Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Info for
    • Authors
    • Reviewers
  • About Us
    • About the Ochsner Journal
    • Editorial Board
  • More
    • Alerts
    • Feedback
  • Other Publications
    • Ochsner Journal Blog

User menu

  • My alerts
  • Log in

Search

  • Advanced search
Ochsner Journal
  • Other Publications
    • Ochsner Journal Blog
  • My alerts
  • Log in
Ochsner Journal

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Info for
    • Authors
    • Reviewers
  • About Us
    • About the Ochsner Journal
    • Editorial Board
  • More
    • Alerts
    • Feedback
Research ArticleOriginal Research

Effects of Thiamine on Cardiac Function in Patients With Systolic Heart Failure: Systematic Review and Metaanalysis of Randomized, Double-Blind, Placebo-Controlled Trials

James J. DiNicolantonio, Carl J. Lavie, Asfandyar K. Niazi, James H. O'Keefe and Tian Hu
Ochsner Journal December 2013, 13 (4) 495-499;
James J. DiNicolantonio
*Wegmans Pharmacy, Ithaca, NY and Saint Luke's Mid America Heart Institute, Kansas City, MO
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carl J. Lavie
†John Ochsner Heart and Vascular Institute, The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA, and Pennington Biomedical Research Center, Baton Rouge, LA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Asfandyar K. Niazi
‡Shifa College of Medicine, Islamabad, Pakistan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James H. O'Keefe
§Mid America Heart Institute at Saint Luke's Hospital, University of Missouri-Kansas City, Kansas City, MO
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tian Hu
||Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

Background Thiamine is an important micronutrient, and thiamine deficiency is prevalent in patients with congestive heart failure.

Methods Using Ovid MEDLINE, PubMed, and Excepta Medica (Embase), we conducted a systematic review and metaanalysis of randomized, double-blind, placebo-controlled trials of thiamine supplementation in patients with congestive heart failure.

Results Compared with placebo (2 trials, n=38), thiamine supplementation resulted in a significantly improved net change in left ventricular ejection fraction (LVEF) (3.28%, 95% confidence interval [CI]: 0.64%, 5.93%).

Conclusion Compared against placebo, thiamine supplementation in 2 randomized, double-blind trials resulted in a significant improvement in net change in LVEF. While further trials are required to establish thiamine's role in patients with systolic heart failure, thiamine may help to improve LVEF in these patients.

Keywords
  • Heart failure
  • stroke volume
  • thiamine deficiency

INTRODUCTION

Congestive heart failure (CHF) is a serious public health concern. Approximately 5 million people in the United States have CHF, and more than 550,000 people are diagnosed with this condition each year.1,2 Although therapies for CHF—including angiotensin-converting enzyme inhibitors, beta-blockers, loop diuretics, and omega-3 fatty acids—have improved morbidity and mortality, mortality rates in patients with CHF remain high.3

Loop diuretics have caused thiamine deficiency in animal and human trials, and the prevalence of thiamine deficiency in patients with CHF is 21%-98%.4-8 A 1995 trial indicated that thiamine supplementation in patients with CHF significantly improved left ventricular ejection fraction (LVEF); resulted in trends for improving left ventricular end-systolic volume (LVESV); and significantly improved New York Heart Association (NYHA) functional class, diuresis, and urinary sodium excretion.9 Thus, we sought to determine the effects of thiamine in patients with CHF by performing a systematic review and metaanalysis of available studies.

METHODS

We reviewed the available literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for conducting systematic reviews of intervention studies.10

Data Sources and Searches

We identified studies through searches of the following sources: Ovid MEDLINE (1997-2011), PubMed (1966-2012), and Embase (1997-2011). To identify further potentially relevant studies missed by the electronic database search, we manually screened reference lists from identified trials and review articles. Searches were restricted to articles written in the English language and were updated using automated weekly email alerts until December 2012.

Study Selection

We selected studies for inclusion on the basis of the following criteria:

  • Study design: Randomized, double-blind, placebo-controlled

  • Types of participants: Systolic HF (LVEF <45%)

  • Intervention: Thiamine

  • Comparator: Placebo

  • Outcomes: LVEF

We excluded studies that did not report LVEF. Two reviewers (JJD and TH) independently screened the titles and abstracts of studies identified by the search strategy and discarded clearly irrelevant studies.

Data Extraction

The following data elements were extracted from each study: the number of patients per arm; the nature of the intervention; patient inclusion criteria, baseline and follow-up blood pressure, heart rate, thiamine-pyrophosphate effect, and LVEF; details of follow-up, and HF etiology (Table 1).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 1.

Characteristics of Trials Included in the Metaanalysis

Data Synthesis and Analysis

The mean net change in LVEF was calculated by subtracting the mean change in the placebo group from the mean change in the thiamine group. Statistical heterogeneity across trials was estimated using Q test and I2 statistic.12 Specifically, P<0.05 in Q test indicates the presence of heterogeneity; I2<30% denotes low heterogeneity, I2=30-50% represents moderate heterogeneity, and I2>50% denotes substantial heterogeneity.13 Analyses were conducted using Stata, version 10 (StataCorp LP, College Station, TX).

RESULTS

Identification and Selection of Studies

The literature search yielded 154 titles, and we reviewed 7 of the 154 on the basis of the inclusion criteria (Figure 1). Of these 7, 2 studies were deemed eligible for inclusion.9,11 Table 1 summarizes the characteristics of the included studies, and Table 2 lists the excluded studies and the reasons for their exclusion.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Process for selecting trials included in this metaanalysis.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 2.

Details of Studies Excluded From the Metaanalysis

Characteristics of Included Studies

The included trials were randomized double-blind studies of thiamine supplementation compared to placebo in systolic HF patients. The trials enrolled a mean of 19 patients with a mean follow-up of 6 weeks.

Study Outcomes

In the study by Schoenenberger and colleagues (n=9), patients who took thiamine had 3.30% (95% confidence interval [CI]: 0.63%, 5.97%) greater LVEF compared to those on placebo.11 Likewise, Shimon et al reported that thiamine resulted in 2.20% greater LVEF than the placebo group (n=29), although the extra improvement was not significant (95% CI: −18.97, 23.37%).9 In our metaanalysis, thiamine supplementation resulted in a significantly improved net change in LVEF (3.28%, 95% CI: 0.64%, 5.93%) compared with placebo (2 trials; n=38; Figure 2). There was no heterogeneity in the results (P=0.92; I2=0.0%).

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Forest plot of net change in ejection fraction: thiamine vs placebo. CI, confidence interval.

DISCUSSION

The preferential improvement in LVEF with thiamine supplementation in patients with systolic HF may be a result of thiamine's direct action on cardiomyocytes (improved energy production and thus improved cardiac function) or may be attributable to a diuretic effect.9,14 A deterioration of LVEF is a powerful predictor of worsening CHF and death.15 Thus, it is possible that thiamine may even confer a reduction in all-cause mortality in patients with systolic HF through an improvement in LVEF.5,9,11 Mortality events were low in the study by Shimon et al: 0 deaths in the thiamine group vs 1 death in the placebo group (ie, 1-week treatment groups).9 Moreover, the Shimon et al study showed improvement in NYHA functional class, LVESV, diuresis, and urinary sodium excretion with the use of thiamine supplementation compared to placebo.9

The findings of this metaanalysis suggest that thiamine supplementation may benefit patients with systolic HF who are also receiving loop diuretics. Although current CHF guidelines do not recommend thiamine supplementation, the evidence discussed above seems to indicate that a large, multicenter trial should be performed to verify the benefit of thiamine in systolic HF patients.5,9,11,16,17

The prevalence of thiamine deficiency in HF patients ranges from 21%-98%.18 Several risk factors can contribute to thiamine deficiency in patients with and without heart failure such as inadequate dietary intake, excess alcohol ingestion, malabsorption syndromes, and medications (such as diuretics, phenytoin, penicillins, cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, sulfonamides, and trimethoprim).19 Comorbid conditions such as infection, trauma, surgery, cancer, fever, and persistent diarrhea and vomiting can also contribute to thiamine deficiency.19

Benefits of thiamine supplementation in patients with HF include improvements in end-systolic volume and NYHA functional class.9 Even patients with mild to moderate HF have shown significant improvements in LVEF and right ventricular area.11 Additionally, thiamine supplementation in HF patients has been shown to improve blood pressure, urine output, and functional capacity along with the LVEF improvement.5 Thus, thiamine supplementation may offer benefits beyond improvements in LVEF in patients with HF.

Some important potential study limitations should be considered. First, although the trials included in our metaanalysis were randomized, double blind, and placebo controlled, they included a small number of patients. However, comparing LVEF between thiamine and placebo showed no heterogeneity between trials (I2=0%). Also, as in most such metaanalyses, various dosages (200-300 mg/d) and formulations (intravenous and by mouth) were used, as typically occurs in clinical situations.

Despite these potential study limitations, we believe that the overall results of this metaanalysis support the use of thiamine in select systolic HF patients, especially those who are on loop diuretics (higher risk of thiamine deficiency) or who are symptomatic despite optimal medical therapy. Certainly, a larger, randomized, double-blind, placebo-controlled trial should be performed to confirm the results of this metaanalysis, as well as to assess thiamine's potential impact on major cardiovascular events, including mortality, in patients with systolic HF.

CONCLUSION

Compared against placebo, thiamine supplementation in 2 randomized, double-blind, placebo-controlled trials resulted in a significantly improved net change in LVEF. Further trials are required to establish thiamine's role in patients with systolic HF.

This article meets the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties Maintenance of Certification competencies for Patient Care and Medical Knowledge.

Footnotes

  • The authors have no financial or proprietary interest in the subject matter of this article.

  • © Academic Division of Ochsner Clinic Foundation

REFERENCES

  1. ↵
    1. American Heart Association
    (2005) (2005) Heart Disease and Stroke Statistics —(American Heart Association, Dallas, TX) Update.
  2. ↵
    1. Bonow RO,
    2. Bennett S,
    3. Casey DE Jr.,
    4. et al.
    (9 20, 2005) American Heart Association Task Force on Performance Measures (Writing Committee to Develop Heart Failure Clinical Performance Measures); Heart Failure Society of America. ACC/AHA clinical performance measures for adults with chronic heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Heart Failure Clinical Performance Measures) endorsed by the Heart Failure Society of America. J Am Coll Cardiol 46(6):1144–1178, pmid:16168305.
    OpenUrlFREE Full Text
  3. ↵
    1. Massie BM,
    2. Shah NB
    (6, 1997) Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. Am Heart J 133(6):703–712, pmid:9200399.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Yui Y,
    2. Itokawa Y,
    3. Kawai C
    (9, 1980) Furosemide-induced thiamine deficiency. Cardiovasc Res 14(9):537–540, pmid:7214397.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Seligmann H,
    2. Halkin H,
    3. Rauchfleisch S,
    4. et al.
    (8, 1991) Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med 91(2):151–155, pmid:1867241.
    OpenUrlCrossRefPubMed
    1. Brady JA,
    2. Rock CL,
    3. Horneffer MR
    (5, 1995) Thiamin status, diuretic medications, and the management of congestive heart failure. J Am Diet Assoc 95(5):541–544, pmid:7722187.
    OpenUrlCrossRefPubMed
    1. Hanninen SA,
    2. Darling PB,
    3. Sole MJ,
    4. Barr A,
    5. Keith ME
    (1 17, 2006) The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol 47(2):354–361, pmid:16412860.
    OpenUrlFREE Full Text
  6. ↵
    1. Zenuk C,
    2. Healey J,
    3. Donnelly J,
    4. Vaillancourt R,
    5. Almalki Y,
    6. Smith S
    (Winter 2003) Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol 10(4):184–188, pmid:14712323.
    OpenUrlPubMed
  7. ↵
    1. Shimon I,
    2. Almog S,
    3. Vered Z,
    4. et al.
    (5, 1995) Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med 98(5):485–490, pmid:7733128.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Liberati A,
    2. Altman DG,
    3. Tetzlaff J,
    4. et al.
    (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ, Jul 21;339:b2700.
  9. ↵
    1. Schoenenberger AW,
    2. Schoenenberger-Berzins R,
    3. der Maur CA,
    4. Suter PM,
    5. Vergopoulos A,
    6. Erne P
    (3, 2012) Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study. Clin Res Cardiol 101(3):159–164, pmid:22057652, Epub 2011 Nov 5.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Higgins JP,
    2. Thompson SG
    (6 15, 2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558, pmid:12111919.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Higgins JPT,
    2. Green S
    (2, 2008]) (2008) Cochrane Handbook for Systematic Reviews of Interventions (John Wiley & Sons Inc, Hoboken, NJ) Version 5.0.0 [updated, The Cochrane Collaboration.
  12. ↵
    1. Bakker SJ,
    2. Leunissen KM
    (9, 1995) Hypothesis on cellular ATP depletion and adenosine release as causes of heart failure and vasodilatation in cardiovascular beriberi. Med Hypotheses 45(3):265–267, pmid:8569549.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Cintron G,
    2. Johnson G,
    3. Francis G,
    4. Cobb F,
    5. Cohn JN
    (6, 1993) Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 87((6 Suppl)):VI17–VI123, pmid:8500235.
    OpenUrlPubMed
  14. ↵
    1. Jessup M,
    2. Abraham WT,
    3. Casey DE,
    4. et al.
    (2009) (2009) focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119(14):1977–2016, pmid:19324967, Apr 14; Epub 2009 Mar 26.
    OpenUrlFREE Full Text
  15. ↵
    1. Krim SR,
    2. Campbell P,
    3. Lavie CJ,
    4. Ventura H
    (3, 2013) Micronutrients in chronic heart failure. Curr Heart Fail Rep 10(1):46–53, pmid:23070580.
    OpenUrlCrossRefPubMed
  16. ↵
    1. Wooley JA
    (Oct-Nov 2008) Characteristics of thiamin and its relevance to the management of heart failure. Nutr Clin Pract 23(5):487–493, pmid:18849553.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Dinicolantonio JJ,
    2. Niazi AK,
    3. Lavie CJ,
    4. O'Keefe JH,
    5. Ventura HO
    (7, 2013) Thiamine supplementation for the treatment of heart failure: a review of the literature. Congest Heart Fail 19(4):214–222, pmid:23910704.
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

Ochsner Journal
Vol. 13, Issue 4
Dec 2013
  • Table of Contents
  • Index by author
Print
Download PDF
Email Article

Thank you for your interest in spreading the word on Ochsner Journal.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Effects of Thiamine on Cardiac Function in Patients With Systolic Heart Failure: Systematic Review and Metaanalysis of Randomized, Double-Blind, Placebo-Controlled Trials
(Your Name) has sent you a message from Ochsner Journal
(Your Name) thought you would like to see the Ochsner Journal web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Effects of Thiamine on Cardiac Function in Patients With Systolic Heart Failure: Systematic Review and Metaanalysis of Randomized, Double-Blind, Placebo-Controlled Trials
James J. DiNicolantonio, Carl J. Lavie, Asfandyar K. Niazi, James H. O'Keefe, Tian Hu
Ochsner Journal Dec 2013, 13 (4) 495-499;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Effects of Thiamine on Cardiac Function in Patients With Systolic Heart Failure: Systematic Review and Metaanalysis of Randomized, Double-Blind, Placebo-Controlled Trials
James J. DiNicolantonio, Carl J. Lavie, Asfandyar K. Niazi, James H. O'Keefe, Tian Hu
Ochsner Journal Dec 2013, 13 (4) 495-499;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • INTRODUCTION
    • METHODS
    • RESULTS
    • DISCUSSION
    • CONCLUSION
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • References
  • PDF

Cited By...

  • Recent Publications by Ochsner Authors: October 2013 - March 2014
  • Google Scholar

More in this TOC Section

  • Adductor Canal Blocks Are Not Associated With Improved Early Postoperative Outcomes in Patients Undergoing Total Knee Arthroplasty
  • Differential Impact of Body Mass Index in Hip Arthroscopy: Obesity Does Not Impact Outcomes
  • Revision Carpal Tunnel Release With Umbilical Cord Allograft: A Four-Year Retrospective Cohort Study
Show more ORIGINAL RESEARCH

Similar Articles

Keywords

  • heart failure
  • stroke volume
  • thiamine deficiency

Current Post at the Blog

American Association for the Advancement of Science Surveys Scientists About Article Publishing Charges—And Uncovers More Problems

Our Content

  • Home
  • Current Issue
  • Ahead of Print
  • Archive
  • Featured Contributors
  • Ochsner Journal Blog
  • Archive at PubMed Central

Information & Forms

  • Instructions for Authors
  • Instructions for Reviewers
  • Submission Checklist
  • FAQ
  • License for Publishing-Author Attestation
  • Patient Consent Form
  • Submit a Manuscript

Services & Contacts

  • Permissions
  • Sign up for our electronic table of contents
  • Feedback Form
  • Contact Us

About Us

  • Editorial Board
  • About the Ochsner Journal
  • Ochsner Health
  • University of Queensland-Ochsner Clinical School
  • Alliance of Independent Academic Medical Centers

© 2023 Ochsner Clinic Foundation

Powered by HighWire