Severe feed restriction in a fish: is the positive effects of nucleotide supplementation on growth recovery explained by one-carbon metabolism?

Charrs ( Salvelinus spp.) are strong candidates for cyclical feed-restriction strategies due to their documented exceptional ability to withstand and recover from feed resources scarcity during winter (Drouin-Johnson et al. 2026; Le François et al. 2023; Savoie et al. 2017). Dietary nucleotides (NT) are supplements used to improve growth and health in fish, yet their integration into feed-restriction programs to enhance growth recovery remains largely unexplored. The one-carbon (1C) metabolism offers a mechanistic framework to investigate these effects, as it relies on vitamin B status and supports methylation reactions central to biosynthesis and growth. A large-scale trial involving S. alpinus × S. fontinalis was conducted, comprising a 90-day fasting period followed by refeeding on a commercial feed with or without NT. Growth and feeding metrics were evaluated alongside key metabolites of 1C metabolism to assess adaptations to fasting-induced vitamin B deficiency and the role of NT in recovery. Starved fish lost 5.2 % of body mass ( p < 0.05) but displayed accelerated growth upon refeeding, further enhanced by NT supplementation by 27.8 % ( p < 0.05), forecasting full compensation after 125 days. Starvation increased homocysteine and decreased methionine concentrations ( p < 0.05), while S-adenosylmethionine, S-adenosylhomocysteine, and formate showed only minor fluctuations. These patterns indicate moderate but reversible fluctuations of 1C metabolism. NT supplementation may exert a methyl-unit sparing effect during refeeding, potentially supporting anabolic recovery. This study uniquely combines commercial-scale growth trials and molecular analyses, providing new insights into a species-adapted feeding strategy that enhances growth recovery performances and metabolic resilience.