The Influence of Food Hardness on the Physiological Parameters of Mastication: A Systematic Review Article in Press: Accepted Manuscript Ingrid Tonni , Giulia Riccardi , Maria Grazia Piancino , Chiara Stretti , Fulvia Costantinides and Corrado Paganelli Archives of Oral Biology, Article 104903, Copyright © 2020 Highlights hard diet increases number of chewing cycles during the entire process of mastication hard diet increases the time between food intake and the first swallowing cycle hard diet increases muscle activity, coordination and changes of masticatory side hard diet increases amplitude and shape of mandibular displacement during mastication Abstract Objective This systematic review had the purpose to collect existing data concerning the influence of food hardness on mastication in adults. Design The review was listed with PROSPERO (CRD42017069760) and was directed following with PRISMA and CRD (Centre for Reviews and Dissemination, University of York) statement. A database search of articles issued from 1998 up to December 2018 was carried-out using four databases: Pubmed, Cochrane Library, Web of Science and Scopus. The lists of references of the articles selected for the review were read to identify any other relevant studies. The included publications were analysed for level of evidence, study design, sample characteristics, test of mastication, primary outcomes and key results. A quality assessment of the articles included in the review was performed. Results 1686 articles were found through database searching. The studies that complied with all the inclusion criteria and were considered for the conclusive analysis were 38 and their methodological quality was scored as moderate/low. The findings of the analysed articles were consistent, despite the presence of different methodologies and the lack of a complete control of the bias. They revealed that the majority of the chewing parameters, which were gathered in four groups: 1) number of cycles, 2) sequence duration, 3) muscle activity and 4) coordination and amplitudes and shape of mandibular displacements, increased in the transition from soft to hard food. Conclusions Hard-diet in adults has an impact on the masticatory function increasing almost all the physiological masticatory parameters, muscle coordination and changes of masticatory side. 1 Introduction Mastication is a dynamic process described by rhythmicity which includes synchronous movements of the jaws, tongue and cheeks to place the bolus between the largest faces of the teeth ( ). A sequence of mastication starts when food is introduced into the oral cavity and ends with swallowing of the bolus. The rhythm of mastication is produced by a central pattern generator (CPG) ( ), which activates a motor driver coordinating the activities of the jaw, tongue and facial muscles ( ). The chewing program adjusts itself to the characteristics of the food, including its hardness ( ). Chewing is not only a function giving nourishment and pleasure but it is an important physiological movement for a good quality of life both during growth and aging. The understanding on the impact of food hardness on chewing is essential to analyse the patients’ capacity to regulate the applied load ( ). The chewing apparatus can produce high forces when moving the mandible. The precision of the movement is imperative for avoiding harm to the stomatognathic system and for amplifying efficiency but also for stimulating growing of craniofacial structures. The load generated by mastication effects the maxillary bones growth maintaining the patency and viscoelasticity of the cranial sutures during aging ( ; ; ; ) and the mandibular growth acting on the development of the condyle and changes in the thickness of the cartilage ( ; ; ; ). Further mastication seems to have considerable effects on general health problems in adults such as dementia ( ) and obesity ( ) and during developmental age such as impaired spatial memory and learning function ( ; ; ). A great number of studies have tried to elucidate the association of mastication with food hardness. Studies regarding the association of food hardness with the physiologic chewing parameters (number of cycles, sequence duration, frequency of mastication, electromyographic activity, kinetic parameters of the cycles etc.) have been reviewed in some articles ( ; ) but not in a systematic way covering the high number of literature relating this association. In this review, the published conclusions on the relationship between mastication and food hardness in adults with normal dental occlusion and function were systematically analysed to expand the understanding of the effect of food hardness on parameters of mastication and to critically assess the methodology of the studies published to date. 2 Methods 2.1 Literature search This systematic review was registered in PROSPERO with the number CRD42017069760 and was directed following the PRISMA and CRD (Centre for Reviews and Dissemination, University of York) statements. A computerized systematic search of studies published from 1998 up to December 2018 was carried out without language restrictions, using the algorithms illustrated in Table 1 , in four electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. Table 1 Algorithms used for the systematic search on Pubmed, Web of science, Scopus and Cochrane Library Database Algorithm Pubmed (("Mastication"[MeSH] and "Diet"[MeSH]) or (chewing and "Diet"[MeSH]) or ("Mastication"[MeSH] and "Food"[MeSH]) or (chewing and "Food"[MeSH]) OR ("Mastication"[MeSH] and bolus) or (chewing and bolus)) AND ((masticatory muscle* or chewing muscle*) or (chewing cycle*or masticatory cycle*) or (masticatory kinematic* or side of mastication) or (chewing pattern or mastication pattern) or (masticatory force or chewing force) or (masticatory performance or masticatory ability) or (tooth surface or occlusal surface) or (periodontal mechanoreceptor or motor control) or (food hardness or food type) or (bolus hardness or bolus toughness) or (food processing) or (food texture) or ("Biological Evolution"[MeSH])) Web of Science "Mastication and Diet" OR "chewing and Diet" OR "Mastication and Food" OR "chewing and Food" OR "Mastication and bolus" OR "chewing and bolus” Scopus "Mastication and Diet" OR "chewing and Diet" OR "Mastication and Food" OR "chewing and Food" OR "Mastication and bolus" OR "chewing and bolus" Cochrane Library ("Mastication"[MeSH]) and "Diet"[MeSH]) OR (chewing and "Diet"[MeSH]) OR ("Mastication"[MeSH]) and "Food"[MeSH]) OR (chewing and "Food"[MeSH]) OR ("Mastication"[MeSH]) and (bolus) OR (chewing and bolus) Articles including a combination of the words mentioned above and studying the association of food hardness with mastication were considered appropriate for inclusion. Two reviewers (GR and CS) independently screened title and abstract (TIAB) to decide which articles were suitable for full text retrieval. The collected documents were analysed for eligibility according to the inclusion and exclusion criteria. The inclusion and exclusion criteria used for this systematic review are shown in Table 2 . After the literature search was accomplished, no more publications were added. The references of each selected paper were also revised and all correlated studies were searched. Table 2 The inclusion and exclusion criteria used for articles selection. Inclusion Criteria Exclusion Criteria Sample Healthy adults with good dental and TMJ status 1) Subjects who have systemic illnesses or eating disorders (at least for the study group) 2) 2) Subjects who have dentures, implants or any rehabilitation of the oral cavity Outcome 1) Collection of data regarding different natural foods or model foods with different hardness 2) Evaluation of different physiological parameters of masticatory function 3) Information regarding different types of food consumption in evolution and effects on masticatory function 1) Data on food with different consistency and data on different parameters of masticatory function is not obtained 2) Data on food bolus comminution before swallowing is collected Analysis Original studies with any relationship between food hardness and mastication Descriptive studies, review, case reports or studies that did not investigate the relationship between food hardness and mastication 2.2 Methodological appraisal The two reviewers analysed articles independently. When there was disagreement on a study, the decision to include or not it was based on discussion and consensus between the two and by a third reviewer (IT) if needed. For all the articles the following items were presented: authors/date, level of evidence, design of the study, characteristics of the sample (size, age, sex, dental and TMJ status), test of mastication, food sample, primary outcomes and key results. The quality of the selected articles was independently assessed by the two authors GR and CS. When there was disagreement, to reach consensus a discussion with a third reviewer was needed (IT). The quality of the articles was assessed using a critical appraisal tool such as the Critical Appraisal Skills programme (CASP) for Cohort Studies ( ). The CASP checklist for Cohort Studies was slightly modified and consisted of nine questions that the two authors (GR and CS) applied to each manuscript. The two authors also assigned a grade (Low/Moderate/High) to each article considering the strengths and weaknesses resulted from the CASP evaluation. The chosen articles were also categorised by the two authors according to the Oxford Centre for Evidence-based Medicine ( , ). 3 Results 3.1 Literature searches The results of the study search are shown in the modified version of the Prisma diagram ( ) ( Fig. 1 ). In total, 1686 publications in English were collected from the search of the 4 databases. After the duplicates were removed, 12 records, which were identified from reference lists, were added. The first evaluation of the references considering the title and abstract eliminated 1584 references. Studies on animals were excluded from the studies. The full texts of seventy-one possibly relevant references were obtained. Thirty-three full-texts that did not fit the inclusion criteria and finally 38 publications were selected for the review. They were read, examined and the relevant information was extracted. They were also classified according to the principles of evidence-based medicine from the strongest (type-1) to the weakest (type-5) evidence. The strength of evidence was 1b for all the included studies. The studies were summarized in Tables 3–7 . Fig. 1 The modified version of the Prisma diagram. Table 3 Summary of the articles on the association between food hardness and masticatory parameters included in the review Reference Level of evidence Type of study Study sample Sample size and sex Sample age Test of mastication Food sample Primary outcomes Key results ) 1b PCS Two groups: healthy adults and elderly with over 25 natural teeth with no mastication problems 20 young and 40 elderly First group: mean age, 26.28 ± 2.78 years. Second group: mean age 79.53 ± 3.48 years Videofluorography and videotapes Thin rice gruel, rice gruel, soft-boiled rice, cooked rice Number of chewing cycles and sequence duration The number of masticatory cycles was significantly decreased from 38.60 to 2.53 for the young. The oral sequence time significantly diminished from 17.26 s (cooked rice) to 11.58 s (soft-boiled rice), 6.08 s (rice gruel) and 2.19 s (thin rice gruel) in the young. 1b PCS Adult subjects with no chronic masticatory problems, no dental work within the last six months and no missing tooth (except third molars) 26 (7 males and 19 females) Range: 21-36 years of age 3D motion capture system (Vicon) Cooked sweet potato, chicken, celery, raw sweet potato Number of chewing cycles, cycle duration, opening and closing duration, vertical and lateral amplitude The number of cycles increases with hardness. Cycle duration did not change between the harder and softer food (p = 0.67). Foods with lower Young’s modulus values were characterised by greater durations of SO (slow opening) and FO (fast opening) (p < 0.01), while foods with high Young’s modulus had longer durations of SC (slow closing) (p < 0.01). Vertical and lateral displacement Increased from soft to harder foods (p < 0.01). 1b PCS Healthy volunteers with no history of major medical or dental problems 13 (9 females and 4 males) Range: 18–31 years of age Videofluorography Banana, cookie, and tofu Number of St2Tr cycles, sequence duration Cookie needed a longer time to be eaten (i.e. mastication and transport) and more St2Tr cycles than banana and tofu. Wada et al. (2016) 1b PCS Students with normal dentition, no history of stomatognathic disorder, xerostomia or dysphasia 15 (10 males and 5 females) Mean age: 25.8 ± 1.7 years Examiners' eyes Boiled rice, cracker, in-house-prepared hard gelatine gel, in-house-prepared soft gelatine gel Number of chewing cycles The chews for cracker, boiled rice, hard gelatine gel and soft gelatine gel were 29.2, 19.5, 28.8, and 19.1 respectively. 1b PCS Volunteers with no masticatory or swallowing dysfunctions and without removable denture prostheses 11 females Range: 22-49 years of age Electromyography 2 types of hydrocolloid gels A and K, with the same fracture load, A with > elastic modulus than K Number of chewing cycles, cycle duration, muscle activity/cycle, muscle activity/sequence, peak to peak amplitude, muscle burst duration, muscle coordination. Cycle duration did not differ between A and K gel. The numbers of chews and the muscle activities were significantly higher for K gel compared with A gel before the first swallowing. Lieberman et al. (2016) 1b PCS Two groups of adults 24 First group: 7 males, 7 females (aged 29 ± 8 years); Second group: 10 male subjects (aged 36 ± 17 years) Electromyography Organic USOs (underground storage organs) and meat. Both were eaten in different ways: unprocessed, processed and cooked Number of chewing cycles, muscle activity/sequence Unprocessed meat required less masticatory effort than underground storage organs (USOs). Compared to unprocessed USOs, one kcal of unprocessed meat required fewer chews and less force to make food ready for swallowing (P = 0.01 and P = 0.02 respectively). Remijn et al. 2015 1b PCS Healthy adults with no dental problems, mouth pain, loose teeth or dentures/implants or problems with temporomandibular joint 12 (6 males and 6 females) Mean age ± SD: 29.1 ± 9.9 years) Electromyography and 3D motion-capture system (Vicon MX 1.7.1, Oxford Metrics, UK). Wheat bread with a chocolate spread and a crunchy biscuit in 2 different size (small and large) Number of chewing cycles, masticatory frequency, cycle duration, opening velocity, opening duration, occlusal duration, muscle coordination, change of masticatory side Number of chewing cycle, cycle duration and masticatory frequency presented no difference between biscuit and bread texture. The occlusal duration and opening duration in biscuit textures were longer than in the bread texture and opening velocity was faster in the biscuit than in the bread textures. There were no differences in closing muscles activities between right and left and the chewing biscuit was characterized by fewer changes in side of mastication than chewing bread, but the error pf measurement was large (low reproducibility) for both the variables. 1b PCS Normal adult females with no abnormalities in the number or position of their teeth, no history of orthodontic treatment or temporomandibular disorders, no occlusal abnormalities or mastication problems 10 females Mean age: 23.0 ± 3.0 years Electromyography Steamed rice, rice cake Number of chewing cycles, sequence duration, cycle duration, Masseter and Hyoid activity/sequence and cycle The number of chewing cycles and sequence duration were greatly bigger for rice cake than for steamed rice (P < 0.05). On the contrary, cycle duration did not change between the foods (rice cake and steamed rice were 0.70 ± 0.13 s and 90.70 ± 0.10 s, respectively). The respective electromyography activity during total chewing of rice cake and steamed were different (P < 0.001). Both the Masseter and Hyoid electromyography activity per cycle were significantly lower for steamed rice than rice cake. Table 4 XXX Reference Level of evidence Type of study Study sample Sample size and sex Sample age Test of mastication Food sample Primary outcomes Key results 1b PCS Two groups: young and older adults with a full set of natural teeth (excluding third molars) with a self-reported good oral health and general health condition 10 Mean age young adults: 23.7 ± 1.1 years Electromyography Raw whole carrot (RWC, harder), raw chopped carrot (RCC), cooked whole carrot (CWC) and cooked chopped carrot (CCC, softer) Number of chewing cycles, sequence duration, masticatory sequence, muscle peak to peak amplitude, maximal bite force and muscle activity/sequence. RWC and RCC needed a higher number of chewing cycles and a longer sequence duration, with a slower frequency of mastication and a greater muscle activity than both CWC and CCC (P < 0,05). There were no difference on mean or maximal electromyography voltages among the four varieties of carrot. Cazal et al. (2015) 1b PCS Healthy young adults with no absent teeth, no users of partial or total dentures, no maxillomandibular discrepancies and any symptomatic disorder of articular and muscular origin. 30 (15 males and 15 females) Range: 18-29 years of age Electromyography Gum, raisins, chewing capsules, peanuts with different viscoelastic properties Number of chewing cycles, masticatory sequence, muscle coordination, muscle activity/sequence The number of chewing cycles and the frequency of mastication remained similar for all the analysed materials. Muscle coordination was statistically different between raisins (43.11%), capsules (44.40%), peanuts (52.62%) and gum (29.69%). Regarding muscle activity/sequence gum was the only material that did not have similarity with the others, raisins, peanuts, and capsules were statistically similar to each other. ) 1b PCS Healthy adults with no temporomandibular disorders or asymmetry of mastication, all with normal class I dental occlusion 14 (9 females and 5 males) Range: 21–24 years of age Videofluoroscopy 6 gr each of hard cookie, raw peeled ripe banana (soft food), and firm tofu (soft food) Number of chewing cycles, number of St2Tr cycles There were fewer chewing cycles for soft than hard food (P = 0.013). Multivariable analysis disclosed a smaller number of St2Tr cycles with soft than hard food (P = 0.01). ) 1b PCS Adults free from masticatory or swallowing disfunction and without removable dental protheses 11 (4 males and 7 females) Mean age: 40 years Electromyography 5 types of hydrocolloid gels from firmest to softest: #4, #12, #16, #6, #14; 2 doses for each type were used: 3 ml (S) and 6 ml (L) Number of chewing cycles, sequence duration, cycle duration, peak-to-peak amplitudes, muscle activity/cycle, muscle activity/sequence Cycle duration remains stable among samples. The other variables were significantly greater in firmer gels such as #4 and #12, while they were less in soft gel such as #14. 1b PCS Healthy adults 8 males Range: 18-21 years of age Electromyography Agar and ‘Ina-agar’, which is a mixture of agar softer and smoother than ordinary agar Muscle coordination Anova did not detect significant main effects of the different test food on the synchronization of the masseter activity. However, the increase of chewing cycles augmented the synchronization in each sequence. Furthermore, the right and left sides masseter activity was more synchronized by repeated chewing of the same test food. 1b PCS Healthy volunteers without tooth loss except third molar, no history of dysphagia, no temporomandibular disorders or orthodontic treatment 8 (4 males and 4 females) Mean age: 27.2+/- 1.7 years Tactile sensor system Swallow-Scan Jellies with three different consistencies: soft, medium, hard Tongue pressure to palate The value of tongue pressure in mastication tended to increase with increasing hardness of jelly at Chs.L and R (The anatomical landmarks Ch. L and Ch. R were at the posterior one-third on the line linking the incisive papillae and the hamular notch). 1b PCS Healthy participants with no dental pathology and no problems or dysfunctions with eating 14 (9 females and 5 males) Range: 22-26 years of age Electromyography Three soft and three hard visco-elastic model types of food Number of chewing cycles, sequence duration, cycle duration, vertical amplitude, muscle peak to peak amplitude, opening, closing and occlusal duration. A larger number of chewing cycles (27.0 +/- 13.9 in hard food and 21.0 +/- 9.5 in soft food); and longer sequence duration (21.3 +/- 7.4 s in hard food and 16.4 +/- 6,6 s in soft food) was found with hard food than with soft food. Cycle duration was not affected by food type. The vertical amplitude of mandible was smaller with the soft food than hard (P < 0.001). Hard food augmented only the duration of opening phase during chewing sequence (P < 0.01). Chewing soft food was related with lower peak amplitude of the masseter in comparison with chewing hard food (P < 0.001). Table 5 XXX 2C PCS Dental students with intact dentition and good oral status 15 Mean age: 22.6 ± 1.3 years Electromyography, Electromagnetic transducer Four gelatine-based visco-elastic (more elastic) model foods differing in hardness Number of chewing cycles, sequence duration, masticatory frequency, occlusal duration, muscles activity/sequence, muscle activity/cycle, vertical amplitude (other kinematic parameters) 2C PCS Dental students: with at least 28 teeth and with molars in Angle's Class I occlusion. No history of orthodontic treatment, free of dental pathology. Any functional disturbance of mastication 15 males Range: 21 and 25 years of age Electromyography Four edible products of jelly confectionery having mainly elastic behaviour and differing in hardness (very soft, soft, hard and very hard) Closing duration, opening duration, closing velocity, opening velocity Table 6 XXX Reference Level of evidence Type of study Study sample Sample size and sex Sample age Test of mastication Food sample Primary outcomes Key results Tomoharu et al. 2009 1b PCS Volunteers with normal occlusion 23 males Mean age: 28.3 years Kineograph 3 types of gum: ordinary chewing gum; harder chewing gum, mix of 75% ordinary and 25% harder Muscle activity/cycle, vertical and lateral amplitude, opening and closing velocity The harder the food, the higher is the decrease of oxygen saturation. Chewing motions were significantly larger and velocity was significantly higher in harder gum. 1b PCS Subjects with normal occlusion and function 12 (9 males, 3 females) Mean age: 24 ± 5 years Kineograph (K6 -I, Myotonics Inc. Tukwila, WA, USA) and multichannel electromyograph (Myotronics Research Inc., Tukwila, WA, USA) Chewing gum (soft food), wine gum (hard food) Cycle duration, cycle velocity, peak to peak amplitude, muscle coordination, vertical and lateral amplitudes, closing angle Cycle duration remained stable. The chewing pattern in the frontal plane was significantly wider (P < 0.01) and higher P < 0.001) with higher peak velocity (P < 0.01) and smaller closure angle (P < 0.05) with hard bolus versus soft bolus. The Electromyographic peak amplitude was higher for the hard than the soft bolus (P < 0.001). The relative increase of peak Electromyographic with food hardness was wider for the masseter contralateral than for the masseter ipsilateral to the side of mastication (P < 0.05) (muscle coordination increase). 1b PCS Healthy subjects 8 males Range: 18–21 years of age Electromyography 2 agar and 2 ‘Ina-agar’, which is a mixture of agar softer and smoother than ordinary agar. Number of chewing cycles, sequence duration, muscle activity/sequence Sequence time, chewing cycles and values of the Masseter electromyography differed significantly among the four agar gels (P < 0.01). Matsubara et al. 2006 1b PCS Adults 11 a Mean age: 28.5 ± 7.1 years Videotapes Colour-changeable chewing gum (soft sample), ordinary chewing gum (hard sample) Number of chewing cycles Number of cycles increased from soft to harder foods. Mishellany 2006 1b PCS Ten consenting Caucasian subjects with healthy dentition and without masticatory disorders 10 Mean age: 37.5 ± 3.7 years Examiners' eyes Six different foods (three nuts and three vegetables) Number of chewing cycles, sequence duration Hard food requiring the largest number of cycles and the longest mastication duration. 1b PCS Healthy subjects 15 males Mean age: 24.1 years Electromyography and Kineograph Two types of model foods presenting different rheological behaviour, elastic or plastic, were developed. Each model food consisted of a four-point graded scale of hardness: very soft, soft, hard and very hard Number of chewing cycles, cycle duration, sequence duration, masticatory frequency, vertical and lateral amplitudes, muscle activity/cycle, muscle activity/sequence Sequence duration, number of cycles, electromyography activity per sequence, and Electromyographic action per cycle were greatly increased with raised hardness whichever the model food type (calculated on the whole sequence). Masticatory frequency did not change significantly with hardness. The vertical amplitude increases significantly with increasing hardness whatever the model food and the amplitudes of the lateral movements increases with hardness only during the first five cycles. Paphangkorakt et al. 2006 1b PCS Dental students 20 Range: 20-24 years of age Videotapes (Panasonic NV-VX3) 3 test foods: pork jerky (1 cm long), fresh asparagus (1 cm long) and almond (approximately 2 cm long) representing tough, soft ductile and brittle food respectively Number of chewing cycles, change of masticatory side Number of cycles increased from softer to harder food (P < 0.001). Side preference is less frequent in almond than in pork jerky and asparagus, leading to change chewing-side more frequently in almond and pork jerky. The cohesiveness of food could affect chewing-side as well, the occurrence of bilateral cycles is greater in almond and in pork jerky compared with asparagus. 1b PCS Healthy volunteer without functional mastication problems and not requiring dental treatment. 10 Mean age: 32.4 years Electromyography 1 type of rice, cooked with different amounts of water (1.5x, 2x, 3x and 4x rice weight) Masticatory frequency, sequence duration, muscle peak to peak amplitude, muscle activity/cycle, muscle activity/sequence, muscle coordination Number of cycles increased with hardness (p < 0.001). Chewing rhythm was not influenced. Mean values for the Electromyographic amplitude and muscle activity/chew for the jaw-closing muscles increased significantly with harder samples containing less water. The electromyography results for rice cooked showed that the softer rice needed the least total mastication activity before swallowing because of the shortest sequence duration (p < 0.001). Table 7 XXX Reference Level of evidence Type of study Study sample Sample size and sex Sample age Test of mastication Food sample Primary outcomes Key results 1b PCS Healthy dentate subjects 87 (25 men and 62 women) Mean age: 42.0 ± 12.1 years Optical motion analysis system 3 natural foods: peanuts, raw carrots and cheese, plus a standardized artificial test food (silicon) Number of chewing cycles The results present that the number of strokes before swallowing is bigger in carrots than peanuts and cheese (P < 0.001). 1b PCS Healthy Volunteers with a complete dentition and without signs or symptoms of oral dysfunction. 67 (38 females and 29 males) Mean age: 42 years Electromyography, Electromagnetic transducer Four gelatine-based visco-elastic model foods differing in hardness Number of chewing cycles, cycle duration, opening duration, closing duration, muscle activity/sequence, vertical amplitude, lateral amplitude Hard food was related to a significant rise in the average number of cycles (p = 0.0001), mean summed Electromyographic activity per sequence and mean vertical amplitude. In the early phase of mastication (2-4 cycles) cycle duration, duration of opening, closing and lateral amplitude also increased significantly. 1b PCS Healthy subjects without signs or symptoms of oral dysfunction 10 (5 women, 5 men) Range: 24–28 years of age Kineograph (Analysing System III) chewing gum, boiled fish paste, peanuts, gummy jelly, pickled Japanese radish, dried squid and giant corn Change of masticatory side Hard food evoked higher masticatory laterality (changes of masticatory side) than soft food. 1b PCS Healthy young adults with at least eight pairs of natural post-canine teeth 25 (11 females, 14 male) Mean age: 25-30 years Electromyography Meat samples of two different textures: T1 tough and dry and T2 tender and juicy Muscle activity/sequence, sequence duration Mean muscular activity and chewing duration were lower during the chewing of tender meat than tough meat. Filipic et al. (2002) 1b PCS Healthy subjects with a complete dental sequence and without signs or symptoms of oral dysfunction 19 (12 males, 7 females) Range: 20-37 years of age Stereo-photo-grametric procedures (ELITE system) Soft food (banana), food of moderate consistency (white bread), solid food (carrot) Vertical and lateral amplitude The average range of vertical mandible amplitude was 8+/−18 mm for banana, 8+/−51 mm for bread and 9+/−18 mm for carrot. The average range of lateral mandible amplitude was 3+/−03 mm for banana, 3+/−27 mm for bread and 4+/−01 mm for carrot. 1b PCS Faculty and stuff of college of Dentistry with Class I normal occlusion without, signs or symptoms of temporomandibular disorders, extensive dental work, or currently undergoing dental treatment 26 (13 males, 13 females) Mean age: 23,6 ± 5 years Optotrak cameras Two gums of different hardness: soft and hard Cycle duration, opening and closing velocity, lateral amplitude Mastication of harder food does not have a longer duration of the chewing cycle. Chewing harder food leads to an increased velocity of the lower jaw in all segments, apart from during the occlusal phase of closing. The cycle shape did not change with different gum but the overall size of the cycle was larger with harder gum. 1b PCS Dental students with intact dentition and good oral status 15 Mean age: 22.6 ± 1.3 years Electromyography, Electromagnetic transducer Four gelatine-based visco-elastic (more elastic) model foods differing in hardness Number of chewing cycles, sequence duration, masticatory frequency, occlusal duration, muscles activity/sequence, muscle activity/cycle, vertical amplitude (other kinematic parameters) Number of chewing strokes and chewing time increased significantly with hardness. Masticatory frequency remained constant. Greater electromyographic activity both during the sequence and a cycle is induced by chewing harder products. Vertical amplitude and occlusal duration increase with hardness in a less significant way. Lateral amplitude, opening and closing velocity increase with harder food only in the early stage of mastication (2-4 cycles). 1b PCS Dental students: with at least 28 teeth and with molars in Angle's Class I occlusion. No history of orthodontic treatment, free of dental pathology. Any functional disturbance of mastication 15 males Range: 21 and 25 years of age Electromyography Four edible products of jelly confectionery having mainly elastic behaviour and differing in hardness (very soft, soft, hard and very hard) Closing duration, opening duration, closing velocity, opening velocity Closing and opening duration and velocity were higher with very hard samples than with very soft samples. 1b PCS Subjects with complete dentition healthy periodontal condition and no history of pain or functional disturbances 12 males Range: 22 to 26 years of age Electromyography Products of standardized test-foods with known hardness (20, 40, 80 kg) Muscle activity/sequence, muscle peak-to-peak amplitude, muscle burst duration Muscle activity/sequence decreased with food hardness. The contraction duration (muscle burst duration) and the peak to peak amplitude during chewing the 20, 40, and 80 kg test-foods were increased respectively. The contraction duration increased more than the peak amplitude (P > 0·05). 3.2 Study designs and population They were all prospective clinical studies (PCS) where adults were asked to chew hard and soft food and the physiological parameters of mastication were evaluated using different methods and compared. Only eight studies ( ; ; ; ; ; ; ; ), included specifically males or females subjects, while all the rest monitored both sexes. The population sample size ranged from 6 to 87 and the sample age went from 18 to 53 years. Three studies had a control group, one ( ) compared adults with children and the other two ( ; ) compared adults with elderly. The group of adults was the only considered for the review. In all of the studies, the subjects were healthy adults with good dental and TMJ status. 3.3 Food hardness influence on physiologic parameters of mastication The physiologic parameters of mastication were sorted in four groups: 1) number of cycles 2) mastication duration 3) muscle activity and coordination and 4) amplitude and shape of mandibular displacement. Tables 8 and 9 show the findings regarding the influence that food hardness has on the masticatory parameters. Table 8 Findings regarding the association between food hardness and masticatory parameters Masticatory Parameters Statistically Significant Increase Not Statistically Significant Increase Statistically Significant Decrease Not Statistically Significant Decrease No changes Number of cycles Number of Chewing cycles ; , Lieberman et al. 2016, , Zhu et al 2015, ; , Shiozawa et al. 2012, ; , Matsubara et al. 2006, ; , Paphangkorakit et al. 2005, ; ; ; Laird et al. 2017, Wada et al. 2016, ; , Mishellany 2006 Iida et al. 2010 Remijn et al. 2015, Cazal et al. 2015 Number of "tongue-pullback" (TPM) Number of St2tr cycles ; Iida et al. 2010 Mastication duration Frequency of mastication Zhu et al. 2015 Remijn et al. 2015, Cazal et al. 2015, ; Cycle duration Laird et al. 2017, ; , Remijn et al. 2015, ; ; ; ; ; Opening duration ; Remijn et al. 2015, Laird et al. 2017 Closing duration Laird et al. 2017, Occlusal duration Remijn et al. 2015 Opening velocity Tomoharu et al. 2009, ; Remijn et al. 2015, ; Closing velocity Tomoharu et al. 2009, ; ; Maximum velocity St1tr duration Sequence duration ; , Zhu et al. 2015, , Shiozawa et al. 2012, ; ; ; ; ; , Remijn et al. 2015, , Mishellany 2006 Iida et al. 2010 Table 9 XXX Masticatory Parameters Statistically Significant Increase Not Statistically Significant Increase Statistically Significant Decrease Not Statistically Significant Decrease No changes Muscle activity and coordination Muscle activity/cycle ; , Shiozawa et al. 2012, Tomoharu et al. 2009, ; ; Muscle activity/sequence Okayama et al. 2016, Lieberman et al. 2016, , Zhu et al. 2015, Cazal et al. 2015, , Ishihara et al. 2010, ; ; ; ; ; ; Muscle burst duration ; Muscle peak-to-peak amplitude ; ; , Zhu et al. 2015 Tongue pressure/palate (mastication) Muscle coordination , , Cazal et al. 2015, ; , Remijn et al. 2015 Bite force (maximal EMG voltage) ; Zhu et al. 2015 Amplitude and shape of mandibular displacement Vertical amplitude Laird et al. 2017, ; , Tomoharu et al. 2009, ; ; , Filipic et al. 2002 Lateral amplitude Laird et al. 2017, , Tomoharu et al. 2009, ; ; ; ; Filipic et al. 2002 Closing angle Change of masticatory side ; Paphangkorakit et al. 2005 Remijn et al. 2015 Tongue lateral amplitude Tongue vertical amplitude 3.3.1 Number of cycles Twenty-nine articles on thirty-eight debated about the effect of food hardness on the masticatory cycles number during the entire process of chewing that starts after the moment of food intake and finishes before the first swallowing cycle. After food intake in the stage 1 transport cycle (St1tr), the “tongue pullback movements” (TPM) moves a piece of solid food from the anterior part of the oral cavity to the region behind the canines for mastication. The first chewing cycle begins when the jaw opening is maximum and finishes at following maximum opening of the mandible. In stage II transport cycle (St2tr), the “tongue sqeezeback movements” (TSM) propels the triturated food, which is pressed posteriorly between the tongue and palate, to the pharynx for swallowing ( ). Eighteen of the twenty-nine articles showed in a statistically significant way that when there is an increase in food hardness the chewing apparatus adapts by increasing the number of chewing cycles. Moreover, the increase of cycles from a soft to a harder diet was also discussed in other 5/29 articles without finding a statistically significance. 3/29 articles presented that the cycles number does not change with hardness of food and only found that eating white rice (soft tissue) required more cycles than chewing udon noodle (hard tissue). The number of TPM during the St1tr cycle ( ) and TSM and St2tr cycles ( ; ; ) increased from soft to harder food. Only found that the number of St2tr cycles is less when chewing udon noodle than white rice. 3.3.2 Mastication duration Twenty-four articles on thirty-eight analysed the parameters of mastication duration in relation to hardness of food. Sixteen articles analysed sequence duration that represents the time between food intake and the first swallowing cycle and includes St1tr, chewing phase and St2tr. 11/16 articles demonstrated a statistically significant increase of sequence duration with food hardness and 4/16 supported the same view without a statistical significance. Only found a decrease of sequence duration with hardness. Masticatory frequency, which is described as the ratio between the number of masticatory cycles and mastication duration was described as increasing ( ), decreasing ( ), or presenting no change ( ; ; ; ; ) with food hardness. Ten studies showed a lack of variation in cycle duration and only ( ) found an increased cycle duration with hard food. However, the durations of the cycle phases differed across foods with different hardness. Opening duration increased with hard food in 4 studies and decreased in . Closing duration rose with hardness in 3 articles and decreased in . The occlusal part of the cycle increased in and and remained steady in . Opening and closing velocity upturned in a significant way with hard food in 3 studies and other 5 studies supported this increase with hardness but without a statistical significance. described an increased maximum velocity of the cycle with harder food. 3.3.3 Muscle activity and coordination Twenty-one of the thirty-eight articles evaluated the activity and coordination of the masticatory muscles. The masticatory muscles activity, which is represented by the area below the electromyographic (EMG) curve, increases significantly with hardness both when considering a single chewing cycle (muscle activity/cycle) (7 articles) or the whole mastication sequence (muscle activity/sequence) (14 articles). Further the variables that express the amplitude and the duration of muscle activity in a chewing cycle increased with hardness. Muscle peak-to-peak amplitude rose in a significant way as showed in , Kohyama et al. (2016; 2014; 2005) and , and muscle burst duration upturned as described in and . Five studies presented as muscle coordination between right and left-side increased significantly with hardness, but on the contrary Miyaoka et al. (2016) and found no changes of muscle coordination with the rise of food hardness. The pressure of the tongue on the palate during mastication increased from soft to harder food ( ). 3.3.4 Amplitude and shape of mandibular displacement Sixteen of the thirty-eight articles evaluated the amplitude and shape of mandibular displacement. Both vertical (8 studies) and lateral (8 studies) amplitude of the chewing cycle increase significantly with hardness. demonstrated that the closure angle of the chewing cycle, which is demarcated by the horizontal line on the basis of the last 2 mm before closing completely, changed with food hardness and was smaller for the hard than for the soft bolus (P < 0.05). ; and found a higher number of changes of the masticatory side with hard food compare with soft food, by contrast suggested that individuals chewing evenly on either side with soft foods might chew only on one side with hard food. The amplitude of the tongue movements in the lateral and vertical dimensions during mastication increase significantly from soft to harder food ( ). 3.4 Quality of the studies The level of evidence, evaluated following the criteria of the Oxford Centre for Evidence-based Medicine ( , ), was 1b for all the articles selected ( Tables 3,4,5,6,7 ). The results of the CASP evaluation are shown in Table 10 . All the studies (n = 38, 100%) addressed a clearly focused issue, measured outcomes to minimise bias and adopted a follow up of subjects complete and long enough. The quality of the studies was also determined taking into consideration the control of confounding factors, such as age, gender, dental and TMJ status, textural properties of food and food size. Table 10 The results of the quality assessment References 1 2 3 4 5 (a) 5 (b) 6 (a) 6 (b) 7 8 9 Quality assessment ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate Laird et al. 2017 ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low Wada et al. 2016 ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate Lieberman et al. 2016 ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low Remijn et al. 2015 ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low ✓ N X ✓ ✓ ✓ ✓ ✓ ✓ N ✓ Moderate Zhu et al. 2015 ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low Cazal et al. 2015 ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low Shiozawa et al. 2012 ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low Wilson et al. 2011 ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate Ishihara et al. 2010 ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate Iida et al. 2010 ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low Tomoharu et al. 2009 ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate Piancino et al 2007 ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate Matsubara et al. 2006 ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate Mishellany 2006 ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low Paphangkorakit et al. 2005 ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low ✓ ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ Moderate ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate ✓ ✓ X ✓ X X ✓ ✓ ✓ ✓ ✓ Low Mioche et al. 2002 ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate Filipic et al. 2002 ✓ N X ✓ X X ✓ ✓ ✓ N ✓ Low ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ Moderate ✓ N ✓ ✓ X X ✓ ✓ ✓ N ✓ Moderate 1 Did the study address a clearly focused issue? 2 Was the cohort recruited in an acceptable way? 3 Was the exposure accurately measured to minimise bias? 4 Was the outcome accurately measured to minimise bias? 5 (a) Have the authors identified all important confounding factors? 5 (b) Have they taken account of the confounding factors in the design and/or analysis? 5 (b) Have they taken account of the confounding factors in the design and/or analysis? 6a. Was the follow up of subjects complete enough? 6b. Was the follow up of subjects long enough? 7. Do you believe the results? 8. Can the results be applied to the local population? 9. Do the results of this study fit with other available evidence? ✓, satisfied; X, not satisfied; N, not applicable. Only two studies controlled all the confounding factors considered to evaluate the relationship between mastication and food hardness ( ; ). Most of the studies (23/38) considered at least three confounding factors. Age was considered in almost all the manuscripts. However only 11 studies ( ; ; ; ; ; ; ; ; ; ; ), analysed the relationship between food hardness and mastication in male and female subjects, separately. Good dental and TMJ status were considered in 32 studies and food or model food size in 30 studies. Textural proprieties were considered in 19 studies but only analysed the effects of plasticity and elasticity on the relationship between food hardness and masticatory parameter. The grade assigned to each article following the CASP evaluation was Moderate (22/38, 58%) and Low (16/38, 42%), however there is a high concordance among the results found in the different studies. 4 Discussion In this review, the influence of food hardness on the physiological parameters of mastication in adults with healthy dental and TMJ status health was investigated by summarizing in a systematic way the findings derived from studies produced during the last twenty years and regarding this topic. A search for studies regarding the association of food hardness and mastication was carried-out in PubMed, Web of Science, Scopus and Cochrane Library. The search strategy had a quite high specificity in order to find as many relevant publications as possible avoiding the possibility of missing data related to the high number of terminologies describing the masticatory process. Studies on animals were excluded because they focus more on the structural changes of the craniofacial structures related to a hard diet. On the other hand, the review aimed to highlight the functional changes of the masticatory physiological parameters influenced by a hard diet. The collected studies are highly representative, being the clinical articles with the highest evidence available (prospective clinical studies, Tables 3–7 ) about the association of food hardness and mastication in adults. 4.1 Quality assessment of the studies One of the two screening questions of CASP determined the quality of the studies taking into consideration the bias related to sample selection. The second question “Was the cohort recruited in an acceptable way?” showed a positive answer for 20/38 (53%) articles, however in the remaining 18/38 (47%) manuscripts the authors did not give information on sample selection. The selection of testing materials is very important in the study of the relationship between food hardness and masticatory function. The main problem is that food is a composite stimulus that is difficult to condense to a single physical aspect such as hardness. Thirteen of the 38 articles used a type of food or model food that is characterized by a pure consistency, 7/38 studies defined the hardness of the food or model food selected on the basis of the of the ratio of the square roots of toughness and modulus of elasticity. The majority of publications considered in the review (17/38) tested food that displays different rheological behaviours. In many studies of this review (22/38), authors used different natural food products, which are not consistent in their hardness and water contents, to create a scale of hardness when recording chewing. The problem raised because the chewing response to a product could depend on different textural properties of the product (such as elasticity, plasticity, stickiness, and brittleness) and not only on the hardness, leading to difficulties in reproducibility of the results. This might explain the fact that masticatory frequency was described in the review as increasing ( ), decreasing ( ), or presenting no change ( ; ; ; ; ) with food hardness. Moreover, , contrarily to the majority of the studies in the review, described a decrease of the chewing cycles number and of the sequence duration with udon noodles respect to white rice. Texture measurement of these Japanese foods showed that white rice was less hard than udon noodle. The findings of the study were possibly related to the higher quantity of liquid of udon noodles, because they are usually eaten as a noodle soup and the fact that udon noodles have a higher stickiness than white rice. Model foods with constant textural proprieties except hardness, were tested in the remaining 16 articles where the differences in masticatory parameters could be correlated directly to hardness. Among the articles in the latter group, evaluated the effect of other rheological characteristics on mastication such as elasticity and plasticity using a regression linear analysis. Two kinds of model foods showing different rheological behaviour, elastic or plastic, were created. Each model food presented four different grades of hardness: very soft, soft, hard and very hard. found that hardness influences more the muscular masticatory parameters (the chewing apparatus adjusts to a rise in food hardness by increasing both the number of cycles and the muscular work) whereas elasticity and plasticity effected more the kinematic characteristics of mastication. observed the impact of brittleness on the masticatory parameters. They used two kinds of hydrocolloid gels called A and K, with the same fracture load (hardness) but A with a higher elastic modulus than K (A tougher than K). Cycle characteristics in the early part of the sequence did not change between A and K gels because they have the same hardness but factors such as chewing cycles number and muscle activities/sequence were significantly lower for A gel compared with K gel before the first swallowing. K gel lost its structure slower than A gel during oral processing because of its brittle characteristics and the muscle effort and the chewing cycles number were seen to decrease more rapidly for A gel. and developed model foods with the same visco-elastic rheological behaviour and constituted a four points scale to evaluate hardness. Their findings highlighted the fact that when pure stimuli are not used to analyse mastication, food hardness is better tested in the early part of the mastication sequence before foods with different rheological proprieties start behaving differently due to changes in their characteristics, leading to a modification and modulation of the masticatory parameters during the chewing sequence ( ). Regarding the confounding factors, only two of the articles in the review ( ; ) did control for all the them, this weakens slightly the consistency of the evidence collected. Age, gender, dental and TMJ status and size of food, beyond textural proprieties that were commented above, were reported as factors related to masticatory parameters ( ). Consequently, the impact of these factors in the investigation should be considered. Age, dental and TMJ status and size of food were considered by the majority of the article in the review. Gender was controlled in 11 articles. employed a general linear model and found that males had a longer chewing duration and achieved more muscle activity/sequence than females. performed a linear regression analysis to evaluate the impact of gender on the chewing cycles number during mastication natural and artificial foods and they did not found differences between males and females. More control for the confounding factors may be necessary in future studies. 4.2 Does mastication change with food hardness? Almost the totality of the articles was in agreement showing an increase of the sequence duration and of the chewing and St2tr cycles with food hardness. The majority of the articles described a larger overall size of the chewing pattern, which characterized the mastication of hard food, with an increased vertical and lateral amplitude and also added with a reduced closing angle. The articles in the review also found an augmented velocity of opening and closing in the chewing cycle ( ; ; ; ; ; ) and an increased maximum velocity ( ). These aspects of the chewing pattern should lead to an increased acceleration of the mandible prior to contact the food and an easier break-down of it. Therefore, the longer sequence duration with an increased cycles number and the increased chewing pattern size together with the velocity reflects a higher efficiency of mastication with hard bolus. Most studies in the review agreed that the time of the chewing cycle did not modify with food hardness whereas authors had contrasting views on the changes in length of the different part of the masticatory cycle (opening, closing and occlusal durations). Moreover, the considered articles showed slightly different opinions regarding the changes of masticatory frequency with food hardness. Discordant findings may depend on the fact that authors studied the chewing cycle and its parts in different phases of the mastication sequence and using also different foods and foods samples with different rheological behaviour (such as plasticity, elasticity etc.). The entire number of manuscripts in the review that studied the muscle work during the entire sequence of chewing showed an increase of the muscular activity with hard food compare with soft food. Most of these articles also supported that muscle activity/cycle, burst duration, peak-to-peak amplitude and maximal bite force rise with food hardness ( ; ; , ; ; ; ; ). The increased muscle force was responsible for the higher velocity of the lower jaw during mastication. When the bolus hardness increased, the coordination between muscles of the masticatory side and the contralateral side improved ( ; , , ; ). The muscular force of the contralateral side is usually lower than on the ipsilateral side, but with hard food the difference in muscular activity between the two sides decreased leading to a better mandibular equilibrium ( ). and did not support this increase in muscle coordination and quoted that the difference between the muscle force of the ipsilateral and contralateral side is not influenced by food hardness. However, considered in his study the pattern of masseter and temporalis muscles activity that is independent of the amplitudinal and durational parameters that were usually analysed in the studies supporting increased muscle coordination with food hardness. identified in their study a large percentage (30%) of Standard Measurement Error (SME) of surface electromyographic (sEMG) measurements. Three studies in the review ( ; ; ) proposed that chewing-side pattern varied with food consistency and precisely that the change of masticatory side was more frequent when chewing hard food. By contrast, described a decrease in the number of changes of masticatory side with hard food. The disagreement could be related to the investigation method, the number of tests and the type of food used. , using the 3D motion-capture system, showed that chewing biscuit is characterized by fewer changes in side of mastication than chewing bread, however they found a large standard measurement error in evaluating the alteration of masticatory side. Visual examination showed a rather adequate validity in studying variations of masticatory side and had the advantage of not using an intra-oral device that might affect with individuals’ usual jaw movements ( ). Moreover, dealt with natural food products and with the problem to standardise the rheological properties of this kind of food. The choice of chewing side might depends on the cohesiveness of the bolus since food with great cohesion (such as fibrous food) is not easily dissociated and usually is chewed unilaterally ( ). There are also articles describing the role of the tongue during the oral processing. During the St1tr, mastication and St2tr phases the pressure that the tongue expressed on the palate and on the alveolar ridge and the amplitude of tongue movements increased going from a soft diet to a harder diet ( ; ; ; ; ). The reported changes of kinematic and EMG variables with food hardness might denote the normal ability of the stomatognathic system to adapt rising the masticatory efficiency, defending the temporomandibular joint and effecting craniofacial growth. The increase of almost all the parameters of mastication together with more muscle coordination and more changes of masticatory side could lead to a more variable and symmetric load on the craniofacial structures. This could reduce the intra-articular pressure and improve the joint lubrification system ( ) avoiding an overload of the temporomandibular joint during the mastication of a hard bolus. Moreover a more variable and symmetric load could explain the results of previous studies that had clearly demonstrated the negative effect of soft diet on the growth of the craniofacial bones during growing ( ; ; ; ) and on the patency of the facial suture during ageing ( , ; ; ). Studies demonstrated that animals grown-up with a harder diet had bigger temporalis and masseter muscles ( ; ) and showed that the association between muscle thickness and craniofacial morphology had been investigate quite a lot. Studies that analysed different diets related to cultural differences ( ), or living styles (non-developed people vs. developed people) ( ; ) seem to confirm the presence of differences in craniofacial development owed to diet consistency and the fact that the need of orthodontic treatment have increased in the last decades. The hypothesis that diet consistency could influence the orofacial development suggests that a hard diet leads to a higher mastication efficiency reducing the percentage of malocclusions. This suggests that a certain type of foods could be selected to encourage the development of chewing abilities and the normal craniofacial development and possibly decrease the necessity for orthodontic treatment. It is also important to highlight how the relation between mastication and food hardness has an impact on obesity and cognitive status in adults. The decrease of the number of chewing cycles and of mastication duration seems to be related to health issues as obesity ( ) and impaired cognitive activity ( ; ; ; ). The improvement of mastication behaviour in the life style is necessary for health promotion and thus, based on the findings of this review, intervention studies concerning the effect of mastication on dietary habits are required. 5 Conclusion Despite the different methodologies used and the presence of bias, the studies’ findings are consistent among them. It is showed that chewing hard food, in comparison with chewing soft food, increases almost all the physiological masticatory parameters, muscle coordination and changes of masticatory side. These findings could explain a more variable and symmetric load on the craniofacial structures that influences their development and well-being, and in part the relation between mastication and general health problems such as obesity and impaired cognitive activity. CRediT authorship contribution statement Ingrid Tonni: Conceptualizazion, Methodology, Writing - original draft, Writing - review & editing, Visualization. Giulia Riccardi: Formal analysis, Investigation, Resources, Writing - review & editing, Visualization. Maria Grazia Piancino: Conceptualizazion, Writing - review & editing, Visualization, Supervision. Chiara Stretti: Formal analysis, Investigation, Resources, Writing - review & editing, Visualization. Fulvia Costantinides: Data curation, Validation, Writing - review & editing, Visualization. Corrado Paganelli: Conceptualizazion, Writing - review & editing, Visualization, Project administration. Declaration of Competing Interestt None. Acknowledgements None. References Akazawa Y., Kitamura T., Fujihara Y., Yoshimura Y., Mitome M., Hasegawa T.: Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus. Int J Mol Med 2013; 31: pp. 307-314. 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