A. Case study
B. More information
C. Editors' comments
E. CPD questions (South Africa, Australia)
A. Case study
A 19-year-old girl had a severe asthma attack after eating a meal consisting
of rump steak, mashed potatoes, and boiled peas and carrots. She was
a known asthmatic, but had had severe asthma attacks only during or
after exercise. (The attacks were in fact exercise-induced.)
She had eaten these
foods before without experiencing any respiratory distress. The only
apparent difference was that this was the first time that she had eaten
instant mashed potatoes. When the ingredients of the mashed potatoes
were studied, the only "unusual" ingredient appeared to be
sulfur dioxide. She was questioned about her intake of other sources
of sulfites. It was determined that she had experienced a severe attack
before, after eating dried fruit. Also, whenever she drank certain fruit
juices, she would either start coughing or develop a tight chest. These
foods all contain significant amounts of sulfites.
How does one confirm
that it is sulfites causing an asthma attack?
In this case, it was quite clear what was causing the attacks, so the
patient was instructed to avoid all sulfite-containing foods and beverages.
But one can confirm a diagnosis by doing a double-blind placebo-controlled
challenge. The patient could be given home-made mashed potato with added
sulfites, and regular home-made mashed potato could be the placebo.
|TIP for Allergy
When entering "Potato (instant, mashed)", "Fruit
(dried)" and "Fruit juice" into the "Pattern
search" function on the main menu of Allergy Advisor,
the program searches for constituents that are common to 2
or 3 of the items entered. "Sulfites/sulphites"
were the only constituent that was common to all 3 food items.
A diet sheet for the avoidance of sulfites in the diet can
be printed for a patient from the "Management" menu
of the program.
B. More information:
Sulfites are the most versatile and widely used of all food additives.
They are most often preservatives, but also offer other useful properties
(discussed below). They are often used for two or more actions.
Sulfites or sulfiting
agents include sulfur dioxide (SO2; E220), sulfurous acid (H2SO3) and
the inorganic sulfite salts that may produce SO2 under certain circumstances.1
These salts include sodium sulfite (E221), sodium bisulfite/sodium hydrogen
sulfite (E222), sodium metabisulfite (E223), potassium metabisulfite
(E224), calcium sulfite (E226), calcium hydrogen sulfite/calcium bisulfite
(E227) and potassiumbisulfite (E228). All of these are chemically equivalent.
The term "sulfites" is often used to refer collectively to
substances with E-numbers 220-228.2,3 After the addition of sulfites
to a food, they are eventually broken down to SO2, which is the active
component that preserves food products.
Sulfites are permitted
additives in food products, although they are subject to certain governmental
regulations regarding their amounts, labelling and marketing. Sulfites
also occur naturally in certain foods (e.g., mushrooms and Parmesan
cheese), especially in fermented foods such as wines.1,4,5
Sulfites in the
comment by FACTS's food scientist, Maritza
Sulfites act as antioxidants that inhibit enzymatic browning of
foods such as fresh fruits, vegetables, shrimp and raw potatoes.
They also prevent non-enzymatic browning of products during and/or
after processing. These products include dehydrated potatoes and
other vegetables, dehydrated fruits, white grape juice, frozen
lemon and lime juice, and some types of vinegar. The broad-spectrum
antimicrobial action of sulfites is useful in fermentation processes
such as wine making and corn wet milling, as well as for sanitizing
equipment in the food and beverage industry. Sulfites are also
used for the bleaching of maraschino cherries, for dough conditioning
for frozen pie and pizza crusts, and in salad bars to keep vegetables
and fruits looking fresh. (But this last use is outlawed in many
be lost during food storage, processing and cooking, but little
data is available regarding the extent of such losses.1,2,4
When SO2 is
added to products, some of the chemical can bind to substances
in the food, such as proteins, starches and sugars. The rest of
the SO2 remains in its free form in the product. The free form
is more easily removed by washing or cooking the food, but this
form poses more of a risk to susceptible individuals than the
the highest level of sulfites are potatoes (any peeled variety),
dried fruits, and shrimp and other seafood (from spraying at sea
or after unloading on the dock).1 Commercial pre-cut French
fries, for example, are dipped in sulfur dioxide to prevent browning,
but when they are cooked, most of the sulfur dioxide is lost.
The person frying the French fries may, however, react to the
SO2 fumes coming off the oil. Dried fruit is generally eaten without
cooking or washing. One would therefore expect dried fruit to
pose a greater risk than cooked French fries. In the case of shrimp,
the unpeeled variety is likely to contain higher levels of SO2
than the peeled, as some SO2 may be removed along with the shell.
equipment and food packaging materials such as plastic bags may
also contain traces, as they may have been sanitized with sulfites.4
of sulfites are present in restaurant foods. A single restaurant
meal may contain more than 200mg of sulfites, whereas the average
US daily diet is estimated to contain only 2-15mg of sulfites.2,9
Sulfites are used in many drugs, including injectables, inhalants and
oral liquid and oral solid preparations. They can also be found in topical,
ophthalmic, rectal and vaginal preparations.10,11
They are used as
preservatives,4 as antioxidants, and in the preparation of
water-soluble derivatives of normally insoluble drugs.2 Small
amounts of sulfites may be used in the original processing of dextrose,
gelatine and starch, which are afterwards frequently incorporated into
pharmaceuticals as inert ingredients.2,3
reactions to sulfites
Adverse reactions have been reported to ingested, inhaled, and parenterally
administered sulfites.6 The reactions may be immediate or
delayed,2 and the reported symptoms include dermatologic,
respiratory, or gastrointestinal signs and symptoms.4,5
occurs most often in asthmatics. These reactions can be severe and potentially
life-threatening. Adverse reactions to sulfites in nonasthmatics are
uncommon. Steroid-dependent asthmatics or those with a higher degree
of airway hyperreactivity are at greater risk of experiencing a reaction
to sulfite-containing foods.1,3,4,5,8
asthma is typically triggered by oral ingestion of a sulfite-containing
food, beverage or drug, but can also be triggered by the inhalation
of SO2. A far lower dose of inhaled sulfites is required to induce a
reaction, compared to ingested sulfites.1
Although there is
some disagreement on prevalence, a number of studies have indicated
that 3-10% of all chronic asthmatics are sulfite-sensitive, with a higher
prevalence in those who are steroid-dependent.1,2,3,6,8,9,12
Studies regard a
drop of more than 20% in FEV1 induced by exposure to a sulfite-containing
food or drink as significant, but even a 10% drop should be regarded
as clinically significant, as patients experience definite symptoms
at this level.13
For normal individuals,
exposure to sulfites at levels set by legislation appears to pose little
risk. Toxicity studies in volunteers showed that ingesting 400mg sulfites
daily for 25 days produces no adverse effects.1,4
The single most
commonly reported reaction is bronchospasm; and the most serious reactions
are anaphylactic shock, loss of consciousness and death.2,3,4,5,9,14
Other reported symptoms
include tachypnea, dyspnea, wheezing, chest tightness, hypotension,
tachycardia, headache, dizziness, weakness, severe flushing, generalized
urticaria, angioedema, tingling, pruritus, rhinitis, conjunctivitis,
dysphagia, abdominal pain and cramping, diarrhoea, nausea and vomiting.
For most of these symptoms, diagnostic challenges were not undertaken
to confirm the reported adverse reaction.1,2,3,4,9
drugs may produce adverse reactions in susceptible individuals.
Sources implicated include intravenous injections containing as
little as 2mg of sodium metabisulfite, eyedrops, inhaled products,
and local dental anesthetic injections containing as little as
0.9mg of sodium bisulfite.2,3,10,12,15 It should be
noted that a far lower dose of sulfite-containing inhalant or
injectable drug is needed to induce a reaction than would be the
case with oral ingestion of sulfite-containing products.
reactions to sulfites in orally administered pharmaceutical solutions
have been reported. Direct topical contact with sulfites, especially
in the presence of moisture, has caused skin reactions in food
service personnel who handle sulfites.2
What is the mechanism
of action of sulfites?
This has not been fully elucidated in the literature.2,3,5,9,16 There
have been reported cases in which sulfite-sensitive patients had positive
skin prick tests to sulfites, which would indicate an IgE-mediated reaction,
but the overwhelming majority of reactions are likely to be non-IgE-mediated.1,2,4,5
Suggested mechanisms are:
Sulfite-oxidase deficiency: It has been proven that asthmatics
have a relative deficiency in the enzyme sulfite-oxidase (which helps
process sulfites in the body), compared to non-asthmatics. In a condition
perhaps similar to lactose intolerance, the enzymes may vary between
individuals, and adverse reactions may occur once the enzyme has been
depleted. More research is, however, needed.2,3,4,5,8
Cholinergic-reflex mechanism: This theory holds that, when a
sulfite-containing food or beverage is ingested, sulfur dioxide is eructed
and then inhaled. The inhalation of the SO2 then stimulates irritant
receptors in the airways, which elicit a bronchosconstriction response.2,3,5,8
It is very likely that there is more than one mechanism present in each
Onset of adverse
reactions to sulfites
After exposure to sulfites through inhalation, intravenous injection
or ingestion of solutions, the onset of an adverse reaction is usually
rapid, occurring immediately or within 1-5 minutes. There have been
several reports of sulfite-sensitivity reactions induced by drinking
acidic sulfite-containing solutions, e.g., fruit juices. Most of these
reactions also occurred immediately after ingestion or within 1-2 minutes.
In acidic sulfite solutions, the predominant sulfiting agent is sulfur
dioxide. Such rapid-onset reactions seem to rule out the possibility
of intestinal absorption occurring before the adverse reaction is elicited.
Some researchers have speculated that in these cases the absorption
occurs by the inhalation of sulfur dioxide that is vaporized from the
solution, or from absorption through the oral mucosa. It has also been
suggested that sulfite-sensitive receptors in the oral cavity trigger
an orobronchial reflex.2,4,9
When sulfites are
taken in capsule form or mixed with food, the onset generally takes
longer (an average of 15-30 minutes), although some reactions to solid
food particles have occurred immediately. Delayed reactions may be attributable
to intestinal absorption.2,9 Sulfite sensitivity reactions are evidently
dose-related, resulting in considerable variability among individuals.
As in the case of lactose intolerance, an individual may be able to
tolerate a dose until his or her stores of enzymes are depleted. The
reaction may occur only once the threshold has been reached.
In general, the double-blind placebo-controlled challenge is regarded
as the gold standard. Patients may be challenged with capsules, neutral
solutions, or acidic solutions of metabisulfite. There is no standardized
procedure for challenging with sulfites. Challenges should be tailored
to a patient's history of reaction. The inhalation option is the most
likely to provoke asthma; a challenge with sulfites in solution is optimal
for patients who have reacted to beverages; and in patients with a history
of response to particular foods, food challenges are preferable.1
Because the mechanism
of action is not clear, double-blind placebo-controlled challenges may
not be useful in all cases of sulfite-sensitivity-for example, where
the mechanism of action is a deficiency in sulfite-oxidase. Enzyme levels
may be variable, and results of the double-blind placebo-controlled
challenge may therefore vary every time it is done.
The CAST blood test
has some value in assisting in diagnosis in some individuals.
In most cases, it
may not even be necessary to do a challenge to confirm the diagnosis.
The patient can merely avoid sulfite-containing products.
In cases where a
definite diagnosis is essential, e.g., where other causes need to be
excluded, the necessary precautions should be taken to assure the safety
of the patient, since life-threatening reactions can occur.8,17,18
The only course of action is to avoid sulfite-treated foods and drugs.
There is no evidence that sulfite-sensitive individuals need to avoid
foods containing less than 10ppm residual SO2 equivalents.1,2,4,17
But this level, in the atmosphere, may be high enough to trigger a reaction
upon inhalation in asthmatics. If a reaction occurs, the necessary medical
treatment should of course be given.
||compiled by Karen du Plessis
Food & Allergy Consulting & Testing Services (FACTS)
PO Box 565
Comments by our editors
Janice M. Joneja Ph. D., RDN
are sensitive to sulfites, especially asthmatics who are at risk
for developing severe asthma, need to be aware of the presence
of "hidden" (i.e. undeclared) sulfites in their food.
This is especially important when eating in restaurants. In order
to provide a measure of safety for sulfite-sensitive consumers,
several manufacturers have attempted to develop simple tests to
detect sulfites; perhaps the most well known of these is manufactured
and distributed by Merck. The test kit contains white plastic
strips with a pad on one end. The padded end of the test strip
is wetted in the test solution and then dipped into the food.
A color change to pink indicates the presence of sulfites; the
intensity of the color being an estimation of the level of sulfite
in the food. However, the test is subject to an unacceptable number
of false negative and positive results. The test only measures
free sulfite, not sulfite bound to the food; it is only sensitive
to 10 ppm and many sensitive people react to sulfite levels well
below that; if the food is colored red or brown the strips cannot
be used because the pink color change is masked; the temperature
of the food can affect the test result. In addition, many foods
cause false positive reactions.
When a test is liable to so many false results it becomes unreliable
to the point where it may be dangerous. At the present time, the
best advice is not to use such a test, but to become informed
about all of the potential sources of sulfites in food and beverages
and avoid them. When eating in a restaurant, make careful enquiries
about the source of the food, and when in doubt, do not eat it.
who are highly sensitive to sulphites need to remember to carry
their inhalers with them when eating or drinking away from home,
in case of inadvertant exposure to a food that has been 'contaminated'
with a food containing sulphites. Although legislation in some
countries does not allow the spraying of salads in salad bars
with a sulphur dioxide containing solution, many ingredients are
purchased from vendors prepared or pre-cut and dipped in a sulphite
solutions to prevent browning.
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. Metcalfe DD, Sampson HS, Simon RA. Food allergy: adverse reactions
to foods and food additives 3rd edition. Blackwell Publishing, 2003.
2. Dalton-Bunnow MF. Review of sulfite sensitivity. Am J Hosp Pharm.
3. Challen RG. Sulphite content of Australian pharmaceutical products.
Med J Aust. 1990 Feb 19;152(4):196-8.
4. Joneja JV. Dealing with Food Allergies. A practical guide to detecting
culprit foods and eating a healthy, enjoyable diet. Bull Publishing
Company, USA, 2003.
5. Lester MR. Sulfite sensitivity: significance in human health. J Am
Coll Nutr. 1995 Jun;14(3):229-32.
6. Gunnison AF, Jacobsen DW. Sulfite hypersensitivity. A critical review.
CRC Crit Rev Toxicol. 1987;17(3):185-214.
7. Montano Garcia ML. [Adverse reactions induced by food additives:
sulfites] Rev Alerg Mex. 1989 May-Jun;36(3):107-9.
8. Giffon E, Vervloet D, Charpin J. [Suspicion on sulfites] Rev Mal
9. Settipane GA. Adverse reactions to sulfites in drugs and foods. J
Am Acad Dermatol. 1984 Jun;10(6):1077-80.
10. Smolinske SC. Review of parenteral sulfite reactions. J Toxicol
Clin Toxicol. 1992;30(4):597-606.
11. Dalton-Bunnow MF. Sulfite content of drug products. Am J Hosp Pharm.
12. Perusse R, Goulet JP, Turcotte JY. Sulfite, asthma and vasoconstrictors.
J Can Dent Assoc. 1989 Jan;55(1):55-6.
13. Steinman HA, le Roux M, Potter PC. Sulphur dioxide sensitivity in
South African asthmatic children. S Afr Med J 1993;83:387-390.
14. Perusse R, Goulet JP, Turcotte JY. Contraindications to vasoconstrictors
in dentistry: Part II. Hyperthyroidism, diabetes, sulfite sensitivity,
cortico-dependent asthma, and pheochromocytoma. Oral Surg Oral Med Oral
Pathol. 1992 Nov;74(5):687-91.
15. Fisher AA. Reactions to injectable local anesthetics. Part IV: Reactions
to sulfites in local anesthetics. Cutis. 1989 Oct;44(4):283-4.
16. Jamieson DM, Guill MF, Wray BB, May JR. Metabisulfite sensitivity:
case report and literature review. Ann Allergy. 1985 Feb;54(2):115-21.
17. Miltgen J, Marotel C, Natali F, Vaylet F, L'Her P. [Clinical aspects
and diagnosis of sulfite intolerance. Apropos of 9 patients] Rev Pneumol
18. Bush RK, Zoratti E, Taylor SL. Diagnosis of sulfite and aspirin
sensitivity. Clin Rev Allergy. 1990 Summer-Fall;8(2-3):159-78.
Questions (For South African dietitians only. Australian
dietitians: where you have relevant learning goals, CPD hours related
to this resource can be included in your APD log.)
You can obtain 2 CPD points for reading
this newsletter and answering the accompanying questions. This
newsletter with questions has been accredited for dietitians.
CPD reference number: DT
HOW TO EARN YOUR CPD POINTS
1. Complete your personal details below.
2. Read the newsletter and answer the questions.
3. Indicate your answers to the questions by making a "X"
in the appropriate block.
4. You will earn 2 CPD points if you answer more than 75% of the
questions correctly. If you score is between 60 and 75%, 1 CPD
point will be allocated. A score of less than 60% will unfortunately
not earn you any CPD points.
5. Make a photocopy for your own records in case your answers
do not reach us.
6. Cut and paste the area indicated below into a e-mail message
and e-mail it to firstname.lastname@example.org
to be received no later than 29 February 2004. Answer sheets received
after this date will not be processed.
ALL THE QUESTIONS
(There is only
one correct answer per question.)
1. Which of the following is the active component that preserves a product?
(b.) Sulfur dioxide
(c.) Sulfurous acid
(d.) Inorganic sulfite salts
2. Which of the
following is not a well-known function of sulfites in the food industry?
3. Which of the
following is not true regarding sulfite-sensitive asthmatics?
(a.) Reactions can be severe and potentially life threatening.
(b.) Steroid-dependent asthmatics are at greater risk of experiencing
a reaction to sulfite-containing foods.
(c.) A far lower dose of inhaled sulfites is required to induce a reaction,
compared to ingested sulfites.
(d.) Sulfite-containing drugs do not affect asthmatics.
4. Which of the
following is seen as a possible mechanism of action of sulfite-sensitive
(a.) IgE-mediated reaction
(b.) Sulfite-oxidase deficiency
(c.) Cholinergic-reflex mechanism
(d.) All of the above
5. True or false:
The onset of an adverse reaction after exposure to sulfites through
inhalation, intravenous injection or ingestion of solutions is usually
rapid, occurring immediately or within 1-5 minutes.
6. True or false:
When sulfites are taken in capsule form or mixed with food, the onset
is generally longer (averaging 15-30 minutes).
7. Which of the
following is suggested as the preferred diagnostic tool for sulfite
(a.) Blood test
(b.) Skin prick test
(c.) Open challenge
(d.) Double-blind placebo-controlled challenge
8. True or false:
Sulfite-sensitive individuals should avoid all foods that contain even
a small amount of sulfite.
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