Protective effect of vitamin C supplementation on periodontal infections

Adequate intake of vitamin C helps in maintaining periodontal health and reduces the possibility of periodontal infections.

Periodontal disease is defined as chronic inflammation of tissues that both anchor and support the teeth. It is characterized by the worsening of the periodontal ligament and alveolar bone due to intricate interactions between the immune system of the host and microbial biofilms. Periodontitis, affecting 20-50% of the global population, continues to pose a major public health challenge despite progress in dental care. The role of nutrition, especially micronutrients, in influencing periodontal health has attracted remarkable scientific interest.

Vitamin C, a powerful antioxidant, is crucial for collagen synthesis and maintaining connective tissue integrity, both vital for periodontal health. Excessive ROS can worsen periodontal damage by harming cellular structures and altering signaling pathways that control inflammatory responses. The antioxidant effects of vitamin C neutralize reactive oxygen species (ROS) during inflammatory processes, preventing periodontal destruction. Furthermore, vitamin C affects immunity by improving the activity of T-lymphocytes and phagocytes, which are vital elements of host defense against periodontal infections.

Interest is rising in how vitamin C and other micronutrients (like calcium and vitamin D) can complementarily benefit gum health. This synergy could improve the effectiveness of supplementation regimens, providing a comprehensive approach to tackling periodontal disease. However, clinical application requires rigorous randomized controlled trials (RCTs). The perplexity of the oral cavity, with its unique environmental settings and microbial dynamics, makes it cumbersome to isolate vitamin C effects. While vitamin C boosts phagocyte function and T-lymphocyte proliferation—essential for combating gum infection-causing microbes —its role as an anti-inflammatory cofactor in clinical settings remains relatively unexplored and lacks well-established causal evidence. This underscores the need for targeted investigations to confirm its potential as a tool for managing periodontal ailments.

RATIONALE BEHIND RESEARCH

Recent research suggests the potential benefits of vitamin C for managing periodontal diseases, but there are few systematic reviews consolidating these findings. Hence, this study was conducted.

OBJECTIVE

The aim was to explore the usefulness of vitamin C supplementation in preventing and addressing periodontal issues and to clarify the biological mechanisms behind these effects.

Literature search

The present investigation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An extensive literature survey was performed across Web of Science, Scopus, and PubMed to include manuscripts from 2010 to 13 April 2024, focusing on the latest and most pertinent research.

Keywords and phrases relevant to the studies exploring the connection between vitamin C and gum health were utilized. For in-depth literature search, boolean operators (AND, OR, NOT) were used to refine and combine search terms. This scheme was devised to target the most pertinent studies related to vitamin C effects on different aspects of gum health.

Inclusion criteria

• Research involving individuals diagnosed with periodontal disorders were included.
• Those studies analyzing the effect of vitamin C use (via diet or supplementation) on gum health and examining clinical outcomes like gum inflammation, pocket depth decrease, bleeding, and retention of alveolar bone were incorporated.
• Inclusion was restricted to peer-reviewed publications in English.
• The review covered a wide range of study designs, such as cross-sectional studies, observational studies, RCTs, cohort studies, and case-control studies.
• Those studies were incorporated that utilized reliable tools or clinical parameters to evaluate periodontal health outcomes, including illness indices, inflammation markers, and radiographic indicators of alveolar bone condition.

Exclusion criteria

• Non-human studies were ruled out.
• Research examining the effects of basic multivitamin formulations or comprehensive dietary patterns excluding vitamin C were eliminated.
• Research that did not offer accurate, quantitative outcomes or sufficient data for a comprehensive analysis related to periodontal health.
• To avoid introducing secondary interpretations and ensure data credibility and reliability, the review omitted grey literature, which included non-peer-reviewed publications, editorials, preprints, conference proceedings, general reviews, comments, systematic reviews, and meta-analyses.

Study selection and data extraction

This study pursued the PICO criteria:

• Population (P) - Individuals affected by periodontal conditions.
• Intervention (I) - Vitamin C intake either through diet or direct supplementation.
• Comparison (C) - The study compared the outcomes of individuals who received vitamin C supplementation with those without or with inadequate vitamin C levels.
• Outcome (O) - The key outcomes included the evaluation of clinical markers of periodontal health (gingival inflammation, bleeding on probing, pocket depth decrease, and bone preservation in the alveolar region).

Data acquisition process included the elimination of duplicate records. Next, abstracts were meticulously screened by two separate reviewers who evaluated each study's applicability according to predetermined inclusion and exclusion criteria. In order to reach consensus, disagreements amongst reviewers were settled by discussion or, if required, consulting with a third reviewer. The overall count of articles from the initial database search was assessed and chosen for final analysis.

This procedure made sure that all relevant facts about how vitamin C affects periodontal health were comprehensively gathered. For each included study, researchers collected data on the type and quantity of vitamin C consumed, whether from dietary sources or supplements, and the methods used to measure vitamin C intake, such as dietary questionnaires or blood serum levels.

Data and statistical analysis

For this systematic review, the authors integrated findings from selected studies using qualitative and quantitative methods to assess vitamin C's role in periodontal health. Investigators organized data on inflammatory markers, periodontal improvements, and vitamin C use, pointing out missing elements. Results were summarized descriptively and compared across various geographic and clinical settings.

Investigators carried out the meta-analysis to investigate the effects of vitamin C on oral health metrics. Utilizing I2 statistic, heterogeneity was examined among research outcomes, with high I2 scores indicating significant variability. Standard statistical software was used for all analyses, and each estimate was accompanied with a 95% confidence interval (CI) to ensure the highest level of accuracy.

Risk of bias and quality assessment

Risk of bias was evaluated using a dual strategy comprising quantitative and qualitative methods. Newcastle–Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to assess the quality of observational studies. Each study was rated based on its quality, with stars awarded to each category, indicating whether it was low, medium, or high-quality.

Cochrane Collaboration’s tool was utilized to assess the risk of bias for RCTs. During the quality inspection procedure, each study was independently examined by two authors and disparities were resolved through discussion with a third author, thus ensuring objectivity and consistency.

Study outcomes

(a) Primary endpoints: Gum inflammation, Periodontal pocket depth, Clinical attachment loss (CAL), Alteration in alveolar bone level, Other clinical measures of gum health

(b) Secondary endpoints: Systemic markers of inflammation, Antioxidant status

(c) Additional data collected:

• Volunteer demographics: Gender, Age, Ethnic identity, Smoking behavior
• Study features: Sample size, Country, Year, Methodology
• Quality of studies (to estimate validity and practicality)
• Nutrient profile and consumption levels of additional essential vitamins and minerals (to determine possible confounding variables and additive  effects with vitamin C)

Outcomes

Study and participant characteristics:

• Total articles identified as per the initial search: 885
• PubMed: 308; Scopus: 241; Web of Science: 336
• Duplicates removed: 113
• Records excluded before screening: 636
• Articles excluded after full-text review: 120 (due to not meeting inclusion criteria or lack of data)
• Total eligible studies included in the final analysis: 16
• Study focus: The meta-analysis examined the impact of vitamin C on periodontal disease across diverse populations and age groups globally
• Total number of participants: 17,853
• Smallest study: 21 participants (Kuzmanova et al.)
• Largest study: 12,980 participants (Lee et al.)
• Age distribution:
• Youngest cohort: Average age of 20.4 years (Hosoda et al.)
• Oldest cohort: Over 75 years (Iwasaki et al.)
• Gender distribution: Varied across studies; some demonstrated a female predominance or nearly equal gender distribution, which was unusual given the typically higher male prevalence in periodontal disease studies

Study quality:

The studies exhibited high heterogeneity (I² = 95.46%), indicating significant variability in study design and population characteristics.

Effect of intervention on the outcome:

Higher vitamin C intake was related to a lessened probability of periodontal disease

• Pooled odds ratio (OR): 1.52 (95% CI: 1.49–1.55)

Individual study ORs:

• Lowest OR: 0.62 (95% CI: 0.38–0.94), that indicated significant protective effects
• Highest OR: 1.66 (95% CI: 1.04–2.64), that indicated raised risk with insufficient vitamin C levels

Maintaining sufficient vitamin C levels can play a crucial role in oral health. This research highlighted the promising benefits of vitamin C for periodontal health. It encompassed studies with diverse methodologies and demographics, highlighting the complex link between vitamin C use and gum health. Larger cohort studies by Lee et al. and Li et al. documented an intermediate benefit of sufficient vitamin C consumption, while Park et al. and Luo et al. reported stronger connections between low vitamin C levels and escalated risk of periodontal illness.

These results suggest that dietary modifications could be a valuable part of preventive dental care. Contrarily, Kuzmanova et al. and Iwasaki et al. portrayed that elevated dietary vitamin C intake markedly diminishes gum illness risk, with odds ratios of 0.62 and 0.72, respectively. These studies recommended that vitamin C supplementation could be highly advantageous for at-risk populations. Additionally, Yoshihara et al. linked low serum vitamin C levels to raised periodontal attachment loss, emphasizing the prominence of adequate nutrition in averting periodontal issues.

The high heterogeneity noted (I² = 95.46%) among the included studies warrants in-depth analysis. This variability may arise from factors like differences in study populations (baseline nutritional status, degree of illness, or demographics), intervention discrepancies (dosage and form of vitamin C), and variations in research methodologies and outcome metrics. Recent investigations on vitamin C's impact on periodontal ligament cells (PDLCs) revealed distinct protective mechanisms. Yan et al. demonstrated that vitamin C promotes osteogenic differentiation in PDL progenitor cells by activating the extracellular signal-regulated kinase (ERK) pathway, which up-regulates proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) expression and enhances the osteogenesis marker Runx2.

This suggests a targeted molecular mechanism for using vitamin C in regenerative medicine for periodontal disease, focusing on the PELP1-ERK axis. Meanwhile, Wu et al. depicted that vitamin C mitigates oxidative stress in PDLCs caused by hydrogen peroxide, minimizing apoptosis and stimulation of apoptosis markers like caspases-9, caspases-3, and poly (ADP-ribose) polymerase. These insights emphasize vitamin C's potential as an agent that combats oxidative stress and assists cellular survival in gum infections. Older studies by Amarasena et al. and Ekuni et al. also yielded notable insights into vitamin C's influence on periodontal health.

Amarasena et al. found a modest inverse connection between serum vitamin C levels and CAL among elderly Japanese individuals, with CAL being 4% higher in those having lower vitamin C levels, even after adjusting for various factors (r = −0.23, p < 0.00005). Contrarily, Ekuni et al. illustrated in a rat model that vitamin C use pronouncedly diminished oxidative markers and lipid accumulation in the aorta, mitigating atherosclerosis progression associated with periodontitis.

Vitamin C intake notably raised plasma levels and the GSH ratio while decreasing markers of oxidative stress and damage in the serum and aorta. Other older studies also shed light on the link between vitamin C levels and periodontal conditions. According to the findings of the study performed by Timmerman et al, a modest negative correlation (r = −0.199, p < 0.05) exists between plasma vitamin C levels and gum attachment loss among Indonesian tea estate workers, with low vitamin C explaining 3.9% of the variance in attachment loss.

Vitamin C deficiency-affected individuals witnessed considerably more attachment loss, highlighting vitamin C's possible involvement in guarding against periodontal breakdown. Conversely, Pussinen et al. found a pivotal link between low levels of vitamin C in plasma and higher serological markers for P. gingivalis (a major pathogen in gum disease) even after the adjustment of confounding factors. This suggests that low vitamin C levels may impact P. gingivalis colonization or healing processes. Together, these studies underscore the relevance of adequate vitamin C intake for maintaining periodontal health and moderating periodontal infection severity.

The clinical implications are significant. Regularly monitoring and boosting dietary vitamin C could become a fundamental part of routine dental care, especially for those at higher risk of periodontal diseases. Dental professionals must integrate dietary assessments and vitamin C supplementation with standard treatments, particularly for those with early disease signs or systemic risk factors. This approach advocates for combining nutritional management with traditional therapies to boost patient results.

Low vitamin C levels or inadequate supplementation are linked to periodontal disease risk, but study results vary widely due to differences in design, population, health definitions, and vitamin C assessment methods. Studies portray both protective and risk associations, indicating a complex role for vitamin C in periodontal health. This accentuates the requirement for personalized  dietary advice and more research. This study supports recent findings on vitamin C's role in gene differentiation at the stem cell level, crucial for future regenerative therapies.

Ascorbic acid's activation of molecular pathways like ERK in periodontal ligament cells highlights its potential to impact stem cell plasticity and differentiation, potentially refining outcomes in tissue engineering and regenerative medicine. To emphasize the need for advanced study on vitamin C's role in periodontal hygiene, specific study designs are recommended that might offer more robust evidence.  To ascertain causality and the efficacy of vitamin C administration over an extended period of time, longitudinal research and RCTs are required. Future research should include diverse populations to examine how genetic, dietary, and environmental factors affect responses.

Dental practitioners should advise patients on optimal vitamin C intake according to current guidelines, recommending 65 to 90 milligrams daily for adults based on age and sex. For those at risk of gum infection, a higher intake customized to individual needs and confirmed by medical care professionals could prove advantageous. Moreover, discussing nutrient-rich foods containing vitamin C, like citrus fruits and leafy greens, during consultations is recommended.  Acquiring knowledge about the effects of various kinds of vitamin C and how they interact with other micronutrients can boost understanding and guide personalized treatment plans for periodontal disease.