Introduction

Definition of ageusia

Ageusia is defined as the total inability to taste. Ageusia is very commonly confused with other taste disorders, including hypogeusia (decreased sensitivity to taste), hypergeusia (increased sensitivity to taste), dysgeusia (abnormal or unpleasant taste), and phantogeusia (taste perceived with no stimulus). Although not life-threatening, the impact of ageusia may contribute to loss of appetite, reduction in weight, complications due to loss of required medications, and deterioration of both physical health and psychological well-being.¹

Epidemiology

Ageusia is rare and affects about 1 to 2 persons in every 1000. Defects in the skull cranial nerves that utilise taste are rare. Although taste function goes through typical decreases with ageing due to physiological changes, ageing does not normally result in total gustation loss.¹

Etiology

Ageusia can be caused by a variety of reasons, including the destruction of cranial nerves (i.e., the lingual and glossopharyngeal) involved with taste, nutritional deficiencies (i.e., zinc), and systemic conditions, including hypothyroidism, diabetes, Sjögren's syndrome, and Crohn's disease. Gastric or brain disorders, tumours, and infections like herpes zoster can disrupt and/or damage the central gustatory pathways. Radiotherapy bursts of energy (e.g., beta, gamma) for the treatment of head and neck cancers will cause degenerative effects and therefore ageusia due to taste bud and salivary gland injury. Local trauma, dental prostheses, oral infections, and medications (especially antibiotics, cardiovascular drugs, and antineoplastics) can also cause ageusia. Ageing may also contribute to diminished taste function.^1,2

Impact on quality of life

Ageusia significantly affects psychological health and overall well-being, particularly in older adults. Because full recovery is often challenging, patient education focusing on coping strategies is essential.¹ This condition is notably prevalent among COVID-19 patients and is closely linked to a decline in oral health-related quality of life, which disrupts daily functioning.³ While some people may recover their taste function, many people have long-lasting effects that affect day-to-day life.^1,3

Pathophysiology of taste loss

There are approximately 10,000 taste buds in the human gustatory system. Taste buds are ovoid, ranging in size from 50 to 70 micrometres. The taste buds are found in several places, including the mucosa of the epiglottis, palate, pharynx, and tongue papillae. All taste buds, regardless of location, have their receptors facing the oral cavity at the apical end of the taste bud. In addition to the receptors, there are at least four distinct cell types in taste buds: basal cells, type I dark cells, type I light cells, and type III intermediate cells. Basal cells are immature and do not extend to the taste pore. Also, only type I dark cells, type I light cells, and type III intermediate cells are the corresponding sensory neural cells that respond to taste stimuli.¹

The firm underlying causes of ageusia reflect the different conditions that result in changes in the health and viability of taste cells. In the case of chemotherapy or radiotherapy, the cells of the taste bud (taste cells) are rapidly renewed or die. When salivary glands are damaged during treatment, however, saliva is no longer produced, and there are important considerations for the transport of tastants to the taste receptor and subsequent signal transduction for taste, which is crucial for taste perception. The complex nature of inter/inflammatory local infections or inflammatory conditions results in taste cell death via apoptosis and impairment of chemosensory hair function, which, together, likely impact taste perception and cognisance.⁴

Nerve injury is one cause of ageusia, especially damage to the chorda tympani, which can occur in otological surgeries or dental procedures, and injury to the lingual branch of the glossopharyngeal nerve, which can occur during tonsillectomy.^5,6 Systemic diseases, including Sjögren's syndrome, diabetes, hypertension, renal and liver disease, and hyperthyroidism, can impact taste buds through either direct alterations to taste bud cells and/or via some neuropathic mechanism.^7,8

Ageing affects taste sensitivity through a decrease in taste cells and likely reduced salivary secretion, as well as undiagnosed or untreated dental problems (plaque). The complete loss of taste is rare, although elderly patients are at risk of the most probable cause of ageusia due to polypharmacy, nutritional deficiencies, and secondary effects of systemic diseases and/or oral diseases.⁹

The initiation of the gustatory pathway occurs in the taste buds. The signals generated at the taste bud are transmitted from the taste buds through cranial nerves VII (facial), IX (glossopharyngeal), and X (vagus) to the paired gustatory (solitary) nuclei in the medulla. From the gustatory nuclei, contributions project to multiple regions of the brain, including the amygdala, pons, hypothalamus, thalamus, and gustatory cortices, forming an integration of the psychological, physical, and physiological (visceral) responses for taste perception along with other responses.¹

Diagnostic approaches

Onset and natural history of symptoms

Ageusia has an acute onset, usually occurring within 2-4 days of illness onset, and may present by itself or be the only symptom at the onset of illness, especially in epidemics, especially as COVID-19 infections. Most patients experience taste function recovery within 3 weeks, but some will experience persistent or prolonged deficits, requiring longer periods to evaluate and treat.¹⁰

Diagnostic specificity

Ageusia is viewed to be a highly specific symptom of COVID-19 even in the absence of common symptoms, such as fever or cough. The specificity provides a useful early symptom for diagnosis in cases of mild or asymptomatic patients.¹¹

Differential diagnosis

Ageusia, aside from viral causes, may occur with:

• Neurological diseases, such as multiple sclerosis (especially thalamic lesions), stroke, or cranial nerve lesions¹²
• Metabolic or systemic disorders, such as diabetes mellitus, chronic kidney disease, and vitamin deficiencies¹²
• If ageusia is accompanied by neurological symptoms, they should undergo neuroimaging and referral to specialists¹²

Diagnostic process

Clinical Evaluation: Assessment begins with detailed history-taking and physical examination, including inspection of cranial nerves (VII, IX, X) and oral structures.

Patient-Reported Symptomatology: Diagnosis is primarily based on self-reported sudden loss of taste, corroborated with structured questionnaires or interviews.^10,11

Associated Symptoms: Ageusia may present alone or with anosmia, myalgia, or fatigue. Notably, isolated ageusia may indicate increased severity and hospitalisation risk.¹⁰

Referral and Testing: Sudden-onset ageusia should prompt COVID-19 testing, especially during outbreaks or pandemic waves.¹¹

In a study by Schäfer et al. (2022), loss of taste was significantly associated with hospitalisation risk, emphasising its role not only in diagnosis but also in prognostication.¹⁰

Taste function tests

• Psychophysical tests are commonly used for the objective measurement of taste function, with the taste strips as the most traditional test used to test sweet, sour, salty, and bitter at differing concentrations, as well as identify differences between normogeusic, hypogeusic, and ageusic patients. Whole-mouth approaches (e.g., sip-and-spit) can evaluate overall sensitivity, while localised approaches (e.g., filter paper disks, electrogustometry) can be used to evaluate regions of lost sensitivity¹³
• Objective assessment of taste function will detect more cases of dysfunction than subjective self-reports, which may underdiagnose the dysfunction. Ageusia, complete loss of taste function, is uncommon; however, conditions such as specific ageusia and loss of one of the taste qualities may occur, especially in trauma or disease states such as COVID-19. Ageusia may be experienced in isolation or alongside similar taste-associated disorders such as hypogeusia or dysgeusia¹³

Current therapeutic strategies

Treatment options for ageusia

Taste retraining therapy

A non-invasive technique that applies rekindled exposure to distinct taste stimuli to stimulate and rehabilitate taste ability. Some improvement can be achieved, depending on the aetiology and extent of dysgeusia.¹⁵

Medication

Infection or inflammation (or even deficiency) is one of the best candidates for treatment. The challenge is to get the right drug for a certain etiology.¹⁵

Surgery

In very rare instances, surgeries that involve an anatomical or neurologic defect may involve nerve grafts or taste bud transplants. Someone with a complete loss of taste might benefit from surgery, but we generally don't know much about the procedures.¹⁵

The approach to managing ageusia will depend first on identifying and treating the underlying etiological cause. In these cases, the disturbances in taste will sometimes resolve spontaneously, particularly if the ageusia is due to a self-limited or viral process. Nutritional supplements may help with ageusia, and these include zinc gluconate (140 mg/day), which is a common nutrient of use in people receiving chemotherapy or radiotherapy. Alpha-lipoic acid (600 mg/day) has also helped patients who may take many months to restore their taste sensation.¹⁴

For patients with dysgeusia or burning mouth syndrome, pharmacological management may include low-dose agents in the class of tricyclic antidepressants or clonazepam. In some severe cases, topical anaesthetics such as lidocaine gel used to alleviate symptoms may be an option. If areas of the lingual or palatal trough are disrupted directly via trauma or surgery that cuts the gustatory nerve supply, there may be the potential for a spontaneous recovery of taste. However, there may be the possibility of a remaining loss of function. For potentially dysfunctional taste associated with xerostomia, artificial saliva substitutes may improve their taste sensation.¹

Emerging interventions

Taste bud regeneration therapies

• Stem Cell Therapy: Scientists are investigating the capabilities of stem cells in regenerating taste buds, especially after ageing, nerve injury, chemotherapy, and radiation¹⁶
• Gene Therapy: Manipulating genes that affect taste receptor function or the regeneration of the nerves could have potential in the future¹⁶

Neuromodulation techniques

• Transcranial Magnetic Stimulation (TMS): TMS is being examined as a possible technique to stimulate gustatory areas of the brain and improve overall taste perception, and has been used previously for other sensory disorders¹⁷
• Transcranial Direct Current Stimulation (tDCS): Low-intensity electrical stimulation to the insular cortex or primary gustatory cortex to improve taste processing¹⁷

Bioelectronic devices

• Advances in Electrogustometry: There are available devices designed to measure taste thresholds and possibly stimulate taste nerves through electrogustometry, which would retrain or enhance taste perception¹⁸
• Wearable Gustatory Devices: Prototypes are being made for devices to provide electrical signals or micro-doses of tastants to a tongue to restore taste perception¹⁸

Drug innovations

• Salivary Gland Modulators: There are drugs able to augment or modify the content of saliva of drugs to improve access to receptors¹⁹
• Growth Factors (e.g., BDNF, NGF): They have a role during nerve repair and may facilitate the recovery of ageusia from a nerve injury¹⁹

Nutraceutical and anti-inflammatory agents

• Alpha-lipoic acid, curcumin, and omega-3 fatty acids: These agents have known neuroprotective properties and are under research for a potential role as a nerve regeneration agent in idiopathic or post-viral ageusia²⁰
• Immunomodulators: These agents are being researched for their potential role in autoimmune-related or COVID-related ageusia to decrease localised inflammation and nerve injury²⁰

Artificial intelligence and digital training

• AI-Guided Taste Training Apps: Sensory retraining plans that use a digital modality for personalised plans that rely on user feedback and machine learning to optimise recovery²¹
• Virtual Reality Gustatory Stimulation: Using multisensory environments to retrain the brain's interpretation of taste-related stimuli may be experimental at this stage²¹

Prognosis and long-term management

The prognosis for ageusia is based on the cause. Temporary causes such as infection or medication side effects will likely resolve because they will resolve on their own; however, patients who have permanent nerve injury or a neurological disorder will likely have a permanent loss of desire of taste.

The plan for managing it in the long term is dependent upon addressing the cause of the ageusia (e.g., discontinuation of offending pharmacotherapy, correction of nutritional deficits), retraining of taste in the appropriate exercises, and providing supplementation such as zinc sulfate or alpha-lipoic acid. Providing supportive care includes modifying diet, ensuring adequate nutrition, and addressing the psychological impact of ageusia. Follow-up appointments, regularly, could ensure the patient has ongoing support as needed and ensure that a multidisciplinary approach is being addressed in complex cases.

Home-based approaches and support techniques to manage ageusia

While there is no recognised treatment for ageusia, the total loss of taste, there are a variety of non-pharmacological approaches to enhance taste perception and enhance quality of life.

Dietary changes

Adding flavours using herbs and spices  (e.g. basil, ginger, cinnamon) that stimulate taste receptor systems 

Adding foods with texture and acidity, including naturally acidic foods (e.g., citrus fruits), to increase sensory stimulation in the oral cavity.

Avoid unnecessarily salty or sweet food substances because they may desensitise taste perception depending on the quantity consumed.¹⁵

Oral hygiene technique

• Brushing twice a day with fluoride toothpaste
• Flossing every day to avoid gingival inflammation
• Having dental assessments to obtain treatment options for oral health problems that are contributing to or causing the underlying issue of loss of gustatory function¹⁵

Sensory training strategies

• Eating mindfully and engaging the sensory experience of eating (this involves paying attention to texture, temperature, and aroma)
• Gradually reintroducing distinct flavours, beginning from mild to more intense flavour profiles, with terminology
• Visual enhancement of the meal to improve enjoyment factors with colour and design/arrangement of food¹⁵

Summary

Ageusia refers to the total loss of taste; approximately 9-12% of patients have taste disorders, with ageusia being one of the rarest. Reports suggest that ageusia occurs in approximately 1 to 2 out of 1,000 people. Ageusia is frequently misdiagnosed as related to taste disorders, such as hypogeusia or dysgeusia. Although ageusia does not threaten life, it can compromise life because ageusia can decrease appetite, potentially reduce weight, require patients to not adhere to their medication regimen, and impact a person’s psychiatric wellness (especially among older adults and those recovering from COVID-19).

Ageusia can involve multiple etiologies, including cranial nerve damage (i.e., CN VII (facial nerve), CN IX (glossopharyngeal nerve), and CN X (vagus nerve)) a lack of nutritional status (ex. zinc deficiency); systemic diseases (ex. diabetes, hypothyroidism, Sjögren's syndrome and  Crohn's disease), medications (e.g, chemotherapy agentsand antibiotics) or radiation for head and neck cancers; neurological diseases; age-related chemosensory changes; oral infections; dental prostheses; and trauma. The pathophysiology of taste is related to damage to taste buds and/or dysfunction of the gustatory pathway (with a specific beginning in taste receptors sending signals via CN VII, IX, and X to the medulla, thalamus, and gustatory cortex). The taste pathways can be disrupted through inflammation, decreased salivary flow, and/or cellular death, and this disruption changes taste perception. Some individuals can experience recovery, particularly if an underlying condition is corrected, but many are left with chronic taste dysfunction, resulting in incomplete or limited recovery, hence the need for long-term management and supportive care.