A. Case study
B. More information
C. Editors' comments
E. CPD questions (South Africa, Australia)
A. Case study
A 31-year-old man
contacted his doctor. Upon his first visit to the bathroom that morning,
he had noticed, in addition to symptoms of a hangover, that his urine
was malodorous. He thought that he might have alcohol poisoning. The
doctor questioned him about his symptoms other than the malodorous urine,
but these appeared to be the same as during previous hangovers. His
wife also had a hangover that morning, but had experienced no change
in urine smell. The patient was asked to describe the food served at
the party the night before. He informed the doctor that there had been
a variety of cheeses, pastries, fruit and quite a few unusual foods
such as asparagus. The patient mentioned that the night before was the
first time since childhood that he had eaten asparagus, as he had not
enjoyed its taste before. The doctor told the patient that the smell
could be a result of eating asparagus. The patient protested as his
wife had eaten the same foods as himself but not experienced any odor
change. The doctor, however, informed him that this does not occur in
all individuals, it is harmless and that the smell would disappear spontaneously.
He asked the patient to contact him if the smell persisted throughout
the day. The patient agreed, but the smell completely disappeared by
|TIP for Allergy
Allergy Advisor offers a search function that is useful in
many situations. In this case report, where, at first, one
has no clue to what could be causing the malodorous urine,
this function can be a shortcut to finding the cause. One
can search through the Allergy Advisor database for a specific
word. For example, if one chooses the "Search & WWW"
bar, and then "Search Database", one can enter the
word "malodorous" or "urine and smell".
It will bring up the sections of the program where this word
is found. In this case, "Asparagus" is found. Reading
through the information under Asparagus, one will find that
ingestion of asparagus is associated with malodorous urine.
B. More information
In February we discussed
beeturia. Now we will cover two more food idiosyncrasies: why urine
becomes malodorous after the ingestion of asparagus, and why water tastes
sweet after the ingestion of artichoke.
ingestion of asparagus is associated with the production of
malodorous (described as "rotten or boiling cabbage"
or "vegetable soup") urine. This occurs in approximately
40-43% of people (a figure of 79% was observed in the United
States) within an hour after eating only a few spears of asparagus.
|It has been
shown to remain with individuals for virtually a lifetime. Those
who produce this odor assume that everyone does, and those who do
not produce it have no idea of its potential olfactory consequences.1,2,3,4,5
Why does this
This phenomena has been regarded as either the result of an inborn error
of metabolism or an inherited (autosomal dominant) trait.5,6
But this appears
to be not true. The urinary excretion of a pungent odorous substance
after asparagus is eaten appears to be universal and the variable is
the ability to detect the related odor. The detection of the odor constitutes
a specific smell hypersensitivity. Those who can smell the odor in their
own urine would thus be able to smell it in the urine of anyone who
has eaten asparagus, whether or not that person was able to smell it
himself. It is possible that this odor sensitivity is a genetic hypersensitivity
or general hyperosmia rather than an inborn error of metabolism. Studies
have suggested that it is a genetically determined specific hypersensitivity
(controlled by a single autosomal dominant gene).6,7
What is evident
is that there also appears to exist a specific hyposmia (hyposphresia)
or anosmia, wherein certain individuals are unable to smell the odor
even from the most fetid urines. A later study suggested that both phenomena
coexist. Some people are excretors while others are nonexcretors; some
people are perceivers (able to smell the odor) while others are nonperceivers
(do not smell it). But this still needs further investigation.7
have been found present in the urine after ingesting asparagus and at
least two different ones have been held responsible for the characteristic
odor. Specifically six discrete sulphur-containing alkyl compounds have
been identified, namely methanethiol, dimethyl sulphide, dimethyl disulphide,
bis-(methylthio)methane, dimethyl sulphoxide and dimethyl sulphone.
But other have also been found present.4,7,8
One study has indicated
that a substance, namely methylmercaptan, appeared in the urine of 40%
of the subjects and suggested that its excretion was an expression of
an autosomal dominant gene.7
and its methanethiol addition product S-methyl-3 (methylthio) thiopropionate
have been postulated to be the odor-causing compounds in most studies
that have been performed, but the metabolic pathway leading to their
formation has not been identified.2,3,7,9
The isolation of
sulfur-containing compounds from the urine after asparagus ingestion
is, however, no indication that they themselves contribute to the odor,
as they may be insufficiently volatile. Due to many queries about the
methods used, more investigations are needed.7,8
Other odors related to foods and diseases:
Some diseases have been described as having characteristic odors. Patients
with diphtheria have a "sweetish" odor, those in a diabetic
coma smell "fruity," yellow fever patients smell like a "butcher
shop," scurvy gives a "putrid" odor and scrofula the
odor of "stale beer," while those with typhoid fever have
an odor like "fresh-baked brown bread." It is said that nurses
in the past confidently diagnosed enteric fever by sniffing the armpits.10
By intelligent use
of the sense of smell, an astute clinician may make a presumptive diagnosis
of a rare metabolic disorder and institute life-saving therapy while
awaiting laboratory confirmation. There is a group of disorders in metabolism
that lead to unusual odors of the body or urine; they are individually
rare, but collectively they make up a sizable portion of acute life-threatening
illnesses of infancy.11
a. The characteristic
odor of phenylketonuria has been described as "musty,"
"wolflike," "barny," "mousy," "horsey,"
and "stale sweaty locker-room towels."10,11,12
b. In maple syrup
urine disease, the odor is described as "caramel-like,"
"malty," or like "maple syrup."10 It was determined
that 4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone), a well-known
flavor impact compound also present in fenugreek, lovage and buckwheat
honey13, is responsible for the characteristic odor in the urine of
affected individuals. The common name given to the disease is thus quite
appropriate, as maple syrup also contains sotolone.14
Ingestion of fenugreek
(a leguminous herb cultivated in southern Europe, northern Africa and
India) resulted in a false suspicion of maple syrup urine disease when
the doctor noticed the characteristic smell of the patient's urine.
It has been reported where the patient was given fenugreek tea15 or
a folk remedy containing the plant.16 Also, false suspicion arose when
the ingestion of fenugreek by mothers in labor resulted in a maple syrup-like
odor in their newborn infants.17
syndrome (or Oasthouse urine disease or Methionine malabsorption
syndrome), which has some resemblances to phenylketonuria, presents
with a distinctive dried malt or hops (as in breweries), dried celery
or yeast odor.10,11
d. Individuals with
hypermethioninemia have been variously described as having a
"fishy," "sweet and fruity," "rancid butter"
or "boiled cabbage" odor.10 It has been suggested that tyrosinosis-tyrosinemia
(or rancid butter syndrome) which presents with a strong offensive odor
resembling that of rancid butter is the same as hypermethioninemia.11
acidemia (or sweaty feet syndrome) often presents with a "cheesy"
or "sweaty feet" odor.10,11
(TMAuria) (also known as fish malodor syndrome or fish odor syndrome)
is an uncommon disorder that causes an accumulation and massive excretion
of the volatile tertiary amine trimethylamine (TMA) in the urine and
other bodily fluids (sweat, expired air, saliva, vaginal secretions
and other bodily secretions).18,19,20 (This should not be confused with
the fishy odor present in Trichomonas vaginitis. This odor is as a result
of anaerobic organisms.) The disease produces a powerful aroma of rotting
fish, and this causes the affected person to have an offensive body
odor.18,21 Trimethylamine is derived from the intestinal bacterial degradation
of foods rich in choline (egg yolk, liver, etc.) and carnitine. TMA
is also formed by reduction of TMA-oxide present in high concentrations
in marine fish.20,22 TMA is normally oxidized by the liver into odorless
trimethylamine N-oxide and then excreted in the urine. This oxidization
is defective in TMA-uria. The above foods can exacerbate the condition.
Dietary adjustments can reduce the excretion of trimethylamine and may
reduce the odour.22
g. Cat's urine
syndrome has neurological symptoms resembling Werdnig-Hoffman's
disease, and the patient's urine has a cat urine-like odor.11
h. Diabetic keto-acidosis
induces a characteristic odor on the breath that has been described
as "sweet" or "fruity."11
For more reading
on the above conditions, I recommend references 10 and 11.
of the tongue to artichoke can make water taste sweet. Experiments
have shown that exposure of the tongue to the extract from one-forth
of an artichoke heart makes water taste as sweet as 2 teaspoons
of sucrose dissolved in 6oz (±168g) of water.
Why does this
It was found that this induced sweetness is produced by temporarily
altering the tongue so that a normally non-sweet substance tastes sweet.
Two substances in artichoke were identified as the major sources of
the sweetness. They are chlorogenic acid (3-caffeoylquinic acid) and
cynarin (1,5-dicaffeoylquinic acid). It is suspected that there are
other substances that also possess similar taste-altering properties,
but these substances have not yet been identified.
There have been
anecdotal reports of other beverages such as milk and wine tasting sweet
after the consumption of artichoke.
Other common food
ingredients have also been shown to alter the taste of water when preceding
it on the tongue. For example, water tastes bitter-sour after exposure
to salt, bitter after sucrose, salty after urea, and sweet after exposure
to acids, quinine, caffeine and potassium chlorate. The major difference
between the artichoke-induced sweet taste of water and other sweet tastes
of water is the duration of the effect. The artichoke-induced sweetness
lasts longer than most of the other flavor changes.
Sweetness can be
induced by exposing the tongue to another plant, miracle fruit (Synsepalum
dulcificum), a small red berry that is native to tropical West African.
However, with miracle fruit, sour substances rather than water are sweetened,
the sweetness lasts much longer (30 minutes or more) than that produced
by artichokes, and fewer individuals fail to observe the effect.
The authors suggested
that the sweetening of substances by temporarily modifying the tongue
may provide an alternative to currently used nonnutritive sweeteners.
They suggested the possibility that research on taste modification may
contribute to the improved palatability of food derived from sources
such as algae or yeast, which may be needed increasingly in the future.23
||compiled by Karen du Plessis
Food & Allergy Consulting & Testing Services (FACTS)
PO Box 565
Comments by our editors
A change in a patient's urine, whether colour, smell or ability,
can result in marked concern and mental stress for the individual
concerned. Beeturia, an example, was discussed in a previous newsletter.
It is important for health professionals to understand the range
of causes that result in these effects. If purely idiosyncratic
responses to a food, understanding and explaining this will prevent
further expensive and unnecessary investigations. It will allow
the health professional to explain this to the patient resulting
in a rapid resolution of the patient's stress instead of the patient
having to wait some time for the results of various expensive
investigations which will confirm this diagnosis.
For more information
on this subject and other allergy and intolerance related topics, visit:
To join a professional
food allergy discussion list where this subject can be discussed further,
go to http://groups.yahoo.com/group/AllergyDietitian
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1. Mitchell SC.
Asparagus and malodorous urine. Br J Clin Pharmacol 1989 May;27(5):641-2.
2. Richer C, Decker N, Belin J, Imbs JL, Montastruc JL, Giudicelli JF.
Odorous urine in man after asparagus. Br J Clin Pharmacol 1989 May;27(5):640-1.
3. White RH. Occurrence of S-methyl thioesters in urines of humans after
they have eaten asparagus. Science 1975 Sep 5;189(4205):810-11.
4. Mitchell SC. Food idiosyncrasies: beetroot and asparagus. Drug Metab
5. Mitchell SC, Waring RH, Land D, Thorpe WV. Odorous urine following
asparagus ingestion in man. Experientia 1987 Apr 15;43(4):382-3.
6. Hoffenberg L. A note on polymorphism: the ability to smell urinary
metabolites of asparagus. Diastema 1983;11:37-8.
7. Lison M, Blondheim SH, Melmed RN. A polymorphism of the ability to
smell urinary metabolites of asparagus. Br Med J 1980 Dec 20-27;281(6256):1676-8.
8. Waring RH, Mitchell SC, Fenwick GR. The chemical nature of the urinary
odour produced by man after asparagus ingestion. Xenobiotica 1987 Nov;17(11):1363-71.
9. Gearhart HL, Pierce SK, Payne-Bose D. Volatile organic components
in human urine after ingestion of asparagus. Clin Chem 1977 Oct;23(10):1941.
10. Cone TE Jr. Diagnosis and treatment: some diseases, syndromes, and
conditions associated with an unusual odor. Pediatrics 1968 May;41(5):993-5.
11. Mace JW, Goodman SI, Centerwall WR, Chinnock RF. The child with
an unusual odor. A clinical resume. Clin Pediatr (Phila) 1976 Jan;15(1):57-62.
12. Beers MH, Berkow R. The Merck Manual of Diagnosis and Therapy Seventeenth
edition. Merck Research Laboratories, NJ, 1999.
13. Zhou Q, Wintersteen CL, Cadwallader KR. Identification and quantification
of aroma-active components that contribute to the distinct malty flavor
of buckwheat honey. J Agric Food Chem 2002 Mar 27;50(7):2016-21.
14. Podebrad F, Heil M, Reichert S, Mosandl A, Sewell AC, Bohles H.
4,5-dimethyl-3-hydroxy-2[5H]-furanone (sotolone)--the odour of maple
syrup urine disease. J Inherit Metab Dis 1999 Apr;22(2):107-14.
15. Sewell AC, Mosandl A, Bohles H. False diagnosis of maple syrup urine
disease owing to ingestion of herbal tea. N Engl J Med 1999 Sep 2;341(10):769.
16. Bartley GB, Hilty MD, Andreson BD, Clairmont AC, Maschke SP. "Maple-syrup"
urine odor due to fenugreek ingestion. N Engl J Med 1981 Aug 20;305(8):467.
17. Korman SH, Cohen E, Preminger A. Pseudo-maple syrup urine disease
due to maternal prenatal ingestion of fenugreek. J Paediatr Child Health
18. Mitchell SC, Smith RL. Trimethylaminuria: the fish malodor syndrome.
Drug Metab Dispos 2001 Apr;29(4 Pt 2):517-21.
19. Treacy E, Johnson D, Pitt JJ, Danks DM. Trimethylaminuria, fish
odour syndrome: a new method of detection and response to treatment
with metronidazole. J Inherit Metab Dis 1995;18(3):306-12.
20. Sela BA, Trau H, Spira A. [Trimethylaminuria: fish-odor syndrome]
Harefuah 1993 Feb 1;124(3):138-9, 183.
21. Akerman BR, Lemass H, Chow LM, Lambert DM, Greenberg C, Bibeau C,
Mamer OA, Treacy EP. Trimethylaminuria is caused by mutations of the
FMO3 gene in a North American cohort. Mol Genet Metab 1999 Sep;68(1):24-31.
22. Rehman HU. Fish odor syndrome. Postgrad Med J 1999 Aug;75(886):451-2.
23. Bartoshuk LM, Lee CH, Scarpellino R. Sweet taste of water induced
by artichoke (Cynara scolymus). Science 1972;178(64):988-90.
Questions (South Africa, Australia)
ALL THE QUESTIONS
1. Which one of the
following is not true regarding the malodorous urine associated with
(a.) The smell is described as being like "rotten or boiling cabbage"
or "vegetable soup."
(b.) It occurs in approximately 40-43% of people.
(c.) It occurs after eating at least 20 spears of asparagus.
(d.) The tendency has been shown to remain with individuals for virtually
2. True or false:
The characteristic odor has been attributed to sulphur-containing compounds
in the urine.
3. Which of the
following terms has not been used to describe the characteristic odor
(d.) dried malt or hops
4. Which food does
not contain the compound that contributes to the odor that is characteristic
of maple syrup urine disease?
(a.) maple syrup
5. Which of the
following conditions has not been associated with a "fishy"
(a.) Isovaleric acidemia
(c.) Trichomonas vaginitis
6. In which of the
following bodily fluids is trimethylamine excreted in the disorder trimethylaminuria?
(d.) All of the above
7. Which of the
following is not true regarding any of the changes in the taste of water
due to food ingredients ingested?
(a.) Bitter-sour taste after exposure to salt
(b.) Sweet taste after exposure to sucrose
(c.) Salty after exposure to urea
(d.) Sweet after exposure to acids, quinine, caffeine and potassium
8. Which of the
following is true regarding the effect of miracle fruit on taste sensation?
(a.) Water taste sweeter.
(b.) Sour substances taste sweeter.
|1. a [ ] b [ ] c [X] d
||2. a [X] b [ ]
||3. a [ ] b [ ] c [ ] d
|4. a [ ] b [ ] c [ ] d
||5. a [X] b [ ] c [ ] d
||6. a [ ] b [ ] c [ ] d
|7. a [ ] b [X] c [ ] d
||8. a [ ] b [X]
1. c. It occurs
after eating at least 20 spears of asparagus.
2. a. True
3. d. dried malt or hops
4. d. wheat
5. a. Isovaleric acidemia
6. d. All of the above
7. b. Sweet taste after exposure to sucrose.
8. b. Sour substances taste sweeter.