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Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs
Open accessAbstract
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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“Beriberi, the disease resulting from severe thiamine (vitamin B1) deficiency affects several organs, including the muscular and peripheral nervous systems [99]. General symptoms include fatigue, ataxia due to muscle weakness in the legs and arms, muscle pain and tenderness, and dyspnoea on exertion.”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [99]
In the citing paper
“An accidental thiamine deficiency in children fed an infant formula erroneously lacking thiamine, resulted in persistent cognitive and motor deficits. Even the children who initially appeared unaffected subsequently displayed a range of cognitive dysfunction, including delayed language acquisition, language impairment and dyslexia, poor coordination skills, and learning disabilities; quoted in [99”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [99]
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“Cerebral beriberi (thiamine (vitamin B1) deficiency) may lead to encephalopathies, characterized by abnormal eye movements, and cognitive impairment, involving a confused, apathetic state and a profound memory disorder, with severe amnesia and loss of recent and working memory.”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [99]
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BackgroundMethodInfluentialMeaselle, J. R., Baldwin, D. A., Gallant, J., Chan, K. L., Green, T., Wieringa, F. T., Borath, M., Sophonneary, P., Hampel, D., Shahab‐Ferdows, S., et al. (2021) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14610 · Cited by 19
Methods and approaches to estimate B vitamin status in dairy cows: Knowledge, gaps and advances
Girard, C. L., & Graulet, B. (2020) · Methods · doi:10.1016/j.ymeth.2020.05.021 · Cited by 19
Lin, S., Leppla, I. E., Yan, H., Probert, J. M., Randhawa, P. A., Leoutsakos, J., Probasco, J. C., & Neufeld, K. J. (2019) · Psychosomatics · doi:10.1016/j.psym.2019.08.002 · Cited by 18
Infantile thiamine deficiency: Redefining the clinical patterns
Qureshi, U. A., Bhat, A. S., Qureshi, U. A., Ahmad, K., Wani, N. A., Bashir, A., & Akram, M. (2020) · Nutrition · doi:10.1016/j.nut.2020.111097 · Cited by 18
Verstraete, J., & Stove, C. P. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab146 · Cited by 18
Nutritional Fish Diseases in Aquaculture: A Human Health Hazard or Mythical Theory: An Overview
Syanya, F. J., Litabas, J. A., Mathia, W. M., & Ntakirutimana, R. (2023) · European Journal of Nutrition & Food Safety · doi:10.9734/ejnfs/2023/v15i81326 · Cited by 18
“Its phosphorylated form, thiamine diphosphate, serves as a cofactor for several enzymes involved in cellular metabolism [97].”
BackgroundBrown, K. H., Hess, S. Y., Moore, S. E., Combs, G. F., Cashman, K. D., McNulty, H., Allen, L. H., Krebs, N. F., Pfeiffer, C. M., Rybak, M. E., et al. (2025) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2025.06.030 · Cited by 17
A fresh look at thiamine deficiency—new analyses by the global thiamine alliance
Bourassa, M. W., Bergeron, G., & Brown, K. H. (2021) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14594 · Cited by 17
Carrot and carotene and multiple health outcomes: an umbrella review of the evidence
Yi, X., Li, J. H., Liao, D., Peng, G., Zheng, X., Xu, H., Zhang, T., & Ai, J. (2023) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.12425 · Cited by 17
Jones, K. S., Parkington, D. A., Bourassa, M. W., Cerami, C., & Koulman, A. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14962 · Cited by 17
Can thiamine substitution restore cognitive function in alcohol use disorder?
Listabarth, S., Vyssoki, B., Marculescu, R., Gleiß, A., Groemer, M., Trojer, A., Harrer, C., Weber, S., & König, D. (2023) · Alcohol and Alcoholism · doi:10.1093/alcalc/agad017 · Cited by 18
“WE) or for patients receiving TS as a prophylactic treatment in AUD have been agreed on (Whitfield et al. 2018).”
Rigutto‐Farebrother, J., & Zimmermann, M. B. (2024) · Nutrients · doi:10.3390/nu16152517 · Cited by 20
“Salt has also proven to be a successful and cost-efficient route to deliver diethylcarbamazine, which is safe and effective at protecting individuals from the devastating effects of lymphatic filariasis [49–51].”
BackgroundTRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition
Sheokand, P. K., James, A. M., Jenkins, B., Lysyganicz, P. K., Lacabanne, D., King, M. S., Kunji, E. R. S., Siniossoglou, S., Koulman, A., Murphy, M. P., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr3723 · Cited by 17
Jeppesen, T. D., Madsen, K. L., Poulsen, N. S., Løkken, N., & Vissing, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081796 · Cited by 16
Clergue‐Duval, V., Coulbault, L., Questel, F., Cabé, N., Lanièpce, A., Delage, C., Boudehent, C., Bloch, V., Segobin, S. H., Naassïla, M., et al. (2022) · Antioxidants · doi:10.3390/antiox11102078 · Cited by 16
“It is rarely impaired and is not an indicator of thiamine status [37,48].”
BackgroundMethodInfluentialGenetic basis of thiaminase I activity in a vertebrate, zebrafish Danio rerio
Richter, C. A., Evans, A. N., Heppell, S. A., Zajicek, J. L., & Tillitt, D. E. (2023) · Scientific Reports · doi:10.1038/s41598-023-27612-5 · Cited by 16
Kareem, O., Mufti, S., Nisar, S., Tanvir, M., Muzaffer, U., Ali, N., SHEIKH, I. A., & Bader, G. N. (2023) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0011324 · Cited by 16
“This again is in consonance with the previous data that reports the presence of thiamine antagonists and thiaminases in various foods like pickles and tea, leading to insufficiency of thiamine in adults [31,51].”
BackgroundResultJarosz, Ł. S., Socała, K., Michalak, K., Wiater, A., Ciszewski, A., Majewska, M., Marek, A., Grądzki, Z., & Właź, P. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06519-z · Cited by 16
“One such vitamin is thiamine (vitamin B 1 ), a deficiency of which causes metabolic disorders associated with a lack of production of enzymes such as pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complex (Whitfield et al. 2018).”
BackgroundMaguire, D., Talwar, D. K., Burns, A., Catchpole, A., Stefanowicz, F. A., Robson, G., Ross, D. P., Young, D., Ireland, A., Forrest, E. H., et al. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-02141-w · Cited by 16
Hess, S. Y., Smith, T. J., Fischer, P. R., Trehan, I., Hiffler, L., Arnold, C. D., Sitthideth, D., Tancredi, D. J., Schick, M., Yeh, J. Z., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2019-036539 · Cited by 16
Macro- and Micronutrients in Milk from Healthy Cambodian Mothers: Status and Interrelations
Whitfield, K. C., Shahab‐Ferdows, S., Kroeun, H., Sophonneary, P., Green, T., Allen, L. H., & Hampel, D. (2020) · Journal of Nutrition · doi:10.1093/jn/nxaa070 · Cited by 16
“Upper secondary 5 (7) 1 (4) 3 (12) 1 (5)”
BackgroundInfluentialBracci, E. L., Keogh, J. B., Milte, R., & Murphy, K. J. (2021) · British Journal Of Nutrition · doi:10.1017/s0007114521002282 · Cited by 16
“Thiamin is a water-soluble vitamin required for cell growth and development (105; 106; 107) .”
BackgroundBiochemical and medical aspects of vitamin B1 research
Makarchikov, A. F., Wins, P., & Bettendorff, L. (2025) · Neurochemistry International · doi:10.1016/j.neuint.2025.105962 · Cited by 15
Fortification of Sugar: A Call for Action
Iwuozor, K. O., Mbamalu, P. S., Olaniyi, B. O., Anyanwu, V. U., Emenike, E. C., & Adeniyi, A. G. (2022) · Sugar Tech · doi:10.1007/s12355-022-01183-7 · Cited by 15
“Within the past decade, thiamine deficiency has been recorded in Asia (Bhutan (Dzed et al. 2015; Tsheten et al. 2016), Vietnam (Nguyen et al. 2016), and Kiribati (Nilles et al. 2018)), Africa (Guinea (Whitfield et al. 2018)), and South America (French Guiana (Mosnier et al. 2017)).”
BackgroundThiamine: An indispensable regulator of paediatric neuro-cardiovascular health and diseases
Mallimoggala, Y. S. P., Biswas, M., Anburaj, S. E., Iqbal, F., Aroor, S., Suryakanth, V. B., & Lewis, L. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05756-4 · Cited by 15
“…gravidarum-induced acute thiamine deficiency; complete resolution of symptoms was achieved with 1000 mg/day IV thiamine supplementation for 3 days [13, 67]. d) Addressing malnutrition and food diversification: Consumption of diverse foodstuffs, especially a diet rich in legumes and vegetables,…”
BackgroundInfluentialIimura, Y., Andoh, S., Kawamata, T., Sato, A., Yokoyama, K., Imai, Y., Tojo, A., Nojima, M., Sugiura, M., & Kuroda, S. (2021) · Journal of Neurosciences in Rural Practice · doi:10.1055/s-0041-1735825 · Cited by 14
“28,29 A lack of thiamine leads to failure of the Krebs cycle.”
Nisar, S., Tanvir, M., Ganie, M. A., Kareem, O., Muzaffer, U., & Wani, I. A. (2022) · Nutrition · doi:10.1016/j.nut.2022.111730 · Cited by 14
Pumpkin, Cauliflower and Broccoli as New Carriers of Thiamine Compounds for Food Fortification
Szymandera-Buszka, K. E., Piechocka, J., Jankowska, A., Przeor, M., & Jędrusek‐Golińska, A. (2021) · Foods · doi:10.3390/foods10030578 · Cited by 14
“It is similar in the case of products such as tea, coffee, raw fish and crustaceans [9,17].”
BackgroundEvolutionary and ecological correlates of thiaminase in fishes
Rowland, F. E., Richter, C. A., Tillitt, D. E., & Walters, D. (2023) · Scientific Reports · doi:10.1038/s41598-023-44654-x · Cited by 13
Thiamine deficiency‐related neuropathy: A reversible entity from an endemic area
Nisar, S., Wani, I. Y., Altaf, U., Muzaffer, U., Kareem, O., Tanvir, M., & Ganie, M. A. (2023) · European Journal of Neurology · doi:10.1111/ene.16155 · Cited by 13
Khalid, W., Arshad, M. S., Nayik, G. A., Alfarraj, S. A., Ansari, M. J., & Guiné, R. P. F. (2022) · Molecules · doi:10.3390/molecules27238201 · Cited by 13
“It provides different nutrients (fatty acids, amino acids, vitamins and minerals) and phytochemicals (polyphenols, glucosinolates and carotenoids) to humans [12].”
BackgroundReynolds, G. L., Epps, S. J., Huntley, A. L., & Atan, D. (2022) · Nutrients · doi:10.3390/nu14153068 · Cited by 12
“Thiamine deficiency is often diagnosed clinically, without biochemical confirmation, because thiamine compounds are photosensitive and only stable for a few hours at room temperature, so specimens need to be transported on ice and in darkness, then rapidly frozen for storage [86].”
BackgroundVinnai, B. Á., Arianti, R., Győry, F., Bacsó, Z., Fésüs, L., & Kristóf, E. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1207394 · Cited by 12
Serra, M. D. R., Mollace, R., Ritorto, G., Ussia, S., Altomare, C., Tavernese, A., Preianò, M., Palma, E., Muscoli, C., Mollace, V., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26093932 · Cited by 12
“…brown rice, and oats), pulses (e.g., beans, peas, and lentils), meat (mainly pork), fi sh (e.g., tuna or salmon), nuts or seeds (e.g., walnuts, almonds, or sun fl ower seeds), and vegetables (e.g., asparagus, spinach, and cauli fl ower), and supplements are key sources of thiamine (Figure 1) [2].”
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
- 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
- hybrid
- doi.org
- 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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