FMO3 and COVID-19

Flavin-containing monooxygenase 3 (FMO3) enzyme is a seemingly insignificant enzyme that normally converts fishy-smelling trimethylamine (TMA) into a neutral trimethylamine-N-oxide (TMAO). The amounts of this highly specialized detoxifying enzyme are highly variable. It depends on the age, sex hormones, infections (estradiol and testosterone, hepatitis virus have been found to reduce FMO3 capacity), obesity traits and diseases such as diabetes. The difference can be up to 20-fold between individuals. Mutations in the FMO3 gene cause low metabolic capacity associated with the disorder trimethylaminuria (TMAU) that attracts little biomedical interest.  This condition, however, might matter more than it seems.

Could there be a link between FMO3 and SARS-CoV-2 infection and vaccination? 

Individuals differ in their susceptibility to viral infections and genes contribute to the risk score. Less than 10% of humans infected with Mycobacterium tuberculosis develop TB, partially because of polymorphism in Tyrosine kinase (TYK2, P1104A) also responsible for severe COVID-19. Early in the pandemic, it was discovered that SARS-CoV-2 infection is dependent on the ACE2 receptor for cell entry and the serine protease TMPRSS2 for spike protein priming. ACE2 expression, indeed, influences COVID-19 risk and a rare variant located close to this gene was found to confer protection against COVID-19, possibly by decreasing ACE2 expression. Interestingly, FMO3 is one of the few genes with expression correlated to ACE2 [Sungnak et al, 2020] along with genes associated with immune functions. 

One of the characteristics of COVID-19 is the appearance of inflammatory processes, which could be leading to increased levels of TMAO. It could contribute to the hypercoagulative state in COVID-19-associated coagulopathy (CAC). SARS-Cov2 was shown to enhance TMAO-induced inflammation.  

Coronavirus disease is associated with increased risk of thrombotic events. According to recent research, low levels of FMO3 protect against thrombosis [Shih et al, 2019] while some FMO3 mutations confer higher risk [Oliveira-Filho et al, 2021]. FMO3 rs1736557 might increase the anti‐platelet efficacy of clopidogrel [Zhu et al, 2021]. Genetic risk can be mediated by gut microbiota [Gabashvili, 2020]. There are also associations with salt tolerance, wound healing, and diseases such as diabetes, renal and cardiovascular conditions increasing risk of severe COVID-19. 

Studying trimethylaminuria-like conditions might help in developing strategies for prevention and therapy of other diseases, including COVID-19.

Our COVID-19 disease and vaccines study [NCT04832932, Gabashvili, 2021] compares side-effects of vaccines and clinical course of infections (including vaccine breakthroughs) in several cohorts including MEBO and TMAU. You can help by enrolling and participating in this online survey in English or Spanish.

REFERENCES

Andreakos E, Abel L, Vinh DC, Kaja E, Drolet BA, Zhang Q, O’Farrelly C, Novelli G, Rodríguez-Gallego C, Haerynck F, Prando C. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection. Nature immunology. 2021 Oct 18:1-6. 

Gabashvili IS. Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights from a Virtually Conducted Clinical Trial. JMIR Dermatology. 2020 Nov 4;3(1):e10508.  

Gabashvili IS. Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for an Ambispective study. medRxiv 2021.06.28.21256779; doi: https://doi.org/10.1101/2021.06.28.21256779

Liu W, Wang C, Xia Y, Xia W, Liu G, Ren C, Gu Y, Li X, Lu P. Elevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy. Acta Diabetologica. 2021 Feb;58(2):221-9.

Janmohamed A, Dolphin CT, Phillips IR, Shephard EA. Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450. Biochemical pharmacology. 2001 Sep 15;62(6):777-86.

Oliveira-Filho AF, Medeiros PF, Velloso RN, Lima EC, Aquino IM, Nunes AB. Trimethylaminuria and Vascular Complications. Journal of the Endocrine Society. 2021 Apr;5(Supplement_1):A313-4. 

Zhu KX, Song PY, Li MP, Du YX, Ma QL, Peng LM, Chen XP. Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease. European Journal of Clinical Pharmacology. 2021 Mar;77(3):359-68.

Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, Talavera-López C, Maatz H, Reichart D, Sampaziotis F, Worlock KB. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature medicine. 2020 May;26(5):681-7.

Shih, D.M., Zhu, W., Schugar, R.C., Meng, Y., Jia, X., Miikeda, A., Wang, Z., Zieger, M., Lee, R., Graham, M. and Allayee, H., 2019. Genetic deficiency of Flavin-containing monooxygenase 3 (Fmo3) protects against thrombosis but has only a minor effect on plasma lipid levels—brief report. Arteriosclerosis, thrombosis, and vascular biology, 39(6), pp.1045-1054. 

Rebuild your Health

There is increasing evidence that intestinal microbial dysbiosis has a role in the pathogenesis of systemic malodor conditions and other metabolic disorders. The most studied non-syndromic malodor condition Trimethylaminuria is usually inherited in an autosomal recessive fashion, which means that two mutations from both parents, both affecting abilities of FMO3 enzyme to catalyze the N-oxidation of trimethylamine into trimethylamine (eg, [Glu158Lys (rs2266782) and Glu308Gly (rs2266780)]), may be needed for a person to have symptoms. Yet genotype is not always predictive of phenotype, not even in this case.

Illustration by Monica Garwood

Studies have shown that the symptoms of metabolic inefficiencies, food intolerance and even allergies can be relieved by changing the composition of intestinal microbes and adjusting dietary components feeding these microbes - to encourage growth of microorganisms properly digesting problem ingredients. Lactose-digesting bacteria Lactobacillus acidophilus, Lactobacillus bulgaricus and Streptococcus thermophilus, for example, can help to digest lactose into useful compounds, instead of offensive gas. On the other hand, the low-FODMAP diet reduces gastrointestinal symptoms by reducing the food that bacteria ferment. For lactose-intolerance, however,  the "O" in FODMAPs - oligosacharides - can be beneficial as Galacto-oligosaccharides (GOS) are useful prebiotics promoting the growth of the right microorganisms. 

Rebuilding the network of microorganisms on and inside our bodies can help to improve the volatiles in the surrounding air, aka body and breath odor. Microbes associated with unpleasant odors include Anaerococcus, Corynebacterium, Campylobacter, and Propionibacterium [1], Gardnerella, Alloprevotella, Sutterella, and species of Candida. Microbes associated with improvements in odors include archaebiotic Methanomassiliicoccus luminyensis, Lactobacillus pentosus KCA1, and Lactobacillus salivarius, but there are more, working together and relying on each other. Our studies (see protocols of microbiome [2] and volatilome [3] trials published on Medrxiv)  identified several microbial strains and volatile compounds associated with improvement of malodor symptoms. We are currently summarizing our results and plan to publish it. Development of personalized protocols and defining the right compositions of probiotics and prebiotics is a long-term research endeavor. Meanwhile, be your own best medical researcher and take control of your wellbeing: 

Step 1: Pull out your fitness journal and create an action plan

• Analyze your diet, everyday activities, exercise and sleep patterns to make initial guesses about things that could be triggering your flareups or making you feel better. Write out a list of these things. 
• Break your goal into small steps and milestones. For example: if you have fructose as a potential trigger on your list, go fructose free for a week. An earlier survey of about 100 body odor and halitosis sufferers indicated stress (34%), food (25%) and environment, including the weather and perfumed products (15%) as main triggers of odors or PATM. Make sure you are not missing something in your diet - like Zinc, Vitamin C, or Vitamin D - insufficient amounts of these vitamins and minerals could also contribute to PATM. 
• Develop metrics for evaluating progress. Some people can't objectively evaluate their malodor or PATM condition. Try to find a trust buddy or take note of how the people around you react when you’re in close proximity. For example, pay attention to the space people leave between you and themselves (assuming COVID-19 is behind us and the 6-feet rule no longer applies!)

Step 2: Change your diet, physical activity and behavior

• Intestinal lining is regenerating every five to seven days, so you need to stick to your diet for at least a week to notice improvements in your symptoms. Most elimination diets are actually recommended for about 3–6 weeks, to allow the antibodies (negatively reacting to problem food components) dissipate. So if your diet seems to be helping, extend it to 3 or 6 weeks. 
• If it is not helping, try the next thing on your list. It should not be just diet - one study showed that bad breath was associated with abnormal sleep patterns. Perhaps you need to reevaluate your clothing material, temperature an humidity or mycotoxins in the environment? Are you getting enough sunlight ? Does your home have a healthy microbiome? Try to eliminate the triggers one at a time. No need to reduce your overall food intake, many people observe malodor or PATM flareups when they are hungry & undernourished. Try to train your body to digest more fiber - but start adding them to your diet little at a time, on weekends when you can safely experiment.   

Step 3: Let go of past hurts

• Stop dwelling on the past. You have the power to change your future. Learn how to express confidence with your body language. Pretend you are comfortable in presence of other people and they will learn to be comfortable in yours. 

RFRERENCES

1. Gabashvili IS. Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights From a Virtually Conducted Clinical Trial. JMIR Dermatology. 2020 Nov 4;3(1):e10508.

2. Gabashvili I.S. Dynamics of the Gut Microbiota in MEBO and PATM conditions: Protocol of a fully remote clinical study. medRxiv. 2020 Aug.24. medRxiv 2020.08.21.20179242; doi: https://doi.org/10.1101/2020.08.21.20179242

3. Gabashvili I.S. Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study medRxiv 2021, Jan. 26 2021.01.25.21250101; doi: https://doi.org/10.1101/2021.01.25.21250101

Seeing Through the Skin

by AURAMETRIX

​Human skin emits light (albeit the glow is extremely weak) and a wide variety of small molecules that may be sometimes "sniffed" by dogs or even other humans. These chemicals tell a story about our health and wellness, things we eat and drink, touch and breathe. Mosquitoes use such emissions to assess our "attractiveness" from indicators such as Indoles (unpleasantly smelling but healthy "inner soil" biomarker) or carbon dioxide (amount of which correlates with the size of the person producing it) in the air.  Sampling air for health indicators is much less invasive than drawing blood and could be an invaluable diagnostic tool. Many applications of gas sensors have been proposed over decades ranging from sweat patches to sensorized garments. Where are we now? What is the 2016 state of the art? Last month, BACtrack won 1st Prize in “Wearable Alcohol Sensor Challenge” Issued by National Institutes of Health. Milo Sensors, employing a different approach to identify ethanol molecules diffusing through the skin, won 2nd prize. BACtrack Skyn will be available in limited quantities later this year, marking an important step from bulky alcohol-monitoring ankle bracelets remotely monitoring offenders to inconspicuous devices. Perhaps, one day, drug patches, too, won't require sending them to a lab for analysis. Human skin is a super-highway of many small molecules reflecting our health and wellbeing. Various devices capable of "seeing" through our skin were announced in the past several years. Some of them - like AIRO watch claiming to detect metabolites in your bloodstream as they are released during and after meals - turned out to be vaporware. The jury is still out on many others like HealbeGobe. And the remaining ones are still in prototyping stages.  EU-funded Biotex textiles and Perspiration Detective patch development at the University of Cincinnati started from detecting sodium ions in sweat as indicators of hydration levels. A tattoo-like electronic sweat sensor built by a team in UCSD demonstrated that measuring a change in lactate might be sufficient to find when an athlete is about to “hit the wall.” Startup Electrozyme, later renamed to Biolinq, was formed to commercialize this technology. The picture shows their prototype of a skin-applied electrochemical sensor that analyses body fluids to provide actionable health information. The goal is to develop temporary tattoo biosensors providing blood level info without accessing blood. Halo Wearables will launch their non-invasive hydration monitoring wearable in early 2016. It is tailored specifically for elite athletes.  Halo's optical sensors track sodium and potassium levels in the user's blood. ​ Researchers from the University of California, Berkeley, Stanford and Lawrence Berkeley National Laboratory have also developed a wearable sensor that can monitor sodium, potassium and lactate levels in sweat. A paper with their findings was published in Nature earlier this year. ​ Startup Xsensio, accepted this year in Mass Challenge accelerator, works on “intelligent stamps” the size of a credit card (Lab-on-Skin wearables) including a unique low-power sensor for sweat analysis. ECHO smart patch from Kenzen aims to "silently follow your health and notify you only when it's most important". It analyzes sodium and potassium in sweat to monitor hydration, lactic acid and glucose analysis energy expenditure.  Existing technologies can detect a general increase or decrease in metabolites rather exact concentrations. So using sweat to accurately monitor clinically important variables such as glucose levels, is still out of reach. But developers are employing innovative approaches to make it possible. A team from Seoul National University, University of Texas and a Massachusetts-based company MC10 are developing a flexible patch that senses glucose in people with diabetes and administers drugs, all in a single device. And there may be easier ways to display all the information collected from various sensors -  perhaps even directly on the body - as the team from the University of Tokyo demonstrated with device measuring oxygen saturation levels in blood. ​We've come a long way from bulky and invasive medical equipment that required the patient to remain in the hospital for monitoring. We have made a lot of progress from the times when all symptoms and signs were recorded with a pencil and paper. There is still a lot more to do before real-time self-managing noninvasive diagnostics reaches a breakthrough, but we are so much closer.

REFERENCES


Andreoni G, Standoli CE, & Perego P (2016). Defining Requirements and Related Methods for Designing Sensorized Garments. Sensors (Basel, Switzerland), 16 (6) PMID: 27240361

Gao W, Emaminejad S, Nyein HY, Challa S, Chen K, Peck A, Fahad HM, Ota H, Shiraki H, Kiriya D, Lien DH, Brooks GA, Davis RW, & Javey A (2016). Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature, 529 (7587), 509-14 PMID: 26819044

Imani S, Bandodkar AJ, Mohan AM, Kumar R, Yu S, Wang J, & Mercier PP (2016). A wearable chemical-electrophysiological hybrid biosensing system for real-time health and fitness monitoring. Nature communications, 7 PMID: 27212140

Lee H, Choi TK, Lee YB, Cho HR, Ghaffari R, Wang L, Choi HJ, Chung TD, Lu N, Hyeon T, Choi SH, & Kim DH (2016). A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Nature nanotechnology, 11 (6), 566-72 PMID: 26999482

Panneer Selvam A, Muthukumar S, Kamakoti V, & Prasad S (2016). A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat. Scientific reports, 6 PMID: 26996103
XXX

Yokota T, Zalar P, Kaltenbrunner M, Jinno H, Matsuhisa N, Kitanosako H, Tachibana Y, Yukita W, Koizumi M, & Someya T (2016). Ultraflexible organic photonic skin. Science advances, 2 (4) PMID: 27152354

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

Of blood and breath: metabolite-based diagnosis of ovarian cancer

Physicians always knew that breath contains clues to diseases. Chemicals in breath often correlate with chemicals in saliva and blood - be it alcohol, anaesthetics or other metabolites (see, for example, this study by Dr Andreas Hengstenberg).

As one of my interests is breath-based detection of ovarian cancer, I took note of the recent paper claiming 99% to 100% accuracy of detecting ovarian cancer by metabolites in blood.
The authors used customized functional support vector machine-based machine-learning algorithms to classify thousands of metabolites measured by mass spectrometry (JEOL AccuTOF™ DART® that allowed to forego conventional liquid chromatography as sufficient resolution was achieved without separation) in peripheral blood. 

100% sensitivity and 100% specificity was achieved with 64-30 split validation technique, while 100% sensitivity and 98% specificity was the accuracy of leave-one-out-cross-validation. Very large number of metabolites, from 2,000 to 3,000 features, contributed to such discriminatory power (see the list of 14,000+ in supplemental material) 
 

Set of 25 canonical metabolic pathways relevant to the uploaded elemental
formulae ranked according to their p-values (hypergeometric distribution).

Histamine, amino acid, fructose and glucose metabolism were among the most prominent processes discriminating cancer and healthy blood.
It's that simple: sugar feeds cancer. Scientists have long found that cancer cells slurp fructose, and that fructose intake can be linked to some cancers. Histamine/polyamine interplay in cancers is also known. Histamine may be involved in inhibition of the local immune response against cancer. Is amino acid metabolism also linked to cancer? Well, what is not.   




Metabolomic biomarkers were always known to have diagnostic potential - cholesterol and glucose are among the oldest and most widely performed diagnostic tests. Yet, most bleeding edge cancer detection platforms are genomic or proteomic in nature.  Of the thousands of known biomarkers, only a handful have made it into the clinic. Existing ovarian cancer tests mostly rely on detecting a protein -  carbohydrate antigen 125. Vermillion's OVA1 and HealthLinx OvPlex tests use five proteins. This may be extended to 7.

Metabolites represent the end products of the genome and proteome, thus metabolomics-based diagnostics  holds the promise of providing powerful diagnostics,  allowing for differentiation of increased and decreased levels of chemicals with low process coefficient of variation.


Metabolomic tests were used for medical diagnostics starting with Hippocrates and Lavoisier. They continue to be explored by modern scientists. Dr Michael Phillips, for example, developed HeartsBreath Test, approved by the US Food and Drug Agency for early diagnosis of heart transplant rejection. Research proved the potential of inexpensive breath tests in discriminating lung, breast, colon and prostate cancers. Let's hope the new article  - along with others - will lead to novel consumer products, not only more academic research and peer-reviewed publications.



Zhou M, Guan W, Walker LD, Mezencev R, Benigno BB, Gray A, Fernández FM, & McDonald JF (2010). Rapid Mass Spectrometric Metabolic Profiling of Blood Sera Detects Ovarian Cancer with High Accuracy. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology PMID: 20699376

On cancers and petroleum spills

Researchers have known for years that smell of cancer patients is chemically different from healthy individuals. One more study featured in British Journal of Cancer brings us a bit closer to an inexpensive, easy-to-use, portable device for home diagnostics. 

Exhaled breath collected from 177 volunteers (patients with lung, colon, breast, and prostate cancers and healthy controls) was examined by gold nanoparticle nanosensor arrays (GNPs) and gas chromatography linked to the mass spectrometry technique (GC-MS). 

GNP sensor resistance responses showed remarkable separation between cancer and healthy controls (Principal Component Analysis results are shown in the Figure: LC, lung cancer;  CC, colon cancer; BC, breast cancer; PC, prostate cancer).

Most of the VOCs reported in this study appear for the first time in the literature, adding to the wide spectrum of chemicals previously proposed as cancer biomarkers. Some of the chemicals -  predictive of  lung and prostate cancers -  are frequently released to the environment through petroleum spills. 

1-methyl-4-(1-methylethyl)-benzene - known as p-cymene  or p-isopropyltoluene -   is utilized by various species for chemical communication. It can be derived from the essential oils of herbs and spices and has biocidal properties against foodborne pathogens such as spoilage yeasts and E. coli O157:H7. p-cymene is the biological precursor of carvacrol that is also an antimicrobial agent (Kiskó and Roller, 2005).  It's decreased with cancer, and is present at higher concentrations in healthy individuals.


Toluene, dodecane and other aromatic components of petroleum are among chemicals found in human breath.

Typical "octane booster" toluene  - present at higher concentrations in lung and prostate cancers - is toxic to living organisms although some bacteria (like P. putida that has toluene operon) are able to grow in its presence (Eaton 1997).

Dodecane, a biogasoline component, is higher in the breath of healthy individuals. It is decreased in lung cancer. One of its derivatives - 2,6,11-trimethyl-dodecane was found in 80% of the males, but in none of the females participating in the study. 

Another aromatic compound, 2-amino-5-isopropyl-8-methyl-1-azulenecarbonitrile, similar to carbonitriles used in manufacturing of fragrance agents, is present at higher concentrations in breast, colon and prostate cancers when compared to healthy controls.

An alcane 3,7-dimethyl-undecane was found to be indicative of allergies. It was previously found to be eliminated from mice odors when they enter reproductive cycle (Achiraman & Archunan, 2006) and proposed to be used in diagnostics of asthma (Dragonieri et al., 2007).

Chemicals in breath can tell not only about cancers, but also relate to other diseases, environmental exposures and dietary behavior. This might decrease discriminative power of  expensive metabolomics technologies and bioinformatics approaches not based on additional knowledge, yet custom-made sensor arrays show great promise.


References


Peng G, Hakim M, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A, Tisch U, & Haick H (2010). Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. British journal of cancer, 103 (4), 542-51 PMID: 20648015



Gabriella Kiskó, Sibel Roller. (2005) Carvacrol and p-cymene inactivate Escherichia coli O157:H7 in apple juice.  BMC Microbiol. 2005; 5: 36

Eaton RW.  (1997) p-Cymene catabolic pathway in Pseudomonas putida F1: cloning and characterization of DNA encoding conversion of p-cymene to p-cumate. J Bacteriol. 1997 May;179(10):3171-80.

Shanmugam Achiraman, Govindaraju Archunan (2006) 1-Iodo-2methylundecane, a putative estrus-specific urinary chemo-signal of female mouse (Mus musculus) Theriogenology 66, 1913–1920

Dragonieri S, Schot R, Mertens BJ, Le Cessie S, Gauw SA, Spanevello A, Resta O, Willard NP, Vink TJ, Rabe KF, Bel EH, Sterk PJ. (2007) An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol. 120(4):856-62. 

Foods and Smells

Image via Wikipedia

How many flavors are out there? We often hear only about these five - sweet, sour, salty, bitter and savory (umami), but there are so many more and they are important not only to our tastes but also health.

Remember that fresh grassy smell wafting up from the newly sliced tomato? It may be it's way of saying  "I'm good for you".

Stephen A. Goff and Harry J. Klee's article "Plant Volatile Compounds: Sensory Cues for Health and Nutritional Value?" published in a 2006 issue of Science explains why odors from foods may be nutritional or health signals that the human nose has learned to recognize.

Among the things emmigrants from less developed countries miss in USA is the scent of fresh tomatoes. One of the volatile compounds associated with the “grassy” tomato flavor, cis-3-Hexenal, is also an indicator of fatty acids essential to the human diet. Wild tomato contained more than three times the amount of that chemical than the cultivated version in the developed world. Two other contributors to tomato flavor — 2- and 3-methylbutanal — are indicators of the presence of essential amino acids and are also three times more common in the wild tomato. Same applies to commercial apples, strawberries, bread, cheese, even wine and beer.

Flavorful curcumin in tumeric has anti-inflammatory properties, compounds in ginger have antioxidants, and there are antimicrobial chemicals that contribute to the scent of onions, garlic, rosemary, sage, clove, mustard, chili peppers and thyme.

There are hundreds of volatile compounds in foods and beverages, often a major factor in how taste of foods is perceived.

What smells people enjoy the most?

Joanne Camas from Epicurious.com lists these 5 food smells:

1. Fried onions cooking
2. Banana bread baking (extra points if it has chocolate chips in it)
3. A perfectly ripe tomato as you slice into it, especially on a warm, sunny day
4. Coffee brewing
5. Garlic bread, fresh out of the oven
Most people commenting on this post listed baked breads and coffee as their top favorites too. Other choices include pies, spices and meats.

Here are some of the responses pulled from different blogs. What are your top five?

chefrosey 12:23:21 PM on 02/01/10

Chocolate
Fresh brewed coffee
Fresh baked bread
Fresh picked strawberries or an orange being peeled!
Any baked good coming out of the oven!

chef330 12:14:17 PM on 02/01/10

1. Onions sauteeing in butter
2. Chocolate Chip Cookies coming out of the oven
3. Just-picked peaches
4. Hot Apple Pie
5. European Butter - you can smell the flavor

Janet Tue Feb 2, 2010 2:22pm PST

apple pie baking in the oven
tralala311 Tue Feb 2, 2010 2:25pm PST

mmmm... GUMBO!!!

Habanero♥™ Tue Feb 2, 2010 2:32pm PST

Bacon, Baking Bread, Turkey, Pumpkin Pie, Molasses Cookies, Cinnamon Rolls.

Sherri Tue Feb 2, 2010 2:53pm PST

Coffee brewing, Chocolate Chip Cookies, Cinnammon Rolls, Bread, Pumkin Pie
__A_YAHOO_USER__ Wed Feb 3, 2010 9:21am PST
i think there's something about a roast that's been slow cooking all day that smells delicious, it'd be on my top 5 for sure.