History of use in food
The lactic acid bacteria are safe and useful organisms that have been widely used in fermented foods. Lactic acid bacteria Lactobacillus plantarum, to which L-137 belongs, are involved in the fermentation of certain foods such as nukazuke, kimchi, sauerkraut, pickles, and yogurt. They have been widely used in diets since ancient times. It has also been revealed that Lactobacillus plantarum not only exists in foods, but also in the mouth and digestive tract of humans.
Based on these facts, it is considered that Lactobacillus plantarum, to which L-137 belongs, are safe lactic acid bacteria with a long history of use in food.
L-137, which was isolated from Southeast Asian fermented food, is also a safe lactic acid bacterium with a long history of use in food.
So far many studies have been conducted, and the safety of HK L-137 has been scientifically verified.
Standard genotoxicity tests such as the reverse mutation test*1, chromosomal aberration test*2, and micronucleus test*3 have been conducted to confirm the absence of genotoxicity in HK L-137.
In addition, a single-dose toxicity study (acute oral toxicity study)*4 has been conducted in mice to confirm the absence of acute toxicity by overdose.
|*1 Reverse mutation test:
||This is a test to predict the presence or absence of genotoxicity by adding the test substance to a culture medium of the bacteria and examining for any change in the characteristic of the bacterial cells. HK L-137 did not change the characteristics of the cells.
|*2 Chromosomal aberration test:
||This is a test that predicts the presence or absence of genotoxicity by adding the test substance to a culture medium of animal cells and evaluating for any influence on cell proliferation and chromosomal morphology. HK L-137 did not affect the proliferation profile or chromosomal morphology of culture cells.
|*3 Micronucleus test:
||This is a test that predicts the presence or absence of genotoxicity by administering the test substance to mice and observing the presence or absence of a micronucleus (chromosomal fragment generated due to chromosomal aberration) in immature erythrocytes in the bone marrow. After continuous oral administration of an excessive amount of HK L-137 (400 mg/kg) for two days to mice, no abnormalities were observed in the frequency of micronucleus generation in immature erythrocytes in the bone marrow.
|*4 Single-dose toxicity study:
||This is a test that evaluates the toxicity of a substance by administering the test substance to mice and examining the type, severity, duration, and changes of the symptoms, as well as the presence or absence of deaths, associated with the administration. During the 14-day observation after the oral administration of an excessive amount of HK L-137 (1000 mg/kg), no abnormalities in the condition of the mice were observed. In addition, no abnormalities were observed in the pathological findings on day 14.
We have confirmed the safety of orally taken HK L-137 in healthy subjects by clinical study (double-blind randomized control study).
In this study, 30 healthy volunteers received one capsule of HK L-137 (10 mg) daily for 12 weeks, and another set of 30 healthy volunteers received one capsule of control (no HK L-137) daily for 12 weeks. The safety endpoints* were examined.
As a result, no abnormalities were observed in any of the endpoints, demonstrating the safety of oral intake of HK L-137.
|* Safety endpoints
- Physical measurements (body weight, blood pressure, and pulse)
- Biochemical tests (total protein, albumin, albumin-globulin ratio, creatine phosphokinase, glutamic-oxaloacetic transaminase, glutamic-pyruvate transaminase, lactic acid dehydrogenase, alkaline phosphatase, γ-glutamyl transpeptidase, leucine aminopeptidase, plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, urea nitrogen, creatinine, uric acid, sodium, chloride, potassium, calcium, inorganic phosphorus, serum iron, and C-reactive protein)
- Hematological tests (white blood cells, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, neutrophils, eosinophils, basophils, monocytes, lymphocytes, and red blood cell morphology)
- Urinalysis (specific gravity, pH, qualitative protein, qualitative glucose, urobilinogen, bilirubin, ketone body, and uric blood)）
The results of these tests have confirmed that HK L-137 is a safe food ingredient.
The results of the safety studies have been published.
Safety studies of LP20 powder produced from heat-killed Lactobacillus plantarum L-137. Hirose Y, Regul Toxicol Pharmacol. 54: 214-20, 2009
Based on the history of use in food and the results of the safety studies, HK L-137 was approved as Self-Affirmed GRAS*1 in the United States in 2009. In the same year, HK L-137 was certified as a Non-Novel Status*2 by EU.
- GRAS is an acronym for the phrase, Generally Recognized As Safe. Its status is confirmed by vigorous review process regulated by the FDA and ensuring the safety as the food.
- Lactobacillus plantarum has a long history of use in food, so HK L-137 has been certified as a conventional food by EU.