Clinical Briefs

By Louis Kuritzky, MD

MRC/BHF Heart Protection Study of Antioxidant Vitamin Supplementation in 20,536 High-Risk Individuals

Observational studies have indicated that intake of antioxidant vitamins (AOV), such as vitamins E, C, and beta-carotene, is inversely related to incidence of vascular disease. It has been postulated that this favorable relationship might be mediated, at least in part, through the demonstrated in vitro inhibition of LDL oxidation afforded by AOV. Oxidized LDL is known to be more atherogenic than native LDL. Though the positive potential for AOV benefits is intellectually appealing, want of a randomized, placebo-controlled interventional trial confirming AOV benefit has limited the enthusiasm of the scientific community. The Heart Protection Study Collaborative Group performed such a trial in the largest ever prospective randomized trial of antioxidants (n = 20,536).

Subjects in the trial were at high risk for vascular disease end points, since all had suffered either previous vascular morbidity or were diabetic. The AOV regimen was 600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily for 5 years.

There was no significant effect of AOV on any measured end point. To the contrary, there was a small increase in LDL and triglyceride levels in persons receiving AOV compared to placebo recipients. This study concluded that recommendation of AOV supplementation is not justified.

Heart Protection Study Collaborative Group. Lancet. 2002;360:23-33.

Prolonged Erections Produced by Dihydrocodeine and Sildenafil

Unless used concomitantly with nitrates, the clinical safety profile of the PDE5 inhibitor sildenafil has been generally very good. Another popular method of erectile dysfunction (ED) treatment, intracavernosal injection, has been associated not uncommonly with the adverse effect of priapism, but this adversity has been noted only in anecdotal case reports with sildenafil. Goldmeier and Lamba report on 2 cases of patients with prolonged erections associated with the combination of dihydrocodeine and sildenafil.

In case 1, a man treated for ED with sildenafil 100 mg had been achieving adequate erections that detumesced appropriately with orgasm. After a minor shoulder injury, for which he was prescribed dihydrocodeine 30 mg, administration of the same sildenafil dose resulted in an erection that persisted 5 hours post-ejaculation. Four days later the patient experienced a 4-hour erection with the same combination. Omission of the dihydrocodeine subsequently restored his previous pattern of appropriate detumescence.

Case 2 describes a patient receiving 100 mg sildenafil for psychogenic ED, who also received dihydrocodeine for soft tissue injury. During the first week of narcotic administration, the patient experienced erections persisting 2-3 hours postejaculation, but this effect disappeared in the next 2 weeks, despite continued concomitant sildenafil-opioid administration. Goldmeier and Lamba state that acute opiate intake heightened cyclic GMP concentrations, resulting in prolonged erections. They suggest that persons receiving sildenafil be cautioned regarding this potential interaction. 

Goldmeier D, Lamba H. BMJ. 2002; 324:1555.

The Effect of Magnesium Supplementation of Blood Pressure: A Meta-Analysis of Randomized Clinical Trials

Magnesium (MAG) participates in vascular tone and reactivity by its involvement in Na-K transport. Parenteral high-dose MAG has been shown to reduce blood pressure (BP) in eclampsia and glomerulonephritis. Whether dietary intake of magnesium effects BP in healthy populations remains uncertain, since interventional trials have produced conflicting results. Jee and colleagues performed a meta-analysis of interventional MAG supplementation trials (n = 20 trials, with 1220 total subjects) to seek further clarification of the relationship between MAG and blood pressure.

Overall, MAG supplementation reduced BP by 0.6/0.8 mm Hg. There was a dose-response relationship, however, with BP reductions of 4.3/2.3 for each 10-mmol increase/day in MAG dose. This meta-analysis encourages the performance of an adequately powered interventional trial for ultimate confirmation of the potential role of MAG supplementation. 

Jee SH, et al. Am J Hypertens. 2002; 15:691-696.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.