Agency Response Letter GRAS Notice No. GRN 000413
CFSAN/Office of Food Additive Safety
August 10, 2012
Mr. Edward A. Steele
EAS Consulting Group, LLC
1940 Duke Street, Suite 200
Alexandria, VA 22314
Re: GRAS Notice No. GRN 000413
Dear Mr. Steele
The Food and Drug Administration (FDA) is responding to the notice, dated December 5, 2011, that you submitted on behalf of Super Beta Glucan, Inc. (Super Beta Glucan) in accordance with the agency’s proposed regulation, proposed 21 CFR 170.36 (62 FR 18938; April 17, 1997; Substances Generally Recognized as Safe (GRAS); the GRAS proposal). FDA received the notice on January 9, 2012, filed it on January 11, 2012, and designated it as GRAS Notice No. GRN 000413. In a letter dated June 13, 2012, Super Beta Glucan limited the intended use of the ingredient to those foods described in the following paragraph.
The subject of the notice is β-glucans derived from Ganoderma lucidum mycelium (β-glucans derived from G. lucidum mycelium).1 The notice informs FDA of the view of Super Beta Glucan that β-glucans are GRAS, through scientific procedures, for use as an ingredient in baked goods and baking mixes, beverages and beverage bases, cereal and cereal products, dairy product analogs, milk and milk products, plant protein products, processed fruits and fruit juices, and soft candy at a level of 150 milligrams (mg) β-glucans derived from G. lucidum mycelium per serving. Super Beta Glucan notes that β-glucans are not intended for foods that have a standard of identity.
Our use of “β-glucans derived from G. lucidum mycelium” in this letter should not be considered an endorsement or recommendation of that term as an appropriate common or usual name for the purpose of declaring the substance in the ingredient statement of foods that contain that ingredient. Title 21 CFR 101.4 states that each ingredient must be declared by its common or usual name. In addition, 21 CFR 102.5 outlines general principles to use when establishing common or usual names for nonstandardized foods. Issues associated with labeling and the appropriate common or usual name of a food are the responsibility of the Office of Nutrition, Labeling, and Dietary Supplements (ONLDS) in the Center for Food Safety and Applied Nutrition.
As part of its notice, Super Beta Glucan includes a statement from a panel of individuals (Super Beta Glucan’s GRAS panel) who evaluated the data and information that are the basis for Super Beta Glucan’s GRAS determination. Super Beta Glucan considers the members of its GRAS panel to be qualified by scientific training and experience to evaluate the safety of substances added to food. Super Beta Glucan’s GRAS panel considered the identity and source of SuperBeta Glucan’s β-glucans product and similarities to other β-glucans that were the subject of prior GRAS notices to FDA. Super Beta Glucan’s GRAS panel evaluated estimates of dietary exposure, method of production, and product specifications as well as published and unpublished studies. Based on this review, Super Beta Glucan’s GRAS panel concluded that β-glucans that meets its established food grade specifications is GRAS under the conditions of its intended use.
Super Beta Glucan describes the identity and composition of β-glucans derived from G. lucidum mycelium. The ingredient is obtained from the cultured mycelium of G. lucidum (ATCC 32472). The ingredient is described as a water soluble, fine, light-beige colored powder. The β-glucans derived from G. lucidum mycelium ingredient is composed of β-glucans (> 50%) and a total carbohydrate content of over 95%.2 The chemical formula for β-glucan is poly-(1-6)-β-D-glucopyranosyl-(1,3)-β-D- glucopyranose, and consists of a β(1,3)-linked glucose backbone with short β(1,6)-linked branches. Super Beta Glucan describes the manufacturing process for β-glucans derived from G. lucidum mycelium. The source of β-glucans is the mushroom species G. lucidum. The mycelium of a standard strain (G. lucidum ATCC 32472) is subcultured and maintained in sterile agar medium under controlled conditions. The manufacturing process starts with preparation of the culture medium containing glucose, galactose, sucrose, mannose, and yeast extract. Following sterilization of the medium, G. lucidum mycelia are introduced and cultured by incubation for 3-5 weeks to allow full growth of the culture. Subsequently, β-glucans in the mycelium are extracted using high speed homogenization and ultrasonic vibration. The resulting solution is then filtered and separated using a ceramic membrane to remove residual, small molecular weight carbohydrates. The concentrated β-glucans derived from G. lucidum mycelium are then dried and ground into powder. The final product is packaged into food grade bags, and samples from each batch are analyzed for the presence of carbohydrates. Super Beta Glucan states that all equipment and materials used in the production process have a history of use in food processing and are in compliance with FDA regulations.
Super Beta Glucan provides sets of specifications for β-glucans derived from G. lucidum mycelium. Specifications include β-glucan composition (≥ 50%), total carbohydrate (> 95%), limits for fat (<1.0%), saturated fat (< 0.5%), protein (< 1.0%), moisture (< 2.0%), ash (< 3.0%), lead (< 0.5 milligrams per kilogram (mg/kg)), mercury (< 0.05 mg/kg), arsenic (< 0.5 mg/kg), and cadmium (< 0.5 mg/kg). In addition, Super Beta Glucan provides results from five batch analyses of β-glucans derived from G. lucidum mycelium that demonstrate conformity with the specifications. Super Beta Glucan also provides additional microbiological specifications to ensure there were no microbial contaminants.
Super Beta Glucan provides estimated daily intakes (EDI) of β-glucans derived from G. lucidum mycelium from the intended uses. Super Beta Glucan states that the intended use of β-glucans derived from G. lucidum mycelium (50% concentration) is substitutional and is present in the same foods and at the same levels as the ingredient that is the subject of GRN 000309. Therefore, Super Beta Glucan does not expect dietary intake to be noticeably affected. Super Beta Glucan uses the same dietary intake calculations as presented in GRN 000309. The mean and 90th percentile (users only) EDI for the total population would be 291.3 and 583.4 mg per person per day (mg/p/day) or 6.3 and 14.5 mg per kg body weight per day (mg/kg bw/day), respectively. This analysis used the United States Department of Agriculture 1994-1996 Continuing Survey of Food Intakes by Individuals survey. Super Beta Glucan states that the β-glucans that are the subject of this notice are not intended for inclusion in infant formula or baby foods.
Super Beta Glucan discusses published information to support the safety of β-glucans. These studies include a subchronic toxicity study in Sprague-Dawley (CD IGS) rats as well as mutagenicity and genotoxicity studies. Super Beta Glucan states that based on the results of the subchronic study, the no observed adverse effect level for β-glucans derived from G. lucidum mycelium was 2000 mg/kg bw/day, the highest dose tested. Super Beta Glucan also states that the source organism, G. lucidum, is non-pathogenic and non-toxigenic and does not produce any mycotoxins.
Super Beta Glucan discusses published human clinical data in addition to published acute, subchronic, and chronic animal studies. The notifier cites this information to further support the intended use of β-glucans derived from G. lucidum mycelium. These studies utilize β-glucans derived from sources other than mushroom mycelium such as Saccharomyces cerevisiae and Aureobasidium pullulans. These studies were not designed to assess safety, however, Super Beta Glucan notes that there were no adverse effects.
Super Beta Glucan considers the potential allergenicity of β-glucans derived from G. lucidum mycelium by reviewing published and unpublished studies. Based on this consideration, Super Beta Glucan does not anticipate allergenic reactions in humans following oral ingestion of either β-glucans or its source organism G. lucidum (Reishi). However, Super Beta Glucan states that β-glucans derived from G. lucidum mycelium will be labeled as mushroom β-glucans so that individuals with mushroom or β-glucan allergy or sensitivity may avoid consumption of the product.
Standards of Identity
In the notice, Super Beta Glucan states its intention to use β-glucans derived from G. lucidum mycelium in several food categories, including foods for which standards of identity exist, located in Title 21 of the Code of Federal Regulations. We note that an ingredient that is lawfully added to food products may be used in a standardized food only if it is permitted by the applicable standard of identity.
Potential Labeling Issues
In discussing the intake of β-glucan from food and pre-existing exposure to β-glucans derived from G. lucidum mycelium, Super Beta Glucan references 21 CFR 101.81 which authorizes a health claim on the relationship between soluble dietary fiber from whole oat and barley sources and reduced risk of coronary heart disease. Under section 403(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), a food is misbranded if its labeling is false or misleading in any particular. Section 403(r) of the FD&C Act lays out the statutory framework for the use of labeling claims that characterize the level of a nutrient in a food or that characterize the relationship of a nutrient to a disease or health-related condition. If products that contain β-glucans derived from G. lucidum mycelium bear any claims on the label or in labeling, such claims are the purview of ONLDS. The Office of Food Additive Safety neither consulted with ONLDS on this labeling issue nor evaluated the information in your notice to determine whether it would support any claims made about β-glucans derived from G. lucidum mycelium on the label or in labeling.
Section 301(ll) of the FD&C Act
The Food and Drug Administration Amendments Act of 2007, which was signed into law on September 27, 2007, amends the FD&C Act to, among other things, add section 301(ll). Section 301(ll) of the FD&C Act prohibits the introduction or delivery for introduction into interstate commerce of any food that contains a drug approved under section 505 of the FD&C Act, a biological product licensed under section 351 of the Public Health Service Act, or a drug or a biological product for which substantial clinical investigations have been instituted and their existence made public, unless one of the exemptions in section 301(ll)(1)-(4) applies. In its review of Super Beta Glucan’s notice that β-glucans derived from G. lucidum mycelium is GRAS for the intended uses, FDA did not consider whether section 301(ll) or any of its exemptions apply to foods containing β-glucans derived from G. lucidum mycelium. Accordingly, this response should not be construed to be a statement that foods that contain β-glucans derived from G. lucidum mycelium, if introduced or delivered for introduction into interstate commerce, would not violate section 301(ll).
Based on the information provided by Super Beta Glucan, as well as other information available to FDA, the agency has no questions at this time regarding Super Beta Glucan’s conclusion that β-glucans derived from G. lucidum mycelium is GRAS under the intended conditions of use. The agency has not, however, made its own determination regarding the GRAS status of the subject use of β-glucans derived from G. lucidum mycelium. As always, it is the continuing responsibility of Super Beta Glucan to ensure that food ingredients that the firm markets are safe, and are otherwise in compliance with all applicable legal and regulatory requirements.
In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter responding to GRN 000413, as well as a copy of the information in this notice that conforms to the information in the GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is available for public review and copying at www.fda.gov/grasnoticeinventory.
Dennis M. Keefe, Ph.D.
Office of Food Additive Safety
Center for Food Safety and Applied Nutrition
1β-glucans are the subject of previous GRAS notices and differ primarily by the source organism. The subject of GRN 000239 is β-glucan from Saccharomyces cerevisiae (bakers yeast) and the subject of GRN 000309 is β-glucan derived from Aureobasidium pullulans (black yeast).
2In an e-mail dated March 16, 2012, the notifier states that the non-β-glucans portion of the preparation consists of monosaccharides and disaccharides (approximately 40%), small amounts of cellulose, chitin, and chitosan (< 3%), trace amounts of triterpenes and triterpenoids (< 0.1%), and nucleosides (< 0.2%).