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Drugs for preventing lung cancer in healthy people.
Cortés-Jofré, M, Rueda, JR, Asenjo-Lobos, C, Madrid, E, Bonfill Cosp, X
The Cochrane database of systematic reviews. 2020;(3):CD002141
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Abstract
BACKGROUND This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer. OBJECTIVES To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations. SEARCH METHODS We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews. SELECTION CRITERIA We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach. MAIN RESULTS In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence). AUTHORS' CONCLUSIONS Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.
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Vitamins and Minerals for Migraine Prophylaxis: A Systematic Review and Meta-analysis.
Okoli, GN, Rabbani, R, Kashani, HH, Wierzbowski, AK, Neilson, C, Mansouri, B, Zarychanski, R, Abou-Setta, AM
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 2019;(2):224-233
Abstract
OBJECTIVE To summarize the findings of randomized controlled trials (RCTs) on the efficacy and safety of vitamins and minerals for migraine prophylaxis. METHODS We systematically searched bibliographic databases and relevant websites for parallel and crossover RCTs reporting efficacy and/or safety of vitamins and/or minerals for migraine prophylaxis. Our primary outcomes were migraine frequency (number of attacks) and duration (hours). Secondary outcomes were severity (intensity), days with migraine, and adverse events. Meta-analysis was conducted when analyzable data were available from at least two trials. RESULTS Eighteen placebo-controlled trials met our eligibility criteria. Only coenzyme Q10 and magnesium contributed to meta-analyses. In adults, compared with placebo, coenzyme Q10 did not significantly decrease migraine frequency (mean difference (MD) -0.44 (-2.14 to 1.26); I2 53%; 2 trials; 97 participants; moderate strength of the evidence), duration (MD -1.97 (-4.82 to 0.87); I2 0%; 2 trials; 97 participants; moderate strength of the evidence), or severity (ratio of means (RoM) -0.05 (-0.20 to 0.11); I2 0%; 2 trials; 97 participants). In adults, compared with placebo, magnesium did not significantly decrease migraine severity (RoM -0.17 (-0.36 to 0.02); I2 48%; 3 trials; 226 participants; low strength of the evidence). Meta-analysis of other vitamins and minerals, and other outcomes were not feasible due to a lack of sufficiently reported data. CONCLUSIONS Based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and safety of vitamins and minerals for migraine prophylaxis.
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Effect of Ascorbic Acid on Mineral and Bone Disorders in Hemodialysis Patients: a Systematic Review and Meta-Analysis.
Ke, G, Huang, J, Zhu, Y, Yang, J, Zhang, Y, Chen, L, Hu, J, Tao, S, Hu, Y, Yang, D, et al
Kidney & blood pressure research. 2018;(5):1459-1471
Abstract
BACKGROUND/AIMS: Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%- 75% decrease in plasma AA levels. Some studies have shown that supplementation of AA can change the outcome of chronic kidney disease-mineral bone disorders (CKD-MBD), but the effect of AA on HD patients with CKD-MBD remains controversial. Consequently, we decided to perform a meta-analysis to evaluate the efficacy of AA supplementation in CKD-MBD patients requiring dialysis. METHODS A search was conducted using Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database up to April 2018 for all English and Chinese language publications. The main indicators of our study were changes in serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) levels after AA treatment. The efficacy of AA was evaluated by weighted mean difference (WMD) and confidence intervals (CI). Cardiovascular events, mortality and adverse events reported during the experiment were also noted. RESULTS In total, 371 patients in six studies were involved in this meta-analysis. Compared to placebo, AA treatment had no positive effect on serum P (353 patients; WMD = -0.05; 95% CI, -0.3 to 0.2; I2 = 28%) or PTH levels (275 patients; WMD = -17.04; 95%CI, -63.79 to 29.72; I2 = 75%). The pooled mean difference of the change of Ca levels from baseline was higher in the AA therapy group versus placebo (353 patients; WMD = 0.15; 95% CI, 0.01 to 0.3; I2 = 0%). No side effects were observed. CONCLUSION Our systematic review and meta-analysis does not support prescription of AA to HD patients with CKD-MBD. AA had no positive effect on CKD-MBD patients as it couldn't influence the serum P or PTH levels but did raise serum Ca levels in the short-term.
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Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life.
Rutjes, AW, Denton, DA, Di Nisio, M, Chong, LY, Abraham, RP, Al-Assaf, AS, Anderson, JL, Malik, MA, Vernooij, RW, Martínez, G, et al
The Cochrane database of systematic reviews. 2018;(12):CD011906
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Abstract
BACKGROUND Vitamins and minerals play multiple functions within the central nervous system which may help to maintain brain health and optimal cognitive functioning. Supplementation of the diet with various vitamins and minerals has been suggested as a means of maintaining cognitive function, or even of preventing dementia, in later life. OBJECTIVES To evaluate the effects of vitamin and mineral supplementation on cognitive function in cognitively healthy people aged 40 years or more. SEARCH METHODS We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov and the WHO Portal/ICTRP from inception to 26th January 2018. SELECTION CRITERIA We included randomised controlled trials that evaluated the cognitive effects on people aged 40 years or more of any vitamin or mineral supplements taken by mouth for at least three months. DATA COLLECTION AND ANALYSIS Study selection, data extraction, and quality assessments were done in duplicate. Vitamins were considered broadly in the categories of B vitamins, antioxidant vitamins, and combinations of both. Minerals were considered separately, where possible. If interventions and outcomes were considered sufficiently similar, then data were pooled. In order to separate short-term cognitive effects from possible longer-term effects on the trajectory of cognitive decline, data were pooled for various treatment durations from 3 months to 12 months and up to 10 years or more. MAIN RESULTS In total, we included 28 studies with more than 83,000 participants. There were some general limitations of the evidence. Most participants were enrolled in studies which were not designed primarily to assess cognition. These studies often had no baseline cognitive assessment and used only brief cognitive assessments at follow-up. Very few studies assessed the incidence of dementia. Most study reports did not mention adverse events or made only very general statements about them. Only 10 studies had a mean follow-up > 5 years. Only two studies had participants whose mean age was < 60 years at baseline. The risk of bias in the included studies was generally low, other than a risk of attrition bias for longer-term outcomes. We considered the certainty of the evidence behind almost all results to be moderate or low.We included 14 studies with 27,882 participants which compared folic acid, vitamin B12, vitamin B6, or a combination of these to placebo. The majority of participants were aged over 60 years and had a history of cardio- or cerebrovascular disease. We found that giving B vitamin supplements to cognitively healthy adults, mainly in their 60s and 70s, probably has little or no effect on global cognitive function at any time point up to 5 years (SMD values from -0.03 to 0.06) and may also have no effect at 5-10 years (SMD -0.01). There were very sparse data on adverse effects or on incidence of cognitive impairment or dementia.We included 8 studies with 47,840 participants in which the active intervention was one or more of the antioxidant vitamins: ß-carotene, vitamin C or vitamin E. Results were mixed. For overall cognitive function, there was low-certainty evidence of benefit associated with ß-carotene after a mean of 18 years of treatment (MD 0.18 TICS points, 95% CI 0.01 to 0.35) and of vitamin C after 5 years to 10 years (MD 0.46 TICS points, 95% CI 0.14 to 0.78), but not at earlier time points. From two studies which reported on dementia incidence, there was low-certainty evidence of no effect of an antioxidant vitamin combination or of vitamin E, either alone or combined with selenium. One of the included studies had been designed to look for effects on the incidence of prostate cancer; it found a statistically significant increase in prostate cancer diagnoses among men taking vitamin E.One trial with 4143 participants compared vitamin D3 (400 IU/day) and calcium supplements to placebo. We found low- to moderate-certainty evidence of no effect of vitamin D3 and calcium supplements at any time-point up to 10 years on overall cognitive function (MD after a mean of 7.8 years -0.1 MMSE points, 95% CI -0.81 to 0.61) or the incidence of dementia (HR 0.94, 95% CI 0.72 to 1.24). A pilot study with 60 participants used a higher dose of vitamin D3 (4000 IU on alternate days) and found preliminary evidence that this dose probably has no effect on cognitive function over six months.We included data from one trial of zinc and copper supplementation with 1072 participants. There was moderate-certainty evidence of little or no effect on overall cognitive function (MD 0.6 MMSE points, 95% CI -0.19 to 1.39) or on the incidence of cognitive impairment after 5 years to 10 years. A second smaller trial provided no usable data, but reported no cognitive effects of six months of supplementation with zinc gluconate.From one study with 3711 participants, there was low-certainty evidence of no effect of approximately five years of selenium supplementation on the incidence of dementia (HR 0.83, 95% CI 0.61 to 1.13).Finally, we included three trials of complex supplements (combinations of B vitamins, antioxidant vitamins, and minerals) with 6306 participants. From the one trial which assessed overall cognitive function, there was low-certainty evidence of little or no effect on the TICS (MD after a mean of 8.5 years 0.12, 95% CI -0.14 to 0.38). AUTHORS' CONCLUSIONS We did not find evidence that any vitamin or mineral supplementation strategy for cognitively healthy adults in mid or late life has a meaningful effect on cognitive decline or dementia, although the evidence does not permit definitive conclusions. There were very few data on supplementation starting in midlife (< 60 years); studies designed to assess cognitive outcomes tended to be too short to assess maintenance of cognitive function; longer studies often had other primary outcomes and used cognitive measures which may have lacked sensitivity. The only positive signals of effect came from studies of long-term supplementation with antioxidant vitamins. These may be the most promising for further research.