Risk Assessment of "Other Substances" – Piperine

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 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 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 piperine, and it is based on previous risk assessments and articles retrieved from a literature search. According to information from NFSA, piperine, derived from black pepper, is an ingredient in food supplements sold in Norway. NFSA has requested a risk assessment of the dose 1.5 mg/day of piperine in food supplements. The total exposure to piperine from other sources than food supplements, such as foods or cosmetics, is not included in the risk assessment. Piperine (( E , E )-piperine) is a naturally occurring alkaloid which is the major pungent compound found in spices like black pepper ( Piper nigrum L.) and long pepper ( Piper longum L.), but it also occurs in Grains of Paradise ( Aframomum melegueta K. Schum.). ( E,E ) piperine is the isomeric form which is used in food supplements. Several isomers structurally related to ( E,E )-piperine are found in pepper with less hot taste, including isopiperine, chavicine and isochavicine. In the European/Western cuisine, black pepper is the major source of piperine in the human diet. Other sources in the diet are piperine (pepper)flavoured finished food products, including beverages and spirits. Piperine is also used in cosmetics as a perfuming agent (CosIng, 2016). The range of doses reported to cause interactions with drugs and phytochemicals when studied in vivo , 5 to 20 mg/kg bw per day in humans and 10 to 50 mg/kg bw per day in animals (Chinta et al., 2015; Srinivasan, 2007; Srinivasan, 2013), exceeded estimated daily intake levels of piperine. Provided that the ingestion of piperine via pepper (food flavouring) or intake of dietary supplements containing P. nigrum or P. longum does not exceed common dietary levels, the risk of adverse piperine-drug and piperine-phytochemical interactions is minimal. Based on a 90-day toxicity study in rats, a no observed adverse effect level (NOAEL) of 5 mg/kg bw per day was set in 2015 by the European Food Safety Authority (EFSA). In the present risk assessment, VKM has used this NOAEL of 5 mg/kg bw per day for the risk characterisation. The risk characterisation is based on the margin of exposure (MOE) approach; the ratio of the NOAEL to the exposure. An acceptable MOE value for a NOAEL-based assessment of piperine based on an animal study is ≥100, which includes a factor 10 for extrapolation from animals to humans and a factor 10 for interindividual human variation. From a daily dose of 1.5 mg piperine, the calculated intake levels are 34.6, 24.5, and 21.4 µg/kg bw per day for children (10 to <14 years), adolescents (14 to <18 years) and adults (³18 years), respectively. Using the MOE approach, for a daily intake of 1.5 mg piperine from food supplements and a NOAEL of 5 mg/kg bw per day, the MOE values are 145, 204 and 234 for children (10 to <14 years), adolescents (14 to <18 years) and adults (≥18 years), respectively. Thus, for a daily intake of 1.5 mg piperine, the MOE values are above 100 for all age groups. VKM concludes that it is unlikely that a daily dose of 1.5 mg piperine from food supplements causes adverse health effects in children (10 to <14 years), adolescents (14 to <18 years) and adults (≥18 years).