Keyword
vitamin C - periodontal disease - nutrition - oral health - tooth
Introduction
Vitamin C (ascorbic acid) is a six-carbon lactone that is synthesized from glucose
in the liver of most mammalian species, but not by humans, nonhuman primates, and
guinea pigs, as they lack the enzyme gulonolactone oxidase.[1] So, human beings are bound to ingest vitamin C in their diet; if it did not occur,
there would be a state of deficiency with a wide spectrum of clinical manifestations.
Scurvy (clinical term for vitamin C deficiency) is a lethal condition if not properly
treated.[2] Therefore, humans must ingest vitamin C to survive. Humans can obtain vitamin C
only exogenously and mainly orally with subsequent gastrointestinal absorption and
distribution. Vitamin C is mainly found in fruits and vegetables. L-ascorbic acid
is an essential nutrient for all humans. The inability of the human body to produce
this molecule is due to the absence of the enzyme L-gulono-1,4-lactone oxidase.[2]
[3] Vitamin C plays a crucial role in various metabolic processes within the human body,
including the regulation of collagen, corticosteroids, neurotransmitter synthesis,
iron absorption, and immune system responses. One of the key functions of vitamin
C is facilitating the formation of collagen intermolecular cross-links, which strengthens
the bonds between lysine and hydroxylysine in adjacent tropocollagen molecules. Without
hydroxylation, the production of procollagen is reduced, leading to its probable accelerated
degradation. Since vitamin C is essential for collagen stabilization, its deficiency
can lead to collagen instability, affecting the periodontal ligaments and potentially
leading to tooth loss.[4]
[5]
[6] Furthermore, L-ascorbic acid is crucial for endothelial cell function and promotes
the proliferation of these cells, likely through its role in enhancing type IV collagen
synthesis. The impact of vitamin C on various proinflammatory cytokines suggests its
potential as a biomarker or adjunctive therapy. High doses of intravenous vitamin
C have been shown to reduce proinflammatory cytokines and C-reactive protein in cancer
patients, while low dietary intake of vitamin C is linked with increased inflammatory
and oxidative stress. Although vitamin C has antioxidant properties, in high doses,
it can act as an oxidant and selectively target cancer cells. Its effect on cell wall
thickness via improved collagen fibers enhances vessel strength.[6] Vitamin C also promotes fibroblast migration in the skin and keratinocyte proliferation,
potentially benefiting wound healing and reducing inflammation in the gums. Overall,
previous research indicates vitamin C's role in reducing inflammation in periodontal
tissues, preventing bacterial infections by enhancing neutrophil phagocytosis, and
improving collagen synthesis and vessel strength, leading to better tissue regeneration.[7]
An overwhelmingly large segment of the global populace, estimated at 90%, is afflicted
by periodontal diseases, as highlighted by references.[7]
[8] When periodontitis advances, it devastates the alveolar bone that plays a crucial
role in anchoring teeth, which can ultimately lead to tooth loss. Additionally, periodontitis
is believed to elevate the risk for a range of other health complications, including
type 2 diabetes mellitus and cardiovascular diseases, and it may negatively impact
pregnancy outcomes.[8]
Periodontal disease is characterized as an inflammatory condition that begins with
a bacterial infection. This infection sets off an atypical response from the host's
immune system, which is primarily responsible for the degradation of periodontal tissue.[4]
[5] A key player in the body's defense against periodontopathogens are the polymorphonuclear
leukocytes (PMNs), which play a pivotal role in warding off these harmful pathogens.[5]
[6] These leukocytes initiate an antimicrobial reaction at the site of infection by
activating several intracellular signaling pathways, including the production of reactive
oxygen species (ROS).[7] While ROS are beneficial in controlling infections, their heightened levels can
be detrimental, causing cytotoxic effects on the tissues supporting the teeth.[8]
[9] It is suggested that oxidative stress induced by PMNs could be a leading cause of
tissue damage in periodontal diseases.[10] Evidence shows that individuals with periodontitis have higher levels of biomarkers
indicating ROS-induced tissue damage compared to healthy controls.[11]
[12]
[13]
Vitamin C, an essential nutrient known for its antioxidative properties, plays a significant
role in neutralizing free radicals and acting as a cofactor for enzymes within cells.[14]
[15] Given its capacity to scavenge excessive ROS, vitamin C is considered a vital dietary
antioxidant crucial for maintaining periodontal health.[16] Beyond its antioxidative function, vitamin C is instrumental in promoting the differentiation
of progenitor cells in the periodontal ligament, which is vital for the prevention
and management of periodontal disease.[17]
In addressing the prevention of periodontal disease, it is crucial to produce evidence
on nutritionally effective strategies. Over the past two decades, a wealth of epidemiological
research has been undertaken to explore the link between vitamin C consumption and
periodontal disease. These studies have also delved into vitamin C's potential in
preventing periodontal disease, with measurements typically based on dietary intake
or blood levels of vitamin C. It is important to note that periodontal disease encompasses
both gingivitis and periodontitis, each with distinct pathological features and possibly
varying relationships with vitamin C intake. Despite the abundance of studies, a comprehensive
systematic review focusing on the association between vitamin C's dietary intake and
blood concentration with periodontal disease, as well as its preventive capabilities,
has yet to be conducted. This study, therefore, seeks to fill this gap by systematically
reviewing the available literature on the subject ([Fig. 1]).
Fig. 1 Antioxidant cellular activity of acid ascorbic.[5]
Methods
For this comprehensive review, the criteria for inclusion were meticulously established
in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines, adopting the structured approach of the population (P; specifically
targeting “human adults”), intervention or exposure (I; focusing on the “impact of
vitamin C on periodontal disease”), comparison (C; comparing “various levels of vitamin
C intake, different concentrations of vitamin C in the blood, or the absence of vitamin
C supplementation”), and outcome (O; evaluating “parameters indicative of periodontal
disease”) model, widely referred to as the PICO model.[18] To ensure a thorough and unbiased assessment of the studies, two independent researchers
undertook the task of evaluating the eligibility of each study. This preliminary screening
process involved a careful review of both the titles and abstracts of potential studies,
guided by the PICO model's framework. The central question guiding this process was:
“Is there an association between vitamin C and periodontal health status?.”
Additionally, to be considered for inclusion in this systematic review, studies were
required to meet several specific criteria: (1) the study must be authored in English,
(2) the publication date falls within the timeframe from July 1998 to June 2018, (3)
the focus of the study is on exploring the association between periodontal disease
and vitamin C, (4) the study subjects are adults, with an age requirement of 18 years
or older, and (5) the study employs quantitative methodologies for the collection
of data. This inclusion criteria set aimed to encompass epidemiological studies involving
adult populations. The exclusion criteria were the coexistence of other pathologies
in samples of adult patients, animal studies, in vitro studies, non-English studies, systemic reviews with meta-analysis, letters, dissertations,
and abstracts.
To gather the necessary literature for this review, an extensive search was conducted
across several key databases: PubMed, EMBASE, Cochrane Library, and Web of Science.
The search strategy employed specific terms aimed at capturing relevant studies, using
combinations such as “periodontal disease and vitamin C” or “periodontal disease and
ascorbic acid” to ensure a comprehensive collection of pertinent research on the subject
([Table 1]).
Table 1
Search strategy with Mesh term
|
PubMed
Scurvy AND periodontal disease (“periodontal disease”[MeSH Terms] OR (“vitamin C”[All
Fields] AND “periodontal disease”[All Fields]) OR “scurvy”[All Fields]) AND (“vitamin
C”[All Fields] OR “scurvy”[MeSH Terms] OR (“periodontal disease”[All Fields] AND “dentistry”[All
Fields]) OR ” dentistry”[All Fields])
|
|
Web of Science
(vitamin C) AND (periodontal disease) (ALL FIELDS)
Scopus
|
|
(vitamin C) AND (periodontal disease)TITLE ABS KEY
|
Selection Criteria and Data Extraction
[Fig. 2] shows the entire selection and search strategy for articles. The research produced
421 articles. Two authors first independently evaluated the studies identified for
compliance with the inclusion and exclusion criteria. Next, the full texts of these
articles were examined. Most of these studies were excluded because they did not analyze
correlations between vitamin C and periodontal disease. After removal of duplicate
records and records that did not meet the inclusion criteria, 14 publications were
selected.
Fig. 2 Search strategy flowchart.
Results
The initial search across various databases for relevant literature on the topic resulted
in the identification of 421 studies. A meticulous manual search process was implemented
to retrieve these records. Subsequent to the elimination of duplicates, a total of
156 records were considered for screening. Following a preliminary review based on
titles and abstracts, 110 of these records were deemed unrelated to the scope of the
review and were thus excluded. This left 46 articles, which underwent a more detailed
analysis to assess their relevance further.
Of these 46 articles deemed potentially relevant, 32 were found not to meet the specific
inclusion criteria established for this review. Consequently, 14 studies were ultimately
selected to be part of this systematic review, as delineated in the presented flowchart.
The composition of these selected studies includes seven cross-sectional studies,[19]
[20]
[21]
[22]
[23]
[24]
[25] two case-control studies,[26]
[27] two cohort studies,[28]
[29] and four randomized controlled trials (RCTs).[18]
[30]
[31] Among the studies not classified as RCTs, six investigated vitamin C intake through
dietary analysis, while another six studies focused on measuring the concentration
of vitamin C in the blood. Interestingly, there was one study that provided insights
into vitamin C levels from both dietary intake and blood concentration perspectives.
The RCTs specifically examined changes in periodontal tissue conditions by comparing
metrics before and after the administration of vitamin C.
The criteria used to assess periodontal disease in these studies were comprehensive,
including various indicators such as the community periodontal index (CPI), pocket
depth (PD), attachment loss (AL), bone loss, clinical attachment level (CAL), bleeding
on probing, gingival index (GI), gingivitis severity index, and sulcus bleeding index
(SBI). These indicators collectively provided a holistic view of the periodontal health
status across the studies included in this review.
Several studies have delved into the connection between the consumption of vitamin
C and the prevalence of periodontal disease, yielding insightful findings. In the
investigation conducted by Lee at al, it was discovered that adults aged 19 and above
who consumed the most vitamin C, specifically more than 132.2 mg/day (falling into
the highest quartile of intake), exhibited significantly lower scores on the CPI in
comparison to those whose intake was at or below 47.34 mg/day, placing them in the
lowest quartile of consumption. Similarly, the research by Park et al highlighted[6] that within a demographic of women and nonsmokers aged between 19 and 39 years,
individuals with a vitamin C intake below the median value of 81.3 mg/day were found
to have a substantially higher proportion of CPI scores equal to or greater than 3,
in contrast to their counterparts who consumed more vitamin C.
Additional large-scale investigations have underscored significant correlations between
the dietary intake of vitamin C and indicators of periodontal health. Tanaka et al
reported that a lack of sufficient vitamin C intake was linked to more severe manifestations
of periodontal disease.[20] Concurrently, another study established that a decreased intake of dietary vitamin
C was associated with an elevated risk of developing periodontal disease.[22] Focusing on the relationship between CAL and the levels of vitamin C in serum/plasma,
three studies have provided valuable insights. Specifically, two of these studies
demonstrated a negative correlation between the extent of AL and plasma vitamin C
levels, indicating that lower levels of plasma vitamin C were associated with greater
AL among participants. Bartold and Van Dyke found that serum vitamin C concentrations
were inversely related to the degree of CAL,[24] suggesting that higher serum vitamin C levels may protect against AL. Additionally,
Nazir reported that the occurrence of severe periodontitis was significantly more
common in individuals with serum vitamin C levels below 8.52 mmol/L compared to those
with higher levels of vitamin C.[23] Moreover, Gokhale et al confirmed a negative correlation between the degree of AL
and plasma vitamin C levels among the examined subjects,[17] further affirming the protective role of vitamin C against periodontal deterioration.
In two distinct case–control studies, identified as[26]
[27] the levels of serum vitamin C were scrutinized by comparing individuals diagnosed
with periodontal disease against healthy control participants. The findings from both
studies unanimously indicated that those suffering from periodontitis exhibited notably
lower levels of serum vitamin C in comparison to the healthy control group.
Furthermore, the efficacy of vitamin C supplementation as a preventive measure against
periodontal disease was explored through four specific studies. Among these, one study
delved into the impact of locally applied vitamin C, through the use of a dentifrice
infused with ascorbic acid, on the health of periodontal tissues.[20] This particular study observed that the application of the ascorbic acid-containing
dentifrice led to a marked improvement in reducing symptoms of gingivitis.[22] Another investigation focused on the consumption of grapefruit and its effect on
periodontal health, revealing that individuals with chronic periodontitis experienced
a significant improvement in their sulcus bleeding index following grapefruit intake.[26]
Additionally, two other studies employing clinical trial methodologies assessed the
combined effects of vitamin C supplementation and nonsurgical treatments for periodontal
disease. In the study conducted by Gokhale et al, it was demonstrated that the conjunction
of nonsurgical periodontal treatment with vitamin C supplementation resulted in a
significant decrease in the SBI among patients diagnosed with gingivitis.[29] However, it was noted across these studies that vitamin C supplementation did not
confer any additional benefits toward the improvement of clinical measures in cases
of periodontitis,[28]
[29] suggesting a nuanced role of vitamin C in periodontal disease management, particularly
emphasizing its beneficial effects in the early stages of gingival inflammation rather
than in advanced periodontitis.
Discussion
All the cross-sectional studies included in this review uniformly found a significant
link between periodontal disease and either the dietary intake of vitamin C or its
blood levels. Specifically, in two case–control studies[26]
[27] individuals diagnosed with periodontitis had noticeably lower serum vitamin C levels
compared to their healthy counterparts. These observations suggest a mechanism wherein
vitamin C, derived from dietary sources, is transported to the periodontal tissue
through the bloodstream, thereby diminishing the risk of periodontal disease development.
Nonetheless, an alternative interpretation arising from the cross-sectional studies
proposes a reverse causality where the observed associations might reflect the impact
of periodontal disease on vitamin C intake, possibly due to compromised mastication
abilities, rather than the influence of vitamin C intake on periodontal health. The
need for longitudinal studies is emphasized to clarify and confirm these associations.[23]
Within this review, two cohort studies[28]
[29] provided evidence supporting a longitudinal relationship between vitamin C intake
and periodontal disease, reinforcing the hypothesis that dietary vitamin C mitigates
inflammatory responses in periodontal disease. However, the reliance on the same population
sample in these two cohort studies calls for further research through additional cohort
studies to solidify the reliability of this observed relationship.
Among the three RCTs discussed, two[13]
[14] indicated positive outcomes on periodontal health indices such as the GI, SBI, and
PD, attributed to vitamin C supplementation. These improvements, particularly in gingival
conditions, underscore vitamin C's potent antioxidative properties, which are thought
to reduce oxidative stress in gingivitis. Moreover, vitamin C's capability to lessen
the cytotoxic and apoptotic activities of Porphyromonas gingivalis in periodontal ligament cells and gingival fibroblasts may contribute to these benefits.
However, these positive effects were not observed in patients with periodontitis,
suggesting that vitamin C's antioxidative potential might be inhibited by factors
produced when inflammation spreads to deeper periodontal tissues, including the alveolar
bone.
Despite these findings, vitamin C supplementation did not show effectiveness in improving
PD, echoing the results of another study that also reported no benefit in PD and attachment
level improvement. This suggests that while vitamin C can induce osteogenic differentiation
of periodontal ligament progenitor cells in vitro, its ability to stimulate alveolar bone regeneration in vivo remains unreported, likely explaining the observed lack of impact on PD reduction
following vitamin C supplementation.[31]
The intervention studies reviewed do present evidence suggesting that vitamin C supplementation
may offer some benefits in managing periodontal disease, supporting the nutrient's
preventive potential against this condition. Furthermore, the consideration that periodontopathic
pathogens might decrease blood vitamin C levels through biodegradation is challenged
by a study indicating that serum ascorbic acid levels in patients with moderate-to-severe
periodontitis remain unchanged after scaling and root planning treatment, suggesting
that while vitamin C levels can influence periodontal health, the reverse is not true.[25]
The review also touched on the effects of other antioxidative vitamins, like vitamin
A and E, on periodontal disease, yet only vitamin C consistently showed an association
with periodontal health improvement, underlining the significance of focusing on vitamin
C's relationship with periodontal disease.[30]
Complex interactions between vitamin C, diabetes, and periodontal disease are highlighted,
with studies suggesting that diabetic conditions might affect the efficacy of vitamin
C due to glucose's interference with vitamin C transportation to cells and stimulation
of the hexose monophosphate shunt. Despite these potential interactions, evidence
indicates that dietary or supplemented vitamin C remains effective, especially in
improving the immune function and potentially benefiting diabetic patients' periodontal
status.[23]
The review also delves into the varying impacts of vitamin C on periodontitis among
smokers and nonsmokers, suggesting complicated interactions between vitamin C's antioxidative
effect and oxidative stress induced by tobacco on periodontal tissues. The need for
further research to unravel these interactions is emphasized.[24]
Lastly, the review discusses limitations such as the diversity in periodontal disease
indicators used across studies, which hinders direct comparisons of study results.
It also notes the influence of confounding factors like smoking and diabetes on the
relationship between vitamin C and periodontal disease, acknowledging the current
evidence as perplexing and calling for more extensive research to clarify these associations.[21]
Conclusion
This review has significantly enhanced the body of scientific knowledge by providing
a comprehensive analysis of the relationship between vitamin C consumption and the
occurrence of periodontal disease. It underscored the preventive role of vitamin C
in halting the advancement of periodontal disease. Nevertheless, there is a pressing
need for more detailed investigations concerning the application of periodontal indicators
and a thorough delineation of the elements that affect this relationship, to deepen
the understanding of the connection between vitamin C and periodontal disease.
Future research directions include the necessity to standardize the indicators used
to measure periodontal disease, enabling more precise comparisons across different
studies. Additionally, it is imperative to delve into how smoking and diabetes might
impact the effectiveness of vitamin C in preventing periodontal disease. The review
also highlights the potential benefits of fostering collaborations between oral health
practitioners and dietitians to boost oral health promotion efforts within communities.
Moreover, it advocates for research into the synergistic effects of vitamin C and
chlorhexidine on the prevention and treatment of periodontal disease. This thorough
examination not only broadens the scientific discourse on the preventive capacity
of vitamin C against periodontal disease progression but also calls for further inquiry
into the utilization of periodontal indicators and the clarification of factors influencing
this correlation, to augment the research on the correlation between vitamin C intake
and periodontal disease.
