Nutrition, Dietetic Products, Novel Food and Allergy

Risk assessment of histidine, methionine, S-adenosylmethionine and tryptophan


Report no: 2013: 10

Published: 11.03.2013

Main message:

In 2011, the Norwegian Scientific Committee for Food Safety (VKM) conducted a risk categorisation of 30 amino acids and amino acid compounds. Based on potential health risks related to high intakes of the amino acids they were categorised into low, moderate or high risk groups. The amino acids histidine, methionine, S-adenosylmethionine (SAM) and tryptophan were categorised into the high risk group in this first screening.

Based on the risk categorisation, the Norwegian Food Safety Authority has requested VKM to conduct a risk assessment of the four amino acids histidine, methionine, SAM and tryptophan added to foods and drinks and in food supplements.

This opinion is limited to the use of single free amino acids in food supplements or fortified foods and drinks, and does not elaborate on risks related to protein hydrolysates or high protein intake.

This opinion has been prepared, evaluated and approved by the VKM Panel on Nutrition, Dietetic products, Novel Food and Allergy. The current opinion is based on conclusions from Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids the US Institute of Medicine (IOM, 2005) and literature identified in a literature search conducted in October 2012.

In their report IOM concluded that there were insufficient data available to evaluate the safety of single free amino acids and that no tolerable upper intake levels (UL) could be established. Histidine, methionine and tryptophan are essential amino acids, whereas SAM is a metabolite from methionine. Mild adverse effects such as nausea and reduced appetite were reported with the use of all four amino acids.

There are indications that intake of methionine during the so called methionine-loading test (100 mg methionine per kg body weight) is associated with adverse health effects such as dizziness, sleepiness and decreased or increased blood pressure. Intake of methionine supplement seems to be a concern for health also because increased concentration of its metabolite homocysteine in plasma may be associated with cardiovascular disease.

Intake of tryptophan supplement (single dose 6 g) has resulted in a significant increase in lipid peroxidation products, indicating an increased oxidative stress level. Intake of tryptophan supplement (4.2 g/day) has been linked to the development of eosinophilia, but this question is still unresolved.

Eosinophilia may have a negative health impact and hence tryptophan might still be considered to be of health concern. Because no dose-response studies or adverse health effects related to dose were found, UL for these four amino acids could not be established. However, in this assessment a tentative guidance level (GL) at 210 mg/day is suggested for methionine, and 220 mg/day is suggested as a tentative daily GL for tryptophan.

The intake of these four amino acids in free form was based on the doses used in food supplements sold in Norway, VKM estimates the intake of free form histidine and SAM to be within an acceptable level, whereas the doses of methionine in supplements available at the Norwegian market is higher than the tentative suggested GL in this assessment.

According to information from the Norwegian Food Safety Authority, supplements with single free tryptophan are not sold on the Norwegian market.


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