One of the more noteworthy features of eating asparagus is the often observed and indeed, discussed consequence - in the form of the distinctly odorous urine of the consumer. Indeed, human physiology seems to go into overtime as the rapidity of this occurrence is remarkable in that this can be noticeable within just a few minutes. Our growing understanding of this process makes for an interesting story of physiological, sensory and genetical intrigue.
gives a brief potted history of key seminal moments in this smelly urine story. The phenomenon of odorous urine was already observed long ago, already being noted by Lemery in 1702 [129
] and later also referred to by many prominent authors and polymaths such as Arbuthnot [130
], Benjamin Franklin [131
] and Proust [132
]. Only later did it become clear that not everyone actually produces smelly urine and furthermore, not everyone can smell it. These first reports from around the mid-18th century have interestingly been proposed to be linked to a change in agronomic practice at that time related to the start of using inorganic and organic S-containing fertilizers to boost plant yield [133
]. ‘Recognition of smelly urine appears coincidental with the start of the use of S containing fertilizers’ [77
] and this relevance of sulphur quickly became clear once the first chemical investigations were carried out.
Looking into which components were potentially causal to asparagus-associated urine odour, in 1891 Nencki first reported a potential link to the presence of one S-compound, methanethiol [134
]. Later results were subsequently questioned as it was considered that the extraction/detection methods used might induce the appearance of artefacts rather than reveal the true in vivo compounds [133
]. Later however, growing numbers of S-compounds were reported [137
]. Waring, using GC-MS, detected 6 S-compounds, including the originally reported methanethiol, as well as dimethyl sulphide—a highly volatile, low odour threshold compound [133
]. Furthermore, both these compounds were also confirmed using trained panellists and standard compound solutions as ‘having a smell reminiscent of asparagus urine odour’. In 2001, Leitner reported in total 12 volatile S-compounds detected in asparagus urine, several of which also have low odour thresholds [140
]. Summarising the literature to date, Pelchat in 2011 provided the most extensive table of sulphur-containing odorants (n = 29) so far found in Asparagus urine [142
]. These results strongly suggest that while S-compounds are potentially causal, it is also likely that the urine odour is the result of a complex mixture rather than a single component. The origin of these S-compounds is still a cause of speculation. Many of these odorants are not found in fresh asparagus [133
] and also not after cooking (where indeed, their highly volatile nature would likely lead to their loss) [73
]. This infers that they arise as the result of human metabolism working on chemical precursors, perhaps through the digestion of compounds such as S-methylmethionine and asparagusic acid [71
]. Interestingly, the latter is considered to be unique to asparagus and is proposed as the ‘ most probable culprit’ as the source of the specific asparagus urine odour [70
]. A theoritical set of chemical conversions from asparagusic acid to the observed odorants has been proposed as being feasible but no evidence has yet been provided [73
]. To elucidate this further we might consider a combination of an untargeted GC-based metabolomics approach coupled to two detection methods in parallel. A Mass Spectrometer would give in depth chemical information on those compounds present and a second detector—the human nose, in the form of a GC-O analysis using a sniffing port, would help us link individual compounds to bioactivities (odour). In this way, we would not only get an unbiased overview of the chemical mixture, but we could reveal any potential links between individual components and their sensory relevance.
More than half a century ago it was recognized and reported for the first time that the phenomenon of humans producing smelly urine is actually not universal [135
]. Allison & McWhirter reported a polymorphism within 115 individuals for the ability to produce and excrete odorous methanethiol after asparagus consumption, with the excreter genotype being dominant [136
]. Mitchel reported that just 43% out of 800 volunteers were ‘excreters’ after asparagus consumption [139
]. In 1980, from a study of 328 Israelis of different ethnic backgrounds it was concluded that some people could not smell asparagus urine and that ca. 10% were the opposite, being ‘hypersensitive’ and still able to detect the odour after significant dilution [138
]. This phenomenon of anosma (smell blindness) is a recognized genetically determined trait [138
] as is hyperosmia or an over-sensitivity for certain odour compounds. Although there may be some ethnical relationships [77
] it is evident that the global population comprises both excreters and non-excreters as well as smellers and non-smellers and indeed, in all possible combinations. Eriksson performed the first 23andMe web-based analysis using voluntary information obtained from 10,000 subjects on the ability to smell ‘asparagus urine’ [141
]. Despite failing to recognize the complication that many volunteers in the cohort will have been in the ‘smeller but non-excreter’ category and hence will give false negative information, the analysis did allow the identification of a genetic link to a region of Chromosome 1. Later, but taking into account the smeller/excreter complexity issues, Pelchat was able to confirm the Eriksson finding and also concluded that the abilities to excrete/smell appear not to be genetically linked [142
]. A later study by Markt et al. remarkedly also failed to recognize the complexity of this odour phenomenon but again reported 50-60% of individuals were anosmic and polymorphic for an SNP in the same Chromosome 1 region where the OR2 olfactory receptors are located as was previously identified [143
So, to conclude this historical investigation which is still ongoing, the central current dogma is that firstly, almost certainly not all asparagus varieties produce the same amounts of substrate, and secondly, while certain individuals can secrete the smelly compounds but not smell them, others can smell the compounds despite not making them themselves and there are those that do both or neither. Thirdly, there also seems to be quantitative variation in both abilities.