In search of lost taste

When millions of people with Covid-19 found their food suddenly tasted of nothing, it prompted public attention and a surge of interest in developing treatments for taste loss. ‘True’ taste loss, however, is a distinct, rare, and still-mysterious condition. 

Eighteen years ago, Duncan Boak was on a night out with friends when he tripped and fell backwards down a flight of stairs, crunching his head against a concrete floor. When he was discharged from hospital and ate his first meal, it tasted of nothing. It was then that he realised he could not smell.

On visiting his GP, Boak was “met with a shrug” and told that there was nothing that could be done about it. Several years later, he came across a book which recounted the story of a woman with a similar experience to his own. It was thus that he learnt about the work of German scientist Professor Thomas Hummel – a smell and taste loss expert based at TU Dresden – and was inspired to get in touch with him. Boak spoke with Hummel and other specialists about the subject, became a lay expert, and founded the charity Fifth Sense in 2012.

‘Fifth sense’ refers not to taste (gustation) but to smell (olfaction): often placed at the bottom of the pile when it comes to the human senses. Boak says that the impacts of losing this sense are unjustly trivialised. They go beyond lack of pleasure in food and can include health complications caused by changes in diet; the danger of not being able to smell smoke, gas and other dangerous substances; and the psychological toll of losing a sense vital for forming memories and emotional bonding. “People will often describe it as a really profound bereavement, such is the emotional resonance of smell,” says Boak. “Take that away, and the world becomes a very different place.”

There is confusion around what smell loss and taste loss mean, with the latter often mistaken as a symptom of the former. This is thanks to ‘taste’ and ‘flavour’ being interchangeable in colloquial English. Taste and smell are separate senses. They both contribute to flavour (along with trigeminal nerve stimulation – our sense of ‘spiciness’). Try putting a sweet in your mouth while pinching your nose; you can taste its sweetness but cannot appreciate the flavour fully until you unpinch your nose.

Most people who find they cannot ‘taste’ actually have little trouble with gustation. Surgeon Professor Carl Philpott, who founded the UK’s first smell and taste clinic, explains: “Because a large proportion of what you appreciate in flavour is because of the smell, if you take that away, somehow it feels to people: well, it’s all gone, I can’t taste. Actually, from a medical point of view, you can taste perfectly fine, but you’ve lost your sense of smell.” He says that 99 per cent of people who come to his clinic have trouble with smell, not taste.

As much as 25 per cent of the population has impaired sense of smell, with greater prevalence among older people. Total smell loss is usually temporary and tends to return when whatever is damaging olfaction – smoking, certain medications, a viral infection – is stopped or treated. Persistent total smell loss is less common. It received little medical or public attention until the pandemic arrived and robbed tens of millions of people of their sense of smell (the SARS-CoV-2 virus binds to the lining of the nose via the ACE2 receptor, damaging olfactory cells in the process). Although an estimated 90 per cent of patients had recovered their senses two years after infection, a large population appears to have lingering sensory problems.

In the UK, there are just a handful of specialist smell and taste clinics, and GPs – through no fault of their own – tend to have limited knowledge about these conditions, hence ‘the shrug’ being such a common reaction. Patients lucky enough to find themselves in a clinic like Philpott’s begin by having the cause of their (usually) smell loss identified. If there is a medical condition causing it, that is treated; if not, it must be treated on its own.

There is no potent, proven treatment for smell loss that works for everyone. One of the more promising approaches, however, is a form of rehabilitation known as ‘olfactory training’, which has built a solid evidence base since being proposed by Hummel in 2009. It emerged from research which found some people could train themselves to smell androstenone (essentially an aphrodisiac for pigs) through repeated exposure, thanks to the plasticity of the olfactory nerve. Inhaling a set of odours – originally rose, lemon, clove and eucalyptus – twice daily for at least three months can help the damaged olfactory nerve regenerate, restoring some smell.

Since Covid-19, a range of olfactory training-based initiatives have emerged. Canadian entrepreneurs have created a virtual training programme called Sniffly. In the UK, Fifth Sense is part of a project to see whether odour-emitting devices in homes could help deliver olfactory training, while University of Nottingham researchers are working with flavour company TasteTech on a study using encapsulated flavours in chewing gum in an effort to regain taste as well as smell.

The surge in smell loss research prompted by the pandemic has also brought about new experimental treatments. UK and US researchers are examining the feasibility of an olfactory implant which functions like a cochlear implant, stimulating regions of the brain lacking input from patients with damaged olfactory nerves. Researchers at Stanford University are testing injections of growth factor-rich plasma – which they hope will encourage damaged olfactory cells to regenerate – while others are trying similar substances applied via a cream or a sponge stuffed up the nose. US researchers have also demonstrated that stem cell therapy can restore olfaction in rats, with exciting implications if this could be replicated in humans.

All these experimental treatments target olfaction, not gustation. This is no bad thing; smell is as important to flavour as taste, and the two interact (so restoring smell can help taste somewhat). ‘True’ taste loss, however, is a problem of its own: rare, poorly understood, and harder yet to treat.

Taste loss shares many causes with smell loss: viral infections like Covid-19, head trauma, neurodegenerative diseases like Parkinson’s, brain tumours, radiotherapy and certain medications can all cause taste disorders (more common than total taste loss are partial taste loss and taste distortion). When a one-in-100 patient comes to a smell and taste clinic with taste loss, sometimes the cause will be clear at once. Sometimes it will be identified after testing.

In 34 per cent of patients with taste disorders, however, no cause will be identified at all. “A lot of [patients with taste loss] are deemed to be idiopathic; we can’t find a cause after investigation,” says Philpott. “You examine their mouth, their tongue, you do a scan, you can do various blood tests, and they all come back normal.” In these cases, taste loss must be treated on its own – but the toolkit for this is even more rudimentary than that for smell loss. It could involve trying to stimulate taste in an analogue of olfactory training. It could, for taste distortion, involve using medications to block signals that make food taste metallic.

The trouble is that true taste loss is so rare it is difficult to collect a large enough sample size to carry out meaningful research (though Philpott and his colleagues are hoping to secure funding for a study of 50,000 people, which could help us better understand its prevalence). For now, Hummel – one of the world’s foremost authorities on smell and taste loss – says that we remain in a state of ignorance about it: “We actually know very little – if anything – about what is happening at a cellular or even molecular level [to cause taste loss].”

Taste is one of the most basic, universal human experiences. Long before the concept of medicine was born, humans instinctively knew to avoid bitter plants, the sensation of bitterness implying toxicity. It is curious, then, that we know so little about how this vital sense can vanish, let alone how to restore it.

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