Sixty seconds on . . . smell training
BMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n1080 (Published 26 April 2021) Cite this as: BMJ 2021;373:n1080Read our latest coverage of the coronavirus pandemic
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Dear Editor
Smell Training and Neuroplasticity
Dr Rimmer”s recent article shows that smell training is helpful in treating loss of smell function in Covid 19 patients. Smelling ground coffee, or a sprig of fresh herbs for about 10 seconds each for two times a day will be of help for treating patients.[1] This function is due to the neuroplasticity of brain. Most Covid 19 patients regain their sense of smell spontaneously. 90 per cent of patients recover their sense of smell after six months. [2]
The COVID-19 virus crosses the blood-brain barrier. The spike protein of the virus is capable of crossing the blood-brain barrier, likely contributing to symptoms of brain fog and other cognitive effects reported by people infected with the virus.
The spike protein of the virus, which is known as the S1 protein, is the key driver that helps the virus to cross the blood-brain barrier [3]. The Covid 19 virus has receptors ACE2 and TMPRSS2 in nasal and olfactory mucosal. Covid 19 virus infection can cause disruption of sustentacular cells as well as mucus producing glandular cells, and this can cause a decreased perception of smell and leave the olfactory epithelium less protected against other viral or bacterial threats. The stem cells of the olfactory epithelium, the basal cells, are most probably not affected by COVID-19 infections [4].
The presence of the ACE2 virus entry protein in nerve terminals suggests an alternative route for brain infection in Covid 19 disease [5].
Smell disturbances are common in Covid 19 disease.
References
1.Rimmer A Sixty seconds on . . . smell training. BMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n1080 (Published 26 April 2021) BMJ 2021;373:n1080
2. Huart C, Philpott CM, Altundag A, et al. Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view. International Forum of Allergy & Rhinology. n/a(n/a). doi:https://doi.org/10.1002/alr.22788
3. Elizabeth M. Rhea, Aric F. Logsdon, Kim M. Hansen, Lindsey M. Williams, May J. Reed, Kristen K. Baumann, Sarah J. Holden, Jacob Raber, William A. Banks, Michelle A. Erickson. The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice. Nature Neuroscience, 2020; DOI: 10.1038/s41593-020-00771-8
4. Klingenstein M, Klingenstein S, Neckel PH, Mack AF, Wagner AP, Kleger A, Liebau S, Milazzo A. Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb. Cells Tissues Organs. 2020;209(4-6):155-164. doi: 10.1159/000513040. Epub 2021 Jan 22. PMID: 33486479
5. Bilinska K, von Bartheld CS, Butowt R. Expression of the ACE2 virus entry protein in the nervus terminalis suggests an alternative route for brain infection in COVID-19. bioRxiv [Preprint]. 2021 Apr 12:2021.04.11.439398. doi: 10.1101/2021.04.11.439398. PMID: 33880469; PMCID: PMC8057234
Competing interests: No competing interests
Re: Sixty seconds on . . . smell training
Dear Editor,
Although it is often stated that 60% of patients with Covid-19 experience varying degrees of smell impairment this information is based on questionnaire analysis. Where standardised olfactory testing is employed the figure is almost 100% (Hawkes 2021)
There have been several attempts at olfactory retraining over the past 12 years. On basic principles one would expect that smell training could work, given the parallels with the other special senses and physiotherapy for motor and cerebellar deficits. Healthy people without smell impairment can lower (improve) their thresholds by training and become wine tasters or perfumers. The first formal trial of smell training was based on a small non-blinded case-control study of 56 people with smell deficits from various causes (Hummel et al 2009). The cases had to repeatedly inhale odours of rose, cloves, eucalyptus and lemon before bedtime and on wakening for 12 weeks. One of 16 control subjects showed lower thresholds after training compared to 11 of 40 patients. Neither group improved on identification scores. Five patients (21%) with smell impairment resulting from upper respiratory infection showed improvement. As reviewed by Doty (2019) there have been several further trials, mostly involving small numbers and without blinding. Some cases were studied for longer periods (e.g. 32 weeks) others used 12 odours instead of 4. In a meta-analysis Sorokowska et al (2017) concluded that there was a positive effect especially for longer training periods and suggested that the benefit derived from enhanced cognitive processing of olfactory information and increased attention to odours. Overall there is no robust scientific evidence for improvement and clearly there is a need for a large double blind trial of olfactory training.
Other approaches designed to accelerate smell recovery that fail to show clear benefit include: acupuncture, alpha-lipoic acid, caroverine, steroids, rasagiline, sodium citrate, theophylline, venlafaxine, vitamins A, B12, D, E and zinc sulphate (Doty 2019).
Where there are olfactory illusions (phantosmias) or distortions (cacosmias) there is anecdotal evidence of benefit with pregabalin, gabapentin or sodium valproate.
Around two-thirds of people with impaired smell sense after Covid-19 recover within two months (Hawkes 2021). So, if your smell sense is persistently impaired by all means try training, it’s harmless and might just help a little. Ideally, relatively pure aromas should be used such as rose, lavender, vanilla, pear, peach, cut grass, orange, chocolate, banana. It is important not to use odours that have significant additional stimulant effect on the non-olfactory nasal epithelium as this region is innervated by the trigeminal nerve. Trigeminal stimulant odours include: onion, alcohol, mint, menthol, chili, ammonia. Any improvement with these ‘impure’ smells could result from training of a healthy trigeminal nerve and indeed this mechanism may be the explanation of benefit observed in smell training trials so far.
References
Doty RL. Treatments for smell and taste disorders: a critical review. Handbook of clinical neurology. 2019 Jan 1;164:455-79.
Hawkes CH. Smell, taste and COVID-19: testing is essential. QJM: An International Journal of Medicine. 2021 Feb;114(2):83-91.
Hummel T, Rissom K, Reden J, Hähner A, Weidenbecher M, Hüttenbrink KB. Effects of olfactory training in patients with olfactory loss. The Laryngoscope. 2009 Mar;119(3):496-9.
Sorokowska A, Drechsler E, Karwowski M, Hummel T. Effects of olfactory training: a meta-analysis. Rhinology. 2017 Mar 1;55(1):17-26.
Competing interests: No competing interests