„Nu îmi mai place friptura”: înţelegerea tulburărilor gustative la pacienții cu cancer

Introduction

Taste disorders are quite frequently encountered complications of radiotherapy or chemotherapy treatments in patients with cancer. Various articles mentioned that as many as 90% of the patients with head and neck cancer undergoing radiotherapy may experience taste disturbances, with female patients being more likely to report symptoms such as dysgeusia, aversion to the smell, and changes in food texture. Approximately 60% of hematology patients undergoing chemotherapy also report changes in taste, with 38% experiencing moderate to severe symptoms^(1-4).

These taste disturbances can significantly impair a patient’s quality of life. Loss of interest in food, resulting in reduced oral intake, may lead to nutritional compromise and weight loss. In some cases, patients may be advised to use feeding tubes to mitigate weight loss. Furthermore, the diminished enjoyment of food can extend to social interactions, leading to increased social isolation and sometimes even the stigma associated with cancer treatment^(5,6).

Anatomy and physiology

Taste perception is mediated through the taste buds that are onion‐shaped organs comprised of 50-100 taste receptors with a life span of 10 to 11 days, located on the tongue, soft palate, pharynx, larynx, uvula, upper third of esophagus, lips and cheeks. When the taste buds are stimulated, there is an activation of G proteins (gustducin, phospholipase C and hydrolysis of phosphatidylinositol-4,5-biphsophonate) that, in turn, leads to nerve depolarization and the impulses are transmitted through the intermediate nerve of the facial nerve (VIIbis) and trigeminal nerves (from the anterior two thirds of the tongue) and through the glossopharyngeal and vagus nerves (from the posterior third of the tongue, oropharynx and esophagus). The information is then conveyed through the nucleus of the solitary tract, then to the thalamus and from there to the post-central gyrus-facial area and olfactory cortex. It is important to mention as well that taste receptors can be found not only in the taste buds but also in other areas of the digestive tract, pancreas, brain and airway epithelium^(2,5-7).

Humans perceive five taste senses: salty, sour (acid), bitter, sweet and umami (savory). An additional taste quality often referred to as “fat taste” has been proposed. Among these, umami is particularly important, as its loss can severely diminish the pleasure and enjoyment of food, directly impacting the quality of life^(2,6,7).

Classification

Taste disturbances can be classified based on the nature of the taste alterations, which are typically divided into the following categories:

• Ageusia, representing a complete absence of taste sense.
• Hypo- or microgeusia, regarded as decreased sense of taste and tasting ability.
• Phantogeusia, in which the patient perceives “phantom” tastes.
• Dysgeusia, commonly used as a general term for any type of taste disorder. It represents a distortion of taste, and it can be further divided into:
  • Cacogeusia, representing an unpleasant taste.
  • Torquegeusia, perceived as a burning like sensation in the mouth.
  • Hypergeusia, or increased sensitivity to common taste.
  • Gustatophobia, representing a dislike of certain tastes.
  • Heterogeusia, in which all food and drinks have the same taste.
  • Presbygeusia, meaning the decline of sense of taste with age^(2,3,7,8).

Dysgeusia can further be categorized into quantitative (ageusia, hypogeusia, hypergeusia) and qualitative forms (parageusia, pseudogeusia, phantogeusia, cacogeusia and agnogeusia). Additionally, taste disturbances may be classified according to the lesion site into epithelial, neural, or central dysgeusias^(7,9).

Pathophysiology

The pathophysiology of taste disorders involves complex interactions among the gustatory system, nervous system, and underlying health conditions. These issues can encompass numerous factors, including:

1. disruption of gustatory receptors

2. nerve damage (e.g., paralysis, surgery)

3. neurological diseases (e.g., stroke, multiple sclerosis, amyotrophic lateral sclerosis)

4. metabolic and nutritional deficiencies (e.g., zinc, copper, iron, vitamins B2, B6 or B12 deficiency, or malnutrition and cachexia)

5. systemic diseases (e.g., hepatic or renal insufficiency, diabetes, cancer)

6. medication side effects, with certain drug classes identified as contributing to taste disturbances, as outlined in Table 1^(2,5,6,10).

Diagnosis

A comprehensive evaluation is essential for accurately diagnosing taste dysfunction. The diagnostic process begins with a thorough physical examination, which should include the following components:

• Oral examination – to assess oral hygiene and to detect conditions such as mucositis, infections, dental issues, or salivary gland dysfunction, which may directly or indirectly affect taste perception.
• Ear, nose and throat examination.
• Neurological examination – to assess the integrity of the cranial nerves (VII, IX and X) responsible for transmitting taste signals, as well as to rule out central nervous system disorders⁽¹³⁾.

In addition to the physical examination, specific tests can provide objective data to support the diagnosis of taste dysfunction:

• Butanol threshold test evaluates the olfactory function, which is intricately linked to taste perception. The patient is presented with ten test substances and an n-butanol threshold test contained in odorant pens known as Sniffin’ Sticks. Each nostril is tested separately⁽¹⁴⁾.
• Whole-mouth taste test assesses the patient’s ability to detect, identify and evaluate the intensity of different basic taste qualities: sweet, sour, salty and bitter. The results are expressed as percentile scores for each taste modality, indicating the extent of taste dysfunction^(5,15).
• Chemical gustometry test examines taste sensitivity for sweet, sour, salty, bitter and umami^(2,5).
• Spatial taste test evaluates the localized taste perception by applying cotton swabs soaked in solutions representing each taste quality to specific regions of the tongue (four quadrants) and the soft palate (each half). The patient identifies the taste quality, allowing for the assessment of regional variations in taste sensitivity^(5,16).
• Electrogustometry is used to measure taste perception by stimulating the tongue with small electrical currents. It does not define taste quality^(5,17).
• Flavor discrimination test can evaluate a person’s ability to perceive and distinguish different tastes⁽¹⁷⁾.
• Salivary flow rate is performed by measuring the unstimulated and stimulated salivary flow rates. Samples are collected, and hyposalivation is defined as less than 0.1 mg/minute unstimulated and 0.5-0.7 mg/minute stimulated salivary flow⁽²⁾.

Taste disturbances could be assessed with the Common Terminology Criteria for Adverse Effects (CTCAE) and the Scale of Subjective Total Taste Acuity (STTA). The CTCAE, developed in 2003 by the National Cancer Institute, is a reporting tool for acute and late adverse effects of cancer treatment. It was published in several versions and it divides adverse effects of cancer treatment into:

• Grade 1 – mild adverse effects
• Grade 2 – moderate adverse effects
• Grade 3 – severe adverse effects
• Grade 4 – life threatening or disabling adverse effects
• Grade 5 – death related to adverse effects.

The STTA was modified from the Late Effects of Normal Tissue/Somatic Objective Management Analytic (LENT/SOMA) scoring system.

A brief review of taste disturbances with the two scales can be found in Table 2^(5,18,19).

Imaging studies such as MRI or PET scan could also be employed especially when there are suspicions of central nervous or gustatory pathways disorders⁽¹¹⁾.

All these diagnostic tools provide a detailed understanding of the patient’s taste perception and help identify the nature and extent of the dysfunction. Once the diagnosis is established, further steps can be taken to investigate underlying causes and develop an appropriate management plan.

Treatment

Spontaneous recovery from gustatory disruptions is relatively common, unlike sensory systems such as vision or hearing. Discontinuation of the causative medication is often the first step, and some patients recover within 1-3 weeks, though full recovery may take up to two years⁽¹¹⁾.

The Canadian Cancer Society, in its literature for patients, has made several dietary recommendations for cancer treatment related dysgeusia with some of them being listed below:

• Keep good dental and oral hygiene.
• Avoid foods that are not appealing.
• Flavor foods with herbs and spices.
• Add sweeteners, sugar or honey for a salty or bitter taste.
• Add lemon juice, vinegar or salt for sweet taste.
• Use plastic cutlery and ceramic or glass cookware to offset metallic taste.
• Serve food cold or at room temperature to decrease food taste and smell.
• Try different sources of protein (e.g., eggs, fish, beans, nuts) if meat tastes bad/different.
• Eat fresh vegetables.
• Blend fresh fruits into shakes, ice cream, or yogurt.
• Use gum or sugar free candies or mints for unpleasant postprandial taste⁽²⁰⁾.

The European Society for Medical Oncology (ESMO), in its guidelines for the management of orphan symptoms, mentions that there was insufficient evidence to conclude that the use of acupuncture may be of benefit for taste disorders. There is an ongoing study in Switzerland (AcuDysg) combining traditional Chinese acupuncture with acupressure for chemotherapy-induced dysgeusia^(18,21).

High-dose zinc supplementation (68 to 86.7 mg per day for up to six months) is an effective treatment for taste disorders caused by zinc deficiency, renal failure, idiopathic taste disorders, and also by cancer treatments⁽²²⁾.

In cancer patients, zinc supplementation showed a potential to decrease taste loss, dry mouth and oral pain, although it had no significant effect on weight, quality of life, fatigue or survival. The risk of side effects from zinc is relatively low, but it must be used with caution in immunocompromised patients since zinc overuse could adversely affect the immune system. While it may help prevent oral toxicities during radiation therapy, it does not appear to alleviate the side effects caused by chemotherapy^(18,23).

A chelated form of zinc and L-carnosine, known under the name of polaprezinc, has been studied for chemo­the­rapy-related dysgeusia. The combination of the sup­plements has a better efficacy than either of them alone, since carnosine has positive effects on zinc absorption and delivery to the tissue. Polaprezinc may help with dysgeusia, since the enzymes found in the taste buds require zinc. A study published in Japan showed that polaprezinc was highly effective in improving dysgeusia, with the exception of the elderly patients, those with pancreatic cancer and those who received gemcitabine^{(1,3,11,18,24)}.

Nevertheless, ESMO mentioned in its guidelines for the management of orphan symptoms about two clinical trials that showed no significant difference between zinc sulphate versus placebo for dysgeusia related to radiotherapy for head and neck cancer or chemotherapy respectively⁽¹⁸⁾.

Miraculin, a protein extracted from the fruit of Synsepalum dulcificum, binds to the taste receptors, generating a sweet sensation that in turn could mask some unpleasant taste for food. But the research was limited to small studies, therefore more research is needed in this domain before recommending miraculin to patients with taste alterations^(18,25).

Oral glutamine at doses of 30 grams daily was studied for taxane-induced dysgeusia, but the results failed to prove a positive outcome and, therefore, it is not recommended for prevention of taste disturbances^(18,25).

Megestrol acetate (Megace®) is an agonist of progesterone receptors that was administered in a randomized placebo control trial in doses of 480 mg/day in patients with advanced cancer and weight loss. The results of the study were encouraging, but the study had several limitations and, therefore, more research is needed^(18,25). 

Amifostine (Ethyol®) is a cytoprotectant agent that could be used to prevent or lessen the oxidative damage to the salivary glands caused by radiation therapy. ESMO does not recommend it, based on the conclusions of two randomized studies which showed that amifostine did not decrease the incidence of dysgeusia^(18,25).

A randomized control study using dronabinol (Marinol®) administered in doses of 2.5 mg twice a day revealed that the patients taking it were two times more likely to report improved taste compared to placebo. Further investigations with larger randomized trials may be needed^(18,25).

Finally, transcranial magnetic stimulation (TMS) widely used for management of depression showed some success in smell and taste disorders, but more research is needed⁽¹¹⁾.

Conclusions

Taste disturbances, though prevalent and impactful, remain under-researched, likely due to their non-life-threatening nature and underreporting by patients. Nonetheless, understanding the pathophysiology, diagnosis and treatment of these disorders is crucial for improving the quality of life of cancer patients and others affected by these conditions. Future research is needed to develop more effective interventions and to better support patients experiencing taste dysfunction.

Autor corespondent: Sorin Buga E-mail: sbuga@coh.org

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

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