. 2018 Aug 27;1430(1):3–43. doi: 10.1111/nyas.13919

Table 6.

Thiamine research opportunities

Biomarkers

Current laboratory reference ranges for thiamine diphosphate (ThDP) are based on the range of thiamine status in populations without thiamine deficiency, and there are no commonly accepted clinically relevant cut‐points for thiamine deficiency based on ThDP. A more appropriate cutoff for deficiency should consider clinical manifestations of thiamine deficiency in at‐risk populations to better assess and define thiamine deficiency.

Research need: Establish deficiency cutoffs for ThDP that are relevant to populations with endemic thiamine deficiency.

Comparing the different biomarker data for thiamine deficiency is currently challenging because there are few studies relating blood ThDP concentrations to the corresponding erythrocyte transketolase activation coefficient (ETKAC) values. Additionally, there are no published data comparing the biomarkers in a deficient population. As both biomarkers are currently used, understanding their interrelationship is important for comparing data from different studies.

Research need: Determine the relationship between whole blood/erythrocyte ThDP concentrations and ETKAC.

There are a number of challenges to assessing thiamine status in low‐ and middle‐income countries (LMIC), including the required cold chain and limited availability of laboratories to analyze thiamine status.

Research need: Development of point‐of‐care diagnostics for rapid assessment of thiamine status.


Owing to the wide variability in clinical presentations, TDDs do not have standardized case definitions. Research need: Develop a set of standardized case definitions for TDDs.
Based on the long‐term follow‐up of the Israeli children who received infant formula that was inadvertently lacking thiamine, it appears that there are long‐term neurological effects of short‐term thiamine deficiency. Long‐term adverse effects on neurodevelopment were even identified in children with subclinical deficiency. Research need: Determine the long‐term effects of subclinical thiamine deficiency.
Current strategies to reduce infantile beriberi include maternal thiamine supplementation, which successfully increases the thiamine content in breast milk. However, long‐term effects of such an intervention on the children have not been studied, especially with respect to their neurocognitive development. Research need: Evaluate the effects of maternal thiamine supplementation on long‐term neurocognitive outcomes in infants.

Thiamine deficiency disorders

Owing to the wide variability in clinical presentations, TDDs do not have standardized case definitions.

Based on the long‐term follow‐up of the Israeli children who received infant formula that was inadvertently lacking thiamine, it appears that there are long‐term neurological effects of short‐term thiamine deficiency. Long‐term adverse effects on neurodevelopment were even identified in children with subclinical deficiency.

Research need: Determine the long‐term effects of subclinical thiamine deficiency.

Current strategies to reduce infantile beriberi include maternal thiamine supplementation, which successfully increases the thiamine content in breast milk. However, long‐term effects of such an intervention on the children have not been studied, especially with respect to their neurocognitive development.

Research need: Evaluate the effects of maternal thiamine supplementation on long‐term neurocognitive outcomes in infants.


Thiamine status is rarely assessed in LMIC, making estimates of the prevalence of deficiency difficult. Improving these estimates would help identify areas where interventions are most needed. Research need: Increase the incorporation of thiamine status assessment in population‐based nutrition and health surveys.

Thiamine deficiency prevalence

Thiamine status is rarely assessed in LMIC, making estimates of the prevalence of deficiency difficult. Improving these estimates would help identify areas where interventions are most needed.

Research need: Increase the incorporation of thiamine status assessment in population‐based nutrition and health surveys.


Some maternal thiamine supplementation programs end 3 months after birth and do not cover the remaining period of exclusive breastfeeding. The lowest effective dose of supplementation has also never been established. Research need: Identify the necessary dose and duration of maternal thiamine supplementation to prevent infantile beriberi.
In many countries, infants older than 6 months of age receive micronutrient powders (MNP) that include thiamine. The impact of this intervention on thiamine status has not been well documented, but it is likely to improve status. Research need: Assess whether MNP improve thiamine status and functional outcomes associated with thiamine, such as language skills or cognitive development.
Patients with severe acute malnutrition (SAM) treated in healthcare centers are often critically ill and may have multiple comorbidities. Since thiamine requirements are increased in critically ill patients, there is a high risk of thiamine insufficiency in these SAM patients. Research need: Determine the appropriate dose of thiamine for the treatment of SAM and specifically the dose that is used in F75 milk, during the early phases of refeeding.

Thiamine deficiency prevention

Some maternal thiamine supplementation programs end 3 months after birth and do not cover the remaining period of exclusive breastfeeding. The lowest effective dose of supplementation has also never been established.

Research need: Identify the necessary dose and duration of maternal thiamine supplementation to prevent infantile beriberi.

In many countries, infants older than 6 months of age receive micronutrient powders (MNP) that include thiamine. The impact of this intervention on thiamine status has not been well documented, but it is likely to improve status.

Research need: Assess whether MNP improve thiamine status and functional outcomes associated with thiamine, such as language skills or cognitive development.

Patients with severe acute malnutrition (SAM) treated in healthcare centers are often critically ill and may have multiple comorbidities. Since thiamine requirements are increased in critically ill patients, there is a high risk of thiamine insufficiency in these SAM patients.

Research need: Determine the appropriate dose of thiamine for the treatment of SAM and specifically the dose that is used in F75 milk, during the early phases of refeeding.