Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial.

BACKGROUND: Thiamin, a water-soluble B-complex vitamin, functions as a coenzyme in macronutrient oxidation and in the production of cellular ATP. Data suggest that thiamin depletion occurs in heart failure (HF). Therefore, thiamin supplementation in HF patients may improve cardiac function. OBJECTIVE: We sought to determine whether oral thiamin supplementation improves left ventricular ejection fraction (LVEF), exercise tolerance, and quality of life among patients with HF and reduced LVEF. METHODS: In this prospective, multicenter, double-blind, placebo-controlled randomized trial, eligible ambulatory patients with HF and reduced LVEF were recruited from 4 academic and community hospitals between 2010 and 2015. Participants were randomly assigned to receive either 200 mg oral thiamin mononitrate per day or placebo for 6 mo. RESULTS: Sixty-nine patients (mean ± SD age: 64 ± 12 y; 83% men; LVEF: 37% ± 11%) were randomly assigned: 34 received placebo and 35 received thiamin supplementation. Erythrocyte thiamin pyrophosphate and urine thiamin concentrations were significantly higher in the supplemented group than in the placebo group at 6 mo (P = 0.02 and <0.001, respectively). At 6 mo, LVEF was significantly higher in the placebo group than in the thiamin group (38%; 95% CI: 36%, 39% compared with 35%; 95% CI: 33%, 37%, P = 0.047) after adjusting for baseline measurements. There were no significant differences in Minnesota Living with Heart Failure score, distance walked in 6 min, and N-terminal prohormone of brain natriuretic peptide concentrations between the 2 groups. One patient (2.9%) in the thiamin-supplemented group and none in the control group died at 6 mo. CONCLUSIONS: In ambulatory patients with HF and reduced LVEF, thiamin supplementation for 6 mo did not improve LVEF, quality of life, or exercise capacity, despite increases in thiamin concentrations. These findings do not support routine thiamin supplementation in the treatment of HF and reduced LVEF.This trial was registered at clinicaltrials.gov as NCT00959075.

Prevalence of Thiamin Deficiency in Ambulatory Patients with Heart Failure.

BACKGROUND: Thiamin is a required coenzyme in energy production reactions that fuel myocardial contraction. Therefore, thiamin deficiency (TD) may aggravate cardiac dysfunction in patients with systolic heart failure (HF). OBJECTIVE: To determine the prevalence of TD in ambulatory participants with HF as well as the relationships between thiamin status and HF severity, dietary thiamin intake, diuretic use, and circulating neurohormones. DESIGN: A cross-sectional study comparing the prevalence of TD in ambulatory patients with HF with that of controls. Demographic, anthropometric, nutrition, medication use, and heart function data were collected from direct interviewing, questionnaires, and medical records. Blood samples were obtained to measure levels of neurohormones and assess TD. PARTICIPANTS/SETTING: Fifty age-matched control participants without HF and 100 outpatients with HF and reduced left ventricular function were recruited from clinics at St Michael's Hospital, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada, between September 2009 and February 2011. MAIN OUTCOME MEASURES: To assess TD, erythrocyte thiamin pyrophosphate (TPP) was measured using high-performance liquid chromatography. TD was defined as TPP<6.07 µg/dL (180 nmol/L). STATISTICAL ANALYSES PERFORMED: Prevalence rates were analyzed using χ2 test. Nonparametric statistics (Jonckheere-Terpstra, Kruskal-Wallis, Spearman's correlation) were used to assess TPP levels in relation to HF severity, medication use and plasma concentrations of F2-isoprostanes, norepinephrine, and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: There was no significant difference in the prevalence of TD in outpatients with HF (6%) and controls (6%) (P=0.99). No relationship was found between heart function, thiamin intake, use or dose of diuretics, and TD. A positive relationship was observed between erythrocyte TPP and F2-isoprostane levels (rs=0.22, P=0.03) but not between erythrocyte TPP and norepinephrine (P=0.45) and NT-proBNP (P=0.58). CONCLUSION: The prevalence of TD was low in ambulatory HF participants suggesting that, unlike hospitalized patients, ambulatory patients may be at a low risk for TD.

Thiamin deficiency and heart failure: the current knowledge and gaps in literature.

The management of heart failure (HF) represents a significant challenge for both patients as well as the healthcare system in industrialized countries. Thiamin is a required coenzyme in the energy-producing reactions that fuel myocardial contraction. Therefore, thiamin deficiency (TD) may contribute to myocardial weakness by limiting the energy available for contraction. Previous studies have reported a wide range in the prevalence of TD in patients with HF (3-91 %). The impact of thiamin supplementation in patients with HF is inconclusive. Studies conducted to date are limited by their small sample size, indirect methods of assessing thiamin concentration, methodological inconsistencies, use of impractical means of thiamin supplementation, a focus on hospitalized patients, and lack a robust technique for the assessment of cardiac function. Future large prospective studies and randomized controlled trials are needed to improve our understanding of any change in nutritional requirements associated with chronic disease as well as the clinical benefit of supplementation.

The role of B vitamins in the management of heart failure.

Heart failure (HF) is the leading cause of morbidity and mortality in industrialized countries, creating a significant burden on both the healthcare system and quality of life. Research efforts continue to explore new pharmaceutical or surgically based approaches to HF management, but the role of nutrition as an adjunct therapy has been largely ignored. Elderly age, anorexia, malabsorption, premature satiety, and disease severity are among the factors identified as contributing to reduced nutrient intakes in patients with HF. These factors suggest that patients with HF are at increased risk of multiple-nutrient deficiencies, including B vitamins. B vitamins may be of particular therapeutic interest because of their key roles as cofactors in energy-producing pathways. Recently, impaired stores of high-energy compounds have been linked with myocardial dysfunction and prognosis in patients with HF. Therefore, deficiencies of B vitamins might contribute to reduced energy stores and disease progression. This review summarizes the existing literature both with respect to the prevalence of B vitamin deficiency as well as evidence from supplementation trials in patients with HF. The findings suggest that most of the literature in this area has focused on thiamin deficiency in patients with HF, whereas other B vitamins remain largely unstudied. Although few sporadic trials suggest a role for B vitamins in the management of HF, none are conclusive. Therefore, there is a need for larger, more robust trials to assist in defining the B vitamin requirements as well as the impact of supplementation on both morbidity and mortality in patients with HF.