Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans

Thiamine micronutrient deficiency (TD) can cause a variety of non-specific symptoms and leads to several thiamine deficiency disorders such as heart failure, polyneuropathy, Wernicke's Encephalopathy and generalized weakness and debility. Symptoms are often vague and non-specific such as fatigue, leg swelling, imbalance, confusion, mood disorders, gastrointestinal upset, and weakness. Hospitalized Veterans may be particularly susceptible to TD due to food insecurity and chronic illnesses which cause inflammation and increased metabolic demands. This study aims to determine the prevalence of TD in hospitalized Veterans which has never been done before. The investigators also seek to identify risk factors causing TD including acute and chronic forms of inflammation, food insecurity, and dietary habits. Lastly, the investigators hope to clarify the abnormally low levels of blood thiamine that correlate with symptoms of TD that improve with replenishment.

Study Overview

• Status: Completed
• Conditions: Thiamine Deficiency; Thiamine Deficiency; Sequelae
• Intervention / Treatment: Dietary supplement: Thiamine repletion

Detailed Description

Background: Thiamine deficiency (TD) causes a variety of thiamine deficiency disorders (TDDs) such as neuropsychiatric disturbances, polyneuropathy, ataxia, weakness and falling, and non-ischemic heart failure. Left untreated, TD can be associated with poor quality of life, loss of independence, and inability to complete activities of daily living. The prevalence of TD in non-alcohol using hospitalized Veterans is not known but is probably much higher than the general population. Loss of functional ability leads to increased need for rehabilitation.

The objective of this proposal is to measure the prevalence of TDDs in Veterans who do not use excess alcohol who are ill enough to require hospitalization, determine if inflammation increases the risk of developing TD, and determine the optimal cutoff points for two biomarkers of TD to diagnose of TDDs. The central hypothesis is that TD prevalence is as high as 25% in hospitalized non-alcoholic Veterans, far greater than the historically reported prevalence of 3% or less, and that TDD's occur in the "low normal" range of current cutoff values for available thiamine bioassays. A secondary hypothesis is that inflammatory conditions, which are known to cause cachexia and malnutrition, put hospitalized Veterans at increased risk as they often present with acute inflammatory conditions. The rationale underlying this proposal is that hospital practitioners currently underdiagnose and undertreat TDDs which leads to continued morbidity and loss of function. If the hypothesis is correct that the prevalence is as high as 25%, this knowledge will increase awareness of the problem and lead practitioners to diagnose and treat them more often. In addition, clarifying the "abnormally low" biomarker cutoff levels by measuring them in Veterans with TDDs is very important as the current "normal" ranges were determined in healthy volunteers. The central hypothesis will be tested by pursuing three specific aims: 1) determine the prevalence of TD, as defined by whole blood and plasma thiamine levels together with symptom responsive disease in consecutively hospitalized medicine patients who do not use excessive alcohol; 2) define TDDs as cases with low or "low normal" thiamine levels and symptoms that improve with thiamine replenishment; 3) determine if acute and chronic inflammatory conditions with elevated biomarkers of inflammation increase the risk of developing TDD. The investigators expect to find the prevalence of TD is closer to 25% and that the low end of "normal" biomarker levels as published by reference laboratories is too low, missing a percentage of TDDs.

Research design: To accomplish these aims, the investigators will utilize a prospective cohort study design to determine the prevalence of TD in consecutively hospitalized non-alcoholic medicine patients, as defined by low or "low normal" thiamine biomarker levels and thiamine responsive symptoms. Nested within this the investigators will conduct an open label treatment study with those exhibiting symptoms and define TDDs as cases with low or "low normal" thiamine levels and symptoms of TD that improve with thiamine administration. Lastly, utilizing a nested case control study design with cases being those with a TDD and controls being asymptomatic Veterans with normal biomarkers, determine if acute and chronic inflammatory conditions with elevated biomarkers of inflammation increase the risk of developing TDDs.

• Study Type: Observational
• Enrollment (Actual): 206

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Reno, Nevada, United States, 89502-0993
      • VA Sierra Nevada Health Care System, Reno, NV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Veterans who are admitted to the medicine service at the VA Sierra Nevada Healthcare System hospital in Reno, NV who do not use alcohol to excess. The Veterans will need to live within 75 miles of the medical center to facilitate return for follow up appointments.

Description

Inclusion Criteria:

• full admission to the hospital medical service (not on observation status)

Exclusion Criteria:

• excess alcohol intake as defined by the National Institute of Alcohol Abuse and Alcoholism
• taking thiamine supplement
• quadriplegic
• lives more than 75 miles from the medical center
• unable to demonstrate capacity to understand the study and provide informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hospitalized non-alcoholic Veterans; Any Veteran with full admission to the VA Sierra Nevada Healthcare System Hospital.	Dietary supplement: Thiamine repletion; If a participant is determined by clinical characteristics or biomarker results to be thiamine deficient, thiamine supplementation was provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Thiamine Deficiency (Low Plasma Thiamine) Out of Total Number of Enrolled Veterans With Plasma Thiamine Results	The percentage of enrolled non-alcoholic veterans who have thiamine deficiency (defined as low plasma thiamine levels) out of the total number of enrolled Veterans with plasma thiamine results.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of Thiamine Deficiency and Inflammation	Determine if there is an association between thiamine deficiency defined by low plasma thiamine levels, and elevated highly sensitive C-reactive protein indicating inflammation.	Baseline
Cut-point Analysis of Thiamine Biomarkers	The investigators will determine the low end of normal thiamine levels in veterans with treatment-responsive thiamine deficiency symptoms using a composite score to compare exam findings before and after treatment with thiamine.	Baseline compared to follow up visit

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: VA Sierra Nevada Health Care System
• Investigators: Principal Investigator: Elisabeth A Mates, MD PhD, VA Sierra Nevada Health Care System, Reno, NV

Publications and helpful links

General Publications

• Mates E, Alluri D, Artis T, Riddle MS. A Retrospective Case Series of Thiamine Deficiency in Non-Alcoholic Hospitalized Veterans: An Important Cause of Delirium and Falling? J Clin Med. 2021 Apr 1;10(7):1449. doi: 10.3390/jcm10071449.
• Gomes F, Bergeron G, Bourassa MW, Fischer PR. Thiamine deficiency unrelated to alcohol consumption in high-income countries: a literature review. Ann N Y Acad Sci. 2021 Aug;1498(1):46-56. doi: 10.1111/nyas.14569. Epub 2021 Feb 11.
• Donnino MW, Carney E, Cocchi MN, Barbash I, Chase M, Joyce N, Chou PP, Ngo L. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010 Dec;25(4):576-81. doi: 10.1016/j.jcrc.2010.03.003. Epub 2010 Jun 19.
• Whitfield KC, Bourassa MW, Adamolekun B, Bergeron G, Bettendorff L, Brown KH, Cox L, Fattal-Valevski A, Fischer PR, Frank EL, Hiffler L, Hlaing LM, Jefferds ME, Kapner H, Kounnavong S, Mousavi MPS, Roth DE, Tsaloglou MN, Wieringa F, Combs GF Jr. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43. doi: 10.1111/nyas.13919. Epub 2018 Aug 27.
• Lee DC, Chu J, Satz W, Silbergleit R. Low plasma thiamine levels in elder patients admitted through the emergency department. Acad Emerg Med. 2000 Oct;7(10):1156-9. doi: 10.1111/j.1553-2712.2000.tb01268.x.
• Smith TJ, Johnson CR, Koshy R, Hess SY, Qureshi UA, Mynak ML, Fischer PR. Thiamine deficiency disorders: a clinical perspective. Ann N Y Acad Sci. 2021 Aug;1498(1):9-28. doi: 10.1111/nyas.14536. Epub 2020 Dec 10.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2022
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): December 30, 2024

Study Registration Dates

• First Submitted: July 27, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: delirium; falls; polyneuropathy; beriberi; thiamine deficiency; Wernicke's encephalopathy; vitamin B1
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Nutrition Disorders; Neuromuscular Diseases; Metabolic Diseases; Peripheral Nervous System Diseases; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Brain Diseases, Metabolic; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Delirium; Polyneuropathies; Thiamine Deficiency; Beriberi; Wernicke Encephalopathy
• Other Study ID Numbers: F4101-P; IRBNet ID 1867369-3 (Other Identifier: VA Sierra Nevada Health Care System)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified data set will be shared upon request made to Dr. Elisabeth Mates

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No