Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283

Abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of the novel food (NF) nicotinamide riboside chloride (NRC) pursuant to Regulation (EU) 2015/2283. The assessment addresses the use of NRC in 'meal replacement products' and 'nutritional drink mixes' at levels up to 300 mg/day for the general population, and in food for special medical purposes (FSMP) and total diet replacement for weight control (TDRWC) (as per Regulation (EU) No 609/2013) at levels up to 500 mg/day in adults. Benchmark dose modelling was carried out on data from the 90-day oral toxicity studies in rats relevant to the safety assessment. Considering the lack of tolerable upper intake level (UL) for nicotinamide in infants and the narrow margin of exposure between the estimated intake in infants and the lower confidence bound of the benchmark doses (BMDL 05 ) estimated by the models, the Panel concludes that the safety of the NF has not been established for use in 'meal replacement products' and 'nutritional drink mixes' under the proposed conditions of use. For FSMP and TDRWC, the proposed maximum use level corresponds to an intake of 210 mg nicotinamide per day, which is below the current UL for nicotinamide of 900 mg/day for adults. The Panel considers that the NF is as safe as pure nicotinamide for use in FSMP and TDRWC. The Panel, however, notes experimental data which indicate several pathways by which intakes of nicotinamide (or its precursors), at levels that are substantially higher than the physiological requirement, might cause adverse effects. The Panel considers that further investigations are required and that a re-evaluation of the UL for nicotinamide may be warranted.

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives

“…The European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods and Allergens (NDA) of the European Commission (EC) concluded that NR and NRCl are “safe for the healthy adult population, excluding pregnant and lactating women, and that an intake of up to 230 mg/day is safe for pregnant and lactating women”. Moreover, for the two active compounds, there are no concerns about genotoxicity and their safety/tolerability in human studies [ 222 , 223 , 224 ]. Three more leading international regulatory authorities, including the U.S. Food and Drug Administration (FDA), Health Canada (HC), and the Therapeutic Goods Administration (TGA) of Australia, concluded that NR is safer for human use than other NAD + metabolites [ 225 ].…”

Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials

“…Mammalian cells cannot import NAD+; so that commercial oral NAD-boosting supplements have been developed, using exogenous NAD + precursors, such as L-tryptophane, nicotinic acid, nicotinamide-mononucleotide, nicotinamide-riboside, and dihydronicotinamide-riboside ( Ratajczak et al, 2016 ; Sinclair, 2018 ; Reiten et al, 2021 ; Zapata-Pérez et al, 2021 ). The use of such boosting compounds is accepted by the European Food Safety Authority Panel ( Baquero et al, 2021 ). NAD-production can also be achieved with activators of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the ex-novo production of NAD ( Hua et al, 2021 ).…”