Do antioxidants increase death rates, and if so, why?

A recent systematic review published in the Journal of the American Medical Association, Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention, concluded: "Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study." The study aroused a few howls of indignation, for example from Alan Gaby, M.D., who claimed that the "exclusion of certain trials skewed results"; that may be, but the study's methodology was specifically designed to exclude biased studies.

Antioxidants enjoy a sterling reputation among the better-educated, mainly those wanting to take charge of their own health. We've been bombarded with the message over the past few decades about free radicals being responsible for aging and assorted illnesses, and that antioxidant supplements will help avoid common health problems by quenching free radicals. Given that bombardment, the average intelligent person, including the aforementioned Dr. Gaby, probably scratched his head in wonder that antioxidants could possibly increase death rates.

However, at least two recent studies have found that antioxidants prevent increases in insulin sensitivity, whether by exercise or diet. It's now becoming increasingly clear that insulin levels correlate with cancer. For example, in Metabolic syndrome, hyperinsulinemia, and colon cancer: a review, we read:

An impressive body of epidemiologic data collected over the past decade indicates that the risk of colon cancer is elevated in those with metabolic syndrome. This evidence includes studies that examined the risk of colon cancer or adenoma in relation to determinants of the metabolic syndrome (obesity, abdominal distribution of adiposity, and physical inactivity), clinical consequences of this syndrome (type 2 diabetes and hypertension), plasma or serum components of the definition of metabolic syndrome (hypertriglyceridemia, hyperglycemia, and low HDL cholesterol), and markers of hyperinsulinemia or insulin resistance (insulin and C-peptide), which is the underlying metabolic defect of the metabolic syndrome. The mechanism underlying these associations is unknown but may involve the influence of hyperinsulinemia in enhancing free or bioavailable concentrations of insulin-like growth factor-1. Future studies should also be based on better measurements of insulin resistance, beta-cell depletion, and insulin responses to better assess which aspects of insulin resistance are most closely related to the risk of colon neoplasia.

Or there's a review by Gerald Reaven of Stanford, the man responsible for identifying the metabolic syndrome, Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Very likely increased insulin levels and insulin resistance are responsible for heart disease as well as cancer, or at least in a great many cases.

Antioxidants prevent dietary or exercise-induced lowering of insulin levels, so they may very well promote cancer, heart disease, diabetes, and all the other diseases of civilization. That is why the result of the review, that antioxidants increase the death rate, is both plausible and biologically credible.