Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Vitamin E is not clearly effective for intermittent claudication

ACP J Club. 1998 Sep-Oct;129:37. doi:10.7326/ACPJC-1998-129-2-037

Source Citation

Kleijnen J, Mackerras D. Vitamin E for the treatment of intermittent claudication. In: The Cochrane Library, Issue 1, 1998. Oxford: Update Software.



Can vitamin E improve subjective, objective, and functional outcomes in patients with intermittent claudication?

Data sources

Studies were identified by searching MEDLINE and EMBASE/Excerpta Medica using the search strategies of the Cochrane Review Group on Peripheral Vascular Diseases, hand searching relevant medical journals, and reviewing the bibliographies of relevant papers.

Study selection

Studies were selected if they were controlled or randomized clinical trials of patients with diagnosed intermittent claudication; if they compared vitamin E treatment with ≥ 1 control treatment; if outcomes included ≥ 1 of the following: subjective pain, disability, walking distance, total treadmill walking distance, treadmill walking distance until pain onset, ankle-arm blood pressure index, vascular surgery, amputation, or death; and if patient follow-up was ≥ 3 months.

Data extraction

Data were extracted on patient characteristics, allocation procedure, double-blinding, drop-outs, vitamin and control treatment doses, analysis methods, outcomes, and author conclusions. Methodologic quality of studies was rated and scored on the basis of 10 predefined criteria.

Main results

5 controlled trials published between 1953 and 1975 were included in the analysis. The trials had sample sizes ranging from 33 to 80 patients, and all used placebo controls. The trials assessed 4 physical outcomes (walking distance to pain and distance to halting, change in number of circuits walking over steps and duration of pain after cessation, change in number of circuits of stepping up and down 2 steps, and number of times the patient could stand on tiptoes at a rate of 35 times/min), used 5 different doses of vitamin E, and lasted from 12 weeks to 18 months. All showed positive effects on ≥ 1 outcome. Data from 2 trials that used similar doses, lasted approximately 8 months, and reported patient subjective evaluation of the treatment were meta-analyzed by using a random-effects model. Vitamin E and placebo groups did not differ for patient subjective assessment of “no change” or “deterioration” of condition (32% vs 64% {relative risk reduction 43%, 95% CI -15% to 73%}*, P = 0.15). No studies reported serious side effects with vitamin E use.


Insufficient evidence exists to recommend treatment with vitamin E in patients with intermittent claudication.

Source of funding: No external funding.

For correspondence: Prof. J. Kleijnen, NHS Centre for Reviews and Dissemination, University of York, York Y010 5DD, England, UK. FAX 44-1904-433-661.

*Numbers calculated from data in article.


By preventing oxidation of low-density-lipoprotein cholesterol, vitamin E may play an important role in the prevention of cardiovascular disease. This systematic review by Kleijnen and Mackerras evaluates the role of vitamin E in improving functional status in patients with intermittent claudication.

Evaluation of this question with only 5 trials that had small samples (total n = 227) is difficult. Over the long term, approximately 50% of patients will have no progression of symptoms or will actually have improved functional status (1). According to the American Heart Association statement on chronic arterial insufficiency of the lower extremities, exercise therapy, smoking cessation, and antiplatelet therapy remain the mainstay of treatment (2). The potential advantage of a safe and inexpensive therapy, such as vitamin E, with the promise of favorable outcomes in cardiovascular disease, deserves proper evaluation for peripheral arterial disease.

Because the trials were done in an era before percutaneous revascularization, antiplatelet therapy, and measures aimed at smoking cessation, the findings may not be generalizable to current practice.

Patients with peripheral vascular disease are at higher risk for cardiovascular morbidity, and the use of vitamin E for prevention of cardiovascular disease has been addressed. A detailed review of large observational studies found a relative risk reduction of 31% to 65% for fatal and nonfatal cardiovascular outcomes when vitamin E was given for ≥ 2 years (3). Because patients with intermittent claudication are at higher risk for cardiovascular disease, it may be appropriate to prescribe vitamin E on this basis alone.

I agree completely with the authors' call for large, double-blind, randomized controlled trials to address the efficacy of vitamin E in patients with claudication.

Michael Farkouh, MD
Mount Sinai Medical CenterNew York, New York, USA

Michael Farkouh, MD
Mount Sinai Medical Center
New York, New York, USA


1. McDaniel MD, Cronenwett JL. Basic data related to the natural history of intermittent claudication. Ann Vasc Surg. 1989;3:273-7.

2. Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996;94:3026-49.

3. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease: a critical review of epidemiologic and clinical trial data. Ann Intern Med. 1995;123:860-72.