• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of bmjBMJ helping doctors make better decisionsSearch bmj.comLatest content
BMJ. Aug 28, 1999; 319(7209): 577.
PMCID: PMC1116451

Role of antioxidant vitamins in prevention of cardiovascular diseases

Meta-analysis seems to exclude benefit of vitamin C supplementation
Andy Ness, senior lecturer in epidemiology
Andy.Ness/at/bris.ac.uk
Matthias Egger, senior lecturer in epidemiology and public health medicine
George Davey Smith, professor of clinical epidemiology

Editor—The first article in the series on evidence based cardiology summarises evidence on the effect of antioxidant vitamins on the risk of cardiovascular disease.1 The summary of the trial evidence for vitamin C supplementation is, however, incomplete, and the authors’ interpretation of the available data on antioxidants is too optimistic.

The authors describe Wilson et al’s trial of vitamin C, in which 538 patients admitted to an acute geriatric unit were randomised to receive 200 mg of vitamin C or placebo daily for six months.2 We are aware of two further trials of vitamin C supplementation in Western populations that have reported on mortality from all causes. Burr et al randomised 297 elderly people with low vitamin C concentrations to receive vitamin C (150 mg a day for 12 weeks and 50 mg a day thereafter) or placebo for two years.3 Hunt et al randomised 199 elderly patients to receive 200 mg of vitamin C or placebo daily for six months.4

We performed a meta-analysis of all three trials using a fixed effects model (figure). Even though the three trials were small and relatively short, the combined results seem to exclude any substantial early benefit of vitamin C supplementation. The overall relative risk shows an increase in mortality of 8%, with the 95% confidence interval ranging from a 7% reduction to a 26% increase in mortality (P=0.29). An earlier meta-analysis of the β carotene trials also showed a moderate adverse effect, which was significant (P=0.005).5

Lonn and Yusuf argue that the strong biological rationale and observational epidemiological data relating antioxidants to lower cardiovascular risk justify ongoing trials. We believe that the disappointing results for vitamin C and β carotene should lead us to re-evaluate critically the status of the antioxidant hypothesis and to consider confounding as an alternative explanation for the lower cardiovascular risk observed in epidemiological studies.5

The ongoing trials of antioxidant vitamins should continue because we need to know whether vitamin supplements—widely used in preparations sold over the counter—produce any benefit or are in fact harmful. When potentially protective dietary constituents are identified in the future it may be more sensible to undertake trials of foods that are rich sources of these constituents rather than supplementation trials.

Figure
Results of meta-analysis of three trials of vitamin C supplementation in elderly subjects, showing mortality from all causes. *Amount that each study contributes to pooled estimate of effect of vitamin C supplements.

References

1. Lonn E, Yusuf S. Emerging approaches in preventing cardiovascular disease. BMJ. 1999;318:1337–1341. . (15 May.) [PMC free article] [PubMed]
2. Wilson TS, Datta SB, Murrell JS, Andrews CT. Relation of vitamin C levels to mortality in a geriatric hospital: a study of the effect of vitamin C administration. Age Ageing. 1973;2:163–170. [PubMed]
3. Burr ML, Hurley RJ, Sweetnam PM. Vitamin C supplementation of old people with low blood levels. Gerontol Clin. 1975;17:236–243. [PubMed]
4. Hunt C, Chakkravorty NK, Annan G. The clinical and biochemical effects of vitamin C supplementation in short-stay hospitalized geriatric patients. Int J Vit Nutr Res. 1984;54:65–74. [PubMed]
5. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of observational studies. BMJ. 1998;316:140–145. [PMC free article] [PubMed]
Aug 28, 1999; 319(7209): 577.

Authors’ reply

Eva Lonn, associate professor of medicine
lonnem/at/fhs.mcmaster.ca
Salim Yusuf, professor of medicine

Editor—We do not believe that there is any major disagreement between our views and those expressed in Ness et al’s letter. The two additional negative trials of vitamin C that they mention were quite small clinical trials, and overall we believe that the clinical trials data for vitamin C remain inconclusive. As we stated in our review article, we found the observational data for vitamin C to be not particularly supportive of a role for the vitamin in reducing cardiovascular risk. The use of vitamin C supplements (in isolation) in cardiovascular prevention is therefore not promising.

The epidemiological data for ß carotene and especially for vitamin E are more promising. We agree with Ness et al that the clinical trials of ß carotene, although performed only in men and in primary prevention settings, have effectively shown the lack of efficacy of supplementation with ß carotene. As the authors are aware, interesting epidemiological data exist for other carotenoids and for diets rich in fruit and vegetables with high contents of carotenoids as potential protective factors in cardiovascular prevention. Further clinical trials data are needed for vitamin E.

We do not believe that our view is too optimistic. As we clearly stated in our paper, we agree that results of clinical trials do not at present support the use of antioxidant vitamin supplements in cardiovascular prevention. We do, however, believe—as do many other investigators around the world—that clinical trials are warranted to clarify this issue, particularly regarding vitamin E.

Several large clinical trials are ongoing or have been completed recently. The GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardio) prevention study, conducted in 12 000 patients after myocardial infarction, reported a modest, non-significant 4.7% reduction in risk for the end point cluster of total mortality, non-fatal myocardial infarction, and cerebrovascular accident. These data further put into question the results of other trials and experimental basic research studies and epidemiological investigations.

We believe that the medical community should await the results of the other ongoing trials of vitamin E, including the study coordinated by our centre. This is the heart outcomes prevention evaluation trial, in 9541 patients, which will provide more conclusive results regarding a potential role for vitamin E in cardiovascular prevention.


Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...