Risk Assessment of "Other Substances" – L-Histidine
Authors: Holvik Kristin , Iversen Per Ole , Vaktskjold Arild , Frøyland Livar , Haugen Margaretha , Løvik Martinus , Skålhegg Bjørn Steen , Stea Tonje Holte , Strand Tor A. , Tell Grethe S. 
Published: August 2020

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 for 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 L-histidine in food supplements, and it is based on previous risk assessments and articles retrieved from a literature search.Histidine; food supplement

According to information from NFSA, L-histidine is an ingredient in food supplements and energy drinks sold in Norway. NSFA has requested a risk assessment of 550 and 600 mg/day of L-histidine from food supplements. The recommended dietary allowance (RDA) for adults of L-histidine is 14 mg/kg body weight/day (IOM, 2005), which corresponds to 980 mg/day for a 70 kg person. Oral doses has a bioavailiability of 80% or higher. Foods rich in histidine are generally protein rich foods such as meat, dairy products, legumes, fish, nuts, seeds, eggs and whole grains. Based on NHANES III (1988-1994), the overall mean intake of Lhistidine from food and food supplements in the United States was 2.2 g/day.

L-histidine is a conditionally essential amino acid which is a normal constituent of most body proteins. L-histidine is also a part of many plasma proteins. It has anti-oxidant and antiinflammatory properties. Moreover, L-histidine is also a precursor of histamine and is necessary for the regulation and metabolism of trace elements such as metal ions. The human body has a large pool of L-histidine in plasma proteins, but also as carnosine in skeletal muscles and in haemoglobin.

Due to the lack of adequate scientific information, a no observed adverse effect level (NOAEL) or lowest observed adverse effect level (LOAEL) have not been identified, and a tolerable upper intake level for histidine has not been established. Effects of histidin supplementation have been studied in trials with duration of up to 3-4 months. Previous risk assessments concluded that supplementation with 4.0 to 4.5 g/day of L-histidine above the dietary content does not have adverse effects in human beings, and new data retrieved in the present literature search were in accordance with these conclusions. No particular population groups have been identified as particularly susceptible to adverse effects of consuming histidine supplements. We have not identified any studies in children or adolescents. 

 VKM concludes that:

In adults (≥18 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects.

In adolescents (14 to <18 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects.

In children (10 to <14 years), the specified doses 550 and 600 mg/day L-histidine in food supplements are unlikely to cause adverse health effects.

Children younger than 10 years were not within the scope of the present risk assessment.