Novel food information: Dyne-NAO

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• Background
• Introduction
• Development of the product
• Dietary exposure
• Chemical assessment
• Microbiology
• Nutrition
• Toxicological assessment
• Allergen assessment
• Conclusion

Background

Health Canada notified AceOne RS, Inc. that it has no objection to the use of Dyne-NAO^® as a food ingredient in meal replacement products at the maximum level of 7 g per serving. The Department conducted a comprehensive assessment of Dyne-NAO^® according to its Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based upon internationally accepted principles for establishing the safety of novel foods.

The following provides a summary of the notification from AceOne RS, Inc. on behalf of Dyne Bio Inc., and the evaluation by Heath Canada. This document contains no confidential business information.

Introduction

Dyne Bio Inc. has developed Dyne-NAO^® through an enzymatic hydrolysis of food grade agar, for use in meal replacement products. Dyne-NAO^® is composed of >90% carbohydrates, of which >69% is non-digestible (dietary fibre).

The Food and Nutrition Directorate has conducted the safety assessment according to its Guidelines for the Safety Assessment of Novel Foods. These guidelines are based on harmonization efforts with other regulatory authorities and reflect international guidance documents in this area (e.g., Codex Alimentarius). The assessment considered the development of Dyne-NAO^®, the specifications and manufacturing method, the intended use, nutritional composition, microbiological, chemical and toxicological information, as well as the presence of potential allergens. AceOne RS, Inc. has provided data to support that Dyne-NAO^® is safe for use as a food ingredient in Canada.

The Food and Nutrition Directorate has a legislated responsibility for the pre-market assessment of novel foods and novel food ingredients as detailed in Division 28 (Novel Foods) of Part B of the Food and Drug Regulations. Dyne-NAO^® is considered to be a novel food under the following part of the definition of novel foods: "(a) a substance, including a microorganism, that does not have a history of safe use as a food".

Development of the product

The starting material, agar, is derived from an edible, non-toxic, non-pathogenic red algae (Gelidium elegans). Dyne-NAO^® is manufactured by enzymatic hydrolysis of agar using β-agarase DagA derived from Streptomyces coelicolor A3(2) M22-2C43. Briefly, the red algae is washed with water and heat treated to form the agar solution and the β‐agarase DagA enzyme is added after the solution has cooled. This enzyme/agar mix is incubated for 16 h at 45°C and then the enzyme is heat inactivated. The solution containing the NAOs is purified by sequential filtration steps, which removes the enzyme, followed by concentrating, spray drying, and packaging.

The petitioner indicated that all substances used in the manufacture of Dyne-NAO^® are food grade, are of high purity, and/or meet their respective specifications set out in the most recent edition of either the Food Chemicals Codex (FCC) and/or the Combined Compendium of Food Additive Specifications established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). In addition, to ensure the quality of Dyne-NAO^®, several quality control check points are incorporated into the manufacturing process. Contamination checks are also conducted in the seed and production fermenters. All finished batches of Dyne-NAO^® undergo quality assurance testing to meet the product specifications prior to release.

The petitioner is responsible for ensuring that the use of any substances in the manufacture of Dyne-NAO^® do not result in a violation of section 4 of the Food and Drugs Act.

Dietary exposure

The petitioner used the US population-based data from the National Health and Nutrition Examination Survey (NHANES 2015-2018) to determine the estimated cumulative daily intakes of Dyne-NAO^® based on intake of the meal replacement food category and a use level of 7g/serving. On a per-user basis, which calculates the maximum potential intake by assuming that individuals are consuming only meal replacement products containing Dyne-NAO^®, the 90th percentile consumption of Dyne-NAO^® ranged from the lowest value of 5.17 g/day in children 2-5 years of age to the highest value of 14.73 g/day in males 19-99 years of age.

Chemical assessment

The petitioner provided analytical data for trace elements (arsenic, cadmium, lead, and mercury) in multiple batches of Dyne-NAO^® and reported low concentrations that were below the established specifications. The proposed use of Dyne-NAO^® is not expected to result in increased dietary exposure to these contaminants.

No food additives are used in the manufacture of Dyne-NAO^® and substances used in the growth and fermentation media are not expected to remain in the final ingredient.

No chemical food safety concerns were identified with the proposed use of Dyne-NAO^®.

Microbiology

The Dyne-NAO^® ingredient involves the use of a microbial β-agarase DagA enzyme derived from a non-transgenic bacterial strain, Streptomyces coelicolor A3(2) M22-2C43, and is classified as a Risk Group 1 (RG1) microorganism by the Public Health Agency of Canada. Risk Group 1 microorganisms are not associated with human disease. Therefore, this bacterial species is considered a non-pathogenic microorganism.

The genome of S. coelicolor A3(2) M22-2C43 was screened through a whole genome sequencing analysis to identify antibiotic resistance genes, and virulence genes. Based on the genes identified, the production strain harbours no virulence factors nor acquired antimicrobial resistance genes.

Microbiological analyses were conducted using five non-consecutive production lots of the finished product Dyne-NAO^® to demonstrate compliance with the set microbiological specifications and to confirm the absence of the β‐Agarase DagA enzyme in the finished product. No pathogenic bacteria have been detected in the finished Dyne-NAO^® product.

No microbial food safety concerns were identified with the proposed use of Dyne-NAO^®.

Nutrition

Dyne-NAO^® is composed of >90% carbohydrates, of which >69% is nondigestible (dietary fibre). Approximately half (>45%) of the carbohydrate content of Dyne-NAO^® is made up of neoagarotetrose (NA4) and neoagarohexose (NA6) at a ratio of 1.1~1.4. The remainder of the carbohydrates are higher molecular weight NAOs, and other smaller carbohydrates, including neoagarobiose (NA2). The preparation also consists of proximates (ash, moisture, crude protein, crude fat, ~9%) and naturally occurring minerals (<1.5%).

Based on the proposed use of Dyne-NAO^®, the intake levels of the minerals present in Dyne-NAO^® were reviewed in the context of the Dietary Reference Intake (DRI) values. The mineral intake from Dyne-NAO^® does not pose a nutritional safety concern.

It is well documented that the consumption of non-digestible carbohydrates has the potential to result in gastrointestinal symptoms such as bloating, belching, flatulence, and laxation^{Footnote 1}. While the likelihood of occurrence of gastrointestinal symptoms increases with the amount of non-digestible carbohydrates consumed, sensitivity can vary between individuals. In an unpublished randomized, double-blind, placebo controlled 12-week clinical study provided by the petitioner, gastrointestinal symptoms (gas and bloating) were reported by four individuals in the test group who were consuming 15 grams of Dyne NAO^® on one eating occasion. These gastrointestinal effects are characterized as transient and mild and not experienced by all consumers. These symptoms are consistent with the effects of other incompletely absorbed carbohydrates and are not considered to be a serious health or safety concern and are expected to resolve once consumption of the food has stopped, or a lower level is consumed.

No nutritional food safety concerns were identified with the proposed use of Dyne-NAO^®.

Toxicological assessment

Toxicological studies (acute, sub-chronic, genotoxicity) were submitted that followed the Organization for Economic Co-operation and Development (OECD) Test Guidelines for Chemicals and Principles of Good Laboratory Practice. Two unpublished randomized, double-blind placebo controlled clinical studies in adults were provided as supportive evidence of safety.

The acute toxicity of Dyne NAO^® in rats was low, with an LD50 of >15000 mg/kg body weight. A no observed adverse effect level (NOAEL) of 7500 mg/kg bw per day, the highest dose tested, was identified in the 90-day repeated dose oral (gavage) toxicity study in rats. No genotoxicity was observed in the available in vitro (i.e., Bacterial Reverse Mutation Test, Chromosome Aberration Test) and in vivo (i.e., Mammalian Erythrocyte Micronucleus Test) genotoxicity studies. Comparing the NOAEL from the 90-day repeated dose toxicity study in rats with the highest estimated daily intake (90th percentile) on a body weight basis, resulted in an adequate margin of exposure (MOE).

Two unpublished randomized, double-blind, placebo controlled clinical studies in adults consuming Dyne-NAO^® were also submitted. No serious adverse effects were reported in subjects that consumed 15 grams of Dyne NAO^® on one eating occasion per day, for 12 weeks.

Based on the available data, no toxicological concerns were identified with the proposed use of Dyne-NAO^®.

Allergen assessment

Almost all food allergens are proteins (FAO/WHO, 2001)^{Footnote 2}. Dyne-NAO^® is made up of >90% carbohydrates.

A search of the literature did not identify any reports of the source of the novel food (Gelidium elegans) as a potential food allergen.

Bioinformatics analyses conducted in accordance with international guidance for allergenicity considerations was submitted and confirmed a lack of homology of the β‐Agarase DagA enzyme used to manufacture the ingredient, with known food allergens.

Based on the available data, no allergenic concerns were identified for the proposed use of Dyne-NAO^®.

Conclusion

Health Canada's review of the information presented in support of the use of Dyne-NAO^® as a food ingredient in Canada does not raise any concerns related to food safety.

The assessment revealed that gastrointestinal symptoms such as gas, bloating, and belching, may be experienced by consumption of meal replacement products containing Dyne-NAO^®. These symptoms are consistent with the effects of other incompletely absorbed carbohydrates, are characterized as mild, transient, and not experienced by all consumers. Therefore, they are not considered to pose a significant health or safety concern.

Health Canada's opinion refers only to the food use of Dyne-NAO^® as an ingredient in meal replacement products at the level specified.

This Novel Food Information document has been prepared to summarize the opinion regarding the subject product provided by the Food Directorate, Health Products and Food Branch, Health Canada. This opinion is based upon the comprehensive review of information submitted by the petitioner according to the Guidelines for the Safety Assessment of Novel Foods.

For further information, please contact:

Novel Foods Section
Food and Nutrition Directorate
Health Products and Food Branch
Health Canada, PL2204A1
251 Frederick Banting Driveway
Ottawa, Ontario K1A 0K9

Email: bmh-bdm@hc-sc.gc.ca