High‐Carbohydrate Diet Enhances Peripheral Nerve Regeneration via Hemoglobin Upregulation in Schwann Cells

ABSTRACT Motor dysfunction resulting from peripheral nerve injury significantly impacts quality of life. Nutritional support is a crucial complementary therapy, yet the specific roles of the three primary macronutrients—carbohydrates, proteins, and fats—in peripheral nerve regeneration remain unclear. This study systematically examined the effects of short‐term and long‐term high‐fat, high‐protein, and high‐carbohydrate diets on regeneration following sciatic nerve injury in mice. Our findings revealed that a short‐term high‐carbohydrate diet markedly enhanced gait restoration, improved nerve conduction velocity, stimulated axonal regrowth, and promoted Schwann cell proliferation and migration, leading to an increased number of myelin layers. In contrast, short‐term high‐fat, long‐term high‐carbohydrate, and long‐term high‐protein diets provided only moderate benefits, while short‐term high‐protein and long‐term high‐fat diets demonstrated minimal effects. Transcriptome sequencing of the injured sciatic nerves indicated significant upregulation of genes related to hemoglobin synthesis in the short‐term high‐carbohydrate group. Immunofluorescence staining confirmed elevated expression of Hba and Hbb in Schwann cells. Additionally, experiments with the Schwann cell line RSC96 demonstrated that overexpression of Hba‐a1 and Hbb‐bs significantly enhanced both proliferation and migration. These results suggest that a high‐carbohydrate diet supports peripheral nerve regeneration by upregulating hemoglobin expression in Schwann cells, thus promoting their proliferation and migration to create a conducive microenvironment for repair. This study highlights that short‐term high carbohydrate intake, as opposed to high protein or fat, is effective in promoting recovery following peripheral nerve injury, providing a new scientific basis for nutritional support during rehabilitation.