UNIVERSIDADE FEDERAL DE SANTA CATARINA CENTRO DE CIÊNCIAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM ODONTOLOGIA Laís Duarte I

UNIVERSIDADE FEDERAL DE SANTA CATARINA CENTRO DE CIÊNCIAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM ODONTOLOGIA

Laís Duarte

Impacto da ativação e instalação de aparelhos ortodônticos na mastigação e nutrição: uma revisão sistemática com meta-análise

Florianópolis 2021

Laís Duarte

Impacto da ativação e instalação de aparelhos ortodônticos na mastigação e nutrição: uma revisão sistemática com meta-análise

Dissertação submetida ao Programa de Pós-graduação em Odontologia da Universidade Federal de Santa Catarina para a obtenção do título de mestre em Odontologia. Orientador: Profa. Dra. Thais Marques Simek Vega Gonçalves

Florianópolis 2021

Ficha de identificação da obra elaborada pelo autor, através do Programa de Geração Automática da Biblioteca Universitária da UFSC.

Duarte, Laís Impacto da ativação e instalação de aparelhos ortodônticos na mastigação e nutrição: uma revisão sistemática com meta análise / Laís Duarte ; orientador, Thais Marques Simek Vega Gonçalves, 2021. 74 p.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós Graduação em Odontologia, Florianópolis, 2021.

Inclui referências.

1. Odontologia. 2. Aparelhos Ortodônticos Fixos. 3. Alinhadores Estéticos. 4. Mastigação. 5. Avaliação Nutricional. I. Marques Simek Vega Gonçalves, Thais . II. Universidade Federal de Santa Catarina. Programa de Pós Graduação em Odontologia. III. Título.

Laís Duarte

Impacto da ativação e instalação de aparelhos ortodônticos na mastigação e nutrição: uma revisão sistemática com meta-análise.

O presente trabalho em nível de mestrado foi avaliado e aprovado por banca examinadora composta pelos seguintes membros:

Prof. Lucas Cardinal da Silva, Dr. Universidade do Sul de Santa Catarina

Profa. Lucianne Cople Maia, Dra. Universidade Federal do Rio de Janeiro

Prof. Luciano José Pereira, Dr. Universidade Federal de Lavras

Certificamos que esta é a versão original e final do trabalho de conclusão que foi julgado adequado para obtenção do título de mestre em Odontologia.

______Profa. Dra. Mariane Cardoso Carvalho Coordenação do Programa de Pós-Graduação

______Profa. Dra. Thais Marques Simek Vega Gonçalves Orientadora

Florianópolis, 2021.

Este trabalho é dedicado à minha família, que através do amor sempre me encoraja a evoluir.

AGRADECIMENTOS

À minha família, por me acolher em todas as minhas escolhas e vibrar a cada conquista. O incentivo de vocês sempre foi essencial para eu ter coragem em evoluir e aprender. Vocês são meus exemplos de amor e fé. Aos amigos, Amanda Crews, Ana Cristina Effting, Bruna Pavesi, Helen Brenda Kim, Júlia Schindler, Mariana Olinger, Marlei Vieira, Riana Hoffman e Yasmin Klas, pela nossa amizade de anos que é motivo de orgulho pra mim. Quero deixar aqui registrada a minha admiração e amor por vocês, por tudo o que representam na minha vida. À minha amiga e dupla, Jéssica Alana Klitzke. Nossa amizade é especial. Obrigada por sempre estar ao meu lado, torcendo por mim. À amiga, Natalia Fiuza Coelho Neta. Pela amizade, presença e incentivo em todas as minhas escolhas. Você faz parte dessa conquista. Aos meus professores de colégio e graduação, Salete Batisti, Nadir Boing Maestri, Ana Cristina Kovalik e Ivens Frischknecht (in memorian). Professores que sempre lembro com carinho e fizeram a diferença durante minha formação. São inspiração na minha vida acadêmica e exemplos de professores que ensinam com amor e dedicação. A todos os amigos, que sempre torceram por mim. O amor e apoio de vocês foi fundamental. A minha orientadora, Profa. Dra. Thais Marques Simek Vega Gonçalves, por todos os ensinamentos durante esses dois anos. Obrigada por todas as oportunidades que foram essenciais para o meu crescimento pessoal e profissional. A sua dedicação e disponibilidade em orientar são admiráveis, és um exemplo pra mim. À minha amiga de Pós-Graduação e segunda revisora desse trabalho, Adriana Pinto Bezerra. Pela contribuição imprescindível para o desenvolvimento desse trabalho, mas principalmente por toda paciência e disponibilidade em sempre dividir o seu conhecimento. Obrigada por toda amizade e parceria. Aos meus amigos da pós-graduação, Matheus Akira Sakurada, Rangel Lidani, Tarla Thaynara Oliveira dos Santos, Gabriela Panca Sabatini e Franciele Quiquio Santiago Floriani, por me acolherem e dividirem comigo essa experiência que é viver o mundo acadêmico.

À Profa. Dra. Analucia Gebler Philippi, e aos Profs. Drs, Maurício Malheiros Badaró e Luis André Mendonça Mezzomo, por todo conhecimento compartilhado, pela amizade e auxílio nas atividades da Pós-Graduação. A Coordenadora do Programa de Pós-Graduação em Odontologia, Prof. Dra. Mariane Cardoso. À secretária do Programa de Pós-Graduação em Odontologia, Débora dos P. Rodrigues Coelho, por todo suporte e disponibilidade. A todos os docentes do Programa de Pós-graduação em Odontologia da Universidade Federal de Santa Catarina, pela contribuição imprescindível para minha formação acadêmica. A todos os servidores e funcionários da Universidade Federal de Santa Catarina, por todo auxílio, disponibilidade e suporte.

APRESENTAÇÃO

Esta revisão sistemática foi escrita originalmente sob a forma de artigo científico na língua inglesa, com o objetivo de ser submetido ao periódico Journal of Dentistry em parceria com o professor e pesquisador da Universidade de Alberta, Prof. Dr. Carlos Flores Mir; juntamente com o Prof. Dr. Luciano José Pereira, professor e pesquisador da Universidade Federal de Lavras.

RESUMO

Objetivo: Revisar sistematicamente a literatura a fim de avaliar o efeito da instalação e da ativação de diferentes aparelhos ortodônticos sobre a mastigação e a nutrição dos pacientes. Material e métodos: Esta revisão sistemática foi conduzida conforme preconizado no PRISMA 2020. A busca bibliográfica incluiu 6 bases de dados eletrônicas (até maio de 2021) e 3 bases de dados da literatura cinzenta, sem restrições de idioma ou tempo de publicação. Apenas estudos que avaliaram a mastigação e nutrição após a instalação e/ou ativação de diferentes aparelhos ortodônticos foram incluídos. O risco de viés foi avaliado com as ferramentas da Cochrane (RoB 2 para estudos clínicos randomizados e ROBINS-I para estudos não randomizados). A qualidade da evidência foi analisada com o GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Esta revisão foi registrada no PROSPERO (CRD42020199510). Os dados foram computados e meta-análises de efeito randômico foram realizadas quando possível (α = 0.05). Resultados: Após aplicação das estratégias de busca e remoção de duplicados, 4226 referências foram incluídas para leitura de títulos e resumos. Foram então selecionados 41 artigos para leitura de texto completo, sendo 27 deles excluídos por diferentes razões. Ao final, 15 artigos foram incluídos, sendo apenas 6 utilizados na análise quantitativa. Os estudos clínicos randomizados incluídos apresentaram risco de viés alto, enquanto os estudos não randomizados variaram entre moderado e alto. A qualidade da evidência avaliada pelo GRADE sugeriu um nível de evidência baixo ou muito baixo. Na análise quantitativa houve redução significativa da performance mastigatória (diferença média padronizada (DMP) 1,07; IC95%: 0,619 a 1,518; p < 0,001) e da força de mordida (DMP -2,542 (IC 95%: -4,867 a -0,217; p = 0,03) nas primeiras 24 a 48 horas da ativação/instalação dos aparelhos fixos labiais. O limiar de deglutição se manteve constante e a mastigação foi totalmente recuperada após 30 dias (p > 0,05). Apenas um estudo avaliou a nutrição, apresentando uma redução significativa no consumo de alimentos ricos em cobre (p = 0,002) e manganês (p = 0,016), além da maior ingestão de calorias e gordura saturada (p < 0,05) após a ativação/instalação dos aparelhos fixos labiais. Os usuários de aparelhos fixos linguais também relatam mais problemas mastigatórios quando comparados aos usuários de aparelhos labiais. Por outro lado, usuários de alinhadores estéticos relataram menor desconforto durante a alimentação quando comparados aos usuários de aparelhos fixos labiais. Conclusões: De maneira geral, a ativação e/ou instalação dos aparelhos ortodônticos labiais reduz a performance mastigatória e força de mordida nas primeiras horas ou semanas. Porém, ambas

variáveis são completamente restabelecidas após 30 dias. Dados sobre o estado nutricional dos pacientes e o impacto dos alinhadores estéticos ou aparelhos fixos linguais são insuficientes para maiores conclusões e necessitam de mais estudos sobre o assunto.

Palavras-chave: Aparelhos Ortodônticos Fixos; Alinhadores Estéticos; Mastigação; Avaliação Nutricional; Revisão Sistemática.

ABSTRACT

Objectives: To systematically review the literature in order to assess the effect of the activation/installation of different orthodontic appliances on patient`s mastication and nutrition. Material and methods. This systematic review was conducted as recommended in PRISMA 2020. Literature search included 6 eletronic databases (until August 2020, last update February 2021) and 3 grey literature databases, without restrict language or publication time. Only studies that evaluated mastication and nutrition after the activation/installation of the orthodontic appliances were included. Risk of bias was assessed using the Cochrane tool (RoB 2 for randomized clinical studies and ROBINS-I for non-randomized studies). The quality of the evidence was analyzed through GRADE (Classification of Recommendations, Evaluation, Development and Evaluation). This review was registered in PROSPERO (CRD42020199510). Data were computed and random effect meta-analyses were performed when possible (α = 0.05) Results: After applying the search strategy in the databases and removing duplicates, 4226 references were included for reading titles and abstracts. Forty-one articles were selected to read the full text, 27 of which were excluded for different reasons. Thus, 15 articles were included, with only 6 used for quantitative analysis. Included randomized clinical trials had a risk of serious bias, while non-randomized trials ranged from moderate to serious. The quality of evidence assessed by GRADE suggested a low or very low level of evidence. The quantitative analysis showed a significant reduction in masticatory performance (standardized mean difference (DMP) 1.069; 95%CI: 0.619 to 1.518; p < 0.001) and in bite force (SMP - 2.542 (CI) 95%: -4.867 to -0.217; p = 0.03) in the first 24 to 48 hours of activation/installation of fixed labial appliances. The swallowing threshold remained constant and mastication was fully recovered after 30 days (p > 0.05). Only one study evaluated nutrition, showed a significant reduction in the consumption of foods rich in copper (p = 0.002) and manganese (p = 0.016), in addition to a higher intake of calories and saturated fat (p < 0.05) after activation/installation of fixed labial appliances. Users of fixed lingual appliances also report more problems with mastication when compared to users of labial appliances. On the other hand, users of clear aligners reported less discomfort during feeding when compared to users of fixed labial appliances. Conclusions: In general, activation/installation of orthodontic labial appliances reduced the masticatory performance in the first hours or weeks. However, masticatory function was completely recovered after 30 days. Data on the nutritional status of

patients or the impact of clear aligners and lingual fixed appliances are insufficient for conclusions and need further studies on the subject.

Keywords: Fixed Orthodontic Appliances; Clear Aligners; Mastication; Nutritional Assessment; Systematic review.

LISTA DE FIGURAS

Fig. 1 Flowchart of selection process (PRISMA 2020). Fig. 2 Risk of bias summary on reviewers’ judgements about each risk of bias item according to the different study designs (2.1. Risk of bias assessment for randomized clinical trials (ROB 2.0 tool); 2.2. Risk of bias assessment for Nonrandomized studies (ROBINS-I tool)).

Fig. 3 Forest plots of masticatory performance (X50) after the activation of fixed labial appliances (3.1. Comparisons between baseline and 24 hours of activation; 3.2. Comparisons between baseline and 30 days of activation; 3.3. Comparisons between 24 hours and 30 days of activation). Fig. 4 Forest plots of swallowing threshold (particle size and number of cycles) after the activation of fixed labial appliances (4.1. Comparisons between baseline and < 48 hours; 4.2. Comparisons between baseline and 30 days of activation; 4.3. Comparisons between baseline and < 48 hours; 4.4. Comparisons between baseline and 30 days of activation). Fig. 5 Forest plots of bite force comparisons before and one week after the activation of fixed labial appliances. Fig. 6 Forest plots of pain levels before and after the activation of fixed labial appliances (6.1. Comparisons between baseline and 24 hours of activation; 6.2. Comparisons between baseline and 48 hours of activation; 6.3. Comparisons between 24 hours and 30 days of activation; 6.4. Comparisons between baseline and 30 days of activation).

LISTA DE TABELAS

Table 1. Summary of descriptive characteristics of included studies (n=15)……………..….49

Table 2. Evidence summaries of the outcomes (The Grading of Recommendations Assessment,

Development and Evaluation – GRADE…………………………………………………...… 54

LISTA DE ABREVIATURAS E SIGLAS

PROSPERO - International prospective register of systematic reviews

PRISMA - Preferred Reporting Items for Systematic Reviews

PICOS – Population, Intervention, Comparison, Outcomes, Studies

LILACS - Latin American and Caribbean Health Sciences

L.D. – Laís Duarte

A.P.B. – Adriana Pinto Bezerra

L.J.P. – Luciano José Pereira

T.M.S.V.G. – Thais Marques Simek Vega Gonçalves

RCT – Randomized Clinical Trial

GRADE – The Grading of Recommendations Assessment, Development and Evaluation

CMA – Comprehensive Meta-Analysis

SMD – Standardized Mean Difference

VAS – Visual Analog Scale

OHIP – Oral Health Impact on Quality of Life

SUMÁRIO 1 INTRODUÇÃO ...... 17 2 OBJETIVOS ...... 21 2.1 Objetivo Geral ...... 21

2.2 Objetivos Específicos ...... 21

3 CAPÍTULO 1 ...... 22 4 CONCLUSÃO ...... 72 REFERÊNCIAS ...... 73

1 INTRODUÇÃO

A mastigação tem como função preparar o alimento para ser deglutição, reduzindo-o em partículas menores e iniciando, assim, o processo digestivo

(PEDERSEN, 2002; VAN DER BILT, 2006). Distúrbios mastigatórios podem interferir na seleção e ingestão dos alimentos, podendo levar às carências nutricionais (N’GOM,

2002). Nos últimos anos, muito tem se estudado sobre fatores odontológicos que podem interferir na mastigação.

Métodos de avaliação objetivos e subjetivos foram desenvolvidos e vêm sendo aprimorados para avaliar a capacidade do aparelho mastigatório (TARKOWSKA, 2017).

A análise da performance mastigatória por meio do peneiramento dos alimentos após a trituração é um bom exemplo dessa avaliação (VAN DER BILT, 2006). Esse método é considerado atualmente como o “padrão ouro” de avaliação da capacidade mastigatória dos indivíduos (TARKOWSKA, 2017). Esse método baseia-se em avaliar o tamanho das partículas trituradas de um alimento ou material teste mastigável, após um determinado número de ciclos mastigatórios (BATES, 1976; VAN DER BILT, 2006).

Estudos anteriores relatam que diferentes fatores podem influenciar a performance mastigatória (HATCH, 2000; MAGALHÃES, 2010; FONTIJN-TEKAMP,

2010). Dentre esses fatores destacam-se a redução nos pares oclusais funcionais, a presença de má-oclusões, utilização de próteses mal adaptadas, a redução da área dos contatos oclusais e a redução da força de mordida (HATCH, 2000; MAGALHÃES, 2010;

FONTIJN-TEKAMP, 2010).

Na ortodontia, em particular, muitos pacientes relatam dor e desconforto durante a mastigação após a ativação dos aparelhos ortodônticos. Porém, poucas evidências sobre a função mastigatória de usuários de aparelhos ortodônticos estão disponíveis (TREIN, 2013; MAGALHÃES, 2014). Além disso, a maioria dos

18 ortodontistas costumam subestimar a dor relacionada à ativação dos aparelhos, visto que as queixas mais comuns costumam reduzir em poucos dias, e quase não são relatadas nas consultas subsequentes (TREIN, 2013).

Acredita-se que a dor e o desconforto possam estar relacionados aos reflexos nociceptivos, muito comuns na movimentação dental inicial do tratamento

(GOLDREICH, 1994). Sabe-se que o movimento dentário ortodôntico é dependente da força aplicada e da resposta biológica do dente e dos tecidos circundantes (GAMEIRO,

2007; KRISHNAN, 2006). Tensões e forças de compressão alteram a vascularização do ligamento periodontal, resultando em um processo inflamatório local com síntese e liberação de neurotransmissores, citocinas, fatores estimuladores de colônias, fatores de crescimento e metabólitos do ácido araquidônico (KRISHNAN, 2006). Esse processo inflamatório agudo fornece um ambiente favorável para a deposição óssea alveolar (lado de tensão) ou reabsorção (lado de compressão), resultando no movimento dentário controlado (GAMEIRO, 2007). Em contrapartida, essa inflamação aguda pode resultar em dor e desconforto, com possíveis consequências para a mastigação (KRISHNAN,

2006; TREIN, 2013).

Os poucos estudos (TREIN, 2013; MAGALHÃES, 2014; GAMEIRO, 2015;

ANDRADE, 2018) que avaliaram a performance mastigatória de pacientes ortodônticos apresentaram dados apenas dos aparelhos fixos labiais. Segundo esses estudos, a performance mastigatória parece ser reduzida durante o pico da dor ortodôntica, ou seja,

24 a 48 horas após a ativação do aparelho (TREIN, 2013; MAGALHÃES, 2014). Após esse período, a inflamação aguda é substituída por um processo crônico que modula a remodelação óssea, reduzindo significativamente a dor (KRISHNAN, 2006). Resultados semelhantes são encontrados em relação à força máxima de mordida (ALOMARI, 2012).

Apesar desses resultados serem bastante interessantes, parece não haver, até o presente

19 momento, revisões sistemáticas publicadas que sintetizem esses resultados e possam embasar tais achados.

Além dos aparelhos fixos labiais, outros tratamentos ortodônticos estão sendo bastante utilizados, destacando-se os aparelhos linguais e os alinhadores estéticos. O aparelho fixo lingual foi introduzido no final dos anos 1970 (FUJITA, 1979), como uma alternativa ortodôntica estética visto que os braquetes ficam praticamente invisíveis no sorriso (KHATTAB, 2013). Porém apesar de sua constante evolução, a ortodontia lingual ainda é considerada uma técnica difícil (ALOBEID, 2018). Mesmo com o desenvolvimento de braquetes linguais personalizados, o impacto na cavidade oral dos pacientes ainda é considerado maior quando comparados com os braquetes labiais (WU,

2011). Pacientes tratados com braquetes linguais personalizados apresentaram maior dificuldade na fala, na deglutição e mudanças na alimentação, além de problemas sociais e desconforto oral (WU, 2011). Uma revisão sistemática prévia (LONG, 2013) revelou que os pacientes que usam aparelhos fixos linguais relatam maior dificuldade na alimentação (OR = 3.59, p < 0.0001), maiores problemas de fala (OR = 8.61, p < 0.0001) e maior incidência de dor na língua (OR = 32.24, p < 0.0001) do que aqueles que usam aparelhos labiais. Entretanto, vale destacar que esses dados foram baseados em avaliações subjetivas dos pacientes, o que necessita de comprovação baseada em análises objetivas, principalmente no que diz respeito ao impacto do aparelho fixo lingual na mastigação.

Outra alternativa de tratamento são os alinhadores estéticos. Esse tratamento é mais recente e foi introduzido no mercado a fim de promover maior estética e conforto durante o tratamento, visto sua natureza removível (FUJIYAMA, 2014). Um estudo

(FLORES-MIR, 2018) comparou a satisfação dos pacientes usuários de aparelhos fixos labiais à daqueles usuários de alinhadores estéticos. De acordo com os resultados, não houve diferenças significantes entre os grupos. De qualquer forma, usuários de

20 alinhadores parecem apresentar menor desconforto durante a alimentação, visto que os aparelhos são removidos durante as refeições. (ALAJMI, 2020).

Em relação ao padrão nutricional dos usuários de aparelhos ortodônticos, a literatura é ainda mais escassa. Os poucos estudos disponíveis revelam que, durante o tratamento ortodôntico, os pacientes relatam alterações de paladar, redução no consumo de alimentos mais consistentes e a necessidade de maior tempo para as refeições

(CARTER, 2015). Essas alterações no hábito alimentar podem estar relacionadas à preocupação com o próprio aparelho ortodôntico, possíveis recomendações do ortodontista, medo de danificar o aparelho ou prejudicar o tratamento e até mesmo constrangimentos sociais durante a alimentação (CARTER, 2015). Em conjunto, todos esses fatores podem contribuir para as restrições alimentares com possível impacto nutricional. No entanto, os estudos que avaliam as alterações nutricionais durante o tratamento ortodôntico são bastante escassos e, até o momento, a confiabilidade dessas evidências ainda não foi avaliada.

De forma geral, fica evidente a necessidade de uma avaliação crítica e sistemática sobre o impacto dos diferentes tratamentos ortodônticos sobre os processos mastigatórios e nutricionais.

2 OBJETIVOS

2.1 OBJETIVO GERAL

Revisar sistematicamente a literatura a fim de avaliar o efeito da instalação e da ativação de diferentes aparelhos ortodônticos sobre a mastigação e a nutrição dos pacientes.

2.2 OBJETIVOS ESPECÍFICOS

• Avaliar os desfechos primários relacionados à mastigação (performance mastigatória, limiar de deglutição, força de mordida, e eletromiografia) e à nutrição (concentração sérica dos nutrientes, medidas antropométricas, ingestão nutricional, questionários sobre dieta) de pacientes usuários de aparelho fixo (labial ou lingual) e alinhadores estéticos após a instalação/ativação dos aparelhos ortodônticos; • Avaliar estatisticamente, através de meta análises, os estudos incluídos por meio da comparação dos resultados prévios e posteriores à instalação/ativação de aparelho fixo ortodôntico ou alinhador estético; • Avaliar o risco de viés e o nível de evidência dos estudos incluídos;

3 CAPÍTULO 1

Activation and installation of orthodontic appliances temporarily impair mastication: a systematic review with meta-analysis. Running title: Masticatory impairment of braces activation.

Laís Duartea, Adriana Pinto Bezerrab, Carlos Flores-Mirc, Graziela De Luca Cantod, Luciano José Pereirae, Thais Marques Simek Vega Gonçalvesf a Graduate Student, Department of Dentistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil, [email protected], ORCID iD: 0000- 0002-7193-7461 b Graduate Student, Department of Dentistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil, [email protected], ORCID iD: 0000-0002-4971-2741 c Professor, Department of Dentistry, University of Alberta, Edmonton, Alberta, Canada, [email protected], ORCID iD: 0000-0002-0887-9385

d Professor, Department of Dentistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil, [email protected], ORCID iD: 0000-0002- 7986-8317

eProfessor, Federal University of Lavras (UFLA), Lavras, Minas Gerais, Brazil, [email protected], ORCID iD: 0000-0002-0502-2554 f Professor, Department of Dentistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil, [email protected], ORCID iD: 0000-0002- 0510-2140

Corresponding author: Dr. Thais Marques Simek Vega Gonçalves Department of Dentistry, Federal University of Santa Catarina R. Eng. Agronômico Andrei Cristian Ferreira, s/n - Trindade, Florianópolis - SC, Brazil, Zip Code: 88040-900, Business Phone number: +554837215845 E-mail: [email protected]

Acknowledgements The authors would like to acknowledge the assistance of the librarian Goreti M. Savi from the Federal University of Santa Catarina.

* Este manuscrito está configurado de acordo com as normas do periódico Journal of Dentistry

ABSTRACT

Objective: This systematic review aimed to investigate the masticatory and nutritional impacts of the activation and/or installation of different orthodontic appliances (fixed labial, lingual appliances and clear aligners).

Data/Sources: Six electronic databases and grey literature were searched (up to May

2021) for relevant studies evaluating mastication and nutrition after activation/installation of orthodontic appliances. This review followed PRISMA and was registered at

PROSPERO (CRD42020199510). The risk of bias (RoB 2 and ROBINS-I) and evidence quality (GRADE) were analyzed.

Study selection: Of the 4226 recorded screened, 15 studies were included. Masticatory performance (SMD 1.069; CI: 0.619, 1.518; P = 0.000) and bite force (SMD -2.542; CI:

-4.867, -0.217; P = 0.03) reduced at the first 24 to 48 hours of fixed labial appliances installation/activation, but they were both recovered after 30 days (P > 0.05). The swallowing threshold remained constant (P > 0.05). Nutritional intake was barely reported but showed cooper (P = 0.002) and manganese (P = 0.016) reductions, with higher calories and fat intake (P < 0.05). Lingual appliances impacted more chewing than labial, and clear aligners wearers reported less harm during chewing (P < 0.001). Low to very low levels of evidence were found.

Conclusions: Mastication was reduced during the first 24 to 48 hours of fixed labial appliance activation/installation, but it was transitory. Insufficient data of clear aligners and lingual appliances jeopardized further conclusions.

Clinical significance: Knowledge about masticatory impairments could help dentists better advise their patients during the orthodontic treatment, especially considering that the changes are temporary.

Keywords: Fixed Orthodontic Appliances; Clear Aligners; Mastication; Nutrition

Assessment; Systematic review.

Introduction

Orthodontic tooth movement depends on the applied force and the tooth's biological response from surrounding tissues [1, 2]. Tensions and compression forces change the vascularity and blood flow of the periodontal ligament, resulting in local inflammatory process with synthesis and release of neurotransmitters, cytokines, colony- stimulating factors, growth factors, and arachidonic acid metabolites [2]. It provides a favorable microenvironment for alveolar bone deposition (tension side) or resorption

(compression side), ultimately resulting in tooth movement [1]. Frequently, this acute inflammatory process is associated with painful sensations and discomfort [2, 3].

Most orthodontists usually underestimate orthodontic pain since patients' complaints do not last long, and it is barely reported right after the activation appointments [3]. Habitually, a chronic process replaces the acute inflammation after the first days of activation, modulating bone remodeling and significantly reducing the pain

[2]. Previous studies [4, 5] reported that orthodontic patients avoid chewing hard and consistent food, adopting a soft diet during the treatment. Moreover, only limited evidence [3, 5] is available on how the orthodontic appliance activation would impact the masticatory function and nutritional behavior.

Other orthodontic treatment modalities are now available besides the conventional fixed labial appliances, including lingual fixed appliances and removable clear aligners.

However, debate still exists on how each orthodontic treatment would affect the masticatory function, especially comparing labial and lingual fixed appliances to clear aligners. Previous studies [3, 5, 6] have shown a significant reduction in masticatory performance 24 hours after fixed labial appliance activation. Moreover, a recent review

[7] reported that patients using fixed lingual appliances would be more likely to suffer from eating difficulty than labial appliances. In contrast, patients using removable clear

27 aligners reported fewer chewing limitations than those using fixed labial appliances [8].

Nevertheless, it is evident the necessity of a critical evaluation of the impact of different orthodontic treatments on masticatory and nutritional processes.

Patients also report a longer time for eating and taste changes [9]. Besides, chewing difficulties may be caused by appliance aesthetics, orthodontist advice, fear of breakage, and even social embarrassments [9]. Taken together, all these factors may contribute to food restrictions and lead to nutritional problems. However, studies evaluating nutritional changes during orthodontic treatment are scarce, and to date, the reliability of this evidence has not been critically assessed yet.

Therefore, the purpose of this systematic review is to evaluate the current evidence on: “How does the activation or installation of different orthodontic appliances affect the masticatory function and nutrition of patients?”

Methods

Protocol and registration

This systematic review was reported accordingly PRISMA updated guidelines

[10]. In addition, the study protocol was developed and registered at the Prospective

University of York; and the National Institute for Health Research) under the registration number CRD42020199510.

Eligibility criteria

The PICOS process (Population, Intervention, Comparison, Outcomes, Studies) was used to formulate the focused question, in which: P) Patients undergoing orthodontic treatment with different types of orthodontic appliances (labial or lingual fixed appliances and removable clear aligners); I) Activation or installation of orthodontic appliances; C)

Baseline period before the activation or installation of other orthodontic appliances; O)

Follow-up measurements of masticatory function (bite force, masticatory performance, swallowing threshold (particle size and/or number of cycles), muscle electromyography, masticatory cycles), nutritional status (nutritional intake, risk of malnutrition, nutrient bioavailability, body mass index), and pain levels; and S) Randomized controlled trials, non-randomized controlled trials, and case series studies (before and after). No language, publication time, or follow-up period restrictions were applied.

Exclusion criteria were as follows: (1) Studies in which the sample consisted of patients with temporomandibular disorders; (2) Studies in which partial edentulous patients were included; (3) Case series with less than ten patients; (4) Animal models or experimental in vitro studies, reviews, letters, conference abstracts, personal opinions, case reports, technical articles; (5) Studies with missing data or which the authors did not provide data.

Information sources and search

Electronic search strategies were developed and adapted according to each of the following databases: Cochrane Library, EMBASE, Latin American and Caribbean Health

Sciences (LILACS), PubMed (including Medline), SCOPUS, and Web of Science. An additional grey literature search was performed on Google Scholar, Open Grey, and

ProQuest. Additionally, the reference lists of included studies were hand-searched, and experts were consulted to identify additional studies, following Greenhalgh and Peacock

(Fig 1) [11]. All database searches were conducted up to May 2021. The reference manager EndNote (version X9, Thomson Reuters) collected references and removed duplicates.

Study selection

The articles' selection was conducted individually and independently by two calibrated authors (L.D. and A.P.B.) in a two-phase process. In phase one, titles and abstracts were screened, and studies that did not fulfil eligibility criteria were excluded.

In phase two, eligibility criteria were applied to the studies' full texts by the same two reviewers. The entire process was conducted using the Rayyan tool [12]. Any disagreement in both phases was resolved by discussion until agreement. Further doubt or discrepancies were discussed and solved with the team and the coordinator

(T.M.S.V.G.).

Data collection process and data items

Two reviewers (L.D. and A.P.B.) performed data extraction independently using spreadsheets (Excel v. 16.49, Microsoft©, CA, USA). Any controversies were discussed and decided with the coordinator (T.M.S.V.G.). Data extraction of the included studies was done by using a structured form. It consisted of study characteristics (author, year of publication, study design, country), population characteristics (sample size, gender, age of participants), intervention details (a type of orthodontic appliance, follow-up time) and outcome (masticatory function, nutritional assessment and pain level). To retrieve any pertinent unreported information, the authors tried up to three attempts to contact corresponding authors.

Assessment of risk of bias

The risk of bias was also independently analyzed by two reviewers (A.P.B. and

L.J.P.). The coordinator (T.M.S.V.G.) was involved in solving disagreements. Different critical appraisal tools were applied according to each type of study. To evaluate the risk of bias of randomized controlled trials (RCTs), the revised Cochrane’s Collaboration tool

RoB 2 [13] was applied. The risk of bias of non-randomized studies was analyzed by non-

30 randomized studies - Intervention tool ROBINS-I [14]. The risk of bias was defined as: a) low risk (bias, if present, is unlikely to alter the results and the answers “seriously” were up to 70% of the questions); b) unclear risk (a risk of bias that raises some doubt about the results; and c) high risk (bias may seriously alter the results) [15]. The Risk-of- bias VISualization (robvis) tool [16] was used to summarize data.

Assessment of Evidence Quality

The Grading of Recommendations Assessment, Development and Evaluation

(GRADE) criteria was used to assess the overall quality of the evidence-based on the rating of risk of bias, consistency, directness, precision, and publication bias [17]. Two independent reviewers (A.P.B. and L.J.P.) were made judgments, and each topic was assessed as having no limitations, serious limitations, or very serious limitations. As a result, the overall quality of the evidence was categorized as high, moderate, low, and very low. A summary of the findings table was generated based on the online software

(GRADEpro GDT; the GRADE Working Group).

Statistical analysis

After data extraction, outcome results from studies with similar methodologies and follow-up times were pooled for statistical analysis. Comparisons between pre/post assessments on masticatory performance, swallowing threshold, bite force and pain were performed. Two studies [6, 18] presented masticatory performance and pain assessments from the same sample of patients; therefore, to prevent overestimating the effect size, only one [6] was included for quantitative analysis. As for other outcomes, there was significant methodological heterogeneity between studies, which jeopardized further meta-analysis of these results.

Meta-analyses were performed using the Comprehensive Meta-Analysis software

(CMA, V. 3, Biosta, Inc., USA). Since CMA requires the pre/post correlation for

31 comparisons between pre/post values of matched groups, and this was not reported in the studies included for meta-analysis, a sensitivity analysis was performed varying the pre/post correlation from 0.1 to 0.9. Results did not change after analysis; therefore, a median correlation of 0.5 was adopted for all comparisons.

The standardized mean difference (SMD) and 95% CI for changes before and after the installation and/or activation of the different oral appliances were estimated using a random-effects model given the inherent heterogeneity of studies. The validity measurements were transformed to draw forest plots. Statistical heterogeneity was also assessed using the I-square statistics, where I2 > 50% was considered a sign of substantial heterogeneity. Clinical heterogeneity across studies was assessed by comparing variability among participants' characteristics, methodological heterogeneity and risk of bias in individual studies. The statistical significance level for all tests was set at 5%.

Results

Study selection

The electronic search of the databases (Supplemental File 1) revealed 15188 references. After duplicate removal, 4226 articles were selected for the title and abstract screening. An additional 196 records were identified through grey literature and hand search of reference lists. After phase one, 41 articles were selected for full-text analysis.

After that, 27 articles were excluded in phase two screening based on eligibility criteria

(Supplemental File 2). One additional article was included from the reference lists' hand- search. In the end, 15 studies were included.

Examiners' agreement expressed as Cohen’s unweighted к yielded к = 0.89 for phase 1 and к = 0.81 for the full-text screening and final selection of the articles. The search strategy details are illustrated in the PRISMA flowchart (Fig. 1).

Study characteristics

Characteristics of the included studies are summarized in Table 1. All 15 studies were published between 1994 and 2020. A total of 480 patients, ranging from 11 to 35 years old (mean of 21.7 years old), were included.

Fixed labial appliances were installed in 341 patients, while 70 individuals were treated with clear aligners and 69 received lingual fixed appliances. (Table 1) Out of the

15 included articles, nine studies [3-6, 18-22] investigated the outcomes exclusively of fixed labial appliances. Two studies compared labial to lingual fixed appliances [23, 24], while another two articles compared labial fixed appliances to clear aligners [8, 25]. The remaining two studies reported outcomes only from clear aligners [26] or fixed lingual appliances [27].

The masticatory function was objectively assessed by different methods, including masticatory performance (X50) [3, 5, 6, 18], swallowing threshold (particle size and number of cycles) [3-5], maximum bite force [19, 21], masseter muscle electromyography [4, 26]. In addition, the subjective aspects of masticatory function were also assessed by visual analogue scale (VAS – 10 cm) [24, 25] and questionnaires [8, 20,

23, 27].

In terms of nutritional assessment, only one study [22] analyzed patient’s nutrition before and after the activation of a fixed labial appliance through a 3-day diet diary.

A secondary outcome of pain experience after orthodontic activation was also assessed in seven studies by using a questionnaire based on VAS (10 cm) [3-6, 18, 19] or

Likert-scale [8]. In addition, one study [20] described pain levels using some questions of Oral Health Impact on Quality of Life (OHIP-16).

Risk of Bias within individual studies

Results from the risk of bias assessment of individual studies are presented in

Figure 2. Overall, the two RCTs [23, 25] presented a serious risk of bias, mainly due to the presence of bias in outcome measurements, since mastication was assessed subjectively through self-reported questionnaires solely. However, no serious problems were detected on the remaining domains (Fig. 2.1).

The risk of bias of non-randomized studies was presented in Figure 2 B. Three studies [18, 19, 21] presented an overall moderate risk of bias, while the remaining ten papers [3-6, 8, 20, 22, 24, 26, 27] presented an overall serious risk of bias. Regarding the first domain, bias was considered serious [3-6, 19, 20, 22, 24, 26, 27] or moderate [18,

19, 21] mainly due to the presence of confounding regarding large differences in male/female proportion and Angle classification distribution in the intervention groups, as well as a poor description of patients’ eligibility criteria, especially the exclusion of individuals with temporomandibular disorders [3-6, 8, 18-20, 22, 24, 26, 27]. Selection of patients after the beginning of the orthodontic treatment contributed to an increase in the risk of selection bias in some studies [4, 8, 22], since patients undergoing treatment for a more extended time might be more adapted to chewing in the presence of an orthodontic appliance. The bias in classification of intervention bias was considered moderate in three studies [4, 6, 22], due to issues with an appropriate description of eligibility criteria and patient selection. One study [8] presented a high risk of bias on account of its retrospective design. Bias due to deviations of intended interventions was considered low for all studies since the evaluation periods considered for this review were short (24 hours to a month). No patients required changes in interventions.

Regarding the increased risk of bias due to missing data, only one study [27] presented moderate risk caused by excluding patients who did not answer the questionnaire correctly. As for bias from outcome measurements, four articles [4, 8, 24,

26] presented moderate risk due to the lack of blinding of outcome accessors or the use of portable equipment based on patient self-assessment, which can lead to erroneous results if instructions and training are not correctly delivered. Since the remaining 11 studies [3, 5, 6, 18-23, 25, 27] evaluated only one intervention group, blinding of outcome assessors would not be possible; therefore, the risk of bias was judged as low for this domain. In addition, no issues were detected in the selection of reported results; thus, all studies were considered low risk for this last domain.

Evidence Quality

Confidence in cumulative evidence was considered low and very low according to the GRADE criteria. Inconsistency was judged to be serious to very serious. The risk of bias across studies was deemed serious since all included studies presented an overall serious risk of bias judgment, mainly arising from confounding factors. In some comparisons, significant heterogeneity between studies (I² > 50%) rendered serious and very serious limitations judgement for inconsistency on masticatory performance and bite force assessments. As for indirectness, none of the outcomes presented issues regarding applicability since the included studies presented results that directly represented the intervention, population and outcomes that were important for the investigation, thus were judged as presenting no serious limitations. Imprecision was regarded as serious for all outcomes due to the small number of patients (less than 400) included in the studies, limiting effect size measurements (Table 2).

Results of individual studies

Studies evaluating Fixed Labial Appliances

Studies comparing the masticatory performance of fixed labial appliances presented more homogeneous methods (sieving method), allowing data meta-analyses

(Supplemental File 3). We compared the chewed particle size (X50) before and 24 hours after activation in the first analysis. The inverse variance random-effects model revealed a significant reduction of masticatory performance after 24 hours of activation (standard mean difference (SMD) = 1.069; 95% CI: 0.619, 1.518; P = 0.000) (Fig. 3.1). When comparing baseline to 30 days after activation, differences were no longer observed

(SMD = 0.078; 95% CI: -0.183, 0.340; P = 0.558) (Fig. 3.2). Moreover, the reduced masticatory function at 24 hours was recovered after 30 days of fixed appliance activation

(SMD = -1.851; 95% CI: -3.442, -0.259; P = 0.023) (Fig. 3.3).

The swallowing threshold tests analyze the particle size (X50) at the moment of individuals’ urge for swallowing and the particular number of cycles used during the process. Only two studies[3, 5] presented the homogeneous methodology of swallowing parameters, allowing data meta-analyses (random effects). No differences in the swallowing threshold particle size were observed when comparing baseline to up to 48 hours of fixed appliance activation (SMD = 0.376; 95%, CI: -0.071, 0.823; P = 0.100)

(Fig. 4.1). Similarly, when comparing baseline to 30 days, the differences were not significant (SMD = -0.014 (95% CI: -0.337, 0.310; P = 0.934) (Fig. 4.2). When considering the swallowing threshold number of cycles, no differences were observed between baseline and 48 hours after activation (Fig. 4.3) or between baseline and 30 days

(Fig. 4.4).

In terms of bite force, significant differences were observed when comparing the baseline to one week after the fixed labial appliance activation (SMD = -2.542 (95% CI:

-4.867, -0,217; P = 0.03) (Fig. 5).

Only one study[22] reported data regarding patients' nutritional changes after activating the fixed labial appliance. Significant intake reduction of copper (P = 0.0018) and manganese (P = 0.016) were observed three days after an orthodontic activation.

Increased total calories and saturated fat consumption (49.32% to 55.54%) was also noticed, while the percentage of calories from carbohydrates (36.71% to 32.14%) decreased.

The fixed labial appliance activation also increased pain levels after 24 hours

(SMD = 1.852; 95% CI: 1.262, 2.442; P = 0.000) (Fig. 6.1) and 48 hours (SMD = 1.547;

95% CI: 1.126, 1.967; P = 0.000) (Fig. 6.2). Pain levels observed in the first 24 hours was also higher than those observed after 30 days (SMD = -1.741; 95% CI: -2.310, -1.173; P

= 0.000) (Fig. 6.3). After 30 days, pain differences from the baseline were not significant

(P = 0.056) (Fig. 6.4).

Studies evaluating Fixed Lingual Appliances

Only three studies [23, 24, 27] reported masticatory outcomes of patients using fixed lingual appliances, and two of them compared patients using lingual appliances to those using labial fixed appliances [23, 24]. However, none of them performed objective assessments of mastication. Instead, only subjective and self-reported parameters were analyzed. Since these subjective parameters presented a heterogeneous methodology, a meta-analysis was not possible.

According to the results of individual studies, a moderate to severe impairment on mastication was observed immediately after the lingual brackets' placement [23, 24].

Patients treated with lingual appliances also reported more oral discomfort, dietary

37 changes, swallowing difficulty, speech disturbances, and social problems than those using labial appliances [24]. No significant differences were found between the groups regarding oral self-care, mastication, and satisfaction [24]. The patients recovered their chewing abilities after one month of the appliance installation or activation. Still, after three months, patients from the lingual group were not yet completely satisfied with the masticatory ability [23, 27].

Studies evaluating Clear Aligners

Three studies [8, 25, 26] evaluated the masticatory outcomes in patients using clear aligners. Two of them [8, 25] compared the mastication of patients using clear aligners to those using fixed labial appliances. Similarly, these two studies evaluated masticatory function using self-report questionnaires [8, 25]. The other study [26] evaluated masticatory muscle electromyographic activity. Thus, a meta-analysis was not feasible.

The electromyographic activity of the masseter muscle significantly increased after the installation and regular activation of clear aligners [26]. However, after two weeks of correct use, muscle activity returned to baseline levels [26]. Thus, the authors suggested that the mere presence of the clear aligner itself seems to be a significant contributing factor to increase masseter activity, rather than the actual tooth pain from orthodontic tooth movement [26].

In terms of self-reported chewing ability, patients using conventional fixed labial appliances reported greater discomfort while chewing than the clear aligner group, especially after the installation and during the first two months of treatment [8]. Patients using clear aligners also reported better chewing ability (P < 0.001), no restrictions on the amounts or types of food (P = 0.02), and less mucosal ulcerations (P = 0.01) [8]. No

38 significant differences in swallowing threshold were found among patients of both groups

[8].

Orthodontic pain of clear aligners wearers was comparable to those using labial appliances [8]. Both groups reported similar pain levels. However, patients with clear aligners experienced more pressure-like pain (P = 0.016), whereas patients with conventional fixed labial appliances reported more throbbing and dull pain (P = 0.037 and .019, respectively) [8]. Similar analgesics consumption was reported by both groups

(P = 0.062) [8].

Discussion

This systematic review is one of the first to evaluate the influence of different orthodontic appliances on mastication and nutrition, mainly focusing on the activation and/or installation period. This review indicated that very few studies had been carried out to explore this topic, and no high‐quality evidence is available, especially regarding nutrition. However, the meta-analysis showed that the masticatory performance and bite force significantly decreased after the installation and/or activation, especially in patients using labial fixed appliances. These masticatory changes are transitory, and it seems to recover within the two to three weeks of treatment. On the other hand, considering that most orthodontic patients are young and in growing age, this temporary masticatory reduction might impact the bioavailability of nutrients with possible consequences to the patient’s nutritional health. However, scarce evidence was found with regards to the nutritional changes, jeopardizing further conclusions.

In respect to the fixed labial appliances, masticatory performance (X50) reduced after 24 hours of activation (SMD = 1.069; 95% CI: 0.619, 1.518; P = 0.000) but, after

30 days, it was recovered entirely (P > 0.05) (Fig. 3). Similar results were reported in

39 previous studies [3, 5, 18], suggesting that this reduction seems to be associated with the acute inflammation process and the peak of the pain symptoms, which generally occur 24 to 48 hours after the activation. Moreover, nociceptors of moved teeth are usually sensitized after the orthodontic force is applied, which may explain the alterations in jaw movement dynamics. Consequently, a reduction was observed in masticatory performance [5].

A second mastication analysis was performed considering the particle size (X50) when swallowing (Fig. 4). Different from the masticatory performance, the swallowing threshold (particle size and number of cycles) was not compromised by the activation or installation of labial fixed appliances (P > 0.05). Previous studies also reported this behavior [3, 5]. Furthermore, it is known that subjects with poor mastication do not necessarily use more chewing strokes to prepare their food, but they usually swallow larger particles [5, 28]. However, this theory was not confirmed in the present review since the particle size remained constant in the different follow-up periods (Fig. 4). In this context, it is important to highlight that only significant changes in the occlusal pattern are related to bigger particle size swallow. Thus, progressive teeth movements and temporary pain may not be strong enough to cause swallowing threshold interferences.

A significant reduction in bite force was also observed one week after the activation of the fixed labial appliance (SMD = -2.542 (95% CI: -4.867 to -0,217; P =

0.032) (Fig. 5). This finding was expected since bite force is one of the most critical factors responsible for masticatory performance variability (R2 = 0.55, P < 0.001)[29].

Also, similar results were observed in previous studies [19, 21], where a reduction of 50% in bite force was noticed after one week of fixed labial appliance installation. This reduction can be related to two main factors: transient changes of occlusal support and pain or sensibility of the periodontal mechanoreceptors. Changes in the occlusal contacts

40 seem to explain 10–20% of maximum bite force variation in adults [30]. These transient changes seem more relevant just after installing the appliances, where a more significant deflection is observed to obtain bracket engagement [31]. Moreover, the pain levels significantly increased in the first 48 hours (SMD = 1.547; 95% CI: 1.126 to 1.967; P =

0.000) after installing the fixed labial appliances, which might have contributed to reducing both bite force and masticatory performance. Therefore, orthodontists should be aware of fixed labial appliances’ effects on general masticatory function, and this information should be given to the patient before the intervention.

Dietary changes might be expected after the appliances are installed, mainly because of the pain but mostly because of the instructions that orthodontists give their patients to avoid eating hard and sweet content foods to reduce caries and prevent the appliances' damage. However, in this present review, only one study [22] investigating nutritional changes after fixed labial appliance activation was found, preventing further analysis. Despite that, the authors reported a substantial reduction in the levels of copper and manganese [22]. Copper is an essential nutrient required for hemoglobin formation and iron transport to bone marrow for red blood cell production [32]. At the same time, manganese plays a crucial role in bone remodelling and glucose metabolism [32].

Deficiencies of these two nutrients are linked to anemia, neutropenia, bone disease, poor reproductive performance, and impaired glucose tolerance [33]. Rich copper and manganese sources are shellfish, organ meats, nuts, whole grains, and vegetables. Some of these foods are usually avoided by orthodontic patients. The authors also reported an increase in total calories and saturated fat after activating a fixed labial appliance, with a reduced carbohydrate intake [22]. Consistent with these findings, Shirazi et al. [34] showed that orthodontic patients present a greater intake of fat and cholesterol and a significantly lower intake of fibre, chromium, and beta-carotene than subjects not using

41 an orthodontic appliance. After the appliance instalation, most patients moved to a soft and fat diet because it was easier to chew and less painful [35]. It is known that a high- fat diet is associated with obesity, increasing the risk of hypertension, cardiovascular disease, atherosclerosis, and noninsulin-dependent diabetes [36].

On the other hand, nutritional alterations, especially regarding nutrient bioavailability (blood nutritional levels), depending on several factors and are not automatically linked to masticatory improvements or impairments. Surprisingly, although orthodontic patients report difficulty eating and chewing due to the pain and discomfort experienced, they felt that their eating habits were healthier than pre-treatment [35].

Nevertheless, these findings were reported by only a few studies, with a small sample and extremely heterogeneous methodologies. Therefore, further researchers are encouraged to analyze the relationship between orthodontic appliances and long-term nutritional changes.

Lingual fixed appliances represent a good alternative for aesthetic orthodontic treatment [37]. However, specific knowledge of its effect on mastication and nutrition is scarce, mainly quantitative and objective measurements. According to Hohoff et al. [27], patients report significantly more chewing difficulties just after the fixed lingual appliance installation, and it remained up to 3 months. However, in comparison to fixed labial appliances, contrasting results were found. According to Khattab et al. [23], patients using fixed lingual appliances were more prone to moderate and severe mastication impairments than those from the fixed labial group, especially following the appliance placement. On the other hand, Wu et al. [24] reported no significant difference in biting or chewing between patients treated with labial and lingual orthodontic appliances.

However, in this prior study, significant dietary changes and avoidance of eating out were more frequently reported by patients treated with lingual appliances than those using

42 labial appliances [24]. Nevertheless, due to the scarce evidence found and these contrasting results, it is challenging to conclude the differences in masticatory capacity, eating behavior or even nutritional changes between the two orthodontic modalities.

Similarly, only a few studies [8, 25, 26] evaluated the masticatory function of clear aligners wearers, but no mention of nutrition outcomes was found. According to

Lou et al. [26], the use of clear aligners produces a transient increase in masseter muscle activity within the first two weeks of treatment, decreasing towards baseline values after that. Compared to fixed labial appliances, patients using clear aligners reported more comfortable eating and chewing, especially immediately following the appliance’s placement [8, 25]. After seven days, clean aligner wearers experienced minimal discomfort [25] and, according to Alajmi et al. [8], the lower masticatory impairments of clear aligners wearers might be related to the fact that the appliance can be temporarily removed during meals, reducing the frequency of tongue or mucosa ulcerations.

Moreover, patients with clear aligners experienced more pressure-like pain. Patients using conventional fixed labial appliances reported more throbbing and dull pain and higher analgesic consumption, even though the total pain levels were similar between groups [8]. These pain sensitivity differences might have also contributed to explaining patients’ higher chewing discomfort using fixed labial appliances.

This systematic review has some limitations, including a lack of high-quality studies, small sample sizes, a limited follow-up period, subjective assessment of the outcomes, and insufficient evidence to support further conclusions, especially fixed lingual appliances and clear aligners. Future randomized clinical trials are needed to understand better the range of masticatory and nutritional alterations during orthodontic treatment. This is likely to help us identify the marked deviations and alleviate causative

43 agents, thereby improving mastication and nutrition quality even during orthodontic treatment.

Conclusions Current evidence suggests a low to a very low level of certainty (GRADE assessment) regarding the effects of different orthodontic appliances on patients’ mastication and nutrition. Weak evidence suggests that the activation and/or installation of fixed labial appliances temporarily reduces the masticatory performance and bite force

(24 to 48 hours). After 30 days, the masticatory function is recovered. Nutritional impact and the effects of fixed lingual appliances and clear aligners over mastication were not conclusive.

Acknowledgments

The authors would like to acknowledge the assistance of the librarian Goreti M.

Savi from the Federal University of Santa Catarina.

Funding

This work was financed in part by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for supporting academic and professional development.

References

[1] G.H. Gameiro, J.S. Pereira-Neto, M.B. Magnani, D.F. Nouer, The influence of drugs and systemic factors on orthodontic tooth movement, J Clin Orthod 41 (2007) 73-78, .

[2] V. Krishnan, Z. Davidovitch, Cellular, molecular, and tissue-level reactions to orthodontic force, Am J Orthod Dentofacial Orthop 129 (2006) 469 e1-32.

[3] M.P. Trein, K.S. Mundstock, L. Maciel, J. Rachor, G.H. Gameiro, Pain, masticatory performance and swallowing threshold in orthodontic patients, Dental Press J Orthod 18

(2013) 117-123.

[4] H. Goldreich, E. Gazit, M.A. Lieberman, J.D. Rugh, The effect of pain from orthodontic arch wire adjustment on masseter muscle electromyographic activity, Am J

Orthod Dentofacial Orthop 106 (1994) 365-370.

[5] I.B. Magalhaes, L.J. Pereira, A.S. Andrade, D.B. Gouvea, G.H. Gameiro, The influence of fixed orthodontic appliances on masticatory and swallowing threshold performances, J Oral Rehabil 41 (2014) 897-903.

[6] A. Silva Andrade, M. Marcon Szymanski, L.N. Hashizume, K. Santos Mundstock, J.

Ferraz Goularte, G. Hauber Gameiro, Evaluation of stress biomarkers and electrolytes in saliva of patients undergoing fixed orthodontic treatment, Minerva Stomatol 67 (2018)

172-178.

[7] H. Long, Y. Zhou, U. Pyakurel, L. Liao, F. Jian, J. Xue, N. Ye, X. Yang, Y. Wang,

W. Lai, Comparison of adverse effects between lingual and labial orthodontic treatment,

Angle Orthod 83 (2013) 1066-1073.

[8] S. Alajmi, A. Shaban, R. Al-Azemi, Comparison of Short-Term Oral Impacts

Experienced by Patients Treated with Invisalign or Conventional Fixed Orthodontic

Appliances, Med Princ Pract 29 (2020) 382-388.

[9] L.A. Carter, M. Geldenhuys, P.J. Moynihan, D.R. Slater, C.E. Exley, S.L. Rolland,

The impact of orthodontic appliances on eating - young people's views and experiences,

J Orthod 42 (2015) 114-122.

[10] M.J. Page, J.E. McKenzie, P.M. Bossuyt, I. Boutron, T.C. Hoffmann, C.D. Mulrow,

L. Shamseer, J.M. Tetzlaff, E.A. Akl, S.E. Brennan, R. Chou, J. Glanville, J.M.

Grimshaw, A. Hrobjartsson, M.M. Lalu, T. Li, E.W. Loder, E. Mayo-Wilson, S.

McDonald, L.A. McGuinness, L.A. Stewart, J. Thomas, A.C. Tricco, V.A. Welch, P.

Whiting, D. Moher, The PRISMA 2020 statement: An updated guideline for reporting systematic reviews, PLoS Med 18 (2021) e1003583.

[11] T. Greenhalgh, R. Peacock, Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources, BMJ 331 (2005) 1064-

1065.

[12] M. Ouzzani, H. Hammady, Z. Fedorowicz, A. Elmagarmid, Rayyan-a web and mobile app for systematic reviews, Syst Rev 5 (2016) 210.

[13] J.A.C. Sterne, J. Savovic, M.J. Page, R.G. Elbers, N.S. Blencowe, I. Boutron, C.J.

Cates, H.Y. Cheng, M.S. Corbett, S.M. Eldridge, J.R. Emberson, M.A. Hernan, S.

Hopewell, A. Hrobjartsson, D.R. Junqueira, P. Juni, J.J. Kirkham, T. Lasserson, T. Li, A.

McAleenan, B.C. Reeves, S. Shepperd, I. Shrier, L.A. Stewart, K. Tilling, I.R. White,

P.F. Whiting, J.P.T. Higgins, RoB 2: a revised tool for assessing risk of bias in randomised trials, BMJ 366 (2019) l4898.

[14] J.A. Sterne, M.A. Hernan, B.C. Reeves, J. Savovic, N.D. Berkman, M. Viswanathan,

D. Henry, D.G. Altman, M.T. Ansari, I. Boutron, J.R. Carpenter, A.W. Chan, R.

Churchill, J.J. Deeks, A. Hrobjartsson, J. Kirkham, P. Juni, Y.K. Loke, T.D. Pigott, C.R.

Ramsay, D. Regidor, H.R. Rothstein, L. Sandhu, P.L. Santaguida, H.J. Schunemann, B.

Shea, I. Shrier, P. Tugwell, L. Turner, J.C. Valentine, H. Waddington, E. Waters, G.A.

Wells, P.F. Whiting, J.P. Higgins, ROBINS-I: a tool for assessing risk of bias in non- randomised studies of interventions, BMJ 355 (2016) i4919.

[15] G.S. Higgins JPT, Cochrane Handbook for Systematic Reviews of Interventions

Version 5.1.0 [updated March 2011]. The Cochrane Collaboration2011.

[16] L.A. McGuinness, J.P.T. Higgins, Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments, Res Synth Methods

12 (2021) 55-61.

[17] E. Manheimer, Summary of Findings Tables: Presenting the Main Findings of

Cochrane Complementary and Alternative Medicine-related Reviews in a Transparent and Simple Tabular Format, Glob Adv Health Med 1 (2012) 90-91.

[18] G.H. Gameiro, C. Schultz, M.P. Trein, K.S. Mundstock, P. Weidlich, J.F. Goularte,

Association among pain, masticatory performance, and proinflammatory cytokines in crevicular fluid during orthodontic treatment, Am J Orthod Dentofacial Orthop 148

(2015) 967-973.

[19] S.A. Alomari, E.S. Alhaija, Occlusal bite force changes during 6 months of orthodontic treatment with fixed appliances, Aust Orthod J 28 (2012) 197-203.

[20] N. Mansor, R. Saub, S.A. Othman, Changes in the oral health-related quality of life

24 h following insertion of fixed orthodontic appliances, J Orthod Sci 1 (2012) 98-102.

[21] A. Prema, G. Vimala, U. Rao, A. Shameer, Gayathri, Occlusal bite force changes during fixed orthodontic treatment in patients with different vertical facial morphology,

Saudi Dent J 31 (2019) 355-359.

[22] D.J. Riordan, Effects of orthodontic treatment on nutrient intake, Am J Orthod

Dentofacial Orthop 111 (1997) 554-561.

[23] T.Z. Khattab, H. Farah, R. Al-Sabbagh, M.Y. Hajeer, Y. Haj-Hamed, Speech performance and oral impairments with lingual and labial orthodontic appliances in the first stage of fixed treatment, Angle Orthod 83 (2013) 519-526.

[24] A. Wu, C. McGrath, R.W. Wong, D. Wiechmann, A.B. Rabie, Comparison of oral impacts experienced by patients treated with labial or customized lingual fixed orthodontic appliances, Am J Orthod Dentofacial Orthop 139 (2011) 784-790.

[25] D.W. White, K.C. Julien, H. Jacob, P.M. Campbell, P.H. Buschang, Discomfort associated with Invisalign and traditional brackets: A randomized, prospective trial,

Angle Orthod 87 (2017) 801-808.

[26] T. Lou, J. Tran, T. Castroflorio, A. Tassi, I. Cioffi, Evaluation of masticatory muscle response to clear aligner therapy using ambulatory electromyographic recording, Am J

Orthod Dentofacial Orthop 159 (2021) e25-e33.

[27] A. Hohoff, D. Fillion, T. Stamm, G. Goder, C. Sauerland, U. Ehmer, Oral comfort, function and hygiene in patients with lingual brackets. A prospective longitudinal study,

J Orofac Orthop 64 (2003) 359-371.

[28] F.A. Fontijn-Tekamp, A. van der Bilt, J.H. Abbink, F. Bosman, Swallowing threshold and masticatory performance in dentate adults, Physiol Behav 83 (2004) 431-

436.

[29] J.P. Hatch, R.S. Shinkai, S. Sakai, J.D. Rugh, E.D. Paunovich, Determinants of masticatory performance in dentate adults, Arch Oral Biol 46 (2001) 641-648.

[30] M. Bakke, A. Tuxen, P. Vilmann, B.R. Jensen, A. Vilmann, M. Toft, Ultrasound image of human masseter muscle related to bite force, electromyography, facial morphology, and occlusal factors, Scand J Dent Res 100 (1992) 164-171.

[31] V. Krishnan, Orthodontic pain: from causes to management--a review, Eur J Orthod

29 (2007) 170-179.

[32] L. Strause, P. Saltman, Role of manganese in bone metabolism., in: C. Kies (Ed.),

Nutritional bioavailability of manganese, American Chemical Society1987.

[33] Recommended Dietary Allowances: 10th Edition, Washington (DC), 1989.

[34] A.S. Shirazi, M.G. Mobarhan, E. Nik, N. Kerayechian, G.A. Ferns, Comparison of dietary intake between fixed orthodontic patients and control subjects, Aust Orthod J 27

(2011) 17-22.

[35] F. Abed Al Jawad, S.J. Cunningham, N. Croft, A. Johal, A qualitative study of the early effects of fixed orthodontic treatment on dietary intake and behaviour in adolescent patients, Eur J Orthod 34 (2012) 432-436.

[36] C.D. Sjostrom, L. Lissner, H. Wedel, L. Sjostrom, Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study, Obes Res 7 (1999) 477-484.

[37] I. Mistakidis, H. Katib, G. Vasilakos, D. Kloukos, N. Gkantidis, Clinical outcomes of lingual orthodontic treatment: a systematic review, Eur J Orthod 38 (2016) 447-458.

Table 1 Main characteristics of the included studies (n=15). Mean Age Experime Follow-up Author, ± Study ntal time (before Nutrition Pain After Year Standard Mastication Outcomes Main conclusions design Groups and after Outcomes activation (Country) Deviation (n) installation) (years) VAS (mm) 4.46 ± 2.67 (T1) 3.07 ± 2.46 Bite Force (N) (T2) Control 418.9 ± 135.8 (T0) Baseline (T0) 1.43 ± 1.91 (normal 152.8 ± 109.5 (T1) One week (T3) Non- occlusion) 212.8 ± 114.3 (T2) Bite force significantly reduces (50%) Alomari et (T1) 0.98 ± 1.60 randomized (n=47) 310.7 ± 142.1 (T3) after the fixed labial appliance al., 2012 19.0 ± 3.4 Two weeks N/A (T4) Clinical Fixed 359.9 ± 135.6 (T4) installation but, with the time, it returns (Jordan) (T2) 0.29 ± 1.12 Trial labial 391.2 ± 129.3 (T5) to the pretreatment levels. 1-6 months (T5) appliance 383.1 ± 135.5 (T6) (T3-T8) 0.50 ± 1.24 (n=47) 397.8 ± 126.8 (T7) (T6) 408.5 ± 123.8 (T8) 0.15 ± 0.70 (T7) 0.24 ± 0.82 (T8) Clear aligner group reported more Likert-scale Clear Clear comfortable eating and chewing Eating limitations (Questionnaire) questionnaire Aligner Aligner compared to fixed labial appliances, due Non- Clear Aligner Clear Aligner Alajmi et (n=30) 32.9±6.9 to the fact that subjects with Invisalign randomized 6 (20%) 5.4 ± 1.8 al., 2019 Fixed Fixed 1 week N/A have the ability to remove their Clinical (Kuwait) Labial Labial appliance temporarily during meals. Trial Fixed Labial Appliance Fixed Labial Appliance Appliance However, clear aligners affect 23 (76.6%) Appliance (n=30) 23.6±5.3 pronunciation and speech delivery in 5.4 ± 2 the short term.

Control VAS (mm) (normal The masticatory performance of Gameiro Non- 9.6 ± 16.7 occlusion) Masticatory Performance (X50) patients using fixed labial appliances is et al., 2015 randomized Baseline (T0) (T0) (n=15) 6.6±2.2 (T0) reduced at 24 hours after arch wire Andrade Clinical 18 ± 4 24 hours (T1) N/A 61.3 ± 32.8 Fixed 8.7±2.0 (T1) placement and returned to basal levels et al, 2018 Trial 1 month (T2) (T1) labial 6.5±1.8 (T2) after 1 month, but remains still lower (Brazil) 13.0 ± 22.3 appliance than that of the controls. (T2) (n=20) EGM Masseter fixed labial < placebo Fixed In comparison to a placebo, the Peanuts (t21 = 3.41, p < 0.05). VAS (mm) Labial activation of fixed labial appliance Non- Chewing gum (t19 = 3.89, 0.29±0.35 Goldreich Appliance significantly decreased the masseter randomized 11-15 Baseline (T0) p < 0.05). (T0) et al., 1994 (n=22) N/A EMG activity while chewing. Clinical Years 48 hours (T1) 4.92±2.59 (Israel) Placebo Orthodontic patients take more strokes Trial Swallowing Threshold (number (T1) Control to prepare the food but the size of the cycles) (n=22) swallowed particles remains constant. fixed labial > placebo (t20 = - 1.77, p< 0.04) Chewing Difficulties After placement of the fixed lingual Hohoff et Non- Fixed Baseline (T0) (Questionnaire) appliance, the patients reported al., 2003 randomized Lingual 34.7 ± 10.4 24 hours (T1) T0 vs. T1 (p < 0.000) N/A N/A significantly more difficulty in (Germany Clinical Appliance 3 months (T2) T1 vs. T2 (p = 0.024) chewing. These difficulties remain up to ) Trial (n=22) T2 vs. T0 (p ≤ 0.001) 3 months before brackets placement. Chewing Difficulties Fixed (Questionnaire) Immediately following appliance Labial Fixed Labial Appliance placement, patients from fixed lingual Baseline (T0) Appliance T0 vs. T1 (p = 0.02) appliances had more moderate to severe Khattab et Randomized Immediately (n=17) T0 vs. T2 (NS) mastication impairment, while only al., 2013 Clinical 21.3 ± 3.1 (T1) N/A N/A Fixed T0 vs. T3 (NS) 17.7% of patients using fixed labial (Syria) Trial 1 month (T2) Lingual Fixed Lingual Appliance appliances reported only moderate 3 months (T3) Appliance T0 vs. T1 (p < 0.001) difficulties. After 1 month, these (n=17) T0 vs. T2 (p = 0.009) differences were not significant. T0 vs. T3 (NS)

Clear aligner therapy produces a Non- Baseline Lou et al., Clear transient increase in masseter muscle randomized One, two, 2021 Aligner 35.3 ± 17.6 EGM Masseter N/A N/A activity within the first two weeks of Clinical three, and four (Canada) (n=17) treatment and decreases towards Trial Weeks baseline thereafter.

Masticatory Performance (X50) 5.6±1.0 (T0) 5.9±1.1 (T1) 7.5±2.8 (T2) 5.9±1.4 (T3) VAS (mm) 5.9±1.5(T4) 10.9 ± 17.2 Masticatory performance is reduced, Swallowing Threshold (X50) (T0) and the swallowing threshold for harder Before (T0) 4.6±1.3 (T0) 22.5 ± 20.3 foods is increased at the peak of Magalhãe Non- Fixed Immediately 4.5±1.2 (T1) (T1) orthodontic pain (48h after archwire s et al., randomized Labial (T1) 21.1 ± 10.4 5.6±3.2 (T2) N/A 52.7 ± 34.4 placement). At long-term follow-up 2014 Clinical Appliance 48 hours (T2) 4,5±1.5 (T3) (T2) examination, masticatory and (Brazil) Trial (n=27) 1 month (T3) 4.2±1.1(T4) 17.8 ± 22.9 swallowing performances return to 3 months (T4) Swallowing Threshold (number (T3) those observed before the appliance of cycles) 7.4 ± 15.5 placement. 34.2±14.7 (T0) (T4) 30.6±11.4 (T1) 34.4±13.4 (T2) 32.2±12.4 (T3) 32.4±13.5(T4) Non- Fixed OHRQoL deteriorates 24 h following Mansor et OHIP-16 (Eating avoidances) OHIP-16 randomized Labial Before (T0) insertion of fixed orthodontic al., 2012 17.8 ± 3.1 1.8±1.0 (T0) N/A 2.0±0.8 (T0) Clinical Appliance 24 hours (T1) appliances, with significant impact over (Malaysia) 4.2±1.0 (T1) 3.5±1.2 (T1) Trial (n=60) the masticatory capacity.

Bite Force (N) Bite force is reduced to 50% of the 469.4± 69.2(T0) Baseline (T0) pretreatment level during the first week 191.7 ± 62.9 (T1) Non- Fixed One week of fixed labial appliance. After aligning Prema et 230.6 ± 60.9(T2) randomized Labial (T1). and leveling stage, the bite force reaches al., 2019 N/A 257.3 ± 42.4 (T3) N/A N/A Clinical Appliance One to six the baseline level in hyperdivergent (India) 306.6 ± 52.2 (T4) Trial (n=30) months (T2- treatment group, while it reaches close 320.6 ± 48.1 (T5) T7) to pretreatment level in hypodivergent 343.9 ± 42.8 (T6) and normodivergent treatment groups. 389.2 ± 38.6 (T7) 3 Days-dairy Cooper 1.23 ± 0.61 (T0) 0.85 ± 0.69 (T1) (p=0.002) It may be beneficial to provide Manganese nutritional guidance to orthodontic Non- Fixed 2.85 ± 1.63 (T0) patients in order to increase the copper Riordan et randomized Labial 12-16 Baseline (T0) 2.08 ± 2.06 (T1) and manganese content of the diet. al., 1997 N/A N/A Clinical Appliance Years 72 hours (T1) (p=0.016) Further research with a larger sample (USA) Trial (n=10) Calories from fat size would uncover the magnitude of the 49.32% to 55.54% effects of orthodontic treatment on Calories from nutrient intake. carbohydrates 36.71% to 32.14%.

Masticatory Performance (X50) Masticatory performance of orthodontic 7.01±2.9 (T0) VAS (mm) patients significantly reduces one day Non- Fixed 10.2±1.1 (T1) after installation and activation of fixed Trein et Baseline (T0) 0.60 ± 0.70 randomized Labial 6.8±1.3 (T2) labial appliance appliances. This period al., 2013 17.3 ± 5.2 24 hours (T1) N/A (T0) Clinical Appliance Swallowing Threshold (X50) represents the peak time of orthodontic (Brazil) 1 month (T2) 66.2 ± 34.5 Trial (n=10) 5.5±2.4 (T0) (T1) pain, which tends to decrease with time 6.2±2.1 (T1) 3.20±3. (T2) with consequently recovery of the 5.9±2.4 (T2) mastication.

Swallowing Threshold (number of cycles) 26.7±9.1 (T0) 31.4±13 (T1) 23.3±10.5 (T2) Difficult in chewing (VAS – mm) Baseline (T0) Immediately following appliance Clear T0 - NS Day 1(T1) placement, fixed labial appliances Aligner T1 - NS Day 2 (T2) produced more discomfort while White et Randomized (n=23) T2 – NS Day 3(T3) chewing than did clear aligners. By day al., 2017 Clinical Fixed N/A T3 – clear < labial (p = 0.04) N/A N/A Day 4 (T4) seven, patients in the aligner group (USA) Trial Labial T4 - clear < labial (p = 0.03) Day 5 (T5) experienced minimal discomfort, Appliance T5 – clear < labial (p = 0.04) Day 6 (T6) consistently less than baseline (n=18) T6 – clear < labial (p = 0.01) Day 7 (T7) discomfort. T7 - clear < labial (p = 0.008) In terms of impact on mastication, there Fixed Fixed VAS (mm) was no significant difference reported in Labial VAS (mm) Labial Dietary changes – biting or chewing between patients Appliance Difficult in chewing – labial vs. Wu et al., Non- Appliance labial < lingual – treated with labial and lingual (20.3 ±4.2) 1 to 12 weeks lingual – NS 2011 randomized (n=30) (p<0.001) orthodontic appliances. Oral impact 1 month Difficult in biting – labial vs. N/A (Hong Clinical Fixed Avoidance of disturbances were most common in the Fixed 3 months lingual – NS Kong) Trial Lingual eating out - labial early phase of treatment. By the end of Lingual Difficult in swallowing – labial < Appliance < lingual – 3 months, oral impacts were comparable Appliance lingual (p<0.05) (n=30) (p<0.001) for those treated with both labial and (21.6±2.2) customized lingual appliances.

Table 2 Results of quality assessment of studies included in the meta-analysis. (The Grading of Recommendations Assessment, Development and Evaluation – GRADE). Certainty assessment Nº of Outcome Study design Risk of bias Inconsistency Indirectness Imprecision Others Certainty studies Masticatory Outcomes Masticatory Performance Observational 3 seriousª seriousb not serious seriousc none ⨁◯◯◯ studies VERY LOW Swallowing Threshold Observational ⨁⨁ (particle size) 2 seriousa not serious not serious seriousc none ◯◯ studies LOW Swallowing Threshold Observational ⨁⨁ (nº of cycles) 3 seriousa not serious not serious seriousc none ◯◯ studies LOW Observational ⨁ Bite Force 2 not serious very seriousd not serious seriousc none ◯◯◯ studies VERY LOW Pain Assessment Observational ⨁⨁ Visual Analogue Scale 6 seriousa not serious not serious seriousc none ◯◯ studies LOW

Explanations: a Serious risk of bias of included studies b Significant heterogeneity (I²=78%) between studies at 24h x 30 days comparisons. c Sample size of less than 400 participants among included studies. d High heterogeneity (I²=94%) between studies.

FIGURES PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources

Identification of studies via databases and registers Identification of studies via other methods

Records identified from: PubMed (n =3832) Records removed before Embase (n=6511) screening: Records identified from: LILACS (n=20) Duplicate records removed Google Scholar (n = 100) Identification Proquest (n =92) Web of Science (n=1222) (n =11377) Scopus (n=3288) Open Grey (n=3) Cochrane Library (n=315) Citation searching (n =1) Total (n= 15188)

Records excluded (n =4185) Records screened (n =4226)

Reports not retrieved (n = 0) Reports sought for retrieval Reports sought for retrieval Reports not retrieved (n =41) (n = 196) (n = 0) Reports excluded: Screening Patients who were using removable appliances differently of clear aligners (n=3); Patients with temporomandibular disorders and/or myofascial pain(n=0); Reports assessed for eligibility Outcomes not evaluated after activation of Reports assessed for eligibility (n =41) fixed appliances/clear aligners (n=19); (n =196) Patients who were not undergoing orthodontic treatment (n=0); Reports excluded (n=195) Studies not evaluating masticatory and nutritional outcomes of patients using fixed orthodontic appliances (n=4); Reviews, letters, conference abstract, personal opinions, case reports, technique articles (n=0); Animal models or experimental in vitro Studies included in review studies (n=0); (n =14) Studies with missing data and not provided Included Reports of included studies by the author (n=0); (n = 1) Studies with less than 10 subjects (n=1).

Fig. 1 Flowchart of selection process (PRISMA 2020).

Fig. 2 Risk of bias summary on reviewers’ judgements about each risk of bias item according to the different study designs (2.1. Risk of bias assessment for randomized clinical trials (ROB

2.0 tool); 2.2. Risk of bias assessment for Nonrandomized studies (ROBINS-I tool)).

Figure 3. Forest plots of masticatory performance (X50) after the activation of fixed labial appliances (3.1. Comparisons between baseline and 24 hours of activation; 3.2. Comparisons between baseline and 30 days of activation; 3.3. Comparisons between 24 hours and 30 days of activation).

Figure 4. Forest plots of swallowing threshold (particle size and number of cycles) after the activation of fixed labial appliances (4.1. Comparisons between baseline and < 48 hours; 4.2.

Comparisons between baseline and 30 days of activation; 4.3. Comparisons between baseline and < 48 hours; 4.4. Comparisons between baseline and 30 days of activation).

Figure 5. Forest plots of bite force comparisons before and one week after the activation of fixed labial appliances.

Figure 6. Forest plots of pain levels before and after the activation of fixed labial appliances

(6.1. Comparisons between baseline and 24 hours of activation; 6.2. Comparisons between baseline and 48 hours of activation; 6.3. Comparisons between 24 hours and 30 days of activation; 6.4. Comparisons between baseline and 30 days of activation).

Supplemental Material

Supplemental Table 1: Terms included on each database search.

SEARCH TERMS AND DATABASES DATABASE SEARCH N. Pubmed ("Orthodontics"[Mesh:NoExp] OR "orthodontic" OR "orthodontics" OR "Orthodontic 3832 Appliances"[Mesh] OR "Orthodontic Appliance" OR "Orthodontic Appliances" OR "Orthodontic Appliances, Fixed"[Mesh] OR "Fixed Orthodontic Appliance" OR "Fixed Orthodontic Appliances" OR "Fixed Functional Appliance" OR "Fixed Functional Appliances" OR "Fixed Retainer" OR "Fixed Retainers" OR "fixed appliance" OR "fixed appliances" OR "Permanent Retainer" OR "Permanent Retainers" OR "fixed treatment" OR "fixed treatments" OR "Activator Appliances"[Mesh] OR "activator appliance" OR "activator appliances" OR "Function Activator" OR "Function Activators" OR "Orthodontic Wires"[Mesh] OR "orthodontic wire" OR "orthodontic wires" OR "orthodontic arch wire" OR "orthodontic arch wires" OR "Tooth Movement Techniques"[Mesh] OR "Tooth Movement" OR "Tooth Movements" OR "Teeth Movement" OR "Teeth Movements" OR "Orthodontic Tooth Movement" OR "Orthodontic Tooth Movements" OR "orthodontic teeth movement" OR "orthodontic teeth movements" OR "orthodontic movement" OR "Orthodontic Brackets"[Mesh] OR "bracket" OR "brackets" OR "Orthodontic Brace" OR "Dental Braces" OR "Dental Brace" OR "Orthodontic Appliances, Removable"[Mesh] OR "Removable Orthodontic Appliance" OR "Removable Orthodontic Appliances" OR "Clear Aligner" OR "clear aligners" OR "Invisalign") AND ("Mastication"[Mesh] OR "Mastication" OR "chewing" OR "masticatory" OR "biting ability" OR "biting abilities" OR "chewing movement" OR "chewing movements" OR "sieving method" OR "mixing ability test" OR "jaw motion" OR "Deglutition"[Mesh] OR "Deglutition" OR swallowing OR "Bite Force"[Mesh] OR "bite force" OR "bite forces" OR "Occlusal Force" OR "Occlusal Forces" OR "Masticatory Force" OR "Masticatory Forces" OR "maximum occlusal force" OR "maximum occlusal forces" OR "Masticatory Muscles"[Mesh] OR "Masticatory Muscles" OR "Masticatory Muscle" OR "Masseter Muscle"[Mesh] OR "Masseter Muscle" OR "Masseter Muscles" OR "muscle thickness" OR "masseter thickness" OR "Electromyography"[Mesh] OR "Electromyography" OR "Electromyographies" OR "Surface Electromyography" OR "Surface Electromyographies" OR "Electromyogram" OR "Electromyograms" OR "electromyographic activity" OR "nutritional intake" OR "nutritional level" OR "nutrient intake" OR "nutrients intake" OR "diet questionnaires" OR "anthropometric measurement" OR "anthropometric measurements" OR "Nutritional Status"[Mesh] OR "nutritional status" OR "Nutrition Status" OR "Nutrition Assessment"[Mesh] OR "nutrition assessment" OR "nutrition assessments" OR "nutritional Assessment" OR "nutritional assessments" OR "nutrition index" OR "nutrition indexes" OR "Nutritional Index" OR "Nutritional Indices" OR "Malnutrition"[Mesh] OR "malnutrition" OR "nutritional deficiency" OR "nutritional deficiencies" OR "undernutrition" OR "malnourishment") Scopus TITLE-ABS-KEY ( orthodontic OR orthodontics OR "Orthodontic Appliance" OR 3288 "Orthodontic Appliances" OR "Fixed Orthodontic Appliance" OR "Fixed Orthodontic Appliances" OR "Fixed Functional Appliance" OR "Fixed Functional Appliances" OR "Fixed Retainer" OR "Fixed Retainers" OR "fixed appliance" OR "fixed appliances" OR "Permanent Retainer" OR "Permanent Retainers" OR "fixed treatment" OR "fixed treatments" OR "activator appliance" OR "activator appliances" OR "Function Activator" OR "Function Activators" OR "orthodontic wire" OR "orthodontic wires" OR "orthodontic arch wire" OR "orthodontic arch wires" OR "Tooth Movement" OR "Tooth Movements" OR "Teeth Movement" OR "Teeth Movements" OR "Orthodontic Tooth Movement" OR "Orthodontic Tooth Movements" OR "orthodontic teeth movement" OR "orthodontic teeth movements" OR "orthodontic movement" OR "bracket" OR "brackets" OR "Orthodontic Brace" OR "Dental Braces" OR "Dental Brace" OR "Removable Orthodontic Appliance" OR "Removable Orthodontic Appliances" OR "Clear Aligner" OR "clear aligners" OR "Invisalign" OR "Activator Orthodontic Appliance" OR "Activator Orthodontic Appliances" OR "orthodontic activator appliance" OR "orthodontic activator appliances" OR "Clear Dental Braces" OR "Clear Dental Brace" OR "invisaligner" OR "invisaligners" ) AND TITLE-ABS-KEY ( "Mastication" OR "chewing" OR "masticatory" OR "biting ability" OR "biting abilities" OR "chewing movement" OR "chewing movements" OR "sieving method" OR "mixing ability test" OR "jaw motion" OR "Deglutition" OR swallowing OR "bite force" OR "bite forces" OR "Occlusal Force" OR "Occlusal Forces" OR "Masticatory

Force" OR "Masticatory Forces" OR "maximum occlusal force" OR "maximum occlusal forces" OR "Masticatory Muscles" OR "Masticatory Muscle" OR "Masseter Muscle" OR "Masseter Muscles" OR "muscle thickness" OR "masseter thickness" OR "Electromyography" OR "Electromyographies" OR "Surface Electromyography" OR "Surface Electromyographies" OR "Electromyogram" OR "Electromyograms" OR "electromyographic activity" OR "nutritional intake" OR "nutritional level" OR "nutrient intake" OR "nutrients intake" OR "diet questionnaires" OR "anthropometric measurement" OR "anthropometric measurements" OR "nutritional status" OR "Nutrition Status" OR "nutrition assessment" OR "nutrition assessments" OR "nutritional Assessment" OR "nutritional assessments" OR "nutrition index" OR "nutrition indexes" OR "Nutritional Index" OR "Nutritional Indices" OR "malnutrition" OR "nutritional deficiency" OR "nutritional deficiencies" OR "undernutrition" OR "malnourishment" )

Web of Science TÓPICO:(Orthodontic OR orthodontics OR "Orthodontic Appliance" OR "Orthodontic 1222 Appliances" OR "Fixed Orthodontic Appliance" OR "Fixed Orthodontic Appliances" OR "Fixed Functional Appliance" OR "Fixed Functional Appliances" OR "Fixed Retainer" OR "Fixed Retainers" OR "fixed appliance" OR "fixed appliances" OR "Permanent Retainer" OR "Permanent Retainers" OR "fixed treatment" OR "fixed treatments" OR "activator appliance" OR "activator appliances" OR "Function Activator" OR "Function Activators" OR "orthodontic wire" OR "orthodontic wires" OR "orthodontic arch wire" OR "orthodontic arch wires" OR "Tooth Movement" OR "Tooth Movements" OR "Teeth Movement" OR "Teeth Movements" OR "Orthodontic Tooth Movement" OR "Orthodontic Tooth Movements" OR "orthodontic teeth movement" OR "orthodontic teeth movements" OR "orthodontic movement" OR "bracket" OR "brackets" OR "Orthodontic Brace" OR "Dental Braces" OR "Dental Brace" OR "Removable Orthodontic Appliance" OR "Removable Orthodontic Appliances" OR "Clear Aligner" OR "clear aligners" OR "Invisalign" OR "Activator Orthodontic Appliance" OR "Activator Orthodontic Appliances" OR "orthodontic activator appliance" OR "orthodontic activator appliances" OR "Clear Dental Braces" OR "Clear Dental Brace" OR "invisaligner" OR "invisaligners") AND TÓPICO: ("Mastication" OR "chewing" OR "masticatory" OR "biting ability" OR "biting abilities" OR "chewing movement" OR "chewing movements" OR "sieving method" OR "mixing ability test" OR "jaw motion" OR "Deglutition" OR swallowing OR "bite force" OR "bite forces" OR "Occlusal Force" OR "Occlusal Forces" OR "Masticatory Force" OR "Masticatory Forces" OR "maximum occlusal force" OR "maximum occlusal forces" OR "Masticatory Muscles" OR "Masticatory Muscle" OR "Masseter Muscle" OR "Masseter Muscles" OR "muscle thickness" OR "masseter thickness" OR "Electromyography" OR "Electromyographies" OR "Surface Electromyography" OR "Surface Electromyographies" OR "Electromyogram" OR "Electromyograms" OR "electromyographic activity" OR "nutritional intake" OR "nutritional level" OR "nutrient intake" OR "nutrients intake" OR "diet questionnaires" OR "anthropometric measurement" OR "anthropometric measurements" OR "nutritional status" OR "Nutrition Status" OR "nutrition assessment" OR "nutrition assessments" OR "nutritional Assessment" OR "nutritional assessments" OR "nutrition index" OR "nutrition indexes" OR "Nutritional Index" OR "Nutritional Indices" OR "malnutrition" OR "nutritional deficiency" OR "nutritional deficiencies" OR "undernutrition" OR "malnourishment")

Embase ('orthodontic'/de OR orthodontic OR 'orthodontics'/de OR orthodontics OR 'orthodontic 6511 appliance'/de OR 'orthodontic appliance' OR 'orthodontic appliances'/de OR 'orthodontic appliances' OR 'fixed orthodontic appliance'/de OR 'fixed orthodontic appliance' OR 'fixed orthodontic appliances' OR 'fixed functional appliance' OR 'fixed functional appliances' OR 'fixed retainer'/de OR 'fixed retainer' OR 'fixed retainers'/de OR 'fixed retainers' OR 'fixed appliance' OR 'fixed appliances' OR 'permanent retainer' OR 'permanent retainers' OR 'fixed treatment' OR 'fixed treatments' OR 'activator appliance'/de OR 'activator appliance' OR 'activator appliances'/de OR 'activator appliances' OR 'function activator' OR 'function activators' OR 'orthodontic wire'/de OR 'orthodontic wire' OR 'orthodontic wires'/de OR 'orthodontic wires' OR 'orthodontic arch wire' OR 'orthodontic arch wires' OR 'tooth movement'/de OR 'tooth movement' OR 'tooth movements' OR 'teeth movement' OR 'teeth movements' OR 'orthodontic tooth movement'/de OR 'orthodontic tooth movement' OR 'orthodontic tooth movements' OR 'orthodontic teeth movement'/de OR 'orthodontic teeth movement' OR 'orthodontic teeth movements' OR 'orthodontic movement'/de OR 'orthodontic movement' OR 'bracket' OR 'brackets' OR 'orthodontic brace' OR 'dental braces' OR 'dental brace' OR 'removable orthodontic appliance'/de OR 'removable orthodontic appliance' OR 'removable orthodontic appliances' OR 'clear aligner'/de OR 'clear aligner' OR 'clear aligners' OR 'invisalign'/de OR 'invisalign' OR 'activator orthodontic appliance' OR 'activator orthodontic appliances' OR 'orthodontic activator appliance' OR 'orthodontic activator

appliances' OR 'clear dental braces' OR 'clear dental brace' OR 'invisaligner' OR 'invisaligners') AND ('mastication'/de OR 'mastication' OR 'chewing'/de OR 'chewing' OR 'masticatory' OR 'biting ability' OR 'biting abilities' OR 'chewing movement' OR 'chewing movements' OR 'sieving method' OR 'mixing ability test' OR 'jaw motion' OR 'deglutition'/de OR 'deglutition' OR 'swallowing'/de OR swallowing OR 'bite force'/de OR 'bite force' OR 'bite forces' OR 'occlusal force'/de OR 'occlusal force' OR 'occlusal forces' OR 'masticatory force'/de OR 'masticatory force' OR 'masticatory forces' OR 'maximum occlusal force' OR 'maximum occlusal forces' OR 'masticatory muscles'/de OR 'masticatory muscles' OR 'masticatory muscle'/de OR 'masticatory muscle' OR 'masseter muscle'/de OR 'masseter muscle' OR 'masseter muscles' OR 'muscle thickness'/de OR 'muscle thickness' OR 'masseter thickness' OR 'electromyography'/de OR 'electromyography' OR 'electromyographies' OR 'surface electromyography'/de OR 'surface electromyography' OR 'surface electromyographies' OR 'electromyogram'/de OR 'electromyogram' OR 'electromyograms' OR 'electromyographic activity' OR 'nutritional intake'/de OR 'nutritional intake' OR 'nutritional level' OR 'nutrient intake'/de OR 'nutrient intake' OR 'nutrients intake' OR 'diet questionnaires' OR 'anthropometric measurement' OR 'anthropometric measurements' OR 'nutritional status'/de OR 'nutritional status' OR 'nutrition status'/de OR 'nutrition status' OR 'nutrition assessment'/de OR 'nutrition assessment' OR 'nutrition assessments' OR 'nutritional assessment'/de OR 'nutritional assessment' OR 'nutritional assessments' OR 'nutrition index' OR 'nutrition indexes'/de OR 'nutrition indexes' OR 'nutritional index'/de OR 'nutritional index' OR 'nutritional indices' OR 'malnutrition'/de OR 'malnutrition' OR 'nutritional deficiency'/de OR 'nutritional deficiency' OR 'nutritional deficiencies' OR 'undernutrition'/de OR 'undernutrition' OR 'malnourishment'/de OR 'malnourishment')

LILACS (tw:(Orthodontic* OR ortodoncia OR ortodontia OR "aparatos ortodóncicos*" OR "aparelhos 20 ortodônticos*" OR "aparato fijo*" OR "aparelho fixo*" OR "Fixed Orthodontic Appliance" OR "activator appliance" OR "aparatos activadores*" OR "aparelhos ativadores" OR "aparelhos ortodônticos ativadores" OR "orthodontic wire*" OR "alambres para ortodoncia" OR "resortes ortodón*" OR "fios ortodônticos" OR "Orthodontic Tooth Movement" OR " Técnicas de Movimiento Dental" OR "Movimiento Denta*" OR "técnicas de movimentação dentária" OR "movimentação dentária" OR "movimentação ortodôntica" OR "Orthodontic brackets" OR "Orthodontic Brace" OR "Dental Brace*" OR "Soportes Ortodón*" OR "Braquetes ortodônticos" OR "Removable Orthodontic Appliance" OR "Aparatos Ortodóncicos Removibles" OR "Clear Aligner" OR "alineador transparente" OR "alineador ortodónticos transparentes" OR "Invisalign*" OR "Alinhador*" OR "Clear Dental Brace" OR "Braquete estético" OR "Clear Dental Brace" )) AND (tw:(mastica* OR "chewing" OR "sieving method" OR "mixing ability test" OR "biting" OR "bite" OR degluti* OR "swallowing" OR "occlusal force" OR "occlusal forces" OR "muscle thickness" OR "masseter" OR "jaw motion" OR "electromyography" OR mastiga* OR "método de peneiramento" OR "teste de habilidade de mistura" OR mordida*or "força oclusal" OR "espessura muscular" OR "movimento mandibular" OR electromiografí* OR "método de cribado" OR "fuerza oclusal" OR "espesor muscular" OR "masetero" OR "movimiento mandibular" OR eletromiografi*)) AND (tw:(nutrition* OR nutrient* OR diet* OR "anthropometric" OR "malnutrition" OR "Undernutrition" OR "Malnourishment" OR "Malnourishments" OR "nutrição" OR antropometri* OR "desnutrição" OR nutricion* OR "desnutricion"))

Google ("Orthodontic" OR "fixed appliance" OR "orthodontic wire" OR "orthodontic movement" OR 3650 Scholar "bracket" OR "Orthodontic Brace" OR "Dental Brace" OR "Clear Aligner" OR "Invisalign") AND ("Mastication" OR "chewing" OR "bite force" OR "nutritional intake" OR "diet questionnaires")

OpenGrey ("Orthodontic" OR "fixed appliance" OR "orthodontic wire" OR "orthodontic movement" OR 3 "bracket" OR "Orthodontic Brace" OR "Dental Brace" OR "Clear Aligner" OR "Invisalign") AND ("Mastication" OR "chewing" OR "bite force" OR "nutritional intake" OR "diet questionnaires")

Cochrane Orthodontic OR orthodontics OR "Orthodontic Appliance" OR "Orthodontic 315 (trials) Appliances" OR "Fixed Orthodontic Appliance" OR "Fixed Orthodontic Appliances" OR "Fixed Functional Appliance" OR "Fixed Functional Appliances" OR "Fixed Retainer" OR "Fixed Retainers" OR "fixed appliance" OR "fixed appliances" OR "Permanent Retainer" OR "Permanent Retainers" OR "fixed treatment" OR "fixed treatments" OR "activator appliance" OR "activator appliances" OR "Function Activator" OR "Function Activators" OR "orthodontic

wire" OR "orthodontic wires" OR "orthodontic arch wire" OR "orthodontic arch wires" OR "Tooth Movement" OR "Tooth Movements" OR "Teeth Movement" OR "Teeth Movements" OR "Orthodontic Tooth Movement" OR "Orthodontic Tooth Movements" OR "orthodontic teeth movement" OR "orthodontic teeth movements" OR "orthodontic movement" OR "bracket" OR "brackets" OR "Orthodontic Brace" OR "Dental Braces" OR "Dental Brace" OR "Removable Orthodontic Appliance" OR "Removable Orthodontic Appliances" OR "Clear Aligner" OR "clear aligners" OR "Invisalign" OR "Activator Orthodontic Appliance" OR "Activator Orthodontic Appliances" OR "orthodontic activator appliance" OR "orthodontic activator appliances" OR "Clear Dental Braces" OR "Clear Dental Brace" OR "invisaligner" OR "invisaligners" in Title Abstract Keyword AND "Mastication" OR "chewing" OR "masticatory" OR "biting ability" OR "biting abilities" OR "chewing movement" OR "chewing movements" OR "sieving method" OR "mixing ability test" OR "jaw motion" OR "Deglutition" OR swallowing OR "bite force" OR "bite forces" OR "Occlusal Force" OR "Occlusal Forces" OR "Masticatory Force" OR "Masticatory Forces" OR "maximum occlusal force" OR "maximum occlusal forces" OR "Masticatory Muscles" OR "Masticatory Muscle" OR "Masseter Muscle" OR "Masseter Muscles" OR "muscle thickness" OR "masseter thickness" OR "Electromyography" OR "Electromyographies" OR "Surface Electromyography" OR "Surface Electromyographies" OR "Electromyogram" OR "Electromyograms" OR "electromyographic activity" OR "nutritional intake" OR "nutritional level" OR "nutrient intake" OR "nutrients intake" OR "diet questionnaires" OR "anthropometric measurement" OR "anthropometric measurements" OR "nutritional status" OR "Nutrition Status" OR "nutrition assessment" OR "nutrition assessments" OR "nutritional Assessment" OR "nutritional assessments" OR "nutrition index" OR "nutrition indexes" OR "Nutritional Index" OR "Nutritional Indices" OR "malnutrition" OR "nutritional deficiency" OR "nutritional deficiencies" OR "undernutrition" OR "malnourishment" in Title Abstract Keyword

ProQuest noft(Orthodontic OR orthodontics OR "Orthodontic Appliance" OR "Orthodontic Appliances" 92 OR "Fixed Orthodontic Appliance" OR "Fixed Orthodontic Appliances" OR "Fixed Functional Appliance" OR "Fixed Functional Appliances" OR "Fixed Retainer" OR "Fixed Retainers" OR "fixed appliance" OR "fixed appliances" OR "Permanent Retainer" OR "Permanent Retainers" OR "fixed treatment" OR "fixed treatments" OR "activator appliance" OR "activator appliances" OR "Function Activator" OR "Function Activators" OR "orthodontic wire" OR "orthodontic wires" OR "orthodontic arch wire" OR "orthodontic arch wires" OR "Tooth Movement" OR "Tooth Movements" OR "Teeth Movement" OR "Teeth Movements" OR "Orthodontic Tooth Movement" OR "Orthodontic Tooth Movements" OR "orthodontic teeth movement" OR "orthodontic teeth movements" OR "orthodontic movement" OR "bracket" OR "brackets" OR "Orthodontic Brace" OR "Dental Braces" OR "Dental Brace" OR "Removable Orthodontic Appliance" OR "Removable Orthodontic Appliances" OR "Clear Aligner" OR "clear aligners" OR "Invisalign" OR "Activator Orthodontic Appliance" OR "Activator Orthodontic Appliances" OR "orthodontic activator appliance" OR "orthodontic activator appliances" OR "Clear Dental Braces" OR "Clear Dental Brace" OR "invisaligner" OR "invisaligners" ) AND noft("Mastication" OR "chewing" OR "masticatory" OR "biting ability" OR "biting abilities" OR "chewing movement" OR "chewing movements" OR "sieving method" OR "mixing ability test" OR "jaw motion" OR "Deglutition" OR swallowing OR "bite force" OR "bite forces" OR "Occlusal Force" OR "Occlusal Forces" OR "Masticatory Force" OR "Masticatory Forces" OR "maximum occlusal force" OR "maximum occlusal forces" OR "Masticatory Muscles" OR "Masticatory Muscle" OR "Masseter Muscle" OR "Masseter Muscles" OR "muscle thickness" OR "masseter thickness" OR "Electromyography" OR "Electromyographies" OR "Surface Electromyography" OR "Surface Electromyographies" OR "Electromyogram" OR "Electromyograms" OR "electromyographic activity" OR "nutritional intake" OR "nutritional level" OR "nutrient intake" OR "nutrients intake" OR "diet questionnaires" OR "anthropometric measurement" OR "anthropometric measurements" OR "nutritional status" OR "Nutrition Status" OR "nutrition assessment" OR "nutrition assessments" OR "nutritional Assessment" OR "nutritional assessments" OR "nutrition index" OR "nutrition indexes" OR "Nutritional Index" OR "Nutritional Indices" OR "malnutrition" OR "nutritional deficiency" OR "nutritional deficiencies" OR "undernutrition" OR "malnourishment")

Supplemental Table 2. Articles Excluded and Reasons for Exclusion (n = 27) Author, year Reasons for exclusion 1. Abed Al Jawad et al, 2011 3 2. Abreu et al, 2015 3 3. Ahlgren et al, 1980 1 4. Alghamdi et al, 2017 3 5. AlQuraini et al, 2019 3 6. Anehus-Pancherz et al, 1989 1 7. Botelho et al, 2009 3 8. Bretz et al, 2018 3 9. Caniklioglu et al, 2005 3 10. Carter et al, 2015 3 11. Choi et al, 2017 3 12. Flores-Mir et al, 2018 3 13. Giannini et al, 2017 3 14. Johal et al, 2013 3 15. Liu et al, 2017 3 16. Nedwed et al, 2005 3 17. Otasevic et al, 2006 5 18. Pancherz et al, 1978 3 19. Poudel et al, 2020 5 20. Satokawa et al, 2017 1 21. Sayar et al, 2017 5 22. Sergl et al, 2000 5 23. Shirazi et al, 2011 3 24. Smith et al, 1984 9 25. Tapeshkina et al, 2020 3 26. Thomas et al, 1995 3 27. Van Den Braber et al, 2002 3

1- Patients who were using removable appliances differently of clear aligners (n=3); 2- Patients with temporomandibular disorders and/or myofascial pain(n=0); 3- Outcomes not evaluated after activation of fixed appliances/clear aligners (n=19); 4- Patients who were not undergoing orthodontic treatment (n=0); 5- Studies not evaluating masticatory and nutritional outcomes of patients using fixed orthodontic appliances (n=4); 6- Reviews, letters, conference abstract, personal opinions, case reports, technique articles (n=0); 7- Animal models or experimental in vitro studies (n=0); 8- Studies with missing data and not provided by the author (n=0); 9- Studies with less than 10 subjects (n=1).

Supplemental Table 3. Characteristics of the studies included in the meta-analyses.

Author, Year Methodology Follow-up Comparisons Observations Masticatory Performance Sieving method Both studies evaluated the same Gameiro et al. T0: Before Artificial test-food Optocal (17 cubes - 3.0 g) Baseline x 24h sample, therefore they were 2015; Silva T1: 24 hs 15 cycles Baseline x 30 days considered as one single study. Andrade et al. T2: 30 days 10 stacked sieves (ranging 5.6 to 0.71 mm) 24h x 30 days 2018 Median particle size (X50) was then calculated. Sieving method T0: Before Artificial test-food Optocal (17 cubes - 3.2 g) T1: Immediately Magalhães et al. 15 cycles T2: 48 hs Baseline x 30 days 2014 10 stacked sieves (ranging 5.6 to 0.71 mm) T3: 30 days Median particle size (X50) was then calculated. T4: 3 months Sieving method Artificial test-food Optocal (17 cubes - 3.0 g) T0: Before Baseline x 24h Trein et al. 2013 15 cycles T1: 24 h Baseline x 30 days 10 stacked sieves (ranging 5.6 to 0.71 mm) T2: 30 days. 24h x 30 days Median particle size (X50) was then calculated.

Swallowing Threshold (median particle size X50 and number of cycles) Sieving method Results from artificial Artificial test-food Optocal (17 cubes - 3.0 g) (Optocal) and natural foods T0: Before Peanuts (3.0 g) (peanuts) were evaluated, but, T1: Immediately Magalhães et al. Baseline x up to 48 hs to increase homogeneity, only Number of cycles until swallowing T2: 48 hs 2014 Time of chewing until swallowing Baseline x 30 days results from artificial food were T3: 30 days meta-analyzed. 10 stacked sieves (ranging 5.6 to 0.71 mm) T4: 3 months

Sieving method T0: Before Artificial test-food Optocal (17 cubes - 3.0 g) Baseline x up to 48 hs Trein et al. 2013 T1: 24 hs Number of cycles until swallowing Baseline x 30 days 10 stacked sieves (ranging 5.6 to 0.71 mm) T2: 30 days Bite Force Battery-operated portable type of OBF gauge (GM10, Nagano Keiki, Tokyo, Japan). Hydraulic pressure gauge (disposable cap) T0: Baseline 1-6 months measurements were Newtons (N) Alomari et al. T1: One week made before the activation of Bilaterally measured Baseline x One Week 2012 T2: Two weeks the appliance; therefore, they First permanent molar region. T3-T8: 1-6 months were not meta-analyzed. 3 measurements with a 15 second rest Averaged maximum OBF was considered

Strain gauge transducer- Digital bite force meter” 1-6 months measurements were (Hariom Electronics, Gujarat, India). made before the activation of Newtons (N) T0: Baseline the appliance; therefore, they Prema et al. 2019 Bilaterally measured T1: One week Baseline x One Week were not meta-analyzed. First permanent molar region. T2-T7: 1-6 months Averaged maximum OBF was considered

Pain Level Gameiro et al. Baseline x 24hs Both studies evaluated the same Visual Analog Scale (VAS) 10 cm T0: Before 2015; Silva Baseline x Up to 48hs sample, therefore they were “no discomfort” and “worst discomfort possible” T1: 24 hs Andrade et al. Baseline x 30 days considered as one single study. T2: 30 days 2018 Pain experienced during chewing 24hs x 30 days Visual Analog Scale (VAS) 10 cm Goldreich et al. “no discomfort” and “worst discomfort possible” T0: Baseline Baseline x Up to 48hs 1994 Pain experienced during chewing T1: 48 hs

Visual Analog Scale (VAS) 10 cm T0: Before “no pain” and “worst pain imaginable” T1: Immediately Magalhães et al. Baseline x Up to 48hs Pain experienced during chewing with artificial food. T2: 48 hs 2014 Baseline x 30 days T3: 30 days T4: 3 months

Visual Analog Scale (VAS) 10 cm Baseline x 24hs T0: Before “without discomfort” and “worst discomfort possible” Baseline x Up to 48hs Trein et al. 2013 T1: 24 hs Baseline x 30 days T2: 30 days 24hs x 30 days

Supplemental Table 4. Risk of bias assessment of randomized clinical trials – ROB 2.0 tool, Cochrane.

Risk of Bias Assessment of Randomized Clinical Trials - ROB 2.0 tool Domains Signalling Khattab et al., White et al., questions 2013 2017 1. Bias arising from the randomization 1.1 Y Y process 1.2 PY PY 1.3 PN N Judgment Low risk Low risk 2. Bias due to deviations from intended 2.1 PY Y interventions 2.2 Y Y 2.3 PY PY 2.4 N N 2.5 N N 2.6 NA NA Judgment Low risk Low risk 3. Risk of bias due to missing outcome data 3.1 Y Y 3.2 NA NA 3.3 NA NA 3.4 NA NA Judgment Low risk Low risk 4. Risk of bias in measurement of the 4.1 PY PY outcome 4.2 N N 4.3 NA NA 4.4 PN NA 4.5 PN NA Judgment Serious Serious 5. Risk of bias in selection of the reported 5.1 PY PY result 5.2 PN PN 5.3 PN PN Judgment Low risk Low risk

Overall Risk of Bias Serious Serious

Supplemental Table 5. Risk of bias in non-randomized studies of interventions – ROBINS-I tool, Cochrane

Risk of Bias In Non-randomized Studies of Interventions - ROBINS-I Domains Signalling Alajmi et Alomari et Andrade et Gameiro Goldreich Hohoff et Lou et Magalhães Mansor et Prema et Riordan et Trein et Wu et al., questions al., 2019 al., 2012 al., 2018 et al., 2015 et al., 1994 al., 2003 al., 2020 et al., 2014 al., 2012 al., 2019 al., 1997 al., 2013 2011 1. Bias due to 1.1 PY PY PY PY PY Y PY PY PY PY PY PY Y confunding 1.2 N NA N N N N N N N NA N N N 1.3 NA NA NA NA NA NA NA NA NA NA NA NA NA 1.4 NI PY NI PN PN PN PN NI NI NA NI Y NI 1.5 NA Y NA NA NA NA PN NA NA NA NA Y NA 1.6 NI NA PN PN N NI N N N NA N PN NI 1.7 NA NA NA NA NA NA NA NA NA NA NA NA NA 1.8 NA NA NA NA NA NA NA NA NA NA NA NA NA Judgment Serious Moderate Serious Moderate Serious Serious Serious Serious Serious Moderate Serious Serious Serious 2. Bias in 2.1 Y N N N Y N N N N N Y N PN selection of 2.2 Y NA NA NA PN NA NA NA NA NA PN NA NA participants 2.3 N NA NA NA PN NA NA NA NA NA PN NA NA into the 2.4 N Y Y Y N Y Y Y Y Y N Y PY study 2.5 Y NA NA NA PN NA NA NA NA NA PN NA NA Judgment Serious Low Risk Low Risk Low Risk Serious Low Risk Low Risk Low Risk Low Risk Low Risk Serious Low Risk Low Risk 3. Bias in 3.1 Y Y PY Y Y Y Y Y Y Y Y Y Y classification 3.2 PN Y Y Y PN Y Y Y Y Y N PY NI of 3.3 PY PN PN PN PN N PN N N PN N PN N intervention Judgment Serious Low Risk Moderate Low Risk Moderate Low Risk Low Risk Low Risk Low Risk Low Risk Moderate Low Risk Low Risk 4. Bias due 4.1 to deviations 4.2 from 4.3 PY Y Y Y Y Y NI NI NI NI NI NI NA intended 4.4 Y Y Y Y Y Y Y Y Y Y Y Y Y intervention 4.5 Y Y Y Y Y Y Y Y Y Y Y Y Y 4.6 NA NA NA NA NA NA NA NA NA NA NA NA NA Judgment Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk 5. Bias due to 5.1 Y Y Y Y Y Y Y Y Y Y Y Y Y missing data 5.2 N N N N N N N N N N N N N 5.3 N N N N Y Y N N N N N N N 5.4 NA NA NA NA NA Y NA NA NA NA NA NA NA 5.5 NA NA NA NA Y NA NA NA NA NA NA NA NA Judgment Low Risk Low Risk Low Risk Low Risk Low Risk Moderate Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk 6. Bias in 6.1 PN N N N PY PN PN PN N N PN N PN measuramen 6.2 PY Y Y PY Y PY Y Y Y Y Y Y Y t outcomes 6.3 Y Y Y Y Y Y Y Y Y Y Y Y Y 6.4 NI NI NI NI NI PN NI NI N NI PN N NI

Judgment Moderate Low Risk Low Risk Low Risk Moderate Low Risk Moderate Low Risk Low Risk Low Risk Low Risk Low Risk Moderate 7. Bias in 7.1 N PN N N N N N N N N N N N selection of 7.2 N PN N N N N N N N N N N N the reported 7.3 N PN N N N N N N N N N N N result Judgment Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk Low Risk

Overall Risk of Bias Serious Moderate Serious Moderate Serious Serious Serious Serious Serious Moderate Serious Serious Serious

4 CONCLUSÃO

Apesar da certeza da evidência ser baixa e o risco de viés ser considerável, a ativação e/ou instalação de aparelhos fixos labiais parece impactar a função mastigatória, mesmo que de forma temporária, reduzindo a performance e a força de mordida. Essa descoberta é importante para auxiliar os clínicos a instruir melhor seus pacientes durante o tratamento visto que essa redução é temporária e a mastigação é completamente restabelecida após 30 dias. Devido aos dados insuficientes, o impacto nutricional e o efeito dos aparelhos fixos linguais e alinhadores estéticos sobre a mastigação e nutrição não foram conclusivos.

REFERÊNCIAS

ALAJMI, S.; SHABAN, A.; AL-AZEMI, R. Comparison of Short-Term Oral Impacts Experienced by Patients Treated with Invisalign or Conventional Fixed Orthodontic Appliances. Med Princ Pract, 29, p.382-388, 2020.

ALOBEID, A.; EL-BIALY, T.; REIMANN, S. et al. Comparison of the efficacy of tooth alignment among lingual and labial brackets: an in vitro study. Eur J Orthod, 40, n.6, p.660- 665, Nov 2018.

ALOMARI, S.A.; ALHAIJA, E.S. Occlusal bite force changes during 6 months of orthodontic treatment with fixed appliances. Aust Orthod J, 28, p.197-203, 2012.

BATES, J.F.; STAFFORD, G.D, Harrison A. Masticatory function - a review of the literature. III. Masticatory performance and efficiency. J Oral Rehabil, 3, n.1, p.57-67, 1976.

CARTER, L. A.; GELDENHUYS, M.; MOYNIHAN, P. J. et al. The impact of orthodontic appliances on eating - young people's views and experiences. J Orthod, 42, p.114-122, 2015.

FLORES-MIR, C.; BRANDELLI, J.; PACHECO-PEREIRA, C. Patient satisfaction and quality of life status after 2 treatment modalities: Invisalign and conventional fixed appliances. Am J Orthod Dentofacial Orthop, 154, n.5, p.639-644, Nov 2018.

FONTIJN-TEKAMP, F.A.; SLAGTER, A.P.; VAN DER BILT, A. et al. Biting and chewing in overdentures, full dentures, and natural dentitions. J Dent Res, 79, n.7, p.1519-24, 2000.

FUJITA, K. New orthodontic treatment with lingual bracket and mushroom arch wire appliance. Am J Orthod, 76, p.657–675, 1979.

FUJIYAMA, K.; HONJO, T.; SUZUKI, M. et al. Analysis of pain level in cases treated with Invisalign aligner: comparison with fixed edgewise appliance therapy. Prog Orthod, 15, n.1, Nov 2014.

GAMEIRO, G.H.; PEREIRA-NETO, J.S.; MAGNANI, M.B.; NOUER, D.F. The influence of drugs and systemic factors on orthodontic tooth movement. J Clin Orthod, 41, p.73-78, 2007.

GOLDREICH, H.; GAZIT, E.; LIEBERMAN, M.A.; RUGH, J.D. The effect of pain from orthodontic arch wire adjustment on masseter muscle electromyographic activity. Am J Orthod Dentofacial Orthop, 106, p.365-370, 1994.

HATCH, J.P.; SHINKAI, R.S.; SAKAI, S. et al. Determinants of masticatory performance in dentate adults. Arch Oral Biol, 46, n.7, p.641-8, Jul 2001.

KHATTAB, T.Z.; FARAH, H.; AL-SABBAGH, R. et al. Speech performance and oral impairments with lingual and labial orthodontic appliances in the first stage of fixed treatment. Angle Orthod, 83, p.519-526, 2013.

KRISHNAN, V.; DAVIDOVITCH, Z. Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop, 129, n.4, p.469.el-469.e132.

LONG, H.; ZHOU, Y.; PYAKUREL, U. et al. Comparison of adverse effects between lingual and labial orthodontic treatment. Angle Orthod, 83, p.1066-1073, 2013.

MAGALHAES, I.B.; PEREIRA, L.J.; ANDRADE, A.S. et al. The influence of fixed orthodontic appliances on masticatory and swallowing threshold performances. J Oral Rehabil, 41, p.897-903, 2014.

N'GOM, P.I.; WODA, A. Influence of impaired mastication on nutrition. J Prosthet Dent, 87, n. 6, p.667-73, 2002.

PEDERSEN, A.M.; BARDOW, A.; JENSEN, S.B.; NAUNTOFTE, B. Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Oral Dis, 8, n.3, p.117-29, May 2002.

TARKOWSKA, A.; KATZER, L.; AHLERS, M.O. Assessment of masticatory performance by means of a color-changeable chewing gum. J Prosthodont Res, 61, n.1, p.9-19, Jan 2017.

TREIN, M.P.; MUNDSTOCK, K.S.; MACIEL, L. et al. Pain, masticatory performance and swallowing threshold in orthodontic patients. Dental Press J Orthod, 18, p.117-123, 2013.

VAN DER BILT, A.; ENGELEN, L.; PEREIRA, L.J. et al. Oral physiology and mastication. Physiol Behav, 89, n.1, p.22-7, Aug 2006.

WU, A.; MCGRATH, C.; WONG, R.W. et al. Comparison of oral impacts experienced by patients treated with labial or customized lingual fixed orthodontic appliances. Am J Orthod Dentofacial Orthop, 139, p.784-790, 2011