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?