition, anthropometric parameters were measured. Results: The total (TC) and low-density lipoprotein (LDL) cholesterol concentrations increased significantly in the AmO group in comparison with RaO (ΔTC 5.52 ± 35 vs. −8.43 ± 17.65 mg/dL; p = 0.002 and 4.43 ± 34.96 vs. −7.55 ± 16.41 mg/dL; p = 0.002, respectively). There were no significant differences in other parameters analyzed between the groups. Conclusion: The use of AmO instead of RaO may increase cardiovascular risk in obese and overweight subjects.

Patients with phenylketonuria (PKU) must restrict their intake of phenylalanine, which can also affect the levels of other essential and non-essential amino acids due to inadequate supply. Therefore, our objective was to assess amino acids in serum samples from 20 PKU patients and compare them with results from 51 healthy subjects. A sample analysis was conducted using liquid chromatography–tandem mass spectrometry. We obtained levels of 28 substances, including amino acids, biogenic amines, carnitine, and acetylcarnitine. Kynurenine (p = 0.000001), tyrosine (p = 0.0002), asparagine (p = 0.001), proline (p = 0.012), and the kynurenine/tryptophan ratio (p < 0.000001) were identified as features that differed between the studied groups, being significantly lower in patients with PKU. Glycine (p = 0.000012), putrescine (p = 0.0055), asymmetric dimethylarginine (p = 0.01), creatinine (p = 0.035) levels, as well as the total level of glucogenic amino acids (p = 0.0018), and the ratios of putrescine/ornithine (p = 0.003) and citrulline/ornithine (p = 0.0043) were significantly higher in the PKU group. In conclusion, the amino acid profiles in patients with PKU differ significantly from those in healthy peers, with potential clinical implications. These findings confirm the importance of metabolic testing in clinical practice and highlight the necessity for adequate dietary monitoring and adjustment.

Objective: Rare disease Background: Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency is an extremely rare autosomal recessive inherited error of metabolism in which gluconeogenesis is impaired, resulting in life-threatening episodes of hypoglycemia and metabolic acidosis. The diagnosis of gluconeogenesis disorders is challenging. In the diagnostic pathway, the molecular test plays a paramount role. Case Report: The aim of the paper is to present the case report of a girl with recurrent episodes of severe hypoglycemia, in whom molecular diagnosis enabled the confirmation of PEPCK - C deficiency. The patient experienced 4 episodes of severe hypoglycemia. Most of them were accompanied by hyperlacticaemia, metabolic acidosis, and elevated liver enzymes. All of the metabolic decompensations were triggered by infectious agents. The episodes resolved after continuous infusion of high-dose glucose. Due to the recurrent character of the disease, a genetic condition was suspected. The differential diagnosis included metabolic and endocrinological causes of hypoglycemia. Two variants in the PCK1 gene were detected: c.265G>A p.(Glu89Lys) in exon 3 and c.925G>A p.(Gly309Arg) in exon 6. As c.925G>A p.(Gly309Arg) is a known pathogenic variant, the second variant was first described in June 2023 in the ClinVar database and described as "with unknown clinical significance". Conclusions: According to the clinical symptoms observed in the presented case, the variant c.265G>A p.(Glu89Lys) in PCK1 gene should be considered likely pathogenic. We suggest considering molecular diagnostics in every patient presented with recurrent, severe hypoglycemia with accompanying liver damage as most accurate, feasible, and reliable method.

This is the first study to evaluate vitamin K status in relation to dietary intake and phenylalanine dietary compliance in patients with phenylketonuria (PKU). The dietary and PKU formula intake of vitamin K was calculated in 34 PKU patients, with vitamin K status determined by the measurement of prothrombin induced by vitamin K absence (PIVKA-II). Blood phenylalanine concentrations in the preceding 12 months were considered. There were significantly more phenylalanine results exceeding 6 mg/dL in patients with normal PIVKA-II concentrations than in those with abnormal PIVKA-II levels (p = 0.035). Similarly, a higher total intake of vitamin K and dietary vitamin intake expressed as μg/day (p = 0.033 for both) and %RDA (p = 0.0002 and p = 0.003, respectively) was observed in patients with normal PIVKA-II levels. Abnormal PIVKA-II concentrations were associated with a lower OR (0.1607; 95%CI: 0.0273–0.9445, p = 0.043) of having a median phenylalanine concentration higher than 6 mg/dL. In conclusion, vitamin K deficiency is not uncommon in phenylketonuria and may also occur in patients with adequate vitamin K intake. PKU patients with better dietary compliance have a higher risk of vitamin K deficiency. The present findings highlight the need for further studies to re-evaluate dietary recommendations regarding vitamin K intake, both concerning formula-based and dietary consumption of natural products.