|
1
|
Bjelakovic G, Nikolova D, Bjelakovic M, Pavlov CS, Sethi NJ, Korang SK, Gluud C. Effects of primary or secondary prevention with vitamin A supplementation on clinically important outcomes: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. BMJ Open 2024; 14:e078053. [PMID: 38816049 PMCID: PMC11141198 DOI: 10.1136/bmjopen-2023-078053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 05/20/2024] [Indexed: 06/01/2024] Open
Abstract
OBJECTIVES This systematic review with meta-analyses of randomised trials evaluated the preventive effects of vitamin A supplements versus placebo or no intervention on clinically important outcomes, in people of any age. METHODS We searched different electronic databases and other resources for randomised clinical trials that had compared vitamin A supplements versus placebo or no intervention (last search 16 April 2024). We used Cochrane methodology. We used the random-effects model to calculate risk ratios (RRs), with 95% CIs. We analysed individually and cluster randomised trials separately. Our primary outcomes were mortality, adverse events and quality of life. We assessed risks of bias in the trials and used Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of the evidence. RESULTS We included 120 randomised trials (1 671 672 participants); 105 trials allocated individuals and 15 allocated clusters. 92 trials included children (78 individually; 14 cluster randomised) and 28 adults (27 individually; 1 cluster randomised). 14/105 individually randomised trials (13%) and none of the cluster randomised trials were at overall low risk of bias. Vitamin A did not reduce mortality in individually randomised trials (RR 0.99, 95% CI 0.93 to 1.05; I²=32%; p=0.19; 105 trials; moderate certainty), and this effect was not affected by the risk of bias. In individually randomised trials, vitamin A had no effect on mortality in children (RR 0.96, 95% CI 0.88 to 1.04; I²=24%; p=0.28; 78 trials, 178 094 participants) nor in adults (RR 1.04, 95% CI 0.97 to 1.13; I²=24%; p=0.27; 27 trials, 61 880 participants). Vitamin A reduced mortality in the cluster randomised trials (0.84, 95% CI 0.76 to 0.93; I²=66%; p=0.0008; 15 trials, 14 in children and 1 in adults; 364 343 participants; very low certainty). No trial reported serious adverse events or quality of life. Vitamin A slightly increased bulging fontanelle of neonates and infants. We are uncertain whether vitamin A influences blindness under the conditions examined. CONCLUSIONS Based on moderate certainty of evidence, vitamin A had no effect on mortality in the individually randomised trials. Very low certainty evidence obtained from cluster randomised trials suggested a beneficial effect of vitamin A on mortality. If preventive vitamin A programmes are to be continued, supporting evidence should come from randomised trials allocating individuals and assessing patient-meaningful outcomes. PROSPERO REGISTRATION NUMBER CRD42018104347.
Collapse
Affiliation(s)
- Goran Bjelakovic
- Department of Internal Medicine, Medical Faculty, University of Nis, Nis, Serbia
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Clinic of Gastroenterohepatology, University Clinical Centre, Nis, Serbia
| | - Dimitrinka Nikolova
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Milica Bjelakovic
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Clinic of Gastroenterohepatology, University Clinical Centre, Nis, Serbia
| | - Chavdar S Pavlov
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Gastroenterology, Botkin Hospital, Moscow, Russian Federation
- Department of Therapy, I.M. Sechenov, First Moscow State Medical University, Moscow, Russian Federation
| | - Naqash J Sethi
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Steven Kwasi Korang
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Christian Gluud
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Regional Health Research, The Faculty of Heath Sciences, University of Southern Denmark, Odense, Denmark
| |
Collapse
|
|
2
|
Basen-Engquist K, Brown P, Coletta AM, Savage M, Maresso KC, Hawk E. Lifestyle and Cancer Prevention. ABELOFF'S CLINICAL ONCOLOGY 2020:337-374.e12. [DOI: 10.1016/b978-0-323-47674-4.00022-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
3
|
Abstract
The incidence and mortality trends of oesophageal cancer are changing significantly across the world with considerable heterogeneity between sex, histological types, ethnic patterns and geographical distribution. Recent oesophageal cancer incidence and mortality trends have been analysed using data available from the WHO mortality database, the GLOBOCAN 2012 database and the Cancer Incidence in Five Continents database managed by the International Agency for Research on Cancer. Huge geographical variation is an epidemiological characteristic of oesophageal cancer, with the highest incidence rates observed in Eastern Asia and in Eastern and Southern Africa and the lowest rates observed in Western Africa. The variation is to the order of more than 21 times between the lowest-incidence and the highest-incidence countries. Although the incidence of squamous cell carcinoma is increasing globally, its incidence rates are decreasing in the USA and a few European countries. However, the decrease in the incidence of squamous cell carcinomas in these countries has been accompanied by a marked increase in adenocarcinoma incidence rates. There is a significant sex variation as well, with men being affected three to four times more commonly than women worldwide. The observed trends reflect significant global variations in the incidence and mortality of oesophageal cancers on the basis of sex, geographical distribution, ethnicity and histology. These epidemiological factors related to oesophageal cancers point out a possibly significant role of molecular epidemiological factors (genetic susceptibility and response to treatment) with major differences likely between the characteristics of Asian and Western populations.
Collapse
|
|
4
|
Evans JR, Lawrenson JG, Cochrane Eyes and Vision Group. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev 2017; 7:CD000253. [PMID: 28756617 PMCID: PMC6483250 DOI: 10.1002/14651858.cd000253.pub4] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C, and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). OBJECTIVES To determine whether or not taking antioxidant vitamin or mineral supplements, or both, prevent the development of AMD. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29 March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 29 March 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in combination) to control. DATA COLLECTION AND ANALYSIS Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We pooled data using a fixed-effect model. We graded the certainty of the evidence using GRADE. MAIN RESULTS We included a total of five RCTs in this review with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias.Four studies reported the comparison of vitamin E with placebo. Average treatment and follow-up duration ranged from 4 to 10 years. Data were available for a total of 55,614 participants. There was evidence that vitamin E supplements do not prevent the development of any AMD (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.06; high-certainty evidence), and may slightly increase the risk of late AMD (RR 1.22, 95% CI 0.89 to 1.67; moderate-certainty evidence) compared with placebo. Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 3.62, 95% CI 0.77 to 16.95; very low-certainty evidence), and four cases of geographic atrophy (RR 2.71, 95% CI 0.28 to 26.0; very low-certainty evidence). Two trials reported similar numbers of adverse events in the vitamin E and placebo groups. Another trial reported excess of haemorrhagic strokes in the vitamin E group (39 versus 23 events, hazard ratio 1.74, 95% CI 1.04 to 2.91, low-certainty evidence).Two studies reported the comparison of beta-carotene with placebo. These studies took place in Finland and the USA. Both trials enrolled men only. Average treatment and follow-up duration was 6 years and 12 years. Data were available for a total of 22,083 participants. There was evidence that beta-carotene supplements did not prevent any AMD (RR 1.00, 95% CI 0.88 to 1.14; high-certainty evidence) nor have an important effect on late AMD (RR 0.90, 95% CI 0.65 to 1.24; moderate-certainty evidence). Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 0.61, 95% CI 0.17 to 2.15; very low-certainty evidence) and 4 cases of geographic atrophy (RR 0.31 95% CI 0.03 to 2.93; very low-certainty evidence). Beta-carotene was associated with increased risk of lung cancer in people who smoked.One study reported the comparison of vitamin C with placebo, and multivitamin (Centrum Silver) versus placebo. This was a study in men in the USA with average treatment duration and follow-up of 8 years for vitamin C and 11 years for multivitamin. Data were available for a total of 14,236 participants. AMD was assessed by self-report followed by medical record review. There was evidence that vitamin C supplementation did not prevent any AMD (RR 0.96, 95% CI 0.79 to 1.18; high-certainty evidence) or late AMD (RR 0.94, 0.61 to 1.46; moderate-certainty evidence). There was a slight increased risk of any AMD (RR 1.21, 95% CI 1.02 to 1.43; moderate-certainty evidence) and late AMD (RR 1.22, 95% CI 0.88 to 1.69; moderate-certainty evidence) in the multivitamin group. Neovascular AMD and geographic atrophy were not reported separately. Adverse effects were not reported but there was possible increased risk of skin rashes in the multivitamin group.Adverse effects were not consistently reported in these eye studies, but there is evidence from other large studies that beta-carotene increases the risk of lung cancer in people who smoke or who have been exposed to asbestos.None of the studies reported quality of life or resource use and costs. AUTHORS' CONCLUSIONS Taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. The same probably applies to vitamin C and the multivitamin (Centrum Silver) investigated in the one trial reported to date. There is no evidence with respect to other antioxidant supplements, such as lutein and zeaxanthin. Although generally regarded as safe, vitamin supplements may have harmful effects, and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane Review on antioxidant vitamin and mineral supplements for slowing the progression of AMD, written by the same review team.
Collapse
Affiliation(s)
- Jennifer R Evans
- London School of Hygiene & Tropical MedicineCochrane Eyes and Vision, ICEHKeppel StreetLondonUKWC1E 7HT
| | - John G Lawrenson
- City University of LondonCentre for Applied Vision Research, School of Health SciencesNorthampton SquareLondonUKEC1V 0HB
| | | |
Collapse
|
|
5
|
Schwingshackl L, Boeing H, Stelmach-Mardas M, Gottschald M, Dietrich S, Hoffmann G, Chaimani A. Dietary Supplements and Risk of Cause-Specific Death, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis of Primary Prevention Trials. Adv Nutr 2017; 8:27-39. [PMID: 28096125 PMCID: PMC5227980 DOI: 10.3945/an.116.013516] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Our aim was to assess the efficacy of dietary supplements in the primary prevention of cause-specific death, cardiovascular disease (CVD), and cancer by using meta-analytical approaches. Electronic and hand searches were performed until August 2016. Inclusion criteria were as follows: 1) minimum intervention period of 12 mo; 2) primary prevention trials; 3) mean age ≥18 y; 4) interventions included vitamins, fatty acids, minerals, supplements containing combinations of vitamins and minerals, protein, fiber, prebiotics, and probiotics; and 5) primary outcome of all-cause mortality and secondary outcomes of mortality or incidence from CVD or cancer. Pooled effects across studies were estimated by using random-effects meta-analysis. Overall, 49 trials (69 reports) including 287,304 participants met the inclusion criteria. Thirty-two trials were judged as low risk-, 15 trials as moderate risk-, and 2 trials as high risk-of-bias studies. Supplements containing vitamin E (RR: 0.88; 95% CI: 0.80, 0.96) significantly reduced cardiovascular mortality risk, whereas supplements with folic acid reduced the risk of CVD (RR: 0.81; 95% CI: 0.70, 0.94). Vitamins D, C, and K; selenium; zinc; magnesium; and eicosapentaenoic acid showed no significant risk reduction for any of the outcomes. On the contrary, vitamin A was linked to an increased cancer risk (RR: 1.16; 95% CI: 1.00, 1.35). Supplements with β-carotene showed no significant effect; however, in the subgroup with β-carotene given singly, an increased risk of all-cause mortality by 6% (RR: 1.06; 95% CI: 1.02, 1.10) was observed. Taken together, we found insufficient evidence to support the use of dietary supplements in the primary prevention of cause-specific death, incidence of CVD, and incidence of cancer. The application of some supplements generated small beneficial effects; however, the heterogeneous types and doses of supplements limit the generalizability to the overall population.
Collapse
Affiliation(s)
- Lukas Schwingshackl
- Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany;
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany
| | - Marta Stelmach-Mardas
- Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Marion Gottschald
- Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany
| | - Stefan Dietrich
- Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany
| | - Georg Hoffmann
- Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria; and
| | - Anna Chaimani
- Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece
| |
Collapse
|
|
6
|
Abstract
Retinol is the naturally occurring form of vitamin A; Retinyl Palmitate is the ester of Retinol and Palmitic Acid. In acute oral studies, Retinol was slightly toxic to mice, and Retinyl Palmitate was practically nontoxic in mice and rats. Large single doses can be lethal. It is recognized that Retinol is essential for reproduction; however, high intake of Retinol has produced adverse effects on several reproductive functions. Vitamin A was nonmutagenic in several in vitro tests. There is no evidence that vitamin A is carcinogenic. However, the vitamin has both enhanced and inhibited responses to viral or chemical carcinogens. Cosmetic products containing 0.1-1% Retinyl Palmitate were, at most, slightly irritating and nonsensitizing when tested on a total of 607 subjects. Results of cumulative irritation tests of two products containing 0.1% Retinyl Palmitate indicated that the products were nonirritating and non-sensitizing. On the basis of the available animal and clinical data presented in this report, it is concluded that Retinyl Palmitate and Retinol are safe as cosmetic ingredients in the present practices of use and concentration.
Collapse
|
|
7
|
Maresso KC, Tsai KY, Brown PH, Szabo E, Lippman S, Hawk ET. Molecular cancer prevention: Current status and future directions. CA Cancer J Clin 2015; 65:345-83. [PMID: 26284997 PMCID: PMC4820069 DOI: 10.3322/caac.21287] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 05/26/2015] [Accepted: 05/28/2015] [Indexed: 12/20/2022] Open
Abstract
The heterogeneity and complexity of advanced cancers strongly support the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (eg, aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the US Food and Drug Administration for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet it has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, several challenges to the field must be addressed. Here, the authors provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results from major randomized controlled trials.
Collapse
Affiliation(s)
- Karen Colbert Maresso
- Program Manager, Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kenneth Y Tsai
- Assistant Professor, Department of Dermatology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Powel H Brown
- Chair, Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eva Szabo
- Chair, Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Scott Lippman
- Director, Moores Cancer Center, University of California, San Diego, San Diego, CA
| | - Ernest T Hawk
- Vice President and Division Head, Boone Pickens Distinguished Chair for Early Prevention of Cancer, Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX
| |
Collapse
|
|
8
|
|
|
9
|
Bevers TB, Brown PH, Maresso KC, Hawk ET. Cancer Prevention, Screening, and Early Detection. ABELOFF'S CLINICAL ONCOLOGY 2014:322-359.e12. [DOI: 10.1016/b978-1-4557-2865-7.00023-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
10
|
Bjelakovic G, Nikolova D, Gluud C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? PLoS One 2013; 8:e74558. [PMID: 24040282 PMCID: PMC3765487 DOI: 10.1371/journal.pone.0074558] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2012] [Accepted: 08/04/2013] [Indexed: 02/07/2023] Open
Abstract
Background and Aims Evidence shows that antioxidant supplements may increase mortality. Our aims were to assess whether different doses of beta-carotene, vitamin A, and vitamin E affect mortality in primary and secondary prevention randomized clinical trials with low risk of bias. Methods The present study is based on our 2012 Cochrane systematic review analyzing beneficial and harmful effects of antioxidant supplements in adults. Using random-effects meta-analyses, meta-regression analyses, and trial sequential analyses, we examined the association between beta-carotene, vitamin A, and vitamin E, and mortality according to their daily doses and doses below and above the recommended daily allowances (RDA). Results We included 53 randomized trials with low risk of bias (241,883 participants, aged 18 to 103 years, 44.6% women) assessing beta-carotene, vitamin A, and vitamin E. Meta-regression analysis showed that the dose of vitamin A was significantly positively associated with all-cause mortality. Beta-carotene in a dose above 9.6 mg significantly increased mortality (relative risk (RR) 1.06, 95% confidence interval (CI) 1.02 to 1.09, I2 = 13%). Vitamin A in a dose above the RDA (> 800 µg) did not significantly influence mortality (RR 1.08, 95% CI 0.98 to 1.19, I2 = 53%). Vitamin E in a dose above the RDA (> 15 mg) significantly increased mortality (RR 1.03, 95% CI 1.00 to 1.05, I2 = 0%). Doses below the RDAs did not affect mortality, but data were sparse. Conclusions Beta-carotene and vitamin E in doses higher than the RDA seem to significantly increase mortality, whereas we lack information on vitamin A. Dose of vitamin A was significantly associated with increased mortality in meta-regression. We lack information on doses below the RDA. Background All essential compounds to stay healthy cannot be synthesized in our body. Therefore, these compounds must be taken through our diet or obtained in other ways [1]. Oxidative stress has been suggested to cause a variety of diseases [2]. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing diseases and death. Despite the fact that a normal diet in high-income countries may provide sufficient amounts of antioxidants [3,4], more than one third of adults regularly take antioxidant supplements [5,6].
Collapse
Affiliation(s)
- Goran Bjelakovic
- The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Internal Medicine, Gastroenterology and Hepatology, Medical Faculty, University of Nis, Niš, Serbia
- * E-mail:
| | - Dimitrinka Nikolova
- The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Christian Gluud
- The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| |
Collapse
|
|
11
|
Myung SK, Yang HJ. Efficacy of Vitamin and Antioxidant Supplements in Prevention of Esophageal Cancer: Meta-analysis of Randomized Controlled Trials. J Cancer Prev 2013; 18:135-43. [PMID: 25337539 PMCID: PMC4189455 DOI: 10.15430/jcp.2013.18.2.135] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2013] [Revised: 06/19/2013] [Accepted: 06/19/2013] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Observational epidemiological studies have shown that higher intakes of vitamins or antioxidants were inversely associated with the risk of esophageal cancer. However, randomized controlled trials (RCTs) have reported no preventive efficacy of vitamin or antioxidant supplements on esophageal cancer. This meta-analysis aimed to investigate the efficacy of vitamin and antioxidant supplements in the prevention of esophageal cancer as reported by RCTs. METHODS We searched PubMed, EMBASE, and the Cochrane Library in May 2013. Two authors independently reviewed and selected eligible articles based on predetermined selection criteria. RESULTS Of 171 articles searched from three databases and relevant bibliographies, 10 RCTs were included in the final analyses. In a fixed-effect meta-analysis of 10 trials, there was no efficacy of vitamin and antioxidant supplements in the prevention of esophageal cancer (relative risk [RR], 1.04; 95% confidence interval [CI], 0.86-1.25; I(2)=0.0%). Also, subgroup meta-analyses showed that vitamin and antioxidant supplements had no preventive efficacy on esophageal cancer both in the high risk (RR, 1.04; 95% CI, 0.85-1.28; n=4) and non-high risk (RR, 1.01; 95% CI, 0.65-1.56; n=6) groups for esophageal cancer. Further, subgroup meta-analyses revealed no preventive efficacy on esophageal cancer by type of methodological quality and type of vitamin and antioxidant supplements. CONCLUSIONS Unlike observational epidemiological studies, this meta-analysis of RCTs suggests that there is no clinical evidence to support the efficacy of vitamin and antioxidant supplements in the prevention of esophageal cancer.
Collapse
Affiliation(s)
- Seung-Kwon Myung
- Department of Family Medicine, Hospital, National Cancer Center
- Cancer Information & Education Branch, National Cancer Control Institute, National Cancer Center
- Center for Cancer Prevention and Detection, Hospital, National Cancer Center, Goyang, Korea
| | - Hyo Jin Yang
- Department of Family Medicine, Hospital, National Cancer Center
- Center for Cancer Prevention and Detection, Hospital, National Cancer Center, Goyang, Korea
| |
Collapse
|
|
12
|
Ulbricht C, Basch E, Chao W, Conquer J, Costa D, Culwell S, Flanagan K, Guilford J, Hammerness P, Hashmi S, Isaac R, Rusie E, Serrano JMG, Ulbricht C, Vora M, Windsor RC, Woloszyn M, Zhou S. An evidence-based systematic review of vitamin A by the natural standard research collaboration. J Diet Suppl 2013; 9:299-416. [PMID: 23157584 DOI: 10.3109/19390211.2012.736721] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
An evidence-based systematic review of vitamin A by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated and reproducible grading rationale. This paper includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
Collapse
|
|
13
|
Taylor PR, Abnet CC, Dawsey SM. Squamous dysplasia--the precursor lesion for esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2013; 22:540-52. [PMID: 23549398 PMCID: PMC3681095 DOI: 10.1158/1055-9965.epi-12-1347] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide, and esophageal squamous dysplasia (ESD) is the only histopathology that predicts the development of ESCC. The prevalence of ESD parallels rates of invasive ESCC and is typically found in 25% or more of adults above the age of 35 years in populations in north central China, where risk for ESCC is among the highest in the world. Results of chemoprevention and early detection studies to prevent progression of ESD suggest that these approaches, coupled with emerging endoscopic therapies, offer promise for the prevention of esophageal cancer mortality in high-risk populations. Future research on ESD and ESCC should focus on finding additional modifiable risk factors and on identifying biomarkers to incorporate into early detection strategies.
Collapse
Affiliation(s)
- Philip R Taylor
- National Cancer Institute, NIH, EPS, 6120 Executive Blvd, Rm 7006, Bethesda, MD 20892, USA.
| | | | | |
Collapse
|
|
14
|
Abstract
Oesophageal carcinoma affects more than 450,000 people worldwide and the incidence is rapidly increasing. Squamous-cell carcinoma is the predominant form of oesophageal carcinoma worldwide, but a shift in epidemiology has been seen in Australia, the UK, the USA, and some western European countries (eg, Finland, France, and the Netherlands), where the incidence of adenocarcinoma now exceeds that of squamous-cell types. The overall 5-year survival of patients with oesophageal carcinoma ranges from 15% to 25%. Diagnoses made at earlier stages are associated with better outcomes than those made at later stages. In this Seminar we discuss the epidemiology, pathophysiology, diagnosis and staging, management, prevention, and advances in the treatment of oesophageal carcinoma.
Collapse
Affiliation(s)
- Arjun Pennathur
- Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | | | | | | |
Collapse
|
|
15
|
Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev 2012:CD000253. [PMID: 22696317 DOI: 10.1002/14651858.cd000253.pub3] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). OBJECTIVES To examine the evidence as to whether or not taking antioxidant vitamin or mineral supplements prevents the development of AMD. SEARCH METHODS We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 January 2012. SELECTION CRITERIA We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. DATA COLLECTION AND ANALYSIS Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We pooled data using a fixed-effect model. MAIN RESULTS We included four RCTs in this review; 62,520 people were included in the analyses. The trials were conducted in Australia, Finland and the USA and investigated vitamin E and beta-carotene supplements. Overall the quality of the evidence was high. People who took these supplements were not at decreased (or increased) risk of developing AMD. The pooled risk ratio for any antioxidant supplement in the prevention of any AMD was 0.98 (95% confidence interval 0.89 to 1.08) and for advanced AMD was 1.05 (95% CI 0.80 to 1.39). Similar results were seen when the analyses were restricted to beta-carotene and alpha-tocopherol alone. AUTHORS' CONCLUSIONS There is accumulating evidence that taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. There is no evidence with respect to other antioxidant supplements, such as vitamin C, lutein and zeaxanthin, or any of the commonly marketed multivitamin combinations. Although generally regarded as safe, vitamin supplements may have harmful effects and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane review 'Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration' written by the same review team.
Collapse
Affiliation(s)
- Jennifer R Evans
- Cochrane Eyes and Vision Group, ICEH, London School of Hygiene & Tropical Medicine, London, UK.
| | | |
Collapse
|
|
16
|
Mayne ST, Ferrucci LM, Cartmel B. Lessons learned from randomized clinical trials of micronutrient supplementation for cancer prevention. Annu Rev Nutr 2012; 32:369-90. [PMID: 22524186 DOI: 10.1146/annurev-nutr-071811-150659] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
This review discusses the results of randomized clinical trials of supplemental micronutrients for cancer prevention completed over the past 20 years, including trials of beta-carotene and retinol, vitamins C and E, selenium, folic acid, and vitamin D. Some trials observed significant reductions in risk, whereas others observed significant increases in risk of the primary cancer endpoint. In considering these trials, it appears that supplementation targeted to populations with low status of the nutrient of interest may prevent cancer, whereas supplementation in populations with higher status or to achieve pharmacological exposures may promote cancer. Observational epidemiologic evidence coupled with these trial results supports the concept of a U-shaped curve for micronutrients in relation to cancer prevention. Based on these data, nutrient supplements are not currently recommended for cancer prevention in the general population. The hypothesis that groups with low nutrient status may benefit from supplementation has yet to be formally tested.
Collapse
Affiliation(s)
- Susan T Mayne
- Yale School of Public Health, Yale University, New Haven, Connecticut 06520, USA.
| | | | | |
Collapse
|
|
17
|
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012; 2012:CD007176. [PMID: 22419320 PMCID: PMC8407395 DOI: 10.1002/14651858.cd007176.pub2] [Citation(s) in RCA: 305] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Our systematic review has demonstrated that antioxidant supplements may increase mortality. We have now updated this review. OBJECTIVES To assess the beneficial and harmful effects of antioxidant supplements for prevention of mortality in adults. SEARCH METHODS We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to February 2011. We scanned bibliographies of relevant publications and asked pharmaceutical companies for additional trials. SELECTION CRITERIA We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. DATA COLLECTION AND ANALYSIS Three authors extracted data. Random-effects and fixed-effect model meta-analyses were conducted. Risk of bias was considered in order to minimise the risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Random-effects model meta-regression analyses were performed to assess sources of intertrial heterogeneity. MAIN RESULTS Seventy-eight randomised trials with 296,707 participants were included. Fifty-six trials including 244,056 participants had low risk of bias. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase. The mean age was 63 years (range 18 to 103 years). The mean proportion of women was 46%. Of the 78 trials, 46 used the parallel-group design, 30 the factorial design, and 2 the cross-over design. All antioxidants were administered orally, either alone or in combination with vitamins, minerals, or other interventions. The duration of supplementation varied from 28 days to 12 years (mean duration 3 years; median duration 2 years). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (21,484 dead/183,749 (11.7%) versus 11,479 dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05) but significantly increased mortality in a fixed-effect model (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I(2)- of 12%. In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. Meta-regression analysis did not find a significant difference in the estimated intervention effect in the primary prevention and the secondary prevention trials. In the 56 trials with a low risk of bias, the antioxidant supplements significantly increased mortality (18,833 dead/146,320 (12.9%) versus 10,320 dead/97,736 (10.6%); RR 1.04, 95% CI 1.01 to 1.07). This effect was confirmed by trial sequential analysis. Excluding factorial trials with potential confounding showed that 38 trials with low risk of bias demonstrated a significant increase in mortality (2822 dead/26,903 (10.5%) versus 2473 dead/26,052 (9.5%); RR 1.10, 95% CI 1.05 to 1.15). In trials with low risk of bias, beta-carotene (13,202 dead/96,003 (13.8%) versus 8556 dead/77,003 (11.1%); 26 trials, RR 1.05, 95% CI 1.01 to 1.09) and vitamin E (11,689 dead/97,523 (12.0%) versus 7561 dead/73,721 (10.3%); 46 trials, RR 1.03, 95% CI 1.00 to 1.05) significantly increased mortality, whereas vitamin A (3444 dead/24,596 (14.0%) versus 2249 dead/16,548 (13.6%); 12 trials, RR 1.07, 95% CI 0.97 to 1.18), vitamin C (3637 dead/36,659 (9.9%) versus 2717 dead/29,283 (9.3%); 29 trials, RR 1.02, 95% CI 0.98 to 1.07), and selenium (2670 dead/39,779 (6.7%) versus 1468 dead/22,961 (6.4%); 17 trials, RR 0.97, 95% CI 0.91 to 1.03) did not significantly affect mortality. In univariate meta-regression analysis, the dose of vitamin A was significantly associated with increased mortality (RR 1.0006, 95% CI 1.0002 to 1.001, P = 0.002). AUTHORS' CONCLUSIONS We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.
Collapse
Affiliation(s)
- Goran Bjelakovic
- Department of InternalMedicine,Medical Faculty, University ofNis,Nis, Serbia.
| | | | | | | | | |
Collapse
|
|
18
|
Myung SK, Kim Y, Ju W, Choi HJ, Bae WK. Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials. Ann Oncol 2009; 21:166-79. [PMID: 19622597 DOI: 10.1093/annonc/mdp286] [Citation(s) in RCA: 101] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND This meta-analysis aimed to investigate the effect of antioxidant supplements on the primary and secondary prevention of cancer as reported by randomized controlled trials. METHODS We searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007. RESULTS Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer [relative risk (RR) 0.99; 95% confidence interval (CI) 0.96-1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97-1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83-1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06-2.17) in a subgroup meta-analysis of four trials. CONCLUSIONS The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.
Collapse
Affiliation(s)
- S-K Myung
- Center for Cancer Prevention and Detection, National Cancer Center, Goyang, Korea.
| | | | | | | | | |
Collapse
|
|
19
|
Guo W, Zhao YP, Jiang YG, Wang RW, Ma Z. Restoring the metabolic disturbance of zinc: May not only contribute to the prevention of esophageal squamous cell cancer. Med Hypotheses 2008; 71:957-9. [DOI: 10.1016/j.mehy.2008.05.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2008] [Revised: 05/11/2008] [Accepted: 05/12/2008] [Indexed: 12/01/2022]
|
|
20
|
Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Aliment Pharmacol Ther 2008; 28:689-703. [PMID: 19145725 DOI: 10.1111/j.1365-2036.2008.03785.x] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory. AIM To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers. METHODS Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random-effects and fixed-effect models meta-analyses. RESULTS We identified 20 randomized trials (211,818 participants) assessing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83-1.06, I(2) = 54.0%). The heterogeneity seemed to be explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96-1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43-0.80, test of interaction P < 0.0005) and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97-1.07, I(2) = 53.5%) but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02-1.07). CONCLUSIONS We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality.
Collapse
Affiliation(s)
- G Bjelakovic
- The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigs-hospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
| | | | | | | |
Collapse
|
|
21
|
Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev 2008:CD004183. [PMID: 18677777 DOI: 10.1002/14651858.cd004183.pub3] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory. OBJECTIVES To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers. SEARCH STRATEGY We identified trials through the trials registers of the four Cochrane Review Groups on gastrointestinal diseases, The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2007), MEDLINE, EMBASE, LILACS, SCI-EXPANDED, and The Chinese Biomedical Database from inception to October 2007. We scanned reference lists and contacted pharmaceutical companies. SELECTION CRITERIA Randomised trials comparing antioxidant supplements to placebo/no intervention examining occurrence of gastrointestinal cancers. DATA COLLECTION AND ANALYSIS Two authors (GB and DN) independently selected trials for inclusion and extracted data. Outcome measures were gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were reported as relative risks (RR) with 95% confidence interval (CI) based on random-effects and fixed-effect model meta-analysis. Meta-regression assessed the effect of covariates across the trials. MAIN RESULTS We identified 20 randomised trials (211,818 participants), assessing beta-carotene (12 trials), vitamin A (4 trials), vitamin C (8 trials), vitamin E (10 trials), and selenium (9 trials). Trials quality was generally high. Heterogeneity was low to moderate. Antioxidant supplements were without significant effects on gastrointestinal cancers (RR 0.94, 95% CI 0.83 to 1.06). However, there was significant heterogeneity (I(2) = 54.0%, P = 0.003). The heterogeneity may have been explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96 to 1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43 to 0.80; test of interaction P < 0.0005), and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). The antioxidant supplements had no significant effects on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97 to 1.07, I(2) = 53.5%), but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02 to 1.07). Beta-carotene in combination with vitamin A (RR 1.16, 95% CI 1.09 to 1.23) and vitamin E (RR 1.06, 95% CI 1.02 to 1.11) significantly increased mortality. Increased yellowing of the skin and belching were non-serious adverse effects of beta-carotene. In five trials (four with high risk of bias), selenium seemed to show significant beneficial effect on gastrointestinal cancer occurrence (RR 0.59, 95% CI 0.46 to 0.75, I(2) = 0%). AUTHORS' CONCLUSIONS We could not find convincing evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, antioxidant supplements seem to increase overall mortality. The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials.
Collapse
Affiliation(s)
- Goran Bjelakovic
- Copenhagen Trial Unit, Centre for Clinical Intervention Research,, Department 3344, Rigshospitalet, Copenhagen University Hospital,, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
| | | | | | | |
Collapse
|
|
22
|
Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2008:CD007176. [PMID: 18425980 DOI: 10.1002/14651858.cd007176] [Citation(s) in RCA: 150] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Animal and physiological research as well as observational studies suggest that antioxidant supplements may improve survival. OBJECTIVES To assess the effect of antioxidant supplements on mortality in primary or secondary prevention randomised clinical trials. SEARCH STRATEGY We searched The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1985 to October 2005), and the Science Citation Index Expanded (1945 to October 2005). We scanned bibliographies of relevant publications and wrote to pharmaceutical companies for additional trials. SELECTION CRITERIA We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Included participants were either healthy (primary prevention trials) or had any disease (secondary prevention trials). DATA COLLECTION AND ANALYSIS Three authors extracted data. Trials with adequate randomisation, blinding, and follow-up were classified as having a low risk of bias. Random-effects and fixed-effect meta-analyses were performed. Random-effects meta-regression analyses were performed to assess sources of intertrial heterogeneity. MAIN RESULTS Sixty-seven randomised trials with 232,550 participants were included. Forty-seven trials including 180,938 participants had low risk of bias. Twenty-one trials included 164,439 healthy participants. Forty-six trials included 68111 participants with various diseases (gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects meta-analysis (relative risk [RR] 1.02, 95% confidence interval [CI] 0.99 to 1.06), but significantly increased mortality in a fixed-effect model (RR 1.04, 95% CI 1.02 to 1.06). In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. In the trials with a low risk of bias, the antioxidant supplements significantly increased mortality (RR 1.05, 95% CI 1.02 to 1.08). When the different antioxidants were assessed separately, analyses including trials with a low risk of bias and excluding selenium trials found significantly increased mortality by vitamin A (RR 1.16, 95% CI 1.10 to 1.24), beta-carotene (RR 1.07, 95% CI 1.02 to 1.11), and vitamin E (RR 1.04, 95% CI 1.01 to 1.07), but no significant detrimental effect of vitamin C (RR 1.06, 95% CI 0.94 to 1.20). Low-bias risk trials on selenium found no significant effect on mortality (RR 0.91, 95% CI 0.76 to 1.09). AUTHORS' CONCLUSIONS We found no evidence to support antioxidant supplements for primary or secondary prevention. Vitamin A, beta-carotene, and vitamin E may increase mortality. Future randomised trials could evaluate the potential effects of vitamin C and selenium for primary and secondary prevention. Such trials should be closely monitored for potential harmful effects. Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.
Collapse
Affiliation(s)
- G Bjelakovic
- Copenhagen University Hospital, Rigshospitalet, Department 3344,Copenhagen Trial Unit, Centre for Clinical Intervention Research, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
| | | | | | | | | |
Collapse
|
|
23
|
Evans JR, Henshaw K. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev 2008:CD000253. [PMID: 18253971 DOI: 10.1002/14651858.cd000253.pub2] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Some observational studies have suggested that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). OBJECTIVES The aim of this review was to examine the evidence as to whether or not taking vitamin or mineral supplements prevents the development of AMD. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (2007, Issue 3), MEDLINE (1966 to August 2007), SIGLE (1980 to 2005/03), EMBASE (1980 to August 2007), National Research Register (2007, Issue 3), AMED (1985 to January 2006) and PubMed (on 24 January 2006 covering last 60 days), reference lists of identified reports and the Science Citation Index. We contacted investigators and experts in the field for details of unpublished studies. SELECTION CRITERIA We included all randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. We included only studies where supplementation had been given for at least one year. DATA COLLECTION AND ANALYSIS Both review authors independently extracted data and assessed trial quality. Data were pooled using a fixed-effect model. MAIN RESULTS Three randomised controlled trials were included in this review (23,099 people randomised). These trials investigated alpha-tocopherol and beta-carotene supplements. There was no evidence that antioxidant vitamin supplementation prevented or delayed the onset of AMD. The pooled risk ratio for any age-related maculopathy (ARM) was 1.04 (95% CI 0.92 to 1.18), for AMD (late ARM) was 1.03 (95% CI 0.74 to 1.43). Similar results were seen when the analyses were restricted to beta-carotene and alpha-tocopherol. AUTHORS' CONCLUSIONS There is no evidence to date that the general population should take antioxidant vitamin and mineral supplements to prevent or delay the onset of AMD. There are several large ongoing trials. People with AMD should see the related Cochrane review "Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration" written by the same author.
Collapse
Affiliation(s)
- J R Evans
- London School of Hygiene & Tropical Medicine, International Centre for Eye Health, Keppel Street, London, UK WC1E 7HT.
| | | |
Collapse
|
|
24
|
De Stefani E, Ronco AL, Boffetta P, Deneo-Pellegrini H, Acosta G, Correa P, Mendilaharsu M. Nutrient intake and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay. Nutr Cancer 2007; 56:149-57. [PMID: 17474860 DOI: 10.1207/s15327914nc5602_5] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
In 1996-2004 a case-control study on nutrient intake, dietary constituents and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. In fact, Uruguay, and especially its northern provinces, which border Brazil, are high-risk areas. The study included 234 cases and 936 controls. The controls were hospitalized patients with non-neoplastic disease, which was not related to tobacco smoking and alcohol drinking, and without recent changes in their diets. Controls were frequency matched to cases on age (10-yr intervals), sex, and residence (Montevideo and other provinces). Dietary constituents were energy adjusted using the residuals method and then categorized in quartiles according to the distribution of the controls. The final model included linoleic acid, lycopene, alpha-carotene, beta-cryptoxanthin, vitamin A, monounsaturated fat, total carbohydrates, beta-carotene, and folate. The odds ratio (OR) for high intake of linoleic acid was 1.4 (95% confidence interval, CI = 1.2-1.6), whereas lycopene displayed a strong protective effect (OR = 0.7; 95% CI = 0.6-0.9). The possible role of these and other dietary constituents in esophageal carcinogenesis is discussed.
Collapse
Affiliation(s)
- Eduardo De Stefani
- Grupo de Epidemiologia, Departamento de Anatomia Patológica, Hospital de Clínicas, Facultad de Medicina, Montevideo, Uruguay.
| | | | | | | | | | | | | |
Collapse
|
|
25
|
Faivre J, Lepage C, Bouvier AM. Données récentes sur l’épidémiologie du cancer de l’œsophage. ACTA ACUST UNITED AC 2005; 29:534-9. [PMID: 15980746 DOI: 10.1016/s0399-8320(05)82124-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Jean Faivre
- Registre des Cancers Digestifs (INSERM EMI 106), Faculté de Médecine, Dijon
| | | | | |
Collapse
|
|
26
|
Lee DH, Anderson KE, Folsom AR, Jacobs DR. Heme iron, zinc and upper digestive tract cancer: The Iowa Women's Health Study. Int J Cancer 2005; 117:643-7. [PMID: 15929082 DOI: 10.1002/ijc.21215] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
We examined associations among dietary heme iron as a possible pro-oxidant, dietary zinc as a possible antioxidant, and the incidence of upper digestive tract cancer; 34,708 postmenopausal women, aged 55-69 years at baseline who completed a food frequency questionnaire, were followed 16 years. There were 75 upper digestive tract cancer cases (52 gastric cancer and 23 esophageal cancer). When heme iron and zinc were mutually adjusted, in dose-response manners, heme iron intake was positively associated with the risk of upper digestive tract cancer, while zinc intake was inversely associated with risk. After adjusting for age, total energy intake, cigarette smoking and alcohol consumption, relative risks for quintiles of heme iron intake were 1.0, 1.53, 2.15, 3.05 and 2.83 (p for trend = 0.06) and corresponding relative risks for zinc intake were 1.0, 0.86, 0.42, 0.37 and 0.13 (p for trend < 0.01). Additional adjustment for body mass index, physical activity, hormone replacement therapy, multivitamin intake and intake of saturated fat, vitamin C, vitamin E and folate did not change the results. Higher intake of heme iron is associated with higher risk, while higher intake of zinc is associated with lower, risk of upper digestive tract cancer.
Collapse
Affiliation(s)
- Duk-Hee Lee
- Department of Preventive Medicine, College of Medicine, Kyungpook National University, Daegu, Korea
| | | | | | | |
Collapse
|
|
27
|
Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev 2004:CD004183. [PMID: 15495084 DOI: 10.1002/14651858.cd004183.pub2] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory. OBJECTIVES To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers. SEARCH STRATEGY We identified trials through the trials registers of the four Cochrane Review Groups on gastrointestinal diseases, The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 1, 2003), MEDLINE, EMBASE, LILACS, and SCI-EXPANDED from inception to February 2003, and The Chinese Biomedical Database (March 2003). We scanned reference lists and contacted pharmaceutical companies. SELECTION CRITERIA Randomised trials comparing antioxidant supplements to placebo/no intervention examining the incidence of gastrointestinal cancers. DATA COLLECTION AND ANALYSIS Two reviewers independently selected trials for inclusion and extracted data. The outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence interval (CI) based on fixed and random effects meta-analyses. MAIN RESULTS We identified 14 randomised trials (170,525 participants), assessing beta-carotene (9 trials), vitamin A (4 trials), vitamin C (4 trials), vitamin E (5 trials), and selenium (6 trials). Trial quality was generally high. Heterogeneity was low to moderate. Neither the fixed effect (RR 0.96, 95% CI 0.88 to 1.04) nor random effects meta-analyses (RR 0.90, 95% CI 0.77 to 1.05) showed significant effects of supplementation with antioxidants on the incidences of gastrointestinal cancers. Among the seven high-quality trials reporting on mortality (131,727 participants), the fixed effect (RR 1.06, 95% CI 1.02 to 1.10) unlike the random effects meta-analysis (RR 1.06, 95% CI 0.98 to 1.15) showed that antioxidant supplements significantly increased mortality. Two low-quality trials (32,302 participants) found no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high- and low-quality trials was significant by test of interaction (z = 2.10, P = 0.04). Beta-carotene and vitamin A (RR 1.29, 95% CI 1.14 to 1.45) and beta-carotene and vitamin E (RR 1.10, 95% CI 1.01 to 1.20) significantly increased mortality, while beta-carotene alone only tended to do so (RR 1.05, 95% CI 0.99 to 1.11). Increased yellowing of the skin and belching were non-serious adverse effects of beta-carotene. In four trials (three with unclear/inadequate methodology), selenium showed significant beneficial effect on gastrointestinal cancer incidences. REVIEWERS' CONCLUSIONS We could not find evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, they seem to increase overall mortality. The potential cancer preventive effect of selenium should be studied in adequately conducted randomised trials.
Collapse
Affiliation(s)
- G Bjelakovic
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Dept. 7102, H:S Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK 2100 Copenhagen, Denmark.
| | | | | | | |
Collapse
|
|
28
|
Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364:1219-28. [PMID: 15464182 DOI: 10.1016/s0140-6736(04)17138-9] [Citation(s) in RCA: 379] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. METHODS With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. FINDINGS We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. INTERPRETATION We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.
Collapse
Affiliation(s)
- Goran Bjelakovic
- The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshospitalet, Copenhagen, Denmark.
| | | | | | | |
Collapse
|
|
29
|
Lu XM, Zhang YM, Lin RY, Liang XH, Zhang YL, Wang X, Zhang Y, Wang Y, Wen H. p53 polymorphism in human papillomavirus-associated Kazakh’s esophageal cancer in Xinjiang, China. World J Gastroenterol 2004; 10:2775-8. [PMID: 15334668 PMCID: PMC4572100 DOI: 10.3748/wjg.v10.i19.2775] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigate the relationship between p53 codon 72 polymorphism and human papillomavirus (HPV) type 16 infection in Kazakh’s esophageal cancer (EC) in Xinjiang, China.
METHODS: Encoding regions of p53 codon 72 and HPV-16 E6 were amplified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction (PCR) methods using pairs of primary esophageal squamous cell carcinoma (SCC) tissue and corresponding normal mucosa, which were collected from 104 patients of Kazakh in Xinjiang, China.
RESULTS: Only arginine allele was detected in 70.1% (39/55) of HPV-16-E6- positive cases but only in 40.8% (20/49) of HPV-16-E6-negative cases (P < 0.05; OR, 3.53; 95%CI, 1.57-7.98). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. The allele frequency of Arg allele in cancer cases (0.68) was higher than that in normal mucosa samples (0.54) (P < 0.05; OR, 1.80; 95%CI, 1.21-2.69).
CONCLUSION: p53 codon 72 Arg homozygous genotype is one of the high-risk genetic factors for HPV-associated SCC of Kazakh. Individuals carrying Arg allele compared to those with Pro allele have an increased risk for esophageal SCC.
Collapse
Affiliation(s)
- Xiao-Mei Lu
- Medical Research Center, 1st Teaching Hospital, Xinjiang Medical University, No.1 Liyushan Road, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Affiliation(s)
- D M Parkin
- International Agency for Research on Cancer, Lyon, France.
| | | | | |
Collapse
|
|
31
|
Peixoto Guimaraes D, Hsin Lu S, Snijders P, Wilmotte R, Herrero R, Lenoir G, Montesano R, Meijer CJ, Walboomers J, Hainaut P. Absence of association between HPV DNA, TP53 codon 72 polymorphism, and risk of oesophageal cancer in a high-risk area of China. Cancer Lett 2001; 162:231-5. [PMID: 11146230 DOI: 10.1016/s0304-3835(00)00643-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
We analyzed TP53 codon 72 polymorphism, HPV DNA in 32 subjects with oesophageal cancer and 57 healthy subjects with normal oesophageal cytology from an area of China with a high prevalence for this cancer (Linxian County, Henan Province). The frequency of the proline allele (0.63) was significantly higher in the Chinese population than in most European or American populations. No significant association was found between TP53 codon 72 genotype and cancer. We also found a low prevalence of HPV DNA (6.7%) in both cancer cases and healthy subjects. Our findings do not support the association between risk of oesophageal cancer, human papilloma virus infection, and TP53 codon 72 polymorphism in a Chinese population at high risk of oesophageal cancer.
Collapse
Affiliation(s)
- D Peixoto Guimaraes
- Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon 08, Cedex, France
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Evans JR, Henshaw K. Antioxidant vitamin and mineral supplementation for preventing age-related macular degeneration. Cochrane Database Syst Rev 2000:CD000253. [PMID: 10796707 DOI: 10.1002/14651858.cd000253] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Some observational studies have suggested that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration. OBJECTIVES The aim of this review is to examine the evidence as to whether or not taking vitamin or mineral supplements prevents the development of age-related macular degeneration. SEARCH STRATEGY We searched the Cochrane Eyes and Vision Group specialised register, the Cochrane Controlled Trials Register - Central, MEDLINE, reference lists of identified reports and the Science Citation Index. We contacted investigators and experts in the field for details of unpublished studies. The most recent searches were conducted in June 1999. SELECTION CRITERIA All randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control were included. We included only studies where supplementation had been given for at least one year. DATA COLLECTION AND ANALYSIS Both reviewers independently extracted data and assessed trial quality. Currently there is only one published trial included in the review so no data synthesis was conducted. MAIN RESULTS One trial is included in the review. This was a primary prevention trial in Finnish male smokers with four treatment groups: alpha-tocopherol alone, beta-carotene alone, alpha-tocopherol and beta-carotene, placebo. The add-on maculopathy study was conducted in a subset of the main trial cohort. 269 cases of maculopathy (14 late stage age-related macular degeneration) were identified. There was no association of age-related macular degeneration with treatment. REVIEWER'S CONCLUSIONS There is no evidence to date that people without age-related macular degeneration should take antioxidant vitamin and mineral supplements to prevent or delay the onset of the disease. The results of five large ongoing trials are awaited.
Collapse
Affiliation(s)
- J R Evans
- 'Glaxo' Department of Ophthalmology Epidemiology, Institute of Ophthalmology (UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD.
| | | |
Collapse
|
|
33
|
|
|
34
|
Abstract
Tobacco and alcohol use are strong risk factors for cancer of the upper gastrointestinal tract. Saturated fat and red meat intake also appear to increase the risk of colorectal cancer. The strongest and most consistent dietary protective factors for gastrointestinal cancer are vegetables and fruits. Some micronutrients show beneficial effects, but the degree of protection is less than that observed from whole plant foods. Substantial decreases in the morbidity and mortality from gastrointestinal cancer could occur with more widespread adoption of dietary guidelines designed for cancer prevention.
Collapse
Affiliation(s)
- D D Hensrud
- Division of Preventive Medicine, Mayo Medical School, Rochester, Minnesota, USA
| | | |
Collapse
|
|
35
|
Wang LD, Zhou Q, Yang CS. Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high-incidence area. J Cell Biochem 1997. [DOI: 10.1002/(sici)1097-4644(1997)28/29+<159::aid-jcb19>3.0.co;2-c] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
36
|
Measurements of cell proliferation in esophageal and gastric cardia epithelia of subjects in a high incidence area for esophageal cancer. World J Gastroenterol 1996; 2:82-85. [DOI: 10.3748/wjg.v2.i2.82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/04/2023] Open
Abstract
AIM: To determine the proliferation patterns of normal and different precancerous lesions of esophageal and gastric cardia epithelia by measuring levels of proliferating cell nuclear antigen (PCNA), Ki-67 and bromodeoxyuridine (BudR) incorporation.
METHODS: One-hundred-and-seventy-five esophageal biopsies and 45 gastric cardia biopsies were collected from symptom-free subjects in Huixian. Of these, 24 esophageal biopsies were incubated with BudR. The avidin-biotin-peroxidase complex (ABC) method was used to detect PCNA, Ki-67 and BudR. Quantitative data of the immunostaining results were recorded as the number of positive cells per mm2 of the biopsied epithelium.
RESULTS: Intense immunostaining for PCNA, Ki-67 and BudR was observed in the cell nuclei of normal tissues and of tissues with different severities of precancerous lesions. For esophageal biopsies, the numbers of both PCNA and Ki-67 increased significantly as the epithelia progressed from normal to basal cell hyperplasia (BCH) and to dysplasia (DYS). The number of PCNA- and Ki-67-positive cells was three times higher than that of BudR in the same category of BCH. For cardia biopsies, the number of Ki-67-positive cells was lower in normal tissues and increased significantly from chronic superficial gastritis (CSG) to chronic atrophic gastritis (CAG) and to DYS.
CONCLUSION: The staining patterns for PCNA and Ki-67 were correlated with the histopathology of the esophagus and gastric cardia. These methods may be useful for screening subjects at high risk for esophageal and gastric cardia cancers and for monitoring the effect of chemoprevention. PCNA is relatively easy to analyze and may prove to be very useful in studies on esophageal cancer.
Collapse
|
|
37
|
Qi Z, Lidong W, Reiyiong G, Ying X, Baocai Z, Qiju L. Reproducibility of esophageal biopsy sampling procedure. Chin J Cancer Res 1995. [DOI: 10.1007/bf02672798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
|
|
38
|
|
|
39
|
Abstract
Zinc is one of the most important trace elements in the body for many biological functions; it is required as a catalytic component for more than 200 enzymes, and as a structural constituent of many proteins, hormones, neuropeptides, hormone receptors, and probably polynucleotides. Due to its role in cell division and differentiation, programmed cell death, gene transcription, biomembrane functioning and obviously many enzymatic activities, zinc is considered a major element in assuring the correct functioning of an organism, from the very first embryonic stages to the last periods of life. This biological role together with the many factors that modulate zinc turnover explains on one hand, the variety of clinical and laboratory signs resulting from its reduced bioavailability, and on the other, the high number of human pathologies characterized by alterations in the zinc pool. As zinc supplementation is efficacious in most of these conditions, it is regarded more as an oriented therapeutical support, than a simple dietary integrator. Furthermore, the relevance of zinc status to many age-associated diseases and, according to experimental studies, the aging itself of the major homeostatic mechanisms of the body, i.e., the nervous, neuroendocrine and immune systems, places zinc in a pivotal position in the economy of the aging organism.
Collapse
Affiliation(s)
- N Fabris
- Research Department, Italian National Research Center on Aging (I.N.R.C.A.), Ancona
| | | |
Collapse
|
|
40
|
Zaridze D, Evstifeeva T, Boyle P. Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer. Ann Epidemiol 1993; 3:225-34. [PMID: 8275193 DOI: 10.1016/1047-2797(93)90023-w] [Citation(s) in RCA: 52] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
This intervention trial carried out in Uzbekistan (former USSR) in an area with a high incidence of oral and esophageal cancer involved random allocation of 532 men, 50 to 69 years old, with oral leukoplakia and/or chronic esophagitis to one of four arms in a double-blind, two-by-two factorial design, with active arms defined by the administration of (a) riboflavin; (b) a combination of retinol, beta-carotene, and vitamin E; or (c) both. Weekly doses were 100,000 IU of retinol, 80 mg of vitamin E, and 80 mg of riboflavin. The dose of beta-carotene was 40 mg/d. Men in the trial were followed for 20 months after randomization. The aim of the trial was to determine whether treatment with these vitamins or their combination could affect the prevalence of oral leukoplakia and/or protect against progression of oral leukoplakia and esophagitis, conditions considered to be precursors of cancer of the mouth and esophagus. A significant decrease in the prevalence odds ratio (OR) of oral leukoplakia was observed after 6 months of treatment in men receiving retinol, beta-carotene, and vitamin E (OR = 0.62; 95% confidence interval (CI): 0.39 to 0.98). After 20 months of treatment, no effect of vitamin supplementation was seen when the changes in chronic esophagitis were compared in the four different treatment groups, although the risk of progression of chronic esophagitis was lower in the subjects allocated to receive retinol, beta-carotene and vitamin E (OR = 0.65; 95% CI: 0.29 to 1.48) A secondary analysis not based on the randomized design revealed a decrease in the prevalence of oral leukoplakia in men with medium (OR = 0.45; 95% CI: 0.21 to 0.96) and high (OR = 0.59; 95% CI: 0.29 to 1.20) blood concentrations of beta-carotene after 20 months of treatment. Risk of progression of chronic esophagitis was also lower in men with a high blood concentration of beta-carotene, odds ratios being 0.30 (95% CI: 0.10 to 0.89) and 0.49 (95% CI: 0.15 to 1.58) for medium and high levels, respectively. A decrease in risk, also statistically not significant, was observed for high vitamin E levels (OR = 0.39; 95% CI: 0.14 to 1.10). These results were based on levels of vitamins in blood drawn after 20 months of treatment.
Collapse
Affiliation(s)
- D Zaridze
- Department of Cancer Epidemiology and Prevention, Russian Academy of Medical Sciences, Moscow
| | | | | |
Collapse
|
|
41
|
|
|
42
|
Abstract
A major limiting factor in the successful implementation of cancer chemoprevention trials has been the determination of endpoints to measure efficacy and success. The use of the ultimate goal of such trials, namely, cancer incidence, as an endpoint has serious feasibility problems, including the need for large numbers of participants, long follow-up periods, and high costs. The application of biological markers as intermediate endpoints to reveal responses to chemopreventive agents within a short time and to act as surrogates for cancer is an attractive concept worthy of intense investigation. This study reviews some potential biological markers, including genetic, cellular, biochemical, and immunological, as well as their possible application to cancer chemoprevention.
Collapse
Affiliation(s)
- R Pillai
- Department of Family and Community Medicine, University of Arizona, Tucson 85724
| | | | | | | |
Collapse
|
|
43
|
Benner SE, Lippman SM, Wargovich MJ, Velasco M, Peters EJ, Morice RC, Hong WK. Micronuclei in bronchial biopsy specimens from heavy smokers: characterization of an intermediate marker of lung carcinogenesis. Int J Cancer 1992; 52:44-7. [PMID: 1500226 DOI: 10.1002/ijc.2910520110] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Bronchial micronuclei, small fragments of extra-nuclear DNA formed during cell division, provide a non-specific but quantifiable marker of DNA damage. Micronuclei have been used to assess carcinogen exposure and as an intermediate endpoint in chemoprevention trials. As part of an ongoing chemoprevention trial, heavy smokers underwent screening bronchoscopy, with biopsies taken at 6 standardized sites. Micronuclei counts were obtained for each site in each of the 40 volunteers found to have squamous metaplasia. Unlike squamous metaplasia, the average micronuclei counts among these heavy smokers were not associated with smoking history. Micronuclei counts were also not associated with the presence or extent of metaplasia. A striking degree of intra-individual variability was observed by comparing the micronuclei counts from different biopsy sites within individuals. The findings suggest that use of micronuclei from single sites may be misleading as a marker of carcinogen exposure or as an estimate of cancer risk. Serial measurements in individuals may provide the most useful information concerning carcinogenic exposure and the impact of chemopreventive agents.
Collapse
Affiliation(s)
- S E Benner
- Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030
| | | | | | | | | | | | | |
Collapse
|
|
44
|
Hunter DJ, Colditz GA, Stampfer MJ, Rosner B, Willett WC, Speizer FE. Diet and risk of basal cell carcinoma of the skin in a prospective cohort of women. Ann Epidemiol 1992; 2:231-9. [PMID: 1342273 DOI: 10.1016/1047-2797(92)90055-u] [Citation(s) in RCA: 84] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
We conducted a prospective study of diet in relation to the incidence of basal cell carcinoma of the skin in a cohort of 73,366 women who were 34 to 59 years old in 1980 and without previous skin or other cancer. During 4 years of follow-up, 771 incident cases of basal cell carcinoma were diagnosed. When adjusted for other risk factors, women in the highest quintile of energy intake were at higher risk of basal cell carcinoma compared with those in the lowest quintile (relative risk, 1.28; 95% confidence interval, 1.02 to 1.60). No significant associations were observed between risk of basal cell carcinoma and energy-adjusted intake of dietary fat, carotenoids with vitamin A activity, and retinol, vitamin C, vitamin D, and vitamin E, either with or without supplements. Use of specific vitamin A, C, D, or E supplements, or multivitamins, did not materially alter risk. Although the period of follow-up was relatively short, these data are most consistent with no major role for these nutrients in the etiology of basal cell carcinoma.
Collapse
|
|
45
|
Abstract
Since the discovery of vitamin A as a fat-soluble growth factor in the early part of the century, research into carotenoids and retinoids has attracted the attention of many scientists. These two groups of compounds are still being actively studied all over the world since many gaps in knowledge exist and new frontiers are being pursued. Recent developments in studies into the possible roles of carotenoids and retinoids beyond their classical functions in vision have created a great deal of excitement in the biomedical community. This review covers a wide range of topics pertaining to these two closely related compounds. Particular emphasis is given to the functions of these compounds and their roles in human nutrition. Various aspects of vitamin A deficiency and studies on carotenoids and retinoids in cancer development and prevention are reviewed in some detail.
Collapse
Affiliation(s)
- E S Tee
- Division of Human Nutrition, Institute for Medical Research, Kuala Lumpur, Malaysia
| |
Collapse
|
|
46
|
Mäenpää P, Karinpää A, Jauhiainen M, Laitinen M, Lappeteläinen R, Kumpusalo E. Effects of low‐fat lactovegetarian diet on health parameters of adult subjects. Ecol Food Nutr 1991. [DOI: 10.1080/03670244.1991.9991173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
|
|
47
|
Abstract
The treatment of carcinoma of the esophagus is a challenging problem to clinicians. The 5-year survival rate of surgery reported from large centers is about 25-30%, with resectability rate around 85-90% and operation mortality rate around 5%. However, this is based on highly selected cases. The 5-year survival rate of radiation therapy is about 9-16%, while the patients receiving radiation therapy were mostly the late cases. Pre-operative radiation seems to improve the results of surgery, but more randomized control clinical studies are needed. A combination of chemotherapy with radiation might improve the short-term response rates. Chemotherapy alone may provide some benefits for patients. Intracavitary microwave hyperthermia might open a possibility in the improvement of treatment results in combination with radiation and/or chemotherapy.
Collapse
Affiliation(s)
- D J Li
- Department of Radiation Oncology, Henan Tumor Hospital and Institute, Zhengzhou, People's Republic of China
| |
Collapse
|
|
48
|
|
|
49
|
Wahrendorf J, Chang-Claude J, Liang QS, Rei YG, Muñoz N, Crespi M, Raedsch R, Thurnham D, Correa P. Precursor lesions of oesophageal cancer in young people in a high-risk population in China. Lancet 1989; 2:1239-41. [PMID: 2573759 DOI: 10.1016/s0140-6736(89)91850-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Young people (15-26 years) were selected from households in a population in China at high risk of oesophageal cancer on the basis of whether a case of oesophageal cancer had (166 participants) or had not (372 participants) occurred in a first-degree relative. In an endoscopic survey 43.5% of the male subjects and 35.9% of the female subjects showed histological signs of chronic oesophagitis. The presence of these precursor lesions was significantly associated in a multivariate logistic model with consumption of burning hot beverages, a family history of oesophageal cancer (including second-degree relatives), infrequent consumption of fresh fruit, and infrequent consumption of dietary staples other than maize.
Collapse
Affiliation(s)
- J Wahrendorf
- German Cancer Research Centre, Institute of Epidemiology and Biometry, Heidelberg
| | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Abstract
The concept of chemoprevention is generating increasing attention among oncologists. This article discusses the issue of dose of chemopreventive agents in relation to the stages of tumor development. Vitamin A-deficient animals have an increased susceptibility to cancer development, and epidemiologic studies have shown an inverse relationship between intake of food rich in vitamin A and/or beta-carotene and cancer risk. These data suggest that physiologic levels of these natural substances exert a protective effect against cancer development. In the presence of precursor lesions, however, this protective effect has been overwhelmed and pharmacologic doses of chemopreventive agents are required to induce regression or to arrest the progression of these lesions. Phase I pharmacologic and toxicologic studies, and Phase II dose-intensity investigation of chemopreventive agents in patients having precancerous lesions need to be carried out. Such studies would enable to select the least toxic effective chemopreventive dose for intervention trials in high-risk populations, which could then be undertaken based on evidence of activity.
Collapse
Affiliation(s)
- P R Band
- Division of Epidemiology, Biometry and Occupational Oncology Cancer Control Agency of British Columbia Vancouver, Canada
| | | | | |
Collapse
|