Low Cholesterol Levels Linked to More Active Crohn Disease, Study Finds

New study findings published in Frontiers in Medicine suggest that serum total cholesterol (TC) levels may serve as a simple, readily available tool for monitoring the clinical severity of Crohn disease (CD). The retrospective cross-sectional study found that decreased levels of TC were significantly associated with a more active inflammatory state in patients with the chronic inflammatory bowel disease (IBD).¹

Researchers are actively seeking more reliable and cost-effective methods to assess CD activity. Current assessment standards, such as the CD Activity Index (CDAI), rely partly on subjective evaluations and may lack stability, whereas the common inflammatory marker C-reactive protein (CRP) requires improved sensitivity. The findings indicate that TC could potentially complement these existing markers.¹

The research team aimed to enhance the understanding of lipid metabolism alterations in CD by comparing serum lipid parameters and serum uric acid (SUA) between patients with CD and healthy controls and evaluating their association with clinical disease activity.¹

The study enrolled 104 patients diagnosed with CD for the first time, alongside 20 healthy volunteers. Patients were categorized based on their CDAI scores into mild activity or moderate activity groups; notably, no patients met the criteria for severe CD. Lipid metabolism indicators including TC, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were assessed.¹

The results showed that patients with CD generally had lower levels of TC, LDL-C, HDL-C, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) compared to the healthy control group. Crucially, the comparison between the 2 CD activity groups revealed that TC and LDL-C levels were significantly lower in patients with moderate disease activity than in those in the mild group.¹

Further statistical analysis highlighted the clinical relevance of this finding. Lower TC was identified as an independent risk factor for more active disease (moderate CD). Specifically, a TC level of 3.5 mmol/L or less was used as a cutoff value to distinguish moderate from mild disease. Moreover, TC levels correlated negatively with both CDAI scores and CRP, implying that as disease activity increased, TC levels tended to decrease.¹

The link between inflammation and abnormal lipid metabolism is a common feature in patients with IBD, often attributed to factors such as chronic inflammation, malabsorption, or reduced food intake.^1,2 The reduced TC observed in study participants with CD, especially those with moderate disease, might be linked to a potential diminishment of acetyl coenzyme A (CoA), which is crucial for cholesterol synthesis. This disruption in cholesterol levels can further impact the body by interfering with the synthesis of steroid hormones and altering bile acid composition, thereby potentially exacerbating intestinal inflammation.¹

The researchers concluded that decreased serum TC levels are associated with a more active inflammatory state in CD. They propose that TC can serve as a simple and inexpensive supplementary biomarker to complement current indicators such as CRP.¹

However, the study’s findings come with caveats, including the small sample size and the absence of patients with small disease. The authors stressed that large-scale, multicenter studies with long-term follow-up are essential to confirm the reliability of TC as a biomarker for CD activity.¹

REFERENCES

1. Ni J, Tang Y, Zhou F, et al. Association between serum total cholesterol levels and Crohn’s clinical disease severity: a retrospective cross-sectional study. Front Med. 2025;12. doi:10.3389/fmed.2025.1708838

2. Hrabovský V, Zadák Z, Bláha V, et al. Cholesterol metabolism in active Crohn’s disease. Wien Klin Wochenschr. 2009;121(7-8):270-275. doi:10.1007/s00508-009-1150-6