Co-administration of Vitamin D and N-Acetylcysteine to Modulate Immunosenescence in Older Adults with Vitamin D Deficiency: A Randomized Clinical Trial

Samira Rastgoo ^1* Katayoun Pourvali ¹ Seyed Ahmad Raeissadat ² Ghazaleh Eslamian ¹ Hamid Zand ¹

• ¹ Faculty of Nutrition Sciences and Food Industry, Shahid Beheshti University of Medical Sciences, Shahid, Iran
• ² Shahid Beheshti University of Medical Sciences, Tehran, Tehran, Iran

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 (RCT) was conducted on older adults with Vit-D deficiency. Eligible participants were randomly assigned to one of four groups to receive either: 1) 1000 IU of Vit-D daily (D1), 2) 1000 IU of Vit-D plus 600 mg of N-acetylcysteine (NAC) daily (D1N), 3) 5000 IU of Vit-D daily (D5), or 4) 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 eight 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.