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Recent Developments in Thiamine Research

WEBINAR

Only

FREE Event

Recent Developments in Thiamine Research

Tuesday, March 9, 2021, 9:00 AM - 12:00 PM EST

Webinar

Presented By

The New York Academy of Sciences

 

Thiamine deficiency remains an urgent public health problem. The reliance on staple crops that are low in thiamine places many populations at risk of thiamine deficiency, and there are several underlying conditions associated with thiamine deficiency. If untreated, the deficiency of this essential vitamin can have lasting developmental and cognitive effects and can be fatal. Over the past several years, the Academy’s Nutrition Science Program has created the Global Thiamine Alliance and led an initiative to identify and address the key gaps in our knowledge of thiamine deficiency, with the ultimate aim of reducing the global burden of this pressing public health issue. This webinar presents the most recent advances in thiamine research.

Registration

Individual
$0

Speakers

Kenneth Brown, MD
Kenneth Brown, MD

UC Davis

Kathleen Chan, MSc
Kathleen Chan, MSc

Mount Saint Vincent University

Dare Baldwin, PhD
Dare Baldwin, PhD

University of Oregon

Jeffrey Measelle, PhD
Jeffrey Measelle, PhD

University of Oregon

Kyly Whitfield, PhD
Kyly Whitfield, PhD

Mount Saint Vincent University

Gary Gibson, PhD
Gary Gibson, PhD

Burke Neurological Institute, Weill Cornell Medicine

Elisabeth Mates, MD, PhD
Elisabeth Mates, MD, PhD

VA Sierra Nevada Healthcare System

Laurent Hiffler, MD
Laurent Hiffler, MD

Cellular Nutrition Research Group

Philip Fischer, MD
Philip Fischer, MD

Mayo Clinic and Sheikh Shakhbout Medical City

Filomena Gomes, PhD
Filomena Gomes, PhD

New York Academy of Sciences

Megan Bourassa, PhD
Megan Bourassa, PhD

New York Academy of Sciences

Frank Wieringa, MD, PhD
Frank Wieringa, MD, PhD

Institut de Recherche pour le Développement

Tuesday

March 09, 2021

9:00 AM

Introduction

Speaker

Megan Bourassa, PhD
New York Academy of Sciences
9:15 AM

Clinical Thiamine Deficiency – What We Know and What We Still Need to Learn

Speaker

Philip Fischer, MD
Mayo Clinic and Sheikh Shakhbout Medical City

Thiamine deficiency is common, especially in South and Southeast Asia where more than half of children in some areas are thiamine deficient. In Myanmar, thiamine deficiency accounts for 17% of deaths in young children, and up to 3% of all babies born in rural Cambodia die due to thiamine deficiency. Clinical manifestations of thiamine deficiency involve most body systems. Cardiorespiratory (pulmonary hypertension and right heart failure presenting as fatigue and tachypnea) and neurologic (central nervous system lesions in the basal ganglia with altered development, peripheral neuropathy with dysesthesias) manifestations of thiamine deficiency are particularly common. The diagnosis depends on a high index of suspicion. The relationships between biomarker (such as thiamine diphosphate) levels and clinical manifestations are incompletely understood, and the clinical findings often overlap with other common conditions. Treatment with thiamine is relatively easy and safe, but the doses and duration of treatment are incompletely studied. The prognosis seems good, especially with acute cardiorespiratory and peripheral neurologic symptoms, but the outcomes of infants with central nervous system involvement are less well understood and likely less favorable. Ongoing research is needed related to an accurate clinical diagnosis of thiamine deficiency disorders, specific treatment protocols, and outcomes with brain involvement.

9:30 AM

Thiamine Deficiency in Adults & Pediatrics in High-Income Countries

Speakers

Filomena Gomes, PhD
New York Academy of Sciences

Thiamine deficiency has been typically associated with alcoholism or as a prevalent problem in low‐ and middle‐income countries (LMICs) whose populations rely on staple foods with a low content of thiamine. We conducted a literature review of published and unpublished data to identify relevant adult cases with confirmed thiamine deficiency of nonalcoholic cause in developed countries. We selected 17 reports with 81 adult cases of confirmed thiamine deficiency affecting adult patients with a wide range of ages and underlying conditions (e.g., cancer, gastrointestinal diseases, heart failure, and obesity). Thiamine deficiency may have been caused by disease‐related malnutrition, bariatric surgery, chronic use of diuretics, repeated vomiting, lack of thiamine in parenteral nutrition formulas, food insecurity, and reliance on monotonous or restrictive diets. Treatment with intravenous thiamine resulted in partial or complete recovery from the symptoms (cardiac, neurologic, and metabolic disorders) for most patients. The number and variety of symptomatic thiamine‐deficient adults identified in this review demonstrates that thiamine deficiency is not exclusive to LMICs and, in high‐income settings, is not exclusive to alcoholic patients. In developed countries, this serious but treatable condition can be expected in patients suffering from various medical conditions or following certain dietary patterns.

Publication available at: https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/nyas.14569

Laurent Hiffler, MD
Cellular Nutrition Research Group

Background: Often thought to be a nutritional issue limited to low and middle income countries (LMIC), Pediatric Thiamine Deficiency (PTD) is perceived as eradicated or anecdotal in high-income countries (HIC). Classic beriberi cases in breastfed infants by thiamine deficient mothers living in disadvantaged socioeconomic conditions are thought to be rare. This study aims to assess PTD in HIC in the 21st century.
Methods: literature searches were conducted to identify case reports of PTD observed in HIC and published between 2000 and 2020. The analyzed variables were: age, country, underlying conditions, clinical manifestations of PTD and response to thiamine supplementation.
Results: 104 articles were identified, totaling 480 PTD cases that were classified into four age groups: neonates, infants, children and adolescents. Eleven categories of predisposing factors of PTD were identified, including genetic causes, lifestyle (diabetes, obesity, excessive consumption of sweetened beverages), eating disorders, cancer, gastrointestinal disorders/surgeries, critical illness and artificial nutrition. Hyperlactatemia and Wernicke encephalopthy were the most frequent clinical manifestations.
Conclusions: The high number of cases identified in 20 years suggests that the prevalence of PTD in HIC is likely to be underestimated. The predisposing factors, clinical presentation and age distribution differ from the PTD pattern observed in LMIC.

9:50 AM

Thiamine Deficiency in Hospitalized Veterans, an Important Cause of Delirium and Falls

Speaker

Elisabeth Mates, MD, PhD
VA Sierra Nevada Healthcare System
10:05 AM

Thiamine and Alzheimer’s Disease

Speaker

Gary Gibson, PhD
Burke Neurological Institute, Weill Cornell Medicine

Background. In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, beta amyloid plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE) and inflammation.
Objective. To collect preliminary data on feasibility, safety and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine.
Methods. A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the AD-Assessment-Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome.
Results. Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p=0.125). Worsening in CDR was 77% lower (p=0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOE ε4 non-carriers. Benfotiamine significantly reduced increases in AGE (p=0.044), and this effect was stronger in the APOE ε4 non-carriers. Exploratory analysis derivation of an FDGPET pattern score showed a treatment effect at one year (p=0.002).
Conclusions Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

10:20 AM

Break

10:30 AM

Global outbreaks and recent thiamine status in the Gambia and Madagascar

Speakers

Megan Bourassa, PhD
New York Academy of Sciences
Frank Wieringa, MD, PhD
Institut de Recherche pour le Développement
10:50 AM

Thiamine Dose Response in Human Milk with Supplementation in Cambodia

Speaker

Kyly Whitfield, PhD
Mount Saint Vincent University
11:05 AM

Role of thiamine supplementation on cognitive and language development in Cambodia

Speakers

Jeffrey Measelle, PhD
University of Oregon
Dare Baldwin, PhD
University of Oregon

Women reliant on mostly rice-based diets can have inadequate thiamine intake, placing breastfed infants at risk of thiamine deficiency and, in turn, physical and cognitive impairments. We investigated the impact of maternal thiamine supplementation doses on infants’ cognitive, motor, and language development across the first year. In this double-blind, four-parallel arm, randomized controlled trial, healthy mothers of exclusively breastfed newborn infants were recruited in Kampong Thom, Cambodia. At 2-weeks postnatal, women (n=335) were randomized to one of four treatment groups to consume one capsule/day with varying amounts of thiamine for 22 weeks: 0 mg, 1.2 mg, 2.4 mg, and 10 mg. At 2-, 12-, 24- and 52-weeks of age, infants were assessed with a battery of direct assessments (e.g., the Mullen Scales of Early Learning; Language Preference Task) and caregiver reported scales of early development. Multiple regression and mixed effects modeling suggest that by 6 months of age, the highest maternal thiamine dose (10 mg/day) held significant benefits for infants’ language development, but generally not for motor or visual reception development. Despite having achieved standardized scores on the Mullen Scales that approximated US norms by 6 months, infants showed a significant drop relative to these norms in both language domains following trial completion, suggesting that nutritional interventions beyond 6 months may be necessary.

11:25 AM

Modelling of salt as a potential fortification vehicle for thiamine in Cambodia

Speaker

Kathleen Chan, MSc
Mount Saint Vincent University

Thiamine deficiency is a public health issue in Cambodia. Thiamine fortification of salt has been proposed in Cambodia; however, the salt intake of lactating women, the target population, is currently unknown. We estimated salt intakes among lactating women (<6 months postpartum) in Kampong Thom province using three methods: repeat observed weighed intake records and 24-hr urinary sodium excretions (n=104), and household salt disappearance (n=331). Usual salt intake was estimated by adjusting observed weighed intake records for intra-individual intakes using the National Cancer Institute method, and a thiamine salt fortification scenario was modelled using a modified EAR-cut point method. Unadjusted salt intake from observed intakes was 9.3 (8.3, 10.3) g/day, and not different from estimated salt intake from urinary sodium excretions, 9.0 (8.4, 9.7) g/day (p=0.3). Estimated salt use from household salt disappearance was higher than other methods of assessment (11.3 (10.7, 11.9) g/person/day). Usual (adjusted) salt intake from all sources was 7.7 (7.4, 8.0) g/day. Assuming no stability losses, a modelled fortification dose of 275 mg thiamine/kg salt could increase thiamine intakes from fortified salt to 2.1 (2.0, 2.2) mg/day, with even low salt consumers reaching the estimated average requirement of 1.2 mg/d from fortified salt alone. These findings, in conjunction with future sensory and stability research, can be used to inform a potential salt fortification program in Cambodia, as well as other countries in the region with suspected thiamine inadequacy.

11:40 AM

Closing Remarks

Speaker

Kenneth Brown, MD
University of California, Davis