Thiamine, also known as vitamin B1, is an essential nutrient that plays important roles in energy metabolism and cellular functions. Thiamine deficiency, if untreated, can lead to serious medical conditions such as beriberi and Wernicke-Korsakoff syndrome. Therefore, testing for thiamine deficiency is important in at-risk populations to allow early detection and treatment.
Who is at risk of thiamine deficiency?
Certain groups are at higher risk of developing thiamine deficiency and should be screened:
- Alcoholics – Heavy alcohol consumption impairs thiamine absorption and utilization.
- Bariatric surgery patients – Reduced food intake and vomiting after surgery can lead to deficiency.
- Cancer patients – Increased metabolic demand combined with reduced intake, vomiting, and chemotherapy side effects increase risk.
- Elderly – Reduced food intake, impaired absorption, and medical conditions like heart failure increase risk in the elderly.
- Pregnant women – Increased demand during pregnancy and lactation can result in deficiency.
- Critically ill patients – Severe illness leads to increased metabolic demand and deficiency.
- Patients on diuretics or parenteral nutrition – These treatments increase thiamine excretion.
- Dialysis patients – Thiamine is removed during dialysis treatments.
- People with diabetes, thyroid disorders, or other conditions that increase metabolic rate.
- People with gastrointestinal disorders that impair thiamine absorption such as Crohn’s disease.
- People with malnutrition from any cause.
What are the symptoms of thiamine deficiency?
Early thiamine deficiency may have nonspecific symptoms including:
- Fatigue
- Irritability
- Poor appetite
- Nausea
- Weight loss
As deficiency progresses, more specific neurological symptoms develop:
- Confusion
- Memory impairment
- Loss of muscle coordination (ataxia)
- Muscle weakness
- Eye movement disorders
- Psychosis
Without treatment, severe thiamine deficiency can lead to permanent neurological damage and conditions such as:
- Wernicke’s encephalopathy – Brain disorder characterized by confusion, paralysis of eye movements, and impaired muscle coordination
- Korsakoff psychosis – Dementia-like condition with severe short-term memory loss, confusion, and confabulation (making up information to fill gaps in memory)
- Beriberi – Disease caused by thiamine deficiency featuring cardiovascular and/or neurological abnormalities
Laboratory Testing
There are several laboratory tests that can be used to assess thiamine status:
Erythrocyte Thiamine Pyrophosphate (eTPP) Levels
Measurement of thiamine pyrophosphate in red blood cells is considered the most reliable indicator of thiamine status in the body. Thiamine pyrophosphate (TPP) is the biologically active form of thiamine. Red blood cell levels reflect tissue levels better than plasma thiamine levels.
- Levels below the reference range indicate thiamine deficiency.
- May remain normal in early deficiency when other tests are abnormal.
- Time consuming test that requires special laboratory equipment – not routinely available at most hospitals.
Thiamine Pyrophosphate Effect (TPPE)
The TPPE test assesses biochemical evidence of thiamine deficiency at the cellular level by measuring the activity of the thiamine-dependent enzyme transketolase in red blood cells:
- Blood is drawn before and after the addition of thiamine pyrophosphate in the lab.
- If addition of thiamine increases transketolase activity by >15-25%, thiamine deficiency is likely.
- Detects early thiamine deficiency before clinical symptoms appear.
- Widely available and rapid, results within hours – useful when urgent testing is needed.
Plasma Thiamine Levels
Directly measures thiamine levels in blood plasma:
- Low plasma levels can indicate deficiency but can be normal in early stages.
- Levels may transiently increase after thiamine intake and do not reflect tissue stores.
- Simple and inexpensive test but lacks sensitivity and specificity in mild deficiency.
Urinary Thiamine Excretion
Measures thiamine excreted in the urine over a 24-hour period:
- Reduced urine thiamine levels suggest deficiency.
- Cumbersome 24-hour urine collection.
- May be normal with marginal deficiency as the body tries to conserve thiamine.
Which test is best?
There is no single gold standard test for thiamine deficiency. The eTPP level is considered the most direct measure of thiamine status but availability is limited. The TPPE test can rapidly confirm deficiency at the cellular level before symptoms occur. For initial screening, the TPPE test is recommended over plasma thiamine levels due to its greater sensitivity and specificity. In advanced deficiency, several tests may be used together to confirm the diagnosis. The choice depends on factors like clinical suspicion, urgency for results, and test availability.
Interpreting thiamine deficiency test results
Reference ranges vary between laboratories so results should always be interpreted using the particular laboratory’s reference values. Typical reference ranges are:
| Test | Normal Range |
|---|---|
| Erythrocyte thiamine pyrophosphate (eTPP) | 170-490 nmol/L |
| Thiamine pyrophosphate effect (TPPE) | <15-25% increase |
| Plasma thiamine | 66-200 nmol/L |
| 24-hour urine thiamine | 66-200 mcg/24 hours |
Results outside the normal reference range suggest possible thiamine deficiency:
- eTPP – Levels below the reference range are consistent with thiamine deficiency. The lower the levels, the more severe the deficiency.
- TPPE – Increases of >15-25% after adding thiamine indicate deficient thiamine status. Higher percentages represent more severe deficiency.
- Plasma thiamine – Levels below the reference range suggest possible deficiency but normal levels do not rule it out.
- 24-hour urine thiamine – Excretion below the normal range can indicate deficiency. Levels may still be normal in marginal deficiency.
Factors affecting test results
Results of thiamine testing can be affected by:
- Recent thiamine intake – Can transiently increase blood or urine levels without reflecting overall status.
- Timing of specimen collection – Levels peak after intake so consistency in timing is optimal.
- Interfering substances – Medications, alcohol use, liver disease, or renal dialysis can affect results.
- Laboratory techniques – Variations in sample handling, test methods, and reference ranges between labs can affect results.
- Illness severity – Depletion of thiamine increases with progression of deficiency so critically ill patients may have lower levels.
Proper patient preparation through temporary discontinuation of supplements, fasting, and consistency in specimen timing can improve test result accuracy.
Treatment
Treatment of thiamine deficiency involves thiamine supplementation, usually by the parenteral route initially. Response to treatment and adequacy of repletion is assessed by clinical improvement and repeated testing:
- Rapid clinical improvement is expected with treatment of deficiency symptoms like confusion, ataxia, and ophthalmoplegia.
- Levels of eTPP normalize within 1-2 weeks with adequate replenishment.
- Repeat TPPE testing should show a decreased TPP effect towards normal.
- Plasma levels increase rapidly but can decrease again quickly as thiamine is taken up by the tissues so repeat testing is not very useful.
Patients at risk of thiamine deficiency, such as alcoholics, should continue on oral thiamine supplementation after initial treatment and have periodic reassessment of thiamine status.
Conclusion
Thiamine deficiency can lead to severe neurological consequences so prompt diagnosis and treatment is critical. Testing for thiamine deficiency is recommended in all at-risk individuals before clinical deficiency occurs. The TPPE test is the preferred initial test due to its sensitivity, specificity and rapid results. Treatment involves parenteral thiamine replacement and clinical and biochemical improvement should be seen with adequate repletion. Regular monitoring and supplementation is needed for those at ongoing risk of deficiency.