Decision on 5-hydroxytryptophan (5-HTP) as a supplemental ingredient in foods

Health Canada's Food and Nutrition Directorate has assessed 5-HTP for use as a supplemental ingredient. This is one of the ingredients the Food and Nutrition Directorate identified for further assessment as set out in Health Canada's Category Specific Guidance for Temporary Marketing Authorization: Supplemented Food^{Footnote 1}.

The assessment considered publicly available information and found the data insufficient to establish acceptable conditions for use as a supplemental ingredient in foods.

Consequently, Health Canada is not acceding to use of 5-HTP as a supplemental ingredient. While 5-HTP is synthesized in the body, its natural occurrence in foods is limited and there is no history of use of its addition to foods.

Health Canada is prepared to accept a request to reconsider this decision under the regulations for supplemented foods. The Appendix of this letter identifies the information required to support reconsideration.

For more information on Health Canada's decision on 5-HTP, please contact the Food and Nutrition Directorate's Submission Management and Information Unit (SMIU) (E-mail: smiu-ugdi@hc-sc.gc.ca). Please use the words "Decision on 5-Hydroxytryptophan" in the subject line of your e-mail.

Appendix – Information to support a request for Health Canada to reconsider the decision on the use of 5-HTP as a supplemental ingredient

General guidance

1. Characterise in detail the 5-HTP that is requested for use.
2. Clearly demonstrate that the toxicological and nutritional safety information apply to use of the requested 5-HTP as a supplemental ingredient in foods.
3. Provide full study reports of safety tests, not summaries. The reports should provide clear, detailed characterisation of the 5-HTP test material, as well as a full description of the study design, including methods used, the type and number of animals treated, the doses administered, and the endpoints measured. Studies should also provide detailed documentation of the test results.

Toxicological information

1. Repeated dose toxicity test of orally administered 5-HTP at doses that would provide adequate evidence of safety, to support its use as a supplemental ingredient; this study should also include standard endpoints characterizing the potential for neurotoxicity.
2. Information on the safety of 5-HTP with respect to its potential drug interactions with monoamine-oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs), which may result in serotonin syndrome.
3. Information on the safety of 5-HTP with respect to the potential clinical impact of alterations in hormone levels (e.g., cortisol, prolactin).
4. Genotoxicity testing of 5-HTP. In general, a basic test battery would be comprised of two or more in vitro tests, or in vitro tests plus an in vivo test to evaluate genotoxic potential. In vivo studies should be conducted via the oral route of exposure.
5. Reproductive and developmental toxicity testing of orally administered 5-HTP at doses that would provide adequate evidence of safety to support its use as a supplemental ingredient suitable for consumption by the general population, including foods that could be consumed by children and individuals who are pregnant or who are trying to become pregnant.

Nutritional information

1. Information that would provide adequate evidence that 5-HTP would not affect digestion or absorption of other nutrients, especially in the intestines, and/or information that 5- HTP would not pose nutritional safety concerns if foods supplemented with 5-HTP were to be consumed frequently over a long period of time in different food matrices.
2. Information on the impact of 5-HTP, as a precursor of serotonin, in regulating the functions of key metabolic organs (e.g., liver and adipose tissue) and its potential clinical outcomes (e.g., obesity, diabetes).

This information is required to address the safety of 5-HTP for use as a supplemental ingredient in foods, not to demonstrate efficacy or to support specific health claims. For substantiation of food health claims, please see Health Canada's guidance Substantiation of Health Claims (Scientific Evidence).^{Footnote 2}