Risk Assessment of "Other Substances" – L-aspartic Acid

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 in food supplements and concentrations in energy drinks given by NFSA. These risk assessments will provide NFSA with the scientific basis while regulating the addition of "other substances" to food supplements and other foods. "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. VKM has not in this series of risk assessments of "other substances" evaluated any claimed beneficial effects from these substances, only possible adverse effects. The present report is a risk assessment of specified doses of L-aspartic acid in food supplements, and it is based on previous risk assessments and articles retrieved from literature searches. According to information from NFSA, L-aspartic acid is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of 3000, 3500, 4000, 4500, 5000 and 5700 mg/day of L-aspartic acid in food supplements. L-aspartic acid is a dispensable dicarboxylic amino acid that can be produced by the transamination of oxaloacetic acid, an intermediate in the metabolism of e.g. glucose and some amino acids. L-aspartic acid is present in frequently consumed foods of animal and plant origin and is also a component of the sweetener aspartame. Dietary intake of aspartic acid in Norway is not known, but data from NHANES III (USA) suggest a mean dietary intake of about 6.5 g/day in adults. The highest intake was seen in men 31 through 50 years of age at the 99th percentile of 15.4 g/day. In the literature review we did not identify any long-term studies in human individuals that could be used for risk assessment. Short-term human studies found no adverse health effect when L-aspartic acid was given in acute doses ranging from 1 to 10 g/day, for time periods between one single dose and four weeks. None of these studies were undertaken to assess the toxicity of L-aspartic acid. In the literature search, two animal studies were identified of which one was a 90-day subchronic toxicity study. In that study, a no observed adverse effect level (NOAEL) of 697 mg/kg bw per day in male rats and 715 mg/kg bw per day in female rats was established. No neurotoxicity was found, however a toxic effect on kidneys and possibly salivary glands was observed at 1400 mg/kg bw per day (lowest observed adverse effect level, LOAEL). For the risk characterisation, the NOAEL of 697 mg/kg bw per day derived from the abovementioned subchronic toxicity study in rats was used for comparison with the estimated exposures from food supplements. The calculated Margin of Exposure (MOE) values for this NOAEL ranged from 5 to 16 for a daily intake of 3000-5700 mg/day of Laspartic acid. These low MOE-values may not be regarded as acceptable since L-aspartic acid has caused toxic effects on the kidneys (regenerative renal tubules with tubular dilation) and acinar cell hypertrophy of salivary glands in rats. Further, direct information regarding potential adverse health effects in humans is not available due to absence of long-term studies. In adults (≥18 years), adolescents (14 to < 18 years) and children (10 to < 14 years), the specified doses 3000, 3500, 4000, 4500, 5000 and 5700 mg/day L-aspartic acid in food supplements may represent a risk of adverse health effects. Children younger than 10 years were not within the scope of the present risk assessment.