Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial

Bonelli, Luigina; Puntoni, Matteo; Gatteschi, Beatrice; Massa, Paolo; Missale, Guido; Munizzi, Francesco; Turbino, Laura; Villanacci, Vincenzo; Censi, Andrea De; Bruzzi, Paolo

doi:10.1007/s00535-012-0691-z

Cited by 27 publications

(22 citation statements)

References 26 publications

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“…That supplementation with antioxidants could have positive effects also after the intervention has terminated has been reported by Bonelli et al [ 45 ]. They evaluated patients with recurrent adenomas and where a supplementation of vitamin A, C and E combined with 200microgram selenium was given during 5 years.…”

Section: Discussionmentioning

confidence: 69%

Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens

2015

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BackgroundSelenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD), and functional class.MethodsFour-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered.FindingsSignificantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95%CI 0.36–0.74; P = 0.0003). The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95%CI 0.27–0.97; P = 0.04), but also in the different functional classes.ConclusionsIn a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

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Section: Discussionmentioning

confidence: 69%

Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens

2015

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“…A recent randomized trial supplementing antioxidant nutrients including Se showed a significant protective effect on CRA recurrence. 9 Three other analyses based on subjects enrolled in randomized CRA prevention trials with Se alone have also considered the association of baseline Se levels and CRA recurrence. The first did not indicate any association, 10 the second observed a significant inverse association, 11 while the third observed a reduced risk in smokers only.…”

Section: What's New?mentioning

confidence: 99%

“…There is much current debate as to whether Se influences development of CRC or its precursor colorectal adenoma (CRA) lesions. A recent randomized trial supplementing antioxidant nutrients including Se showed a significant protective effect on CRA recurrence . Three other analyses based on subjects enrolled in randomized CRA prevention trials with Se alone have also considered the association of baseline Se levels and CRA recurrence.…”

mentioning

confidence: 99%

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Hughes

Fedirko

Jenab

et al. 2014

Intl Journal of Cancer

175

158

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Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case–control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X‐ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non‐significant lower CRC risk (IRR = 0.92, 95% CI: 0.82–1.03 per 25 μg/L increase). However, sub‐group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70–0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82–0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72–0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86–1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.

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“…Among 20 RCTs, 13 had low ROB in most of the criteria and were categorized as RCTs with low ROB in our analysis 16–21,26,28,30,31,34,72,81. The remaining seven trials showed either unclear or high ROB according to most criteria 27,29,32,33,35,36,71. Because of differences in ROB, we carried out a sensitivity analysis by restricting to RCTs with low ROB.…”

Section: Resultsmentioning

confidence: 99%

Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

Veettil

Teerawattanapong

Ching³

et al. 2017

OTT

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BackgroundProtective effects of several chemopreventive agents (CPAs) against colorectal adenomas have been well documented in randomized controlled trials (RCTs); however, there is uncertainty regarding which agents are the most effective.MethodsWe searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA) of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome). Using NMA, we ranked CPAs based on efficacy.ResultsWe identified 20 eligible RCTs enrolling 12,625 participants with a history of colorectal cancer or adenomas who were randomly assigned to receive either a placebo or one of 12 interventions. NMA using all trials demonstrated that celecoxib 800 mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45–0.83), celecoxib 400 mg/day (RR 0.70, 95% CI 0.55–0.87), low-dose aspirin (RR 0.75, 95% CI 0.59–0.96) and calcium (RR 0.81, 95% CI 0.69–0.96) were significantly associated with a reduction in the recurrence of any adenomas. NMA results were consistent with those from pairwise meta-analysis. The evidence indicated a high (celecoxib), moderate (low-dose aspirin) and low (calcium) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality. NMA ranking showed that celecoxib 800 mg/day and celecoxib 400 mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800 mg/day and celecoxib 400 mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI 0.27–0.52 vs RR 0.48, 95% CI 0.38–0.60, respectively).ConclusionThe available evidence from NMA suggests that celecoxib is more effective in reducing the risk of recurrence of colorectal adenomas, followed by low-dose aspirin and calcium. Since cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib) are associated with important cardiovascular events and gastrointestinal harms, more attention is warranted toward CPAs with a favorable benefit-to-risk ratio, such as low-dose aspirin and calcium.

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Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial

Abstract: Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.

Cited by 27 publications

References 26 publications

Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens

Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

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