18 years, absence of medical conditions that could decrease salivary flow). Unstimulated whole saliva was collected during ten minutes, and salivary flow rate (ml/min), pH, and bicarbonate concentration (mmol/l) were measured using a Radiometer ABL 520. The 5 percentile of salivary flow rate and bicarbonate concentration was considered the lower limit of normality. Results: median salivary flow rate was 0.48 ml/min (range: 0.1-2 ml/min). Age younger than 44 years was associated with higher flow rates (OR 2.10). Compared with women, men presented a higher flow rate (OR 3.19) and buffer capacity (OR 2.81). Bicarbonate concentration correlated with salivary flow rate. The lower-end values of normal flow rate and bicarbonate concentration were 0.15 ml/min and 1.800 mmol/l, respectively. The presence of obesity, smoking, and alcohol consumption did not influence salivary parameters. Conclusions: in healthy volunteers, salivary flow rate depends on age and gender, and correlates with buffer capacity. Obesity, smoking, and alcohol use do not influence salivary secretion.]]>
18 años, sin factores conocidos que disminuyan la secreción salivar). Se ha recogido la saliva total, sin estímulo, durante 10 minutos, determinando su débito (ml/min), pH y capacidad tampón (concentración de bicarbonato en mmol/l) mediante autoanalizador Radiometer ABL 520. Se han calculado los límites inferiores del débito salivar y concentración de bicarbonato por el percentil 5. Resultados: la mediana del débito salivar es 0,48 ml/min (rango 0,1-2). La mayor edad condiciona una disminución del débito salivar; los sujetos con edad < 44 años presentan mayor flujo salivar respecto a edad superior (OR 2,10). Los hombres presentan mayor secreción salivar respecto a las mujeres (OR 3,19). La concentración de bicarbonato se correlaciona positivamente con el débito salivar; los hombres presentan una mayor capacidad tampón respecto a las mujeres (OR 2,81). Los límites inferiores de la normalidad del débito y concentración de bicarbonato son 0,15 ml/min y 1,800 mmol/l, respectivamente. La obesidad y los hábitos tabáquico y alcohólico no modifican las características de la secreción salivar. Conclusiones: la edad y sexo influyen sobre el débito salivar; la capacidad tampón se relaciona positivamente con el débito salivar. Los hábitos tabáquico y alcohólico, así como la obesidad no modifican la secreción salivar.]]>
| ORIGINAL PAPERS |
Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy volunteers
C. Fenoll-Palomares, J. V. Muñoz-Montagud1, V. Sanchiz2, B. Herreros2, V. Hernández2, M. Mínguez2 and A. Benages2
Medicina Familiar y Comunitaria. Centro de Atención Primaria. Rafelbunyol, Valencia. 1Centro de Especialidades. Burjassot. Valencia. 2Service of Gastroenterology. Hospital Clínico Universitario. Universitat de Valencia, Spain
ABSTRACT
Objectives: to assess the salivary flow rate, pH, and buffer capacity of healthy volunteers, and their relationships with age, gender, obesity, smoking, and alcohol consumption, and to establish the lower-end value of normal salivary flow (oligosialia).
Methods: a prospective study was conducted in 159 healthy volunteers (age > 18 years, absence of medical conditions that could decrease salivary flow). Unstimulated whole saliva was collected during ten minutes, and salivary flow rate (ml/min), pH, and bicarbonate concentration (mmol/l) were measured using a Radiometer ABL 520. The 5 percentile of salivary flow rate and bicarbonate concentration was considered the lower limit of normality. ]]>
Results: median salivary flow rate was 0.48 ml/min (range: 0.1-2 ml/min). Age younger than 44 years was associated with higher flow rates (OR 2.10). Compared with women, men presented a higher flow rate (OR 3.19) and buffer capacity (OR 2.81). Bicarbonate concentration correlated with salivary flow rate. The lower-end values of normal flow rate and bicarbonate concentration were 0.15 ml/min and 1.800 mmol/l, respectively. The presence of obesity, smoking, and alcohol consumption did not influence salivary parameters.
Conclusions: in healthy volunteers, salivary flow rate depends on age and gender, and correlates with buffer capacity. Obesity, smoking, and alcohol use do not influence salivary secretion.
Key words: Saliva. Salivary flow rate. Salivary buffer capacity. Oligosialia.
Fenoll-Palomares C, Muñoz-Montagud JV, Sanchiz V, Herreros B, Hernández V, Mínguez M, Benages A. Unstimulated salivary flow rate, pH, and buffer capacity of saliva in healthy volunteers. Rev Esp Enferm Dig 2004; 96: 773-783.
Recibido: 24-06-04.
Aceptado: 30-06-04.
Correspondencia: Adolfo Benages. Servicio de Gastroenterología. Hospital Clínico Universitario. Avda. Blasco Ibáñez, 17. 46010 Valencia. e-mail: benages@uv.es
INTRODUCTION
Saliva plays a critical role in oral homeostasis, as it modulates the ecosystem within the oral cavity (1). Lubrication of the alimentary bolus, protection against virus, bacteria and fungi, buffer capacity, protection and repair of the oral mucosa, and dental remineralization are some of the functions of saliva (2-4). Taking this into account, quantitative and/or qualitative alterations in salivary secretion may lead to local (caries, oral mucositis, candidiasis, oral infections, chewing disorders) or extra-oral (dysphagia, halitosis, weight loss) adverse effects (5-7).
]]> Xerostomia or "dry mouth" is usually the clinical expression of decreased salivary secretion; however, it may occur without a low salivary flow rate (8).Xerostomia is a common condition (9) that leads patients to visit many specialist clinics (gastroentrologists, dentists, internal medicine doctors), as it may develop in many local and systemic diseases (Sjögren's syndrome, diabetes mellitus, drug exposures, radiation to the head or neck) (10-13); nevertheless, in older patients xerostomia may develop in the absence of any disease (14-15), which may be explained by an ageing-related decrease in salivary secretion.
It has been suggested that ageing leads to a decrease in salivary flow rate as a consequence of parenchymal atrophy (16-21). Alternatively, some authors showed that healthy old people had a normal salivary flow rate with a great functional reserve, mainly in the parotid glands (22-26).
The buffer capacity of saliva is an important factor, which plays a role in the maintenance of salivary pH, and in dental remineralization. The buffer capacity of saliva basically depends on bicarbonate concentration (27); it correlates with salivary flow rate (28), as any factor decreasing salivary flow rate tends to decrease its buffer capacity and to increase the risk of caries development (29).
Other factors that may influence salivary flow rate and the buffer capacity of saliva are gender, smoking status, and alcohol consumption. Women show a lower salivary flow rate (30-32) and decreased buffer capacity (29). The relationship between salivary secretion and smoking or alcohol consumption is controversial, as normal secretion and the presence of hyposialia have both been reported (33-37).
The aim of this study was to analyze unstimulated salivary flow rate, salivary pH, and salivary buffer capacity in a group of healthy subjects, as well as their relationship with age and gender, together with other individual factors (obesity, smoking status, alcohol consumption), in order to establish normal ranges in the healthy population in our area.
MATERIAL AND METHODS
An observational prospective study on healthy volunteers who signed an informed consent, from April 1998 to May 2000. Volunteers were included if they were older than 18, did not suffer from acute or chronic diseases of the oral mucosa or salivary glands, did not complain of "oral dryness" or "oral burning", did not suffer from acute infectious diseases, systemic illness or cardiac, renal, respiratory or hepatic failure, and had not received therapeutic radiation to the head or neck region; women were not to be pregnant or were using safe contraceptive methods (except anovulatories). Volunteers were excluded from the study if they did not meet inclusion criteria or did not sign an informed consent.
Every patient was explored by the same stomatologist to rule out acute or chronic diseases of the oral mucosa or salivary glands. Demographic features were collected (age, gender, height, and weight), as well as smoking status and alcohol consumption. In each patient the body mass index was determined, and if greater than 30 the subject was considered obese (38). The subject was considered a smoker if he smoked, regardless of the number of cigarettes, and an alcohol consumer if alcohol intake was greater than 60 g/day in men or 40 g/day in women.
Study of salivary secretion
]]> The study of salivary secretion was performed without any stimulus in the morning (9 to 11 a.m.), under standard temperature and humidity conditions. All subjects refrained from eating, drinking or smoking for a minimum of 2 h before saliva collection.Subjects were comfortably seated and, after a few minutes of relaxation, they were trained to avoid swallowing saliva and asked to lean forward and spit all the saliva they produced for 10 minutes into a graduated test tube, through a glass funnel. The whole volume collected for 10 minutes was then measured.
To determine salivary pH and bicarbonate concentration, an analyzer Radiometer ABL 250 was used. To diminish the error probability, each sample was analyzed three times, and the mean value was assumed to be the real one.
We analyzed the following variables of salivary secretion: salivary flow rate (ml/min), macroscopic appearance (transparent, turbid or bloody), pH, and buffer capacity expressed as bicarbonate concentration (mmol/l).
Statistical study
A descriptive analysis of variables was performed. To assess the normal distribution of quantitative variables, a Kolmogorov-Smirnov test was used. Variables with a normal distribution were compared using Student's t test or an ANOVA test (when comparing more than two groups). Non-parametric tests (Mann-Whitney U, Kruskal-Wallis) were used to compare variables without a normal distribution. To assess the correlation between quantitative variables, Pearson's coefficient was used. A Chi-square test was used to compare qualitative variables. Variables which obtained a p value less than 0.1 were included in a multivariate analysis (logistic regression, step forward method). Statistical significance was assumed if p lt; 0.05. The statistical analysis was performed with an SPSS 11.5 pack for Windows (SPSS Inc., Chicago, Illinois).
RESULTS
Subjects
One hundred and fifty-nine patients made up the study group (52 males, 107 females) (Table I). Age was similar for both men and women (p = 0.796); obese people were younger than non-obese individuals (31.94 ± 9.64 vs 45.52 ± 14.03 years, p < 0.001); smokers were younger than non-smokers (36.85 ± 11.75 vs 46.69 ± 14.18 years, p < 0.001); subjects who did not drink alcohol were older than those with alcohol consumption (45.46 ± 14.56 vs 36.83 ± 9.54 years, p = 0.001).
Features of saliva are shown in table I. Unstimulated salivary flow rate does not present a normal distribution. According to Navazesh (39), who defined hyposialia (basal flow rate equal or less than 0.16 ml/min), only eight subjects (5.03%) were under this level; these subjects, compared with those with a normal flow rate, have a lower pH (6.5390 ± 0.3605 vs 6.8036 ± 0.2782, p = 0.011) and a lower bicarbonate concentration (3.5625 ± 3.0654 mmol/l vs 5.8611 ± 2.7248 mmol/l, p = 0.022). In the subjects with hyposialia, the aspect of saliva was more frequently turbid (6/8 subjects).
A significant positive correlation was found between salivary flow rate, pH, and bicarbonate concentration (r = 0.322, p < 0.001, and r = 0.425, p lt; 0.001, respectively), and between pH and bicarbonate concentration (r = 0.736, p = 0.001).
Relationship between salivary parameters and demographic variables
Men showed a greater flow rate than women (median 0.57 ml/min, range 0.15-2 vs 0.42 ml/min, range 0.10-2, p < 0.001). Between men and women no differences were found in salivary pH (6.8400 ± 0.3199 in men vs 6.7661 ± 0.2686 in women, p = 0.128), but men's buffer capacity was higher (6.626 ± 3.1239 mmol/l vs 5.3171 ± 2.4989 mmol/l, p = 0.010).
To analyze the role of age, percentiles 25 and 75 were determined (32 and 54 years, respectively). We found that older patients presented a significant lower salivary flow rate (Table II), but no differences were found in pH or buffer capacity between these three age groups (Table III). Age correlated significantly with flow rate (r = -0.222, p = 0.005), but not with pH (r = -0.106, p = 0.185) or bicarbonate concentration (r = -0.030, p = 0.710).
]]>
Salivary variables in obese subjects, smokers or alcohol consumers did not differ from those in non-obese, non-smoking or non-alcohol consuming volunteers (Tables II and IV).
Univariate analysis
To study salivary variables with respect to qualitative variables and age (younger or older than the median age), they were classified into two categories (lower or greater than the median value). Table V shows the results of this analysis.
The variable "hyposialia" (defined according to Navazesh) (39), has not been analyzed, as it was present in only 8/159 volunteers (5.03%); but it is worth noting that 6 of them were women, 7 of them were older than 44, and none of them was obese, a smoker or an alcohol consumer.
Multivariate analysis
Salivary flow rate above the median value was associated with younger age (< 44 years) (OR 2.10, CI95% 1.08-4.05, p = 0.027) and male gender (OR 3.19, CI95% 1.56-6.50, p = 0.001). Women showed a pH under the median value (OR 2.13, CI95% 1.081-4.207, p = 0.029), whereas in men bicarbonate concentration tended to be above median values (OR 2.81, CI95% 1.39-5.67, p = 0.004).
]]> DISCUSSIONNowadays, to offer better health care to people a trend is seen towards integrating medical and odontological knowledge (40); hence, gastroenterologists should learn about salivary disorders, as saliva is the initial responsible of the digestive process. On the other hand, the longevity of population, novel therapeutic techniques and increased drug usage may affect oral structures, including salivary glands, which could favor the development of local diseases or extra-oral disorders.
Measurement of salivary secretion can be accomplished by different methods: a) resting or unstimulated whole saliva secretion; b) stimulated whole saliva secretion; and c) glandular saliva collection (mainly from parotid glands) with or without stimulation. Unstimulated whole saliva reflects basal salivary flow rate, is present in our mouths for about 14 hours a day, and is the secretion that provides protection to oral tissues. Stimulated saliva represents the secretion during food intake (physiologic stimulation), and is present in our mouths for up to 2 hours (3). So, the study of unstimulated salivary secretion is an accurate method to analyze salivary gland status, while stimulated saliva is useful for the study of the functional reserve. In our study we have chosen to measure unstimulated saliva, as it is an easy, non-invasive and comfortable procedure, which favors its use in population studies.
Age influences salivary secretion, probably due to the physiologic process of ageing (16-21). Our results confirm this aspect, as we observed than older age is associated with decreased non-stimulated salivary flow rate (r = -0.222, p = 0.005), while in younger people (< 44 years) flow rate is greater than in people older than 44 years (OR 2.10).
According to our data, salivary flow is greater in men than in women (OR 3.19); this finding is not related to age, as both groups (men and women) did not show differences in this variable. Similar results are shown in other studies (30-32), and it is suggested that these differences may be explained by salivary gland size, which is smaller in women (41). Decreased salivary secretion in women may be related to the greater frequency or "oral dryness" seen in females (3).
Data about the influence of age in the literature are controversial, and this could be a consequence of some methodological biases: variability in age groups, collection of unstimulated and/or stimulated saliva, inclusion of medicated subjects, etc. (30).
Our data on the buffer capacity of saliva agree with those published in other studies (27-29), as we found a positive correlation with flow rate and a lower bicarbonate concentration in women. From our series, we may consider that there is a decreased buffer capacity when bicarbonate concentration is lower than 1,800 mmol/l (percentile 5).
It has been postulated that juvenile obesity is a risk factor of oral disorders (42), caries among them (43); the work of Power et al. (44) did not show any differences in salivation patterns between obese and non-obese subjects, while other authors found that in young obese people salivary secretion was higher than in the control group (45). Smoking increases salivary flow in the short term (46), but in long-term smokers no differences have been shown versus non-smokers in flow rate (47,48); it has been reported a decrease of pH (47) and buffer capacity (49) in smokers, but normal values of both parameters have also been described (48,50). Acute intake of alcoholic drinks decreases salivary secretion (37); however, in chronic alcoholism, with or without hepatic disorder, data are controversial, as a decrease in salivary flow has been reported (34,51), as well as a normal (35) or increased flow (52).
In our study, obesity, smoking, and alcohol consumption do not imply alterations on salivary features (flow and buffer capacity); however, we cannot draw firm conclusions due to the low number of subjects with these conditions.
Reduction of salivary flow has been related to a sensation of "dry mouth"; despite frequent complaints about this symptom and the impairment in quality of life that it involves, it has only been trivially studied in clinical practice (11,53). Xerostomia is mainly related to drug ingestion (anticholinergics, sympatheticomimetics, drugs acting on serotonin or noradrenalin receptors, etc.) (54), therapeutic radiation of the head and neck, and autoimmune diseases such as Sjögren's syndrome. In a study of 100 patients older than 60 years who complained of xerostomia, the most prevalent etiology was Sjögren's syndrome, followed by iatrogenic xerostomia and idiopathic xerostomia; the authors found hyposialia (unstimulated flow rate lt; 0.2 ml/min) in 65% of patients (55).
]]> The diagnostic of hyposialia can be established according to flow rate, but no consensus has been reached regarding cut-off values, which makes it difficult to compare studies of salivary secretion and "dry mouth". In our series, we considered hyposialia if salivary flow was lower than percentile 5 (0.15 ml/min), which is similar to the value found by Navazesh (0,16 ml/min) (8); in the literature, values to define hyposialia vary from 0.10 (56) to 0.20 ml/min (55). In our series, four healthy volunteers had hyposialia without a sensation of "dry mouth" (2.5%); all of them were women older than the median age, non-obese, non-smokers, and who did not consume alcohol.To evaluate our results about the flow rate and buffer capacity of saliva in healthy subjects, and to demonstrate its diagnostic usefulness (especially the cut-off value to define hyposialia), it would be necessary that patients diagnosed with xerostomia be studied.
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