Vitamin D Sufficiency Revisited: Evidence of a Dose-Response Effect for MASLD in Adults at Risk

Background and Aims:Vitamin D plays a pivotal role in liver health, influencing multiplesteps in the development of steatosis, fibrosis, and extrahepatic complications in metabolicdysfunction-associated steatotic liver disease (MASLD). However, serum vitamin D con-centrations that confer optimal hepatic protection in MASLD remain unclear. We thereforeaimed to investigate the association between vitamin D status and MASLD and to explorewhether higher vitamin D concentrations confer incremental protection beyond current suf-ficiency cut-offs.Method:We conducted a multicenter cross-sectional study of1039 adultswith at least one cardiometabolic risk factor for MASLD diagnosis, recruited between2022 and 2024. Participants that reported excessive alcohol intake (>30 g/day for men,>20 g/dayfor women) and other etiologies of liver disease were excluded. Serum vitaminD levels were measured, with >= 20 ng/mL defined as sufficiency. MASLD (controlledattenuation parameter [CAP]>= 248 dB/m) and significant fibrosis (liver stiffness mea-surement [LSM]>= 8 kPa) were assessed using vibration-controlled transient elastography.Missing vitamin D values were imputed with multiple imputation. Associations betweenvitamin D status, MASLD and fibrosis were examined using multivariable logistic regres-sion models adjusted for potential confounders.Results:Participants had a mean age of52.2 +/- 13.0 years; 51.6% were male and mean BMI was 30.1 +/- 5.8 kg/m2. Vitamin D suffi-ciency and obesity were present in 81.2% (95% CI: 78.4-84.9) and 54.7% (95% CI:51.3-58.0),respectively. Vitamin D sufficiency was associated with lower odds of MASLD (crudeOR = 0.47, 95% CI: 0.33-0.67) and significant fibrosis (crude OR = 0.46, 95% CI: 0.28-0.76).After adjusting for potential confounders, the association between Vitamin D sufficiencyand MASLD remained clinically relevant but did not reach statistical significance (adjustedOR = 0.60, 95% CI: 0.36-1.03,p= 0.06). In contrast, the association between Vitamin Dsufficiency and significant fibrosis was both clinically relevant and statistically significant(adjusted OR = 0.48, 95% CI: 0.246-0.916,p= 0.03). When Vitamin D was categorized intoquartiles, participants in the highest quartile (>= 44 ng/dL) had 61% lower odds of MASLDin the adjusted model (adjusted OR = 0.39, 95% CI: 0.21-0.71) compared with participantsin the lowest quartile (<= 22 ng/mL). No significant dose-dependent associations wereobserved for fibrosis.Conclusions: Vitamin D levels showed a dose-dependent decrease in the odds of MASLD among at-risk adults. While the protective effect on fibrosis was notdose-dependent, these findings collectively suggest vitamin D as a potentially modifiablefactor in MASLD prevention and management.