James J. DiNicolantonio, PharmD
Saint Luke’s Mid America Heart Institute
4401 Wornall Road 600
Kansas City, MO 64111
(607) 738-8853
jjdinicol@gmail.com

“Thiamine Supplementation for the Treatment of Heart Failure: A Review of The Literature,”
Congest Heart Fail, 2013 Jul-Aug;19(4):214-22. 30309 (3/2014)

Kirk Hamilton: Can you please share with us your educational background and current position?

James J. DiNicolantonio: I am a Doctor of Pharmacy as well as a cardiovascular research scientist at

Saint Luke’s Mid America Heart Institute.

KH: What got you interested in studying the role of thiamine (vitamin B1) in heart failure?

JJD: I had read numerous articles on the benefits of thiamine supplementation in patients with heart failure and decided to perform a systematic review to see what the overall effect and outcomes were with supplemental thiamine in heart failure patients.

KH: Is heart failure increasing in frequency? What are the hypothesized causes of this increase?

JJD: The prevalence of heart failure is indeed increasing in the United States. The most likely scenario is the toxic dietary environment that we currently live in (high in refined, processed, sugary foods), which lead to insulin resistance, hypertension and probably ultimately to heart failure.

KH: How about this hypothesis of why there is increasing heart failure. I totally agree with your comments on a “toxic dietary environment” that increases risk factors to heart failure. But how about a synergy between a rapidly expanding aging population; plus medications, such as the massive use of statins, while improving some dynamics of vascular health and inflammation, ultimately reduce energy production in the heart muscle by blocking CoQ10 production leading to a weakened heart; plus we have more pharmacology and technology to keep a sick heart pumping, or rescue people from sudden death, leaving a heart with reduced energy production capacity and increased risk to subsequent failure? Said in a more concise fashion, I believe some of our modern medical therapies, while keeping people alive, are actually weakening the energy production capacity of our hearts leading to more failure.

JJD: Certainly an aging population will contribute to an increased prevalence of heart failure. Another possible contributor could be the recommendations (including the AHA) and other heart failure societies for severe sodium restriction. Several randomized trials in patients with systolic heart failure have shown that restricting intake to 1.8 grams of sodium per day actually increases death and heart failure readmissions in patients with systolic heart failure compared to a more normal sodium intake of 2.8 grams of sodium per day. Thus, the very strict AHA recommendations to restrict sodium to < 1.5 grams per day in this population could be causing more harm than good in these patients.  In regards to statins possibly increasing heart failure due to a reduction in CoQ10, I am not so sure about the clinical relevance of the reduction in CoQ10 with statins and worsening heart failure. I think the data is more compelling with statins reducing CoQ10 in relation to worsening myalgia (muscle pain), which I have pointed out in prior publications (i.e. DiNicolantonio JJ. CoQ10 and L-carnitine for statin myalgia? Expert Rev Cardiovasc Ther. 2012 Oct;10(10):1329-33. doi: 10.1586/erc.12.92. Review.). While atorvastatin is one of the most notorious statins for lowering CoQ10 levels its lipophilic properties actually allow it to penetrate into cardiomyocytes (heart cells) where it seems to have antioxidative properties and perhaps even giving it a greater ability to lower oxidative LDL concentrations in the heart versus non-lipophilic statins. I have published data before showing that Lipitor actually increases left ventricular ejection fraction, lowers brain natriuretic peptide, and lower cardiac sympathetic nervous system activity (which are all very good things, especially in heart failure patients), where none of these benefits were shown with rosuvastatin (DiNicolantonio JJ, Lavie CJ, Serebruany VL, O’Keefe JH. “Statin wars: the heavyweight match–atorvastatin versus rosuvastatin for the treatment of atherosclerosis, heart failure, and chronic kidney disease.” Postgrad Med. 2013 Jan;125(1):7-16. doi: 10.3810/pgm.2013.01.2620. Review.). Additionally, atorvastatin has been shown to reduce heart failure hospitalizations and mortality in those with heart failure (although these trials were not specifically designed to test these outcomes in this population), which varies from the two negative heart failure trials testing rosuvastatin (CORONA and GISSI-HF).

KH: What is the biochemistry of thiamine that might alter the pathophysiology of heart failure?

JJD: Most heart failure patients are on loop diuretics, which deplete the body of thiamine. Thus,supplemental thiamine will replace what has been lost by these medications, and can improve myocardial energetics. This will subsequently improve heart failure outcomes because the heart can now work more efficiently. There is also the likely mechanism that thiamine has inherent benefits of its own such as vasodilation, reducing after load, and thus improving ejection fraction and symptoms of heart failure.

KH: What was the therapeutic daily dose range of thiamine used in these studies? How was it taken? With meals or away from meals? In a single dose or divided dose?

JJD: Here is a table from our publication where we recommend what doses of thiamine for what situation.

TABLE V. Dosage for Thiamine
Recommended Daily Allowance: 1.1–1.2 mg/d Orally
Supplemention:

• Risk of thiamine deficiency – 100 mg 3 times daily until thiamine levels normalize
• Proven thiamine deficiency – 200 mg 3 times daily until thiamine levels normalize
• Alcoholics without encephalopathy – 50 mg/d orally
• Patients on a refined grain diet – 5–15 mg/d orally
• Mild neuropathy – 10–20 mg/d orally for 2 weeks
• Severe neuropathy – 20–30 mg/d orally for several weeks
• Wet beriberi -100 mg/d intravenous for several days
• Prophylactic dose in heart failure – 10–20 mg/d orally

KH: Were blood levels of thiamine, erythrocyte transketolase, or other functional tests of vitamin B1 status, or other biochemical markers taken before, during or after the interventions? If so did they correlate with symptoms and supplementation with vitamin B1?

JJD: In one trial – Shimon et al 1995, thiamine pyrophosphate effect (%) was measured at baseline and at end of study, which did correlate with thiamine benefit.

KH: Can you tell us about your study and the basic results?

JJD: The systematic review showed that thiamine deficiency is not uncommon in those with heart failure, and that thiamine supplementation in patients with heart failure may improve cardiac function, urine output, weight loss, and signs and symptoms of heart failure.

KH: Were there any side effects with the thiamine therapy? How was the patient compliance?

JJD: Thiamine seems to be extremely well tolerated without any noted side effects. It did not seem apparent how compliant patients were to thiamine in the trials (even in large trials it is hard to find data relating to compliance in interventional treatments).

KH: Who is a candidate for thiamine therapy? All subjects with heart failure? Only those with a proven deficiency of thiamine?

JJD: The Table above should help to ascertain who/what situations thiamine supplementation may be

KH: Are not diuretics a risk factor for thiamine-induced heart failure?

JJD: Loop diuretics, especially at higher doses, have been shown to produce thiamine deficiency. One study showed that furosemide at 80 mg/day or higher lead to 98% of patients being thiamine deficient.

KH: Are there any other nutraceuticals that you might use along with thiamine in heart failure patients (i.e. CoQ10, carnitine, magnesium, ribose, lipoic acid, etc.)?

JJD: There is data that CoQ10 may improve mortality in heart failure patients (QSYMBIO trial) and CoQ10 with selenium 200mg/day may also improve mortality (this was shown in a relatively recent randomized trial as well – Alhagen 2012 Int J Cardiol). L-carnitine has been shown to also improve mortality in cardiomyopathy patients in a randomized trial (Rizos 2000, Am Heart J). While ribose and lipoic acid may theoretically improve outcomes in heart failure patients, but I am unaware of any randomized trials showing this.

In a placebo-controlled study, magnesium orotate (6 g daily for one month, 3 g daily for 11 months) in patients with severe congestive failure, showed a 75.7% survival rate in the orotate group versus a significantly less survival rate (51.5%) in those receiving placebo (p<0.05). (Stepura OB, Martynow AI. Magnesium orotate in severe congestive heart failure (MACH). Int J Cardiol 2009 May 1;134(1):145-7.)

The best evidence comes from GISSI-HF, where 1 gram of EPA/DHA significantly improved mortality in almost 10,000 patients with heart failure. This is why the new 2013 Heart Failure guidelines give a recommendation from fish oil (EPA/DHA) in this population.

KH: How can the public or health professionals use this information?

JJD: I hope that this will help clinicians and patients realize that supplements (along with diet and medications) may improve multiple disease states, and hopefully will bring more awareness to the fact that currently we are not testing for thiamine deficiency on a regular basis in those with heart failure or those on loop diuretics. And also that we are certainly not using the most appropriate tests to verify thiamine deficiency (which are not even readily available to most clinicians).

KH: While I don’t do more functional tests, like erythrocyte transketolase, routinely in patients, I routinely do serum thiamine blood levels on almost all my elderly patients and frequently find deficiencies. These serum levels can be easily ordered through a major laboratory like, Quest Laboratories. And, Medicare for now pays for it. So there should be no excuse for physicians, except for ignorance or apathy towards nutritional compounds to treat disease, to not screen for thiamine status. Any comments? JJD: I agree that there is no excuse for not picking up thiamine deficiency. More importantly, thiaminedeficiency occurs in the cell well before it can be shown out in the serum. Thus, someone can have a normal blood thiamine level and actually be quite deficient in thiamine. On the same note, if someone is deficient in thiamine via a serum measurement, they have probably been thiamine deficient for some time, but better late than never.

KH: Do you have any further comments on this very interesting subject?

JJD: We recently published a meta-analysis showing that thiamine supplementation in randomized, double-blind, placebo-controlled trials significantly improves left ventricular ejection fraction in systolic heart failure patients (Dinicolantonio JJ, Lavie CJ, Niazi AK, O’Keefe JH, Hu T. Effects of thiamine on cardiac function in patients with systolic heart failure: systematic review and metaanalysis of randomized, double-blind, placebo-controlled trials. Ochsner J. 2013 Winter;13(4):495-9.). For more details, here is the link to that publication: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865826/

KH: Thank you very much for participating in this interview and sharing your expertise on this subject.

JJD: Thank you for giving me the opportunity to share my thoughts on our recent publication.

Story Source and PDF of Interview
PubMed Reference
Journal Reference