Summary: Researchers have identified an organelle within neurons we use to perceive different odors.
Researchers at Umeå University have discovered a previously unknown cellular component, an organelle, inside neurons that we use to perceive smell.
The discovery may have implications for further research on impaired sense of smell, which is a common symptom of COVID-19.
“A prerequisite for finding a treatment for impaired sense of smell is to first understand how the sense of smell works, says Staffan Bohm,” Professor at the Department of Molecular Biology at Umeå University.
What the researchers have discovered is a so-called organelle inside nerve cells, that has not previously been observed. The newly discovered organelle has been given the name multivesicular transducosome by the researchers. The discovery was made possible thanks to Umeå University’s unique microscopy infrastructure.
Organelles are distinct “workstations” inside cells that can be compared to the different organs of the body, i.e., different organelles have different functions in the cell. Most organelles are common to different cell types, but there are also organelles with specific functions that only occur in certain cell types.
Olfactory nerve cells have long projections, or cilia, that protrude into the nasal cavity and contain the proteins that bind odorous substances and thus initiate nerve impulses to the brain. The conversion of odor into nerve impulses is called transduction and the newly discovered organelle, contains only transduction proteins.
The role of the transductosome is to both store and keep transduction proteins separate from each other until they are needed. Upon olfactory stimulation, the outer membrane of the organelle ruptures, releasing the transduction proteins so that they can reach the cilia of the neuron, and smell is perceived.
Release of vesicles with transduction proteins in electron microscope magnification.
The researchers also discovered that the transductosome carries a protein called retinitis pigmentosa 2, RP2, which is otherwise known to regulate transduction in the eye’s photoreceptor cells. If the RP2 gene is mutated, it can cause a variant of the eye disease retinitis pigmentosa that damages the eye’s light-sensitive cells.
“A question for further research is whether the transductosome has a role in vision and whether it is present in brain neurons that are activated by neurotransmitters and not light and smell. If so, the discovery may prove even more significant,” says Staffan Bohm.
The transducosome was discovered when researcher Devendra Kumar Maurya used a new technique called correlative microscopy. The technique combines electron microscopy and confocal microscopy so that a cell’s internal structures and the location of different proteins can be imaged simultaneously.
Crucial to the discovery was Devendra’s method development, which enabled the technique to be used to analyze intact neurons in tissue sections.
Abstract
A multivesicular body-like organelle mediates stimulus-regulated trafficking of olfactory ciliary transduction proteins
Stimulus transduction in cilia of olfactory sensory neurons is mediated by odorant receptors, Gαolf, adenylate cyclase-3, cyclic nucleotide-gated and chloride ion channels. Mechanisms regulating trafficking and localization of these proteins in the dendrite are unknown.
By lectin/immunofluorescence staining and in vivo correlative light-electron microscopy (CLEM), we identify a retinitis pigmentosa-2 (RP2), ESCRT-0 and synaptophysin-containing multivesicular organelle that is not part of generic recycling/degradative/exosome pathways.
The organelle’s intraluminal vesicles contain the olfactory transduction proteins except for Golf subunits Gγ13 and Gβ1. Instead, Gβ1 colocalizes with RP2 on the organelle’s outer membrane.
The organelle accumulates in response to stimulus deprivation, while odor stimuli or adenylate cyclase activation cause outer membrane disintegration, release of intraluminal vesicles, and RP2/Gβ1 translocation to the base of olfactory cilia.
Together, these findings reveal the existence of a dendritic organelle that mediates both stimulus-regulated storage of olfactory ciliary transduction proteins and membrane-delimited sorting important for G protein heterotrimerization.
In some relationships, women are the heart, the vision, and the brains. In our marriage, my wife is the nose.
“What happened to the milk that was in the fridge?” she’ll ask.
“I drank it.”
“Didn’t you notice it went bad?”
Or …
“You were eating sardines again, weren’t you?” she’ll accuse.
“I had ’em for lunch 2 days ago!”
Or …
“There’s something dead in the house,” she’ll insist.
Sure enough, in the basement, behind the couch, is a tiny dead mouse. Slideshow
“Women generally have a better sense of smell than men,” says Richard Doty, PhD, director of the Smell and Taste Center at the Hospital of the University of Pennsylvania. “And the disparity between the genders gets greater with age.”
The reason is not well understood, but it appears to be a cradle-to-grave advantage. “If you put breast pads [from nursing mothers] in a bassinet and observe the rooting or orienting behavior of babies, the females will generally be more responsive,” he says. And when researchers in Brazil autopsied the brains of men and women over 55 with jobs that could optimize their sense of smell (restaurant kitchens, for example), they found the women had 43% more cells in their olfactory bulbs on average than the men.
It’s just one of many fascinating facts being uncovered about our sense of smell, or olfaction. COVID-19’s adverse effect on olfaction brought it popular and scientific attention. We saw a push to develop a quick, simple, and affordable test for smell loss. (The Monell Chemical Senses Center in Philadelphia delivered a 1-minute, $1 SCENTinel rapid smell test.)
COVID-19 also produced a unique smell loss, with less than a third of those with the disease having any nasal blockage. We used to think congestion caused smell loss, but now we know that’s not always the case. Scientists are re-examining how viruses damage the olfactory system, both short- and long-term.
These are heady times for otolaryngologists, those who study and treat disorders of the nose. It was not always so. Darwin regarded smell as a rudimentary sense because its use in hunting, detecting danger, and other primal activities is now far less critical. And in a 2019 U.K. survey, 250 adults effectively turned up their noses at smell, ranking it the least valued of our five senses.
But smell remains crucial to our well-being. We’re learning more and more that our sense of smell is closely linked to our health – and could one day be used for monitoring our health and predicting disease.
What Happens When You Smell Something
Consider what happens when we detect an odor – something we do thousands of times a day. For something to have a smell, it must give off molecules. We inhale these molecules into the tops of our noses, where 6 million to 10 million specialized receptor cells await. Some molecules contain multiple chemicals, so they bind to families of receptors, creating a scent pattern.
Once this happens, the receptor cells message the olfactory bulb at the base of the brain, and the process of recognition and reaction begins. Sometimes, that happens right away (rotting flesh). Other times, it takes a bit. (“Hmm, what notes are you finding in the chardonnay?”) And sometimes, nothing registers at all. (When you have a cold, mucus prevents the molecules from fighting through.)
Joel Mainland, PhD, a neuroscientist and researcher at the Monell Center, estimates there are that 40 billion molecules that can have an odor. Some of these odors may smell the same or be undetectable by humans. It’s impossible to know for sure how many we can detect, but Doty puts it at “tens or even hundreds of thousands.”
Our sense of taste operates in a similar fashion, which is why people often confuse the two senses. Sensory cells in taste buds that line the tongue, back of the mouth, and palate detect chemicals in food molecules and relay that information to the brain. As we chew and swallow, some of these molecules are forced up through the nasal cavity to our old friends, the olfactory receptors, who contribute to the process.
To grasp this, Doty recommends pinching your nose shut while chewing a piece of chocolate. Closing the passageway between the oral and nasal cavities prevents food molecules from getting through, and you from tasting anything. The same thing happens when you have a cold.
Your Sense of Smell
Sinus specialist Jordan S. Josephson, MD, explains why our sense of smell is so important.
“Most things we think of as taste depend upon the smell system,” he says. “That’s why a significant number of people who come into our clinic complaining of being unable to taste anything actually have a smell problem.”
The same receptors found in the nose have also turned up in the kidneys, heart, and lungs. Why that’s so isn’t clear, but Mainland believes it’s because these cells have multiple functions. For example, some appear in the “carotid body,” a small cluster of cells near the carotid artery in the neck, and “seem to be able to sense how much oxygen and carbon dioxide is present – basically measuring and responding to lactate as if it were an odor.”
Smells can also trigger memories, such as a sniff of a perfume that makes you think of the person who wore it, or the aroma of food cooking that reminds you of your grandmother. These “olfactory flashbacks” happen because the brain’s smell-processing center links to its emotion and memory hub. A study from Wheeling Jesuit University in West Virginia found that the smell of cinnamon improved brain function and working memory, a finding that could help us treat dementia.
What Your Sense of Smell Can Tell You About Your Health
Jayant Pinto, MD, a professor of surgery at University of Chicago Medicine, likens smell loss to a canary in a coal mine. “It doesn’t directly cause death,” he says, “but it’s a harbinger.”
In a 2014 study, he gave smell tests to 3,000 people ages 57 to 85. Five years later, he checked back. Nearly 40% of those who did poorly on the original test had died, compared to 19% who scored moderately and 10% who tested well. He calculated that a significant loss of smell is a stronger predictor of 5-year mortality (the likelihood of dying in the next 5 years) than emphysema, cancer, heart attack, stroke, diabetes, or congestive heart failure.
This study has since been replicated, so the association isn’t a one-time fluke. Other research links olfactory dysfunction to many neurodegenerative diseases (Parkinson’s, Alzheimer’s, epilepsy) and autoimmune disorders (multiple sclerosis, Crohn’s, myasthenia gravis).
“Smell dysfunction can be a very early indicator of these things,” says Doty, so if you notice anything amiss, it can’t hurt to consult a doctor or arrange to be tested for olfactory problems. You can use the SCENTinel rapid smell test mentioned earlier or the gold-standard University of Pennsylvania/Sensonics’ Smell Identification Test (around $30). Both are self-administered and involve scratching and sniffing cards with various scents. The results provide a baseline for your sense of smell and may also indicate disease. For example, “about 90% of people who develop Parkinson’s had demonstrable smell loss early on,” Doty says.
It may even be possible to smell disease. My wife, “the nose,” is a registered nurse at our local hospital. Many years ago, when she was pregnant, she walked into a patient’s room and had to turn around right away. “There was an overwhelming smell of decomposition,” she recalls, “like if you were hiking and came upon a dead animal.”
The patient in that room had stage IV cancer, and she insists she could smell it. (Her hypersensitivity ended with the birth of our child.)
“In the 19th century, the smell of acetone [nail polish remover] in the breath was regarded as indicative of diabetes,” says Doty. “There’s also a metabolic disorder called maple syrup disease where the urine is sweet-smelling. There are many other examples in the medical literature where skin odor is related to certain diseases. There’s no reason why changes in the body that occur with certain diseases, if they end up in our saliva or blood, couldn’t be discerned by a dog or even a human.”
Whether “super-smellers” – people with a hypersensitive sense of smell – exist is controversial. But Doty and Mainland agree that the smeller spectrum varies widely. Just as with everything else, some people are better at it than others.
You May Not Be Sick – Just Aging
Like hearing and vision, our sense of smell gradually weakens over time. Doty’s research shows that 75% of people over 80 have “some demonstrable deficit.” Between ages 65 and 80, this is true for half the population. And among those over 65, 5% to 15% have no sense of smell at all (a condition called anosmia).
This decline is believed to be caused, at least in part, by the colds we catch over the years. “The olfactory endothelium, or membrane at the top of the nose, accumulates little islands of damage called metaplasia every time we have a bad cold,” explains Doty. “So, by the time we’re in our 60s and 70s, something that otherwise would be innocuous, like the common cold, can take us over the waterfall.”
A big area of research right now is whether age-related smell loss can be slowed or stopped, and if our sense of smell can be improved. Not really: Receptor cells can’t be strengthened by working them out, so to speak. And once they’re damaged by viruses, accident, or aging, they can’t be regenerated.
But you can learn to smell better. The trendy notion of “olfactory training” is a little misleading; it’s the brain that can be trained. We can teach ourselves to recognize and identify new scents. Mainland tries to smell new things every day, even going as far as to order unique scents from perfumers to sample. Wine sommeliers essentially do the same thing, exposing themselves to many varieties of wine to learn their scent nuances.
The Future of Smell Research
As Darwin noted, we no longer spend our days sniffing the ground and tracking prey. But the genes that governed these ancient behaviors are still with us, explains neuroscientist Marissa Kamarck, PhD. And not only can scientists detect the original or ancestral version of these genes (so-called non-functional or pseudo genes), but they can also identify variants or newer versions of them. In a recent study that she co-authored with Mainland, Kamarck found evidence for the theory that our sense of smell, as a species, may be degrading.
“We found that most often, the variants that predicted lower intensity [for smells] were the newer variants,” she says. “And in olfaction, our genes are mutating faster than in other families of genes,” Mainland says.
If anything is happening, it will take centuries to unfold. And any ability to smell that we have lost may have been replaced or compensated for by our gaining new ones. (Like smelling a gas leak, something prehistoric man had no need to recognize or fear.) Like every other part of us, our sense of smell is always evolving.
Even more intriguing discoveries lie ahead. Mainland points out that the mapping from chemical structure to olfactory perception is unknown (unlike in vision, where wavelength translates into color, and in hearing, where frequency predicts pitch).
“There is not a scientist or perfumer in the world who can view a novel molecular structure and predict how it will smell,” he says. His research goal is to develop that.
Indeed, a recent global survey by the Ericsson ConsumerLab found that most consumers expect to be able to smell movies and even products digitally through an “Internet of Senses” by 2030.
Imagine that. If my wife is at work, I could text her a sample scent of the milk to see if it’s safe to drink.
About 5% of people who lost smell or taste had persistent dysfunction at 6 months.
Two and a half years into the pandemic, a clearer understanding of the natural history of COVID-19–associated smell and taste dysfunction finally is emerging. Three groups have evaluated the timeline of such dysfunction.
In a meta-analysis, researchers combined data from 18 observational studies of patients with COVID-19–associated smell and taste dysfunction to determine the time course of recovery and identify risk factors for persistence. Data from 3700 patients (collected before emergence of Omicron) were included. Included studies varied widely in methodology and setting; most relied on self-report.
Key findings were:
Among patients reporting loss of smell, the proportions who recovered by day 30, 60, 90, and 180 were 74%, 86%, 90%, and 96%, respectively.
Among patients reporting loss of taste, the proportions who recovered by day 30, 60, 90, and 180 were 79%, 88%, 90%, and 98%, respectively.
Persistent dysfunction in smell and taste at 6 months were reported in 5.6% and 4.4% of patients, respectively.
Women were less likely to recover smell and taste than were men.
Patients with nasal congestion and more-severe smell dysfunction were less likely to recover.
Comment
These results should help clinicians in counseling patients whose quality of life is affected by smell and taste dysfunction following COVID-19. However, the results are limited by lack of information on COVID-19 variants, vaccination status, and treatments received. Reassuringly, other studies from Brazil and Italy suggest that smell and taste dysfunction occur much less frequently with Omicron than with prior variants and that recovery can continue beyond 6 months.
Humans are largely not aware of their olfactory powers, which serve many purposes; newborn babies have strong olfactory responses
Experts think when we shake hands with a new person, we use our sense of smell to size them up
Plants use odors to attract bees for pollination and to warn other plants about pests
Dogs have amazing olfactory abilities because of their large noses, which can even detect cancer
Most of what we think is taste actually comes from our sense of smell
This article was previously published April 20, 2019, and has been updated with new information.
We humans do not appreciate our sense of smell. Compared to other senses like vision and hearing, we tend to ignore the information from our sense of smell with the exception of flowers, food being prepared and, of course, those lucky people who have discovered aromatherapy.
But according to the documentary, “Smell — Our Most Underestimated Sense,” our sense of smell affects us much more than we realize. Certainly, we know that it protects us from dangers like fire because we smell the smoke, explosions because we smell natural gas and food poisoning because we smell spoilage. But few realize our sense of smell also lets us “read” other people much like dogs “read” each other by sniffing.
Of course, the olfactory read that humans conduct is not as obvious as that of dogs sniffing but, according to this film, people will oftentimes sniff their hands after shaking hands with someone new, indicating that important information has been gained. The sense of smell also helps newborns bond with their mothers, and “smell dysfunction” can impair such bonding.
Nevertheless, smell is so underappreciated people interviewed in the documentary said they would rather lose it than their “access to technology,” such as their smart phones. If you’re inclined to agree, after watching this remarkable documentary, you just might change your mind.
Aromatherapy Takes a Clue From Nature
I am a big believer in aromatherapy, which is based on the use of essential oils, also called volatile oils. In addition to inducing relaxation and sleep, and reducing blood pressure1 and stress, aromatherapy may be beneficial for depression,2 anxiety,3 dementia4 and pain relief.5
According to “Smell — Our Most Underestimated Sense,” plants and flowers also use these healing fragrances for themselves! For example, flowers deliberately emit the chemical signals of a female bee so that the male bee will “mate” with the flower and pollinate it. Certain birds, butterflies, bats, moths and even honey possum also pollinate flowers.
The irreplaceable services of these pollinators are seriously threatened by pesticides and chemicals, posing an environmental crisis. It is important to remember that every time you shop for organic food you vote against these harmful chemicals that are creeping into our daily life.
Interestingly, the least pretty flowers are often the most fragrant ones, because they cannot rely on their visual beauty to attract pollinators says the documentary, Moreover, plants can emit odors to warn other plants of impending insect attacks, just as animals warn others about imminent predators.
Sensing Others Through Our Sense of Smell
Many have heard of the phenomenon of menstrual synchrony in which women who live or work together can begin to have their periods at the same time.6 In a T-shirt sniff study, says the documentary, women’s testosterone levels changed in response to the scent of another woman, depending on where that woman was in her monthly cycle — though, of course, the women were not consciously aware of this.
Paul Moore, a professor at Bowling Green State University who specializes in chemical ecology and the role chemical signals play in an organism’s ecological role, explains the reaction like this:7
“The chemical senses, I call them ninjas — they’re hidden. So, they go into our brain, and we’re not aware of it, we’re not conscious of it, so it makes us respond emotionally, respond physiologically, before we actually think about the response. So, it’s very subtle and it’s very hidden …
Testosterone is tied very much to social dominance and in competitiveness and aggression. And up-regulating or down-regulating testosterone through chemical signals could change your competitiveness.”
Why would this happen? From an evolutionary standpoint, fertility could be governed by a competition won by dominant females so that less “alpha” females would cease to compete for males at a certain time.
The Hidden Powers of a Handshake
Our sense of smell does not just determine sexual rivals and fertility competition. In one study cited by the documentary, a hidden camera filmed people meeting strangers for the first time and sometimes shaking their hands. Greeters who shook hands smelled their hands afterward twice as often as those who didn’t shake hands, presumably accessing the “information” the handshake gleaned.
Shaking hands is likely a human version of dogs sniffing each other — a way of acquiring a lot of social information in one quick impression, says Moore. When dogs sniff each other upon meeting, for example:
“They’re sniffing and saying, ‘Oh, I played with you last week. You’re a good dog to play with,’ or ‘I smell you from last week. You were a little mean, so I’m not going to play with you.’ They’re going to pick up their dominant status, social status, their reproductive status, what they’ve eaten. All that kind of stuff that you and I would share in a conversation with words, they share with chemical signals. Their whole world is sense of smell.”
Man’s Best Friend Can Save Our Lives
One of the most dramatic facts shared in “Smell — Our Most Underestimated Sense,” is dogs’ proven ability to detect cancer in humans from subtle smells in breath, skin and more. Dogs have up to 300 million receptor nerve cells that detect smell (compared to 5 million in humans) and some dogs have been successfully trained to detect human cancers.
In a 2015 study published in the Israel Medical Association Journal,8 two dogs picked out the breast cancer cell cultures that they had been trained to detect 100 percent of the time. These “detective” dogs even picked out cancer specimens they were not trained to detect, but they never picked out control (noncancer) specimens, meaning “false positives,” which plague diagnostic methods that are more high-tech than dogs.
The dogs picked out early-stage cancer as well as advanced cancer with amazing accuracy and specificity — a skill that would clearly save lives. In a 2017 study published in the European Journal of Cardio-Thoracic Surgery,9 a trained dog was also able to detect early lung cancer from the exhaled breath of patients with remarkable accuracy. Here is what the researchers wrote:
“After appropriate training, we exposed the dog (a 3-year-old cross-breed between a Labrador retriever and a pitbull) to 390 samples of exhaled gas collected from 113 individuals (85 patients with LC [lung cancer] and 28 controls, which included 11 patients without LC and 17 healthy individuals) for a total of 785 times.
The trained dog recognized LC in exhaled gas with a sensitivity of 0.95, a specificity of 0.98, a positive predictive value of 0.95 and a negative predictive value of 0.98.”
Other Cancers Are Being Detected by Dogs
Canine olfactory abilities are also being studied in the screening for colorectal cancer (CRC) which takes the lives of approximately 50,630 Americans per year.10 This is what researchers writing in a 2010 article in BMJ said:11
“Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99.
The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease.”
Such noninvasive and economical methods for early detection of colorectal cancer that avoid colonoscopy are sorely needed. Currently the occult blood test is one of the few affordable tests in the doctors’ colorectal cancer arsenal.
Dogs can also detect the specific volatile organic compounds associated with prostate cancer in urine samples with high estimated sensitivity and specificity according to a 2015 study.12
And, in a 2013 study, dogs correctly identified all 42 blood samples of patients with ovarian cancer, achieving an accuracy rate of 100 percent.13 Even more encouraging, the dogs could determine whether cancer cells remained after surgery, which is crucially important since doctors generally cannot determine if residual cancer cells remain.
How Were Dogs’ Medical Abilities Discovered?
How did an awareness of such canine abilities and their possible use in medicine develop? Here is how the researchers trace the origins of such dog detections:
“The idea of using a dog’s olfactory sense for the early detection of cancer was first raised by Williams and Pembroke and reported in The Lancet in 1989. These authors described the case of a patient who visited the clinic because her dog showed a particular interest in a skin nevus she had. Following its excision, the pathological examination revealed malignant melanoma.”
A 2013 case report in BMJ (previously the British Medical Journal) reported a similar phenomenon.14
“Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised.”
Another Important Function of Our Sense of Smell
Do you like different flavored jelly beans? People tasting them in “Smell — Our Most Underestimated Sense” quickly discovered that most of the “taste” was from their sense of smell not their sense of taste. When they were asked to pinch their noses, most tasted nothing.
One subject said he tasted “nothing so far.” Another said, the jelly bean had “like, a sweetness, but I don’t know the flavor.” Once the subjects unpinched their noses they could describe the exact flavor of the jelly bean — which was really a smell. The loss of smell had a profound effect on Anna Barnes, featured in the documentary.
“I had a bad hit to the head, so I was kind of recovering from that. And then about a week afterwards, I thought, ‘Hold on, something’s not quite right here.’ It became very clear to me, when I was well enough to go outside, that I’d lost my smell, because back then, the sewerage was open sewerage.
So, I lost my appetite for the first, I would say, four months. I was kind of retraining myself to remember, ‘Oh, no, you have to eat’ …
When I lost my taste, fruit tasted for me, terrible. It’s just gross. Fruit just tastes really slimy. It’s all about texture … I also had some early, you know, mix-ups, of accidentally drinking vodka, thinking it was water. And, you know, all the kind of stereotypical things that I guess people worry about.”
It is clear that from “reading” other people to determining dangers to our enjoyment of food, our sense of smell is crucial — and certainly more important than our access to technology if we were asked to choose. Just as eye-opening is the ability of man’s best friends to use their olfactory natural abilities to detect cancers as accurately as the most high-tech machines.
Summary: Study reveals the mechanism behind why certain food and drink aromas smell disgusting to people with parosmia.
Source: University of Reading
For people with parosmia, or distorted sense of smell, the aroma of freshly ground coffee can be as disgusting as burning rubbish.
Now, researchers have discovered the secrets of why certain food and drinks smell (and likely taste) disgusting to people with parosmia.
In new research published in Communications Medicine, a team of scientists have found that certain highly potent odour molecules found in coffee trigger the sense of disgust which is associated with parosmia. Take 2-furanmethanethiol – the most potent aroma molecule that you’ve never heard of before. It is one of those molecules that has been driving people to their wit’s end.
By trapping the aroma of coffee, the team were able to test coffee compounds on volunteers who had parosmia and compare their reaction with those who didn’t.
From the hundred or so aroma compounds present in coffee, people with parosmia could point to those responsible for the sense of disgust. Among the 29 volunteers, scientists found 15 commonly identified compounds that triggered parosmia.
Dr Jane Parker, Associate Professor of Flavour Chemistry and Director of the Flavour Centre at the University of Reading said:
“This is solid evidence that it’s not all “in the head”, and that the sense of disgust can be related to the compounds in the distorted foods. The central nervous system is certainly involved as well in interpreting the signals that it receives from the nose.
The parosmic experience is a combination of the two mechanisms which produces the distorted perception of everyday foods, and the associated sense of disgust.
“We can now see that certain aroma compounds found in foods are having this particular effect. It will, we hope, be reassuring for those with parosmia to know that their experience is “real”, that we can identify other foods which may also be triggers and, moreover, suggest “safe” foods that are less likely to cause a problem. This research provides useful tools and strategies for preventing or reducing the effect of the triggers.”
Mr Simon Gane, one of the researchers, from the Royal National Ear, Nose and Throat and Eastman Dental Hospital said: “We still have a long way to go in understanding this condition, but this research is the first to zoom in on the mechanism in the nose. We now know this has to be something to do with the nerves and their receptors because that’s how these molecules are detected.”
Some of the most cited food and drinks that set off parosmia in sufferers include:
Coffee
Onions
Garlic
Chicken
Green peppers
The study used a technique called GC-Olfactometry. The aroma from the coffee is introduced into one end of a very long and narrow pipe called a capillary. Some of the aroma compounds travel through the capillary faster than others. The fastest ones come out of the other end first and the slower ones come out later, thereby separating the compounds out so that the volunteers could smell them and describe them one by one.
Now, researchers have discovered the secrets of why certain food and drinks smell (and likely taste) disgusting to people with parosmia. Image is in the public domain
Prior to the global pandemic caused by Covid-19, parosmia was a rare condition known to occur after infections such as cold, flu or sinus infections, with very little awareness about the causes and treatments for the disease.
During the pandemic Covid-19 symptoms included loss of smell and taste in 50-60% of cases, of which about 10% developed parosmia. While, since the Omicron variant, loss of smell and taste has become a less common symptom (estimated to occur in about 10-20% of cases) and parosmia cases are likley to be fewer in number, parosmia is still estimated to affect 2 million people in Europe.
Loss of smell and taste—a hallmark symptom of COVID-19—was not on the minds of a group of Yale School of Medicine researchers when they embarked on a study in the spring of 2020.
The scientists, led by Joseph Vinetz, MD, an infectious diseases specialist, were interested to find out if an oral medication used to treat pancreatitis could reduce the viral load (the amount of virus in your body) of SARS-CoV-2 and improve symptoms in people newly diagnosed with COVID-19.
The study, which is available on a preprint site and has not yet been published in a peer-reviewed journal, ran from June 2020 to April 2021. It showed that the medication, called camostat mesylate, did little to lessen viral load. But, to the researchers’ surprise, it brought a different type of benefit.
“The patients who received the drug didn’t lose any sense of smell or taste. That was a ‘wow’ factor,” says Dr. Vinetz.
This matters because loss of smell, known as anosmia, and loss of taste are common COVID-19 symptoms. For many, the senses return as the infection fades. But for others, the effect lingers in varying degrees. (With the omicron variant, those symptoms can still occur, but not as often as it has with other variants.)
How the ‘surprise’ finding on loss of taste and smell was discovered
Dr. Vinetz says he was originally motivated to look into camostat mesylate after he saw an April 2020 study published in Cell that showed how this medicine could prevent SARS-CoV-2 from entering cells.
Dr. Vinetz recruited several colleagues to collaborate, including Anne Spichler Moffarah, MD, Ph.D., an infectious diseases specialist, and Gary Desir, MD, chair of the Department of Internal Medicine. Geoffrey Chupp, MD, director of the Yale Center for Asthma and Airways Disease, ran the clinical trial.
The Phase II randomized trial enrolled 70 participants who tested positive for COVID-19 within three days of starting the study. Participants took the medicine four times a day for seven days.
Although the trial was stopped once it was clear that the main objective of reducing viral load was not occurring, the researchers think the surprise findings about loss of smell and taste warrant additional study.
“My daughter had COVID a year ago and she still has trouble smelling and tasting things,” says Dr. Desir. “This drug seems to be able to modulate that loss of smell and taste. It has very few side effects and has been studied extensively. This could be the type of treatment that is given to someone with COVID at the onset of the infection.”
This matters because loss of smell, known as anosmia, and loss of taste are common COVID-19 symptoms. Image is in the public domain
If the drug were to be approved for this purpose, the doctors believe it could be a game-changer. “It wouldn’t be an expensive medication. Our idea was that everyone would take it if they were diagnosed because it’s hard to predict who will lose their sense of smell or taste, and it’s better to prevent it than to wait for it to happen,” Dr. Desir says.
Additional benefits found for those with COVID-19
There were also other benefits to this medication, as the study showed that those who received it reported notable improvements related to fatigue, compared to those who received a placebo.
“People who got camostat mesylate in the trial started feeling less tired and better overall after day four, which was statistically different from the placebo group,” Dr. Vinetz says.
“And there were essentially no adverse effects in the camostat mesylate group.”
Whether camostat mesylate could help restore sense of taste or smell in someone who has lost it is unknown, he adds. “More studies would help us with that,” Dr. Chupp says.
In order for camostat mesylate to become available for use in preventing the COVID-19-related loss of taste or smell, there would need to be a Phase III clinical trial and an application filed to the Food and Drug Administration (FDA) for emergency use authorization. All of this would take some time, Dr. Chupp explains.
Still, the doctors are hopeful their surprise discovery can make a positive impact on the fight against COVID-19. “A drug such as camostat mesylate presents an opportunity,” says Dr. Chupp
We all come to rely on the senses that we have available to us. If we are lucky, then we have access to all five: sight, sound, taste, touch, and smell. For some people, they are not so lucky and have to rely more on the ones they do have. Researchers have found that your sense of smell could now be used to predict the onset of Alzheimer’s.
A recent study was carried out at the Massachusetts General Hospital and involved a total of 183 older adults. To begin with, all were given brain imagining and medical assessments in order to test their cognitive functioning abilities. The study then involved participants completing a four-point test that included evaluating ten different common smells such as mint, lemon, and strawberry. Participants that had difficulty recalling these smells were found to be suffering from the early stages of Alzheimer’s disease.
Don’t start to panic if you do have a poorer sense of smell than you did before. It doesn’t automatically mean that you have Alzheimer’s. Our smell tends to decline as we get older, so this could be one reason behind it. But if you do have any concerns, then have your doctor check it out. Alzheimer’s is a horrible, debilitating disease, and the earlier it can be diagnosed the better the chance of effective treatment options.
There is still no cure for it and is the six largest cause of death. But, there are still a few things we can all do to try and prevent ourselves from getting it. They are:
-Exercise regularly. Not just your body, but your brain too. Regularly complete crosswords or read or complete some other form of mental stimulation as a way to preserve your brain.
-Keep your head protected and always wear a helmet as head trauma has been linked to Alzheimer’s.
-Maintain a healthy diet. Those high in vegetables such as leafy greens and broccoli have been proven to reduce the rate of cognitive decline in patients.
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