• Sintesi dell'articolo
• Bibliografia
• English version
• Plain language summary

Sintesi dell'articolo

I carotenoidi sono composti liposolubili naturalmente presenti in molti tipi di frutta e verdura, con attività antiossidante. Alfa, beta e gamma-carotene sono considerati provitamine in quanto convertibili nella forma attiva della vitamina A. Tutti i caroteni posseggono attività antiossidante così come la vitamina E, la vitamina C ed il selenio.

I dati di molti studi osservazionali condotti in precedenza, sia su animali sia sull’uomo, suggerivano come gli antiossidanti avessero effetti benefici sulla salute e sul prolungamento della vita. Tuttavia, i risultati di altri studi osservazionali dimostrarono invece effetti nulli se non addirittura dannosi.

Si è dunque reso necessario riassumere gli effetti degli antiossidanti in prevenzione esaminando i dati dei soli studi clinici randomizzati con gruppo di controllo (Randomized Clinical Trial - RCT). In questa revisione sistematica sono stati inclusi 67 RCT, per un totale di 232550 pazienti, cui sono stati somministrati, in modo casuale, integratori alimentari contenenti antiossidanti (beta-carotene, vitamina A, vitamina E, vitamina C e selenio) oppure placebo. 21 RCT sono stati condotti su 164439 persone sane, mentre 46 RCT includevano 68111 pazienti con diverse patologie (gastrointestinali, cardiovascolari, oculari, dermatologiche, remautiche, endocrine o renali).

Complessivamente, i supplementi antiossidanti non hanno diminuito la mortalità in nessun caso.
In particolare, nell’analisi di RCT a basso rischio di errore, si è evidenziato un aumento significativo della mortalità per l’assunzione di beta-carotene, vitamina A e vitamina E, con uguale effetto nei soggetti sani o malati.
Non è stato dimostrato alcun effetto nei trial che hanno utilizzato la vitamina C, mentre altri studi hanno dimostrato un debole effetto del selenio sulla riduzione della mortalità.

I risultati di questa revisione sistematica dimostrano che gli integratori contenenti antiossidanti non dovrebbero essere usati in prevenzione né sulla popolazione generale né su pazienti affetti da patologie varie, mentre i dati sulla vitamina C e il selenio sono ancora insufficienti.
L’uso degli integratori considerati in questa revisione non deve tuttavia essere confuso con la somministrazione dei supplementi per la cura di specifiche patologie, o in pazienti con carenze accertate, né con gli antiossidanti normalmente contenuti nella frutta e verdura.

Bibliografia

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 of Systematic Reviews 2008, Issue 2. Art. No.: CD007176. DOI: 10.1002/14651858.CD007176.

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English version

Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases
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 of Systematic Reviews 2008, Issue 2. Art. No.: CD007176. DOI: 10.1002/14651858.CD007176.

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.

Plain language summary

No evidence to support antioxidant supplements to prevent mortality in healthy people or patients with various diseases

Previous research on animal and physiological models suggest that antioxidant supplements have beneficial effects that may prolong life. Some observational studies also suggest that antioxidant supplements may prolong life, whereas other observational studies demonstrate neutral or harmful effects. Randomised trials have largely been neutral. We need evidence from randomised trials to decide if antioxidant supplements should be used for prevention.
The present systematic review includes 67 randomised clinical trials. In total, 232,550 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Twenty-one trials included 164,439 healthy participants. Forty-six trials included 68111 participants with various diseases (including gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified diseases).
Overall, the antioxidant supplements did not seem to reduce mortality. A total of 17880 of 136,023 participants (13.1%) randomised to antioxidant supplements and 10136 of 96527 participants (10.5%) randomised to placebo or no intervention died. In the analyses of the trials with low risk of bias, beta-carotene, vitamin A, and vitamin E significantly increased mortality. There were no significant differences between the effects of antioxidant supplements in healthy participants (primary prevention trials) or participants with various diseases (secondary prevention trials). Randomised trials with adequate bias control found no significant effect of vitamin C. In some of our analyses, selenium seems to reduce mortality.
The current evidence does not support the use of antioxidant supplements in the general population or in patients with certain diseases. The combined evidence suggests that additional research on antioxidant supplements is needed. The evidence on vitamin C and selenium was not conclusive. Future trials could focus on vitamin C and selenium and should assess both potential beneficial and harmful effects. Conduct of additional primary and secondary prevention trials on vitamin A, beta-carotene, and vitamin E seems questionable, at least in the dosage range examined.
The present review does not assess antioxidant supplements for treatment of specific diseases (tertiary prevention), antioxidant supplements for patients with demonstrated specific needs of antioxidants, or the effects of antioxidants contained in fruits or vegetables. Further research and systematic reviews on these types of interventions are therefore warranted.