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PloS One 2020Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant...
Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.
Topics: Adolescent; Adult; Aged; Amino Acids; Cancer Survivors; Child; Fatigue Syndrome, Chronic; Female; Humans; Inflammation; Lymphoma; Male; Middle Aged; Surveys and Questionnaires; Tryptophan; Vitamin B 6; Young Adult
PubMed: 31923274
DOI: 10.1371/journal.pone.0227384 -
Cancer Cell Jan 2020Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and...
Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK-an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6-as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. PDXK disruption reduced intracellular concentrations of key metabolites needed for cell division. Furthermore, disruption of PLP-dependent enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products partially rescued PDXK disruption induced proliferation blockage. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.
Topics: Animals; CRISPR-Cas Systems; Cell Line, Tumor; Cell Proliferation; GTP Phosphohydrolases; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute; Membrane Proteins; Mice; Monomeric GTP-Binding Proteins; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor); Polyamines; Pyridoxal Phosphate; RNA, Small Interfering; Vitamin B 6
PubMed: 31935373
DOI: 10.1016/j.ccell.2019.12.002 -
Nutrients Jun 2017Although vitamins play a major role in health, and their deficiency may be linked to symptoms of optic-nerve dysfunction, the association between serum vitamin levels... (Meta-Analysis)
Meta-Analysis Review
Although vitamins play a major role in health, and their deficiency may be linked to symptoms of optic-nerve dysfunction, the association between serum vitamin levels and glaucoma in humans remains controversial. In this study, articles in the PubMed, Web of Science, and EMBASE databases were searched up to 25March 2017. Nine studies on primary open-angle glaucoma (POAG), four studies on normal tension glaucoma (NTG), and six studies on exfoliative glaucoma (EXG) were retrieved. The combined results showed no differences in the levels of serum vitamin B₆ between POAG ( = 0.406) and EXG ( = 0.139) patients and controls. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were 2.792 ng/mL (-3.793 to 9.377) and 1.342 ng/mL (-3.120 to 0.436), respectively. There was no difference between POAG ( = 0.952), NTG ( = 0.757), or EXG ( = 0.064) patients and controls in terms of serum vitamin B. The WMDs with 95% CIs were 0.933 pg/mL (-31.116 to 29.249), 6.652 pg/mL (-35.473 to 48.777), and 49.946 pg/mL (-102.892 to 3.001), respectively. The serum vitamin D levels exhibited no differences ( = 0.064) between POAG patients and controls; the WMD with 95% CI was 2.488 ng/mL (-5.120 to 0.145). In conclusion, there was no association found between serum vitamin B₆, vitamin B, or vitamin D levels and the different types of glaucoma.
Topics: Glaucoma; Glaucoma, Open-Angle; Humans; Sensitivity and Specificity; Vitamin B 12; Vitamin B 6; Vitamin D
PubMed: 28635642
DOI: 10.3390/nu9060636 -
Drug Design, Development and Therapy 2019To systematically evaluate the efficacy and safety of sodium cantharidinate and vitamin B6 (SC/B6) combined with conventional medical treatment (CMT) for the treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the efficacy and safety of sodium cantharidinate and vitamin B6 (SC/B6) combined with conventional medical treatment (CMT) for the treatment of patients with advanced digestive system neoplasms (DSNs).
METHODS
The Cochrane Library, Embase, PubMed, Web of Science, Chinese Scientific Journal Database (VIP), China National Knowledge Infrastructure, and Wanfang databases were searched for clinical trials using SC/B6 for DSNs. Outcome measures, including therapeutic efficacy, quality of life (QoL), and adverse events, were extracted and systematically evaluated.
RESULTS
Data from 24 trials including 1,825 advanced DSN patients were included. Compared with CMT alone, its combination with SC/B6 significantly improved the patients' overall response rate (OR =2.25, 95% CI =1.83-2.76, <0.00001), disease control rate (OR =2.41, 95% CI =1.85-3.15, <0.00001), and QoL improvement rate (OR =2.75, 95% CI =2.13-3.55, <0.00001). Moreover, adverse events caused by chemotherapy, including leukopenia, nausea and vomiting, gastrointestinal side effects, hepatotoxicity, diarrhea, transaminase disorder, myelosuppression, anorexia, and anemia, were significantly alleviated (<0.05) when SC/B6 was applied to DSN patients. Nephrotoxicity, thrombocytopenia, hand-foot syndrome, and oral mucositis were not significantly alleviated in patients receiving combination therapy (>0.05).
CONCLUSION
The combination of SC/B6 and CMT is more effective in treating DSNs than CMT alone. This combination alleviates the adverse effects associated with chemotherapy and improves the QoL of DSN patients, and its application in the clinic is worth promoting.
Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cantharidin; Digestive System Neoplasms; Humans; Patient Safety; Randomized Controlled Trials as Topic; Vitamin B 6
PubMed: 30643386
DOI: 10.2147/DDDT.S190674 -
Proceedings of the National Academy of... Mar 2022Pyridox(am)ine 5 -phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5 -phosphate (PLP), the active form of vitamin B6 required...
Pyridox(am)ine 5 -phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5 -phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy. These patients often exhibit different types of seizures and variable comorbidities. Recently, the gene has also been implicated in epilepsy in adults. It is unclear how these phenotypic variations are linked to specific alleles and to what degree diet can modify their expression. Using CRISPR-Cas9, we generated four knock-in alleles, , , , and , in which the endogenous was replaced by wild-type human complementary DNA (cDNA) and three epilepsy-associated variants. We found that these knock-in flies exhibited a wide range of phenotypes, including developmental impairments, abnormal locomotor activities, spontaneous seizures, and shortened life span. These phenotypes are allele dependent, varying with the known biochemical severity of these mutations and our characterized molecular defects. We also showed that diet treatments further diversified the phenotypes among alleles, and PLP supplementation at larval and adult stages prevented developmental impairments and seizures in adult flies, respectively. Furthermore, we found that h had a significant dominant-negative effect, rendering heterozygous flies susceptible to seizures and premature death. Together, these results provide biological bases for the various phenotypes resulting from multifunction of , specific molecular and/or genetic properties of each variant, and differential allele-diet interactions.
Topics: Alleles; Amino Acid Sequence; Animals; Diet; Drosophila melanogaster; Epilepsy; Humans; Phenotype; Pyridoxaminephosphate Oxidase; Sequence Homology, Amino Acid; Vitamin B 6
PubMed: 35217610
DOI: 10.1073/pnas.2115524119 -
Nutrients May 2023The relationship between vitamin B levels and the development and progression of lung cancer remains inconclusive. We aimed to investigate the relationship between B...
The relationship between vitamin B levels and the development and progression of lung cancer remains inconclusive. We aimed to investigate the relationship between B vitamins and intrapulmonary lymph nodes as well as localized pleural metastases in patients with non-small cell lung cancer (NSCLC). This was a retrospective study including patients who underwent lung surgery for suspected NSCLC at our institution from January 2016 to December 2018. Logistic regression models were used to evaluate the associations between serum B vitamin levels and intrapulmonary lymph node and/or localized pleural metastases. Stratified analysis was performed according to different clinical characteristics and tumor types. A total of 1498 patients were included in the analyses. Serum vitamin B levels showed a positive association with intrapulmonary metastasis in a multivariate logistic regression (odds ratio (OR) of 1.016, 95% confidence interval (CI) of 1.002-1.031, = 0.021). After multivariable adjustment, we found a high risk of intrapulmonary metastasis in patients with high serum vitamin B levels (fourth quartile (Q4) vs. Q1, OR of 1.676, 95%CI of 1.092 to 2.574, = 0.018, for trend of 0.030). Stratified analyses showed that the positive association between serum vitamin B and lymph node metastasis appeared to be stronger in females, current smokers, current drinkers, and those with a family history of cancer, squamous cell carcinoma, a tumor of 1-3 cm in diameter, or a solitary tumor. Even though serum vitamin B levels were associated with preoperative NSCLC upstaging, B did not qualify as a useful biomarker due to weak association and wide confidence intervals. Thus, it would be appropriate to prospectively investigate the relationship between serum vitamin B levels and lung cancer further.
Topics: Female; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Neoplasm Staging; Lung; Lymph Nodes; Vitamin B 6; Pyridoxine; Vitamins
PubMed: 37242223
DOI: 10.3390/nu15102340 -
Roczniki Panstwowego Zakladu Higieny 2011Contemporary sport requires a lot of effort from sportsmen, frequently exceeding their maximum physical and mental efficiency. Athletes often report poor dietary habits...
Contemporary sport requires a lot of effort from sportsmen, frequently exceeding their maximum physical and mental efficiency. Athletes often report poor dietary habits and reach for magnesium and vitamin B supplements to avoid dietary deficiencies. The aim of this study was to determine magnesium and vitamin B6 content in daily food rations of Polish athletes and to verify the justification of diet supplementation. Magnesium and vitamin B6 concentrations were determined in 62 collected and 12 reconstructed daily food rations of elite Polish runners. Flame atomic absorption spectrometry and HPLC methods were used for quantification of magnesium and vitamin B6, respectively. The analyzed female diets provided daily 256 +/- 111 mg of magnesium and 2.04 +/- 0.63 mg of vitamin B6 whereas male diets provided 284 +/- 58 mg of magnesium and 2.12 +/- 0.68 mg of vitamin B6. Computer analysis calculated 159-181% higher content o magnesium and vitamin B6 comparing to determined laboratory values. The results of this study indicate that in the analyzed daily food rations of athletes low magnesium intake was observed, thus diet supplementation with this mineral may be justified. Daily food rations fulfilled RDA for vitamin B6, thus supplementation with this vitamin was not justified.
Topics: Adult; Athletes; Dietary Supplements; Energy Intake; Feeding Behavior; Female; Humans; Magnesium; Male; Nutritional Requirements; Nutritional Status; Poland; Vitamin B 6; Young Adult
PubMed: 22435297
DOI: No ID Found -
Brain & Development May 2020The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures...
BACKGROUND
The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures (FS), which poses a great diagnostic challenge for clinicians. Excitotoxicity is speculated to be the pathogenesis of AESD. Vitamin B6 (VB6) is essential for the biosynthesis of gamma-aminobutyric acid, an inhibitory neurotransmitter. The aim of this study is to investigate our hypothesis that VB6 deficiency in the brain may play a role in AESD.
METHODS
We obtained cerebrospinal fluid (CSF) samples from pediatric patients with AESD after early seizures and those with FS. We measured pyridoxal 5'-phosphate (PLP) and pyridoxal (PL) concentrations in the CSF samples using high-performance liquid chromatography with fluorescence detection.
RESULTS
The subjects were 5 patients with AESD and 17 patients with FS. Age did not differ significantly between AESD and FS. In AESD, CSF PLP concentration was marginally lower (p = 0.0999) and the PLP-to-PL ratio was significantly (p = 0.0417) reduced compared to those in FS.
CONCLUSIONS
Although it is impossible to conclude that low PLP concentration and PLP-to-PL ratio are causative of AESD, this may be a risk factor for developing AESD. When combined with other markers, this finding may be useful in distinguishing AESD from FS upon initial presentation.
Topics: Brain Diseases; Child, Preschool; Female; Humans; Infant; Male; Pyridoxal; Pyridoxal Phosphate; Seizures; Vitamin B 6
PubMed: 32107100
DOI: 10.1016/j.braindev.2020.02.002 -
European Journal of Nutrition Jun 2020Short telomeres and B vitamin deficiencies have been proposed as risk factors for age-related diseases and mortality that interact through oxidative stress and...
PURPOSE
Short telomeres and B vitamin deficiencies have been proposed as risk factors for age-related diseases and mortality that interact through oxidative stress and inflammation. However, available data to support this concept are insufficient. We aimed to investigate the predictive role of B vitamins and homocysteine (HCY) for mortality in cardiovascular patients. We explored potential relationships between HCY, B vitamins, relative telomere length (RTL), and indices of inflammation.
METHODS
Vitamin B6, HCY, interleukin-6 (IL-6), high-sensitive-C-reactive protein (hs-CRP), and RTL were measured in participants of the Ludwigshafen Risk and Cardiovascular Health Study. Death events were recorded over a median follow-up of 9.9 years.
RESULTS
All-cause mortality increased with higher concentrations of HCY and lower vitamin B6. Patients in the 4th quartile of HCY and vitamin B6 had hazard ratios (HR) for all-cause mortality of 2.77 (95% CI 2.28-3.37) and 0.41(95% CI 0.33-0.49), respectively, and for cardiovascular mortality of 2.78 (95% CI 2.29-3.39) and 0.40 (95% CI 0.33-0.49), respectively, compared to those in the 1st quartile. Multiple adjustments for confounders did not change these results. HCY and vitamin B6 correlated with age-corrected RTL (r = - 0.086, p < 0.001; r = 0.04, p = 0.031, respectively), IL-6 (r = 0.148, p < 0.001; r = - 0.249, p < 0.001, respectively), and hs-CRP (r = 0.101, p < 0.001; r = - 0.320, p < 0.001, respectively). Subjects with the longest telomeres had a significantly higher concentration of vitamin B6, but lower concentrations of HCY, IL-6, and hs-CRP. Multiple regression analyses identified HCY as an independent negative predictor of age-corrected RTL.
CONCLUSIONS
In conclusion, hyperhomocysteinemia and vitamin B6 deficiency are risk factors for death from any cause. Hyperhomocysteinemia and vitamin B6 deficiency correlate with increased mortality. This correlation might, at least partially, be explained by accelerated telomere shortening induced by oxidative stress and systemic inflammation in these circumstances.
Topics: Cardiovascular Diseases; Female; Germany; Health Surveys; Homocysteine; Humans; Inflammation; Male; Middle Aged; Risk Assessment; Telomere Shortening; Vitamin B 6
PubMed: 31129702
DOI: 10.1007/s00394-019-01993-8 -
Molecules (Basel, Switzerland) Jan 2010Vitamin B6 is an intriguing molecule that is involved in a wide range of metabolic, physiological and developmental processes. Based on its water solubility and high... (Review)
Review
Vitamin B6 is an intriguing molecule that is involved in a wide range of metabolic, physiological and developmental processes. Based on its water solubility and high reactivity when phosphorylated, it is a suitable co-factor for many biochemical processes. Furthermore the vitamin is a potent antioxidant, rivaling carotenoids or tocopherols in its ability to quench reactive oxygen species. It is therefore not surprising that the vitamin is essential and unquestionably important for the cellular metabolism and well-being of all living organisms. The review briefly summarizes the biosynthetic pathways of vitamin B6 in pro- and eukaryotes and its diverse roles in enzymatic reactions. Finally, because in recent years the vitamin has often been considered beneficial for human health, the review will also sum up and critically reflect on current knowledge how human health can profit from vitamin B6.
Topics: Amino Acids; Health; Humans; Vitamin B 6
PubMed: 20110903
DOI: 10.3390/molecules15010442