Part Two: Perspectives on Olfactory and Gustatory Dysfunction Pathophysiology, Management, and Relevance to COVID-19: Current Approaches.

Context: The phenomena of olfactory and gustatory dysfunction disorders (OGD) are hardly unique to COVID-19. However, the widespread incidence of OGD as sequelae of COVID-19 has provoked rejuvenated interest in these long existing, but poorly studied maladies. Objective: This second of a three-part review discusses past and current approaches for treatment of OGD, not restricted to those that COVID-19 has caused, with the intention to lay a foundation for consideration of new paradigms for evaluation and management of OGD. Design: The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting: The Liebell Clinic, Virginia Beach, VA, USA. Conclusions: The epidemiology and hypotheses of pathophysiology of post-COVID OGD has been addressed via numerous studies and reviews. However, extremely limited evidence of effective treatment for chronic OGD, in general, exists, Global demand for any treatment capable of reducing or resolving it is unprecedented. Past and present treatment approaches and recently initiated clinical trials, since the onset of the pandemic, have yet to yield any significant results.

Perspectives on the Pathophysiology, Management, and Relevance of Olfactory and Gustatory Dysfunction to COVID-19, Part One.

Context: Amelioration of olfactory and gustatory dysfunction (OGD) disorders has become a common requirement due to COVID-19. Although it's hardly exclusive to COVID-19, OGD's prevalence requires exploration of therapeutic and restorative modalities, on the broadest scale possible. No specific medication or treatment of any noteworthy efficacy exists for OGD. Objective: As Part 1 of a three-part article, a narrative review intended to examine the known causes of OGD, not restricted to COVID-19, and frame their relevance for development of new treatments or the repurposing of existing ones. Design: The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting: The Liebell Clinic, Virginia Beach, VA, USA. Results: Scientific investigation into mechanisms and treatment of OGD appears to be historically limited and unremarkable. Medical literature spanning decades reports a bleak clinical outlook with an abundance of speculation and hypotheses. Limited evidence of effective or reliable treatment exists, especially for chronic cases. Conclusions: With a dismal lack of medical support for a suddenly prevalent, but hardly novel set of maladies of taste and smell perception; the imperative for multifaceted and broad investigations across all medical disciplines is without question. Global urgency for the development of any treatment capable of reducing or resolving OGD triggered by COVID-19 is unprecedented. Part 2 of the current author's three-part series will address the details of current and past treatment approaches and clinical trials.

Japan's Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis.

Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan's Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 µg/dL and 60-80 µg/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50-82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.

Taste disorders following cancer treatment: report of a case series.

PURPOSE: To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste change after cytotoxic therapies. METHODS: Patients with acute myeloid leukemia (AML), multiple myeloma (MM), and head and neck cancer (HNC) were evaluated for taste function. Chemical gustometry was conducted assessing chemosensory qualities that included sweet, sour, salty, bitter, umami, and spicy. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and the Scale of Subjective Total Taste Acuity (STTA) were used to describe taste symptoms. Saliva flow rates were measured to determine the presence of hyposalivation. Patients were provided treatment trials for taste dysfunction, including zinc supplements, or medications that included clonazepam, megestrol acetate, and the cannabinoid dronabinol. RESULTS: According to STTA, hematology cases reported the incidence of grades 2 and 3 taste disturbances as 60% and 40%, respectively. For HNC patients, the incidence of grades 2 and 3 was 44% each. Gustometry tests confirmed dysgeusia in all patients evaluated. In the hematology group, 80% of patients exhibited a decrease in sweet taste perception, and no patients correctly identified umami taste. In the HNC group, most patients could not identify salt taste, 66% of patients reported "no sensation" with spicy taste, bitter taste was reduced in some, and increased or altered in others, while only one patient could identify umami taste. In the hematologic and HNC patient groups, 80% and 66% reported grade 2 dry mouth, respectively, according to CTCAE 4.0. After treatment for taste dysfunction, 71% of all patients in the present study reported improvements in taste function. CONCLUSIONS: Persisting dysgeusia in cancer survivors may be assessed by patient report and taste testing. The taste most affected in our patients was umami. Treatment trials with current interventions for dysgeusia appeared effective and should be considered in cancer survivors. Understanding taste and flavor function during and following cancer treatment is important in developing rational prospective preventive and interventional strategies.

Metallic taste in cancer patients treated with chemotherapy.

BACKGROUND: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic taste in chemotherapy treated cancer patients. METHODS: Literature search for metallic taste and chemotherapy was performed in PubMed up to September 2014, resulting in 184 articles of which 13 articles fulfilled the inclusion criteria: English publications addressing metallic taste in cancer patients treated with FDA-approved chemotherapy. An additional search in Google Scholar, in related articles of both search engines, and subsequent in the reference lists, resulted in 13 additional articles included in this review. Cancer patient forums were visited to explore management strategies. FINDINGS: Prevalence of metallic taste ranged from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases. No studies have been performed to investigate the influence of metallic taste on dietary intake, body weight, and quality of life. Several management strategies can be recommended for cancer patients: using plastic utensils, eating cold or frozen foods, adding strong herbs, spices, sweetener or acid to foods, eating sweet and sour foods, using 'miracle fruit' supplements, and rinsing with chelating agents. INTERPRETATION: Although metallic taste is a frequent side effect of chemotherapy and a much discussed topic on cancer patient forums, literature regarding metallic taste among chemotherapy treated cancer patients is scarce. More awareness for this side effect can improve the support for these patients.

[Treatment outcome in patients with taste disturbance].

The importance of taste has been recently evaluated from the standpoint of quality of life, but few reports exist on the clinical status of taste disturbance. We classified taste disturbance by cause and studied the effect of treatment and recovery duration. Subjects were 321 patients with taste disturbance, i.e., 131 men and 190 women (mean age: 59.9 years). Electrogustometry (EGM) and filter paper disks (FPD) were used to assess taste function in all subjects. We also asked them all about the degree of symptoms using visual analog scale (VAS). Statistical analysis was done using the unpaired t-test, with p<0.05 considered significant. Patients were treated with zinc sulfate, ferrotherapy, herbal medicine, and minor tranquilizers. Causes of taste disturbance were classified into idiopathic, post-common-cold, drug-induced, psychogenic, constitutional, and iron deficiency. Idiopathic taste disturbance was the commonest cause (125 cases, 38.9%), followed by drug-induced (62 cases, 19.3%), and post common cold (38 cases, 11.8%). Drug induced and psychogenic taste disturbance have increased. Recovery from symptoms was 79/103 (76.7%) in idiopathic taste disturbance, 24/33 (72.7%) in post-common-cold, and 14/17 (82.4%) in iron deficiency. Recovery took 22.2 weeks. Recovery was 32/50 cases (62.4%) in drug induced, taking 48 weeks. For all causes, EGM and FPD results were not associated with the degree of symptoms. Both tests tended to show delayed improvement compared to symptoms. Cases taking more than 6 months from symptom onset to medical examination showed significantly lower improvement and longer recovery time than those taking 6 months on less (p = 0.04).