Lean NAFLD is associated with low Vitamin D (4-11% of adults have this liver problem)

Serum vitamin D and lean non-alcoholic fatty liver disease: a nonlinear 'L-shaped' association in a national cross-sectional study - Feb 2026

Ann Med. 2026 Dec;58(1):2634463. doi: 10.1080/07853890.2026.2634463 PDF behind paywall

Background: While the association between vitamin D and non-alcoholic fatty liver disease (NAFLD) is well-established in obese populations, its role in lean NAFLD remains controversial.

Objective: This study aimed to investigate the potential nonlinear dose-response relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and lean NAFLD by leveraging large-scale data from the National Health and Nutrition Examination Survey (NHANES).

Methods: We conducted a cross-sectional analysis of 4,201 adults with BMI < 25 kg/m2. Lean NAFLD was defined using the US Fatty Liver Index (USFLI). The association between serum vitamin D and lean NAFLD was assessed employing multivariable logistic regression models, alongside more advanced techniques including restricted cubic splines (RCS) and generalized additive models (GAM) to capture potential nonlinearity.

Results: Initial linear models revealed no significant association. However, subsequent nonlinear analyses uncovered a pronounced 'L-shaped' curve relationship (P-nonlinear < 0.05). A segmented regression approach identified an inflection point at 60.3 nmol/L.

Notably, at serum vitamin D levels below this threshold, concentrations were significantly inversely associated with lean NAFLD risk (Odds Ratio [OR] = 0.71, 95% Confidence Interval [CI]: 0.57-0.89). Conversely, above this inflection point, the inverse association attenuated and plateaued. The robustness of this nonlinear association was corroborated by the GAM analysis.

Conclusion: This large-scale study is the first to identify a significant 'L-shaped' nonlinear association between serum vitamin D and lean NAFLD, wherein the association is most potent at concentrations below approximately 60 nmol/L. This finding highlights an epidemiological inflection point and underscores the need for nonlinear approaches in future research.

Prevelance of adult NAFLD: lean (BMI<25) 4-11%, regular (BMI>25) 30-32% Perplexity

In population studies, lean non-alcoholic fatty liver disease (lean NAFLD) appears in roughly 4–11% of the general adult population, while any non-alcoholic fatty liver disease (NAFLD) affects about 30–32% of adults worldwide. pmc.ncbi.nlm.nih

Lean NAFLD prevalence

  • A 14‑country meta‑analysis reported global lean NAFLD prevalence of about 4.1% in the overall population. frontiersin
  • Another large meta‑analysis found lean NAFLD prevalence around 5.1% in the general population. med.stanford
  • A pooled analysis of 30 studies reported lean NAFLD prevalence of 11.2% in the general population, and about 25.3% of all NAFLD patients were lean. pmc.ncbi.nlm.nih
  • In the U.S., age‑adjusted prevalence of lean NAFLD has been estimated at 6.3% among adults. pmc.ncbi.nlm.nih

Taken together, current data suggest that lean NAFLD typically affects on the order of one in 20–25 adults, though estimates vary by region, diagnostic method, and BMI cut‑offs. pmc.ncbi.nlm.nih

Overall NAFLD prevalence

  • A 2022 Lancet Gastroenterology systematic review estimated global NAFLD prevalence at 32.4% (about one in three adults), with an increase from ~25.5% before 2005 to ~37.8% in 2016 or later. thelancet
  • Another very large pooled analysis (479 studies, 78 million participants) reported a global NAFLD prevalence of 30.2%. sciencedirect
  • A global incidence/prevalence review similarly describes NAFLD affecting roughly 30% of people worldwide. pubmed.ncbi.nlm.nih
  • In North America specifically, prevalence estimates are often in the mid‑30% range (for example, about 35.3% in one meta‑analysis and up to 47.8% in another U.S. dataset). pubmed.ncbi.nlm.nih

So, for a simple working summary: lean NAFLD ≈ 4–11% of adults; any NAFLD ≈ 30–32% of adults globally, higher in some regions such as the Americas. e-cmh

Is Vitamin D associated with Lean NAFLD? Perplexity - Feb 2026

Yes. Low vitamin D status is associated with NAFLD in general, and recent data indicate this association also holds in non‑obese/lean NAFLD, although findings are not entirely uniform. pmc.ncbi.nlm.nih Jan 2025

Evidence in lean / non‑obese NAFLD
  • A 2025 cohort of non‑obese and lean adults found that insufficient serum 25(OH)D independently increased NAFLD risk, even in those without insulin resistance, and concluded that vitamin D deficiency is an independent contributor to non‑obese/lean NAFLD. pmc.ncbi.nlm.nih
  • Earlier work from Korea showed an inverse association between 25(OH)D and NAFLD “even in subjects with normal total body fat,” suggesting relevance beyond classical obesity. nature
  • In contrast, a Chinese study that stratified by BMI reported that low vitamin D was associated with NAFLD in obese but not in lean participants, with lean NAFLD patients having vitamin D levels comparable to lean controls. pubmed.ncbi.nlm.nih

Overall, observational evidence in lean populations is mixed but is now leaning toward vitamin D deficiency being a risk or independent contributor in non‑obese/lean NAFLD, at least in some cohorts. pubmed.ncbi.nlm.nih

Evidence across all NAFLD
  • Multiple observational studies and meta‑analyses show that NAFLD patients have lower 25(OH)D levels than controls and that serum vitamin D is inversely associated with NAFLD presence and sometimes severity. pubmed.ncbi.nlm.nih
  • One meta‑analysis reported NAFLD patients had on average ~0.9 ng/mL lower 25(OH)D and that higher vitamin D was associated with lower odds of NAFLD (OR ~0.64). pubmed.ncbi.nlm.nih
  • Mechanistically, vitamin D is proposed to exert anti‑inflammatory, anti‑fibrotic, and anti‑lipogenic effects in the liver, giving biological plausibility to the association. xiahepublishing
Intervention data
  • RCTs and meta‑analyses of vitamin D supplementation in established NAFLD show modest improvements in glycemic control, insulin resistance, and some lipid parameters, with more variable effects on liver enzymes and steatosis itself. frontiersin
  • These trials were conducted mainly in typical (often overweight) NAFLD; targeted trials in strictly lean NAFLD are still lacking, so causality and therapeutic effect specifically in lean NAFLD remain unproven. pubmed.ncbi.nlm.nih
Practical interpretation
  • For now, vitamin D deficiency seems to be a marker of higher NAFLD risk overall and, in at least some cohorts, in non‑obese/lean individuals as well. pmc.ncbi.nlm.nih
  • It is reasonable to ensure adequate 25(OH)D in patients with or at risk of lean NAFLD, but supplementation should be viewed as a potentially supportive measure, not a stand‑alone treatment, pending more lean‑specific RCTs. nature

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Created February 2026
Tags: Liver