Questions and Answers Regarding Health Canada's Proposal to Amend the Food and Drug Regulations to Permit the Use of the Enzyme Asparaginase in Certain Food Products

Clarification of Information
Asparaginase and Human Health
Questions about Health Canada's Approach to Mitigating the Risks Posed by Acrylamide in Food by the Addition of Asparaginase to Food
Food Additive Regulation and Use in Canada
Questions about the On-line Proposal and Consultation
Informing the Public on Asparaginase Use in Foods
Other Questions

Health Canada's Bureau of Chemical Safety, Food Directorate, received hundreds of comments relating to the proposal to amend the Food and Drug Regulations to permit the use of the enzyme asparaginase in certain food products. The questions and answers below respond to the most common questions that were posed by members of the public, and also address some of the misconceptions and inaccuracies that were reported about Health Canada's proposal.

For more detailed information on certain subjects that relate to Health Canada's proposal to permit the use of asparaginase in certain foods, follow the hyperlinks that are provided in the text below.

Clarification of Information

Question 1. How does acrylamide get into food?

Answer 1. Acrylamide is not an intentionally or unintentionally added chemical contaminant in food. Health Canada scientists have investigated why some foods, especially certain fried foods, can have higher levels of acrylamide. They have shown that acrylamide is not present in any ingredient of these food items prior to cooking and is not a contaminant inadvertently added at any stage of food preparation. Rather, acrylamide forms from the interaction of natural components in plant-based foods when cooked at sufficiently high temperatures, and once formed cannot be removed from food. The amount of acrylamide that forms can vary depending on the properties of the food product and the method of cooking.

Question 2. Asparaginase is permitted as a therapeutic drug in Canada. Is Health Canada proposing to add a drug to some foods?

Answer 2. No. It is not possible for asparaginase, when used in food, to have a therapeutic effect on the human body. When used in food processing, asparaginase can only act on the food to which it has been added. Health Canada is proposing to add the enzyme asparaginase to certain foods in order to reduce the amount of the amino acid asparagine that is already naturally present in foods. Under specific cooking conditions, asparagine can react with certain carbohydrates in the food to form acrylamide, a potential human carcinogen. By reducing the amount of asparagine in the food prior to cooking or processing, the amount of acrylamide that can be formed will also be reduced.

The proposed use of asparaginase in food is very different from the therapeutic use of asparaginase for two key reasons. Firstly, small amounts of asparaginase are added to foods before they are cooked and the heat from cooking inactivates the asparaginase enzyme that is present. In addition, asparaginase is unstable under acidic conditions, such as those that exist in the stomach. Any small amount of the inactive enzyme that humans could ingest in food would be broken down in the acidic environment of the stomach and passed through the digestive system. In order to act as a chemotherapeutic agent, asparaginase must be in its active form to be effective and it must be injected into muscle or veins and not given orally. Inactive asparaginase, consumed as part of a food, would be digested in the stomach like other proteins (including other enzymes) in food and would not have any therapeutic effects on the body.

Question 3. Is Health Canada proposing to add asparaginase only to "junk food"?

Answer 3. No. Health Canada's proposal would allow the food additive use of asparaginase in such foods as bread, white and whole wheat flour, baked goods, French fries, potato chips, ready-to-eat breakfast cereals, and certain types of flavours called reaction flavours. While food manufacturers would not be required to use asparaginase, Health Canada has encouraged the food industry to find ways to reduce acrylamide levels in food.

Question 4. Is it common to use enzymes in food processing?

Answer 4. Yes. Enzymes are proteins that are naturally synthesized in the cells of plants, animals and microorganisms and are therefore minor components of many foods. Enzymes have been used in food processing for centuries. For example, rennet was discovered for its ability to coagulate milk and make cheese, while the enzymes in yeast ferment grape juice to make wine. Most of the enzymes that are used today by the food industry are isolated from microorganisms, some of which are genetically modified to optimize the production of the desired enzyme.

Question 5. Is Health Canada proposing to add a genetically modified organism to our foods?

Answer 5. No. The enzyme itself does not contain any genetically modified material; however the organism that produces asparaginase has been genetically modified. Health Canada received submissions for the possible food additive use of the enzyme asparaginase from two different genetically modified microorganisms. Before any enzyme is used in food processing, it is extracted from the source organism and purified.

Asparaginase and Human Health

Question 6. Has Health Canada conducted toxicity studies for asparaginase?

Answer 6. Health Canada does not conduct toxicity studies for food additive submissions from industry. Health Canada requires that industry undertake such studies and submit the outcomes for critical review by its scientists. Health Canada's scientists review all safety studies provided as part of the submission, as well as any available studies published in the scientific literature. If insufficient safety data or other deficiencies in the submitted data are identified, additional information or studies are requested by Health Canada. Health Canada will only consider making a regulatory amendment to permit the use of a food additive, under specified conditions, when Health Canada scientists are satisfied that the food additive is of suitable quality, is effective for the intended purpose, and does not pose a hazard to the health of the consumer.

Question 7. Are there any long-term toxicity studies in humans at the concentrations that would be used in foods.

Answer 7. Various toxicity studies were evaluated. Long-term toxicity studies in humans were not considered necessary in order to establish the safety of asparaginase when used as a food additive. This is because long-term exposure to asparaginase when used as a food additive is not possible. The enzyme is inactivated when the food to which it has been added is cooked; therefore, no active enzyme remains in food products when they are consumed. Further, the residual inactive asparaginase, as for any other protein, would be broken down by acid and digestive enzymes in the human gastrointestinal tract and eliminated through the digestive system.

Despite the fact that asparaginase is not absorbed into the body, various toxicity studies were evaluated. In one study, rats were fed the active form of asparaginase for up to 90 days at doses more than 500 times higher than the possible human exposure to inactive asparaginase. There were no adverse effects observed in that study or any of the other toxicological studies conducted, which included additional oral toxicity studies, a developmental toxicity study, and genotoxicity assays.

Along with the results of toxicological studies conducted in animals at high doses, additional information about the biological properties of the substance, the reactivity of the substance with cellular genetic material, and the metabolic breakdown of the substance were considered in the determination of safety.

Confidence in the conclusions of the safety assessment are increased when it is considered that asparaginase is only active during food processing and is inactivated by heat. Health Canada, health authorities in other countries, and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) have a high degree of confidence in the safety of the use of asparaginase in small amounts as anticipated by the proposed applications.

Question 8. Could asparaginase in food cause an allergic reaction or hypersensitivities?

Answer 8. It is very unlikely that the consumption of residual asparaginase in food would cause an allergic reaction or hypersensitivities. Based on an internationally accepted approach to determine the potential allergenicity of proteins (including enzymes), there was no evidence of any similarity between the asparaginase protein sequence with known toxins or food allergens. Furthermore, food allergens are typically resistant to heat and digestive enzymes. Asparaginase is susceptible to breakdown by both heat and digestion. Therefore, it is very unlikely that the consumption of asparaginase would cause an allergic reaction. This is supported by the lack of any reports of adverse allergic-type reactions from countries where the same asparaginase enzyme has already been approved for use.

Question 9. Have there been studies of possible chemical interactions between asparaginase and other natural or synthetic chemicals to which Canadians are exposed (e.g., food additives, medications, environmental contaminants)?

Answer 9. As for food processing enzymes in general, chemical reactions with asparaginase after it has been consumed in food by humans is considered very unlikely because asparaginase has already been inactivated by heat (cooking) and is then broken down in the gastrointestinal tract and metabolised like any other ingested protein.

Question 10. What are the breakdown products of asparagine and do they pose a risk to human health?

Answer 10. There are no health risks associated with the breakdown products of asparagine from the enzymatic reaction that takes place during food processing. Humans are regularly exposed to much higher levels of each breakdown product through the diet relative to the levels produced by the use of asparaginase. In food, asparaginase hydrolyzes asparagine to aspartic acid and ammonia, and can also react with glutamine to form glutamic acid. Aspartic acid and glutamic acid are naturally present in foods such as meat, poultry, fish and eggs. The majority of ammonia remaining in the final food products is converted to ammonium. The levels of ammonia and ammonium that are generated are very low and each is an important component of normal metabolic processes.

Question 11. Will there be guidelines to ensure that the asparaginase used in foods is inactivated by cooking?

Answer 11. Specific guidelines to ensure the inactivation of asparaginase during cooking are not necessary. The foods that would be permitted to contain asparaginase undergo heating before the food is consumed. The cooking temperatures that are required to make these foods edible are sufficiently high to inactivate asparaginase.

Question 12. Is asparagine an amino acid that is important to humans? Where will people obtain this amino acid if its levels in the proposed foods are reduced or eliminated through the use of asparaginase?

Answer 12. Asparagine is not required in the diet because the body can synthesize asparagine using compounds generated during normal metabolic processes. Nonetheless, there are numerous dietary sources of asparagine from both plant and animal proteins, such as asparagus, potatoes, whole grains, diary products, eggs, and seafood.

Question 13. Can the enzyme asparaginase affect amino acids in our body?

Answer 13. No. When added to the proposed foods, the enzyme asparaginase will only have an effect during the processing of the food. It cannot affect the human body. In the human body there is no exposure to the active form of asparaginase when ingested because it is deactivated by cooking and is broken down by acid and digestive enzymes in the gastrointestinal tract.

Question 14. Would the body mount an immune response against the inactivated asparaginase enzyme similar to the body's response to dead viruses in vaccines?

Answer 14. No. Unlike medicines or vaccines which are administered by intramuscular or subcutaneous injection into the body where the immune system can be stimulated to create antibodies, the consumption of residual inactivated asparaginase enzyme in food would not stimulate an immune response. The enzyme is broken down in the gastrointestinal tract by acid and digestive enzymes and metabolised like any other ingested protein.

Question 15. Would asparaginase help those that suffer from celiac disease, food sensitivities, and food allergies to tolerate more food products?

Answer 15. No. The purpose of using asparaginase in foods is to reduce the levels of acrylamide that form in certain carbohydrate-rich foods during cooking. Based on the current scientific evidence, reducing acrylamide levels in such foods would not help people with celiac disease, food sensitivities, or food allergies tolerate such foods.

Questions about Health Canada's Approach to Mitigating the Risks Posed by Acrylamide in Food by the Addition of Asparaginase to Food

Question 16. If Health Canada is so concerned about the formation of acrylamide in food, why is this the first time the public has heard about it?

Answer 16. Health Canada is committed to maintaining transparency and does this primarily by posting information on its website, through news releases, by direct responses to citizen inquiries, and through scientific publications. Since the discovery of acrylamide in foods by Swedish scientists in 2002, Health Canada has been making information on acrylamide in food, including its research and evaluation activities, available on its website (Acrylamide in Food). Furthermore, Health Canada's discovery of the major mechanism of formation of acrylamide in food was published in the Journal of Agricultural and Food Chemistry in 2003.

Question 17. Too many chemicals and enzymes are already added to foods - why is Health Canada proposing to add something else to our foods to counteract the effects of acrylamide for which there are no conclusive human health risks?

Answer 17. The Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) consider acrylamide a known carcinogen in experimental animals and have determined that the estimated intake of acrylamide from certain foods may be a human health concern. JECFA has called for strategies to reduce exposure to acrylamide. Health Canada scientists participated in the JECFA evaluations and concur with its recommendations. Further research on the human health effects of dietary exposure to acrylamide is required before the risks are fully understood, however these studies take years to complete. In the meantime, Health Canada is proactively responding to JECFA's recommendation to reduce exposure to foodborne acrylamide and has strongly encouraged the food industry to develop and implement acrylamide reduction strategies. Some food processors, in Canada and internationally, have adjusted their cooking instructions to ensure that acrylamide levels are reduced in their food products, whether prepared at home or in a restaurant. The use of asparaginase in food processing is another solution to reducing acrylamide that the food industry has proposed.

Question 18. Canadians have been consuming acrylamide for centuries without any known adverse health effects - why is Health Canada interested in reducing the acrylamide levels in foods now?

Answer 18. It is difficult to determine if our historic exposure to acrylamide in food has had a detrimental effect on human health. However, it is well-known that the Canadian diet has changed over the years to include more carbohydrate-rich foods that are baked or fried, thus Canadians' exposure to acrylamide has likely increased over time. Since acrylamide is a known carcinogen in laboratory animals, Health Canada is working proactively to reduce human exposure to acrylamide in food.

Question 19. Does Health Canada really think that adding asparaginase to certain foods is going to make a significant difference to the long-term health of Canadians?

Answer 19. Allowing for the addition of asparaginase to certain foods is considered one of several tools available to reduce exposure to acrylamide, including the continued promotion of a healthy diet in accordance with Health Canada's Eating Well with Canada's Food Guide. Health Canada's proactive efforts to reduce Canadians' exposure to foodborne acrylamide have the potential to make a significant positive impact on human health, particularly given that the Canadian diet continues to include foods that contain acrylamide.

Question 20. Would Health Canada be encouraging the consumption of "junk foods" by proposing to add asparaginase to them?

Answer 20. The proposed uses of asparaginase encompass some foods considered as "junk foods" (e.g., cakes, cookies, French fries, potato chips) but also staple foods such as bread, flour, and breakfast cereals. In Eating Well with Canada's Food Guide and other publications, Health Canada recommends, and will continue to do so, that the consumption of foods that are high in calories, fat, sugar, or salt should be limited.

Question 21. Why doesn't Health Canada use its resources to educate Canadians on healthy food and lifestyle choices?

Answer 21. Health Canada has spent significant resources over the last several years updating its publication, Eating Well with Canada's Food Guide, which includes information about healthy food and lifestyle choices. Health Canada, as well as the Public Health Agency of Canada, have created several websites that provide information about healthy living, such as: It's Your Health - Obesity and Tips to Get Active. Furthermore, in 2007 nutrition labelling became mandatory for all prepackaged foods using a Nutrition Facts table of specified content and format. Health Canada has also developed an on-line resource to help Canadians interpret and understand this table. In addition, the federal, provincial and territorial governments are working together on the Canadian Healthy Living Strategy.

Question 22. Why doesn't Health Canada eliminate "junk food" from the market and only allow the sale of whole foods?

Answer 22. Health Canada encourages Canadians to follow a healthy diet and make healthy lifestyle choices. In addition, Health Canada requires nutritional labelling on most prepackaged foods to help Canadians make informed food choices. However, Health Canada cannot force people to eat well nor can it control the products developed by food manufacturers, provided that foods that are available in Canada meet certain safety requirements. It is consumer demand that influences the market and the availability of a variety of food products.

Question 23. Why doesn't Health Canada tax unhealthy foods as a method to discourage their consumption?

Answer 23. Taxation of food products is not part of Health Canada's current mandate for food and nutrition. Rather, Health Canada works to promote healthy diet and lifestyle choices through a variety of initiatives (see Question 21).

Question 24. Will there be restrictions on marketing and advertising so that "junk foods" that contain asparaginase are not marketed as healthy foods?

Answer 24. Asparaginase will be included on the list of ingredients of most pre-packaged foods (see Question 37) but no claims related to reduced acrylamide formation will be made on the product label. Health Canada does not have control over the marketing and advertizing campaigns (e.g. print or televised media) of food manufacturers. However, Health Canada and the Canadian Food Inspection Agency do play a role in ensuring that food labels are accurate, are not misleading, and do not make false claims.

Question 25. Can acrylamide form in foods from other pathways besides the conversion of asparagine. Is Health Canada researching the other possible formation pathways?

Answer 25. Health Canada scientists were among the first to demonstrate how acrylamide forms in certain heat-processed foods - when the naturally occurring amino acid asparagine reacts with certain naturally occurring sugars such as glucose. This reaction only takes place when the temperature during food processing is sufficiently high; a temperature which varies depending on the properties of the product and the method of cooking. There is consensus amongst researchers that the reaction between asparagine and sugars described above is responsible for virtually all of the acrylamide formed during food processing. Only small amounts of acrylamide could form from other naturally occurring substances in foods through other chemical reactions.

Question 26. Instead of adding this enzyme directly to foods, why isn't this enzyme sold in packet or capsule form at the grocery store, drug store, and at fast food outlets?

Answer 26. In order to be effective in reducing acrylamide formation in foods, asparaginase needs to be added to carbohydrate-rich foods prior to cooking. Therefore, this would not be a suitable solution to reducing acrylamide formation if it were added to pre-cooked ready-to-eat foods obtained from the grocery store, restaurants, or fast food establishments. Asparaginase sold in packet or capsule form would only be a useful tool to reduce acrylamide exposure when used at home during the preparation of foods prior to them being cooked.

Food Additive Regulation and Use in Canada

Question 27. Is Health Canada simply accepting the decisions of other countries by proposing to allow asparaginase in certain foods?

Answer 27. No. Food additives that are not currently permitted in foods sold in Canada may be proposed for use by a petitioner by sending a food additive submission to Health Canada's Bureau of Chemical Safety, Food Directorate. This submission must contain detailed information about the additive, its proposed use, the results of safety tests, and information on its effectiveness for its intended use. Scientists from Health Canada then conduct a detailed and rigorous pre-market evaluation of the submission that focuses on safety. Health Canada's safety assessment of food additives is conducted independently of those of other countries. Only once Health Canada scientists are satisfied that the food additive is of suitable quality, is effective for the intended purpose, and does not pose a hazard to the health of the consumer, would Health Canada consider making a regulatory amendment to permit the use of the food additive under certain conditions within food for sale in Canada.

Question 28. Why do food additives need to be used in foods at all?

Answer 28. Food additives are used for a variety of functions and include colouring agents that give certain foods an appetizing appearance, anticaking agents that keep powders such as salt free-flowing, preservatives that prevent or delay undesirable spoilage in food such as cured meats, and certain sweeteners that are used to sweeten foods without appreciably adding to their caloric value. In addition to satisfying the requirements of the pre-market safety evaluation, petitioners must demonstrate to Health Canada that the proposed food additive is effective for its intended use.

Question 29. How will Health Canada ensure that food manufacturers will not add asparaginase to additional foods in the future?

Answer 29. To date, Health Canada has received two food additive submissions proposing the use of asparaginase in certain food products. If the food industry wishes to use asparaginase in additional foods in the future, another formal application, revision, and approval process would have to be undertaken and an amendment would need to be made to food additive tables in the Food and Drug Regulations.

Question 30. The proposal for the addition of asparaginase to certain foods would permit its use at a concentration consistent with "Good Manufacturing Practice" (GMP), which is not prescriptive. How will Health Canada regulate the actual levels of asparaginase that are used in foods?

Answer 30. All enzymes that are used as food additives in Canada, along with various other food additives, have a permitted maximum level of use that is consistent with GMP. The Food and Drug Regulations define GMP as the minimum amount of a food additive that is required to accomplish the technical effect for which the additive is intended. Since the use of enzymes or other food additives add to the food manufacturer's cost, there is no motivation on the part of the food manufacturer to add a greater concentration of a food additive than is necessary to achieve the desired technical effect.

Questions about the On-line Proposal and Consultation

Question 31. Who is the "petitioner"?

Answer 31. The "petitioner" is the company that is proposing to amend the Food and Drug Regulations to allow the use of asparaginase in certain food products. In the case of asparaginase, there are two different petitioners that have each developed a method of producing asparaginase from different microbiological source organisms. Health Canada's privacy and confidentiality policy does not permit the release of third party information, which includes company names.

Question 32. Are there patent numbers for the process of adding asparaginase to carbohydrate-rich foods. Can these be released to the public?

Answer 32. Health Canada does not consider patent numbers as part of its submission evaluation process and is therefore not aware of whether there are patent numbers associated with this process. As an aside, the Canadian Patents Database is available on-line.

Question 33. Is the method of purifying the enzyme from the fungal sources regulated? Is the isolated enzyme free from fungal toxins and in a pure form?

Answer 33. As with other food additives, Health Canada is responsible for conducting a pre-market safety assessment of enzymes intended for use in food processing. Furthermore, the asparaginase preparations proposed for use by both petitioners have been subject to toxicological testing and have proven to meet the internationally accepted specifications for enzyme preparations established by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) and the Food Chemicals Codex (FCC), which is published by the U.S. Pharmacopia.

Both JECFA and the FCC require that enzymes produced by microorganisms are made using a pure culture of source organisms under a controlled fermentation process and do not contain mycotoxins or other undesirable substances. The petitioners demonstrated that their isolated enzyme preparations met these requirements. It is the ongoing legal responsibility of the manufacturer to comply with these established standards to ensure the safety of their enzyme preparation.

Question 34. What do the units "ASNU" represent?

Answer 34. The units "ASNU" represent the activity of the enzyme. The activity of the enzyme is used to quantify the amount of enzyme. When asparaginase converts the L-asparagine into L-aspartate (aspartic acid) and ammonia, that chemical conversion is measured. One ASNU is the amount of enzyme that produces one micromole ammonia per minute under specific reaction conditions. Therefore, the amount of asparaginase added to food preparations is indicated by the amount of enzyme activity required for that particular food application.

Informing the Public on Asparaginase Use in Foods

Question 35. How can the public keep informed about Health Canada's activities relating to food safety and comment on these activities if they so wish?

Answer 35. Health Canada consults Canadians on proposed changes to the Food and Drug Regulations through the Government of Canada's official newspaper, the Canada Gazette, in particular Canada Gazette, Part I. Consultations may also take place through Health Canada's Food and Nutrition Consultation and Public Involvement websites. You can also subscribe to Health Canada's Food Additives e-Notice, Chemical Contaminants e-Notice, and Food Allergies e-Notice, free services that send subscribers information about regulatory and scientific developments relating to these subjects in Canada. Additionally, Health Canada's Food Directorate maintains a website that provides information about the Directorate's work and welcomes questions and comments from the public at any time.

Question 36. When will foods that contain asparaginase be sold on the Canadian market and will Health Canada disseminate this information to Canadians?

Answer 36. Once notification of the approval of a new food additive is published in Canada Gazette, Part II, food manufacturers may begin to use it in the foods for which it was approved by Health Canada. Asparaginase may be added to the approved foods at the discretion of the manufacturer and its use will not be mandated by Health Canada. Publication in Canada Gazette, Part II could take a considerable period of time from the closing date of this consultation. Health Canada recommends checking Canada Gazette, Part II for notification that asparaginase has been approved as a food additive in Canada. Citizens may also read the labels of prepackaged foods or contact food manufacturers directly to determine if their food products contain asparaginase.

Question 37. How will Health Canada ensure that Canadians can avoid consuming the enzyme asparaginase in their foods if they so choose?

Answer 37. All food additives are required to be labelled on the list of ingredients on pre-packaged foods according to requirements within the Food and Drug Regulations. There are, however, a few exceptions. Section B.01.009 of the Regulations lists certain foods, of which flour is one, for which ingredients and ingredient components are not required to be labelled. This means that if asparaginase has been added to flour and this flour is used as an ingredient in bread or any other bakery product, the ingredients of that flour, which would include asparaginase, would not have to be labelled on the final pre-packaged food (e.g., bread, rolls, cakes, and cookies). Flour sold at the retail level, however, would have to include asparaginase on its label if it contains this enzyme. A consumer would therefore be required to inquire with individual bakeries to determine if their product uses flour that contains asparaginase. The Canadian Food Inspection Agency (CFIA) oversees all food labelling issues that are not related to health and safety. A summary of the comments received by Health Canada in response to the public consultation have been shared with the CFIA and any additional comments about the labelling of asparaginase should be addressed to this Agency.

Question 38. How will the public know if asparaginase is used in foods purchased from fast food outlets and restaurants?

Answer 38. Individuals will need to inquire at the point of sale to determine if asparaginase is used in certain foods that are purchased from public food establishments.

Page details

Date modified:: 2010-08-16

Language selection

Search