The available evidence indicates thatγ-tocopherol has more potential for colon cancer prevention thanα-tocopherol, but little is known about the effects of foods and supplements on tocopherol levels in human colon. This study randomized 120 subjects at increased colon cancer risk to either a Mediterranean or a Healthy Eating diet for 6 mo. Supplement use was reported by 39% of the subjects, and vitamin E intake from supplements was twofold higher than that from foods. Serumα-tocopherol at baseline was positively predicted by dietary intakes of synthetic vitamin E in foods and supplements but not by naturalα-tocopherol from foods. For serumγ-tocopherol, dietaryγ-tocopherol was not a predictor, but dietary α-tocopherol was a negative predictor. Unlike with serum, the data supported a role for metabolic factors, and not a direct effect of diet, in governing concentrations of bothα- andγ-tocopherol in colon. The Mediterranean intervention increased intakes of naturalα-tocopherol, which is high in nuts, and decreased intakes ofγ-tocopherol, which is low in olive oil. These dietary changes had no significant effects on colon tocopherols. The impact of diet on colon tocopherols therefore appears to be limited.