The use of LactoSpore® as a food ingredient

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Health Canada has notified Sabinsa Corporation that it has no objection to the sale of LactoSpore® to be used as a food ingredient in a variety of foods as described below. The Department conducted a comprehensive safety assessment of Lactospore® according to its Guidelines for the Safety Assessment of Novel Foods.

Background:

The following provides a summary of the notification from Sabina Corporation and the evaluation by Heath Canada. This document contains no confidential business information.

1. Introduction

Sabina Corporation has developed LactoSpore® for use as a food ingredient in a variety of baked goods and baking mixes, beverages and beverage bases, breakfast cereals, chewing gum, coffee and tea, condiments and relishes, confections and frostings, dairy product analogs, fruit juices, frozen dairy desserts and mixes, fruit and water ices, gelatins, puddings and fillings, grain products and pastas, milk and milk products, nuts, plant protein products, processed fruits, processed vegetables and vegetable juices, snack foods, soft candies, soups and soup mixes, sugar and sweet sauces, toppings, and syrups excluding infant formula products.

LactoSpore® is a powder preparation of spores of Bacillus coagulans strain MTCC 5856, standardised with food grade maltodextrin to obtain commercial formulations of three different concentrations of B. coagulans MTCC 5856 spores. The final levels in food would be 2 x 109 colony forming units (CFU) per serving for an estimated daily intake (EDI) of 36.4 x 109 CFU.

The safety assessment performed by Food Directorate scientific evaluators was conducted according to Health Canada's Guidelines for the Safety Assessment of Novel Foods. The assessment considered the microbiological, nutritional, chemical and toxicological safety of LactoSpore® as a food ingredient.

The Food Directorate has a legislated responsibility for the pre-market assessment of novel foods and novel food ingredients under Division 28 of Part B of the Food and Drug Regulations. The Bacillus coagulans strain MTCC 5856 (LactoSpore®) is considered a novel food under the following part of the definition for novel foods:

“a) a substance including a microorganism that does not have a history of safe use as a food.

2. Product Development

LactoSpore® is manufactured from B.coagulans strain MTCC 5856 using a process consisting of an inoculum preparation, fermentation, centrifugation, filtration, and spray drying. A pure culture of B.coagulans MTCC 5856 strain is inoculated into sterile medium (22-24 hours at 37 °C), and then transferred to a larger apparatus for fermentation in sterile media (35-37 hours at 37 to 39 °C) under agitation and aeration. Throughout the fermentation process, pH and temperature conditions are monitored to ensure optimal strain production. Microscopic checks are conducted periodically to confirm the purity of the culture.

Following the fermentation, the culture is centrifuged to separate the biomass from the medium. The biomass of bacterial spores is filtered through a sterile stainless steel 100 mesh filter, and then spray-dried at high temperatures (up to 115 °C) for 2 hours. The resulting powder is combined with food grade maltodextrin to obtain commercial formulations of three different concentrations of B.coagulans MTCC 5856 spores (LactoSpore® 6 billion CFU/g, LactoSpore® 15 billion CFU/g, and LactoSpore® 100 billion CFU/g).

Process information provided indicates that LactoSpore® is produced under a quality control system that includes critical control points and control measures to ensure that all relevant food safety hazards are identified and adequately controlled at each step within the LactoSpore® production and packaging. The manufacturing process, as described, is sufficient to produce microbiologically safe products

3. Dietary Exposure

LactoSpore® is intended to be used as a food ingredient at the inclusion level of 2 x 109 CFU per serving in a variety of foods listed above. The proposed food categories do not include foods intended exclusively for infants and toddlers.

Estimated daily intake (EDI) of 36.4 x 109 CFU based on the consumption of 18.2 servings of food per day from USDA data (as reported in GRAS GRN 601) was provided. This EDI is very conservative as it assumes that nearly all food products consumed will contain LactoSpore®, and it is a reasonable approximation to Canadian daily serving intakes based on the available Canadian Community Health Survey data.

4. Chemical Assessment  

Analytical testing for chemical contaminants such heavy metals, arsenic, cadmium, lead, mercury and chromium was provided for different lots of LactoSpore® and the results demonstrated compliance with set specifications. Exposure calculated based on these results were estimated to have a negligible impact on background exposure to these contaminants in the typical Canadian diet and are well below doses associated with human health concerns. Therefore, LactoSpore® does not pose a concern to human health from a chemical contaminants perspective.

5. Microbiological Assessment

The B. coagulans strain MTCC 5856 used in LactoSpore® is a non-genetically modifiedbacterialstrain originally isolated from green malt or fermented barley. This strain was deposited in the Microbial Type Culture Collection (MTCC) and assigned number MTCC-5856 in September 2013. The strain is well characterized morphologically, phenotypically and genetically. It is a microaerophilic, spore forming, thermotolerant, L-lactic acid producing bacterium that possesses high tolerance to acid and bile salt. Biochemical, physiological, and genotypic characterisation data provided confirmed the identity of the B. coagulans strain MTCC 5856 and its stability over three years of commercial scale production.

Taxonomically, this bacterial strain belongs to the species B. coagulans classified as a Risk Group 1 microorganism by the Public Health Agency of Canada. Risk Group 1 microorganisms are not associated with human disease. Therefore, B. coagulans as a species is considered a non-pathogenic microorganism.

The B. coagulans MTCC 5856 preparationwas tested to confirm susceptibility to antibiotics. The strain was also shown through genetic sequence analysis to not contain any antimicrobial resistance genes towards clinically relevant antibiotics.

Additionally, the strain was tested for the presence of enterotoxin genes commonly identified as playing a major role in causing human illness, namely hemolytic enterotoxin gene (hblC), non-hemolytic enterotoxin genes (nheA, nheb, nheC), and cytotoxin K (cystK). The B. coagulans MTCC 5856 preparation was found to not contain any genetic sequences matching the aforementioned enterotoxin genes.

Taken together, the B. coagulans MTCC 5856 strain is free of genes for antibiotic resistance or toxins that are known to exist in other pathogenic Bacillus spp.

Test results were provided for the presence of microbial contaminants in the final spore preparation, specifically Staphylococcus aureus, Salmonella spp., Pseudomonas aeruginosa, coliforms, Escherichia coli, enterobacteriaceae, yeast and mold. All testing was conducted according to USP or FDA-BAM methods. Certificates of analysis for nine production lots demonstrated compliance with these specifications. No safety concerns were found regarding the food use of LactoSpore® from a microbiological perspective.

6. Nutritional Assessment

Clinical data was examined to demonstrate the safety and tolerability of the proposed daily serving quantity of 2x109 cfu B. coagulans strain MTCC 5856. The results show that LactoSpore® was well tolerated and the few adverse events reported, which included nausea, stomach pain and upset, and bloating were similar to the placebo group and are considered to be non-serious, self-limiting, and unlikely to pose nutritional safety concerns.

An in vitro study provided suggested that B. coagulans strain MTCC 5856 may survive the upper gastrointestinal tract. It produces lactic acid, a metabolite that has been shown to support gut health by lowering the luminal pH and inhibiting the growth of bacterial pathogens. B. coagulans MTCC 5856 fermentation of fibre in vitro also results in the production of short-chain fatty acids (SCFAs) such as acetic, propionic and butyric acid that play a role in gut health through various mechanisms including providing an energy source for colonocytes.

Based on the data provided, there are no nutritional safety concerns with the food use of LactoSpore®.

7. Toxicological Assessment

There were no pre-clinical toxicity studies provided for the B. coagulans strain MTCC 5856 spore preparation specifically, however published pre-clinical studies for other B. coagulans strains showed an overall low acute toxicity.

Results from repeat dose oral toxicity studies in rats from 90 days up to 1 year conducted in compliance with the Organization for Economic Co-operation and Development (OECD) testing guidelines under Good Laboratory Practices (GLP) showed no adverse effects. For instance, in a one-year dietary study in rats, a No Observable Adverse Effect Level (NOAEL) of 1948 mg/kg body weight (bw) per day (equivalent to 134 x 109 CFU/kg bw per day), the highest dose tested, was established. In addition, no adverse effects were reported in a one-generation reproductive study (OECD 415) resulting in a NOAEL of 2372 mg/kg bw/day (equivalent to 1.63 x 1011 CFU/kg bw per day) for the parental generation and 3558 mg/kg bw per day (equivalent to 2.45 x 1011 CFU/kg bw per day) for the F1 offspring (the highest dose tested).

A bacterial reverse mutation assay and clinical toxicity studies for B. coagulans strain MTCC 5856 spore preparation were examined. The results of the Ames test (OECD Test No. 471) performed with LactoSpore® did not show any mutagenic activity. Additional published toxicological studies for B. coagulans indicate no mutagenic, clastogenic, or genotoxic effects.

Three double-blind, randomized placebo-controlled clinical studies were examined. In these studies, healthy adults (n = 40) or participants with irritable bowl syndrome (n = 36 and 40) received B. coagulans MTCC 5856 at a dose of 2 x 109 CFU per day for 30 or 90 days. No safety issues were identified. The results suggest that B. coagulans MTCC 5856 at a dose of 2 x 109 CFU per day for up to 90 days is well tolerated.

Taken together, the NOAEL of 1948 mg/kg per day (equivalent to 134 x 109 CFU/kg bw/day) established in the 1-year dietary study in rats, and the Estimated Daily Intake (EDI) for B. coagulans MTCC 5856 of 36.4 x 109 CFU per day (equivalent to 0.52 x 109 CFU/kg bw per day for an individual weighing 70 kg), the margin of exposure (MOE) of LactoSpore® is estimated to be 258.

The weight of evidence provided (which includes the absence of adverse effects in the animal studies reviewed, the lack of genotoxicity, and the tolerance observed in clinical studies) suggests that the margin of exposure is considered sufficient from a toxicological safety perspective.

An allergen statement was provided confirming the absence of common food allergens and their derivatives, both in the product and in the manufacturing plant. No potential for residues of common food allergens other potential allergenic concerns were identified. The current opinion is solely with respect to the suitability for sale as a food ingredient. It is not an opinion with respect to processing aids, additives, or any other substances that are used in the manufacture of Lactospore®.

Conclusion:

Health Canada has reviewed  the information presented in support of the food use of LactoSpore® as a food ingredient (with no health claims) in a variety of foods and concluded that food products containing LactoSpore® do not raise concerns and safety concerns. It is the continuing responsibility of the manufacturers/sellers/distributors to ensure that their products are in compliance with all applicable statutory and regulatory requirements.

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.

(Également disponible en français)

For further information, please contact:

Novel Foods Section
Food Directorate
Health Products and Food Branch
Health Canada, PL2204A1
251 Frederick Banting Driveway
Ottawa, Ontario K1A 0K9
hc.bmh-bdm.sc@canada.ca

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