Soy Allergens: Shock of the New
By Kaayla Daniel, Ph.D, CNN
Author of The Whole Soy Story

Soy is one of the top allergens.
 
In the 1980s, Stuart Berger, MD, labeled soy one of the seven top allergens -- one of the "sinister seven." At the time, most experts listed soy around tenth or eleventh. Bad enough, but way behind peanuts, tree nuts, milk, eggs, shellfish, fin fish and wheat. Today soy is widely accepted as one of "the big eight" that cause immediate hypersensitivity reactions.
 
Food allergies are abnormal inflammatory responses of the immune system to dust, pollen, a food or some other substance. Those that involve an antibody called immunoglobulin E (IgE) occur immediately or within an hour. Reactions may include coughing, sneezing, runny nose, hives, diarrhea, facial swelling, shortness of breath, a swollen tongue, difficulty swallowing, lowered blood pressure, excessive perspiration, fainting, anaphylactic shock or even death.
 
Delayed allergic responses to soy are less dramatic, but are even more common. These are caused by antibodies known as immunoglobulins A, G or M (IgA, IgG or IgM) and occur anywhere from two hours to days after the food is eaten. These have been linked to sleep disturbances, bedwetting, sinus and ear infections, crankiness, joint pain, chronic fatigue, gastrointestinal woes and other mysterious symptoms.
 
Food "intolerances", "sensitivities" and "idiosyncrasies" to soy are commonly called "food allergies", but differ from true allergies in that they are not caused by immune system reactions but by little-understood or unknown metabolic mechanisms. Strictly speaking, gas and bloating, common reactions to soy and other beans are not true allergic responses. However, they might serve as warnings of the possibility of a larger clinical picture involving allergen-related gastrointestinal damage.
 
PROFIT vs RISK
The soybean industry knows that some people experience severe allergic reactions to its products. In a recent petition to the Food and Drug Administration (FDA), Protein Technologies International (PTI) identified "allergenicity" as one of the "most likely potential adverse effects associated with ingestion of large amounts of soy products." Yet PTI somehow concluded that "the data do not support that they would pose a substantial threat to the health of the US population."
 
This statement is hardly reassuring to the many children and adults who suffer allergies to soy products. And it ignores a substantial body of evidence published during the 1990s showing that some of these people only learn for the first time about their soy allergies after experiencing an unexpectedly severe or even life-threatening reaction. Although severe reactions to soy are rare compared to reactions to peanuts, tree nuts, fish and shellfish, Swedish researchers recently concluded, "Soy has been underestimated as a cause of food anaphylaxis".
 
A BAD HAMBURGER
The Swedes began looking into a possible soybean connection after a young girl suffered an asthma attack and died after eating a hamburger that contained only 2.2 percent soy protein. A team of researchers collected data on all fatal and life-threatening reactions caused by food between 1993 and 1996 in Sweden, and found that the soy-in-the-hamburger case was not a fluke, and that soy was indeed the culprit. They evaluated 61 cases of severe reactions to food, of which five were fatal, and found that peanut, soy and tree nuts caused 45 of the 61 reactions. Of the five deaths, four were attributed to soy.
 
The four children who died from soy had known allergies to peanuts but not to soy. The amount of soy eaten ranged from one to ten grams -- typical of the low levels found when soy protein is used as a meat-extending additive in readymade foods such as hamburgers, meatballs, spaghetti sauces, kebabs, sausages, bread and pastries.
 
When soy is "hidden" in hamburgers and other "regular" foods, people often miss the connection to soy. And allergic reactions to soy do not always occur immediately, making cause and effect even harder to establish. As reported in the Swedish study, no symptoms -- or very mild symptoms -- occurred for 30 to 90 minutes after the consumption of the food containing soy. Then, the children suffered fatal asthma attacks. All had been able to eat soy without any adverse reactions right up until the dinner that caused their deaths.
 

 
If your child is allergic to peanuts, you must eliminate all soy as well as all peanuts from your child's diet. Your child's life may depend upon it.
 
Take care even if your child has never reacted poorly to soy in the past. Some sensitive children have "hidden" soy allergies that manifest for the first time with a severe -- even fatal -- reaction to even the low levels of "hidden" soy commonly found in processed food products. Those at the highest risk suffer from asthma as well as peanut allergy. Other risk factors are other food allergies; a family history of peanut or soy allergies; a diagnosis of asthma, rhinitis or eczema; or a family history of these diseases.
 
SOURCE: Swedish National Food Administration.
 
The Swedish study was not the first study to report "fatal events" after eating soy. Food anaphylaxis is most often associated with reactions to peanuts, tree nuts, shellfish -- occasionally fish or milk -- but soy has its own rap sheet. Anaphylactic reactions to bread, pizzas or sausage extended with soy protein date back at least to 1961. Subsequent studies have confirmed that the risk may be rare but is very real.
 
The increasing amount of "hidden" soy in the food supply is undoubtedly responsible for triggering many allergic reactions not attributed to soy. French researchers who studied the frequency of anaphylactic shocks caused by foods reported that the food allergen remained unknown in 25 percent of cases. They noted the prevalence of "hidden" and "masked" food allergens and stated that they saw "a strikingly increased prevalence of food-induced anaphylactic shock in 1995 compared to a previous study from 1982". This period coincided with a huge increase in the amount of soy protein added to processed foods.
 
None of these studies has attracted much media attention. Nor have health agencies issued alerts. For example, Ingrid Malmheden Yman, Ph.D, of the Swedish National Food Administration and coauthor of the study, wrote to the Ministry of Health in New Zealand at the request of an allergy sufferer Two years before the article -- first published in Swedish -- came out in English, she informed the agency that children with severe allergy to peanut should avoid intake of soy protein. To be on the safe side she further advised parents to make an effort to "avoid sensitization" by limiting both peanuts and soybeans during the third trimester of pregnancy, during breast feeding, and by avoiding the use of soy formula.
 
Controversy has raged since the 1920s as to whether or not babies could be sensitized to allergens while still in utero. In 1976, researchers learned that the fetus is capable of producing IgE antibodies against soy protein during early gestation and newborns can be sensitized through the breast milk of the mother and later react to foods they've "never eaten". Families who would be well advised to take these precautions seriously include those with individuals who have known peanut and/or soy allergies, vegetarians who would otherwise eat a lot of soy foods during pregnancy or lactation and parents considering the use of soy infant formula.
 
Because the numbers of children with allergies to peanuts are increasing, we can expect to see greater numbers of children and adults reacting severely to soy. Peanuts and soybeans are members of the same botanical family, the grain-legume type and scientists have known for years that people allergic to one are often allergic to the other. Other children at risk for an undetected but potentially life-threatening soy allergy include those with allergies to peas, lima beans or other beans, a diagnosis of asthma, rhinitis, eczema or dermatitis, or family members with a history of any of those diseases. Reactions to foods in the same botanical family can be cumulative, resulting in symptoms far more severe than either alone.
 
SOY'S ALLERGENIC PROTEINS
Scientists are not completely certain which components of soy cause allergic reactions. They have found at least 16 allergenic proteins, and some researchers pinpoint as many as 25 to 30. Laboratories report immune system responses to multiple fractions of the soy protein, with no fraction the most consistently antigenic.
 
Some of the most allergenic fractions appear to be the Kunitz and Bowman-Birk trypsin inhibitors. As we saw in Chapter 12, food processors have tried in vain to completely deactivate these troublesome proteins without irreparably damaging the remainder of the soy protein. Having failed to accomplish this, the soy industry has decided to promote these "antinutrients" as cancer preventers. To date their proof remains slim, although cancer statistics might improve if enough people died from anaphylactic shock first. Although extremely rare, death from allergic reaction to trypsin inhibitor has been matter of public record since the New England Journal of Medicine carried a report in 1980. The Kunitz trypsin inhibitor has been identified as one of three allergic components in soy lecithin, a soy product often considered hypoallergenic because it is not supposed to include any soy protein, but invariably contains trace amounts.
 
The soybean lectin -- another anti-nutrient now promoted as a disease preventer -- has also been identified as an allergen. As we discussed in Chapter 14 , whenever there is damage to the intestinal lining, the "leaky gut" syndrome, soy lectins can easily pass into the bloodstream, triggering allergic reactions, Indeed, this is very likely because both soy allergens and saponins, another antinutrient (see Chapter 15) are known to damage the intestines.
 
Histamine toxicity can also resemble allergic reactions. In allergic persons, mast cells release histamine, causing a response that strongly resembles an allergic reaction to food. In cases of histamine toxicity, the histamine comes readymade in the food. This is most often associated with reactions to cheese and fish, but soy sauce also contains high levels of histamine. Researchers who have calculated the histamine content of foods consumed at a typical oriental meal report that histamine intake may easily approach toxic levels.
 
PROCESSING MATTERS
The way that the soybean is grown, harvested, processed, stored and prepared in the kitchen can all affect its allergencity.
 
Raw soybeans are the most allergenic while old-fashioned, fermented products (miso, tempeh, natto, shoyu and tamari) are the least. Modern soy protein products processed by heat, pressure and chemical solvents lose some of their allergenicity, but not all. Partially hydrolyzed proteins and soy sprouts, which are quickly or minimally processed, remain highly allergenic.
 
The industry newsletter The Soy Connection states that highly refined oils and lecithin "are safe for the soy-allergic consumer." Unfortunately, many allergic persons who have trusted such reassurances have ended up in the hospital. Highly susceptible people cannot use either safely. Adverse reactions to soy oils -- taken either by mouth as food or via tube feeding -- range from the nuisance of sneezing to the threat of anaphylactic shock.
 
If soy oil and lecithin were 100 percent free of soy protein, they would not be able to provoke allergic symptoms. Variable conditions, quality control and processing methods used when the vegetable oil industry separates soy bean protein from the oil make the presence of at least trace amounts of soy protein possible, even likely. Though healthier in many respects, the cold pressed soy oils sold in health food stores can be deadly for the allergic consumer. They may contain as much as 100 times the amount of trace protein found in the highly refined soy oils sold in supermarkets.
 
Soy protein is likely to appear in margarine. Above and beyond any stray protein that remains after the processing of the soy oil, food manufacturers commonly use soy protein isolates or concentrates to improve the texture or spreadability of these products. This occurs most often in low-fat or "low trans" products. (See Chapter 6.)
 
HIDDEN DANGER
People allergic to soy protein face danger 24/7. Hidden soy exists in thousands of everyday foods, cosmetics and industrial products such as inks, cardboards, paints, cars, and mattresses. The four Swedish fatalities are only the best known of thousands of reported cases of people who experienced severe allergic reactions to soy after inadvertently eating foods that contained soybean proteins. Of 659 food products recalled by the US Food and Drug Administration (FDA) in 1999, 236 (36 percent) were taken off the market because of undeclared allergens. The three factors responsible for the undeclared allergens were: omissions and errors on labels (51 percent), cross contamination of manufacturing equipment (40 percent), and errors made by suppliers of ingredients (5 percent). It wasn't inspectors, however, but U.S. consumers who fingered 56 percent of the undeclared allergens and alerted the FDA after experiencing adverse reactions.
During 2002, the Canadian Food Inspection agency (CFIA), which takes soy allergies seriously, has recalled bagels, donuts, rolls, pizza and other items containing undeclared soy protein. Although agencies in many countries claim to be stepping up efforts to enforce labeling laws, enforcement is difficult even when officials make it a priority. The chief problem is that few methods reliably detect and quantify minute amounts of allergens in foods.
 
Even when soy-containing ingredients are accurately listed on food labels, consumers may easily miss the soy connection. A study of 91 parents of children allergic to peanuts, milk, egg, soy, and/or wheat revealed that most parents failed to correctly identify allergenic food ingredients, and that milk and soy presented the most problems. Only 22 percent of the parents with soy allergies correctly identified soy protein in seven products. The researchers concluded: "These results strongly support the need for improved labeling with plain-English terminology and allergen warnings as well as the need for diligent education of patients reading labels.
 
CLEARING THE AIR
Allergic reactions occur not only when soy is eaten but when soybean flour or dust is inhaled. Among epidemiologists, soybean dust is as known an "epidemic asthma agent. From 1981-1987, soy dust from grain silo unloading in the harbor caused 26 epidemics of asthma in Barcelona, seriously affecting 687 people and leading to 1,155 hospitalizations. No further epidemics occurred after filters were installed, but a minor outbreak in 1994 established the need for monitoring of preventive measures. Reports of the epidemic in Barcelona led epidemiologists in New Orleans to investigate cases of epidemic asthma that occurred from 1957 -1968 when more than 200 people sought treatment at a Charity Hospital. Investigations of weather patterns and cargo data from the New Orleans harbor identified soy dust from ships carrying soybeans as the probable cause. No association was found between asthma-epidemic days and the presence of wheat or corn in ships in the harbor. The researchers concluded: "The results of this analysis provide further evidence that ambient soy dust is very asthmogenic and that asthma morbidiy in a community can be influenced by exposures in the ambient atmosphere".
 
The first report of "occupational asthma" appeared in the Journal of Allergy in 1934. W. W. Duke described six persons whose asthma was triggered by dust from a nearby soybean mill and predicted that in the future soy could become a major cause of allergy. Today it is well established that soybean dust is an occupational hazard of working in bakeries, animal feed factories, food processing plants and health food stores and co-ops with bulk bins. Most victims develop their "occupational asthma" over a period of time. In one well-documented case, a 43-year old woman spent six years working in a food processing plant in which soybean flour was used as a meat extender before developing asthma. Symptoms of sneezing, coughing and wheezing would begin within minutes of exposure to soy flour and resolve two hours after the exposure cased.
 
Rare reactions to soy have also occurred to asthmatic patients using inhalers with bronchodilators containing soy-derived excipients. Bronchospasms with laryngospasms and cutaneous rash have occurred even in patients who were otherwise not affected by soy allergy.
 
SOY INFANT FORMULA
For years the soy industry billed soy formula as "hypoallergenic." Herman Frederic Meyer, MD, Department of Pediatrics, Northwestern University Medical School, categorized soy formulas as "hypo-allergic preparations"in his 1961 textbook Infant Foods and Feeding Practice and named Mull Soy, Sobee, Soyalac and Soyola products as good examples. Over the years the soy industry has promoted this and similar misinformation in advertising, labels and educational literature by ignoring relevant studies in favor of largely irrelevant studies based on guinea pigs. As late as 1989, John Erdman, Ph.D. -- a researcher honored in 2001 by the soy industry for his "outstanding contributions to increasing understanding and awareness of the health benefits of soy foods and soybean constituents" -- still claimed "hypoallergenicity" for soy in the American Journal of Clinical Nutrition. A subsequent Letter to the Editor corrected his misinformation.
 
FUDGING STATISTICS
The soy industry today has shifted from claiming hypoallergenicity for soy to minimizing its extent. That has been fairly easy, for no one seems to know quite how many sufferers there are. Estimates are rough at best because diagnoses of allergy include anything from parental complaints of spitting, fussiness, colic and vomiting to laboratory provings using RAST and ELISA tests, to clinical challenges and elimination diets. Because the tests are not completely reliable and anecdotal evidence tends to be taken lightly, many cases are not counted. The figures cited most often delineate 0.3 to 7.5 percent of the population as allergic to cow's milk and 0.5 to 1.1 percent as allergic to soy. However, evidence suggests that soy protein is at least as antigenic as milk protein, especially when gastrointestinal complaints and delayed hypersensitivity (non-IgE) reactions are taken into account.
 
On the soy-industry website "Soy and Human Health," Clare Hasler, Ph.D., of the University of Illinois Urbana, Champaign, picks the low 0.5 percent figure and claims that soy protein is rated 11th among foods in terms of allergenicity. This may have been true in the 1970s (her source is dated 1979), but soy is widely acknowledged as one of the "big eight" today. Indeed, one prominent researcher puts soy in the top six and another in the top four foods causing hypersensitivity reactions in children.
 
Soy formula is a far from optimal solution for bottle-fed infants who are allergic to dairy formulas. As we will see in Chapter 22 and 23, the plant estrogens in soy can interfere with proper development of the infant's thyroid, brain and reproductive systems. Soy formula also falls short as a solution to a cow's milk allergy. Symptoms such as diarrhea, bloating, vomiting and skin rashes sometimes go away when infants are switched from dairy formula to soy, but the relief is usually only temporary. In many infants they return with a vengeance within a week or two. As Dr. Stefano Guandalini , Department of Pediatrics, University of Chicago, writes, "A significant number of children with cow's milk protein intolerance develop soy--protein intolerance when soy milk is used in dietary management". Interestingly enough, researchers recently detected and identified a soy protein component that cross reacts with caseins from cow's milk. Cross reactions occur when foods are chemically related to each other.
 
Matthias Besler of Hamburg, Germany, and an international team of allergy specialists report on the website www.allergens.de that adverse reactions caused by soybean formulas occur in at least 14 to 35 percent of infants allergic to cow's milk.
 
On another valuable allergy website www.medicine.com Dr. Guandalini reports the results of an unpublished study of 2108 infants and toddlers in Italy, of which 53 percent of the babies under three-months old who had reacted poorly to dairy formula also reacted to soy formula. Although experts generally attribute this high level of reactivity to the immature -- hence vulnerable -- digestive tract of infants, this study showed that 35 percent of the children over one-year old who were allergic to cow's milk protein also developed an allergy to soy protein. In all, 47 percent had to discontinue soy formula.
 
Infants who are allergic to dairy formulas are allergic to soy formulas so often that researchers have begun advising pediatricians to stop recommending soy and start prescribing hypoallergenic hydrolyzed casein or whey formulas. A study of 216 infants at high risk for developing allergies revealed comparable levels of eczema and asthma whether they were drinking cow's milk formula or the more "hypoallergenic" soy formula. Upon conclusion of the study, the message was clear. Only "exclusive breast feeding or feeding with a partial whey hydrolysate formula is associated with the lower incidence of atopic disease and food allergy. This is a cost-effective approach to the prevention of allergic disease in children".
 
No one can make a good argument that soy formula is hypoallergenic, but many still say that its soy proteins may be less sensitizing than cow's milk proteins. When babies develop soy intolerance, the blame tends to go to earlier damage done to the intestines by cow's milk protein. This has led some physicians to recommend starting infants off from birth on soy formula. This does not stop a tendency to develop food allergies. As C. D. May, Department of Pediatrics, National Jewish Hospital and Research Center in Denver, put it: "Feeding a soy product from birth for 112 days did not prevent a brisk antibody response to cow milk introduced subsequently, comparable to or greater than the antibody response seen when cow milk products were fed from birth.
 
BOWELED OVER
Children diagnosed with "allergic colitis" suffer from bloody diarrhea, ulcerations and tissue damage, particularly to the sigmoid area of the descending colon. The leading cause in infants is cow's milk allergy, but 47 to 60 percent of those infants react the same way to soy formula. Curiously, inflammatory changes in the mucus lining of the intestines.appear even in infants who seem to be tolerating soy -- no diarrhea, no hives, blood in the stool or other allergic signs. One study showed that clinical reactions occurred in 16 percent of the children on soy formula, but that histological and enzymologic intestinal damage occurred in an additional 38 percent of the children. This second group showed damage to the intestinal cells and tissues as viewed under a microscope and through blood tests indicating increased levels of xylose, an indigestible sugar used to diagnose "leaky gut" and other intestinal disorders. The researchers also found depleted levels of sucrase, lactase, maltase, and alkaline phosphatase -- evidence that the infants' digestive capacity was compromised, their stress levels increased, and immune systems challenged.
 
Most gastrointestinal problems connected to soy formula involve non-IgE delayed immune reactions. However, local IgE reactions may contribute to these problems by triggering the formation of immune complexes that alter the permeability of the gut mucosa. As C Carini, the lead author in an Annals of Allegy study, wrote, "The resultant delayed onset symptoms could be viewed as a form of serum sickness with few or many target organs affected".
 
The baby's small intestine is at special risk. Scanning electron microscopy and biopsies have revealed severe damage to the small intestine, including flattening and wasting away of the projections (known as villi) and cellular overgrowth of the pits (known as crypts). Allergic reaction may not be the sole cause here as the observed destruction dovetails with that caused by soy antinutrients known as lectins and saponins, with the lectins possibly doing double duty as allergic proteins. (See Chapter14). Villi are the projections clustered over the entire mucous surface of the small intestine where nutrient absorption takes place. Flattening and atrophy of the villi lead to malnutrition and failure to thrive, with a clinical picture very similar to that found in children and adults afflicted with celiac disease.
 
Celiac disease is a serious malabsorption syndrome most commonly associated with gluten (a protein fraction found in wheat and some other grains) and dairy intolerance. Few people know that there is also a connection with soy. Some adults with celiac disease experience diarrhea, headache, nausea and flatulence even on a gluten-free diet when they eat a tiny amount of soy. And a study of 98 infants and children with multiple gastrointestinal allergies revealed that 62 percent had both soy and milk allergies and 35 percent both soy and gluten.
 
OUTGROWING SOY ALLERGIES
Allergy specialists say that "most" young children "outgrow" their sensitivities. This makes sense-- to a point. If infants develop soy allergies because of immature digestive tracts and immune systems, the risk of developing a soy allergy would decrease with age and many children would outgrow their soy allergies. Yet other studies -- even by the same authors -- reveal that only a minority of subjects outgrow them.
 
One study showed that 26 percent of children suffering from soy, egg, milk, wheat and peanut allergies lose their hypersensitivity after one year. While peanut -- soy's even more allergenic relative -- may have skewed those results, another study found that only two out of eight infants outgrew soy allergies after 25 months. And many children who "successfully" outgrow food allergies develop respiratory allergies. A study of 322 children showed that only six percent still experienced food sensitivity after five years, but 40 percent of those children "grew into" respiratory allergies. This was true of milk, egg, chocolate, soy and cereals, in that order. Yet this study is often cited as proof that "most" children "successfully" outgrow their allergies.
 
Children are more likely to outgrow allergies to cow's milk or soy than allergies to peanuts, fish or shrimp, but will continue to react to them if they these foods often enough. And treatment of these allergies requires total exclusion of the offending food. Soy-induced enterocolitis, for example, will resolve after six months to two years of strictly avoiding soy. As families of allergic youngsters know, keeping soy off the dinner table and out of the snacks provided at daycare centers and schools can be challenging. Even in non-vegetarian families, soy is ubiquitous in the processed food supply. As a result, sensitization to soy has increased, is not necessarily outgrown, and can either reemerge or develop later in life.
 
SHOCK OF THE NEW
Evidence is mounting that soy allergies are on the rise because of genetic engineering.
 
The York Nutritional Laboratories in England --one of Europe's leading laboratories specializing in food sensitivity -- found a 50 percent increase in soy allergies in 1998, the very year in which genetically engineered beans were introduced to the world market. York's researchers noted that one of the 16 proteins in soybeans most likely to cause allergic reactions was found in concentrations higher by 30 percent or more in Monsanto's genetically modified (GM) soybeans. The York researchers sent their findings to British Health Secretary Frank Dobson, urging the government to act on the information and impose an instant ban on GM food pending further safety tests. Dr. Michael Antonion, a molecular pathologist at Guy's Hospital, Central London, observed, "This is a very interesting if slightly worrying development. It points to the fact that far more work is needed to assess their safety. At the moment, no allergy tests are carried out before GM foods are marketed and that also needs to be looked at".

People allergic to GM soybeans may not even be allergic to soy. The culprit can be foreign proteins introduced into the soybean. People allergic to Brazil nuts but not to soy have shown allergies to GM soybeans in which Brazil nut proteins were inserted to increase the level of methionine and improve the overall amino acid profile of soy. Scientists say that such problems can be prevented by doing IgE-binding studies, by accounting for physico-chemical characteristics of proteins and referring to known allergen databases. That might have identified the Brazil nut problem, but there is no way to assess the risk of de novo sensitization, which happens when experiments generate new allergens.
 
For more information, and a complete list of sources and references, please read The Whole Soy Story.

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