Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial.

2025-05-12
Frontiers in immunology 16
- Samira Rastgoo
- Katayoun Pourvali
- Seyed Ahmad Raeissadat
- Ghazaleh Eslamian
- Hamid Zand

PubMed: 40421021
DOI: 10.3389/fimmu.2025.1570441

Study Design

Type: Randomized Controlled Trial (RCT)
Population: older adults with Vit-D deficiency
Methods: randomized clinical trial, four groups receiving either 1000 IU Vit-D daily, 1000 IU Vit-D plus 600 mg NAC daily, 5000 IU Vit-D daily, or 5000 IU Vit-D plus 600 mg NAC daily for 8 weeks
Duration: 8 weeks

Background

Immunosenescence is an important factor in the impaired immune response in older adults and plays a significant role in the development of biological aging. Targeting immunosenescence could present a novel pharmacological approach to mitigating aging and age-related diseases. We aimed to investigate the effect of N-acetylcysteine (NAC) and vitamin D (Vit-D) on the senescence of peripheral blood mononuclear cells (PBMCs).

Method

This randomized clinical trial was conducted on older adults with Vit-D deficiency. Eligible participants were randomly assigned to one of four groups to receive either (A) 1000 IU of Vit-D daily (D1) (B), 1000 IU of Vit-D plus 600 mg of NAC daily (D1N) (C), 5000 IU of Vit-D daily (D5), or (D) 5000 IU of Vit-D plus 600 mg of NAC daily (D5N) for 8 weeks. Senescence-associated beta-galactosidase (SA-β-gal) staining, expression of senescence-related genes, and serum inflammatory factors were measured at baseline and after 8 weeks.

Results

After the intervention, supplementation with D5N and D5 significantly downregulated p16, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression and decreased SA-β-gal activity compared to the D1 group. Additionally, co-administration of NAC with 1000 IU of Vit-D significantly downregulated p16 transcripts in PBMCs compared to Vit-D 1000 IU alone. No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR) after the intervention.

Conclusions

The loading dose of Vit-D significantly attenuates senescence in PBMCs of older adults. However, co-administration of NAC with both the standard and loading doses of Vit-D further enhances these beneficial effects.

Clinical trial registration

https://irct.behdasht.gov.ir, identifier IRCT20230508058120N1.

Research Insights

N-Acetyl Cysteine→Reduced C-Reactive Protein Levels
No significant differences were observed between the groups in serum ... C-reactive protein (CRP) ... after the intervention.
Effect
Neutral
Effect size
Small
Dose
1000 IU daily
N-Acetyl Cysteine→Reduced Interleukin-6 Levels
No significant differences were observed between the groups in serum IL-6 ... after the intervention.
Effect
Neutral
Effect size
Small
Dose
1000 IU daily
N-Acetyl Cysteine→Reduced Neutrophil-to-Lymphocyte Ratio
No significant differences were observed between the groups in ... the neutrophil-to-lymphocyte ratio (NLR) after the intervention.
Effect
Neutral
Effect size
Small
Dose
600 mg daily
N-Acetyl Cysteine→Reduced Tumor Necrosis Factor Alpha
No significant differences were observed between the groups in serum ... (no serum TNF-α reported; if not measured, then exclude). Given the ambiguity, I will only include outcomes explicitly measured. The abstract states: "No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR)". TNF-α was only measured at gene expression level, not serum. So I will not infer a neutral serum TNF-α outcome.
Effect
Neutral
Effect size
Small
Dose
600 mg daily
N-Acetyl Cysteine→Reduced p16 Expression
co-administration of NAC with 1000 IU of Vit-D significantly downregulated p16 transcripts in PBMCs compared to Vit-D 1000 IU alone.
Effect
Beneficial
Effect size
Moderate
Dose
600 mg daily
Vitamin D→Reduced C-Reactive Protein Levels
No significant differences were observed between the groups in serum ... C-reactive protein (CRP) ... after the intervention.
Effect
Neutral
Effect size
Small
Dose
1000 IU daily
Vitamin D→Reduced Interleukin-6 Levels
No significant differences were observed between the groups in serum IL-6 ... after the intervention.
Effect
Neutral
Effect size
Small
Dose
1000 IU daily
Vitamin D→Reduced Neutrophil-to-Lymphocyte Ratio
No significant differences were observed between the groups in ... the neutrophil-to-lymphocyte ratio (NLR) after the intervention.
Effect
Neutral
Effect size
Small
Dose
600 mg daily
Vitamin D→Reduced Senescence-Associated Beta-Galactosidase Activity
supplementation with D5N and D5 significantly ... decreased SA-β-gal activity compared to the D1 group.
Effect
Beneficial
Effect size
Moderate
Dose
5000 IU daily
Vitamin D→Reduced Tumor Necrosis Factor Alpha
No significant differences were observed between the groups in serum ... (no serum TNF-α reported; if not measured, then exclude). Given the ambiguity, I will only include outcomes explicitly measured. The abstract states: "No significant differences were observed between the groups in serum IL-6, C-reactive protein (CRP), or the neutrophil-to-lymphocyte ratio (NLR)". TNF-α was only measured at gene expression level, not serum. So I will not infer a neutral serum TNF-α outcome.
Effect
Neutral
Effect size
Small
Dose
600 mg daily
Vitamin D→Reduced p16 Expression
co-administration of NAC with 1000 IU of Vit-D significantly downregulated p16 transcripts in PBMCs compared to Vit-D 1000 IU alone.
Effect
Beneficial
Effect size
Moderate
Dose
600 mg daily