Thiamine &Heart FailureELIZABETH BAUGH, DIETETIC INTERNAPRIL 27, 2016

About Me

Dietetic Intern Coordinated Program in Dietetics

Purdue University Pre and post presentation questionnaires Disclosure: no relevant financial or

nonfinancial relationships to disclose.

Overview

Goal & Objectives Introduction to thiamine

Intake, absorption, storage, RDA’s, toxicity & supplements Deficiency

Types, symptoms, at risk populations Medications & Research Our Contribution

Goal

To educate clinical nutrition staff of the benefits of initiation of thiamin supplementation for heart failure patients as a routine part of the initial nutrition assessment

Currently there are no hospital guidelines for thiamine supplementation initiation

Objectives

Understand the benefits of thiamine supplementation in the hospital setting

Determine when a patient may be at a higher risk for thiamine deficiency based off medical history and food recall

Recognize mediations that can have an adverse effect on thiamine levels

Understand dosing for thiamine deficiency

Introduction

Introduction

Thiamine (thiamin), Vitamin B1 Water soluble Energy, metabolism, growth & cell development Coenzyme & non-coenzyme functions Synthesis of pentose Used in the Krebs cycle for NADH production Membrane and nerve conduction Synthesized in large intestine, unknown amount

Dietary Intake

Meats - Pork Whole grains, enriched & fortified - cereals, brown rice Harmful: heating, pH>8, anti-thiamine factors Two forms: free form & phosphorylated form (TPP or TDP)

Image: http://www.namrata.co/wp-content/uploads/2012/08/T1.bmp

Absorption & Storage

Most effective upper jejunum Phosphorylated form

Hydrolyzed before absorption Dietary sources: active transport Pharmacological doses: passive diffusion Low intake absorption increases

No noticeable storage 40% is stored in muscle

Half-life is 9.5 to 18.5 days, regular supply Adult: 25-30mg, 80% is TPP form

Recommended Dietary Allowance for Thiamine

Age Male Female Pregnant or lactating

Birth – 6 months 0.2mg 0.2mg  

7-12 months 0.3mg 0.3mg  

1-3 years 0.5mg 0.5mg  

4-8 years 0.6mg 0.6mg  

9-13 years 0.9mg 0.9mg  

14-18 years 1.2mg 1.0mg 1.4mg

19-50 years 1.2mg 1.1mg 1.4mg

51+ years 1.2mg 1.1mg  

Usual Intake

Deficiency is rare due to many fortified and enriched foods

U.S. population with intake below EAR – 6%

Average dietary intake: Men – 1.95mg/d Women – 1.39mg/d

Average dietary & supplements intake: Men – 4.89mg/d Women – 4.9mg/d

Toxicity

No upper levels established

Lack of toxicity Rapid decline in absorption – intake >5mg Water soluble

Intravenous thiamine supplement Headaches, convulsions, cardiac arrhythmias, anaphylactic shock Administration should be dispersed over 30 minutes

Supplements

Multivitamin – 1.5mg of thiamine – 100% of DV Forms: Thiamine mononitrate & Thiamine hydrochloride

Stable & water soluble

World Health Organization (WHO) recommendations for adults

50-100mg/day

10mg/day 3-5mg/day Total time

Mild deficiency

Oral, 1 week Oral, 6 weeks 7 weeks

Severe deficiency

Intravenous, 1 week

Intravenous, 1 week

Oral, 6 weeks 8 weeks

Measurement

Offered with IU HealthWhole blood

measurement Direct measurement of

erythrocyte TPP More sensitive than ETKA Whole blood testing

90% of thiamine content of whole blood is TPP form

Cost & time

Not offered with IU HealthPlasma blood measurement <10% of thiamine is in plasma Low specificity & sensitivity Urinary Thiamine excretion, not tissue storage Erythrocyte transketolase

activity (ETKA) measurement

actual level of thiamine in tissue

“Serious and potentially irreversible neurologic damage can occur with untreated TD, practitioners should treat the patient without laboratory confirmation of deficiency and monitor and evaluate resolution of signs and symptoms.”

-Frank L, Thamin in Clinical Practice, JPEN (2015)

Deficiencies

Types of Deficiencies Early:

Dry beriberi Neurologic

Wet beriberi High-output cardiac

Gastroenterologic Late:

Wernicke’s encephalopathy Neuropsychiatric

Administration of supplemental thiamine quickly cures beriberi

http://www.daviddarling.info/encyclopedia/B/beriberi.html

Early Symptoms

No specific threshold for serum thiamine that will indicate TD

Weight loss Anorexia Confusion Short term memory loss Muscle weakness Enlarged heart

Symptoms of Wet Beriberi

Heart failure with high cardiac output Edema in the lower extremities Tachycardia or bradycardia Lactic acidosis Dyspnea Heart hypertrophy and dilatation Respiratory distress Systemic venous hypertension Bounding arterial pulsations

Shoshin Beriberi

Severe form of wet beriberi Sudden onset of heart failure Cardiovascular collapse Metabolic acidosis Severe hemodynamic instability Can lead to death

Symptoms of Dry Beriberi

Brisk tendon reflexes Peripheral neuropathy Muscle weakness Pain of upper and lower extremities Gait ataxia Convulsions

Gastroenterologic Symptoms

Slow gastric emptying Nausea Vomiting Jejunal dilatation Megacolon Constipation

Wernicke’s Encephalopathy

Later stage of thiamine deficiency Polyneuropathy Ataxia Ocular changes Confusion Short-term memory loss Korsakoff psychosis

Populations At Risk For Deficiency

Alcohol dependence Most common cause of thiamine deficiency Ethanol reduces gastrointestinal absorption, liver stores, &

phosphorylation Inadequate intake of essential nutrients

Older adults Possible reasons: low intake, chronic diseases, medications, low

absorption Risk of deficiency particularly high for elderly who reside in an

institution Diabetes

Thiamine plasma levels 76% lower in type 1 diabetics Thiamine plasma levels 50-75% lower in type 2 diabetics

Populations At Risk For Deficiency

HIV/AIDS Possible malnutrition due to catabolic state associated with AIDS Thiamine deficiency under diagnosed

Post bariatric surgery Risk for severe thiamine deficiency due to malabsorption

Genetic Beriberi Rare, but occurs when body looses ability to absorb thiamine

Breastfed infants If mother is lacking thiamine, infant will as well if milk is only source of

nutrition

Medications & Research

Medications

No known medical interactions Certain medications can alter levels

Diuretics Furosemide – Lasix

Most frequently prescribed diuretic More than heart failure & lack of research

Chemotherapy Fluorouracil – Adrucil

Used to stop or slow cancer cell growth

Furosemide

Mixed reviews as to if furosemide at various doses is significant 32 heart failure patients receiving 40mg/d or >80mg/d of

furosemide. >80mg/d resulted in 98% of patients with severe TD (24/25) 40mg/d resulted in 57% of patients with severe TD (4/7) Thiamine deficiency occurs in a substantial proportion of CHF

failure patients being treated with furosemide

Furosemide may be inhibit TPP levels at the cellular level by inhibiting uptake or blocking phosphorylation

Spironolactone & Furosemide

Spironolactone Potassium sparing diuretic

Spironolactone & furosemide combined Patients with heart failure who received both had

significantly higher thiamine levels compared to furosemide alone

Prevalence of Thiamine Deficiency in Hospitalized Patients with Congestive

Heart Failure 100 congestive heart failure patients (CHF) & 50 control subjects CHF patents were on furosemide Thiamine supplements, other supplements Erythrocyte TPP measurements Findings:

TD occurred 33% in CHF patients versus 12% in control Multivitamin was found to have a significant association with

better thiamine status in CHF patients Did not find a significant relationship between TD and

furosemide dose, urine volume, or urine thiamine excretion

Hanninen S, Darling P, Sole M, Barr A, Keith M. The Prevalence of Thiamin Deficiency in Hospitalized Patients With Congestive Heart Failure. J Am Coll Cardiol. 2006; 47(2): 354-361.

Prevalence of Thiamine Deficiencyin Hospitalized Patients with Congestive Heart Failure

TD was related to urine thiamine loss, non-use of thiamine containing supplements, and preserved renal function

Increased urine thiamine excretion was the only significant positive predictor of thiamine status

Decreased renal function was significantly associated with better thiamine status in CHF patients Decreased renal function prevents excessive thiamine

loss, preventing TD

Hanninen S, Darling P, Sole M, Barr A, Keith M. The Prevalence of Thiamin Deficiency in Hospitalized Patients With Congestive Heart Failure. J Am Coll Cardiol. 2006; 47(2): 354-361.

Left Ventricle Ejection Fraction & Thiamine

9 patients, diuretics – unknown what type Congestive heart failure & left ventricle ejection fraction <40% Thiamine (300mg) or placebo

28 days, 6 week washout period, cross over to second 28 day period Left ventricle ejection fraction baseline for both groups was

29.5% Result: Thiamine treatment resulted in an increase in LVEF of

3.9% Thiamine supplementation has positive effects on cardiac

function for patients taking diuretic drugs for symptomatic CHF

Schoenenberger A, Schoenenberger-Berzins R, Maur C Suter P, Vergopoulos A, Erne P. Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot Study. Clin Res Cardiol. 2012; 101:159–164.

Our Contributation

Our Contributation

Be an advocate for early thiamine supplementation Work towards early initiation of thiamine supplementation when

patient is placed on diuretics or at risk for deficiency IU Methodist options:

Oral nutrition supplements Enteral nutrition Parenteral nutrition Multivitamins Thiamine supplements

Brief Review

RDA Men: 1.2mg Women: 1.1mg Lactating or pregnant:

1.4mg

World Health Organization (WHO) recommendations for adults 50-100mg/

day10mg/day 3-5mg/day Total time

Mild deficiency

Oral, 1 week Oral, 6 weeks

7 weeks

Severe deficiency

Intravenous*, 1 week

Intravenous*, 1 week

Oral, 6 weeks

8 weeks

*Intravenous injection should be dispersed over 30+ minutes

Oral Nutrition Supplements

Product Mg/serving

Servings per day to meet RDA

Ensure Clear 0.3 4

Ensure Complete 0.38 3.15

Glucerna 0.38 3.15

Nepro with Carbsteady 0.58 3

Consider: cumulative nutrition dose

Nutrition Support

Enteral Nutrition

Parenteral Nutrition 6mg thiamine per 10mL per day

Mg/L Product1.7 Vivonex RTF 2.1 Vital High Protein2.3 Jevity 1.2 &1.5. Osmolite 1.2, Promote 2.4 Nepro with Carbsteady 2.5 Vital AF 1.22.6 TwoCal3 Impact Peptide 1.5, Osmolite 1.5, Vital 1.5

Multivitamins & Thiamine Supplements

Multivitamins – contain thiamine hydrochloride

Thiamine Supplements Injection – 100mg/2mL Oral tablets – 50mg & 100mg

Adult multivit w/ minerals 3mg per tabletPediatric multivitamin w/ minerals (Flintstones)

3mg per 2 tablets

Prenatal Vitamin 1.8mg per tabletHD multivit, Adult or ocular multivit, Flintstones

1.5ng per tablet

CF & Bariatric multivitamin 1.5mg per 2 tabletsLiquid adult multivitamin 1.5mg per 15mLPediatric multivitamins – with or without iron

0.5mg per 1mL

Objectives Review

Understand the benefits of thiamine supplementation in the hospital setting

Determine when a patient may be at a higher risk for thiamine deficiency based off medical history and food recall

Recognize mediations that can have an adverse effect on thiamine levels

Understand dosing for thiamine deficiency

References Thiamine. Medline Plus. https://www.nlm.nih.gov/medlineplus/druginfo/natural/965.html.

Updated March 17, 2015. Accessed April 20, 2016. Beriberi. Medline Plus. https://www.nlm.nih.gov/medlineplus/ency/article/000339.htm.

Updated August 17, 2014. Accessed April 20, 2016. Thiamin. National Institutes of Health.

https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/. Updated February 11, 2016. Accessed April 20, 2016.

Hanninen S, Darling P, Sole M, Barr A, Keith M. The Prevalence of Thiamin Deficiency in Hospitalized Patients With Congestive Heart Failure. J Am Coll Cardiol. 2006; 47(2): 354-361.

Schoenenberger A, Schoenenberger-Berzins R, Maur C Suter P, Vergopoulos A, Erne P. Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot Study. Clin Res Cardiol. 2012; 101:159–164.

Frank L. Thiamin in Clinical Practice. JPEN. 2015; 39(5): 503-520. Sica D. Loop Diuretic Therapy, Thiamine Balance, and Heart Failure. Congest Heart Fail.

2007; 13(4): 244-247. Katta N, Balla S, Alpert M. Does Long-Term Furosemide Therapy Cause Thiamine

Deficiency in Patients with Heart Failure? A Focused Review. AM J MED. 2016. Rieck J, Halkin H, Almog S, et al. Urinary loss of thiamine is increased by low doses of

furosemide in healthy volunteers. J Lab Clin Med. 1999; 134: 238-243

Thank You!

Questions?