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Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study.

  • 2025-12
  • Clinical biochemistry 140
    • Yubin Lei
    • Anik Forest
    • Caroline Daneault
    • Ying Liu
    • Kostas Pantopoulos
    • Adisak Tantiworawit
    • Arintaya Phrommintikul
    • Siriporn Chattipakorn
    • Nipon Chattipakorn
    • Christine Des Rosiers
    • Gary Sweeney

Study Design

Type
Randomized Controlled Trial (RCT)
Population
62 Thai TDT patients
Methods
randomized cohort, six-month cocktail therapy involving standardized blood transfusions and iron chelator therapy, with the intervention group additionally receiving 600 mg oral NAC daily and the control group receiving a placebo
Blinding
Double-blind
Duration
six months

Objectives

Oxidative stress, driven by iron imbalance from recurrent blood transfusions, is a major contributor to cardiometabolic complications in transfusion-dependent thalassemia (TDT). N-acetylcysteine (NAC), a glutathione precursor, is a well-known antioxidant with cardioprotective effects achieved by mitigating the impact of oxidative stress on cell metabolism. Current study aimed to evaluate the effect of a six-month NAC intervention by focusing on previously reported changes in the plasma lipidome in TDT patients. Design & Methods A randomized cohort of 62 Thai TDT patients was divided into two groups: both received six months of cocktail therapy involving standardized blood transfusions and iron chelator therapy, with the intervention group additionally receiving 600 mg oral NAC daily and the control group receiving a placebo. Plasma lipidomic profiling was performed using mass spectrometry to assess 339 previously annotated lipid features significantly altered in TDT patients. Clinical parameters, including heart rate variability (HRV), were measured before and after the intervention.

Results

NAC treatment significantly altered 152 plasma lipid features (P < 0.03), 78 of which were also altered in the placebo group. Importantly, 29 lipid features (26 unique lipids) were restored toward healthy control levels following NAC treatment. Within this subset, circulating diacylglycerophosphocholines PC(14:0_20:4) and cholesteryl ester CE 18:3 positively correlated with HRV, a clinical marker markedly improved in NAC-treated patients.

Conclusions

Six-month oral NAC intervention modified the plasma lipidomic profile in TDT patients, partially restoring lipid species likely disrupted by chronic oxidative stress. The observed correlation between NAC-responsive lipids and improved HRV suggests a potential cardioprotective effect. These findings highlight the potential of NAC as an adjunctive therapy to mitigate cardiometabolic complications in TDT.

Research Insights

  • N-Acetyl Cysteine→Improved Heart Rate Variability

    circulating diacylglycerophosphocholines PC(14:0_20:4) and cholesteryl ester CE 18:3 positively correlated with HRV, a clinical marker markedly improved in NAC-treated patients.

    Effect
    Beneficial
    Effect size
    Small
    Dose
    600 mg oral daily
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