High-dose Multivitamins Adversely Affect Coronary Plaque Composition

VANCOUVER (Reuters Health) – High-dose multivitamin supplements promote the development of fibrosis at the site of angioplastic intervention, according to findings presented by Montreal investigators during the Canadian Cardiovascular Congress 2000.

This effect may help explain why high-dose multivitamins did not prevent restenosis or improve vascular remodeling in the Multi-Vitamins and Probucol Trial (MVP), previously reported by the Montreal group. The MVP trial involved 317 patients who were randomly assigned to either probucol 500 mg b.i.d., or 700 IU vitamin E plus 500 mg vitamin C plus 30,000 IU beta carotene b.i.d., or both, or placebo. Treatment was started 30 days before undergoing angioplasty and was continued for six months following the procedure.

To determine the effect of high-dose multivitamin supplementation on plaque composition, intravascular ultrasound (IVUS) was used to assess 111 segments in 94 patients analyzed at follow-up.

“The changes we saw in plaque content on IVUS are compatible with an increase in fibrosis in the arterial wall at the site of angioplasty,” Dr. Jean-Claude Tardif, director of clinical research, Montreal Heart Institute told Reuters Health, “and in relation to angioplasty, fibrosis prevents the process of beneficial vascular remodeling, which is not good.”

Dr. Tardif also noted that these observations are “entirely compatible” with their previously reported findings from the MVP trial.

The doses of the vitamins used in the MVP trial were very high, but as Dr. Tardif explained, the trial was started in 1994. “At that time we did not want to be criticized for not giving high enough doses of multivitamins, so yes, you could say that the doses we used were high. But it’s also important for people to realize that vitamins are not as benign as they think they are, especially when taken in high doses.”

Findings from the MVP trial indicated that probucol decreased the rate of stenosis by 50% and late luminal loss by 68%, which was “quite a dramatic effect,” Dr. Tardif observed. However, concerns about adverse effects related to probucol, including a reduction in high density lipoprotein levels, led to its subsequent withdrawal from the market.

Montreal researchers are now working with a probucol analog that maintains the same potent antioxidant effects as the original formulation had, without incurring the same unwanted effects.

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