A trial of micronutrient supplementation in patients with heart failure

  • Nicholas McKeag

Student thesis: Doctoral ThesisDoctor of Philosophy


Heart failure is a common condition in the Western world, particularly among elderly persons, and, with an ever-aging population, the incidence is expected to increase. Diet in the setting of heart failure is important—patients with this condition are advised to consume a low-salt diet and monitor their weight closely. Nutritional status of patients with heart failure is also important—those with poor nutritional status tend to have a poor long-term prognosis. A growing body of evidence suggests an association between heart failure and micronutrient status. Reversible heart failure has been described as a consequence of severe thiamin and selenium deficiency. However, contemporary studies suggest that a more subtle relationship may exist between micronutrients and heart failure. A small intervention study has suggested potential benefits of multiple micronutrient supplementation in patients with heart failure.

The aim of this thesis was to examine the effect of a multiple micronutrient supplement in a larger group of patients with chronic stable heart failure. This was performed by conducting a randomized, double-blind, placebo-controlled trial. Seventy-nine patients with chronic stable heart failure were randomized to treatment with a multiple micronutrient supplement (Table 2.1) or placebo.

The primary end-point of the study was left ventricular ejection fraction (TVEF), assessed using cardiovascular magnetic resonance imaging or 3-dimensional echocardiography. The secondary end-points were: quality of life (assessed using the Minnesota Living With Heart Failure Questionnaire), physical functioning (assessed using six-minute walk test distance), blood levels of N-terminal prohormone of brain natriuretic peptide, blood levels of C-reactive protein, blood levels of pro- and anti-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6 and interleukin- 10) and urinary levels of a marker of oxidative stress (8-iso-prostaglandin F2 alpha).

All end-points were assessed at baseline and after 12 months of treatment with the study medication. Compliance with the study medication was assessed by measuring blood levels of a number of micronutrients contained within the multiple micronutrient supplement. In addition, all patients completed the European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire at baseline and after 12 months of treatment with the study medication.

Analysis of the food frequency questionnaire, completed at baseline, revealed evidence of high intakes of protein, carbohydrate and fibre and sub-optimal intakes of the micronutrients riboflavin, vitamin A, vitamin D, calcium, magnesium, zinc and selenium in this population. However, there was evidence of bias in reporting of dietary intake within the sample.

Ninety-one percent of the population had evidence of vitamin D deficiency of sub- optimal status.

Blood levels of ferritin, vitamin D, vitamin B6, pyridoxal, vitamin B12, folate and vitamin A increased significantly in the active treatment group relative to placebo, indicating good compliance with the study medication. There was no evidence of a large change in dietary intake over the course of the study.

With respect to the primary end-point, complete follow-up data were available for 68 subjects (35 patients in the placebo group and 33 patients in the multiple micronutrient supplement group). There was no evidence of a significant effect of multiple micronutrient supplementation on LVEF. In addition, there was no evidence of a significant effect of multiple micronutrient supplementation on any of the secondary end-points.
This study, therefore, provides no evidence to support the routine treatment of such patients with chronic stable heart failure with a multiple micronutrient supplement.
Date of AwardJul 2013
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorPascal McKeown (Supervisor), Michelle McKinley (Supervisor), Mark Harbinson (Supervisor) & Jayne Woodside (Supervisor)

Cite this