HIGHER BLOOD vitamin A levels were associated with slower lung function decline in people with lymphangioleiomyomatosis (LAM), a study combining patient follow-up with laboratory experiments has found.
However, the cellular findings revealed a more complex picture: vitamin A metabolites increased proliferation in lung-derived cultures. The research therefore identifies a potential biological pathway without establishing vitamin A supplementation as a treatment.
Researchers measured serum retinol, the circulating form of vitamin A, in 653 patients across 4,502 clinical visits. LAM is a rare cystic lung disease, predominantly affecting women, in which abnormal cells contribute to progressive lung damage.
Analyses accounted for factors including initial lung function, tuberous sclerosis complex status, sirolimus treatment and follow-up time. Sirolimus inhibits the mTOR pathway, which becomes overactive following loss of tuberous sclerosis complex gene function in LAM cells.
Higher retinol concentrations were associated with better percentage-predicted forced expiratory volume in 1 second (FEV1) and diffusing capacity for carbon monoxide (DLCO) in adjusted analyses, both measures relevant to respiratory function.
For the progression analysis, researchers required at least three consecutive visits within a higher or lower vitamin A category. Higher levels were defined relative to the laboratory’s upper normal value, rather than as concentrations exceeding the normal range.
Adjusted annual FEV1 decline was approximately 1.01 percentage points of predicted values in the higher category, compared with 1.32 in the lower category (p=0.003). The annual change in DLCO did not differ significantly between categories.
This distinction is important because the findings do not demonstrate the same longitudinal association across every measure of lung function.
The laboratory work examined retinoid signalling and microphthalmia-associated transcription factor (MITF), which regulates genes linked to the melanosomal features of LAM cells. Approximately 80% of genes upregulated in sampled LAM nodules were retinoic acid-dependent.
Despite the favourable clinical association, retinol metabolites stimulated proliferation in heterogeneous lung-derived cell cultures. The researchers suggest that effects on surrounding lung tissue, repair processes and different cell populations may help explain this apparent mismatch, although those mechanisms remain unresolved.
Because the clinical analysis was observational, it cannot establish whether higher retinol itself slowed disease progression. Controlled studies are needed to explore causality and distinguish potentially beneficial tissue effects from stimulation of abnormal cells before supplementation can be evaluated as a therapeutic strategy.
Reference
Pacheco-Rodriguez G et al. Vitamin A levels are associated with a decrease in lymphangioleiomyomatosis progression and MITF-mediated cell growth. Respir Res. 2026. https://doi.org/10.1186/s12931-026-03759-3
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