Individual oxidative stress and inflammation responses to vitamin C supplementation: Aggregated sets of n-of-1 trials

Nastos, GG, Lolli, L, Atkinson, G ORCID: 0000-0002-5459-9042, Theodorou, AA, Paschalis, V, Kyparos, A, Nikolaidis, MG and Margaritelis, NV Individual oxidative stress and inflammation responses to vitamin C supplementation: Aggregated sets of n-of-1 trials. Free Radical Biology and Medicine. ISSN 0891-5849 (Accepted)

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Abstract

Background: Personalized antioxidant supplementation is promoted to optimize redox balance and inflammation profile.
Objective: To quantify the short-term effects of vitamin C supplementation on redox and inflammatory outcome measures and explore the potential for supplement response heterogeneity in participants with vitamin C inadequacy through aggregated sets of multi-cycle n-of-1 trials.
Methods: Eight healthy young males (age 25.56 ± 3.15 years, body mass 68.24 ± 9.70 kg) completed four supplementation (vitamin C 1g) and four placebo trials administered on repeated occasions in
randomized sequences following a 1-month run-in period. Vitamin C, F2-isoprostanes, interleukin-6, and tumor necrosis factor-α were assessed as primary outcomes. Separate within-participant linear mixed effects modelling and meta-analytic models estimated replicate-averaged treatment effects and person by-treatment response variation to vitamin C supplementation.
Results: Supplementation resulted in a statistically significant increase in plasma vitamin C of 20.6 μmol/L (95% confidence interval [CI]: 16.8 to 24.5). This mean treatment effect was lower than our selected clinically important threshold of 23 μmol/L. Vitamin C supplementation reduced F2-isoprostanes by 25.9 pg/mL (CI: 22.2 to 29.6 pg/mL), interleukin-6 by 1.2 pg/mL (CI: 0.7 to 1.7 pg/mL),and tumor necrosis factor-α by 0.5 pg/mL (CI: 0.2 to 0.9 pg/mL). The participant-by-treatment variance component from linear mixed-effects modelling was not statistically significant for all outcomes(P>0.05), agreeing with the small τ-statistics for all outcomes. Shrinkage-adjusted estimates also showed strong shrinkage toward the mean, indicating that the observed response variation mainly reflected random within-person cycle-to-cycle variability rather than true inter-individual variability.
Conclusions: Replicate-averaged treatment effects of vitamin C supplementation on our study outcomes were statistically significant, but heterogenous treatment effects were not detected between participants with baseline inadequacy. Cycle-to-cycle within-participant variation was larger than the observed inter-individual variability for each primary outcome response, suggesting that, if clinically relevant, "average treatment" may suffice for people prone to vitamin C inadequacy.

Item Type:	Article
Uncontrolled Keywords:	0304 Medicinal and Biomolecular Chemistry; 0601 Biochemistry and Cell Biology; 1101 Medical Biochemistry and Metabolomics; Biochemistry & Molecular Biology; 3101 Biochemistry and cell biology; 3205 Medical biochemistry and metabolomics
Subjects:	T Technology > TX Home economics > TX341 Nutrition. Foods and food supply R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Elsevier
Date of acceptance:	30 March 2026
Date Deposited:	01 Apr 2026 12:55
Last Modified:	01 Apr 2026 12:55
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28324

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