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

Abstract

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.

Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?

“…Whereas the trial led by Seligmann et al in the nineties showed that the beneficial effect of thiamine on left ventricular ejection fraction was associated with better functional capacity (improved by at least one NYHA class) [ 153 ], it was confirmed in a more recent study by Schoenenberger et al in which no change in walking time was observed in patients with improved left ventricular ejection fraction after thiamine supplementation period [ 165 ]. This raises questions about the real usefulness of thiamine supplementation in HF therapy, especially as other trials failed to demonstrate any benefit of vitamin B1 (dose ranging from 100 mg to 300 mg per day) although thiamine circulating level increased [ 15 , 166 , 167 , 168 ]. These studies not only failed to show a beneficial effect on cardiac function (FE) [ 15 , 167 ] but also failed to show an improvement in the quality of life of HF patients [ 15 , 166 , 167 , 168 ].…”

“…This raises questions about the real usefulness of thiamine supplementation in HF therapy, especially as other trials failed to demonstrate any benefit of vitamin B1 (dose ranging from 100 mg to 300 mg per day) although thiamine circulating level increased [ 15 , 166 , 167 , 168 ]. These studies not only failed to show a beneficial effect on cardiac function (FE) [ 15 , 167 ] but also failed to show an improvement in the quality of life of HF patients [ 15 , 166 , 167 , 168 ]. So far, the evaluation of thiamine supplementation as a new tool in HF therapeutics has shown mixed results and conclusions from the aforementioned studies are not clear because of the small sample size, short duration of follow-up, lack of any dietary assessment of thiamine intake, as well as the lack of precisely defined inclusion criteria.…”

“…Vitamin supplementations have already been part of treatments of specific diseases for many years [ 11 , 12 ] and have also been tested in the frame of HF with variable degrees of success [ 13 ]. However, conflicting results from a series of small clinical studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ] only showed that more research is needed to better define which type of vitamin supplementation protocol should be implemented and which HF etiologies and stages of the syndrome should selectively be targeted by these potential treatments. To face the profound metabolic disorders described in HF, the big family of B vitamins are emerging as promising supplements to manage HF for two main reasons; first, B vitamins are highly involved in numerous elementary processes of cardiac energy metabolism [ 21 ] and second, B vitamins are deficient in HF patients due to the use of diuretics, malnutrition, and advanced age [ 22 , 23 ].…”

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF)

“…Another trial of 50 stable HFrEF patients (mean age 61.4 years) showed no change to LVEF after 1 month of thiamine supplementation (300mg/day), but there was an improvement in patient-reported peripheral edema [7]. A recent trial of 69 stable HFrEF patients (mean age 56.7 years) found no changes in LVEF and NT-proBNP after 6 months of thiamine supplementation (200mg/day) [8].…”

“…Older adults aged ≥65 years are more susceptible to thiamine deficiency [4], and may be more likely to benefit from thiamine supplementation. The two negative trials of thiamine supplementation did not enrich their sample for older age [7,8]. In addition, older adults are often underrepresented in randomized trials of pharmacologic agents in HF as they may not tolerate the target doses of HF medications or may have comorbidities that lead to exclusion [9].…”