Causes of vitamin B1 deficiency include alcohol-misuse disorders, inadequate intake of thiamine (e.g., fasting, starvation, malnutrition), malabsorptive conditions (e.g., gastrointestinal surgery, recurrent vomiting and/or diarrhoea), and conditions with increased demand for thiamine (e.g., cancer, infection).[13]Galvin R, Bråthen G, Ivashynka A, et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408-18.
https://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03153.x
http://www.ncbi.nlm.nih.gov/pubmed/20642790?tool=bestpractice.com
Alcohol
In the developed world, vitamin B1 deficiency presenting as Wernicke's encephalopathy occurs mainly in people with alcohol misuse disorders, particularly in the context of poor nutritional intake.[3]Chandrakumar A, Bhardwaj A, 't Jong GW. Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. J Basic Clin Physiol Pharmacol. 2018 Oct 2;30(2):153-62.
https://www.degruyter.com/document/doi/10.1515/jbcpp-2018-0075/html
http://www.ncbi.nlm.nih.gov/pubmed/30281514?tool=bestpractice.com
Alcohol may block the active-transport mechanism for the absorption of thiamine in the gastrointestinal tract.[3]Chandrakumar A, Bhardwaj A, 't Jong GW. Review of thiamine deficiency disorders: Wernicke encephalopathy and Korsakoff psychosis. J Basic Clin Physiol Pharmacol. 2018 Oct 2;30(2):153-62.
https://www.degruyter.com/document/doi/10.1515/jbcpp-2018-0075/html
http://www.ncbi.nlm.nih.gov/pubmed/30281514?tool=bestpractice.com
[14]Thomson AD. Mechanisms of vitamin deficiency in chronic alcohol misusers and development of the Wernicke-Korsakoff syndrome. Alcohol Alcohol Suppl. 2000;35:2-7.
http://www.ncbi.nlm.nih.gov/pubmed/11304071?tool=bestpractice.com
[15]Subramanya SB, Subramanian VS, Said HM. Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process. Am J Physiol Gastrointest Liver Physiol. 2010 Jul;299(1):G23-31.
https://journals.physiology.org/doi/full/10.1152/ajpgi.00132.2010
http://www.ncbi.nlm.nih.gov/pubmed/20448146?tool=bestpractice.com
Diet
Vitamin B1 (thiamine) is an essential micronutrient obtained through the diet.[10]Whitfield KC, Bourassa MW, Adamolekun B, et al. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43.
https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/nyas.13919
http://www.ncbi.nlm.nih.gov/pubmed/30151974?tool=bestpractice.com
In countries where diets are low in thiamine, such as Southeast Asia where there is high consumption of thiamine-depleted polished rice, vitamin B1 deficiency is more common.[10]Whitfield KC, Bourassa MW, Adamolekun B, et al. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43.
https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/nyas.13919
http://www.ncbi.nlm.nih.gov/pubmed/30151974?tool=bestpractice.com
[12]Johnson CR, Fischer PR, Thacher TD, et al. Thiamin deficiency in low- and middle-income countries: disorders, prevalences, previous interventions and current recommendations. Nutr Health. 2019 Jun;25(2):127-51.
http://www.ncbi.nlm.nih.gov/pubmed/30798767?tool=bestpractice.com
The germ cells of whole grains and seeds are rich in thiamine.
Increased caloric intake, as seen in patients with obesity, results in an increased load on metabolic pathways and demand for micronutrients.[16]Maguire D, Talwar D, Shiels PG, et al. The role of thiamine dependent enzymes in obesity and obesity related chronic disease states: a systematic review. Clin Nutr ESPEN. 2018 Jun;25:8-17.
http://www.ncbi.nlm.nih.gov/pubmed/29779823?tool=bestpractice.com
Inadequate or absent thiamine supplementation in total parenteral nutrition can cause vitamin B1 deficiency.[17]Ferrie S. Case report of acute thiamine deficiency occurring as a complication of vitamin-free parenteral nutrition. Nutr Clin Pract. 2012 Feb;27(1):65-8.
http://www.ncbi.nlm.nih.gov/pubmed/22227728?tool=bestpractice.com
Infantile beriberi can occur in infants exclusively breastfed by mothers deficient in vitamin B1.[9]Kareem O, Nisar S, Tanvir M, et al. Thiamine deficiency in pregnancy and lactation: implications and present perspectives. Front Nutr. 2023 Apr 20;10:1080611.
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1080611/full
http://www.ncbi.nlm.nih.gov/pubmed/37153911?tool=bestpractice.com
Thiaminases break down thiamine in food, and thiamine antagonists can interfere with the absorption of thiamine. Certain foods that contain thiaminases (e.g., fermented fish, shellfish) or thiamine antagonists (e.g., tea, coffee, betel nuts, red cabbage) can result in vitamin B1 deficiency.[18]Wilson RB. Pathophysiology, prevention, and treatment of beriberi after gastric surgery. Nutr Rev. 2020 Dec 1;78(12):1015-29.
https://academic.oup.com/nutritionreviews/article/78/12/1015/5835520
http://www.ncbi.nlm.nih.gov/pubmed/32388553?tool=bestpractice.com
Refeeding syndrome
There is increased demand for thiamine during refeeding (reinstitution of nutrition following a period of undernutrition) because it is a co-factor in glucose-dependent metabolic pathways. Vitamin B1 deficiency can, therefore, present as part of refeeding syndrome.[19]Reber E, Friedli N, Vasiloglou MF, et al. Management of refeeding syndrome in medical inpatients. J Clin Med. 2019 Dec 13;8(12):2202.
https://www.mdpi.com/2077-0383/8/12/2202
http://www.ncbi.nlm.nih.gov/pubmed/31847205?tool=bestpractice.com
[20]da Silva JSV, Seres DS, Sabino K, et al. ASPEN consensus recommendations for refeeding syndrome. Nutr Clin Pract. 2020 Apr;35(2):178-95.
https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10474
http://www.ncbi.nlm.nih.gov/pubmed/32115791?tool=bestpractice.com
Patients with a lower body mass index, or with no oral intake for an extended period, are at increased risk for refeeding syndrome.[20]da Silva JSV, Seres DS, Sabino K, et al. ASPEN consensus recommendations for refeeding syndrome. Nutr Clin Pract. 2020 Apr;35(2):178-95.
https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.10474
http://www.ncbi.nlm.nih.gov/pubmed/32115791?tool=bestpractice.com
[21]Corsello A, Trovato CM, Dipasquale V, et al. Refeeding syndrome in pediatric age, an unknown disease: a narrative review. J Pediatr Gastroenterol Nutr. 2023 Dec 1;77(6):e75-83.
https://onlinelibrary.wiley.com/doi/10.1097/MPG.0000000000003945
http://www.ncbi.nlm.nih.gov/pubmed/37705405?tool=bestpractice.com
Surgery
Gastrointestinal surgery, including bariatric surgery, may lead to vitamin B1 deficiency.[22]Oudman E, Wijnia JW, van Dam M, et al. Preventing Wernicke encephalopathy after bariatric surgery. Obes Surg. 2018 Jul;28(7):2060-8.
https://link.springer.com/article/10.1007/s11695-018-3262-4
http://www.ncbi.nlm.nih.gov/pubmed/29693218?tool=bestpractice.com
[23]Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures – 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society For Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists - executive summary. Endocr Pract. 2019 Dec;25(12):1346-59.
https://www.endocrinepractice.org/article/S1530-891X(20)42802-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/31682518?tool=bestpractice.com
[24]Restivo A, Carta MG, Farci AMG, et al. Risk of thiamine deficiency and Wernicke's encephalopathy after gastrointestinal surgery for cancer. Support Care Cancer. 2016 Jan;24(1):77-82.
http://www.ncbi.nlm.nih.gov/pubmed/25931232?tool=bestpractice.com
[25]Patel JJ, Mundi MS, Hurt RT, et al. Micronutrient deficiencies after bariatric surgery: an emphasis on vitamins and trace minerals [Formula: see text]. Nutr Clin Pract. 2017 Aug;32(4):471-80.
http://www.ncbi.nlm.nih.gov/pubmed/28609642?tool=bestpractice.com
Deficiency can result from a decrease in the mucosal absorptive surface of the ileum following surgery, sustained postoperative vomiting, or poor oral intake.[7]Polegato BF, Pereira AG, Azevedo PS, et al. Role of thiamin in health and disease. Nutr Clin Pract. 2019 Aug;34(4):558-64.
http://www.ncbi.nlm.nih.gov/pubmed/30644592?tool=bestpractice.com
[26]Pacei F, Tesone A, Laudi N, et al. The relevance of thiamine evaluation in a practical setting. Nutrients. 2020 Sep 13;12(9):2810.
https://www.mdpi.com/2072-6643/12/9/2810
http://www.ncbi.nlm.nih.gov/pubmed/32933220?tool=bestpractice.com
Vitamin B1 deficiency has been reported in 16% to 29% of patients planning to undergo bariatric surgery for obesity.[16]Maguire D, Talwar D, Shiels PG, et al. The role of thiamine dependent enzymes in obesity and obesity related chronic disease states: a systematic review. Clin Nutr ESPEN. 2018 Jun;25:8-17.
http://www.ncbi.nlm.nih.gov/pubmed/29779823?tool=bestpractice.com
Genetic causes
Several rare syndromes of thiamine metabolism dysfunction have been described. These syndromes result from genetic defects in thiamine transport and metabolism and are generally detected in younger individuals.[27]Ortigoza-Escobar JD, Alfadhel M, Molero-Luis M, et al. Thiamine deficiency in childhood with attention to genetic causes: survival and outcome predictors. Ann Neurol. 2017 Sep;82(3):317-30.
http://www.ncbi.nlm.nih.gov/pubmed/28856750?tool=bestpractice.com
[28]Marcé-Grau A, Martí-Sánchez L, Baide-Mairena H, et al. Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics, and functional studies. J Inherit Metab Dis. 2019 Jul;42(4):581-97.
http://www.ncbi.nlm.nih.gov/pubmed/31095747?tool=bestpractice.com
Mutations in SLC19A2 (thiamine transporter-1), SLC19A3 (thiamine transporter-2), TPK1 (thiamine pyrophosphokinase), and SLC25A19 (mitochondrial thiamine pyrophosphate carrier) exhibit well-defined clinical phenotypes.[27]Ortigoza-Escobar JD, Alfadhel M, Molero-Luis M, et al. Thiamine deficiency in childhood with attention to genetic causes: survival and outcome predictors. Ann Neurol. 2017 Sep;82(3):317-30.
http://www.ncbi.nlm.nih.gov/pubmed/28856750?tool=bestpractice.com
Thiamine-responsive megaloblastic anaemia (TRMA) syndrome is a rare disease characterised by thiamine-responsive anaemia, diabetes, and deafness; it is caused by recessively inherited mutations in the SLC19A2 gene.[28]Marcé-Grau A, Martí-Sánchez L, Baide-Mairena H, et al. Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics, and functional studies. J Inherit Metab Dis. 2019 Jul;42(4):581-97.
http://www.ncbi.nlm.nih.gov/pubmed/31095747?tool=bestpractice.com
[29]Habeb AM, Flanagan SE, Zulali MA, et al. Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome. Diabetologia. 2018 May;61(5):1027-36.
https://link.springer.com/article/10.1007/s00125-018-4554-x
http://www.ncbi.nlm.nih.gov/pubmed/29450569?tool=bestpractice.com
Mutations in SLC19A3, TPK1, and SLC25A19 genes predominantly result in neurological sequelae with episodic encephalopathy, often triggered by febrile illness or infection.[27]Ortigoza-Escobar JD, Alfadhel M, Molero-Luis M, et al. Thiamine deficiency in childhood with attention to genetic causes: survival and outcome predictors. Ann Neurol. 2017 Sep;82(3):317-30.
http://www.ncbi.nlm.nih.gov/pubmed/28856750?tool=bestpractice.com
[28]Marcé-Grau A, Martí-Sánchez L, Baide-Mairena H, et al. Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics, and functional studies. J Inherit Metab Dis. 2019 Jul;42(4):581-97.
http://www.ncbi.nlm.nih.gov/pubmed/31095747?tool=bestpractice.com
Pre-existing conditions and their treatment
Malignancy can be associated with anorexia, nausea and vomiting, malabsorption, and accelerated metabolism of thiamine, placing patients with cancer at increased risk of vitamin B1 deficiency.[30]Isenberg-Grzeda E, Rahane S, DeRosa AP, et al. Wernicke-Korsakoff syndrome in patients with cancer: a systematic review. Lancet Oncol. 2016 Apr;17(4):e142-8.
http://www.ncbi.nlm.nih.gov/pubmed/27300674?tool=bestpractice.com
[31]Isenberg-Grzeda E, Alici Y, Hatzoglou V, et al. Nonalcoholic thiamine-related encephalopathy (Wernicke-Korsakoff syndrome) among inpatients with cancer: a series of 18 cases. Psychosomatics. 2016 Jan-Feb;57(1):71-81.
https://www.sciencedirect.com/science/article/pii/S0033318215001589
http://www.ncbi.nlm.nih.gov/pubmed/26791514?tool=bestpractice.com
Patients with gastrointestinal and haematological malignancies are particularly at risk because there are multiple mechanisms by which these cancers can lead to vitamin B1 deficiency, either through increased metabolism of thiamine (by fast-growing cancer cells) or causes of inadequate thiamine supply (e.g., mucositis, gastrointestinal obstruction, gastrointestinal tract resection, total parenteral nutrition).[30]Isenberg-Grzeda E, Rahane S, DeRosa AP, et al. Wernicke-Korsakoff syndrome in patients with cancer: a systematic review. Lancet Oncol. 2016 Apr;17(4):e142-8.
http://www.ncbi.nlm.nih.gov/pubmed/27300674?tool=bestpractice.com
Some chemotherapeutic agents interfere with thiamine function.[30]Isenberg-Grzeda E, Rahane S, DeRosa AP, et al. Wernicke-Korsakoff syndrome in patients with cancer: a systematic review. Lancet Oncol. 2016 Apr;17(4):e142-8.
http://www.ncbi.nlm.nih.gov/pubmed/27300674?tool=bestpractice.com
Renal replacement therapy causes loss of water soluble vitamins, such as vitamin B1.[32]Berger MM, Broman M, Forni L, et al. Nutrients and micronutrients at risk during renal replacement therapy: a scoping review. Curr Opin Crit Care. 2021 Aug 1;27(4):367-77.
https://journals.lww.com/co-criticalcare/fulltext/2021/08000/nutrients_and_micronutrients_at_risk_during_renal.7.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34039873?tool=bestpractice.com
This may occur due to losses in the effluent fluid, in addition to poor oral intake.[33]Lumlertgul N, Cameron LK, Bear DE, et al. Micronutrient losses during continuous renal replacement therapy. Nephron. 2023;147(12):759-65.
http://www.ncbi.nlm.nih.gov/pubmed/37611551?tool=bestpractice.com
Case reports suggest that women with hyperemesis gravidarum are at risk of vitamin B1 deficiency, which may lead to Wernicke’s encephalopathy if untreated, especially during refeeding.[34]Oudman E, Wijnia JW, Oey M, et al. Wernicke's encephalopathy in hyperemesis gravidarum: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2019 May;236:84-93.
http://www.ncbi.nlm.nih.gov/pubmed/30889425?tool=bestpractice.com
[35]Erick M. Gestational malnutrition, hyperemesis gravidarum, and Wernicke's encephalopathy: what is missing? Nutr Clin Pract. 2022 Dec;37(6):1273-90.
http://www.ncbi.nlm.nih.gov/pubmed/36250744?tool=bestpractice.com
HIV infection and AIDS have been associated with increased risk of vitamin B1 deficiency.[36]Le Berre AP, Fama R, Sassoon SA, et al. Cognitive and motor impairment severity related to signs of subclinical Wernicke's encephalopathy in HIV infection. J Acquir Immune Defic Syndr. 2019 Jul 1;81(3):345-54.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6565459
http://www.ncbi.nlm.nih.gov/pubmed/30958387?tool=bestpractice.com
Magnesium is a co-factor for thiamine-containing enzymes.[16]Maguire D, Talwar D, Shiels PG, et al. The role of thiamine dependent enzymes in obesity and obesity related chronic disease states: a systematic review. Clin Nutr ESPEN. 2018 Jun;25:8-17.
http://www.ncbi.nlm.nih.gov/pubmed/29779823?tool=bestpractice.com
Thus, an adequate supply of magnesium is required in order for thiamine to function optimally. Causes of magnesium deficiency include increased loss of magnesium (e.g., diarrhoea following bariatric surgery), low dietary intake (e.g., in alcohol-related liver disease), increased urinary loss of magnesium in distal tubular dysfunction, and drugs (e.g., proton-pump inhibitors).[16]Maguire D, Talwar D, Shiels PG, et al. The role of thiamine dependent enzymes in obesity and obesity related chronic disease states: a systematic review. Clin Nutr ESPEN. 2018 Jun;25:8-17.
http://www.ncbi.nlm.nih.gov/pubmed/29779823?tool=bestpractice.com
[37]Liu M, Yang H, Mao Y. Magnesium and liver disease. Ann Transl Med. 2019 Oct;7(20):578.
https://atm.amegroups.org/article/view/29876/26354
http://www.ncbi.nlm.nih.gov/pubmed/31807559?tool=bestpractice.com
[38]Ahmed F, Mohammed A. Magnesium: The forgotten electrolyte-a review on hypomagnesemia. Med Sci (Basel). 2019 Apr 4;7(4):56.
https://www.mdpi.com/2076-3271/7/4/56
http://www.ncbi.nlm.nih.gov/pubmed/30987399?tool=bestpractice.com