Cochrane Briefs

Am Fam Physician. 2005 Feb 1;71(3):465-466.

Efficacy of Antioxidants in GI Cancer Prevention

Clinical Question

Does supplementation with antioxidant vitamins prevent gastrointestinal (GI) cancer?

Evidence-Based Answer

There is no evidence that supplementation with beta carotene or vitamins A, C, or E prevents GI cancer. Data for selenium is inconsistent and based on poor-quality studies, and supplementation with this mineral should not be recommended routinely. Most importantly, combinations of antioxidant vitamins appear slightly to increase overall mortality rates.

Practice Pointers

Until recently, vitamin E and other antioxidants had been considered safe and possibly effective in the prevention of heart disease and various malignancies. However, a recent meta-analysis1 of studies of vitamin E supplementation for prevention of heart disease found no benefit and even a possible increase in risk at dosages above 400 IU per day. In the current Cochrane review, Bjelakovic and colleagues identified 14 randomized controlled trials of more than 170,000 patients that compared beta carotene, selenium, and vitamins A, C, and E with placebo for prevention of GI cancer.

No single antioxidant or combination of antioxidants significantly reduced the incidence of esophageal, gastric, colorectal, pancreatic, or hepatic cancer. When the results of all antioxidants and antioxidant combinations for a particular cancer were integrated, there was no effect on the incidence of that cancer. There was a trend in favor of selenium for prevention of esophageal, colorectal, and hepatocellular cancer, but it was not statistically significant, and the studies were of limited quality. Most importantly, when the results for all studies were combined using one statistical approach, overall mortality was increased in patients taking antioxidants (relative risk [RR], 1.06; 95 percent confidence interval [CI], 1.02 to 1.10). However, only a trend was noted when a more conservative approach was used (RR, 1.06; 95 percent CI, 0.98 to 1.15). When the selenium trials were excluded, both analyses showed a statistically significant increase in mortality, which was particularly strong in patients taking beta carotene and vitamin A (RR, 1.29; 95 percent CI, 1.14 to 1.45) or beta carotene and vitamin E (RR, 1.10; 95 percent CI, 1.01 to 1.20).

Bjelakovic G, et al. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev. 2004;(4):CD004183.


1. Miller ER 3d, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.

Delaying Antibiotics for Respiratory Infections

Clinical Question

What effect does delayed prescribing of antibiotics have on the clinical course of respiratory infections and the likelihood of complications?

Evidence-Based Answer

Delayed prescribing appears to be a reasonable and safe option in patients with cough and in those who do not appear very ill, but it cannot be recommended for children with sore throat unless streptococcal pharyngitis has been ruled out. Delayed prescribing of antibiotics results in a small increase in symptoms in some groups of patients at day 3. However, this risk must be balanced against the benefits of fewer antibiotic side effects, less antibiotic resistance, and lower cost.

Practice Pointers

Delayed prescribing is one strategy for reducing antibiotic use for common respiratory tract infections (RTIs). Most of these infections are viral and do not benefit from the use of antibiotics. Delayed prescribing means giving patients a prescription but suggesting that they not fill it unless they begin to feel worse or develop specific symptoms, or requiring that patients call the practice or pick up a prescription at a later date if their symptoms persist or worsen. A previous systematic review1 showed that delayed antibiotic prescribing for RTIs reduces by one half the number of patients who take an antibiotic. In this review, Spurling and colleagues identified seven good-quality randomized controlled trials that assigned patients to immediate or delayed antibiotics and followed them prospectively to determine their clinical outcomes.

The studies included patients with sore throat, common cold, otitis media, and cough. The results were mixed. In three studies of unselected children with sore throat (many of whom likely had streptococcal infection), patients in the delayed antibiotic group were more likely to have a fever on day 3. Findings were similar for pain and malaise: some studies found a benefit with immediate antibiotics, and some did not. Studies showing a benefit tended to enroll sicker patients.

Delayed antibiotic prescribing often is used in adults with cough; only one study considered this group, and it found no difference in outcomes. There were no consistent differences in reconsultation rates or complications between patients who received delayed treatment and those who received treatment immediately.

Spurling G, et al. Delayed antibiotics for symptoms and complications of respiratory infections. Cochrane Database Syst Rev. 2004;(4):CD004417.


1. Arroll B, Kenealy T, Kerse N. Do delayed prescriptions reduce antibiotic use in respiratory tract infections? A systematic review [published correction appears in Br J Gen Pract 2004;54:138]. Br J Gen Pract. 2003;53:871-7.

Copyright © 2005 by the American Academy of Family Physicians.
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