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Journal of the National Cancer Institute Mar 2017Vitamin B6 is involved in many biochemical reactions and might play a role in carcinogenesis. We summarized the evidence linking vitamin B6 to cancer risk. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin B6 is involved in many biochemical reactions and might play a role in carcinogenesis. We summarized the evidence linking vitamin B6 to cancer risk.
METHODS
We conducted a systematic review of both observational and intervention studies investigating the relationship between vitamin B6 intake or blood levels of its bioactive form pyridoxal-5'-phosphate (PLP) and the risk of any type of cancer. Random-effects meta-analysis was used to calculate pooled relative risks (RRs) and their 95% confidence intervals (CIs) across studies for high vs low categories of vitamin intake or PLP levels. We also performed a random-effects dose-response meta-analysis.
RESULTS
We identified 121 observational studies (participants, n = 1 924 506; cases, n = 96 , 436) and nine randomized controlled trials (RCTs; participants, n = 34 911; cases, n = 2539) considering 19 tumor sites. High intake of dietary (food only) vitamin B6 was statistically significantly associated with lower risk of all cancers (relative risk [RR] = 0.78, 95% CI = 0.73 to 0.84) and specific tumors, with special regard to gastrointestinal carcinomas (RR = 0.68, 95% CI = 0.61 to 0.75). An inverse association was also observed between high PLP levels and the risk of all cancers (RR = 0.66, 95% CI = 0.58 to 0.76) and single tumor sites, the most consistent results being those for gastrointestinal tumors (RR = 0.56, 95% CI = 0.48 to 0.65). There was a statistically significant inverse linear relationship between cancer risk and both vitamin B6 dietary intake and PLP levels. When total (food and supplements) intake was considered, the associations were weaker or null. Findings from RCTs did not support a protective effect of vitamin B6 against cancer, although this evidence was graded as low level.
CONCLUSIONS
Epidemiological evidence supports the potential of vitamin B6 as a cancer risk reduction agent and the role of PLP as a cancer screening biomarker, especially for gastrointestinal tumors. However, inconsistent findings from total intake and intervention studies suggest that vitamin B6 might also be an indicator of other dietary protective micronutrients.
Topics: Diet; Dose-Response Relationship, Drug; Humans; Neoplasms; Observational Studies as Topic; Protective Factors; Pyridoxal Phosphate; Randomized Controlled Trials as Topic; Risk Assessment; Vitamin B 6
PubMed: 28376200
DOI: 10.1093/jnci/djw230 -
The Cochrane Database of Systematic... Apr 2015Tardive dyskinesia is a chronic and disabling abnormal movement disorder affecting the muscles of the face, neck, tongue and the limbs. It is a common side effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia is a chronic and disabling abnormal movement disorder affecting the muscles of the face, neck, tongue and the limbs. It is a common side effect of long-term antipsychotic medication use in individuals with schizophrenia and other related psychotic disorders. While there are no known effective treatments for tardive dyskinesia to date, some reports suggest that pyridoxal 5 phosphate may be effective in reducing the severity of tardive dyskinesia symptoms.
OBJECTIVES
To determine the effectiveness of pyridoxal 5 phosphate (vitamin B6 or Pyridoxine or Pyridoxal phosphate) in the treatment of neuroleptic-induced tardive dyskinesia among people with schizophrenia and other related psychotic disorders.
SEARCH METHODS
The Cochrane schizophrenia group's register of clinical trials was searched (January 2013) using the phrase: [*Pyridoxal* OR *Pyridoxine* OR *P5P* OR *PLP* OR *tardoxal* OR *Vitamin B6* O *Vitamin B 6* R in title, abstract or index terms of REFERENCE, or interventions of STUDY. References of relevant identified studies were handsearched and where necessary, the first authors of relevant studies were contacted.
SELECTION CRITERIA
Studies described as randomised controlled trials comparing the effectiveness pyridoxal 5 phosphate with placebo in the treatment of neuroleptic-induced tardive dyskinesia among patients with schizophrenia.
DATA COLLECTION AND ANALYSIS
The review authors independently extracted data from each selected study. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a fixed-effect model. For continuous data, we calculated mean differences (MD) with 95% CIs, again based on a fixed-effect model. We assessed risk of bias for each included study and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rate quality of evidence.
MAIN RESULTS
Of the 12 records retrieved by the search, three trials published in 2001, 2003 and 2007, involving 80 inpatients with schizophrenia, aged 18 to 71 years, admitted in a psychiatric facility and followed up for a period nine weeks to 26 weeks, were included. Overall, pyridoxal 5 phosphate produced a significant improvement in tardive dyskinesia symptoms when compared with placebo, assessed by a change in Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of the first phase of the included studies (2 RCTs n = 65, RR 19.97, CI 2.87 to 139.19, low quality evidence). The endpoint tardive dyskinesia score (a measure of its severity) assessed with the ESRS, was significantly lower among participants on pyridoxal 5 phosphate compared to those on placebo (2 RCTs n = 60, MD -4.07, CI -6.36 to -1.79, low quality evidence).It was unclear whether pyridoxal 5 phosphate led to more side effects (n = 65, 2 RCTs, RR 3.97, CI 0.20 to 78.59, low quality evidence) or caused deterioration in tardive dyskinesia symptoms when compared to placebo (n = 65, 2 RCTs, RR 0.16, CI 0.01 to 3.14, low quality evidence). Five participants taking pyridoxal 5 phosphate withdrew from the study because they were not willing to take more medications while none of the participants taking placebo discontinued their medications (n = 65, 2 RCTs, RR 8.72, CI 0.51 to 149.75, low quality evidence).There was no significant difference in the endpoint positive and negative psychiatric symptoms scores, measured using the Positive and Negative symptoms Scale (PANSS) between participants taking pyridoxal 5 phosphate and those taking placebo. For the positive symptoms: (n = 15, 1 RCT, MD -1.50, CI -4.80 to 1.80, low quality evidence). For negative the symptoms: (n = 15, 1 RCT, MD -1.10, CI -5.92 to 3.72, low quality evidence).
AUTHORS' CONCLUSIONS
Pyridoxal 5 phosphate may have some benefits in reducing the severity of tardive dyskinesia symptoms among individuals with schizophrenia. However, the quality of evidence supporting the effectiveness of pyridoxal 5 phosphate in treating tardive dyskinesia is low, based on few studies, short follow-up periods, small sample sizes and inadequate adherence to standardised reporting guidelines for randomised controlled trials among the included studies.
Topics: Adult; Aged; Antipsychotic Agents; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Pyridoxal Phosphate; Randomized Controlled Trials as Topic; Schizophrenia; Vitamin B Complex
PubMed: 25866243
DOI: 10.1002/14651858.CD010501.pub2 -
Cancer Epidemiology, Biomarkers &... May 2022Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.
METHODS
A literature search until August 2020 in MEDLINE, EMBASE, and Web of Science was performed. Studies were included if they assessed circulating blood, urine, or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.
RESULTS
A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC [n = 4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22]. Additionally, an inverse association was seen with pyridoxal 5'-phosphate (PLP) levels (n = 4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D, and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched-chain amino acids with PDAC risk, but due to differences in measures reported, a meta-analysis could not be performed.
CONCLUSIONS
Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC.
IMPACT
Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.
Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Glucose; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 34810209
DOI: 10.1158/1055-9965.EPI-21-0616 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2020Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of...
BACKGROUND
Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of choice. However, despite the use of acetylcysteine, some patients who ingest very large doses of paracetamol or who reach hospital late in the course of their poisoning, develop acute liver failure. Some will develop metabolic acidosis indicating mitochondrial toxicity.
OBJECTIVE
We review the experimental and clinical data reported with the use of cimetidine, fomepizole, and calmangafodipir in the treatment of paracetamol toxicity to determine if these treatments alone or in combination with acetylcysteine might be of benefit.
METHODS
We searched Ovid Medline 1946-2020, Embase 1947-2020, Scopus 2004-2020, Cochrane Databases of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov 1997-2020 for records including the concepts of paracetamol poisoning and cimetidine, fomepizole, calmangafodipir, and acetylcysteine. We included basic science studies in animals and all available study types in humans. We reviewed the reference lists of included articles to search for references missed in the original search. We registered the protocol in PROSPERO.
RESULTS
We completed all search strategies on 20 August 2019, 27 January 2020, and 15 June 2020. These produced 6,826 citations. We identified and deleted 2,843 duplicate resulting in a total of 3,856 unique citations. After applying inclusion and exclusion criteria, 89 studies remained. The largest numbers of studies described the past use of cimetidine, and the more recent use of fomepizole. There is good animal evidence that cimetidine blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. Early case reports were inconclusive regarding the benefit to humans in paracetamol poisoning. Two comparative trials found no benefit of cimetidine in paracetamol poisoning, but few patients had severe poisoning. There is good animal evidence that fomepizole blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. There are no comparative trials of fomepizole for acute paracetamol poisoning. Case reports are inconclusive due to multiple other interventions including the use of acetylcysteine in all cases. The benefit of fomepizole as adjunct treatment has not been demonstrated. Calmangafodipir, a drug mimicking superoxide dismutase, has emerged as a potential treatment for severe paracetamol toxicity because the formation of superoxide free radicals appears to explain part of the mitochondrial toxicity of extremely large paracetamol overdoses. Calmangafodipir has reached Phase I/II trial of safety in humans with acute paracetamol overdose. Planning for a Phase III study of efficacy is currently underway.
CONCLUSIONS
The vast majority of patients with acute paracetamol overdose enjoy excellent outcomes with acetylcysteine alone. Although cimetidine and fomepizole inhibit CYP 2E1 in animals, there is insufficient evidence to recommend their use either as a primary treatment or adjunct therapy in paracetamol poisoning. Calmangafodipir remains investigational.
Topics: Acetaminophen; Acetylcysteine; Acidosis; Animals; Antidotes; Cimetidine; Drug Overdose; Edetic Acid; Fomepizole; Humans; Mitochondria; Pyridoxal Phosphate
PubMed: 32762579
DOI: 10.1080/15563650.2020.1798979