Oral L-arginine supplementation for fracture healing: a systematic review of preclinical studies


arginine; supplementation; fracture healing; non-union; delayed union

Published online: Jan 22 2023


Anissa Feby Canintika, Ismail Hadisoebroto Dilogo, Guntur Utama Putera, Muhammad Yafidy

From the Department of Orthopaedics and Traumatology, Faculty of Medicine-Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia


Introduction: Approximately 5 to 10% of all patients with fractures experience deficient fracture healing that results in fracture nonunions. Previous studies have shown that nitric oxide production from arginine could improve fracture healing by improving local blood supply, supplementing growth factors, and improving collagen synthesis. Apart from its simple oral mode of administration, this amino acid provides a non-toxic and inexpensive option for fracture healing. To date, no systematic reviews regarding oral L-arginine supplementation for fracture healing are available. We present the first systematic review of oral L-arginine supplementation for fracture healing.

Methods: A systematic literature search was carried out using PubMed, Google Scholar, and ScienceDirect until February 1, 2021 using a combination of text words. No date limits were set. Studies investigating the use of oral L-arginine supplementation for fracture healing were included. Reference lists of relevant publications were assessed for additional references. In addition, bibliographies from other reviews were searched.

Results: Four studies were included. Of these, 3 were animal studies, and the other one was an in vitro study. Animals that were given oral L-arginine supplementation had significantly increased angiogenesis, reduced defect area, higher osteoblasts and osteoclasts, and higher rate of bone formation compared to controls.

Conclusions: The available preclinical studies suggest that oral L-arginine supplementation is a potential new therapy for fracture healing. This amino acid supplement is not only affordable and non-toxic; it is also simple. Further clinical studies are required to investigate the optimal dose of oral L-arginine supplementation for fracture healing in human subjects.