Thiamine (Vitamin B1)
Thiamine supports energy metabolism through thiamine diphosphate, also called thiamine pyrophosphate (ThDP/TPP). Deficiency can cause neuropathy, cardiac failure and Wernicke encephalopathy (WE). The main risk settings in reconstructive practice are prolonged inadequate intake, persistent vomiting after bariatric surgery, alcohol dependence and refeeding risk.[1][2][22]
Give parenteral thiamine without waiting for a blood result or MRI. Do not delay emergency glucose treatment for hypoglycemia; give thiamine concurrently or as soon as possible. For planned feeding or sustained dextrose administration in a patient at risk of refeeding syndrome, give thiamine before starting nutrition when feasible. A preventive 100 mg dose is not a complete treatment course for suspected WE.[9][23][24][25]
Biochemistry and requirements
Thiamine is absorbed in the small intestine; limited stores require a continuing dietary supply. Depletion can develop over weeks, and vomiting or severe malnutrition can accelerate the clinical problem.[2][22][28]
ThDP is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-ketoacid dehydrogenase and transketolase. The first three support oxidative fuel metabolism. Transketolase transfers carbon units in the nonoxidative pentose phosphate pathway; it does not directly generate NADPH. Impaired oxidative metabolism can produce lactate accumulation and organ dysfunction.[3][6]
The adult RDA is 1.2 mg/day for men, 1.1 mg/day for women and 1.4 mg/day during pregnancy or lactation.[28] These dietary requirements differ from preventive doses in high-risk settings and treatment doses. Sources include enriched or whole grains, pork, fish and legumes; dairy is a relatively poor source. No oral tolerable upper intake level has been established because adverse-effect data are insufficient. This does not eliminate the rare hypersensitivity or anaphylaxis risk of parenteral treatment.[28][25]
Assessing thiamine status
| Assessment | Interpretation |
|---|---|
| Whole-blood or erythrocyte ThDP | Direct assessment used by clinical laboratories; interpret against the assay's reference range, symptoms and treatment history. A normal result does not reliably exclude WE. Obtain a pretreatment sample if this causes no treatment delay. |
| Erythrocyte transketolase activity coefficient (ETKAC) | Stimulated divided by basal enzyme activity. A commonly used deficiency-risk threshold is >1.25, equivalent to >25% activation. Cutoffs and methods are not internationally standardized.[6] |
| Plasma/serum thiamine | Strongly influenced by recent intake and does not reliably represent longer-term tissue status. |
| Clinical assessment and response | Neurologic findings, nutrition history and response support diagnosis. Persistent symptoms require reassessment; lack of immediate recovery does not by itself exclude deficiency. |
Both direct and functional assays have limitations. ETKAC interpretation can be affected by sample handling, erythrocyte turnover and chronic deficiency; blood tests should support, rather than postpone, treatment of a clinical emergency.[6][7][27]
Risk factors
| Mechanism | Important settings |
|---|---|
| Inadequate intake | Alcohol dependence, starvation, prolonged vomiting, severe restriction, nutrition support without adequate vitamins |
| Impaired absorption | Bariatric/gastric surgery, chronic gastrointestinal disease, alcohol-associated malabsorption |
| Increased losses | Renal replacement therapy; loop diuretics may contribute in a nutritionally vulnerable patient |
| Increased requirement | Refeeding, pregnancy with poor intake, critical illness |
| Impaired utilization | Alcohol-related effects and magnesium deficiency |
Risk depends on the combination of intake, losses and illness. A medication or operation alone does not define it.[1][2][22]
After bariatric surgery, estimates vary substantially by procedure, follow-up, supplementation and study. A 2024 meta-analysis of 41 studies estimated deficiency prevalence of 7% before surgery, 19% at three months, 9% at six months and 6% at one year; the three-month confidence interval was very wide (0–68%).[11] The separate 2022 pooled estimate of 27% used a different evidence set.[10][11]
Clinical manifestations
Neurologic and cardiac beriberi
Dry beriberi commonly produces a symmetric, length-dependent sensorimotor neuropathy with weakness, sensory symptoms and reduced reflexes. Rapid presentations can resemble other acute neuropathies.[4][12]
Wet beriberi can cause vasodilation, edema and heart failure; fulminant Shoshin beriberi can present with shock and lactic acidosis. Suspected cardiac beriberi with instability requires urgent hospital treatment with parenteral thiamine and cardiovascular support. Improvement can be rapid, but recovery depends on severity and coexisting disease.[1][22]
Wernicke encephalopathy and Korsakoff syndrome
WE is a clinical emergency. Confusion or memory disturbance, eye-movement abnormalities and gait or cerebellar dysfunction may occur in different combinations; absence of the complete classic triad does not exclude it. The Caine approach considers at least two of dietary deficiency, oculomotor abnormalities, cerebellar dysfunction, and altered mental state or memory impairment, particularly in alcohol-related disease.[7][13][27]
Korsakoff syndrome can leave persistent severe memory impairment after WE. Recovery varies, and neither progression nor irreversibility is inevitable.[8][27]
MRI can support the diagnosis, with symmetric abnormalities around the medial thalami, mammillary bodies, periaqueductal region and other vulnerable structures. A normal MRI does not exclude WE and imaging must not delay treatment. Atypical lesions and diffusion restriction occur.[5][13][14][15]
Treatment and prevention: use the correct regimen
| Situation | Guideline-based approach |
|---|---|
| Suspected/established WE | UK alcohol-treatment guidance recommends 300–500 mg IV three times daily for 3–5 days, with daily review. If symptoms persist after the first 5 days, continue 300–500 mg IV daily for a further 3–5 days and while clinical improvement continues; reassess other causes and follow with oral treatment.[25] For patients after bariatric surgery or otherwise at high risk of thiamine deficiency, Table 2 of the 2025 ASMBS Wernicke Task Force paper recommends 500 mg IV three times daily for at least 5 days and until no further clinical improvement, followed by 300 mg orally two or three times daily until risk factors resolve and then 100 mg orally daily indefinitely, with frequent in-person reassessment for relapse.[30] Use the institution's specialist protocol and appropriate infusion/monitoring arrangements. |
| Alcohol-withdrawal prophylaxis | ASAM describes 100 mg IV/IM daily for 3–5 days; parenteral administration is preferred with malnutrition, malabsorption or severe withdrawal complications. Oral thiamine can also be offered. This is a prevention regimen, not the WE treatment regimen above.[9] |
| High risk of WE without signs of WE (alcohol-related) | Regimens vary. UK guidance uses 200–300 mg IV/IM daily for 3–5 days, with review and subsequent oral therapy. New neurologic signs require escalation to treatment dosing.[25] |
| Bariatric prevention | The 2016 ASMBS micronutrient guideline recommends at least 12 mg/day (Grade C, BEL 3), preferably 50 mg once or twice daily (Grade D, BEL 4) from a B-complex or multivitamin. For patients at high risk of deficiency during bariatric or medical weight-loss treatment, the 2025 ASMBS Wernicke Task Force recommends 100 mg orally daily beginning at least two weeks before treatment, continuing during weight-loss medication use and for at least three months after surgery, then at least 12 mg daily indefinitely.[30] Persistent vomiting or neurologic symptoms require assessment and empiric treatment.[26] |
| Bariatric deficiency without an acute neurologic/cardiac emergency | The 2016 ASMBS micronutrient guideline recommends oral thiamine 100 mg two or three times daily until symptoms resolve (Grade D, BEL 4). Use parenteral treatment when clinically indicated, including inability to retain or absorb oral therapy; suspected WE requires the emergency pathway.[26] For symptomatic thiamine deficiency, the 2025 ASMBS Wernicke Task Force advises 100 mg IV or IM daily for one to three doses, or until symptoms resolve and oral intake is adequate.[30] |
| Refeeding risk | ASPEN recommends 100 mg before planned feeding or dextrose-containing IV fluids in patients at risk. For severe starvation, chronic alcohol dependence, or other high risk for deficiency and/or signs of deficiency, it recommends 100 mg daily for 5–7 days or longer. Choose a route that can be delivered and absorbed reliably.[24] |
| Pregnancy with vomiting requiring admission or severely reduced intake | RCOG recommends thiamine (Grade D): 100 mg orally three times daily or IV vitamin-B complex, especially before dextrose or parenteral nutrition. Suspected WE requires urgent specialist treatment, not prophylaxis alone.[29] |
Check and correct hypomagnesemia, which can impair response. IV administration requires staff and equipment able to manage hypersensitivity. Rare reactions do not justify withholding indicated emergency treatment.[9][25]
The optimal WE dose is not settled by strong comparative evidence. Dingwall's 2022 randomized studies included 393 asymptomatic at-risk and 127 symptomatic alcohol-misuse patients. They found no clear cognitive or neurologic advantage of higher doses over the short follow-up. Substantial missing follow-up, incomplete dosing and limited recruitment of very ill patients restrict interpretation, and the results do not establish dose equivalence.[27]
Glucose and refeeding
Hypoglycemia is corrected immediately. ASAM permits glucose and thiamine in either order or concurrently. The glucose-before-thiamine literature largely comprises case reports and indirect evidence; the concern is prolonged carbohydrate administration without thiamine replacement in a depleted patient, and it does not justify delaying a lifesaving glucose dose.[9][23]
For planned nutrition, identify refeeding risk, provide thiamine, and check potassium, magnesium and phosphate before starting. ASPEN recommends checking these electrolytes every 12 hours during the first three days in high-risk patients, adjusting to the clinical situation. Thiamine alone does not prevent electrolyte shifts or replace a monitored feeding plan. Routine thiamine levels are unlikely to guide refeeding prophylaxis. See Perioperative Nutrition.[24]
Heart failure and sepsis: replacement is different from routine adjunct therapy
In heart failure, a meta-analysis of eight RCTs with 384 patients did not find improvement in LVEF, NYHA class, BNP or quality of life from routine thiamine supplementation. Keith's 69-patient trial likewise did not support routine treatment of stable ambulatory HF. This does not argue against treating actual deficiency or beriberi. Loop-diuretic use alone is not an indication for universal preoperative thiamine testing or supplementation.[16][17][18]
Large trials have not supported the vitamin C–hydrocortisone–thiamine combination as routine sepsis treatment:
| Trial | Population and comparison | Main result |
|---|---|---|
| VITAMINS, 2020 | 216 randomized; 211 in the primary analysis; combination versus hydrocortisone alone | No improvement in time alive and free of vasopressor support.[19] |
| ACTS, 2020 | 205 randomized, 200 treated; combination versus placebo | No significant improvement in SOFA score change over 72 hours.[20] |
| VICTAS, 2021 | 501 randomized; combination versus placebo | No significant increase in ventilator- and vasopressor-free days. Administrative termination before the intended maximum enrollment limits certainty.[21] |
These combination trials do not isolate thiamine's effect in patients with confirmed deficiency.
Applying this to reconstruction
- Before surgery. review intake, weight loss, bariatric anatomy, vomiting, alcohol dependence and supplementation. Test when the result will aid management; do not order universal screening based solely on loop-diuretic use or any vomiting in the previous month.
- During prolonged ileus, fistula care or nutritional rehabilitation. assess refeeding risk and ensure vitamin provision in the nutrition prescription. A fixed number of NPO days does not replace assessment of baseline nutrition and actual intake.
- With unexplained confusion, ataxia or ocular findings. consider WE alongside other postoperative emergencies, obtain urgent assessment and give appropriate parenteral treatment without waiting for confirmatory tests.
- After treatment. correct the underlying cause, ensure adequate magnesium and broader nutrition, and continue supplementation and monitoring according to ongoing risk and response.
These steps apply the risk-based guidance above; routine thiamine for every reconstructive patient has not been shown to improve surgical outcomes.[9][22][24][26]
See Also
References
1. Sliwa K, Viljoen CA, Hasan B, Ntusi NAB. "Nutritional Heart Disease And Cardiomyopathies: JACC Focus Seminar 4/4." Journal of the American College of Cardiology. 2022. doi:10.1016/j.jacc.2022.08.812
2. Mrowicka M, Mrowicki J, Dragan G, Majsterek I. "The Importance of Thiamine (Vitamin B1) in Humans." Bioscience Reports. 2023;43(10):BSR20230374. doi:10.1042/BSR20230374
3. Calderón-Ospina CA, Nava-Mesa MO. "B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin." CNS Neuroscience & Therapeutics. 2020;26(1):5–13. doi:10.1111/cns.13207
4. Gwathmey KG, Grogan J. "Nutritional neuropathies." Muscle & Nerve. 2020;62(1):13–29. doi:10.1002/mus.26783
5. Manzo G, De Gennaro A, Cozzolino A, et al. "MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy: A Review." BioMed Research International. 2014;2014:503596. doi:10.1155/2014/503596
6. Jones KS, Parkington DA, Cox LJ, Koulman A. "Erythrocyte Transketolase Activity Coefficient (ETKAC) Assay Protocol for the Assessment of Thiamine Status." Annals of the New York Academy of Sciences. 2021;1498(1):77–84. doi:10.1111/nyas.14547
7. Sinha S, Kataria A, Kolla BP, Thusius N, Loukianova LL. "Wernicke Encephalopathy — Clinical Pearls." Mayo Clinic Proceedings. 2019;94(6):1065–1072. doi:10.1016/j.mayocp.2019.02.018
8. Wijnia JW. "A Clinician's View of Wernicke-Korsakoff Syndrome." Journal of Clinical Medicine. 2022;11(22):6755. doi:10.3390/jcm11226755
9. American Society of Addiction Medicine. "Clinical Practice Guideline on Alcohol Withdrawal Management." 2020. Recommendations V.7–V.11. Full guideline.
10. Bahardoust M, Eghbali F, Shahmiri SS, et al. "B1 Vitamin Deficiency After Bariatric Surgery, Prevalence, and Symptoms: A Systematic Review and Meta-Analysis." Obesity Surgery. 2022;32(9):3104–3112. doi:10.1007/s11695-022-06178-7
11. Karimi Behnagh A, Eghbali M, Abdolmaleki F, Abbasi M, Mottaghi A. "Pre- And Post-Surgical Prevalence of Thiamine Deficiency in Patients Undergoing Bariatric Surgery: A Systematic Review and Meta-Analysis." Obesity Surgery. 2024;34(2):653–665. doi:10.1007/s11695-023-06896-6
12. Mauermann ML, Staff NP. "Peripheral Neuropathy." JAMA. 2026;335(3):255–266. doi:10.1001/jama.2025.19400
13. Sechi G, Serra A. "Wernicke's Encephalopathy: New Clinical Settings and Recent Advances in Diagnosis and Management." The Lancet Neurology. 2007;6(5):442–455. doi:10.1016/S1474-4422(07)70104-7
14. Hiraga A, Kojima K, Kuwabara S. "Typical and Atypical MRI Abnormalities in Wernicke's Encephalopathy: Correlation With Blood Vitamin B1 Levels." Journal of the Neurological Sciences. 2024;461:123045. doi:10.1016/j.jns.2024.123045
15. Chu K, Kang DW, Kim HJ, Lee YS, Park SH. "Diffusion-Weighted Imaging Abnormalities in Wernicke Encephalopathy: Reversible Cytotoxic Edema?" Archives of Neurology. 2002;59(1):123–127. doi:10.1001/archneur.59.1.123
16. Xu M, Ji J, Lu Q, et al. "The Effects of Thiamine Supplementation on Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." Complementary Therapies in Medicine. 2022;70:102853. doi:10.1016/j.ctim.2022.102853
17. Keith M, Quach S, Ahmed M, et al. "Thiamin Supplementation Does Not Improve Left Ventricular Ejection Fraction in Ambulatory Heart Failure Patients: A Randomized Controlled Trial." The American Journal of Clinical Nutrition. 2019;110(6):1287–1295. doi:10.1093/ajcn/nqz192
18. Chow SL, Bozkurt B, Baker WL, et al. "Complementary and Alternative Medicines in the Management of Heart Failure: AHA Scientific Statement." Circulation. 2023;147(2):e4–e30. doi:10.1161/CIR.0000000000001110
19. Fujii T, Luethi N, Young PJ, et al. "Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial." JAMA. 2020;323(5):423–431. doi:10.1001/jama.2019.22176
20. Moskowitz A, Huang DT, Hou PC, et al. "Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial." JAMA. 2020;324(7):642–650. doi:10.1001/jama.2020.11946
21. Sevransky JE, Rothman RE, Hager DN, et al. "Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial." JAMA. 2021;325(8):742–750. doi:10.1001/jama.2020.24505
22. Wilson RB. "Pathophysiology, Prevention, and Treatment of Beriberi After Gastric Surgery." Nutrition Reviews. 2020;78(12):1015–1029. doi:10.1093/nutrit/nuaa004
23. Schabelman E, Kuo D. Glucose before thiamine for Wernicke encephalopathy: a literature review. J Emerg Med. 2012;42(4):488–494. doi:10.1016/j.jemermed.2011.05.076.
24. da Silva JSV, Seres DS, Sabino K, et al. ASPEN consensus recommendations for refeeding syndrome. Nutr Clin Pract. 2020;35(2):178–195. Table 6. doi:10.1002/ncp.10474.
25. UK Department of Health and Social Care. Clinical guidelines for alcohol treatment. 2025; section 16.9.4, Wernicke encephalopathy. Current guidance.
26. Parrott J, Frank L, Rabena R, et al. American Society for Metabolic and Bariatric Surgery integrated health nutritional guidelines for the surgical weight loss patient—2016 update: micronutrients. Surg Obes Relat Dis. 2017;13:727–741. doi:10.1016/j.soard.2016.12.018. Full guideline.
27. Dingwall KM, Delima JF, Binks P, Batey R, Bowden SC. What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke–Korsakoff syndrome? Results of a randomized controlled trial. Alcohol Clin Exp Res. 2022;46:1133–1147. doi:10.1111/acer.14843.
28. NIH Office of Dietary Supplements. Thiamin: fact sheet for health professionals. Dietary requirements and safety.
29. Nelson-Piercy C, Dean C, Shehmar M, et al. The management of nausea and vomiting in pregnancy and hyperemesis gravidarum (Green-top Guideline No. 69). BJOG. 2024;131:e1–e30. doi:10.1111/1471-0528.17739.
30. Patterson E, Kurian M, Sann N, et al. "ASMBS literature review & clinical guidelines on prevention, diagnosis, and treatment of Wernicke’s encephalopathy and Wernicke-Korsakoff syndrome." Surg Obes Relat Dis. 2025;21(7):707–718. doi:10.1016/j.soard.2025.03.009