Vitamin B12 in Health and Disease

Vitamin B12 is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B12, and to evaluate the causes and consequences of sub-clinical vitamin B12 deficiency. Vitamin B12 deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B12 deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B12 is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health

Paracetamol use and risk of ovarian cancer: A meta-analysis

Aim: Ovarian cancer remains the most fatal gynaecological malignancy. Several observational studies have examined paracetamol as a potential chemopreventive agent. The nonconclusive nature of the epidemiological evidence prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Methods: A comprehensive search for articles published up to 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Results: Eight studies (four case-control and four cohort studies), published between 1998 and 2004, were included. We found no evidence of publication bias or heterogeneity among the studies. The analysis revealed an inverse association between paracetamol use and ovarian cancer risk. This association was marginally significant assuming a random-effects model (RR = 0.84, 95% CI 0.70, 1.00), but not statistically significant assuming a fixed-effects model (RR = 0.90, 95% CI 0.80, 1.01). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association. Furthermore, our results provided evidence for a dose effect; 'regular use' was associated with a statistically significant 30% reduction in the risk of developing ovarian cancer compared with non-use (RR = 0.70, 95% CI 0.51, 0.95). Conclusions: Our meta-analysis supports a protective association between paracetamol use and ovarian cancer, and provides evidence for a dose effect. However, the question of paracetamol's potential association with ovarian cancer deserves further verification, since proof of chemoprevention would represent a major public health advance. © 2005 Blackwell Publishing Ltd

Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: Evidence from a meta-analysis of 12 studies

OBJECTIVES: Recent experimental research on a class of pharmacological agents that reduce plasma cholesterol, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), has shown promise in pancreatic cancer chemoprevention. While the mechanism remains unclear, several epidemiological studies have also evaluated the relationship between statin use and pancreatic cancer. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. METHODS: A comprehensive search for articles published up to December 2007 was performed, reviews of each study were conducted, and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Twelve studies (3 randomized placebo-controlled trials [RCTs], 4 cohort, and 5 case-control studies) contributed to the analysis. The studies were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and pancreatic cancer among either the RCTs (RR 0.99, 95% CI 0.44-2.21) or the observational studies (RR 0.86, 95% CI 0.60-1.24). Similarly, we found no evidence of publication bias. However, a high heterogeneity was detected among the observational studies. CONCLUSION: Despite the chemopreventive potential of statins demonstrated in experimental studies, our results do not support the hypothesis that these agents reduce the risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia. © 2008 by Am. Coll. of Gastroenterology

Statin use and the risk of prostate cancer: A metaanalysis of 6 randomized clinical trials and 13 observational studies

Statins have been suggested to prevent prostate cancer. Our aim was to examine statin use in relation to both total prostate cancer and the more clinically important advanced prostate cancer, through a detailed metaanalysis of the epidemiologic studies published on the subject in peer-reviewed literature. A comprehensive search for articles published up to November 2007 was performed, reviews of each study were conducted and data were abstracted. Prior to metaanalysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup and sensitivity analyses were also performed. Nineteen studies [6 randomized clinical trials (RCTs), 6 cohort and 7 case-control studies] contributed to the analysis. There was no evidence of an association between statin use and total prostate cancer among either RCTs (RR = 1.06, 95% CI: 0.93-1.20) or the observational studies (RR = 0.89, 95% CI: 0.65-1.24). However, high heterogeneity was detected among the observational studies. Moreover, long-term statin use did not significantly affect the risk of total prostate cancer (RR = 0.93, 95% CI: 0.77-1.13). In contrast, synthesis of the available reports that had specifically examined statin use in relation to advanced prostate cancer indicated a protective association (RR = 0.77, 95% CI: 0.64-0.93). Our results do not support the hypothesis that statins reduce the risk of total prostate cancer. However, further research is required to investigate whether the particular association of statin use with lower risk of advanced prostate cancer is indeed causal. © 2008 Wiley-Liss, Inc

Do nonsteroidal anti-inflammatory drugs affect the risk of developing ovarian cancer? A meta-analysis

Aim: The relationship between the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, and the risk of ovarian cancer has been controversial. This study examines the strength of this association by conducting a detailed meta-analysis of the studies published in peer-reviewed literature on the subject. Methods: A comprehensive search for articles published up to April 2004 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated. Results: Ten reports (six case-control and four cohort studies), published between 1998 and 2004, were identified. There was no evidence of an association between aspirin use and ovarian cancer risk either assuming a random-effects model (RR = 0.92, 95% CI 0.80, 1.06), or a fixed-effects model (RR = 0.93, 95% CI 0.81, 1.06). Similarly, we did not find evidence of an association between non-aspirin NSAID use and ovarian cancer, both on the basis of a random-effects model (RR = 0.86, 95% CI 0.68, 1.08), and on the basis of a fixed-effects model (RR = 0.88, 95% CI 0.76, 1.01). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, our analysis did not show decreasing risks with increasing frequency or duration of use, features often associated with causal relationships. Conclusions: Our meta-analysis findings do not support that NSAID use plays a role in the chemoprevention of ovarian cancer. Future research should examine potential relationships between specific NSAIDs and ovarian cancer, taking into account the possible biases that may have affected this meta-analysis. © 2005 Blackwell Publishing Ltd

Use of statins and risk of haematological malignancies: A meta-analysis of six randomized clinical trials and eight observational studies

Aims: Statins have been suggested to prevent haematological malignancies. Several epidemiological studies have evaluated this association, while randomized controlled trials (RCTs) on cardiovascular outcomes have provided relevant data as secondary end-points. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published in peer-reviewed literature. Methods: A comprehensive search for articles published up to December 2006 was performed, reviews of each study were conducted and data abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects model. Results: Fourteen studies (six RCTs, seven case-control and one cohort study) contributed to the analysis. Studies were grouped on the basis of study design, and two separate meta-analyses were conducted. There was no evidence of an association between statin use and haematological malignancies among either RCTs (RR = 0.92, 95% CI 0.72, 1.16) or the observational studies (RR = 0.83, 95% CI 0.53, 1.29). Similarly, we found no evidence of publication bias. However, high heterogeneity was detected among the observational studies. Conclusion: Our meta-analysis findings do not support a potential role of statins in the prevention of haematological malignancies. © 2007 The Authors

Statins and the risk of colorectal cancer: A meta-analysis of 18 studies involving more than 1.5 million patients

Purpose: Statins have been suggested to prevent colorectal cancer. Several epidemiologic studies have evaluated this association, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Methods: A comprehensive search for studies published up to December 2006 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates with 95% CIs were calculated using the fixed- and random-effects models. Results: Eighteen studies involving more than 1.5 million participants contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of colorectal cancer either among RCTs (RR = 0.95; 95% CI, 0.80 to 1.13; n = 6) or among cohort studies (RR = 0.96; 95% CI, 0.84 to 1.11; n = 3). However, statin use was associated with a modest reduction in the risk of colorectal cancer among case-control studies (RR = 0.91; 95% CI, 0.87 to 0.96; n = 9). Low evidence of publication bias or heterogeneity was found. Conclusion: Our meta-analysis results do not support the hypothesis that statins strongly reduce the risk of colorectal cancer, when taken for management of hypercholesterolemia. However, we cannot rule out a modest reduction in risk or an effect associated with higher doses of statins. © 2007 by American Society of Clinical Oncology

Statins and cancer risk: A literature-based meta-analysis and meta-regression analysis of 35 randomized controlled trials

Purpose: A growing body of literature suggests that statins may have chemopreventive potential against cancer. Our aim was to examine the strength of this association through a detailed meta-analysis and meta-regression analysis of randomized controlled trials (RCTs). Methods: A comprehensive search for trials published up to 2005 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random-and fixed-effects models. Subgroup, sensitivity, and meta-regression analyses were also conducted. Results: Thirty-five RCTs of statins for cardiovascular outcomes contributed to the analysis (n = 109,143). The degree of variability between trials was consistent with what would be expected to occur by chance alone. Statin use was not associated with a substantially increased or decreased overall risk of cancer (RR = 0.99; 95% CI, 0.94 to 1.04). Similarly, statin use did not significantly affect respiratory cancer risk (RR = 0.95; 95% CI, 0.83 to 1.09). However, the meta-regression analysis indicated that age of study participants modified the association between statin use and cancer risk (P = .003). Conclusion: Our findings do not support a protective effect of statins against cancer. However, this conclusion is limited by the relatively short follow-up periods (4.5 years on average) of the studies analyzed. Thus, it is important to continue monitoring the long-term safety profiles of statins. Until then, physicians need to be vigilant in ensuring that statin use remains restricted to the approved indications. © 2006 by American Society of Clinical Oncology