Volatile Characters
On
You’ve heard of genomics, proteomics and metabolomics. Next up is volatilomics, the study of Volatile Organic Compounds. Science is rife with acronyms – in some dark room a linguistic post-grad (LPG) is surely tapping out a vaporous thesis (VT) on acrynomics – and scientists refer to volatile organic compounds as VOC’s.
When most people think of VOCs they think of benzene or formaldehyde, toxins given off by paint, particle board and foam insulation, which can accumulate in our homes and create health problems. Not all VOC’s are toxic, however. We make VOC’s in our own bodies which are released into the air around us, producing an exometabolic profile in our immediate environment.
The VOC metabolic profile of an organism is referred to as its ‘volatilome’, and it can tell us volumes about its diet and its health, as well as the lotion it rubs on its skin.
You can change your volatilome with foods, and asparagus and coffee are the two best-known examples of this.
If you eat asparagus for dinner you will smell it when you pee next morning; a mix of methanethiol, S-methylthioacrylate, S-methyl-3-(methylthio)thiopropionate and related compounds (1, 2). These are metabolites of asparagusic acid, a sulphur compound used by asparagus plants to fight off nematode infections (3).
If you started the day with coffee, your next sample will smell like coffee because it will contain the coffee flavour compound 5-hydroxymethyl-2-furoic acid (4, 5). More sensitive noses may detect 4-hydroxy-2,5-dimethyl-3 (2H) furanone glucaronide after eating strawberries (6), and 1′-hydroxyestragole, 1′-hydroxyestragole glucuronide and p-allylphenol glucuronide after consuming fennel (7).
Other VOC’s are signposts for illness. Unsurprisingly, the urine of patients with maple syrup urine disease smells like maple syrup (8, 9). The urine of tyrosinemia patients smells rancid (9) the urine of individuals with trimethylaminuria has a fishy odor (9, 10), and uncontrolled diabetics produce urine with a sweet or fruity smell. Parkinsonian patients smell woody and musky (11). But our senses only go so far. Humans are not very good at smelling out disease.
You can most easily turn up the gain by switching from a human to a canine nose. Dr Dogg can diagnose bladder cancer (12, 13), and prostate cancer (14, 15) from urine samples, with high levels of accuracy. He can also diagnose colorectal cancer from stool samples (16) and lung cancer from breath samples (17).
In this last case Snoop’s accuracy was initially found to be lower (17), but when animal experts (as opposed to medics) examined the set-up, they found the dogs’ under-performance was due to inappropriate sampling techniques. Integrating correct sampling methods into the dogs’ training improved their hit rate significantly (18).
This makes dogs valuable diagnosticians, but there’s more …
Using VOC’s given off by skin, man’s best friend can diagnose skin cancers and distinguish between benign pigmented moles, basal cell cancer and melanoma (19). Dogs can even sniff out cancers deeper under the skin such as breast cancer (20), and their chemo-detective skills work on biopsy samples too (21).
Pet scans are still holding their own (22, 23), but not everybody likes a mutt and far more money can be made selling using lab equipment to scan and identify VOC’s. And to be fair, these systems have their strengths. They enable very high throughput screening, and they don’t need to be taken for walks.
e-Noses are currently being picked to study interstitial lung disease (24), cancers of the lung (25, 26), breast (27-29), prostate (30), kidney (31) and bladder (32), Alzheimer’s (33, 34), Parkinsonism (11, 35), and a wide range of infections (36).
Some think these approaches are sufficiently specific to be used as a stand-alone diagnostic (36, 37), others say we are not there yet (23); so in future we may see sniffer dogs and analytical technology integrated into bimodal bionic screening systems (ie 13, 38, 39). In the meantime, if your dog starts looking at you sideways, you may want to invite your neighbor’s dachshund in for a second opinion. Especially if you are one of those paranoid people who agonise over Covid.
It appears that many PCR tests for Covid have been deliberately manipulated to give false positive results, by using up to 40 replication cycles when most specialists agree that the cut-off should be between 30 to 35 cycles (40). The higher the number of cycles, the greater the risk of false positives. Go figure.
Dogs are harder to ‘adjust’ upwards in this way and are extremely good at detecting Covid in breath, saliva and sweat (41-45). In today’s heavily politicised situation I would rather put my faith in a dog than some pharma-paid dogsbody who might be financially motivated to bump case numbers up (46). I am referring here to administrators and political figures, not doctors.
A dog can screen up to 250 people an hour (47) and dog teams have been used successfully for airport screening with near 100% accuracy (48); making vaccine passports, as pushed by noted libertarian and former Stasi afficionada Frau Merkel, somewhat redundant. Angela’s murky background and manipulative nature is revealed in ‘The First Life of Angela M’ (49), which remained in Der Speigel’s bestseller list for 18 weeks yet for some reason does not exist on ebay or Amazon.
Other respiratory tract infections produce VOC’s too. eNose technology is being developed in this area (50) and may find an application in early screening for TB (51), which would be a boon in developing nations and, increasingly, our prison system (52).
The latest chapter in volatilomics is nutrivolatilomics.
I mentioned asparagus and coffee above, but this developing science uses e-Noses to monitor VOC’s produced in the body in minuscule amounts by a more extensive range of foods. This can be used for dietary monitoring. The first batch of test systems could tell, for example, if you had recently consumed cheese, milk or soy products (53-55).
This will be invaluable next time you meet a virtue-signalling Starbuck Millenial who claims they only eat plant foods. Take a small blood or urine sample when they are not looking, put it through a combination of dynamic headspace vacuum transfer In Trap extraction and gas chromatography coupled with mass spectrometry, and you will know within hours if they were telling the truth – or lying.
There is a slightly more substantial side to nutrivolatilomics.
As public health has gone so far downhill after the nutrition transition (56), scientists all over the world are conducting clinical trials of different dietary interventions in the hope of finding the combination to this global health lock.
They ask their trial subjects what they eat, they use food diaries, and they try to cross-reference dietary patterns with health outcomes.
Unfortunately, as Dr Gregory House explained, everybody – not just Millenials – lies. People are also forgetful, biased, skewed and hopelessly subjective, which is why lab rats are so much better than humans except for the minor detail that they are not human. Nutrivolatilomics provides a way of recording what people really eat, so that scientists can jump to more informed conclusions. The latest generation of e-Noses can measure the consumption not only of soy and dairy but also of fish, eggs, fruits, carotenoid-rich vegetables, tea … and the list is growing (57).
Most of this research, IMHO, soaks up time and resources that could be used to better effect elsewhere.
The modern diet kills us with a pathogenic combination of chronic inflammation, Type B malnutrition, dysbiosis and excess glycemic load. Neutralize these with the usual pharmaco-nutritional tools and you revert to pre-transitional health, cutting the risk of degenerative disease by up to 90% (58, 59).
The same principles, by the way, apply to your dog.
Next week: Food to die for from – and why we have to get back to the garden.
Image credit: Shutterstock
References
- White, R.H. 1975. Occurrence of S-methyl thioesters in urines of humans after they have eaten asparagus. Science 189: 810-811.
- Waring RH, Mitchell SC, Fenwick GR. The chemical nature of the urinary odour produced by man after asparagus ingestion. 1987 Nov;17(11):1363-71.
- Takasugi M, Yachida Y, Anetai M, Masamune T, Kegasawa, K. 1975. Identification of asparagusic acid as a nematicide occurring naturally in roots of asparagus. Chemistry Letters 1975: 43-44.
- Mack CI, Egert B, Liberto E, Weinert CH, Bub A, Hoffmann I, Bicchi C, Kulling SE, Cordero C. Robust Markers of Coffee Consumption Identified Among the Volatile Organic Compounds in Human Urine. Mol Nutr Food Res. 2019 May;63(10):e1801060.
- Husoy T, Haugen M, Murkovic M, Joebstl D, Stolen LH, Bjellaas T, Ronningborg C, Glatt H, Alexander J. Dietary exposure to 5-hydroxymethylfurfural from norwegian food and correlations with urine metabolites of short-term exposure. Food Chem. Toxicol.2008;46:3697–3702.
- Roscher R, Koch H, Herderich M, Schreier P, Schwab W. Identification of 2,5-dimethyl-4-hydroxy-3[2h]-furanone beta-d-glucuronide as the major metabolite of a strawberry flavour constituent in humans.Food Chem. Toxicol. 1997;35:777–782.
- Zeller A., Horst K., Rychlik M. Study of the metabolism of estragole in humans consuming fennel tea. Chem. Res. Toxicol.2009;22:1929–1937.
- Podebrad F, Heil M, Reichert S, Mosandl A, Sewell AC, Böhles H. 4,5-dimethyl-3-hydroxy-2[5h]-furanone (sotolone)—The odour of maple syrup urine disease. Inherited Metab. Dis. 1999;22:107–114.
- European urinalysis guidelines—Summary. J. Clin. Lab. Invest.2000;60:1–96.
- Rehman HU. Fish odour syndrome. Med. J. 1999;75:451–452.
- Trivedi DK, Sinclair E, Xu Y, Sarkar D, Walton-Doyle C, Liscio C, Banks P, Milne J, Silverdale M, Kunath T, Goodacre R, Barran P. Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum. ACS Cent Sci. 2019 Apr 24;5(4):599-606.
- Willis C, Church S, Guest C, Cook W, McCarthy N, Bransbury A, Church M, Church J. Olfactory detection of human bladder cancer by dogs: Proof of principle study. Med. J.2004.
- Cornu JN, Cancel-Tassin G, Ondet V, Girardet C, Cussenot O. Olfactory detection of prostate cancer by dogs sniffing urine: A step forward in early diagnosis. Eur. Urol. 2011;59:197–201.
- Guest C, Harris R, Sfanos KS, Shrestha E, Partin AW, Trock B, Mangold L, Bader R, Kozak A, Mclean S, Simons J, Soule H, Johnson T, Lee WY, Gao Q, Aziz S, Stathatou PM, Thaler S, Foster S, Mershin A. Feasibility of integrating canine olfaction with chemical and microbial profiling of urine to detect lethal prostate cancer.PLoS One. 2021 Feb 17;16(2):e0245530.
- Taverna G, Tidu L, Grizzi F, Torri V, Mandressi A, Sardella P, La Torre G, Cocciolone G, Seveso M, Giusti G, Hurle R, Santoro A, Graziotti P. Olfactory system of highly trained dogs detects prostate cancer in urine samples. J Urol. 2015 Apr;193(4):1382-7.
- Sonoda H, Kohnoe S, Yamazato T, Satoh Y, Morizono G, Shikata K, Morita M, Watanabe A, Morita M, Kakeji Y, Inoue F, Maehara Y. Colorectal cancer screening with odour material by canine scent detection. 2011 Jun;60(6):814-9.
- Jezierski T, Walczak M, Ligor T, Rudnicka J, Buszewski B. Study of the art: canine olfaction used for cancer detection on the basis of breath odour. Perspectives and limitations. J Breath Res. 2015 May 6;9(2):027001.
- Guest CM, Harris R, Anjum I, Concha AR, Rooney NJ. A Lesson in Standardization – Subtle Aspects of the Processing of Samples Can Greatly Affect Dogs’ Learning. Front Vet Sci. 2020 Aug 18;7:525.
- Willis CM, Britton LE, Swindells MA, Jones EM, Kemp AE, Muirhead NL, Gul A, Matin RN, Knutsson L, Ali M. Invasive melanoma in vivo can be distinguished from basal cell carcinoma, benign naevi and healthy skin by canine olfaction: a proof-of-principle study of differential volatile organic compound emission. Br J Dermatol. 2016 Nov;175(5):1020-1029.
- Thuleau A, Gilbert C, Bauër P, Alran S, Fourchotte V, Guillot E, Vincent-Salomon A, Kerihuel JC, Dugay J, Semetey V, Kriegel I, Fromantin I. A New Transcutaneous Method for Breast Cancer Detection with Dogs. 2019;96(2):110-113.
- Yoel U, Gopas J, Ozer J, Peleg R, Shvartzman P. Canine Scent Detection of Volatile Elements, Characteristic of Malignant Cells, in Cell Cultures. Isr Med Assoc J. 2015 Sep;17(9):567-70.
- Wen Q, Boshier P, Myridakis A, Belluomo I, Hanna GB. Urinary Volatile Organic Compound Analysis for the Diagnosis of Cancer: A Systematic Literature Review and Quality Assessment. Metabolites. 2020 Dec 29;11(1):17.
- Hanna GB, Boshier PR, Markar SR, Romano A. Accuracy and Methodologic Challenges of Volatile Organic Compound-Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis. JAMA Oncol. 2019 Jan 1;5(1):e182815.
- Krauss E, Haberer J, Maurer O, Barreto G, Drakopanagiotakis F, Degen M, Seeger W, Guenther A. Exploring the Ability of Electronic Nose Technology to Recognize Interstitial Lung Diseases (ILD) by Non-Invasive Breath Screening of Exhaled Volatile Compounds (VOC): A Pilot Study from the European IPF Registry (eurIPFreg) and Biobank. J Clin Med. 2019 Oct 16;8(10):1698.
- Liu H, Wang H, Li C, Wang L, Pan Z, Wang L. Investigation of volatile organic metabolites in lung cancer pleural effusions by solid-phase microextraction and gas chromatography/mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jan 15;945-946:53-9.
- Jia Z, Zhang H, Ong CN, Patra A, Lu Y, Lim CT, Venkatesan T. Detection of Lung Cancer: Concomitant Volatile Organic Compounds and Metabolomic Profiling of Six Cancer Cell Lines of Different Histological Origins. ACS Omega. 2018 May 31; 3(5):5131-5140.
- Silva CL, Perestrelo R, Silva P, Tomás H, Câmara JS. Volatile metabolomic signature of human breast cancer cell lines. Sci Rep. 2017 Mar 3;7:43969.
- Taware R, Taunk K, Kumar TVS, Pereira JAM, Câmara JS, Nagarajaram HA, Kundu GC, Rapole S.Extracellular volatilomic alterations induced by hypoxia in breast cancer cells. 2020 Jan 24;16(2):21.
- Silva C, Perestrelo R, Silva P, Capelinha F, Tomás H, Câmara JS. Volatomic pattern of breast cancer and cancer-free tissues as a powerful strategy to identify potential biomarkers. 2019 Jul 21;144(14):4153-4161.
- Lima AR, Araújo AM, Pinto J, Jerónimo C, Henrique R, Bastos ML, Carvalho M, Guedes de Pinho P. Discrimination between the human prostate normal and cancer cell exometabolome by GC-MS. Sci Rep. 2018 Apr 3; 8(1):5539.
- Amaro F, Pinto J, Rocha S, Araújo AM, Miranda-Gonçalves V, Jerónimo C, Henrique R, de Lourdes Bastos M, Carvalho M, de Pinho PG. Volatilomics Reveals Potential Biomarkers for Identification of Renal Cell Carcinoma: An In Vitro Approach. 2020 Apr 27;10(5):174.
- Rodrigues D, Pinto J, Araújo AM, Monteiro-Reis S, Jerónimo C, Henrique R, de Lourdes Bastos M, de Pinho PG, Carvalho M. Volatile metabolomic signature of bladder cancer cell lines based on gas chromatography-mass spectrometry. 2018 Apr 17;14(5):62.
- Orr ME, Reveles KR, Yeh C-K, Young EH, Han X. Can oral health and oral‐derived biospecimens predict progression of dementia? Oral Dis. 2020 Mar; 26(2): 249–258.
- Mazzatenta A, Pokorski M, Sartucci F, Domenici L, Di Giulio C. Volatile organic compounds (VOCs) fingerprint of Alzheimer’s disease. Respir Physiol Neurobiol. 2015 Apr;209:81-4.
- Sinclair E, Walton-Doyle C, Sarkar D, Hollywood KA, Milne J, Lim SH, Kunath T, Rijs AM, de Bie RMA, Silverdale M, Trivedi DK, Barran P. Validating Differential Volatilome Profiles in Parkinson’s Disease. ACS Cent Sci. 2021 Feb 24;7(2):300-306.
- Belizário JE, Faintuch J, Malpartida MG. Breath Biopsy and Discovery of Exclusive Volatile Organic Compounds for Diagnosis of Infectious Diseases. Front Cell Infect Microbiol. 2021 Jan 7;10:564194.
- Silva CL, Passos M, Câmara JS. Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry. Br J Cancer. 2011 Dec 6;105(12):1894-904.
- Biehl W, Hattesohl A, Jörres RA, Duell T, Althöhn U, Koczulla AR, Schmetzer H. VOC pattern recognition of lung cancer: a comparative evaluation of different dog- and eNose-based strategies using different sampling materials. Acta Oncol. 2019 Sep;58(9):1216-1224.
- Boedeker E, Friedel G, Walles T. Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening. Interact Cardiovasc Thorac Surg. 2012 May;14(5):511-5.
- https://www.stress.org/open-letter-from-medical-doctors-and-health-professionals-to-all-belgian-authorities-and-all-belgian-media
- Jendrny P, Schulz C, Twele F, Meller S, von Köckritz-Blickwede M, Osterhaus ADME, Ebbers J, Pilchová V, Pink I, Welte T, Manns MP, Fathi A, Ernst C, Addo MM, Schalke E, Volk HA. Scent dog identification of samples from COVID-19 patients – a pilot study. BMC Infect Dis. 2020 Jul 23;20(1):536.
- Grandjean D, Sarkis R, Lecoq-Julien C, Benard A, Roger V, Levesque E, Bernes-Luciani E, Maestracci B, Morvan P, Gully E, Berceau-Falancourt D, Haufstater P, Herin G, Cabrera J, Muzzin Q, Gallet C, Bacqué H, Broc JM, Thomas L, Lichaa A, Moujaes G, Saliba M, Kuhn A, Galey M, Berthail B, Lapeyre L, Capelli A, Renault S, Bachir K, Kovinger A, Comas E, Stainmesse A, Etienne E, Voeltzel S, Mansouri S, Berceau-Falancourt M, Dami A, Charlet L, Ruau E, Issa M, Grenet C, Billy C, Tourtier JP, Desquilbet L. Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study. PLoS One. 2020 Dec 10;15(12):e0243122.
- Dickey T, Junqueira H. Toward the use of medical scent detection dogs for COVID-19 screening. J Am Osteopath Assoc. 2021 Feb 1;121(2):141-148.
- Else H. Can dogs smell COVID? Here’s what the science says.2020 Nov 23 doi: 10.1038/d41586-020-03149-9.
- Grandjean D., Sarkis R., Tourtier J.P., Julien C., Desquilbet L. Detection dogs as a help in the detection of COVID-19: can the dog alert on COVID-19 positive persons by sniffing axillary sweat samples? Proof-of-concept study.2020 doi: 10.1101/2020.06.03.132134.
- https://www.usatoday.com/story/news/factcheck/2020/04/24/fact-check-medicare-hospitals-paid-more-covid-19-patients-coronavirus/3000638001/
- https://www.sciencealert.com/dogs-deployed-at-helsinki-airport-can-detect-covid-19-with-near-perfect-accuracy
- Jones R.T., Guest C., Lindsay S.W., Kleinschmidt I., Bradley J., Dewhirst S., Last A., Logan J.G. Could bio-detection dogs be used to limit the spread of COVID-19 by travellers? J Trav Med.2020 Aug 12 doi: 10.1093/jtm/taaa131.
- The First Life of Angela M. Piper Verlag, authors Reuth RG & Lachmann G, 2013.
- Licht JC, Grasemann H. Potential of the Electronic Nose for the Detection of Respiratory Diseases with and without Infection. Int J Mol Sci. 2020 Dec 10;21(24):9416.
- Banday K., Pasikanti K., Chan E., Singla R., Rao K., Chauhan V., Nanda R. Use of urine volatile organic compounds to discriminate tuberculosis patients from healthy subjects. Chem.2011;83:5526–5534.
- H.O. Health Topics: Tuberculosis. https://www.who.int/tb/areas-of-work/population-groups/prisons-facts/en/
- Münger LH, Trimigno A, Picone G, Freiburghaus C, Pimentel G, Burton KJ, Pralong FP, Vionnet N, Capozzi F, Badertscher R, Vergères G. Identification of Urinary Food Intake Biomarkers for Milk, Cheese, and Soy-Based Drink by Untargeted GC-MS and NMR in Healthy Humans. J Proteome Res. 2017 Sep 1;16(9):3321-3335.
- Trimigno A, Münger L, Picone G, Freiburghaus C, Pimentel G, Vionnet N, Pralong F, Capozzi F, Badertscher R, Vergères G. GC-MS Based Metabolomics and NMR Spectroscopy Investigation of Food Intake Biomarkers for Milk and Cheese in Serum of Healthy Humans. 2018 Mar 23;8(2):26.
- Fuchsmann P, Tena Stern M, Münger LH, Pimentel G, Burton KJ, Vionnet N, Vergères G. Nutrivolatilomics of Urinary and Plasma Samples to Identify Candidate Biomarkers after Cheese, Milk, and Soy-Based Drink Intake in Healthy Humans. J Proteome Res. 2020 Oct 2;19(10):4019-4033.
- Popkin BM. The nutrition transition: an overview of world patterns of change. Nutr Rev. 2004 Jul;62(7 Pt 2):S140-3.
- Shibutami E, Ishii R, Harada S, Kurihara A, Kuwabara K, Kato S, Iida M, Akiyama M, Sugiyama D, Hirayama A, Sato A, Amano K, Sugimoto M, Soga T, Tomita M, Takebayashi T. Charged metabolite biomarkers of food intake assessed via plasma metabolomics in a population-based observational study in Japan. PLoS One. 2021 Feb 10;16(2):e0246456.
- Clayton P, Rowbotham J. How the mid-Victorians worked, ate and died. Int J Environ Res Public Health. 2009 Mar;6(3):1235-53.
- Charlton J, Murphy M, editors. The Health of Adult Britain 1841–1994. 2. National Statistics; London, UK: 2004.