Effect of Daily Vitamin C Supplementation with or Without Flavonoids on Periodontal, Microbial, and Systemic Conditions Before and After Periodontal Therapy: A Case Series from an RCT

Abstract

Purpose: To investigate the effect of vitamin C supplementation with or without flavonoids on periodontal conditions, and microbial and systemic variables before and after non-surgical periodontal treatment (NSPT). Materials and Methods: A case series derived from a randomized controlled trial was conducted to explore the effects of daily vitamin C supplementation, with or without flavonoids, on periodontal conditions. The study population was recruited from patients with periodontitis who had been referred to the Department of Periodontology at the Academic Centre for Dentistry Amsterdam (ACTA). The study consisted of a 2-month observation of untreated periodontitis followed by a 3-month period after NSPT. Descriptive statistics, correlation and clustering analyses, and dimensionality reduction methods were used to evaluate the interventions' impact. Results: Due to COVID-19, the study was prematurely terminated and reported findings from 13 patients. Results indicate a correlation between higher plasma vitamin C levels and reduced gingival inflammation, suggesting benefits for untreated periodontal conditions. Clustering analysis showed no differences based on supplementation type, indicating it did not affect outcomes, and microbiological data had limited effects. Principal Component Analysis visualized clusters and illustrated no distinct groups corresponding to supplementation types. Violin plots highlighted variability, with one cluster comprising individuals with more severe periodontal conditions. Conclusions: Higher plasma vitamin C levels were associated with lower gingival inflammation. However, daily vitamin C supplementation, with or without flavonoids, did not show additional benefits on periodontal conditions before or after treatment. Clustering suggests that periodontal severity, rather than supplementation, influenced patient profiles. The study's small sample size limits the generalizability of the findings.

Keywords: case series; flavonoids; periodontitis; supplementation; vitamin C.

Figure 1

Timeline and procedures performed.

Figure 2

Interleaved scatter plots of parameters at T0, T1, and T2. (a): Body mass index (BMI). (b): Waist circumference (WC). (c,d): Blood pressure (BP) systolic (c) and diastolic (d). (e): Bleeding on probing (BoP). (f): Periodontal inflamed surface area (PISA). (g,h): Mean probing pocket depth (PPD) on all sides (g) and interproximal (h). (i): Clinical attachment level (CAL). (j): High sensitivity C-reactive protein (hs-CRP). (k): HbA1c. (l): Creatine. (m): High-density lipoprotein. (n): Low-density lipoprotein. (o): Triglycerides. (p): Total cholesterol. (q): Vitamin C levels. (r–w): Consumption of fruit (r,s), vegetables (t,u), and wine (v,w) in the last seven days (last week) and on the previous day (yesterday).

Figure 3

Spearman correlation between PISA and vitamin C at T0 (a), T1 (b), and T2 (c).

Figure 4

Relative abundances of genera are shown per individual. “Unknown” refers to taxa unclassified at the genus level, while “Other” combines genera present at a relative abundance of less than 2% in all samples.

Figure 5

This figure presents three-dimensional Principal Component Analysis (PCA) visualizations of individuals classified into two clusters (represented in orange and blue) based on k-means clustering results. The plane that separates the two clusters is visible as a green line from the selected perspectives. The annotations at each data point consist of the unique Subject ID followed by a letter indicating the supplement group: ‘F’ for Fibers and ‘C’ for vitamin C. Panels a to c illustrate the PCA outcomes at time points T0 (a), combined T1 and T0 (b), and combined T2 and T1 (c), without including microbiological data. Panels (d–f) represent the PCA with the same variables as in panels a to c but include microbiological data (32 genera at each time point).

Figure 6

This figure presents violin plots of periodontal variables for two clusters (depicted in orange and blue) derived from k-means clustering without the microbiological data presented in Figure 5a–c. Each violin plot displays the median using a dashed line, the interquartile range using dotted lines, and a rotated kernel density plot, which shows the data distribution for that variable. These selected periodontal parameters differentiated the clusters the most. The violin plots show the periodontal variables from the clustering at T0 (Row (a)), at T1 from clustering T0 and T1 (Row (b)), and at T2 from clustering T1 and T2 (Row (c)).