Methods and results Thirty CHF patients [age 75.4 (0.7), mean (SEM), LV ejection fraction (LVEF) 35%] were randomized to receive capsules containing a combination of high-dose micronutrients (calcium, magnesium, zinc, copper, selenium, vitamin A, thiamine, riboflavin, vitamin B6, folate, vitamin B12, vitamin C, vitamin E, vitamin D, and Coenzyme Q10) or placebo for 9 months in a double-blind fashion. All subjects were on stable optimal medical therapy for at least 3 months before enrolment. At randomization and at study end, tumour necrosis factor- and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute walk test and QoL were assessed. Cardiac magnetic resonance scanning was performed to evaluate cardiac dimensions and LVEF. Two patients died during follow-up. The remaining patients (14 randomized to placebo and 14 to micronutrients) were well matched for LV function, symptoms, and exercise capacity. At the end of the follow-up period, LV volumes were reduced in the intervention group with no change in the placebo group [–13.1 (17.1)% vs. +3.8 (10.0)%; P<0.05]. LVEF increased by 5.3±1.4% in the intervention group and was unchanged in the placebo group (P<0.05). Patients taking micronutrients also had a significant improvement in QoL score between enrolment and study end [+9.5 (1.6)%; P<0.05], whereas those taking placebo had a slight deterioration [–1.1 (0.8)%; P=0.12]. Six-minute walk test and inflammatory cytokine levels remained unchanged in both groups.