Risk Assessment of "Other Substances" – Glycine

ABSTRACT

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet; NFSA), assessed the risk of "other substances" in food supplements and energy drinks sold in Norway. VKM has assessed the risk of doses given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating "other substances" in food supplements. "Other substances" are described in the food supplement directive 2002/46/EC as substances other than vitamins or minerals that have a nutritional and/ or physiological effect. It is added mainly to food supplements, but also to energy drinks and other foods. In this series of risk assessments of "other substances" VKM has not evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of glycine in food supplements, and it is based on previous risk assessments and articles retrieved from two literature searches. Glycine is a non-essential amino acid which is synthesised from 3-phosphoglycerate via serine, or derived from threonine, choline and hydroxyproline via inter-organ metabolism involving primarily the liver and kidneys. Endogeneous synthesis is estimated to be in the magnitude of 8 g per day in adults. Glycine is a constituent of all proteins in the human body. It also functions as a neurotransmitter, and can play both stimulatory and depressant roles in the brain. Data on dietary intake of glycine in Norway are not available. Based on NHANES III (1988-1994), the overall mean intake of glycine from food and food supplements in the United States was 3.2 g per day. Thus, the combined dietary intake and endogenous synthesis is more than 11 g per day. Because glycine is not considered an essential amino acid, a dietary requirement in healthy humans has not been established. Foods rich in glycine are generally protein rich foods such as meat, fish, dairy products and legumes. According to information from NFSA, glycine is an ingredient in food supplements sold in Norway. NSFA has requested a risk assessment of 20, 50, 100, 300, 500 and 650 mg/day of glycine from food supplements. There is a lack of relevant supplementation studies with glycine in humans designed to address adverse effects and/or dose-response relationship, and none of the previous reports reviewed concluded with a no observed adverse effect level (NOAEL). For the current risk assessment, two literature searches were conducted, one for human studies and one for animal studies. No human studies were found that can be used for suggesting a "value for comparison", and there are no scientific data in the published literature suitable for assessing the specific doses in the terms of reference. The value for comparison used in this risk characterisation is 20 mg/kg per day. This value is derived from a study in rats in which the NOAEL was estimated at 2000 mg/kg per day. Using an uncertainty factor of 100, this corresponds to 20 mg/kg per day or 1.4 g per day for a person weighing 70 kg. This is more than twice as high as the highest dose for consideration in the present risk assessment, and it is far below the combined dietary intake and endogenous synthesis estimated at more than 11 g per day. No particular vulnerable groups for glycine supplements have been identified. VKM concludes that In adults (≥18 years), the specified doses 20, 50, 100, 300, 500 and 650 mg/day of glycine from food supplements are unlikely to cause adverse health effects. In adolescents (14 to <18 years), the specified doses 20, 50, 100, 300, 500 and 650 mg/day of glycine from food supplements are unlikely to cause adverse health effects. In children (10 to <14 years), the specified doses 20, 50, 100, 300, 500 and 650 mg/day of glycine from food supplements are unlikely to cause adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.