Effectiveness of a natural product for xerostomia (dry mouth)

Relation

Levrini L, Azzi L, Bossi S. The effectiveness of a dietary supplement with carnosine andHibiscus sabdariffaL. (Aqualief^TM) in patients with xerostomia: a randomized, placebo-controlled, double-blind study.Klin Ter. 2020;171(4):e295-301.

Study objective

To determine whether a combination ofHibiscus sabdariffaL. and carnosine significantly improve dry mouth compared to placebo

Draft

Prospective, double-blind, placebo-controlled study at a single center (Clinica Odontoiatria dell’Università degli Studi dell’Insubria, Varese, Italy)

Participant

Sixty patients, gender not specified, with xerostomia according to the Dry Mouth Questionnaire

Inclusion criteria

Xerostomia grade 1-2 according to RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer)

Exclusion criteria

Use of medications to treat hyposalivation (e.g., pilocarpine), grade 3 xerostomia or worse, and patients with hyposalivation or salivary flow less than 0.1 mL/min

Study parameters assessed

Modified Thomson questionnaire for subjective information about the severity of dry mouth before and after treatment. Researchers used a dry mouth questionnaire (DMQ) to assess dry mouth, difficulty swallowing, dryness while eating, dryness of the face, dry eyes, dry lips, and dryness of the inside of the nose at baseline and after 6 days of treatment on a scale of 1–3 (1=never, 2=sometimes, 3=very often). They measured saliva production using the spitting method every 30 seconds for 5 minutes in a tube without stimulation for a resting saliva measurement. Then there was a break of 2 minutes, saliva stimulation by chewing paraffin wax, and repetition of the spitting method for 5 minutes to obtain a stimulated saliva sample. The researchers measured the pH of resting and stimulated saliva using a pH electrode.

intervention

Aqualief^TM(Helsinn Healthcare SA, Lugano, Switzerland) is a 400 mg mucoadhesive smooth tablet. With normal salivation, it dissolves in about 2 hours. It contains carnosine and dried calyxesHibiscus sabdariffa. Placebo tablets had the same appearance and size without the 2 ingredients. Participants took the tablets 3 times daily after meals for 6 consecutive days.

analysis

The researchers analyzed the data using descriptive statistics. They analyzed the DMQ results using the Wilcoxon signed rank test. They used the man-WhitneyU2 independent sample test to compare the 2 groups at baseline. Student’s t test was used for stimulated and unstimulated salivary flow rates and pH values. statistical significance,P, was set to less than 0.05. Researchers conducted statistical analyzes on GraphPad Prism version 6.00.

Results

The researchers examined 64 patients, enrolled them and assigned them to either the treatment or placebo group. No patient was lost to follow-up. On the DMQ, 32% reported dry mouth very often and 68% sometimes. The mean pH value of saliva at baseline was 6.2. The mean salivary flow rate at baseline was 0.43+0.22 ml/minute. The average age was 53+20 years in the treatment group and 50+20 years in the placebo group. The recipes used were similar between the two groups.

Saliva production in the treatment group was almost three times higher than in the placebo group, along with an improvement in saliva pH that could reduce the formation of dental caries.

pH: 6 days of treatment resulted in a significant increase in saliva pH of 6.2+0.5 to 6.4+0.6,P<0.05. At baseline, 4 of the participants in the treatment group had a cariogenic pH of<5.5; everything improved with treatment. In the placebo group the pH was 6.2+0.5 and increased non-significantly to 6.3+0.5. Stimulated saliva increased significantly from 6.3 in the treatment group+0.5 to 6.6+0.5,P<0.01. Those with stimulated pH at baseline were corrected by treatment.

Amount of saliva: Saliva production at rest increased by 19% in the placebo group,P<0.05, while production increased by 56% in the treatment group,P<0.0001. Stimulated saliva production remained unchanged in the placebo group but increased from 0.85 to 1.08 ml (27%) in the treatment group.P<0.05.

Symptomology: Based on the DMQ, only the treatment group had significant improvement in dry mouth, difficulty swallowing dry food, and nasal dryness. No patient in either group reported any adverse events during or after the study.

Key insights

The placebo group only had an improvement in saliva production, but the authors argued that this may have been due to mechanical stimulation from a foreign body in the mouth. The treatment group had improvement in saliva pH, pH of saliva production and stimulated saliva production. Saliva production in the treatment group was almost three times higher than in the placebo group, along with an improvement in saliva pH that could reduce the formation of dental caries.

Practice implications

Xerostomia can be caused by burning mouth syndrome (as in 8 patients in this study), oncological treatment including radiation and chemotherapy (28 in this study), human immunodeficiency virus (HIV; 2 in this study), antihypertensive and selective serotonin reuptake inhibitor (SSRI) drugs (13 in this study), lateral Cheilitis (2 in this study) and others (7 in this study), as well as diabetes, stroke, dementia, tobacco, alcohol, botulism poisoning, cystic fibrosis, aging, some antihistamines, appetite suppressants, sedatives, anxiety, stress and unknown causes.¹In this study, almost half of the cases were due to side effects of cancer treatment.

Carnosine (beta-alanyl-L-histidine) is a dipeptide discovered in 1900 by Russian chemists Gulewitsch and Amiradzižbi and is found in the brain, kidneys, and skeletal muscles of fish, birds, and mammals.²It can scavenge reactive oxygen species and reactive nitrogen species, bind aldehydes and ketones, form metal chelates, buffer hydrogen ions, regulate factor 4E protein, and extend cell lifespan.^3.4Its concentration is higher in postmitotic adult cells than in actively dividing cells.³Muscle carnosine levels are low in young children (4-5 years old), much higher during the early teenage growth spurt (14 years old), and then decline in adulthood.⁵Therefore, oxidative phosphorylation appears to be beneficial for ATP (adenosine triphosphate) production and is higher in fast-twitch muscles than in slow-twitch muscles.⁶

Neurological studies with carnosine have shown suppression of amyloid accumulation in mouse models of Alzheimer's dementia.⁷Parkinson's disease in humans,^8.9and schizophrenia in humans.^10,11Carnosine as a 5% solution has also been shown to be beneficial in slowing cataract development in cattle and humans.¹²I first became aware of it in 1998 through an English summary of a Russian article, which I persuaded Ganady Raskin, MD, ND, to give me a cursory translation of for clinical use; I have since used carnosine eye drops as a 1% solution of N-acetylcarnosine with benefit for some patients. The key to clinical success with carnosine in most studies is the use of a form that is resistant to degradation by the enzyme carnosinase, such as N-acetylcarnosine, acetyl-L-carnosine and homocarnosine.³

In the current study, the authors provide a cursory overview of carnosine and the reference provided for their 1-sentence reviewHibiscus sabdariffa(HS) from the Malvaceae family actually stands for carnosine, not HS. This plant probably originated in India or Saudi Arabia, with domestication dating back to before 4000 BC. BC in western Sudan.¹²HS sepals or calyxes that envelop the flowers contain at least 4 organic acids, 2 anthocyanins and at least 33 flavonoids and phenolic acids.¹²HS has been shown to be an antioxidant, hepatoprotective, nephroprotective, and antihypertensive in type 2 diabetics in humans; increase corticosterone during pregnancy and breastfeeding; and have a good safety profile.¹³It may be in this formula for its anti-inflammatory effects. Clinically, I find HS useful for hypertension and the effects of stress-induced anxiety.

The pH value of saliva is a critical factor in the development of dental caries. A constant pH value of less than 5.5 can lead to tooth demineralization. The pH range of saliva is usually between 6.2 and 7.6, with an average of 6.7.¹⁴In a recent study on saliva pH and type 2 diabetes, the control group without diabetes had a saliva pH of 7.88, while the diabetics had a saliva pH of 6.51.¹⁴

The article is well written. The researchers do not provide the reasons for combining carnosine and HS, nor do they describe the amount of each ingredient or how the HS was extracted. The study included patients with multiple causes of xerostomia, but in the final analysis there was no indication whether one or more conditions had a better outcome compared to other causes, nor was the distribution of diagnoses among the 2 treatment groups reported. Six days of treatment is a very short study, and the extent of sustained benefit after the study is unclear. Whether a longer duration of treatment would result in better outcomes is also unknown.

Summary

During a 6-day trial period with Aqualief^TMThe treatment group showed a significant improvement in saliva pH, saliva production and stimulated saliva production compared to the placebo group. Almost half of the subjects suffered from xerostomia due to side effects of chemotherapy and/or radiation treatment, suggesting that patients with these causes of their xerostomia may benefit from this supplement.