From perinatal thiamine insufficiency to growth-phase airway phenotypes: A developmental hypothesis on craniofacial growth, functional oral tongue space, and collapsibility

• Perinatal thiamine insufficiency may constrain craniofacial morphogenesis. • Reduced oral tongue space promotes mouth breathing and hyoid descent. • Sequence increases airway collapsibility and risk of sleep-disordered breathing. • Processed diets, alcohol, and diuretics can induce functional thiamine scarcity. • Biomarkers, organoids, and biomechanics provide feasible testing strategies. Craniofacial growth, oral posture, and airway collapsibility arise from interacting developmental, metabolic, and biomechanical factors, yet the potential contribution of perinatal micronutrient status remains underexplored. It is hypothesized that perinatal thiamine (vitamin B1) insufficiency, by constraining thiamine-dependent flux through pyruvate/α-ketoglutarate dehydrogenases and transketolase in the pentose phosphate pathway, creates a bio-energetic/redox bottleneck in cranial neural crest cells during critical windows of craniofacial morphogenesis and palatogenesis. The developmental phenotype is expected to include subtle maxillo-mandibular undergrowth and palatal shape changes that reduce functional oral tongue space, favor mouth breathing, and promote a downward resting position of the hyoid bone, thereby increasing upper airway collapsibility and sleep-disordered breathing (SDB) risk. Perinatal thiamine status is both measurable and modifiable. The model can be tested using biomarker-anchored cohorts, organoid/animal systems, and finite element simulations. Modern, highly processed diets may induce functional thiamine scarcity via increased demand, reduced availability, and increased losses, thereby priming early developmental risks even without frank deficiency. If corroborated, perinatal micronutrition plus interceptive functional/orthopedic care may lessen the burden of a hyoid-descent-prone airway phenotype while respecting SDB heterogeneity.

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Journal
Medical Hypotheses
Published
2025-12-21
DOI
https://doi.org/10.1016/j.mehy.2025.111864
Primary Topic
Alcoholism and Thiamine Deficiency
Type
article
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article

From perinatal thiamine insufficiency to growth-phase airway phenotypes: A developmental hypothesis on craniofacial growth, functional oral tongue space, and collapsibility

Björn U. Winter
Medical Hypotheses
Alcoholism and Thiamine Deficiency
article

From perinatal thiamine insufficiency to growth-phase airway phenotypes: A developmental hypothesis on craniofacial growth, functional oral tongue space, and collapsibility

Björn U. Winter
article en

Abstract

• Perinatal thiamine insufficiency may constrain craniofacial morphogenesis. • Reduced oral tongue space promotes mouth breathing and hyoid descent. • Sequence increases airway collapsibility and risk of sleep-disordered breathing. • Processed diets, alcohol, and diuretics can induce functional thiamine scarcity. • Biomarkers, organoids, and biomechanics provide feasible testing strategies. Craniofacial growth, oral posture, and airway collapsibility arise from interacting developmental, metabolic, and biomechanical factors, yet the potential contribution of perinatal micronutrient status remains underexplored. It is hypothesized that perinatal thiamine (vitamin B1) insufficiency, by constraining thiamine-dependent flux through pyruvate/α-ketoglutarate dehydrogenases and transketolase in the pentose phosphate pathway, creates a bio-energetic/redox bottleneck in cranial neural crest cells during critical windows of craniofacial morphogenesis and palatogenesis. The developmental phenotype is expected to include subtle maxillo-mandibular undergrowth and palatal shape changes that reduce functional oral tongue space, favor mouth breathing, and promote a downward resting position of the hyoid bone, thereby increasing upper airway collapsibility and sleep-disordered breathing (SDB) risk. Perinatal thiamine status is both measurable and modifiable. The model can be tested using biomarker-anchored cohorts, organoid/animal systems, and finite element simulations. Modern, highly processed diets may induce functional thiamine scarcity via increased demand, reduced availability, and increased losses, thereby priming early developmental risks even without frank deficiency. If corroborated, perinatal micronutrition plus interceptive functional/orthopedic care may lessen the burden of a hyoid-descent-prone airway phenotype while respecting SDB heterogeneity.

Medical HypothesesVol. 207
International Craniofacial Institute (US)
Zero hunger
Openalex Percentile: Top 32%
Alcoholism and Thiamine Deficiency
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From perinatal thiamine insufficiency to growth-phase airway phenotypes: A developmental hypothesis on craniofacial growth, functional oral tongue space, and collapsibility — Björn U. Winter · Medical Hypotheses (2025) | TGRS Research Map | TGRS