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Cited by 336Alcoholism and Thiamine DeficiencyChild Nutrition and Water AccessNutrition, Health, and Society Studies

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Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs

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Whitfield, Kyly C., Bourassa, Megan W., Adamolekun, Bola, Bergeron, Gilles, Bettendorff, Lucien, Brown, Kenneth H., Cox, Lorna, Fattal‐Valevski, Aviva, Fischer, Philip R., Frank, Elizabeth L., Hiffler, Laurent, Hlaing, Lwin Mar, Jefferds, Maria Elena, Kapner, Hallie, Kounnavong, Sengchanh, Mousavi, Maral P.S., Roth, Daniel E., Tsaloglou, Maria‐Nefeli, Wieringa, Frank, Combs, Gerald F.·2018·Annals of the New York Academy of Sciences
DOI 10.1111/nyas.13919PMC PMC6392124
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Abstract

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month-specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high-risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing.

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Figures

Figure 1 Thiamine diphosphate is a cofactor required for several metabolic processes, shown in bold text. Adapted from Thurnham.9
Figure 1 Thiamine diphosphate is a cofactor required for several metabolic processes, shown in bold text. Adapted from Thurnham.9CC BY-NC · PubMed Central
Figure 2 The three thiamine‐dependent enzymes and their role in the pathogenesis of cell death in thiamine deficiency. Adapted from Fattal‐Valevski.10 Dashed lines represent indirect pathways. ThDP, thiamine diphosphate.
Figure 2 The three thiamine‐dependent enzymes and their role in the pathogenesis of cell death in thiamine deficiency. Adapted from Fattal‐Valevski.10 Dashed lines represent indirect pathways. ThDP, thiamine diphosphate.CC BY-NC · PubMed Central
Figure 3 The sequential reactions involved in the erythrocyte transketolase (ETK) assay.
Figure 3 The sequential reactions involved in the erythrocyte transketolase (ETK) assay.CC BY-NC · PubMed Central
Figure 4 Comparison of the erythrocyte ThDP assay and ETKAC values from medical and surgical patients who were determined to be at risk of thiamine deficiency (from Talwar et al.17). ThDP, thiamine diphosphate; ETKAC, erythrocyte transketolase activation coefficient.
Figure 4 Comparison of the erythrocyte ThDP assay and ETKAC values from medical and surgical patients who were determined to be at risk of thiamine deficiency (from Talwar et al.17). ThDP, thiamine diphosphate; ETKAC, erythrocyte transketolase activation coefficient.CC BY-NC · PubMed Central
Figure 5 Clinical spectrum of thiamine deficiency disorders. Adapted from the WHO, 1999.39
Figure 5 Clinical spectrum of thiamine deficiency disorders. Adapted from the WHO, 1999.39CC BY-NC · PubMed Central
Figure 6 An example of a proposed case definition of thiamine deficiency disorder (TDD).
Figure 6 An example of a proposed case definition of thiamine deficiency disorder (TDD).CC BY-NC · PubMed Central
Figure 7 Clinical guidelines for empirical treatment of suspected thiamine deficiency disorders (TDDs). LMIC, low‐ and middle‐income countries; IDP, internally displaced person; TDD, thiamine deficiency disorder.
Figure 7 Clinical guidelines for empirical treatment of suspected thiamine deficiency disorders (TDDs). LMIC, low‐ and middle‐income countries; IDP, internally displaced person; TDD, thiamine deficiency disorder.CC BY-NC · PubMed Central
Figure 8 Map depicting countries where the estimated per capita availability of thiamine in the national food supply (as per food balance sheets) is below the recommended nutrient intake for men of 1.2 mg/day (in turquoise), and countries where rice or wheat flour fortification is in place to address low thiamine availability (in yellow). Countries where the estimated mean thiamine availability is greater than or equal to 1.2 mg/day are in gray.
Figure 8 Map depicting countries where the estimated per capita availability of thiamine in the national food supply (as per food balance sheets) is below the recommended nutrient intake for men of 1.2 mg/day (in turquoise), and countries where rice or wheat flour fortification is in place to address low thiamine availability (in yellow). Countries where the estimated mean thiamine availability is greater than or equal to 1.2 mg/day are in gray.CC BY-NC · PubMed Central
Figure 9 Comparison of infant mortality rates by month of age in Cambodia based on DHS data. CDHS, Cambodian Demographic and Household Survey.
Figure 9 Comparison of infant mortality rates by month of age in Cambodia based on DHS data. CDHS, Cambodian Demographic and Household Survey.CC BY-NC · PubMed Central
Figure 10 A proposed approach for assessing a country's risk of thiamine deficiency disorders (TDDs) and the actions the countries could consider taking to prevent or eliminate TDD cases.
Figure 10 A proposed approach for assessing a country's risk of thiamine deficiency disorders (TDDs) and the actions the countries could consider taking to prevent or eliminate TDD cases.CC BY-NC · PubMed Central
Figure 11 Educational poster outlining common signs of infantile beriberi (in Khmer).
Figure 11 Educational poster outlining common signs of infantile beriberi (in Khmer).CC BY-NC · PubMed Central

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Citations

Cites

Show all 211 references

Research works printed but not linked: 13

  1. FAO & World Health Organization, 2005, Vitamin and Mineral Requirements in Human Nutrition, 1
  2. Turck D., 2016, EFSA scientific opinion on dietary reference values for thiamin, EFSA J, 14, e04653
  3. 10.1371/journal.pntd.0000969 · DOI
  4. Tajahmady A., 2004, Une épidémie de béribéri infantile à Mayotte, avril–juillet 2004, Bull. Epidemiol. Hebdo., 45, 213
  5. Murase C., 2013, Shoshin beirberi in a young man living on Japanese rice balls, J. Gen. Intern. Med., 28, S390
  6. Bailey A.L., 1990, A normal phase high performance liquid chromatographic method for the determination of thiamin in blood and tissue samples, J. Micronutr. Anal., 7, 147
  7. Hurrell R., 1999, The Mineral Fortification of Foods
  8. Institute of Medicine, 1998, Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic acid, Biotin, and Choline
  9. Otten J., 2006, Dietary Reference Intakes: the Essential Guide to Nutrient Requirements
  10. Pillaiyar P., 1981, Household parboiling of parboiled rice, Kishan World, 8, 20
  11. 10.1016/S0033-3549(04)50217-0 · DOI
  12. Isela R., 2005, Alimentación y estado nutricio de mujeres embarazadas derechohabientes del Instituto Mexicano del Seguro Social en un área suburbana de la Ciudad de México, Ginecol. Obs. Mex., 73, 3
  13. Eliana Duran F., 2007, Dietetic adequation of micronutrients in pregnant women, Rev. Chil. Nutr., 34, 321

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Metadata

Authors
Whitfield, K. C., Bourassa, M. W., Adamolekun, B., Bergeron, G., Bettendorff, L., Brown, K. H., Cox, L., Fattal‐Valevski, A., Fischer, P. R., Frank, E. L., Hiffler, L., Hlaing, L. M., Jefferds, M. E., Kapner, H., Kounnavong, S., Mousavi, M. P. S., Roth, D. E., Tsaloglou, M., Wieringa, F., & Combs, G. F.
Affiliations
  • Mount Saint Vincent University (CA)
  • New York Academy of Sciences (US)
  • University of Tennessee Health Science Center (US)
  • University of Liège (BE)
  • Gates Foundation (US)
  • MRC Elsie Widdowson Laboratory (GB)
  • Tel Aviv University (IL)
  • Mayo Clinic (US)
  • University of Utah (US)
  • Médecins Sans Frontières (ES)
  • Ministry of Health and Sports (MM)
  • Centers for Disease Control and Prevention (US)
  • Independent contractor New York New York
  • Ministry of Health (LA)
  • Harvard University (US)
  • University of Toronto (CA)
  • Diagnostics For All (US)
  • Institut de Recherche pour le Développement (FR)
  • Tufts University (US)
Corresponding author
Combs, Gerald F.
ORCID
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2018-08-27
Volume
1430
Issue
1
Pages
3-43
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/nyas.13919
PMC
PMC6392124
OpenAlex
W2889058844
Cited by
336
References
211
Citations by year
2026: 44 · 2025: 41 · 2024: 46 · 2023: 59 · 2022: 43 · 2021: 52 · 2020: 33 · 2019: 17 · 2018: 1
FWCI
17.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of the New York Academy of Sciences (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
  • Medecins Sans Frontieres Field Research (Medecins Sans Frontieres) (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion, cc-by)
Funders
Bill and Melinda Gates Foundation
Topics
  • Health Sciences › Medicine › Clinical Neurology › Alcoholism and Thiamine Deficiency
  • Health Sciences › Nursing › Nutrition and Dietetics › Child Nutrition and Water Access
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Nutrition, Health, and Society Studies
Keywords
thiamine deficiency, beriberi, infantile beriberi, infant mortality, food fortification, thiamine supplementation, food balance sheets, grain milling, rice washing, micronutrient deficiency, prevalence, neurodevelopmental outcomes
MeSH terms
Food, Fortified, Humans, Public Health, Risk Factors, Thiamine Deficiency, Global Health, Prevalence, Dietary Supplements

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