When Whole-Blood Thiamine Is Not Low: Repeated Clinical-Biomarker Discordance and a Case-Generated Hypothesis
Year: 2026
Type: preprint
Study design: Case Report
Abstract: Whole-blood thiamine pyrophosphate (TPP) is a well-supported biomarker of thiamine status, but a non-low result is not a validated universal exclusion criterion for clinically relevant thiamine-dependent dysfunction. This case-generated perspective examines three whole-blood thiamine measurements obtained during substantial multisystem illness. On February 15, 2023, before dedicated B1 supplementation began in 2026, the reported 'Vitamin B1, WB' concentration was 105 nmol/L (reference interval 64-201); the measured B1 species was not specified. The patient reports that a review of personal medication records showed no B-complex use within one month before or after that collection. Whole-blood TPP was 210 nmol/L on February 10, 2026 and 415 nmol/L on June 18, 2026 (reference interval 70-180 for each), after prior or during active thiamine supplementation. The aggregate phenotype was closely concordant with historically described multisystem manifestations of beriberi, although individual findings were nonspecific. We call the coexistence of this clinical state with non-low laboratory values 'clinical-biomarker discordance' without assuming blood-tissue biochemical discordance. Published evidence supports whole-blood TPP for status assessment while showing that concentration and erythrocyte function need not classify every patient identically; biomarker performance depends on the diagnostic target; and clinically supported Wernicke encephalopathy can occur with within-range whole-blood thiamine. Human genetic and functional studies separately establish the biological roles of thiamine transport, TPP formation, and mitochondrial delivery. The 2023 measurement is the least supplementation-confounded laboratory anchor; the two 2026 values are not untreated replications. Reported treatment observations were heterogeneous: several oral forms produced no meaningful principal-symptom change, TTFD-containing supplementation was partially associated with improvement, one early repeated-dose IM period coincided with uniquely broad improvement, later IM effects were shorter or absent, and IV-associated outcomes were limited or discordant. The observations establish coexistence of substantial illness with non-low blood results, not the adequacy or inadequacy of an unmeasured thiamine-dependent tissue function. We postulate that, in some pathological states, a non-low whole-blood thiamine result may offer substantially less exclusionary reassurance concerning a clinically relevant thiamine-dependent target than its reference-range classification suggests. This hypothesis does not establish tissue-specific deficiency, a responsible compartment or mechanism, assay failure, or causation from treatment response.
Author: Farley, Dale
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225656055