The Smell of Stress and Fear

Can we recognize if people around us are stressed, anxious or fearful without observing their facial expressions, body language and actions or hearing their voice and messages? Can we understand if we are stressed ourselves without assessing our heart rate, blood pressure, noticing dry throat, sweating, drops or surges in energy? Yes, we can - by using our nose - as humans, too, recognize and transmit their emotions through chemical senses.

When we are stressed or panic we become more sensitive to odors (Buróna et al., 2015), ranking neutral odors as unpleasant (Krusemark et al, 2013). Chronic stress will actually dull the senses (Yuan & Slotnick, 2013), but that's another story.

When other people are stressed, we can feel it without seeing or hearing them. Numerous experiments showed that we can recognize emotions from sweat alone. We might not be able to tell why, but experience sympathy by smelling odors of those taking exams vs just exercising on a bike (Prehn-Kristensen et al 2009), become more cooperative when smelling hard work, more submissive when detecting that other people's health status prioritizes their needs, more fearful when detecting chemical clues coming from people watching horror movies (Zhou and Chen, 2009, de Groot et al., 2012) and exhibit risk taking behavior when detecting other people's anxieties (Haegler et al, 2010).

What is the exact chemistry of stress, anxiety and fear? We are getting close to deciphering it. Stress, for example, might be recognized by six biomarkers, including indole and 2-methyl-pentadecane (Turner et al, 2013) that are also indicators of COPD (Martinez-Lozano Sinues et al, 2014) and heart disease. 

Correlating chemicals to health and wellness conditions is not easy. Acetone in breath, for example, has attracted the interest of clinical researchers for more than 60 years. Several dozen independent studies using various techniques and methods showed that much more complex analysis is required with long-term measurements of various health and environmental indicators including diet, treatments and prior medical history (Dowlaty, Yoon, and Galassetti, 2013). Aurametrix provides an integrated platform for such analysis, but until we sift through all the data, if you are stressed out, just take a deep breath and relax. Inhale confidence, exhale doubt.

REFERENCES

Haegler, K., Zernecke, R., Kleemann, A., Albrecht, J., Pollatos, O., Brückmann, H., & Wiesmann, M. (2010). No fear no risk! Human risk behavior is affected by chemosensory anxiety signals Neuropsychologia, 48 (13), 3901-3908 DOI: 10.1016/j.neuropsychologia.2010.09.019

Prehn-Kristensen A, Wiesner C, Bergmann TO, Wolff S, Jansen O, Mehdorn HM, Ferstl R, & Pause BM (2009). Induction of empathy by the smell of anxiety. PloS one, 4 (6) PMID: 19551135

Dowlaty N, Yoon A, & Galassetti P (2013). Monitoring states of altered carbohydrate metabolism via breath analysis: are times ripe for transition from potential to reality? Current opinion in clinical nutrition and metabolic care, 16 (4), 466-72 PMID: 23739629

de Groot JH, Smeets MA, Kaldewaij A, Duijndam MJ, & Semin GR (2012). Chemosignals communicate human emotions. Psychological science, 23 (11), 1417-24 PMID: 23019141

Krusemark EA, Novak L, Gitelman D, Li W. (2013) When the sense of smell meets emotion: Anxiety-state-dependent olfactory processing and neural circuitry adaptation. Journal of Neuroscience. 33(39):15324 –15332.

Martinez-Lozano Sinues P, Meier L, Berchtold C, Ivanov M, Sievi N, Camen G, Kohler M, Zenobi R Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. Respiration; International Review of Thoracic Diseases [2014, 87(4):301-310] PMID: 25545545

Yuan TF, Slotnick BM. Roles of olfactory system dysfunction in depression. (2014) Prog Neuropsychopharmacol Biol Psychiatry. 54:26-30. doi: 10.1016/j.pnpbp.2014.05.013. 

Body Odor and Skin Bacteria

Our bodies are rainforests of microbes feeding off the leftovers from our meals and contributing to a variety of body odors. 

Human skin is inhabited and re-populated depending on health conditions, age, genetics, diet, the weather and climate zones, occupations, cosmetics, soaps, hygienic products and moisturizers. All these factors contribute to the variation in the types of microbes. Population of viruses, for example, can include a mixture of good ones - like bacteriophages fighting acne-causing Propionibacterium  - and bad ones  - as highly contagious Mesles. Bacterial communities include thousands of species of Actinobacteria, Bacteroidetes, Cyanobacteria, Proteobacteria, and fungi Malassezia.

Nat Rev Microbiol. 2011 April; 9(4): 244–253.

Nat Rev Microbiol. 2011 April; 9(4): 244–253.

These microbes form communities and have active social lives, cooperating to our good and bad experiences. They converse chemically - in many specific dialects and in universal Esperanto-like languages some of which even we could listen to  - by sampling and understanding smells. 

Humans are among the smelliest animals. And very capable in telling smells apart,  even if the only difference in two molecules is that their structures are mirror images of one another. But unlike dogs that appreciate a garbage bin as much as we appreciate the smell of fresh flowers, we don't properly interpret smells and like to complain about body odors. As we don't know all that much about chemical nature of our surroundings and rely on context and psychological factors, like feeling an intrusion in our experiences of the world. 

Maybe we have something to learn from the science of smells? 

In  a recent review of axillary microbiota, German researchers gave a good lesson in organic chemistry, listing major chemicals, enzymes and microbes responsible for body odor. Let's take a look. 

As was also shown in previous studies, Staphylococcus and Corynebacterium spp. are the most abundant organisms colonizing moist areas and emitting chicken-sulfury, onion-like and clary-sage like odors. The strain of Staphylococcus haemolyticus is producing some of the most offensive sulfury smells. Corynebacterium jeikeium K411 is another species that can compete on the strength of the odor. 

The major odor-causing substances are sulphanyl alkanols, steroid derivatives and short volatile branched-chain fatty acids. 

Most common sulphanyl alkanol in human sweat, 3-methyl-3-sulfanylhexan-1-ol is produced by bacteria in several ways, particularly in glutathione biodetoxification pathway, from molecules synthesized after consuming proteins (due to aminoacids L-cysteine, L-glutamic acid and glycin). This chemical,  besides being a major descriptor of human sweat odor,  is also present in beers. Its S-enantiomer (75%) is described as a classical body odor (sweat) with onion-like tones. Interestingly, the opposite enantiomer, (R)-3-methyl-3-sulfanylhexan-1-ol, is fruity and grapefruit-like. 

Another set of molecules produced by Corinebacterium are most prominent in Caucasian men and some Asians. The odor is hircine - resembling of goats with fatty and cheesy notes or cumin-spice like. The food sources contributing to this odor are proteins and animal fats. 

Pheromones androstenol and androstenone, metabolites of sexual hormones, are also odorous. The latter is especially interesting as to some of us it smells like vanilla while to others is smells like urine.

Sweaty-feet and cheesy smelling isovaleric and propionic acids and sour-vinegary acetic acid are also adding to the spectrum of human odors.  They can smell different to different people too - some people have genetic makeup making them hypersensitive to these smells, but others are much more tolerant and forgiving. The food sources of sourish smells are protein-rich. Lactic acid is found in cheeses, yogurt, soy sauce, sourdough, meats and pickled vegetables. It can be also produced from the breakdown of carbohydrates during exercise and used as additional fuel. Glycerol is created from triglycerides found in fats and oils.  

So next time you are exposed to body odor, try to understand what could be causing it. It is not easy as it is a combination of many factors such as hormonal fluctuations, mental or physical stress, metabolism and microbes. It could be perfectly normal or result from a medical condition of the person who has the smell and your own olfactory abilities. But the smells are fascinating clues to health and  the basics can be learned by most everyone.

REFERENCES

Fredrich E, Barzantny H, Brune I, & Tauch A (2013). Daily battle against body odor: towards the activity of the axillary microbiota. Trends in microbiology, 21 (6), 305-12 PMID: 23566668

Grice EA, & Segre JA (2012). The human microbiome: our second genome. Annual review of genomics and human genetics, 13, 151-70 PMID: 22703178

Stevenson, R., & Repacholi, B. (2005). Does the source of an interpersonal odour affect disgust? A disease risk model and its alternatives. European Journal of Social Psychology, 35 (3), 375-401 DOI: 10.1002/ejsp.263

Troccaz M, Starkenmann C, Niclass Y, van de Waal M, Clark AJ.  ( 2004) 3-Methyl-3-sulfanylhexan-1-ol as a major descriptor for the human axilla-sweat odour profile.Chem Biodivers. 2004 Jul;1(7):1022-35. PMID: 17191896

Lenochová P, Vohnoutová P, Roberts SC, Oberzaucher E, Grammer K, Havlíček J (2012) Psychology of fragrance use: perception of individual odor and perfume blends reveals a mechanism for idiosyncratic effects on fragrance choice. (PMID:22470479) Free full text article  PLoS One [2012, 7(3):e33810]

Barzantny H, Brune I, Tauch A. (2012) Molecular basis of human body odour formation: insights deduced from corynebacterial genome sequences. Int J Cosmet Sci. 2012 Feb;34(1):2-11. doi: 10.1111/j.1468-2494.2011.00669.x. Epub 2011 Jul 25.  PMID: 21790661

I Know What You Ate This Summer

Despite active foodstagramming and foodteresting, and eagerness to show pictures of meals and diet reports to friends on social media, we don't really want others to know everything we eat. But they might know anyway.

Why worry about NSA, when Google, Facebook, Amazon and many others know what we might be eating. Cameras record our ways to groceries and restaurants, credit cards record our purchases, food chains know our weaknesses, clothes shops know how, as a result, our pant sizes change over time. One day phones will know what we ate too.  As both short- and long-term diets change our breath-prints - creating signature metabolites in exhaled breath.

A recent Dutch study actually looked at what gluten-free eating does to our breath. Just 4 week of dieting lead to remarkable - though reversible -  differences. (As detected in 20 healthy individuals by gas chromatography coupled with mass spectrometry (TD-GC-tof-MS) in combination with chemometric analysis ). A set of twelve volatile compounds that distinguish gluten-free eaters along with information from Aurametrix knowledgebase is listed in the table below.

Compound	Odor	Notes
2-butanol	strong alcoholic	1-Butanol smells like permanent marker (Sharpie)
octane	Gasoline-like, car exhaust	octyl chloride smells faintly of oranges
2-propyl-1 pentanol	green banana	1-Pentanol smells like paint thinner
nonanal	strong fruity or floral	attracts mosquitoes
dihydro-4-methyl-2(3H)-furanone	strong coconut aroma	5-butyl-4-methyloxolan-2-one is known as "whisky lactone"
nonanoic acid	rancid beer, old cooking oil	armpits of males over 30
dodecanal	Soapy, waxy, aldehydic, citrus, orange rindy with floral nuances	Pure, synthetic qualities of this fatty aldehyde are used in traces in perfumery for "fresh laundry"-like effects.

Reference

Baranska A, Tigchelaar E, Smolinska A, Dallinga JW, Moonen EJ, Dekens JA, Wijmenga C, Zhernakova A, & van Schooten FJ (2013). Profile of volatile organic compounds in exhaled breath changes as a result of gluten-free diet. Journal of breath research, 7 (3) PMID: 23774130

When it Smells Like Team Spirit

Why do we connect and collaborate, deciding to "walk in the light of creative altruism" instead of the "darkness of destructive selfishness"?

Is it because of subtle behavioral clues that make us "click" and consider the other person a part of the group? Or is it because it smells like team spirit?

It very well might be. We (literally) smell love, victory, fear, along with chemicals that motivate us to cooperate. As was recently shown in double-blind placebo-controlled studies that quantitatively measured generosity and cooperation. Androstadienone, a rather unpleasant smelling molecule abundant in male sweat could make us more cooperative and more likely to think of the other person as "one of us". This molecule, created from male sex hormone testosterone possibly with the help of coryneform bacteria living under arms, was previously shown to have an effect on women - depending on social context and the time in their menstrual cycle. Even though androstadienone does not smell particularly plaasant - rather musky, with subtle urine-like and alcohol notes - merely smelling it is sufficient to maintain high levels of energy-boosting hormone cortisol  - possibly by inhibiting an enzyme (the 11β-hydroxysteroid dehydrogenase type 1 aka 11β-HSD1) responsible for its reactivation from cortisone.

Androstadienone

Androstadienone is related to another steroid estratetraenol found in the urine of pregnant women. Both molecules in large concentrations can affect mood -  improving it in females (also increasing their feeling of being focused and sensitivity to pain) while suppressing males. High testosterone males might even get depressed. So it might not be a good idea to sweat too much, but the right amount of sweating is actually helpful. If you are a male. When it comes to men deciding to cooperate with women, chemistry alone is less helpful. As in the old monkey experiment (Michael and Zumpe, 1982) where the best female strategy was to block male's access to other female monkeys. So, don't sweat it ladies. Just be dominant.

REFERENCES

Huoviala P, & Rantala MJ (2013). A Putative Human Pheromone, Androstadienone, Increases Cooperation between Men. PloS one, 8 (5) PMID: 23717389

Lundström JN, Hummel T, & Olsson MJ (2003). Individual differences in sensitivity to the odor of 4,16-androstadien-3-one. Chemical senses, 28 (7), 643-50 PMID: 14578126

 Michael RP, Zumpe D.  (1982) Influence of olfactory signals on the reproductive behaviour of social groups of rhesus monkeys (Macaca mulatta). J Endocrinol. 95(2):189-205. PMID: 7175415

Inhale and feel it with your heart

All you need is love. Or failing that chocolate.
And not only because dark chocolate could lower the risk of heart disease, blood pressure and sugar levels. As Dr. Schieberle's team recently discovered that heart could sense and enjoy the sweet smell of chocolate too. When they put small odor-emitting molecules from chocolate on one side of a dish, cells actually moved towards the aroma.

The heart, the lungs, the blood, the sperm and testis all have the abilities to recognize chemicals responsible for smells. Genomic studies (Deldmesser et al, 2006) showed that many tissues have working genes responsible for the perception of flavors. Sperm of sea urchines is able to recognize the odor and swim toward the egg. Human sperm might very well be capable of "smelling" their way to the egg too. And white blood cells sense the odors of bacteria to rush to the site of infection in the wound. Unfortunately, cancer cells can also sense their way out of the tumor in the direction of blood vessels, leading to metastasis. Smells can guide social preferences, trigger positive or negative memories, help to lose weight, reduce anxiety or give you nightmares. Smells can make or brake, kill or heal. They can have therapeutic or diagnostic use helping to understand gene-environment health paradigms and paving new avenues for future health care strategies.

REFERENCES

Feldmesser E, Olender T, Khen M, Yanai I, Ophir R, & Lancet D (2006). Widespread ectopic expression of olfactory receptor genes. BMC genomics, 7 PMID: 16716209

Schieberle P, & Molyneux RJ (2012). Quantitation of sensory-active and bioactive constituents of food: A Journal of Agricultural and Food Chemistry perspective. Journal of agricultural and food chemistry, 60 (10), 2404-8 PMID: 22369090

Schieberle P., Do cells in the blood, heart and lungs smell the food we eat? 245th  Chemistry of Energy and Food, National Meeting & Exposition of the American Chemical Society, New Orleans, LA, April 7-11, 2013

Odors and Infections

Many illnesses are associated with distinct odors. Especially those caused by infectious or opportunistic microbes inside the body or on its surfaces.  Body odor of someone infected with C. difficile, for example, can appear "swampy", Rotavirus gives sharply sweet putrid smell that some people associate with wet dogs. H. pylori can create a range of foul odors, and pseudomonas infections can smell like grapes and bitter almonds. 

Infections like C. difficile are usually linked to a general imbalance of the intestinal microbiota, often referred to as dysbiosis. This means that the odors could be coming from several microbial species, hence could be different for different individuals. Does it mean odor-based diagnostics will never be enough specific?

Not according to a 2-year-old beagle from Netherland, named Cliff. After just a little over two months of training, the beagle learned to identify the C. diff toxin by sniffing people or their samples. During one test, he was able to identify 25 out of 30 infected patients and 265 of 270 non-infected individuals. He also correctly identified 50 of 50 C. diff positive stool samples and 47 of 50 samples from people that did not have this infection. That's sensitivity of 100% for samples and 83-93% for sniffing the air around the patients, and a specificity of 94-100%! And it took him less than 10 minutes to accurately perform 300 diagnostic tests.  

Dogs already do the dirty work with detecting molds. They can examine an office building with 200 rooms in just 8 hours, a task that would take us several days of measuring  moisture, probably without any result. Electronic noses would be of great help and many years of research are finally being translated into useful technologies - to be integrated with refrigerators and mobile phones. But until we are able to build smart devices to detect odors without labor-intensive dog training, perhaps we could train our own nozzles. Studies have shown we do get better with practice. 


REFERENCES

Bomers MK, van Agtmael MA, Luik H, van Veen MC, Vandenbroucke-Grauls CM, & Smulders YM (2012). Using a dog's superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study. BMJ (Clinical research ed.), 345 PMID: 23241268

Poulton J, Tarlow MJ. (1987) Diagnosis of rotavirus gastroenteritis by smell. Arch Dis Child. 1987 Aug;62(8):851-2. PMID: 3662595

Arnaud Tognetti, Megan N Williams, Nathalie Lybert, Mats Lekander, John Axelsson, Mats J Olsson, Humans can detect axillary odor cues of an acute respiratory infection in others, Evolution, Medicine, and Public Health, Volume 11, Issue 1, 2023, Pages 219–228, https://doi.org/10.1093/emph/eoad016

Come out smelling like a rose

You are what you eat. And you smell like your food. Well, it's actually a bit more complicated - as we emit complex combinations of volatile chemicals produced from food by our own metabolic system as well as microbes that call us home. Same foods can be translated into a wide range of odors, depending on the individual. People exhibit a large variety of smells, much more diverse than animals or plants. Thanks to variations in our digestive enzymes, diets, supplements, medicines, perfumes, detergents, clothes, cars and a lot of other chemicals we are exposed to via different routes. And there are many ways to smell of a rose - for example, by putting a few petals in the pocket, wearing Sa Majeste La Rose or drinking rose oil.

As confirmed by gas-chromatograph mass spectrometry using a thermo desorption system and a selective ion mode (Akiyama et al., 2006), linalool, citronellol and geraniol, which are the main components of rose essential oil, are emitted from our palms after an oral intake of rose oil. The aroma starts to increase 30 minutes after ingestion and reaches its peak within an hour, then slowly decreases, wearing off more than 100 times in the next 6 hours. Citronellol seems to evaporate the fastest, and linalool lingers a little longer than the other two compounds, but, of course, this may very well differ for different individuals.

A new "functional food" - Deo Perfume Candy  - is an attempt to take the sciences of smells and foods to a whole new level by creating a sweet treat intended to make you smell good. The main active ingredient of this candies is Geraniol. It is extracted from rose oil, which in its turn is extracted from real rose petals - one gram of oil per two thousand petals. Small amounts of citric acid and tangerine oil are added for more flavor. An healthy food company Beneo partnered with Bulgarian candy maker, Alpi, to develop this nutricosmetics  treat. At present it is sold exclusively on Amazon and has already collected 5 reviews - ranging from a praise of the observed fresh-just-showered smell to complaints of the need to eat a buck load of candies to see some kind of effect. Does it really work? It might for some of us. With the right chemistry and metabolism, and the right combination of everything else. You can enter it in Aurametrix as Deo Perfume Candy and check back later to see how it worked for others. Or just log what you normally eat and wear to find how your body could react to Geraniol.

You might want to compare it with “Fuwarinka” or Otoko Kaoru's chewing gum - despite a name that translates to "man smell" it also contains rose-flavored geraniol. Although one tester reported to smell like an apple-flavored soap after chewing it.  You can also experiment with the "coming soon" edible perfume from Netherlands, and its mystery ingredient (transformed by the body enzymes and excreted through the skin’s surface through perspiration). There will be more to come.

The possibilities are endless and so are the human odor outcomes.

REFERENCES

AKIYAMA, A., IMAI, K., ISHIDA, S., ITO, K., KOBAYASHI, T., NAKAMURA, H., NOSE, K., & TSUDA, T. (2006). Determination of Aromatic Compounds in Exhalated from Human Skin by Solid-Phase Micro Extraction and GC/MS with Thermo Desorption System BUNSEKI KAGAKU, 55 (10), 787-792 DOI: 10.2116/bunsekikagaku.55.787