Next Article in Journal
Exploring the Relationship between Sugar and Sugar Substitutes—Analysis of Income Level and Beverage Consumption Market Pattern Based on the Perspective of Healthy China
Previous Article in Journal
Oats Lower Age-Related Systemic Chronic Inflammation (iAge) in Adults at Risk for Cardiovascular Disease
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 14
Issue 21
10.3390/nu14214473
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Impact of a Specific Collagen Peptide Food Supplement on Periodontal Inflammation in Aftercare Patients—A Randomised Controlled Trial

by
Yvonne Jockel-Schneider
*,
Peggy Stoelzel
,
Jeanine Hess
,
Imme Haubitz
,
Stefan Fickl
and
Ulrich Schlagenhauf
Department of Periodontology, University Hospital Wuerzburg, Pleicherwall 2, D-97070 Wuerzburg, Germany
*
Author to whom correspondence should be addressed.
Nutrients 2022, 14(21), 4473; https://doi.org/10.3390/nu14214473
Submission received: 28 September 2022 / Revised: 21 October 2022 / Accepted: 21 October 2022 / Published: 25 October 2022
(This article belongs to the Topic Oral Health Management for Children, Adolescents, and Adults)
Browse Figure
Versions Notes

Abstract

:
Background: This controlled clinical trial evaluated the impact of a specific collagen peptide food supplement on parameters of periodontal inflammation in aftercare patients. Methods: A total of 39 study patients were enrolled. At baseline, bleeding on probing (BoP; primary outcome), gingival index (GI), plaque control record (PCR), recession (REC) and probing pocket depth (PPD) for the calculation of the periodontal inflamed surface area (PISA) were documented. After subsequent professional mechanical plaque removal (PMPR), participants were randomly provided with a supply of sachets containing either a specific collagen peptide preparation (test group; n = 20) or a placebo (placebo group; n = 19) to be consumed dissolved in liquid once daily until reevaluation at day 90. Results: PMPR supplemented with the consumption of the specific collagen peptides resulted in a significantly lower mean percentage of persisting BoP-positive sites than PMPR plus placebo (test: 10.4% baseline vs. 3.0% reevaluation; placebo: 14.2% baseline vs. 9.4% reevaluation; effect size: 0.86). Mean PISA and GI values were also reduced compared to baseline, with a significant difference in favor of the test group (PISA test: 170.6 mm2 baseline vs. 53.7 mm2 reevaluation; PISA placebo: 229.4 mm2 baseline vs. 184.3 mm2 reevaluation; GI test: 0.5 baseline vs. 0.1 reevaluation; GI placebo: 0.4 baseline vs. 0.3 reevaluation). PCR was also significantly decreased in both experimental groups at revaluation, but the difference between the groups did not reach the level of significance. Conclusions: The supplementary intake of specific collagen peptides may further enhance the anti-inflammatory effect of PMPR in periodontal recall patients.

1. Introduction

Professional mechanical plaque control complemented by efficacious oral hygiene is the established standard of supportive periodontal aftercare (SPC) [1]. Its validity has been verified by numerous studies [2,3,4,5,6]. Nevertheless, even in the majority of successfully treated cases, a small but clinically relevant amount of periodontal inflammation persists, reflected by the number of periodontal pockets with remaining bleeding on probing (BoP), which is associated with an increased risk of disease recurrence or progression [7,8,9,10]. As the occurrence of disease-promoting bacterial dysbiosis is strongly promoted by an increased inflammatory status of the host, the use of adjuvant therapeutics that modulate inflammation at the local and/or systemic level is advocated to further improve the outcome of mechanical plaque control [11,12]. This may involve the systemic or local administration of drugs that either inhibit the inflammatory response or actively promote its resolution [13], as well as targeted changes in the daily diet of patients [14,15,16,17,18] or the consumption of food supplements such as probiotics or omega-3 fatty acids [19,20,21,22]).
The list of known anti-inflammatory food supplements also includes certain collagen peptides that have been successfully evaluated as therapeutic adjuncts in the control of rheumatoid arthritis, which shares common risk factors and aetiological pathways with periodontitis [23,24,25].
In animal and human interventional trials, the consumption of collagen peptides high in hydroxyproline, glycine and proline resulted in improved wound healing and the remediation of impaired immune system function [26,27]. The preventive addition of glycine to the culture media of isolated intestinal epithelial cells mitigated the negative impact of inflicted oxidative stress at the cellular level [28]. In addition, high glycine concentrations in the cell culture media of porcine intestinal epithelial cells improved the barrier function of tight junctions [29].
Furthermore, the addition of specific collagen hydrolysates to the culture media of bacteria derived from the oral or intestinal microbiota had a significant impact on the selective microbial utilization of amino acids [30,31]. It also favoured the synthesis of short-chain fatty acids, which, among other benefits, are known to enhance the maturation of regulatory T-cells and the sealing of epithelial barriers [32].
Based on these in vitro observations, the oral administration of specific collagen peptides in patients suffering from chronic osteoarthritis has already entered clinical practice and resulted in a relevant reduction in pain and functional impairments [33,34,35].
It was the aim of this study to assess the impact of the adjuvant consumption of a specific, commercially available collagen peptide food supplement on parameters of periodontal inflammation in a cohort of aftercare patients.

2. Material and Methods

2.1. Study Design

This investigation was designed as a two-arm, double blind, parallel group, randomised placebo-controlled trial with a 3-month observation period.
The study protocol was established in accordance with the Helsinki Declaration of 1975, as revised in 2013, and the criteria of good clinical practice. It was approved by the ethics committee of the University of Wuerzburg (file # 37/18-me) and registered with clinicaltrials.gov (identifier # NCT03765125). All participants were informed about the objectives and risks in personal interviews and were included in the study after having given written informed consent.

2.2. Study Population

Study patients were recruited from treated chronic periodontitis patients who were in regular supportive aftercare at the Department of Periodontology of the University Hospital of Wuerzburg. The study was conducted between 21 September 2018 (first patient in) and 26 August 2019 (last patient out).

2.3. Eligibility Criteria

Eligibility criteria for study participation were a minimum of 10 natural teeth, a history of treated chronic periodontitis followed by regular supportive periodontal aftercare and the presence of mild-to-moderate chronic gingivitis equal to a gingival index (GI) score of 1 or 2 at a minimum of three teeth.

2.4. Exclusion Criteria

Exclusion criteria were the manifestation of inflammatory oral mucosal diseases other than periodontitis, the presence of xerostomia, pregnancy, acute infections, smoking > 10 cigarettes per day, the intake of antibiotics and/or anti-inflammatory drugs < 4 weeks prior to screening and the presence of chronic systemic diseases (e.g., diabetes).

2.5. Experimental Preparations

Both experimental preparations to be consumed by the study patients were manufactured and supplied by GELITA AG (Eberbach, Germany).
The test preparation (Verisol®B, GELITA AG, Eberbach, Germany) consisted of a mixture of specific, bioactive collagen peptides with an average molecular weight of approximately 2 kDa and an average particle size of about 150 μm. The placebo preparation consisted of silica (Evonik, Germany) being identical regarding taste, smell and color, as well as particle size and consistence to the test preparation. Both experimental preparations were manufactured in compliance with the European Community (EC) regulation 852/2004 on the hygiene of foodstuffs and packaged in individual code-labelled sachets containing the daily dosage of 5 g. According to the manufacturer’s information, the daily dose of the collagen hydrolysate administered for improving skin conditions is usually 2.5 g [36,37]. Evidence from other medical fields concerning the therapy of knee joint pain [38] or osteoporosis [39] as well as unpublished pretrial data on the impact of collagen peptides on gingivitis suggested that doubling the dosage to 5 g daily may be advisable.

2.6. Sequence of Study Intervention

The sequence of the study intervention is schematically depicted in Figure 1.

2.6.1. Visit 1 Baseline (Day 0)

At baseline, the parameters bleeding on probing (BoP; primary outcome), probing pocket depth (PPD), gingival recession (REC), gingival index (GI) and plaque control record (PCR) were assessed on all teeth. A general health profile of the participants, including current intake of medications and frequency of smoking, was documented using a questionnaire. Assessment of BoP and calculation of the Periodontal Inflamed Surface Area (PISA)-Index, REC, PPD and BoP were recorded at six sites per tooth (mesio-buccal, buccal, disto-buccal, disto-oral, oral, mesio-oral) using a manual periodontal probe (UNC-15) (Hu-Friedy, Chicago, IL, USA), measured to the nearest millimeter. Any bleeding spot appearing within 30 s after probing was recorded as a BoP-positive site.
Subsequently, all teeth were cleaned supra- and subgingivally by standard PMPR using hand instruments and ultrasonic scalers followed by air polishing with a low-abrasive erythritol cleaning powder.
Finally, all participants randomly received a supply of code-labelled sachets containing either the experimental collagen peptide preparation (test group; n = 20) or the placebo preparation (control group; n = 19).
The preparations had to be consumed once daily suspended in cold or warm beverages or other aqueous foods. Consumption time could be chosen freely at one’s own discretion, regardless of the timing of oral hygiene or meals.
Unused sachets should be returned at the follow-up appointment.

2.6.2. Visit 2 Reevaluation (Day 90)

At the follow-up appointment on day 90, BoP, PPD, REC, GI and PCR were recorded again as described before, and unused sachets returned by the participants were collected.
The total amount of periodontal inflammation present in each patient was calculated from the recorded BoP, REC and PPD scores using the PISA-Index [40].

2.6.3. Assessment of Gingival Index (GI)

The GI is used to assess the degree of inflammation of the gingiva. In the variation of the GI according to Lobene [41] applied here, the degree of inflammation was assessed visually on the basis of colour and surface changes as well as swelling. The GI was recorded on the buccal aspect of all teeth.

2.6.4. Assessment of PCR

The extent of plaque coverage of the teeth was quantified using the Plaque Control Record (PCR) [42]. Briefly, the crown of a tooth is divided into four quadrants, and the presence/absence of bacterial plaque on each quadrant is assessed. The percentage of tooth quadrants covered by bacterial plaque is then calculated. Before recording the PCR all tooth surfaces were dried by an air-syringe to make adhering bacterial plaque visible.

2.6.5. Assessment of Consumption Compliance

Consumption compliance was calculated by subtracting the number of unused, returned sachets from the total number of sachets provided at baseline. Consumption of the study preparation was considered to be per protocol when ≤10% of the supplied sachets were returned unused.

2.6.6. Adverse Events

The study participants were instructed to report any adverse events immediately, whether related or unrelated to the consumption of the experimental preparations, and were specifically asked at the end of the study about the occurrence of adverse events during the trial.

2.6.7. Blinding, Randomisation and Examiner Calibration

All clinical examinations were conducted by one experienced clinician who was blinded to the group assignment of the study patients.
To minimize intra-examiner variability of periodontal measurements, examiner calibration was performed according to Hefti et al. and Grossi et al. [43,44]. Random allocation of the experimental preparation was ensured using a computer-generated randomisation list with a block size of four.

2.7. Statistical Analysis

2.7.1. Primary Study Outcome and Null Hypothesis

The primary outcome of this trial was defined as the change in the percentage of BoP-positive probing sites between baseline and the end of the study with the null hypothesis of no significant differences between both experimental groups.

2.7.2. Secondary Study Outcomes

Secondary study outcomes were differences in the recorded mean scores of GI, PCR and PISA (calculated from PPD and REC) at baseline and day 90.

2.7.3. Sample Size Calculation

In order to be able to verify a difference of 20% in the reduction of BoP-positive sites between the test and control group at day 90 with a power of 90%, significance level α = 0.05 and an estimated standard deviation of ±20%, sample size calculation resulted in a group size of 2 × 19 study patients when using the Mann–Whitney U test (G-Power, Version 3.1.9.4).

2.7.4. Statistical Data Analysis

Data distribution was examined using probit diagrams with Lillefors limits. As most of the data deviated from a normal distribution, rank tests were used throughout. The difference between study groups was analysed with the Mann–Whitney U test. The change from baseline to post-intervention within groups was analysed with a Wilcoxon signed-rank test. Dichotomous values were tested with Fisher’s exact test.
All data are presented as mean ± SD or median with (25% tail, 75% tail); WinMEDAS statistical software package was used for all statistical analyses. All the tests in the descriptive analysis were conducted as two-sided tests. The significance level was set to p ≤ 0.05. Assessment of the study data was performed as an intention-to-treat analysis.

3. Results

3.1. Recruitment, Drop-Outs, Protocol Violations

From a total of 83 screened patients, 49 were recruited for study participation. Six of them withdrew their consent prior to baseline examination. Finally, 43 patients were randomly assigned to the test (n = 23) or the control group (n = 20). After the baseline visit, three study patients (two test /one control) left the study due to time conflicts, and one study participant (test group) left due to developing serious illness unrelated to the consumed study preparation.
The remaining 39 patients (test n = 20 and control n = 19) completed the study per protocol and were included in the data analysis. Recruitment and drop-outs are depicted as a CONSORT [45] flow diagram in Figure 1.

3.2. Reporting of Adverse Events

During the course of the trial, no adverse events were reported by the study patients.

3.3. Periodontal and General Health Profile

Periodontal and general health-related parameters are shown in Table 1. In the placebo group, the percentage of male study patients was significantly higher than in the test group (67% vs. 33%). All other recorded individual differences were small and statistically not significant.

3.4. Percentage of BoP-Positive Sites (Primary Outcome)

The percentage of BoP-positive sites at baseline and at day 90 are depicted in Table 2. At baseline, the mean percentage of BoP-positive sites did not differ significantly between the groups (10.4% vs. 14.2% respectively). At reevaluation, the mean percentage of BoP-positive sites had significantly decreased to 3.0% in the test group (p < 0.00014), whereas in the controls, a reduction to 9.4% did not reach the level of significance (p < 0.07). The difference between the groups was significant (p < 0.017). The calculated effect size for the reduction of BoP was 0.86 ± 0.33 SD.

3.5. Secondary Study Outcomes

The data of the secondary outcomes PISA, GI and PCR are shown in Table 3.

3.6. Periodontal Inflamed Surface Area (PISA)

At baseline, the recorded mean PISA score did not differ significantly between the groups (test: 170.6 mm2, control: 229.4 mm2). At day 90, the mean PISA score of the test group was significantly lower compared to baseline (53.7 mm2; p < 0.00036), whereas the mean PISA score of the control group was not significantly different from baseline (184.3 mm2; p = 0.3). The difference between the groups at reevaluation (test: 53.7 mm2, control: 184.3 mm2) was significant (p ≤ 0.011).

3.7. Gingival Index (GI)

At baseline, the mean GI score was significantly higher in the test group than in the controls (GI 0.5 vs. GI 0.4; p ≤ 0.044). The mean GI score at day 90 was significantly reduced compared to baseline in both experimental groups (test: GI 0.1 (p ≤ 0.00011)); control: GI 0.3 (p ≤ 0.022)). The difference between the groups proved to be significant (p ≤ 0.029).

3.8. Plaque Control Record (PCR)

Baseline mean PCR scores did not differ significantly between the groups (test: 25.6%; control: 25.4%). At day 90, the mean PCR score was significantly reduced compared to the baseline (test: 9.6% (p < 0.00025); control:18.1% (p < 0.012)). The difference between the groups did not reach the level of significance (p ≤ 0.58).

4. Discussion

The results of this controlled clinical trial suggest that the addition of a specific collagen peptide-containing food supplement to the daily diet of periodontal aftercare patients may further improve the anti-inflammatory efficacy of PMPR, as shown by a significantly lower percentage of BoP-positive sites in the test group at reevaluation.
The difference in the primary outcome was also associated with significantly more pronounced improvements in the secondary outcomes of PISA and GI, corresponding to a significantly greater decrease in overall periodontal inflammatory burden.
The reduction in periodontal inflammation observed in the control group after PMPR was well within the range reported in systematic reviews of the efficacy of PMPR in periodontal aftercare [2,5]. Nevertheless, an observed mean percentage of BoP-positive sites of 9.4% at reevaluation is still close to the definition of gingival inflammation according to the current classification [7].
By contrast, the addition of specific collagen peptide consumption to PMPR led to a mean BoP score of only 3.0% at reevaluation. The observed improvement of mean PISA and GI scores in the test group correspond to this situation, with a persisting mean PISA score of only 53.7 mm2 compared to 184.3 mm2 in the controls. This demonstrates that the anti-inflammatory efficacy of adjuvant collagen peptide consumption in the control of periodontal inflammation is comparable to the benefits of the adjuvant use of antimicrobial agents reported by a recent meta-analysis [46].
Mean PCR also decreased significantly between baseline and reevaluation, without significant differences between the groups. This indicates that the observed beneficial impact of collagen peptide consumption on periodontal inflammation is not primarily due to improved plaque control. It rather appears to be based on a systemic immune modulation and/or the resolution of disease-promoting bacterial dysbiosis. This is in line with the findings of other clinical trials evaluating the impact of dietary changes on gingival inflammation [14,15,17,18] and the dysbiosis model of periodontitis development [47].
The proposed modulation of the immune system as well as the presumed resolution of bacterial dysbiosis may be due to the high L-arginine content of the specific collagen peptides used in this study (7.8 g/100 g). The oxidation of L-arginine to L-citrulline by the activity of a nitric oxide synthases (NOS) is a well-known pathway for the formation of nitric oxide (NO), an essential signalling molecule involved in a multitude of physiological processes in the human body. NO formation plays a major role in the development of inflammatory conditions as well as in their resolution and prevention [48]. It reduces, for example, the synthesis of the chemo-attractive protein MCP-1 [49] and inhibits leucocyte adherence to vascular walls as well as platelet aggregation and activation [50]. As far as we know, there have been no previous clinical trials assessing the impact of dietary collagen peptides on periodontal inflammation. However, the results of our study confirm the positive findings of investigations that assessed the anti-inflammatory effect of collagen peptide consumption in patients suffering from chronic osteoarthritis [33,34,35] as well as endothelial dysfunction [51].
In addition to directly modulating the immune response of the host, the presence and formation of NO also has a profound impact on the composition and metabolism of the orodigestive microbiota [18,51,52,53,54,55]. NO is found in significant quantities in dental plaque [56] and has a pronounced inhibitory effect against periodontal pathogens [52,53,57].
An increase in salivary nitrite as an alternative source of physiological NO-formation [58] was accompanied by a resolution of disease-promoting dysbiosis in gingivitis-associated bacterial biofilms [18,59]. In addition, the ingested collagen peptides may also act as a prebiotic. Their microbial fermentation in the colon increases the concentration of tissue-protective antioxidants as well as the concentration of short-chain fatty acids, which are important mediators of lymphocyte maturation [32,60,61].
Relevant limitations of this study are the comparatively short observation period of 3 months without long-term follow-up, the small number of participants and the lack of documentation of dietary behaviour or adherence to a standardised diet. These are in line with the reported restrictions of other clinical trials evaluating the impact of specific dietary intervention [15,21]. They also reflect the fact that it is very difficult to successfully conduct studies involving food restrictions in human volunteers or patients over a long period of time due to a steadily decreasing level of compliance [62].
As mean PCR and GI scores also improved significantly in the placebo group, the impact of a positive Hawthorne effect may not be ruled out. Nevertheless, the significant difference between both experimental groups regarding mean GI scores at day 90 in favor of the test group suggests a significantly more pronounced reduction in inflammation not attributable to improved oral hygiene alone.
Therefore, future studies should aim to recruit larger cohorts of periodontitis patients with a higher inflammatory burden and provide an observation period of at least 6–12 months to test the clinical relevance of the findings obtained in this pilot study. Additionally, the optimal dosage of administration needs to be established. As the effect of a collagen peptide preparation on the microbiota and the host response is decisively influenced by its specific composition [32], the results observed with the consumption of this study preparation may not be transferred to similar preparations with a different composition without further clinical evaluation.

5. Conclusions

Supplementing professional plaque control with the daily consumption of specific collagen peptides may have the potential to further improve the outcome of established periodontal aftercare therapy. Due to the limits of the present investigation, however, further research is needed before a general recommendation for daily practice can be given.

Author Contributions

All authors contributed significantly to the manuscript by writing the draft, evaluating the data and critically revising the manuscript. Y.J.-S. and U.S. jointly conceived the design of the study, contributed to the interpretation of the data and wrote the manuscript. P.S. recruited all study patients. Y.J.-S. recorded the study parameters. Professional mechanical plaque removal (PMPR) was performed by J.H. S.F. contributed to data analysis and the acquisition of external funding to finance the study. I.H. performed the bioinformatics/statistical analysis. All authors have read and agreed to the published version of the manuscript.

Funding

This trial was funded by GELITA AG (Eberbach, Germany), manufacturer and supplier of the experimental bioactive collagen peptide preparations. The company was not involved in data recording, data analysis or the interpretation of the data. It received the manuscript for approval prior to submission but did not interfere with wording, content or emphasis. It was supported by the Open Access Publication Fund of the University of Wuerzburg.

Institutional Review Board Statement

The study protocol was established in accordance with the Helsinki Declaration of 1975, as revised in 2013, and the criteria of good clinical practice. It was approved by the ethics committee of the University of Wuerzburg (file # 37/18-me) and registered with clinicaltrials.gov (identifier # NCT03765125).

Informed Consent Statement

All participants were informed about the objectives and risks in personal interviews and were included in the study after having given written informed consent.

Data Availability Statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Sanz, M.; Herrera, D.; Kebschull, M.; Chapple, I.; Jepsen, S.; Beglundh, T.; Sculean, A.; Tonetti, M.S. PEFP Workshop Participants and Methodological Consultants. Treatment of stage I–III periodontitis-The EFP S3 level clinical practice guideline. J. Clin. Periodontol. 2020, 47 (Suppl. 22), 4–60. [Google Scholar] [CrossRef] [PubMed]
  2. Trombelli, L.; Franceschetti, G.; Farina, R. Effect of professional mechanical plaque removal performed on a long-term, routine basis in the secondary prevention of periodontitis: A systematic review. J. Clin. Periodontol. 2015, 42 (Suppl. 16), S221–S236. [Google Scholar] [CrossRef] [PubMed]
  3. van der Weijden, F.; Slot, D.E. Oral hygiene in the prevention of periodontal diseases: The evidence. Periodontology 2000 2011, 55, 104–123. [Google Scholar] [CrossRef] [PubMed]
  4. Chapple, I.L.C.; Mealey, B.L.; Van Dyke, T.E.; Bartold, P.M.; Dommisch, H.; Eickholz, P.; Geisinger, M.L.; Genco, R.J.; Glogauer, M.; Goldstein, M.; et al. Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Periodontol. 2018, 89 (Suppl. 1), S74–S84. [Google Scholar] [CrossRef]
  5. Needleman, I.; Nibali, L.; Di Iorio, A. Professional mechanical plaque removal for prevention of periodontal diseases in adults--systematic review update. J. Clin. Periodontol. 2015, 42 (Suppl. 16), S12–S35. [Google Scholar] [CrossRef]
  6. Sanz, M.; Baumer, A.; Buduneli, N.; Dommisch, H.; Farina, R.; Kononen, E.; Linden, G.; Meyle, J.; Preshaw, P.M.; Quirynen, M.; et al. Effect of professional mechanical plaque removal on secondary prevention of periodontitis and the complications of gingival and periodontal preventive measures: Consensus report of group 4 of the 11th European Workshop on Periodontology on effective prevention of periodontal and peri-implant diseases. J. Clin. Periodontol. 2015, 42 (Suppl. 16), S214–S220. [Google Scholar] [CrossRef]
  7. Caton, J.G.; Armitage, G.; Berglundh, T.; Chapple, I.L.C.; Jepsen, S.; Kornman, K.S.; Mealey, B.L.; Papapanou, P.N.; Sanz, M.; Tonetti, M.S. A new classification scheme for periodontal and peri-implant diseases and conditions—Introduction and key changes from the 1999 classification. J. Clin. Periodontol. 2018, 45 (Suppl. 20), S1–S8. [Google Scholar] [CrossRef]
  8. Lang, N.P.; Suvan, J.E.; Tonetti, M.S. Risk factor assessment tools for the prevention of periodontitis progression a systematic review. J. Clin. Periodontol. 2015, 42 (Suppl. 16), S59–S70. [Google Scholar] [CrossRef]
  9. Lang, N.P.; Joss, A.; Tonetti, M.S. Monitoring disease during supportive periodontal treatment by bleeding on probing. Periodontology 2000 1996, 12, 44–48. [Google Scholar] [CrossRef]
  10. Matuliene, G.; Pjetursson, B.E.; Salvi, G.E.; Schmidlin, K.; Bragger, U.; Zwahlen, M.; Lang, N.P. Influence of residual pockets on progression of periodontitis and tooth loss: Results after 11 years of maintenance. J. Clin. Periodontol. 2008, 35, 685–695. [Google Scholar] [CrossRef]
  11. Corbella, S.; Calciolari, E.; Alberti, A.; Donos, N.; Francetti, L. Systematic review and meta-analysis on the adjunctive use of host immune modulators in non-surgical periodontal treatment in healthy and systemically compromised patients. Sci. Rep. 2021, 11, 12125. [Google Scholar] [CrossRef] [PubMed]
  12. Donos, N.; Calciolari, E.; Brusselaers, N.; Goldoni, M.; Bostanci, N.; Belibasakis, G.N. The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic review of randomized, placebo-controlled clinical studies. J. Clin. Periodontol. 2020, 47 (Suppl. 22), 199–238. [Google Scholar] [CrossRef] [Green Version]
  13. Hajishengallis, G.; Hasturk, H.; Lambris, J.D. C3-targeted therapy in periodontal disease: Moving closer to the clinic. Trends Immunol. 2021, 42, 856–864. [Google Scholar] [CrossRef] [PubMed]
  14. Baumgartner, S.; Imfeld, T.; Schicht, O.; Rath, C.; Persson, R.E.; Persson, G.R. The impact of the stone age diet on gingival conditions in the absence of oral hygiene. J. Periodontol. 2009, 80, 759–768. [Google Scholar] [CrossRef] [PubMed]
  15. Woelber, J.P.; Gartner, M.; Breuninger, L.; Anderson, A.; Konig, D.; Hellwig, E.; Al-Ahmad, A.; Vach, K.; Dotsch, A.; Ratka-Kruger, P.; et al. The influence of an anti-inflammatory diet on gingivitis. A randomized controlled trial. J. Clin. Periodontol. 2019, 46, 481–490. [Google Scholar] [CrossRef]
  16. Bartha, V.; Exner, L.; Schweikert, D.; Woelber, J.P.; Vach, K.; Meyer, A.L.; Basrai, M.; Bischoff, S.C.; Meller, C.; Wolff, D. Effect of the Mediterranean diet on gingivitis. A randomized controlled trial. J. Clin. Periodontol. 2022, 49, 111–122. [Google Scholar] [CrossRef]
  17. Jockel-Schneider, Y.; Gossner, S.K.; Petersen, N.; Stolzel, P.; Hagele, F.; Schweiggert, R.M.; Haubitz, I.; Eigenthaler, M.; Carle, R.; Schlagenhauf, U. Stimulation of the nitrate-nitrite-NO-metabolism by repeated lettuce juice consumption decreases gingival inflammation in periodontal recall patients: A randomized, double-blinded, placebo-controlled clinical trial. J. Clin. Periodontol. 2016, 43, 603–608. [Google Scholar] [CrossRef]
  18. Jockel-Schneider, Y.; Schlagenhauf, U.; Stolzel, P.; Gossner, S.; Carle, R.; Ehmke, B.; Prior, K.; Hagenfeld, D. Nitrate-rich diet alters the composition of the oral microbiota in periodontal recall patients. J. Periodontol. 2021, 92, 1536–1545. [Google Scholar] [CrossRef]
  19. Widyarman, A.S.; Theodorea, C.F. Novel Indigenous Probiotic Lactobacillus reuteri Strain Produces Anti-biofilm Reuterin against Pathogenic Periodontal Bacteria. Eur. J. Dent. 2022, 16, 96–101. [Google Scholar] [CrossRef]
  20. Chatterjee, D.; Chatterjee, A.; Kalra, D.; Kapoor, A.; Vijay, S.; Jain, S. Role of adjunct use of omega 3 fatty acids in periodontal therapy of periodontitis. A systematic review and meta-analysis. J. Oral Biol. Craniofac. Res. 2022, 12, 55–62. [Google Scholar] [CrossRef]
  21. Deore, G.D.; Gurav, A.N.; Patil, R.; Shete, A.R.; Naiktari, R.S.; Inamdar, S.P. Omega 3 fatty acids as a host modulator in chronic periodontitis patients: A randomised, double-blind, palcebo-controlled, clinical trial. J. Periodontal. Implant Sci. 2014, 44, 25–32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Schlagenhauf, U.; Jakob, L.; Eigenthaler, M.; Segerer, S.; Jockel-Schneider, Y.; Rehn, M. Regular consumption of Lactobacillus reuteri-containing lozenges reduces pregnancy gingivitis: An RCT. J. Clin. Periodontol. 2016, 43, 948–954. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Nik-Azis, N.M.; Mohd, N.; Mohd Fadzilah, F.; Mohamed Haflah, N.H.; Mohamed Said, M.S.; Baharin, B. Rheumatoid arthritis serotype and synthetic disease-modifying anti-rheumatic drugs in patients with periodontitis: A case-control study. PLoS ONE 2021, 16, e0252859. [Google Scholar] [CrossRef]
  24. Bartold, P.M.; Lopez-Oliva, I. Periodontitis and rheumatoid arthritis: An update 2012–2017. Periodontology 2000 2020, 83, 189–212. [Google Scholar] [CrossRef]
  25. de Molon, R.S.; Rossa, C., Jr.; Thurlings, R.M.; Cirelli, J.A.; Koenders, M.I. Linkage of Periodontitis and Rheumatoid Arthritis: Current Evidence and Potential Biological Interactions. Int. J. Mol. Sci. 2019, 20, 4541. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  26. Wu, G.; Bazer, F.W.; Burghardt, R.C.; Johnson, G.A.; Kim, S.W.; Knabe, D.A.; Li, P.; Li, X.; McKnight, J.R.; Satterfield, M.C.; et al. Proline and hydroxyproline metabolism: Implications for animal and human nutrition. Amino Acids 2011, 40, 1053–1063. [Google Scholar] [CrossRef] [Green Version]
  27. Li, P.; Yin, Y.L.; Li, D.; Kim, S.W.; Wu, G. Amino acids and immune function. Br. J. Nutr. 2007, 98, 237–252. [Google Scholar] [CrossRef] [Green Version]
  28. Howard, A.; Tahir, I.; Javed, S.; Waring, S.M.; Ford, D.; Hirst, B.H. Glycine transporter GLYT1 is essential for glycine-mediated protection of human intestinal epithelial cells against oxidative damage. J. Physiol. 2010, 588, 995–1009. [Google Scholar] [CrossRef]
  29. Li, W.; Sun, K.; Ji, Y.; Wu, Z.; Wang, W.; Dai, Z.; Wu, G. Glycine Regulates Expression and Distribution of Claudin-7 and ZO-3 Proteins in Intestinal Porcine Epithelial Cells. J. Nutr. 2016, 146, 964–969. [Google Scholar] [CrossRef] [Green Version]
  30. Dai, Z.L.; Li, X.L.; Xi, P.B.; Zhang, J.; Wu, G.; Zhu, W.Y. L-Glutamine regulates amino acid utilization by intestinal bacteria. Amino Acids 2013, 45, 501–512. [Google Scholar] [CrossRef]
  31. Slomka, V.; Hernandez-Sanabria, E.; Herrero, E.R.; Zaidel, L.; Bernaerts, K.; Boon, N.; Quirynen, M.; Teughels, W. Nutritional stimulation of commensal oral bacteria suppresses pathogens: The prebiotic concept. J. Clin. Periodontol. 2017, 44, 344–352. [Google Scholar] [CrossRef] [PubMed]
  32. Larder, C.E.; Iskandar, M.M.; Kubow, S. Gastrointestinal Digestion Model Assessment of Peptide Diversity and Microbial Fermentation Products of Collagen Hydrolysates. Nutrients 2021, 13, 2720. [Google Scholar] [CrossRef] [PubMed]
  33. Bello, A.E.; Oesser, S. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: A review of the literature. Curr. Med. Res. Opin. 2006, 22, 2221–2232. [Google Scholar] [CrossRef] [PubMed]
  34. Garcia-Coronado, J.M.; Martinez-Olvera, L.; Elizondo-Omana, R.E.; Acosta-Olivo, C.A.; Vilchez-Cavazos, F.; Simental-Mendia, L.E.; Simental-Mendia, M. Effect of collagen supplementation on osteoarthritis symptoms: A meta-analysis of randomized placebo-controlled trials. Int. Orthop. 2019, 43, 531–538. [Google Scholar] [CrossRef]
  35. Puigdellivol, J.; Comellas Berenger, C.; Perez Fernandez, M.A.; Cowalinsky Millan, J.M.; Carreras Vidal, C.; Gil Gil, I.; Martinez Pagan, J.; Ruiz Nieto, B.; Jimenez Gomez, F.; Comas Figuerola, F.X.; et al. Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine in Pain Reduction and Functional Capacity in Osteoarthritis Patients. J. Diet. Suppl. 2019, 16, 379–389. [Google Scholar] [CrossRef]
  36. Proksch, E.; Schunck, M.; Zague, V.; Segger, D.; Degwert, J.; Oesser, S. Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacol. Physiol. 2014, 27, 113–119. [Google Scholar] [CrossRef]
  37. Hexsel, D.; Zague, V.; Schunck, M.; Siega, C.; Camozzato, F.O.; Oesser, S. Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails. J. Cosmet. Dermatol. 2017, 16, 520–526. [Google Scholar] [CrossRef]
  38. Zdzieblik, D.; Brame, J.; Oesser, S.; Gollhofer, A.; Konig, D. The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial. Nutrients 2021, 13, 523. [Google Scholar] [CrossRef]
  39. Zdzieblik, D.; Oesser, S.; Konig, D. Specific Bioactive Collagen Peptides in Osteopenia and Osteoporosis: Long-Term Observation in Postmenopausal Women. J. Bone Metab. 2021, 28, 207–213. [Google Scholar] [CrossRef]
  40. Nesse, W.; Abbas, F.; van der Ploeg, I.; Spijkervet, F.K.; Dijkstra, P.U.; Vissink, A. Periodontal inflamed surface area: Quantifying inflammatory burden. J. Clin. Periodontol. 2008, 35, 668–673. [Google Scholar] [CrossRef]
  41. Lobene, R.R.; Weatherford, T.; Ross, N.M.; Lamm, R.A.; Menaker, L. A modified gingival index for use in clinical trials. Clin. Prev. Dent. 1986, 8, 3–6. [Google Scholar] [PubMed]
  42. O’Leary, T.J.; Drake, R.B.; Naylor, J.E. The plaque control record. J. Periodontol. 1972, 43, 38. [Google Scholar] [CrossRef] [PubMed]
  43. Hefti, A.F.; Preshaw, P.M. Examiner alignment and assessment in clinical periodontal research. Periodontology 2000 2012, 59, 41–60. [Google Scholar] [CrossRef] [PubMed]
  44. Grossi, S.G.; Dunford, R.G.; Ho, A.; Koch, G.; Machtei, E.E.; Genco, R.J. Sources of error for periodontal probing measurements. J. Periodontal. Res. 1996, 31, 330–336. [Google Scholar] [CrossRef] [PubMed]
  45. Schulz, K.F.; Altman, D.G.; Moher, D.; Group, C. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. PLoS Med. 2010, 7, e1000251. [Google Scholar] [CrossRef] [Green Version]
  46. Figuero, E.; Herrera, D.; Tobias, A.; Serrano, J.; Roldan, S.; Escribano, M.; Martin, C. Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review and network meta-analyses. J. Clin. Periodontol. 2019, 46, 723–739. [Google Scholar] [CrossRef]
  47. Hajishengallis, G.; Lamont, R.J. Beyond the red complex and into more complexity: The polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol. Oral Microbiol. 2012, 27, 409–419. [Google Scholar] [CrossRef] [Green Version]
  48. Raubenheimer, K.; Bondonno, C.; Blekkenhorst, L.; Wagner, K.H.; Peake, J.M.; Neubauer, O. Effects of dietary nitrate on inflammation and immune function, and implications for cardiovascular health. Nutr. Rev. 2019, 77, 584–599. [Google Scholar] [CrossRef]
  49. Zeiher, A.M.; Fisslthaler, B.; Schray-Utz, B.; Busse, R. Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. Circ. Res. 1995, 76, 980–986. [Google Scholar] [CrossRef]
  50. Kubes, P.; Suzuki, M.; Granger, D.N. Nitric oxide: An endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. USA 1991, 88, 4651–4655. [Google Scholar] [CrossRef]
  51. Gambardella, J.; Khondkar, W.; Morelli, M.B.; Wang, X.; Santulli, G.; Trimarco, V. Arginine and Endothelial Function. Biomedicines 2020, 8, 277. [Google Scholar] [CrossRef] [PubMed]
  52. Backlund, C.J.; Sergesketter, A.R.; Offenbacher, S.; Schoenfisch, M.H. Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens. J. Dent. Res. 2014, 93, 1089–1094. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Backlund, C.J.; Worley, B.V.; Sergesketter, A.R.; Schoenfisch, M.H. Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide. J. Dent. Res. 2015, 94, 1092–1098. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Nambu, T.; Wang, D.; Mashimo, C.; Maruyama, H.; Kashiwagi, K.; Yoshikawa, K.; Yamamoto, K.; Okinaga, T. Nitric Oxide Donor Modulates a Multispecies Oral Bacterial Community-An In Vitro Study. Microorganisms 2019, 7, 353. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Vanhatalo, A.; Blackwell, J.R.; L’Heureux, J.E.; Williams, D.W.; Smith, A.; van der Giezen, M.; Winyard, P.G.; Kelly, J.; Jones, A.M. Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans. Free Radic. Biol. Med. 2018, 124, 21–30. [Google Scholar] [CrossRef]
  56. Schreiber, F.; Stief, P.; Gieseke, A.; Heisterkamp, I.M.; Verstraete, W.; de Beer, D.; Stoodley, P. Denitrification in human dental plaque. BMC Biol. 2010, 8, 24. [Google Scholar] [CrossRef] [Green Version]
  57. Shim, J.S.; Park, D.S.; Baek, D.H.; Jha, N.; Park, S.I.; Yun, H.J.; Kim, W.J.; Ryu, J.J. Antimicrobial activity of NO-releasing compounds against periodontal pathogens. PLoS ONE 2018, 13, e0199998. [Google Scholar] [CrossRef]
  58. Lundberg, J.O.; Weitzberg, E.; Gladwin, M.T. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 2008, 7, 156–167. [Google Scholar] [CrossRef]
  59. Chen, T.; Marsh, P.D.; Al-Hebshi, N.N. SMDI: An Index for Measuring Subgingival Microbial Dysbiosis. J. Dent. Res. 2022, 101, 331–338. [Google Scholar] [CrossRef]
  60. Ao, J.; Li, B. Amino acid composition and antioxidant activities of hydrolysates and peptide fractions from porcine collagen. Food Sci. Technol. Int. 2012, 18, 425–434. [Google Scholar] [CrossRef]
  61. Kim, C.H. Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids. Cell Mol. Immunol. 2021, 18, 1161–1171. [Google Scholar] [CrossRef] [PubMed]
  62. Kwan, M.W.; Wong, M.C.; Wang, H.H.; Liu, K.Q.; Lee, C.L.; Yan, B.P.; Yu, C.M.; Griffiths, S.M. Compliance with the Dietary Approaches to Stop Hypertension (DASH) diet: A systematic review. PLoS ONE 2013, 8, e78412. [Google Scholar] [CrossRef] [PubMed]
Nutrients 14 04473 g001 550
Figure 1. Recruitment, drop-outs and protocol violations during the study observation period.
Figure 1. Recruitment, drop-outs and protocol violations during the study observation period.
Nutrients 14 04473 g001
Table
Table 1. Demographics and general health profile.
Table 1. Demographics and general health profile.
VariableTest GroupControl Groupp-Value
n = 20n = 19
Age (yrs)
median (CI)		59.6 (56.6–62.6)(55.2–63.1)pU = 0.94
Male gender no. (%)6 (33%)12 (67%)Pc = 0.036
No. of teeth median (CI)25 (22–27)26 (24–29)pU = 0.23
PPD baseline (mm)
median (CI)		2.9 (2.7–3.1)2.9 (2.6–3.1)pU = 0.64
Occasional Smoking
(<10 cigarettes/day)		2 (10%)2 (10.2%)Pc = 1.0
Osteoarthritis1 (5%)1 (5.3%)Pc = 1.0
Hypertension2 (10%)2 (10.5%)Pc = 1.0
Hypothyroidism5 (25%)1 (5.3 %)Pc = 0.18
Median (CI)—median (25%; 75% confidence interval); pU from Mann–Whitney U test; Pc from chi-square test.
Table
Table 2. Percentage of sites being positive for bleeding on probing (BoP).
Table 2. Percentage of sites being positive for bleeding on probing (BoP).
VisitTest Group
n = 20
mean ± SD 		Control Group
n = 19
mean ± SD		pU between Groups
BoP %
Baseline 		10.4 ± 7.014.2 ± 10.30.29
BoP %
Day 90 		3.0 ± 3.89.4 ± 9.90.017
pW within the groups0.000140.07
SD: standard deviation; pU (Mann–Whitney U test); pW (Wilcoxon signed rank test).
Table
Table 3. Periodontal Inflamed Surface Area (PISA), Gingival Index (GI) and Plaque Control Record (PCR).
Table 3. Periodontal Inflamed Surface Area (PISA), Gingival Index (GI) and Plaque Control Record (PCR).
VisitTest Group
n = 20
mean ± SD		Control Group
n = 19
mean ± SD		pU between Groups
PISA (mm2)
Baseline 		170.6 ± 129.9229.4 ± 161.60.23
PISA (mm2)
Day 90 		53.7 ± 70.5184.3 ± 214.70.011
pW within the groups0.000360.3
GI
Baseline		0.5 ± 0.3 0.4 ± 0.2 0.044
GI
Day 90 		0.1 ± 0.2 0.3 ± 0.20.029
pw within the groups0.000110.022
PCR%
Baseline 		25.6 ± 19.525.4 ± 14.3 0.81
PCR%
Day 90 		9.6 ± 10.3 18.1 ± 15.9 0.14
pw within the groups0.00250.012
SD: standard deviation; pU (Mann–Whitney U test); pW (Wilcoxon signed rank test).
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Jockel-Schneider, Y.; Stoelzel, P.; Hess, J.; Haubitz, I.; Fickl, S.; Schlagenhauf, U. Impact of a Specific Collagen Peptide Food Supplement on Periodontal Inflammation in Aftercare Patients—A Randomised Controlled Trial. Nutrients 2022, 14, 4473. https://doi.org/10.3390/nu14214473

AMA Style

Jockel-Schneider Y, Stoelzel P, Hess J, Haubitz I, Fickl S, Schlagenhauf U. Impact of a Specific Collagen Peptide Food Supplement on Periodontal Inflammation in Aftercare Patients—A Randomised Controlled Trial. Nutrients. 2022; 14(21):4473. https://doi.org/10.3390/nu14214473

Chicago/Turabian Style

Jockel-Schneider, Yvonne, Peggy Stoelzel, Jeanine Hess, Imme Haubitz, Stefan Fickl, and Ulrich Schlagenhauf. 2022. "Impact of a Specific Collagen Peptide Food Supplement on Periodontal Inflammation in Aftercare Patients—A Randomised Controlled Trial" Nutrients 14, no. 21: 4473. https://doi.org/10.3390/nu14214473

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop