The Mystery of “Metal Mouth” in Chemotherapy

Abstract

Of all the oral sensations that are experienced, “metallic” is one that is rarely reported in healthy participants. So why, then, do chemotherapy patients so frequently report that “metallic” sensations overpower and interfere with their enjoyment of food and drink? This side-effect of chemotherapy—often referred to (e.g., by patients) as “metal mouth”—can adversely affect their appetite, resulting in weight loss, which potentially endangers (or at the very least slows) their recovery. The etiology of “metal mouth” is poorly understood, and current management strategies are largely unevidenced. As a result, patients continue to suffer as a result of this poorly understood phenomenon. Here, we provide our perspective on the issue, outlining the evidence for a range of possible etiologies, and highlighting key research questions. We explore the evidence for “metallic” as a putative taste, and whether “metal mouth” might therefore be a form of phantageusia, perhaps similar to already-described “release-of-inhibition” phenomena. We comment on the possibility that “metal mouth” may simply be a direct effect of chemotherapy drugs. We present the novel theory that “metal mouth” may be linked to chemotherapy-induced sensitization of TRPV1. Finally, we discuss the evidence for retronasal olfaction of lipid oxidation products in the etiology of “metal mouth.” This article seeks principally to guide much-needed future research which will hopefully one day provide a basis for the development of novel supportive therapies for future generations of patients undergoing chemotherapy.

Explaining Crossmodal Correspondences Between Colours and Tastes

“…5 That said, we are not aware of any data having yet been collected on the colour associations of metallic taste sensations. This is despite the growing interest in the latter, given their increasingly frequent occurrence among those undergoing chemotherapy (e.g., Pirkwieser et al, 2021;Reith & Spence, 2020).…”

“…And, looking to the present/future, various other “basic” tastes have been put forward by researchers (thus far with varying degrees of support). These include metallic (e.g., Reith & Spence, 2020 ; though see also Ikeda, 1909/2002), starchy ( Lapis et al., 2016 ; though, once again, see also Ikeda, 1909/2002), calcium ( Tordoff et al., 2012 ), and fatty (acid) taste (e.g., see Mattes, 2009 ; see also Chale-Rush et al., 2007 ; DiPatrizio, 2014 ). One might wonder whether these putative basic tastes (though see Delwiche, 1996 ; Erikson, 2008 ; Hartley et al., 2019 ) also have colours, or other visual appearance properties, associated with them.…”

Metallic: A Bivalent Ambimodal Material Property?

“…Metal ions activate the human taste receptor TAS2R7 (Behrens et al, 2019;Wang et al, 2019), hence suggesting a link to the perception of bitter tastes (Reith & Spence, 2020). Indeed, consistent with such a view, those reporting chemotherapy-induced metallic sensations have been reported to exhibit enhanced sensitivity to bitterness (IJpma et al, 2017).…”

“…Indeed, many patients undergoing chemotherapy report sensations such as a metallic taste, a bad taste, or the taste of blood, among other symptoms. These metallic tastes are also uniformly negatively valenced (see Reith & Spence, 2020, for a recent review). However, that said, it is currently unclear to what extent the metallic sensations that many patients undergoing chemotherapy report (e.g., IJpma et al, 2015), refer to a specific descriptor tied to a particular sensation, or class of sensations, or whether instead the term might actually be used as a general descriptor for any kind of unpleasant mouth sensation, regardless of its phenomenal quality (see Reith & Spence, 2020, for a detailed discussion of this point; see also Ruiz-Ceamanos et al, submitted).…”

“…At the same time, however, one of the most intriguing features of those sensations that people choose to describe as metallic is that the valence attached varies dramatically as a function of the sensory modality to which the term is applied. While metallic visual impressions tend to be positively valenced (i.e., pleasant and attractive), they are mostly negative when referred to in the context of stimulation by (or involving) the chemical senses (see Reith & Spence, 2020, for a recent review). The shiny visual surface properties of certain metals have long appealed, especially in the case of precious metals such as silver and gold (e.g., Aldersey-Williams, 2011).…”