Smell: health and disease

Healthy smell

What is a "healthy" smell? Can smells influence health? Bad smells signify a possible hazard (see Functions of Smell) so some diseases smell bad, but not all, for example the breath of diabetics  smells sweet. What is a “good” smell and why are there good smells? Perfume is just an adornment, good food smells do not please when you are full, and flowers smell for insect pollinators not for us humans, besides many flowers smell bad (attracting flies to pollinate).

The smell after rain - geosmin

To answer the question “why have good smell”? Smell can be therapeutic and curative herbs smell pleasant (see Therapeutic use of smell). Lemon aroma in a doctor's waiting room resulted in fewer reported health symptoms. Lemon is associated with cleanliness and freshness and this aroma altered people's psychological state so they felt better and complained of fewer symptoms. Lemon essential oil has been shown to have anti-depressant properties in both animal and human studies. How does this work? Many studies have been carried out to determine the mechanisms involved (see Therapeutic use of smell).

Night flowering cactus. Flower opens at around 2am, smells beautiful and dies at dawn.

Smell as an indicator of health
Body odour has a number of functions (see "Smell and mate selection"), one of which is to tell us when to wash. We notice a build up of our body odour, some more quickly than others (!) and we find the smell unpleasant - is this another potential hazard? Well, we need to remove dead skin and grime to prevent a build up of fungi and bacteria that could lead to disease and infection. The bacteria are one of the factors in the production of bad smell.Can the smell of your breath reveal information about your health and disease? Exciting new research is beginning to show that it can. Dogs can sniff out cancer and the NHS is thinking of using them to do so - yes really, dogs are cheaper than doctors.

Image from Barkpost.com

A fascinating and alarming study by Pinto in Martha McClintock's lab shows that olfactory loss is a predictor of death. In a population of 3000 from 57-85 years old, 39% of those with anosmia (loss of smell) were dead in 5 years compared to 10% of those with a normal sense of smell. This was the greatest predictor of death other than acute liver damage. Why is this? Well, it's not clear but the smell receptor cells are very exposed to the environment and pollution and also to viruses. Viruses can enter the body and get to the brain via the olfactory receptor cells, for example see the viral theory of Parkinson's Disease. Also, these cells are constantly renewing themselves so if they stop doing so this is bad news for the rest of the body. Basically the take home story is that the sense of smell is linked in unknown ways to factor(s) influencing our mortality. We should pay more attention to our sense of smell.

Smell of disease

Plague doctor

There is anecdotal and scientific evidence to suggest that different diseases have particular smells. Most of us recognise that our smell changes when we are ill. In earlier times doctors placed much more importance on a patient's smell - in particular the smell of their stools.
Typhus - sickly odour, another report says "smell of mice"
Smallpox - sweet, pungent rotten stench
Diphtheria - peculiar, penetrating "mousy" smell
Rheumatism - acid smell
Diabetes - sweet, or fermenting fruit (acetone)
Plague - sweet smell (?)
Schizophrenia - some people with the disease have a characteristic smell. The chemical exuded in the sweat of these patients causing the distinct odor is trans-3-methyl-2-hexenoic acid (MHA). It has a goat-like odour. These patients cannot detect the MHA as well as the study group without schizophrenia (full paper here).
Asthma - exhaled nitric oxide levels are much higher in people with asthma. Nitric oxide (NO) is a sharp sweet-smelling gas at room temperature.  After two decades of careful development, a handheld detection device was approved by the FDA some years ago. It is now widely used by doctors to help make a diagnosis.
Parkinson's disease - In a recent news story, Joy Milne is reported as being able to sniff out people with Parkinson's disease (PD). This was followed up by a lab in Edinburgh who tested her ability and found her to be remarkably accurate. Scientists believe that changes in the skin of people with early Parkinson's produces a particular odour linked to the condition. They hope to find the molecular signature responsible for the odour and then develop a simple test such as wiping a person's forehead with a swab. The charity Parkinson's UK is now funding researchers at Manchester, Edinburgh and London to study about 200 people with and without Parkinson's (BBC News Oct, 2015). Results from Perdita Barran's lab identified a distinct volatiles-associated signature of PD, including altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of PD (https://dx.doi.org/10.1021%2Facscentsci.8b00879).

Electronic noses are being developed to identify infections and lung diseases (eg TB) and dogs can be trained to detect cancer; they have been approved for use in an NHS trial. Whereas it is more obvious why bacterial infections smell it is less clear why and how other diseases such as cancer smell. What it is precisely that dogs are detecting is unknown at present. We all have a distinct and unique normal body odour and this clearly changes when we are sick.

In a recent study Professor Matts Olsson at the Karolinska Institute gave human volunteers something that activated their immune system and then collected their sweat. Their smell was rated as more unpleasant than controls. It is not known which chemicals are given off to account for this change but we communicate our health state by changing our smell - diesease smells.

There is a smell of disease. Is there therefore a smell of health or is it just the absence of "bad"aroma?

Function of pleasant smell
Smell is difficult to describe in words and on that topic here is an interesting WIRED magazine article. An ethnic tribe in Thailand, the Maniq, have a rich vocabulary for smells. Asifa Majid, a psycholinguist at Radboud University in the Netherlands has been studying the languages of the Jahai and Maniq tribes (read full paper). In the Maniq culture herbs are sought after for their health-giving properties.
A lot of medicinal herbs have a pleasant fragrance and are healing or disease-preventing and are hunted in the forests by their smell. Also, in Maniq culture pleasant smells are associated with cosmetic products, cleanliness and hygeine and they wear such pleasant "cosmetic" smells in necklaces.  Here is a positive function of pleasant smell that confers adaptive advantage. Furthermore it points to the origins of our fascination (and obsession) with perfume. Early cultures collected pleasant smelling herbs, plants because they were medicinal, curative, or represented cleanliness and hygeine.  Pleasant smell equates with health.

A Maniq child in Satun province, Thailand

Smell memory influences health via immune system
The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odour-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. Rachel Herz has been pre-eminent in this research area and Herz and colleagues characterized odour-evoked autobiographic memories as being more emotional than those elicited by other sensory stimuli. Functional magnetic resonance imaging (fMRI) was used to demonstrate that the amygdala is more strongly activated when autobiographic memories are evoked by olfactory cues than by other sensory cues, such as visual ones. The amygdala is critical for the expression of emotion, and heightened activity of the amygdala represents an intense emotional experience. Odour-evoked autobiographic memory is accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signalling molecules that modulate inflammation. Participants in a study by Matsunaga and colleagues experienced positive emotions and autobiographic memories when nostalgic odours were presented to them. The levels of peripheral proinflammatory cytokines (e.g. interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) were significantly. Brain imaging indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odour-evoked autobiographic memory correlating with a reduction in inflammatory mediators.

Inflammation is linked to many diseases including depression so if odour-evoked memories can reduce inflammation this would be beneficial. Treatments for depression targeting the immune system are being explored.

Anosmia

If you have lost your sense of smell then check my Anosmia website and you should definitely go to the excellent website 5th Sense dealing with this problem and the super helpful Smell Trainingwebsite, of which more below.

Smell Training

There is accumulating evidence that you can enhance your sense of smell by smell training that is, sniffing a number of distinctive aromas regularly (once or twice a day). This is particularly relevant to the recovery of the sense of smell following temporary viral anosmia/hyposmia. Visit the Smell Training website for much helpful and interesting information and follow @smelltraining on twitter.

Olfactory bulb volume correlates with olfactory function (2) and volume loss occurs in some pathologies such as depression, schizophrenia, epilepsy, MS, Alzheimer's disease and posttraumatic or postviral olfactory loss.

Repeated exposure to odours leads to improvement in olfactory function and has been shown to improve recovery of patients suffering from postviral olfactory loss (1, 3) and to prevent olfactory deterioration in older people (5).

A recent study from Hummel's lab put smell training to the test (4). Normal subjects were selected for smell training - 4 months, one nostril (other nostril blocked by finger pressure), 10s, 4 odorants: phenyl ethyl alcohol (rose-like), eucalyptol (eucalyptus), citronellal (lemon) and eugenol (cloves) - based on the 4 primary odours of the Henning prism (Henning, 1916). Both OBs increased in size 11.3% in trained side, 13.1% in untrained side.
Olfactory input therefore increased OB volume. The suggestion is that both bottom-up and top-down mechanisms must be involved since both untrained and trained OBs increased in size.

They found no correlation between OB volume and olfactory function and no effects of gender or age were observed. Furthermore, training did not improve olfactory function, in fact, PEA thresholds worsened. However, it has been previously shown that training improves function in those with olfactory loss and specific anosmias. As they admit the study was hampered by a lack of control group, self-report of compliance and failure to record an increase olfactory function.

1. Damm, M. et al. (2014) doi:10.1002/lary.24340.
2. Hummel, T. et al. (2013) doi:10.1016/j.neuroscience.2013.01.044.
3. Hummel, T. et al. (2009) doi:10.1002 /lary.20101.
4. Negoias, S.et al. (2016)  doi 10.1007/s11682-016-9567-9
5. Schriever, V.A. et al. (2014). doi:10.1111/jgs.12669.

Improving your sense of smell

If you want to improve your sense of smell then sniff things a lot. Wear perfume, experiment with them, mix them. Learn a smell vocabulary.  The Maniq tribe (see "Function of pleasant smell" above) have many "smell" words which are abstract and don't just describe the smelly object. Perfumers use terms like "green", "woody", "chypre" (Chypre is French for Cyprus and the concept of the chypre smell was coined by Francois Coty in 1917 for a perfume - fresh citrus accord, woody-oakmoss base and patchouli). Smell words get stored in another brain region. Storing information about a smell in two brain regions, one concerned with smell and the other concerned with language, improves recall and recognition. Get pregnant! Mum's-to-be often have an increased sense of smell but it's very unpredictable. If you are a mouse, have sex, this causes the release of prolactin (it does in humans too) and, in mice, prolactin causes neurogenesis of olfactory cells. Humans? Don't know! But what I do know is that women of child bearing age can increase their sensitivity by regular training. A colleague, Pam Dalton, had a group of such women test their thresholds for odorants every day. They improved their sensitivity by several orders of magnitude. Men couldn't do this. It is thought to be due to the fact that women can recruit more brain processing power to such a smell task than men. Women have the capacity to do this because in evolution they have had to be responsible for early childcare and this means choosing non-toxic food for themselves and their offspring. Other possibilities for enhancing a normal sense of smell were suggested by Wired magazine.