Anne D. Carle

Long term use of triclosan toothpaste and thyroid function

The long term effects of usage of triclosan-containing toothpaste on thyroid function are currently unknown. Triclosan is structurally similar to thyroid hormones and reductions in serum thyroid hormone levels have been observed in animal studies following oral administration of triclosan. Therefore, an assessment of thyroid function over 4 years was undertaken in a subset of individuals in a randomised, placebo controlled clinical trial comparing the effects of 0.3% triclosan toothpaste with placebo toothpaste in subjects with coronary heart disease. Thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), antithyroglobulin antibody (anti-TGab) and antithyroid peroxidase antibody (TPOab) were measured. Paired serum samples at year 1 and year 5 from 132 subjects (64 triclosan group, 68 placebo group) were analysed. At year 1 there were no significant differences in thyroid function between the groups: mean (SD) TSH 1.4 (0.8) and 1.6 (0.9) mU/L, triclosan and placebo groups respectively, fT4 15.8 (2.2) and 15.2 (2.1) pmol/L; fT3 4.8 (0.5) and 4.8 (0.5) pmol/L. Similarly, for antithyroid antibodies there were no group differences at year 1. Median (25th, 75th percentile) for anti-TGab, 38 (34, 42) and 37 (30, 42) U/mL triclosan and placebo groups respectively; anti-TPOab, 15 (10, 22) and 18 (10, 24) U/mL. At year 5, fT4 was the only measure to show a significant difference between groups (mean and 95% Confidence Interval) 15.6 (15.1, 16.1) and 14.7 (14.2, 15.1) pmol/L triclosan and placebo respectively (p=0.01). This reflects reduced levels in the placebo group but no change in the triclosan group. In conclusion, over 4 years triclosan toothpaste had no detectable effect on thyroid function. The data support the view that 0.3% triclosan in toothpaste is safe and free of significant thyroid adverse effects.

The influence of a triclosan toothpaste on adverse events in patients with cardiovascular disease over 5-years.

Adverse effects of long-term usage of triclosan-containing toothpaste in humans are currently unknown. We assessed the effect of long-term use of 0.3% triclosan-toothpaste on serious adverse events (SAEs) in patients with cardiovascular disease (CVD). 438 patients with a history of stable CVD were entered into the 5-year longitudinal Cardiovascular and Periodontal Study at Prince Charles Hospital, Brisbane, Australia and randomised into test (triclosan) or placebo groups. There were no significant differences in demographics or clinical features between the groups. Patients were examined at baseline, and annually for 5-years. SAEs were classified according to the System Organ Classes defined by MedDRA (Medical Dictionary for Regulatory Activities). Results were analysed using chi square and Kaplan Meier analysis. Overall, 232 patients (123 in the triclosan group; 109 in the placebo group) experienced 569 SAEs (288 in the triclosan group and 281 in the placebo group). There was no significant difference between the groups in numbers of patients experiencing SAEs (p=0.35) or specific cardiovascular SAEs (p=0.82), nor in time to the first SAE or first cardiovascular SAE, irrespective of gender, age or BMI after adjusting for multiple comparisons (p>0.05). The adjusted odds of experiencing an SAE were estimated to increase by 2.7% for each year of age (p=0.02) and the adjusted odds of experiencing a cardiovascular SAE were estimated to increase by 5.1% for each unit increase in BMI (p=0.02). Most cardiovascular events were related to unstable angina or myocardial infarcts, 21 were associated with arrhythmia and 41 were vascular events such as aortic aneurysm and cerebrovascular accident. Within the limitations of the present study the data suggest that the use of triclosan-toothpaste may not be associated with any increase in SAEs in this CVD population. The long-term impact of triclosan on hormone-related disease, such as cancer, in humans remains to be determined.

Influence of a triclosan toothpaste on periodontopathic bacteria and periodontitis progression in cardiovascular patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE Triclosan/copolymer toothpaste is effective in controlling plaque and gingivitis and in slowing the progression of periodontitis. This study describes its influence on microbiological and clinical outcomes, over a 5-year period, in patients with established cardiovascular disease (CVD). MATERIAL AND METHODS Four-hundred and thirty-eight patients were recruited from the Cardiovascular Unit at The Prince Charles Hospital, Brisbane, Australia, and randomized to triclosan or placebo groups. Six sites per tooth were examined annually for probing pocket depth and loss of attachment. These outcomes were analysed, using generalized linear modelling, in 381 patients who had measurements from consecutive examinations. Concurrent load of the periodontal pathogens Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Tannerella forsythia and Porphyromonas gingivalis was determined, using quantitative real-time PCR, in 437 patients with baseline plaque samples. Group comparisons were expressed as geometric means. The chi-square test was used to test for differences between the two groups of patients with regard to the proportion of patients with different numbers of bacterial species. RESULTS There was no difference in general health or periodontal status between the groups at baseline. There was a significant reduction in the number of interproximal sites showing loss of attachment between examinations, by 21% on average (p < 0.01), in the triclosan group compared with the placebo group. The prevalence of patients with F. nucleatum and A. actinomycetemcomitans was high and remained relatively constant throughout the 5 years of the study. In contrast, the prevalence of T. forsythia and P. gingivalis showed more variability; however, there was no significant difference between the groups, at any time point, in the prevalence of any organism. A significant difference in the geometric means for P. gingivalis (p = 0.01) was seen at years 1 and 4, and for F. nucleatum (p = 0.01) and in the total bacterial load (p = 0.03) at year 2; however, these differences were not statistically significant following a Bonferroni correction for multiple comparisons. There was no difference between the groups in the geometric means for each organism at year 5. CONCLUSION Within the limitations of the study, these data suggest that the use of triclosan/copolymer toothpaste significantly slowed the progression of periodontitis in patients with CVD but that it had little influence on key subgingival periodontopathic bacteria in these patients over the 5 years of the study.

The Influence of Triclosan on Biomarkers of Cardiovascular Risk in Patients in the Cardiovascular and Periodontal Study (CAPS): A Randomized Controlled Trial

BACKGROUND Triclosan toothpaste is effective in controlling plaque and gingivitis and slowing progression of periodontitis; however, its influence on inflammatory biomarkers of cardiovascular disease (CVD), as well as on kidney and liver function, is unknown. METHODS Patients recruited from the Cardiovascular Unit at Prince Charles Hospital, Brisbane, Australia, were randomized to triclosan (n = 193) or placebo (n = 190) groups and assessed for total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, C-reactive protein, erythrocyte sedimentation rate (ESR), hemoglobin, total white cell count (WCC), estimated glomerular filtration rate (eGFR), and liver function enzymes, annually for 5 years. A standard mixed model for each marker included group, sex, age, hypertension, diabetes, periodontal status, statin and anti-inflammatory drug use, and smoking as covariates. Changes in eGFR, WCC, and ESR were further analyzed using transition modeling. RESULTS Triclosan toothpaste led to a greater decrease in TC (P = 0.03), LDL cholesterol (P = 0.04), and HDL cholesterol (P = 0.05) than placebo toothpaste. ESR increased at a slower rate in the triclosan group (P ≈ 0.06) and was less likely to increase and more likely to improve in males on statins but not anti-inflammatory drugs in the triclosan group versus the placebo group. Markov modeling of the binary response for eGFR (greater than or less than/equal to the baseline median value) showed that patients with diabetes in the placebo group were significantly (P ≈ 0.05) more likely to deteriorate than either patients with diabetes in the triclosan group or patients without diabetes in each group. CONCLUSIONS These data suggest that triclosan toothpaste may influence some inflammatory biomarkers of CVD, but not kidney or liver function. However, it is unclear if this influence is clinically significant.