Severe feed restriction in a fish: Is the positive effect of nucleotide supplementation on growth recovery explained by the nutrient cycling framework of 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. 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 (1 C) 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 1 C 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 but displayed accelerated growth upon refeeding, further enhanced by NT supplementation by 27.8%, forecasting full compensation after 125 days. Starvation increased homocysteine and decreased methionine concentrations ( P -value < 0.05), while S-adenosylmethionine, S-adenosylhomocysteine, and formate showed only minor fluctuations. These patterns indicate moderate but reversible fluctuations of 1 C 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.