TABLE 2.

Preclinical Studies: Treatment Protocols After Musculoskeletal Injuries^a

Study	Treatment and Restrictions	Route of Exposure	Dosage	Frequency	Duration	Conditions	Results	Conclusion
Omeroglu et al25 (2009)	None; weightbearing without immobilization	Intraperitoneally	150 mg vitamin C (1.5 mL)	Once on day of injury and then once every 2 days	3 days, 10 days, and 21 days	Allowed to move freely in cages with free access to food and water	Significant difference in type I collagen production on 10th day, mean collagen fiber diameter and active fibroblasts higher in vitamin C group, and more evident angiogenesis on 3rd day	Low dose of vitamin C irrigation may be of potential use to promote healing
Sarisozen et al33 (2002)	None; weightbearing without immobilization	Intraperitoneally	200 mg/kg vitamin C	Once per day for 3 days and then 3 times per week	14 days and 21 days	Free access to food and water	Vitamin C group had accelerated bone matrix mineralization and increased amount of collagen	Vitamin C supplementation accelerated fracture healing
Hung et al19 (2013)	Tendon repair; immobilization for 2 weeks	Local injection	5 mg/mL or 50 mg/mL vitamin C (50 μL total volume)	Once	2 weeks and 6 weeks	N/A	No significant difference at 2 weeks between groups, significant improvement in gliding resistance at 6 weeks in vitamin C group, 5 mg/mL of vitamin C had significant reduction in fibrotic size at 6 weeks compared with control group, and less peritendinous adhesion in vitamin C group	Local injection of vitamin C solution can reduce extent of tendon adhesion after tendon repair
Giordano et al15 (2012)	None; weightbearing without immobilization	Intraperitoneally	200 mg/kg vitamin C	Once per day	2 weeks, 4 weeks, and 6 weeks	Caged with access to water and standard feed ad libitum containing no vitamin C	No significant histological or histomorphological differences	Vitamin C supplementation did not accelerate fracture healing process
Duygulu et al5 (2007)	None; N/A	Intraperitoneally	500 mg/kg vitamin C (+ 100 mg/kg zymosan per day for first 5 days)	Once per day	21 days	Caged laboratory conditions with standard diet and water	Oxidative stress impaired bone healing; histopathological, radiographic (bony union), and electromyographic (collagen fibrils) evaluations for vitamin C group were similar to that of control group; and significant difference in zymosan-only group for improved fracture healing	Free oxygen radicals have role in disruption of fracture healing, and vitamin C can partially prevent negative effects
Yilmaz et al41 (2001)	None; weightbearing	Intramuscularly	0.5 mg/kg vitamin C	Once	5 days, 10 days, 15 days, and 20 days	Caged with rat food, unlimited access to water, and unrestricted activity	No significant difference between groups overall; and vitamin C group was faster in chondroid cell development, chondrocyte hypertrophy, and fibrocartilaginous callus development than control group (P > .05)	Although there was no difference in quality of fracture healing, vitamin C–supplemented group was faster in healing process compared with controls
Fu et al10 (2013)	ACL reconstruction; weightbearing without immobilization	Intraoperative irrigation solution	3 mg/mL, 10 mg/mL, or 30 mg/mL (10 mL) vitamin C	Once	1 day, 4 days, 7 days, and 6 weeks	Caged	Vitamin C group had significantly reduced serum C-reactive protein levels at day 1, 3 mg/mL of vitamin C led to better restoration of anteroposterior knee stability at 6 weeks compared with control group, 3 and 10 mg/mL of vitamin C significantly reduced graft deterioration at 6 weeks, and no significant difference between groups at 42 weeks for graft incorporation	Low dose of vitamin C demonstrated short-term improvements after ACL reconstruction compared with controls, but there were no significant differences in ACL graft incorporation between groups

^aThe intervention was initiated on postinjury day 0 in all studies (n = 7). ACL, anterior cruciate ligament; N/A, not available.