Complementary Therapies in Clinical Practice xxx (2014) 1e6
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Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial L.C. Mourão a, D.M. Cataldo b, H. Moutinho b, R.G. Fischer c, A. Canabarro a, c, * a
Department of Periodontology, School of Dentistry, Universidade Veiga de Almeida (UVA), Rio de Janeiro, Brazil Instituto Hahnemanniano do Brasil (IHB), Rio de Janeiro, Brazil c Department of Periodontology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil b
a b s t r a c t Keywords: Chronic periodontitis Non-surgical periodontal treatment Homeopathy
Background and objective: The aim of this study was test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP) in patients with chronic periodontitis (CP). Materials and Methods: 50 patients with CP were randomly allocated to one of two treatment groups: SRP (C-G) or SRP þ H (H-G). Assessments were made at baseline and after 3 and 12 months of treatments. The local and systemic responses to the treatments were evaluated by clinical and serologic parameters, respectively. Results: Both groups displayed significant improvements, however, using clinical attachment gain and reductions in HDL, LDL and Total Cholesterol, Triglycerides, Glucose and Uric acid, from baseline to 1 year, as criteria for treatment success, H-G performed significantly better than C-G. Conclusion: The findings of this 1-year follow-up randomized clinical trial suggest that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction Chronic periodontitis (CP) is a chronic inflammatory disease resulting from the disruption of homeostasis between subgingival microbiota and host defenses [1]. Periodontal breakdown develops when the microbial load within a periodontal pocket overwhelms the local and systemic host defense mechanisms [2]. Advanced CP with deep periodontal pockets affects approximately 10e15% of world’s adult population [3]. Although severe clinical attachment loss (CAL) is usually only evident in a few sites [4], CP often becomes more severe with age [5] and, if no treatment is given, many teeth could be lost [5,6]. CP may also aggravate preexisting diseases, because it impacts the systemic components of the host protective responses [7]. Despite the recognition that systemic factors can alter the risk to CP, only recently has evidence begun to emerge, still under investigation, that infections of the
* Corresponding author. Department of Periodontology, School of Dentistry, Universidade Veiga de Almeida (UVA), Rua Ibituruna 108, casa 3, sala 201, Tijuca, CEP 20271-020 Rio de Janeiro, Brazil. Tel.: þ552125748871; fax: þ552132343024. E-mail addresses: [email protected], [email protected] (A. Canabarro).
oral cavity are able to influence the occurrence and severity of certain conditions and systemic diseases [8]. Scaling and root planning (SRP) is the gold standard treatment for patients with chronic periodontitis. Nevertheless, in recent years, different therapeutic strategies have been proposed to improve the results of SRP [9], because some factors may limit the success of treatment by SRP, such as root anatomy, furcations and deep probing depths [10]. Many therapeutic options have been used in the treatment of chronic periodontitis, especially surgical and antibiotic approaches [11,12]. However, they have only been showing modest clinical attachment gain over SRP [11,12], usually associated with some adverse effects [13,14], leaving room for new treatment options. Furthermore, such approaches are only used to treat the local symptoms and often fail to treat the whole person. Homeopathy (H) is a system based on the principle of “like cures like” [15,16]. Homeopathy states that a disease can be cured using a diluted form of a substance that induces the same symptoms in a healthy person [16]. H is effective against many pathologies, relatively inexpensive, has high patient satisfaction and a low incidence of side effects [17]. In fact, some dentists have been using homeopathic medicines in everyday practice as an adjunct to conventional treatment for a
http://dx.doi.org/10.1016/j.ctcp.2014.03.003 1744-3881/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mourão LC, et al., Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial, Complementary Therapies in Clinical Practice (2014), http://dx.doi.org/10.1016/j.ctcp.2014.03.003
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range of chronic pathologies, including CP [17]. However, studies assessing the efficacy of such treatments are not available yet [18]. The use of homeopathy in our first 3-month follow-up study was intended to balance the physiological and metabolic function systemic of CP patients. Patients have used specific homeopathic medicines as an adjuvant of SRP in order to promote an additional effect on the treatment of CP [19]. The aim of this randomized clinical trial was to compare the clinical and serologic effects of homeopathy plus SRP to those of conventional mechanical treatment. The present report presents the results at 3 and 12 months after treatment.
and analyzed. The randomization list was transferred to individual sealed opaque envelopes sequentially numbered which were passed to the periodontist (LSM), each one containing the name of the next treatment in a card. Fifty subjects with CP participated in this “Single-Blind Randomized Controlled Clinical Trial”, 40 of them participated in the former study. Half of the subjects received an additional homeopathic therapy. The main characteristics of both groups are shown in Table 1.
2. Materials and methods
2.2.1. Conventional periodontal therapy (SRP) All patients were submitted to conventional non-surgical periodontal treatment by a “blind” and experienced periodontist (LSM) who did not know which patients were getting the active treatment or not. The proposed therapy had the following stages: 1. First visit (60 min): personal oral hygiene instructions (how to use hand toothbrush and dental floss), a brief description of periodontal disease and its local and systemic effects (w20 min) and supragingival scaling (w40 min) that was performed by ultrasonic scaler tips (Profi Neo, Dabi Atlante, Ribeirão Preto, SP, Brazil). The patients were asked not to use any antiseptic mouthwashes. Other visits: consultations for subgingival SRP e the number of consultations needed to obtain clinical outcome was standardized to four (one per quadrant, in total 4 weeks). If there was no tooth in a given quadrant, the number of visits was reduced to the number of quadrants present. Instrumentation was performed by hand with subgingival curettes (Gracey curettes, Trinity, Sao Paulo, SP, Brazil), for 10 min per tooth. Supportive treatment sessions were carried out at 3, 6, 9 and 12 months after the completion of active therapy. Oral hygiene procedures were reinforced and supragingival calculus is removed with ultrasonic scaler tips.
2.1. Participants In continuation of our previous study on the effects of periodontal treatment plus homeopathy on clinical and serologic parameters [19], potential subjects eligible for the study of both genders, aged from 35 to 70 years old, were identified from the population referred to the periodontal clinic of Center for Health at the Universidade Veiga de Almeida (UVA), Rio de Janeiro, Brazil. All of them were submitted to a complete periodontal examination for a periodontal diagnosis, after approval by the Ethics and Research Committee of UVA (CEP/UVA protocol number 285-11). Patients who fulfilled the study inclusion/exclusion criteria were invited to participate in the study. Inclusion criteria: The presence of clinical attachment level (CAL) 3 mm in proximal sites of two non-adjacent teeth. Bone loss confirmed by periapical radiographs and bleeding on probing (BOP) should also be present [20]. The exclusion criteria were: patients who had received periodontal treatment in the last year and individuals with aggressive periodontitis. And for both groups: smokers, being pregnant or nursing, patients with a medical condition that could affect the periodontal tissues such as HIV, or any other significant systemic disease that could interfere in the periodontium (diabetes etc), patients that had used medications such as non-steroidal anti-inflammatory, or antibiotic therapy within the last 6 months. 2.1.1. Randomization and allocation concealment Participants were randomly assigned to receive one of the two treatments by a computer-generated table. Restricted randomization was used, stratifying people by age, number of teeth and average CAL in order to avoid unequal balance between the two treatments (Table 1). The randomization table was sent to a “blind” participant (AC) that was the only one who knew the code. The randomization code was only broken when all data were collected Table 1 Main characteristics of the participants of control (C-G) and homeopathy (H-G) groups. Characteristics
C-G
Age (Years) Gender: male/female Smoking: yes/no Number of teeth PI (%) BOP (%) CAL (mm) PPD (mm) Severity of CP (Severe/Moderate)a Extension of CP (Generalized/Localized)b
48.4 10/15 No 24.45 74.97 50.84 4.66 4.17 9/16 18/7
a
H-G 8.5
3.15 7.26 10.66 0.31 0.13
47.7 12/13 No 23.65 70.64 52.96 4.50 4.23 7/18 19/6
8.7
4,41 8.00 14.33 0.55 0.24
Obs: Severe CP: CAL 5 mm and Moderate CP: CAL < 5 mm. Generalized CP: 30% of sites with CAL >2 mm and Localized CP: 2 mm [23]. Non-significative. b
2.2. Treatment protocols
2.3. Additional homeopathic therapy 25 patients (H-G) were also submitted to the homeopathic protocol which had been validated in a previous study [19]: 1) Depurative medicine (helps cleanse waste products and toxins from our body): Berberis 6CH (Farmácia-Escola Prof. José Barros da Silva, Rio de Janeiro, Brazil). Posology: two tablets twice daily for 45 days. 2) Acute Drug (drugs that treat illness which has an abrupt onset and needs immediate attention): Mercurius solubilis/Belladona/ Hepar sulphur e 6CH (Farmácia-Escola Prof. José Barros da Silva, Rio de Janeiro, Brazil). Posology: two tablets three times a day for 15 days. 3) Nosodes (homeopathic remedies prepared from a product of disease such as infected tissues or causal organisms): Pyrogenium e 200 CH (Farmácia-Escola Prof. José Barros da Silva, Rio de Janeiro, Brazil). Posology: a single weekly dose, total of 2 weeks. 2.4. Clinical parameters A standard periodontal probe (Trinity) with graduations at 1 mm interval was used for the clinical examination. CAL was considered the primary outcome. All other evaluated parameters were secondary outcomes. The distance from the cementoenamel junction to the bottom of the periodontal pocket (CAL) was recorded at six points of all teeth (except the third molars), three in the buccal (mesiobuccal, buccal, and distobuccal) and three lingual or palatal (mesiopalatal or mesiolingual, lingual or palatal and disto-lingual or disto-palatal).
Please cite this article in press as: Mourão LC, et al., Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial, Complementary Therapies in Clinical Practice (2014), http://dx.doi.org/10.1016/j.ctcp.2014.03.003
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Measurement of the pocket probing depth (PPD) was determined by measuring the distance from the gingival margin to the base of the sulcus or pocket. The presence or absence of bleeding on probing (BOP) was also recorded at each of the 6 sites around all teeth. Plaque Index (PI) was used to measure the presence or absence of supragingival plaque. Visible plaque was recorded at six points of all teeth, except third molars, before periodontal probing [21]. Clinical parameters were recorded at baseline, 3 and 12 months. 2.5. Examiner calibration Examiner calibration was performed during the development of a pilot study that preceded the present investigation. All measures of CAL, BOP and PI were carried out by just one examiner (LSM) at different times, observing intervals of one week. All teeth from eight patients with CP and six sites per tooth were examined. The Inter-Class Correlation Coefficient (ICC) was 0.82 (p ¼ 0.57, t test), 0.99 (p ¼ 0.93, t test) and 0.97 (p ¼ 0.92, t test) for CAL, BOP and PI, respectively, which indicated a statistically acceptable intraexaminer agreement. 2.6. Serologic parameters Blood tests were requested of all participants and were carried out in laboratories in Rio de Janeiro, Brazil, that used the same methodologies. The constituents of the lipid profile were measured by the enzymatic colorimetric method. Total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were obtained also by the enzymatic colorimetric method (Automation, Modular Roche Diagnostics AG, Mannheim, Germany). The fasting plasma glucose (mg/dL) was determined by the GOD-PAD Automation method
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(Roche). Uric acid was measured by a colorimetric test kit Pap 80 (ABX Diagnostic e SP, Montpellier, France). Serologic parameters were recorded at baseline, 3 and 12 months. 2.7. Statistics 2.7.1. Sample size calculation The minimum sample size based on a 2-group comparison with the independent t test was estimated to be 20 cases in each group, considering a confidence level of 95%. However, in order to compensate for any possible drop-outs, a 25% increase in the calculated sample size was carried out. Sample size was calculated to provide 80% power to detect statistically significant differences in mean levels of the primary outcome (CAL) between the 2 treatments that are as small as 88% of the applicable standard deviation, using the 2-sided 0.05 significance test. The estimated standard deviation of CAL was calculated to be 0.44 and the minimum detectable difference 0.39 based on data from the former study [19]. 2.7.2. Statistical data analysis Statistical evaluation was done using SPSS 17.0 for Windows (SPSS Inc., Chicago, IL). The normality of the numerical data (gender, age and metabolic systemic parameters) was evaluated by the KolmogoroveSmirnov test. Subsequently, parametric tests for independent and related samples were used to analyze differences between the 2 groups and for intragroup comparison. p < 0.05 was considered significant. 3. Results Fig. 1 shows the flow chart of the participants.
Fig. 1. Flow chart of the participants.
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Duncan post-hoc test: Baseline > 3 months ¼ 12 months) but not in C-G (p ¼ 0.180, ANOVA).
3.1. Clinical parameters A periodontist masked to the treatment group was the examiner (DMC). 3.1.1. PI At baseline and at 12 months, similar levels of plaque were observed in the H-G and C-G groups (Table 2), however, at 90 days, there was significantly less plaque in H-G than in C-G (Table 2). Comparing the baseline, 3-month and 12-month values, there was a significant intragroup reduction in H-G (p ¼ 0.005, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months). However, this reduction was not observed in C-G (p ¼ 0.180, ANOVA). 3.1.2. BOP Similar levels of bleeding on probing were observed with no significant difference between the H-G and C-G groups at baseline, 3 and 12 months (Table 2). However, there was a progressive significant intragroup reduction in both groups, comparing the baseline, 3-month and 12-month values (p ¼ 0.000 for H-G and C-G, Duncan post-hoc test: Baseline > 3 months > 12 months for H-G and C-G). 3.1.3. CAL The initial evaluation of CAL at baseline showed similar values for H-G and C-G, with no significant difference between them (Table 2). However, after 3 and 12 months, there was a significant CAL gain in H-G in comparison to C-G (Table 2). In fact, a significative CAL gain in H-G in comparison to C-G (0.33 vs 0.09 mm, respectively) was observed from baseline to 1 year (Table 2). Furthermore, a significant intragroup CAL reduction was observed in H-G (p ¼ 0.020, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months) but not in C-G (p ¼ 0.455, ANOVA). 3.1.4. PPD Similar levels of probing pocket depth were observed in the H-G and C-G groups with no significant difference between them at baseline, 3 and 12 months (Table 2). However, a significant intragroup PPD reduction was observed in H-G (p ¼ 0.005, ANOVA,
Table 2 Clinical results of homeopathy (H-G) and control (C-G) groups at baseline, 3 months and 12 months. Clinical parameters
PI PI PI PI
(%) at baseline (%) at 3 months (%) at 12 months (%) reduction from baseline to 1 year BOP (%) at baseline BOP (%) at 3 months BOP (%) at 12 months BOP (%) reduction from baseline to 1 year CAL (mm) at baseline CAL (mm) at 3 months CAL (mm) at 12 months CAL (mm) gain from baseline to 1 year PPD (mm) at baseline PPD (mm) at 3 months PPD (mm) at 12 months PPD (mm) reduction from baseline to 1 year
H-G
Mean (SD)
C-G
Intergroup analysis (p-value)
70.64 5.88 27.84 58.77
(8.00) (3.78) (10.97) (22.21)
74.97 12.39 29.83 59.38
(7.26) (10.00) (13.08) (20.56)
0.054 0.004* 0.567 0.921
52.96 25.95 8.82 83.80
(14.33) (8.28) (6.18) (10.14)
50.84 24.52 10.11 80.90
(10.66) (8.19) (6.42) (10.67)
0.557 0.543 0.473 0.330
4.50 4.17 4.17 0.33
(0.55) (0.42) (0.41) (0.44)
4.66 4.54 4.57 0.09
(0.31) (0.37) (0.35) (0.14)
0.215 0.002* 0.001* 0.01*
4.23 3.86 4.04 0.25
(0.24) (0.47) (0.30) (0.31)
4.17 3.89 4.05 0.19
(0.13) (0.78) (0.29) (0.18)
0.338 0.899 0.961 0.463
3.2. Serologic parameters Individuals in H-G compared with CeP showed statistically similar baseline levels of all serologic parameters studied, except Uric Acid (Table 3). At 3 and 12 months, no difference was observed between both groups. However, a significant reduction was observed in all H-G parameters (LDL, HDL, Total cholesterol, triglycerides, glucose and uric acid) from baseline to 1 year in comparison with C-G parameters (Table 3). Intragroup comparisons showed a significant reduction in all parameters in H-G from baseline to 3 months (LDL, p ¼ 0.035, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months; Total cholesterol, p ¼ 0.031, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months; Triglycerides, p ¼ 0.027, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months; glucose, p ¼ 0.000, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months and Uric Acid, p ¼ 0.000, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months), except for HDL (p ¼ 0.266, ANOVA). This reduction was not observed in C-G (LDL, p ¼ 0.816, ANOVA; HDL, p ¼ 0.583, ANOVA; Total cholesterol, p ¼ 0.320, ANOVA; Triglycerides, p ¼ 0.763; ANOVA; Glucose, p ¼ 0.075, ANOVA; Uric Acid, p ¼ 0.692, ANOVA). 4. Discussion After the conventional periodontal treatment alone or the treatment associated with homeopathy, there was a significant
Table 3 Serologic results of homeopathy (H-G) and control (C-G) groups at baseline, 3 months and 12 months. Serologic parameters
H-G
C-G
Intergroup analysis (p-value)
LDL (mg/dL) at baseline Mean 168.95 (88.83) 129.35 (35.85) 0.050 LDL (mg/dL) at 3 months (SD) 125.88 (50.89) 125.33 (30.91) 0.964 LDL (mg/dL) at 12 months 125.06 (54.22) 131.29 (34.05) 0.629 LDL (mg/dL) reduction 43.90 (43.52) 1.70 (10.33) 0.000* from baseline to 1 year HDL (mg/dL) at baseline 47.89 (9.96) 51.94 (14.19) 0.248 HDL (mg/dL) at 3 months 51.60 (7.56) 51.47 (9.52) 0.957 HDL (mg/dL) at 12 months 50.12 (6.15) 48.81 (10.05) 0.582 HDL (mg/dL) reduction 2.23 (7.34) 2.97 (8.78) 0.027* from baseline to 1 year Total (mg/dL) at baseline 231.20 (98.90) 201.53 (36.33) 0.169 Total (mg/dL) at 3 months 192.28 (55.41) 187.98 (29.96) 0.734 Total (mg/dL) at 12 months 181.68 (33.42) 192.52 (29.35) 0.229 Total (mg/dL) reduction 49.52 (78.76) 9.45 (18.23) 0.016* from baseline to 1 year Tri (mg/dL) at baseline 153.04 (70.65) 156.24 (78.06) 0.880 Tri (mg/dL) at 3 months 114.40 (47.32) 142.52 (61.02) 0.075 Tri (mg/dL) at 12 months 115.84 (47.78) 146.04 (64.80) 0.067 Tri (mg/dL) reduction 37.20 (41.50) 10.12 (23.51) 0.007* from baseline to 1 year Glu (mg/dL) at baseline 103.40 (12.80) 97.39 (9.24) 0.064 Glu (mg/dL) at 3 months 90.04 (5.51) 92.44 (6.26) 0.157 Glu (mg/dL) at 12 months 91.36 (7.23) 96.80 (8.93) 0.022* Glu (mg/dL) reduction 12.04 (11.64) 0.71 (10.70) 0.000* from baseline to 1 year Uric (mg/dL) at baseline 6.43 (1.32) 5.41 (1.58) 0.017* Uric (mg/dL) at 3 months 4.79 (0.93) 5.11 (1.21) 0.302 Uric (mg/dL) at 12 months 4.83 (0.99) 5.40 (1.50) 0.120 Uric (mg/dL) reduction 1.60 (1.23) 0.18 (1.25) 0.000* from baseline to 1 year LDL: LDL cholesterol; HDL: HDL cholesterol; Total: Total cholesterol; Tri: Triglycerides; Glu: glucose; Uric: Uric acid.
Please cite this article in press as: Mourão LC, et al., Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial, Complementary Therapies in Clinical Practice (2014), http://dx.doi.org/10.1016/j.ctcp.2014.03.003
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reduction for most clinical parameters in both groups, showing the importance of conventional periodontal treatment in improving periodontal health. However, a significant reduction of serologic outcomes was only observed in H-G, showing that H not only helps SRP to improve local parameters but also balances the physiological and metabolic function systemic of CP patients. Non-surgical periodontal treatment was performed on both groups (C-G and H-G) as it is still the gold standard treatment for CP [22]. Patients were monitored for a period of 12 months. After the treatment (3 and 12 months), there was a significant CAL gain in HG compared to C-G. These results suggest the efficacy of H working together with mechanical removal of dental biofilm to reduce the edema and to heal the periodontal tissue [19]. At baseline, high values of PI and BOP were observed in both groups. These results are in agreement with a previous study which showed that CP probably reduces the motivation for a satisfactory oral hygiene [23]. After 3 months of treatment, there was significantly less plaque in H-G than in C-G but such difference was not observed at 12 months. Although the levels of PI and BOP enhanced from 3 months to 12 months, all individuals showed low levels of them at the end of the study comparing to baseline values (Table 2). They received personal oral hygiene instructions which should contributed to the biofilm control and consequently reduce the bleeding [24]. The results of the systemic metabolic levels in H-G showed significant reductions in all parameters in comparison to C-G from baseline to 12 months. According to some authors the level of anxiety and stress can lead to increased cholesterol [25], uric acid and triglycerides levels [26]. As homeopathic medicines are useful for the management of symptoms like anxiety, depression and insomnia, they are associated to serum levels reduction of cholesterol, triglycerides, and low-density lipoprotein [27]. Furthermore, it seems that chronic diseases are related to a liver block. When high serum uric acid levels persist, there may be urate precipitation in the synovial fluid of the TMJ and periodontal tissue due to the liver block mentioned above [28,29]. Homeopathy is one of the most frequently used systems of alternative medicine especially indicated for the treatment of individuals “as a whole”, making it a natural choice for the treatment of chronic diseases [16]. Several studies have reported positive results when H was used to treat diseased organisms. However, many different low dose preparations have been proven effective only in basic “in vitro” research experiments [30]. The medicines used in this study were based on the whole symptomatic of periodontal disease and were selected according to the similia principle. This homeopathic protocol was validated in a previous study [19]. In this study, patients did not use any placebo medicine. Furthermore, they were not blinded about receiving or not the homeopathic therapy. Masking (blinding) of patients and examiners can eliminate measurement bias, although this is difficult to achieve when an identical placebo is not used as a comparison to the test intervention. Since the patients were unblinded, we cannot exclude the possibility that the clinician/examiner would have been informed intentionally or otherwise by the patients. Although the use of placebo both in clinical practice and in research is controversial [31], the use of placebo should be considered in future researches, in order to avoid the potential for risk of bias in interpreting the results. Many studies have been undertaken to understand the mechanism of the action of drugs [32]. In general, research focuses on the physical and chemical changes in the structure and function of the human body. This materialistic view does not help us to understand how homeopathic medicines act in the body. In fact, there is not a definitive mechanism of action for homeopathy [33] but it also
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happens with approved allopathic drugs. Almost 18% of them lack a well-defined mechanism of action [32]. Homeopathy could be understood by quantum mechanism concepts [34]. Quantum theory includes electromagnetic fields and waves that translate into vibrating “quantum” fields which can take the form of quanta or particles [35]. Homeopathy refers to this energy field as the vital force (VF). Based on the Law of Similars, H treatment aids the VF as it attempts to restore a holistic balance [36]. The results observed in this study probably are explained by the synergistic effects of the homeopathic medicines used. Concluding, a significant improvement after 1 year of follow-up in patients submitted to SRP þ H was observed. In fact, these results were expected since homeopathy is most effective in terms of adding value to conventional therapies and in reducing the demand for allopathic drugs [37]. 5. Conclusion The findings of this 1-year follow-up randomized clinical trial suggest that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients. Conflict of Interest The authors declare that they have no conflict of interest. The study was self-funded by the authors and their institutions. References [1] Sanz M, van Winkelhoff AJ. Periodontal infections: understanding the complexity e consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol 2011;38:3e6. [2] Teughels W, Dekeyser C, van Essche M, Quirynen M. One-stage, full-mouth disinfection: fiction or reality? Periodontol 2000 2009;50:39e51. [3] Petersen PE, Ogawa H. Strengthening the prevention of periodontal disease: the WHO approach. J Periodontol 2005;76:2187e93. [4] Brown LJ, Brunelle JA, Kingman A. Periodontal status in the United States, 1988e1991: prevalence, extent, and demographic variation. J Dent Res 1996;75:672e83. [5] Locker D, Slade GD, Murray H. Epidemiology of periodontal disease among older adults: a review. Periodontol 2000 1998;16:16e33. [6] Harris RJ. Untreated periodontal disease: a follow-up on 30 cases. J Periodontol 2003;74:672e8. [7] Ebersole JL, Machen RL, Steffen MJ, Willmann DE. Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin Exp Immunol 1997;107:347e52. [8] Williams RC, Barnett AH, Claffey N, Davis M, Gadsby R, Kellett M, et al. The potential impact of periodontal disease on general health: a consensus view. Curr Med Res Opin 2008;24:1635e43. [9] Sanz I, Alonso B, Carasol M, Herrera D, Sanz M. Nonsurgical treatment of periodontitis. J Evid Based Dent Pract 2012;12:76e86. [10] Research, Science and Therapy Committee of the American Academy of Periodontology. Treatment of plaque-induced gingivitis, chronic periodontitis, and other clinical conditions. J Periodontol 2001;72:1790e800. [11] Heitz-Mayfield LJ, Trombelli L, Heitz F, Needleman I, Moles D. A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis. J Clin Periodontol 2002;29(Suppl. 3): 92e102. [12] Sgolastra F, Gatto R, Petrucci A, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as adjunctive therapy to scaling and root planning in the treatment of chronic periodontitis: a systematic review and meta-analysis. J Periodontol 2012;83:1257e69. [13] Cortellini P. Minimally invasive surgical techniques in periodontal regeneration. J Evid Based Dent Pract 2012;12(Suppl. 3):89e100. [14] Seymour RA. Antibiotics in dentistry e an update. Dent Update 2013;40:319e 22. [15] Srivastava P. Periodontal diseases and homeopathy. Homeopath J 2012;5: 1e3. [16] Witt CM, Lüdtke R, Baur R, Willich SN. Homeopathic medical practice: longterm results of a cohort study with 3981 patients. BMC Public Health 2005;2005(5):115e23. [17] Eames S, Darby P. Homeopathy and its ethical use in dentistry. Brit Dent J 2011;210:299e301.
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[18] Joos S. Review on efficacy and health services research studies of complementary and alternative medicine in inflammatory bowel disease. Chin J Integr Med 2011;17:403e9. [19] Mourao LS, Moutinho H, Canabarro A. Additional benefits of homeopathy in the treatment of chronic periodontitis: a randomized clinical trial. Complement Ther Clin Pract 2013;19:246e50. [20] Tonetti MS, Claffey N. European Workshop in Periodontology group C. Advances in the progression of periodontitis and proposal of definitions of a periodontitis case and disease progression for use in risk factor research. J Clin Periodontol 2005;32:210e3. [21] Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J 1975;25:229e35. [22] Preshaw PM, Hefti AF, Jepsen S, Etienne D, Walker C, Bradshaw MH. Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review. J Clin Periodontol 2004;31:697e707. [23] Leão AT, Sheiham A. The development of a socio-dental measure of dental impacts on daily living. Community Dent Health 1996;13:22e6. [24] Lang NP, Tonetti MS. Periodontal risk assessment (PRA) for patients in supportive periodontal therapy (SPT). Oral Health Prev Dent 2003;1:7e16. [25] Cutler CW, Shinedling EA, Nunn M, Jotwani R, Kim BO, Nares S, et al. Association between periodontitis and hyperlipidemia: cause or effect? J Periodontol 1999;70:1429e34. [26] Schlesinger N. Dietary factors and hyperuricaemia. Curr Pharm Des 2005;11: 4133e8. [27] Nayak C, Singh V, Singh K, Singh H, Gupta J, Lamba CD, et al. Management of distress during climacteric years by homeopathic therapy. J Altern Complement Med 2011;17:1037e42.
[28] Lopez NS, Quintero A, Casanova PA, Ibieta CI, Baelum V, Lopez R. Effects of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: a controlled clinical trial. J Periodontol 2011;83:267e78. [29] Khosla P, Gogia A, Agarwal PK, Pahuja A, Jain S, Saxena KK. Concomitant gout and rheumatoid arthritis e a case report. Indian J Med Sci 2004;58:349e52. [30] Clausen J, van Wijk R, Albrecht H. Infection models in basic research on homeopathy. Homeopathy 2010;99:263e70. [31] Simon R. Are placebo-controlled clinical trials ethical or needed when alternative treatments exist? Ann Intern Med 2000;133:474e5. [32] Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, et al. Identifying mechanism-of-action targets for drugs and probes. Proc Natl Acad Sci U S A 2012;109:11178e83. [33] Jütte R, Riley D. A review of the use and role of low potencies in homeopathy. Complement Ther Med 2005;13:291e6. [34] Walach H. Generalized entanglement: a new theoretical model for understanding the effects of complementary and alternative medicine. J Altern Complement Med 2005;11:549e59. [35] Saxena A, Jacobson J, Yamanashi W, Scherlag B, Lamberth J, Saxena B. A hypothetical mathematical construct explaining the mechanism of biological amplification in an experimental model utilizing picoTesla (PT) electromagnetic fields. Med Hypotheses 2003;60:821e39. [36] Milgrom LR. Toward a unified theory of homeopathy and conventional medicine. J Altern Complement Med 2007;13:759e69. [37] Fisher P. Homeopathy and the Lancet. Evid Based Complement Altern Med 2006;3:145e7.
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Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial L.C. Mourão a, D.M. Cataldo b, H. Moutinho b, R.G. Fischer c, A. Canabarro a, c, * a
Department of Periodontology, School of Dentistry, Universidade Veiga de Almeida (UVA), Rio de Janeiro, Brazil Instituto Hahnemanniano do Brasil (IHB), Rio de Janeiro, Brazil c Department of Periodontology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil b
a b s t r a c t Keywords: Chronic periodontitis Non-surgical periodontal treatment Homeopathy
Background and objective: The aim of this study was test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP) in patients with chronic periodontitis (CP). Materials and Methods: 50 patients with CP were randomly allocated to one of two treatment groups: SRP (C-G) or SRP þ H (H-G). Assessments were made at baseline and after 3 and 12 months of treatments. The local and systemic responses to the treatments were evaluated by clinical and serologic parameters, respectively. Results: Both groups displayed significant improvements, however, using clinical attachment gain and reductions in HDL, LDL and Total Cholesterol, Triglycerides, Glucose and Uric acid, from baseline to 1 year, as criteria for treatment success, H-G performed significantly better than C-G. Conclusion: The findings of this 1-year follow-up randomized clinical trial suggest that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients. Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction Chronic periodontitis (CP) is a chronic inflammatory disease resulting from the disruption of homeostasis between subgingival microbiota and host defenses [1]. Periodontal breakdown develops when the microbial load within a periodontal pocket overwhelms the local and systemic host defense mechanisms [2]. Advanced CP with deep periodontal pockets affects approximately 10e15% of world’s adult population [3]. Although severe clinical attachment loss (CAL) is usually only evident in a few sites [4], CP often becomes more severe with age [5] and, if no treatment is given, many teeth could be lost [5,6]. CP may also aggravate preexisting diseases, because it impacts the systemic components of the host protective responses [7]. Despite the recognition that systemic factors can alter the risk to CP, only recently has evidence begun to emerge, still under investigation, that infections of the
* Corresponding author. Department of Periodontology, School of Dentistry, Universidade Veiga de Almeida (UVA), Rua Ibituruna 108, casa 3, sala 201, Tijuca, CEP 20271-020 Rio de Janeiro, Brazil. Tel.: þ552125748871; fax: þ552132343024. E-mail addresses: [email protected], [email protected] (A. Canabarro).
oral cavity are able to influence the occurrence and severity of certain conditions and systemic diseases [8]. Scaling and root planning (SRP) is the gold standard treatment for patients with chronic periodontitis. Nevertheless, in recent years, different therapeutic strategies have been proposed to improve the results of SRP [9], because some factors may limit the success of treatment by SRP, such as root anatomy, furcations and deep probing depths [10]. Many therapeutic options have been used in the treatment of chronic periodontitis, especially surgical and antibiotic approaches [11,12]. However, they have only been showing modest clinical attachment gain over SRP [11,12], usually associated with some adverse effects [13,14], leaving room for new treatment options. Furthermore, such approaches are only used to treat the local symptoms and often fail to treat the whole person. Homeopathy (H) is a system based on the principle of “like cures like” [15,16]. Homeopathy states that a disease can be cured using a diluted form of a substance that induces the same symptoms in a healthy person [16]. H is effective against many pathologies, relatively inexpensive, has high patient satisfaction and a low incidence of side effects [17]. In fact, some dentists have been using homeopathic medicines in everyday practice as an adjunct to conventional treatment for a
http://dx.doi.org/10.1016/j.ctcp.2014.03.003 1744-3881/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Mourão LC, et al., Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial, Complementary Therapies in Clinical Practice (2014), http://dx.doi.org/10.1016/j.ctcp.2014.03.003
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range of chronic pathologies, including CP [17]. However, studies assessing the efficacy of such treatments are not available yet [18]. The use of homeopathy in our first 3-month follow-up study was intended to balance the physiological and metabolic function systemic of CP patients. Patients have used specific homeopathic medicines as an adjuvant of SRP in order to promote an additional effect on the treatment of CP [19]. The aim of this randomized clinical trial was to compare the clinical and serologic effects of homeopathy plus SRP to those of conventional mechanical treatment. The present report presents the results at 3 and 12 months after treatment.
and analyzed. The randomization list was transferred to individual sealed opaque envelopes sequentially numbered which were passed to the periodontist (LSM), each one containing the name of the next treatment in a card. Fifty subjects with CP participated in this “Single-Blind Randomized Controlled Clinical Trial”, 40 of them participated in the former study. Half of the subjects received an additional homeopathic therapy. The main characteristics of both groups are shown in Table 1.
2. Materials and methods
2.2.1. Conventional periodontal therapy (SRP) All patients were submitted to conventional non-surgical periodontal treatment by a “blind” and experienced periodontist (LSM) who did not know which patients were getting the active treatment or not. The proposed therapy had the following stages: 1. First visit (60 min): personal oral hygiene instructions (how to use hand toothbrush and dental floss), a brief description of periodontal disease and its local and systemic effects (w20 min) and supragingival scaling (w40 min) that was performed by ultrasonic scaler tips (Profi Neo, Dabi Atlante, Ribeirão Preto, SP, Brazil). The patients were asked not to use any antiseptic mouthwashes. Other visits: consultations for subgingival SRP e the number of consultations needed to obtain clinical outcome was standardized to four (one per quadrant, in total 4 weeks). If there was no tooth in a given quadrant, the number of visits was reduced to the number of quadrants present. Instrumentation was performed by hand with subgingival curettes (Gracey curettes, Trinity, Sao Paulo, SP, Brazil), for 10 min per tooth. Supportive treatment sessions were carried out at 3, 6, 9 and 12 months after the completion of active therapy. Oral hygiene procedures were reinforced and supragingival calculus is removed with ultrasonic scaler tips.
2.1. Participants In continuation of our previous study on the effects of periodontal treatment plus homeopathy on clinical and serologic parameters [19], potential subjects eligible for the study of both genders, aged from 35 to 70 years old, were identified from the population referred to the periodontal clinic of Center for Health at the Universidade Veiga de Almeida (UVA), Rio de Janeiro, Brazil. All of them were submitted to a complete periodontal examination for a periodontal diagnosis, after approval by the Ethics and Research Committee of UVA (CEP/UVA protocol number 285-11). Patients who fulfilled the study inclusion/exclusion criteria were invited to participate in the study. Inclusion criteria: The presence of clinical attachment level (CAL) 3 mm in proximal sites of two non-adjacent teeth. Bone loss confirmed by periapical radiographs and bleeding on probing (BOP) should also be present [20]. The exclusion criteria were: patients who had received periodontal treatment in the last year and individuals with aggressive periodontitis. And for both groups: smokers, being pregnant or nursing, patients with a medical condition that could affect the periodontal tissues such as HIV, or any other significant systemic disease that could interfere in the periodontium (diabetes etc), patients that had used medications such as non-steroidal anti-inflammatory, or antibiotic therapy within the last 6 months. 2.1.1. Randomization and allocation concealment Participants were randomly assigned to receive one of the two treatments by a computer-generated table. Restricted randomization was used, stratifying people by age, number of teeth and average CAL in order to avoid unequal balance between the two treatments (Table 1). The randomization table was sent to a “blind” participant (AC) that was the only one who knew the code. The randomization code was only broken when all data were collected Table 1 Main characteristics of the participants of control (C-G) and homeopathy (H-G) groups. Characteristics
C-G
Age (Years) Gender: male/female Smoking: yes/no Number of teeth PI (%) BOP (%) CAL (mm) PPD (mm) Severity of CP (Severe/Moderate)a Extension of CP (Generalized/Localized)b
48.4 10/15 No 24.45 74.97 50.84 4.66 4.17 9/16 18/7
a
H-G 8.5
3.15 7.26 10.66 0.31 0.13
47.7 12/13 No 23.65 70.64 52.96 4.50 4.23 7/18 19/6
8.7
4,41 8.00 14.33 0.55 0.24
Obs: Severe CP: CAL 5 mm and Moderate CP: CAL < 5 mm. Generalized CP: 30% of sites with CAL >2 mm and Localized CP: 2 mm [23]. Non-significative. b
2.2. Treatment protocols
2.3. Additional homeopathic therapy 25 patients (H-G) were also submitted to the homeopathic protocol which had been validated in a previous study [19]: 1) Depurative medicine (helps cleanse waste products and toxins from our body): Berberis 6CH (Farmácia-Escola Prof. José Barros da Silva, Rio de Janeiro, Brazil). Posology: two tablets twice daily for 45 days. 2) Acute Drug (drugs that treat illness which has an abrupt onset and needs immediate attention): Mercurius solubilis/Belladona/ Hepar sulphur e 6CH (Farmácia-Escola Prof. José Barros da Silva, Rio de Janeiro, Brazil). Posology: two tablets three times a day for 15 days. 3) Nosodes (homeopathic remedies prepared from a product of disease such as infected tissues or causal organisms): Pyrogenium e 200 CH (Farmácia-Escola Prof. José Barros da Silva, Rio de Janeiro, Brazil). Posology: a single weekly dose, total of 2 weeks. 2.4. Clinical parameters A standard periodontal probe (Trinity) with graduations at 1 mm interval was used for the clinical examination. CAL was considered the primary outcome. All other evaluated parameters were secondary outcomes. The distance from the cementoenamel junction to the bottom of the periodontal pocket (CAL) was recorded at six points of all teeth (except the third molars), three in the buccal (mesiobuccal, buccal, and distobuccal) and three lingual or palatal (mesiopalatal or mesiolingual, lingual or palatal and disto-lingual or disto-palatal).
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Measurement of the pocket probing depth (PPD) was determined by measuring the distance from the gingival margin to the base of the sulcus or pocket. The presence or absence of bleeding on probing (BOP) was also recorded at each of the 6 sites around all teeth. Plaque Index (PI) was used to measure the presence or absence of supragingival plaque. Visible plaque was recorded at six points of all teeth, except third molars, before periodontal probing [21]. Clinical parameters were recorded at baseline, 3 and 12 months. 2.5. Examiner calibration Examiner calibration was performed during the development of a pilot study that preceded the present investigation. All measures of CAL, BOP and PI were carried out by just one examiner (LSM) at different times, observing intervals of one week. All teeth from eight patients with CP and six sites per tooth were examined. The Inter-Class Correlation Coefficient (ICC) was 0.82 (p ¼ 0.57, t test), 0.99 (p ¼ 0.93, t test) and 0.97 (p ¼ 0.92, t test) for CAL, BOP and PI, respectively, which indicated a statistically acceptable intraexaminer agreement. 2.6. Serologic parameters Blood tests were requested of all participants and were carried out in laboratories in Rio de Janeiro, Brazil, that used the same methodologies. The constituents of the lipid profile were measured by the enzymatic colorimetric method. Total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were obtained also by the enzymatic colorimetric method (Automation, Modular Roche Diagnostics AG, Mannheim, Germany). The fasting plasma glucose (mg/dL) was determined by the GOD-PAD Automation method
3
(Roche). Uric acid was measured by a colorimetric test kit Pap 80 (ABX Diagnostic e SP, Montpellier, France). Serologic parameters were recorded at baseline, 3 and 12 months. 2.7. Statistics 2.7.1. Sample size calculation The minimum sample size based on a 2-group comparison with the independent t test was estimated to be 20 cases in each group, considering a confidence level of 95%. However, in order to compensate for any possible drop-outs, a 25% increase in the calculated sample size was carried out. Sample size was calculated to provide 80% power to detect statistically significant differences in mean levels of the primary outcome (CAL) between the 2 treatments that are as small as 88% of the applicable standard deviation, using the 2-sided 0.05 significance test. The estimated standard deviation of CAL was calculated to be 0.44 and the minimum detectable difference 0.39 based on data from the former study [19]. 2.7.2. Statistical data analysis Statistical evaluation was done using SPSS 17.0 for Windows (SPSS Inc., Chicago, IL). The normality of the numerical data (gender, age and metabolic systemic parameters) was evaluated by the KolmogoroveSmirnov test. Subsequently, parametric tests for independent and related samples were used to analyze differences between the 2 groups and for intragroup comparison. p < 0.05 was considered significant. 3. Results Fig. 1 shows the flow chart of the participants.
Fig. 1. Flow chart of the participants.
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Duncan post-hoc test: Baseline > 3 months ¼ 12 months) but not in C-G (p ¼ 0.180, ANOVA).
3.1. Clinical parameters A periodontist masked to the treatment group was the examiner (DMC). 3.1.1. PI At baseline and at 12 months, similar levels of plaque were observed in the H-G and C-G groups (Table 2), however, at 90 days, there was significantly less plaque in H-G than in C-G (Table 2). Comparing the baseline, 3-month and 12-month values, there was a significant intragroup reduction in H-G (p ¼ 0.005, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months). However, this reduction was not observed in C-G (p ¼ 0.180, ANOVA). 3.1.2. BOP Similar levels of bleeding on probing were observed with no significant difference between the H-G and C-G groups at baseline, 3 and 12 months (Table 2). However, there was a progressive significant intragroup reduction in both groups, comparing the baseline, 3-month and 12-month values (p ¼ 0.000 for H-G and C-G, Duncan post-hoc test: Baseline > 3 months > 12 months for H-G and C-G). 3.1.3. CAL The initial evaluation of CAL at baseline showed similar values for H-G and C-G, with no significant difference between them (Table 2). However, after 3 and 12 months, there was a significant CAL gain in H-G in comparison to C-G (Table 2). In fact, a significative CAL gain in H-G in comparison to C-G (0.33 vs 0.09 mm, respectively) was observed from baseline to 1 year (Table 2). Furthermore, a significant intragroup CAL reduction was observed in H-G (p ¼ 0.020, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months) but not in C-G (p ¼ 0.455, ANOVA). 3.1.4. PPD Similar levels of probing pocket depth were observed in the H-G and C-G groups with no significant difference between them at baseline, 3 and 12 months (Table 2). However, a significant intragroup PPD reduction was observed in H-G (p ¼ 0.005, ANOVA,
Table 2 Clinical results of homeopathy (H-G) and control (C-G) groups at baseline, 3 months and 12 months. Clinical parameters
PI PI PI PI
(%) at baseline (%) at 3 months (%) at 12 months (%) reduction from baseline to 1 year BOP (%) at baseline BOP (%) at 3 months BOP (%) at 12 months BOP (%) reduction from baseline to 1 year CAL (mm) at baseline CAL (mm) at 3 months CAL (mm) at 12 months CAL (mm) gain from baseline to 1 year PPD (mm) at baseline PPD (mm) at 3 months PPD (mm) at 12 months PPD (mm) reduction from baseline to 1 year
H-G
Mean (SD)
C-G
Intergroup analysis (p-value)
70.64 5.88 27.84 58.77
(8.00) (3.78) (10.97) (22.21)
74.97 12.39 29.83 59.38
(7.26) (10.00) (13.08) (20.56)
0.054 0.004* 0.567 0.921
52.96 25.95 8.82 83.80
(14.33) (8.28) (6.18) (10.14)
50.84 24.52 10.11 80.90
(10.66) (8.19) (6.42) (10.67)
0.557 0.543 0.473 0.330
4.50 4.17 4.17 0.33
(0.55) (0.42) (0.41) (0.44)
4.66 4.54 4.57 0.09
(0.31) (0.37) (0.35) (0.14)
0.215 0.002* 0.001* 0.01*
4.23 3.86 4.04 0.25
(0.24) (0.47) (0.30) (0.31)
4.17 3.89 4.05 0.19
(0.13) (0.78) (0.29) (0.18)
0.338 0.899 0.961 0.463
3.2. Serologic parameters Individuals in H-G compared with CeP showed statistically similar baseline levels of all serologic parameters studied, except Uric Acid (Table 3). At 3 and 12 months, no difference was observed between both groups. However, a significant reduction was observed in all H-G parameters (LDL, HDL, Total cholesterol, triglycerides, glucose and uric acid) from baseline to 1 year in comparison with C-G parameters (Table 3). Intragroup comparisons showed a significant reduction in all parameters in H-G from baseline to 3 months (LDL, p ¼ 0.035, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months; Total cholesterol, p ¼ 0.031, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months; Triglycerides, p ¼ 0.027, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months; glucose, p ¼ 0.000, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months and Uric Acid, p ¼ 0.000, ANOVA, Duncan post-hoc test: Baseline > 3 months ¼ 12 months), except for HDL (p ¼ 0.266, ANOVA). This reduction was not observed in C-G (LDL, p ¼ 0.816, ANOVA; HDL, p ¼ 0.583, ANOVA; Total cholesterol, p ¼ 0.320, ANOVA; Triglycerides, p ¼ 0.763; ANOVA; Glucose, p ¼ 0.075, ANOVA; Uric Acid, p ¼ 0.692, ANOVA). 4. Discussion After the conventional periodontal treatment alone or the treatment associated with homeopathy, there was a significant
Table 3 Serologic results of homeopathy (H-G) and control (C-G) groups at baseline, 3 months and 12 months. Serologic parameters
H-G
C-G
Intergroup analysis (p-value)
LDL (mg/dL) at baseline Mean 168.95 (88.83) 129.35 (35.85) 0.050 LDL (mg/dL) at 3 months (SD) 125.88 (50.89) 125.33 (30.91) 0.964 LDL (mg/dL) at 12 months 125.06 (54.22) 131.29 (34.05) 0.629 LDL (mg/dL) reduction 43.90 (43.52) 1.70 (10.33) 0.000* from baseline to 1 year HDL (mg/dL) at baseline 47.89 (9.96) 51.94 (14.19) 0.248 HDL (mg/dL) at 3 months 51.60 (7.56) 51.47 (9.52) 0.957 HDL (mg/dL) at 12 months 50.12 (6.15) 48.81 (10.05) 0.582 HDL (mg/dL) reduction 2.23 (7.34) 2.97 (8.78) 0.027* from baseline to 1 year Total (mg/dL) at baseline 231.20 (98.90) 201.53 (36.33) 0.169 Total (mg/dL) at 3 months 192.28 (55.41) 187.98 (29.96) 0.734 Total (mg/dL) at 12 months 181.68 (33.42) 192.52 (29.35) 0.229 Total (mg/dL) reduction 49.52 (78.76) 9.45 (18.23) 0.016* from baseline to 1 year Tri (mg/dL) at baseline 153.04 (70.65) 156.24 (78.06) 0.880 Tri (mg/dL) at 3 months 114.40 (47.32) 142.52 (61.02) 0.075 Tri (mg/dL) at 12 months 115.84 (47.78) 146.04 (64.80) 0.067 Tri (mg/dL) reduction 37.20 (41.50) 10.12 (23.51) 0.007* from baseline to 1 year Glu (mg/dL) at baseline 103.40 (12.80) 97.39 (9.24) 0.064 Glu (mg/dL) at 3 months 90.04 (5.51) 92.44 (6.26) 0.157 Glu (mg/dL) at 12 months 91.36 (7.23) 96.80 (8.93) 0.022* Glu (mg/dL) reduction 12.04 (11.64) 0.71 (10.70) 0.000* from baseline to 1 year Uric (mg/dL) at baseline 6.43 (1.32) 5.41 (1.58) 0.017* Uric (mg/dL) at 3 months 4.79 (0.93) 5.11 (1.21) 0.302 Uric (mg/dL) at 12 months 4.83 (0.99) 5.40 (1.50) 0.120 Uric (mg/dL) reduction 1.60 (1.23) 0.18 (1.25) 0.000* from baseline to 1 year LDL: LDL cholesterol; HDL: HDL cholesterol; Total: Total cholesterol; Tri: Triglycerides; Glu: glucose; Uric: Uric acid.
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reduction for most clinical parameters in both groups, showing the importance of conventional periodontal treatment in improving periodontal health. However, a significant reduction of serologic outcomes was only observed in H-G, showing that H not only helps SRP to improve local parameters but also balances the physiological and metabolic function systemic of CP patients. Non-surgical periodontal treatment was performed on both groups (C-G and H-G) as it is still the gold standard treatment for CP [22]. Patients were monitored for a period of 12 months. After the treatment (3 and 12 months), there was a significant CAL gain in HG compared to C-G. These results suggest the efficacy of H working together with mechanical removal of dental biofilm to reduce the edema and to heal the periodontal tissue [19]. At baseline, high values of PI and BOP were observed in both groups. These results are in agreement with a previous study which showed that CP probably reduces the motivation for a satisfactory oral hygiene [23]. After 3 months of treatment, there was significantly less plaque in H-G than in C-G but such difference was not observed at 12 months. Although the levels of PI and BOP enhanced from 3 months to 12 months, all individuals showed low levels of them at the end of the study comparing to baseline values (Table 2). They received personal oral hygiene instructions which should contributed to the biofilm control and consequently reduce the bleeding [24]. The results of the systemic metabolic levels in H-G showed significant reductions in all parameters in comparison to C-G from baseline to 12 months. According to some authors the level of anxiety and stress can lead to increased cholesterol [25], uric acid and triglycerides levels [26]. As homeopathic medicines are useful for the management of symptoms like anxiety, depression and insomnia, they are associated to serum levels reduction of cholesterol, triglycerides, and low-density lipoprotein [27]. Furthermore, it seems that chronic diseases are related to a liver block. When high serum uric acid levels persist, there may be urate precipitation in the synovial fluid of the TMJ and periodontal tissue due to the liver block mentioned above [28,29]. Homeopathy is one of the most frequently used systems of alternative medicine especially indicated for the treatment of individuals “as a whole”, making it a natural choice for the treatment of chronic diseases [16]. Several studies have reported positive results when H was used to treat diseased organisms. However, many different low dose preparations have been proven effective only in basic “in vitro” research experiments [30]. The medicines used in this study were based on the whole symptomatic of periodontal disease and were selected according to the similia principle. This homeopathic protocol was validated in a previous study [19]. In this study, patients did not use any placebo medicine. Furthermore, they were not blinded about receiving or not the homeopathic therapy. Masking (blinding) of patients and examiners can eliminate measurement bias, although this is difficult to achieve when an identical placebo is not used as a comparison to the test intervention. Since the patients were unblinded, we cannot exclude the possibility that the clinician/examiner would have been informed intentionally or otherwise by the patients. Although the use of placebo both in clinical practice and in research is controversial [31], the use of placebo should be considered in future researches, in order to avoid the potential for risk of bias in interpreting the results. Many studies have been undertaken to understand the mechanism of the action of drugs [32]. In general, research focuses on the physical and chemical changes in the structure and function of the human body. This materialistic view does not help us to understand how homeopathic medicines act in the body. In fact, there is not a definitive mechanism of action for homeopathy [33] but it also
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happens with approved allopathic drugs. Almost 18% of them lack a well-defined mechanism of action [32]. Homeopathy could be understood by quantum mechanism concepts [34]. Quantum theory includes electromagnetic fields and waves that translate into vibrating “quantum” fields which can take the form of quanta or particles [35]. Homeopathy refers to this energy field as the vital force (VF). Based on the Law of Similars, H treatment aids the VF as it attempts to restore a holistic balance [36]. The results observed in this study probably are explained by the synergistic effects of the homeopathic medicines used. Concluding, a significant improvement after 1 year of follow-up in patients submitted to SRP þ H was observed. In fact, these results were expected since homeopathy is most effective in terms of adding value to conventional therapies and in reducing the demand for allopathic drugs [37]. 5. Conclusion The findings of this 1-year follow-up randomized clinical trial suggest that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients. Conflict of Interest The authors declare that they have no conflict of interest. The study was self-funded by the authors and their institutions. References [1] Sanz M, van Winkelhoff AJ. Periodontal infections: understanding the complexity e consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol 2011;38:3e6. [2] Teughels W, Dekeyser C, van Essche M, Quirynen M. One-stage, full-mouth disinfection: fiction or reality? Periodontol 2000 2009;50:39e51. [3] Petersen PE, Ogawa H. Strengthening the prevention of periodontal disease: the WHO approach. J Periodontol 2005;76:2187e93. [4] Brown LJ, Brunelle JA, Kingman A. Periodontal status in the United States, 1988e1991: prevalence, extent, and demographic variation. J Dent Res 1996;75:672e83. [5] Locker D, Slade GD, Murray H. Epidemiology of periodontal disease among older adults: a review. Periodontol 2000 1998;16:16e33. [6] Harris RJ. Untreated periodontal disease: a follow-up on 30 cases. J Periodontol 2003;74:672e8. [7] Ebersole JL, Machen RL, Steffen MJ, Willmann DE. Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin Exp Immunol 1997;107:347e52. [8] Williams RC, Barnett AH, Claffey N, Davis M, Gadsby R, Kellett M, et al. The potential impact of periodontal disease on general health: a consensus view. Curr Med Res Opin 2008;24:1635e43. [9] Sanz I, Alonso B, Carasol M, Herrera D, Sanz M. Nonsurgical treatment of periodontitis. J Evid Based Dent Pract 2012;12:76e86. [10] Research, Science and Therapy Committee of the American Academy of Periodontology. Treatment of plaque-induced gingivitis, chronic periodontitis, and other clinical conditions. J Periodontol 2001;72:1790e800. [11] Heitz-Mayfield LJ, Trombelli L, Heitz F, Needleman I, Moles D. A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis. J Clin Periodontol 2002;29(Suppl. 3): 92e102. [12] Sgolastra F, Gatto R, Petrucci A, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as adjunctive therapy to scaling and root planning in the treatment of chronic periodontitis: a systematic review and meta-analysis. J Periodontol 2012;83:1257e69. [13] Cortellini P. Minimally invasive surgical techniques in periodontal regeneration. J Evid Based Dent Pract 2012;12(Suppl. 3):89e100. [14] Seymour RA. Antibiotics in dentistry e an update. Dent Update 2013;40:319e 22. [15] Srivastava P. Periodontal diseases and homeopathy. Homeopath J 2012;5: 1e3. [16] Witt CM, Lüdtke R, Baur R, Willich SN. Homeopathic medical practice: longterm results of a cohort study with 3981 patients. BMC Public Health 2005;2005(5):115e23. [17] Eames S, Darby P. Homeopathy and its ethical use in dentistry. Brit Dent J 2011;210:299e301.
Please cite this article in press as: Mourão LC, et al., Additional effects of homeopathy on chronic periodontitis: A 1-year follow-up randomized clinical trial, Complementary Therapies in Clinical Practice (2014), http://dx.doi.org/10.1016/j.ctcp.2014.03.003
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[18] Joos S. Review on efficacy and health services research studies of complementary and alternative medicine in inflammatory bowel disease. Chin J Integr Med 2011;17:403e9. [19] Mourao LS, Moutinho H, Canabarro A. Additional benefits of homeopathy in the treatment of chronic periodontitis: a randomized clinical trial. Complement Ther Clin Pract 2013;19:246e50. [20] Tonetti MS, Claffey N. European Workshop in Periodontology group C. Advances in the progression of periodontitis and proposal of definitions of a periodontitis case and disease progression for use in risk factor research. J Clin Periodontol 2005;32:210e3. [21] Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J 1975;25:229e35. [22] Preshaw PM, Hefti AF, Jepsen S, Etienne D, Walker C, Bradshaw MH. Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review. J Clin Periodontol 2004;31:697e707. [23] Leão AT, Sheiham A. The development of a socio-dental measure of dental impacts on daily living. Community Dent Health 1996;13:22e6. [24] Lang NP, Tonetti MS. Periodontal risk assessment (PRA) for patients in supportive periodontal therapy (SPT). Oral Health Prev Dent 2003;1:7e16. [25] Cutler CW, Shinedling EA, Nunn M, Jotwani R, Kim BO, Nares S, et al. Association between periodontitis and hyperlipidemia: cause or effect? J Periodontol 1999;70:1429e34. [26] Schlesinger N. Dietary factors and hyperuricaemia. Curr Pharm Des 2005;11: 4133e8. [27] Nayak C, Singh V, Singh K, Singh H, Gupta J, Lamba CD, et al. Management of distress during climacteric years by homeopathic therapy. J Altern Complement Med 2011;17:1037e42.
[28] Lopez NS, Quintero A, Casanova PA, Ibieta CI, Baelum V, Lopez R. Effects of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: a controlled clinical trial. J Periodontol 2011;83:267e78. [29] Khosla P, Gogia A, Agarwal PK, Pahuja A, Jain S, Saxena KK. Concomitant gout and rheumatoid arthritis e a case report. Indian J Med Sci 2004;58:349e52. [30] Clausen J, van Wijk R, Albrecht H. Infection models in basic research on homeopathy. Homeopathy 2010;99:263e70. [31] Simon R. Are placebo-controlled clinical trials ethical or needed when alternative treatments exist? Ann Intern Med 2000;133:474e5. [32] Gregori-Puigjané E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, et al. Identifying mechanism-of-action targets for drugs and probes. Proc Natl Acad Sci U S A 2012;109:11178e83. [33] Jütte R, Riley D. A review of the use and role of low potencies in homeopathy. Complement Ther Med 2005;13:291e6. [34] Walach H. Generalized entanglement: a new theoretical model for understanding the effects of complementary and alternative medicine. J Altern Complement Med 2005;11:549e59. [35] Saxena A, Jacobson J, Yamanashi W, Scherlag B, Lamberth J, Saxena B. A hypothetical mathematical construct explaining the mechanism of biological amplification in an experimental model utilizing picoTesla (PT) electromagnetic fields. Med Hypotheses 2003;60:821e39. [36] Milgrom LR. Toward a unified theory of homeopathy and conventional medicine. J Altern Complement Med 2007;13:759e69. [37] Fisher P. Homeopathy and the Lancet. Evid Based Complement Altern Med 2006;3:145e7.
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