What's that fatty odor?

Body odor is closely associated with diet. Deciphering the chemistry of human odor is not an easy task - only about 5% of odorous molecules are usually recovered from collection containers, and not all of the molecules are identified in complex spectra. Volatile fatty acids, alcohols, and aromatic ring compounds comprise a substantial fraction of smelly molecules, yet very little is known about the origin and factors controlling their production in humans. Fortunately for some (and not so fortunately for others), the human nose can capture and discriminate many smell signatures. Could this discrimination be used to connect the dots between diet and body odor? MEBO Research has just started an anonymous study using the Aurametrix health analysis tool to find out.

Aurametrix's knowledge base provides a wide selection of foods and symptoms, including different types of odors recognizable by the human nose. Participants in the study have been recording some of their food intake and activities on days when their symptoms are better or worse than average, entering items they suspect might be contributing to or alleviating their body odor on those days. The tool's analysis engine then lets them explore all the possible cause-effect relationships. In addition, Aurametrix performs automated analyses across the entire user community and displays cumulative results as "aggregate correlations." The figure on the right is an excerpt from these results.

Although the study has only just begun, the preliminary results already look very interesting. One example is fatty odor. Aurametrix linked several dietary chemicals to unpleasant "fatty odor" emanating from skin based on Aura entries of several participants. The top chemicals so far are:  Vitamin K1 (phylloquinone), Octadecanoic acid, FODMAPs, Beta-carotene,  Carbohydrates and Monosaccharides. Another interesting result (although there were fewer observations) is that Vitamin B12 obtained from diet seemed to help prevent fatty body odor.

• Could Vitamin K1 really contribute to "fatty" odor?  Could 6 observations derived from different users' Auras be just a coincidence? Vitamin K is proposed to increase production of alkaline phosphatase in intestines. This enzyme produces a number of different substances, some of which have a peculiar sweetish smell.  Chlorophyll, usually recommended to combat body odor and supposedly makes odor "sweeter," is an excellent source of vitamin K1. And so is Asparagus that gives urine a disagreeable odor.
• Octadecanoic (Stearic) acid was also linked to fatty odor in 6 observations. This saturated fatty acid is most abundant in animal fats and cocoa butter, and also in nuts and seeds (peanuts, flax), cheese, cookies and candies. Its smell is fairly mild, yet can be detected by the human nose (Bolton and Halpern, 2010). Besides, it slowly converts in the liver to heart-healthy oleic acid which has a faintly fatty odor with a hint of dead insects. It could also metabolize into other compounds and incorporate into liver lipids or follow alternative routes.
• FODMAPs, highly fermentable but poorly absorbed short-chain carbohydrates and polyols, were found to be an important dietary factor contributing to gastrointestinal symptoms. Perhaps FODMAPs, carbohydrates and monosacharides in particular could also contribute to odor in the absence of GI discomfort?
• Beta-carotene is another heart-healthy chemical with anticancerous properties important in human nutrition as a source of Vitamin A. Tobacco, tea, many spices and flowers owe their flavors to chemicals metabolized from beta-carotene. One of such chemicals is warm and woody beta-Ionone that smells of blackberry at lower concentrations and fatty-cheesy at higher concentrations.

The chemistry of odors and their origins is undoubtedly very complex. Yet, these preliminary results show that together we may find the answers to many health-related questions. With more participants, we'll soon connect the dots between diet and body odor. Want to participate? Write to:

References

Bolton B, & Halpern BP (2010). Orthonasal and retronasal but not oral-cavity-only discrimination of vapor-phase fatty acids. Chemical senses, 35 (3), 229-38 PMID: 20100787

Dunkel M, Schmidt U, Struck S, Berger L, Gruening B, Hossbach J, Jaeger IS, Effmert U, Piechulla B, Eriksson R, Knudsen J, & Preissner R (2009). SuperScent--a database of flavors and scents. Nucleic acids research, 37 (Database issue) PMID: 18931377

Colonoscopy for everyone! ..or Gonna Buy Me A Dog

New research from Japan brings good news: dogs can be almost as accurate as a colonoscopy exam.

In patients with colorectal cancer (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 watery 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.  

As simple as that: exhaling 100-200 ml into a breath sampling bag and storing it in a Ziploc bag at 4°C until a trained dog has a change to sniff it can be enough for diagnostics. Just one breath sample! And it was almost as good as a watery stool sample obtained during colonoscopy or this joyous examination itself.

There have been many research studies that dogs, rats and even moth can detect scents pertaining to human disease. Ordinary household dogs can be trained to distinguish breath odors (McCulloch et al 2006). For some cancers, sensitivity can be as high as 100% (Horvath et al 2008).

Unfortunately, sophisticated mass-spectrometry, gas chromatography and software tools interpreting the signals are still not as good as our four-legged friends that are never getting lost in the noise of disease-unrelated flavors.
But we are getting better in identifying specific chemicals responsible for various conditions - from alkanes  - such as pentane in breath of IBD patients and polystyrene foam or aromatic components of petroleum in cancer breath to blends of fatty acids like oleic and linoleic acids forming the smell of death.

Perhaps pet rats will find their use as pocket doctors before men-made sensors are developed to cope with infections, medical conditions, even fear and anxiety that also have a distinctive odor signature. In any case, Dr. Sonoda and his colleagues bring us a reassuring word that not every frequent visitor to the GI doctor's office will have to experience the joys of a colonoscopy.


Sonoda H, Kohnoe S, Yamazato T, Satoh Y, Morizono G, Shikata K, Morita M, Watanabe A, Morita M, Kakeji Y, Inoue F, & Maehara Y (2011). Colorectal cancer screening with odour material by canine scent detection. Gut PMID: 21282130


Other published literature on olfactory signatures in gastrointestinal disease:

Cheu HW, Brown DR, Rowe MI (1989) Breath hydrogen excretion as a screening test for the early diagnosis of necrotizing enterocolitis. Am J Dis Child 1989;143:156–9.

Pelli MA, Trovarelli G,, Capodicasa E, Breath alkanes determination in ulcerative colitis and Crohn's disease. Dis Colon Rectum 1999;42:71–6.

Pelton NS, Tivey DR, Howarth GS, A novel breath test for the non-invasive assessment of small intestinal mucosal injury following methotrexate administration in the rat. Scand J Gastroenterol 2004;9:1015–16.

Tibble JA, Sigthorsson G, Foster R, Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology 2002;123:450–60.

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. 

Hormonal Manipulation of Olfactory Cues, or How to Lose a Guy in 10 days

Image via Wikipedia

Body odors are important cues used for social and sexual discrimination. As was shown many times, animals can easily smell age-, health- and genetics-related  differences.  Recent study of our large-eyed relatives, ring-tailed lemurs, demonstrate that drugs can alter body scents and change behavior.

Researchers examined changes in endocrine and  semiochemical profiles of sexually mature female lemurs treated with hormonal contraceptives during their breeding season. Genetic diversity and kinship were estimated using 11–14 microsatellite loci and pairwise genetic distances. Gas chromatography-mass spectrometry (GCMS) was used to detect the volatile compounds in odor. A rater blind to the treatments scored lemur male behavior in regards to female odors. 

The conclusion? Contraceptives change chemical ‘signature’, minimizing distinctiveness and genetic fitness cues. No more can the males determine which females are genetically and physically beautiful. All contracepted females lost their individuality and started to smell funny.  

What about hormones and chemicals in our food?  Maybe one day humans will wake up and realize that something is lost? May it will happen  sooner rather than later...

For those interested in helping with our research of human environmental malodor - check our studies or this call for collaboration.   



Jeremy Chase Crawford,, Marylène Boulet,, & Christine M. Drea (2010). Smelling wrong: hormonal contraception in lemurs alters critical female odour cues Proc. R. Soc. B published online before print July 28, 2010

Odor-prints: individual but genetic connections unclear

Odor is like fingerprints or facial features - it's unique.  Yet no single measurement could be easily applied to recognize an individual.

GC/MS measurements can be used to analyze mixtures of acids, alcohols, aldehydes, hydrocarbons, esters, ketones, and nitrogenous molecules in human odor. Complex algorithms mining patterns help to pinpoint the signatures. But could these signatures be easily derived from genetic makeups?

Recent article published in the Journal of Chemical Ecology looked at the usual suspects -  major histocompatibility locus (MHC) and found that these genes do not determine major patterns. 


Volatile carboxylic acids are the most diverse class of known axillary odorants, and the pattern of these acids is genetically determined. These acids  - like vast majority of human odorous compounds - are produced by human microbiome, in this case by skin bacteria. Odors of 12 families, comprising 3 to 6 siblings,were analyzed with comprehensive two-dimensional gas chromatography (GC x GC) and time-of-flight mass spectrometry (ToF MS). the analysis onfirmed the presence of individual signatures. but failed to find odors specific to HLA genes.

Even though paternally inherited HLA-associated odors were proposed to influence women odor preferences, genetic basis of odors may be more complicated than previously thought.

References

Natsch A, Kuhn F, & Tiercy JM (2010). Lack of Evidence for HLA-Linked Patterns of Odorous Carboxylic Acids Released from Glutamine Conjugates Secreted in the Human Axilla. Journal of chemical ecology PMID: 20623248

Thompson EE, Haller G, Pinto JM, Sun Y, Zelano B, Jacob S, McClintock MK, Nicolae DL, Ober C. (2010) Sequence variations at the human leukocyte antigen-linked olfactory receptor cluster do not influence female preferences for male odors. Hum Immunol. 2010 Jan;71(1):100-3. PMID: 19833159 
 
Jacob S, McClintock MK, Zelano B, Ober C (2002) Paternally inherited HLA alleles are associated with women's choice of male odor. Nature Genet 30: 175-179  PMID: 11799397  PDF
 

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.