Table 3.

Effect of supplements on prevention and therapy of surgical/traumatic wounds

References	Number of subjects (n)	Patient population characteristics	Intervention; additional intake of nutrient/day	Period of supplementation (days)	Study design	Parameters of wound healing	Results
Pories et al.29	20	Healthy men with surgical wounds Age: 25 (mean) BMI: n.d.	Verum  Zinc, 150 mg Control  No supplement	n.d.	Randomized, controlled	Time to wound closure Healing rate Wound volume (end of study)	V<C V>C V<C
Vaxman et al.30	40	Healthy subjects with ambulatory surgery for tattoo resection (7 and 14 days after starting supplementation) Age: V: 27±1, P: 24±1 BMI: n.d.	Verum  Vit C, 1,000 mg, Pantothenic acid, 200 mg (Hoffmann-La Roche) Placebo  n.d.	21	Randomized, double-blind, placebo-controlled	Skin/scars  Fibroblast count (d8, d21)  Hydroxyproline (d8, d21) Scars  Width, complication score, pain, stress, and stiffness (d80)  Hypertrophy, rigidity, and color (d80)	V>P V=P V=P V>P
Vaxman et al.31	27	Healthy subjects with ambulatory surgery for tattoo resection (7 and 14 days after starting supplementation) Age: n.d. BMI: n.d.	Verum 1  Vit C, 1,000 mg, Pantothenic acid, 200 mg (Hoffmann-La Roche) Verum 2  Vit C, 3,000 mg, PA, 300 mg (Hoffmann-La Roche)	21	n.d.	Skin/scars  Fibroblast count (d8, d21)  Hydroxyproline (d8, d21) Scars  Breaking strength (d80)  Width, complications, pain, stress, elastic stiffness, rigidity, and pain (d80)	V1 ↑, V2 ↑, V1=V2 V1 ↓, V2 ↓, V1=V2 V2>V1 V1=V2
de Luis et al.34	47	Patients with oral and laryngeal cancer undergoing elective surgerya Age: 61±2 BMI: 25.1±0.7	Verum  Enteral formula enriched with arginine (10.9 gb) and fiber Control Isocaloric, isonitrogenous enteral formula without arginine and fiber	≥10c	Randomized, controlled	Wound-healing complications  Fistulas  Wound infection	V<C V=C
Oguz et al.40	109	Patients with colorectal cancer undergoing surgery, without metabolic disorders, emergency surgery, and abdominoperineal resection Age: 54±10 BMI: 23.0±2.5	Verum  Glutamine (Dipeptiven®; Fresenius–Kabi), 1.0 g/kg BW, i.v. Control  No glutamine	6 days pre- and 5 days postoperatively	Randomized, controlled	Wound-healing complications  Wound infection  Wound dehiscence  Intra-abdominal abscess	V<C V<C V<C
de Luis et al.35	72	Patients with oral and laryngeal cancer undergoing elective surgerya Age: 62±1 BMI: 24.5±0.6	Verum  Enteral formula enriched with arginine (17 g) Control  Isocaloric, isonitrogenous enteral formula without arginine	≥10f 16±9 (mean±SD)	Randomized, controlled	Wound-healing complications  Fistulas  Wound infection	V<C V=C
De Luis et al.36	72	Patients with oral and laryngeal cancer undergoing elective surgerya Age: 62±1 BMI: 26.4±0.7	Verum  Enteral formula enriched with arginine (6.1 g) and fiber Control  Isocaloric, isonitrogenous enteral formula without arginine	≥10d	Randomized, controlled	Wound-healing complications  Fistulas  Wound infection	V<C V=C
Debats et al.32	18	Patients undergoing autografting as a part of reconstructive surgerye Age: 48±3 BMI: 27.0 (mean)	Verum  Arginine, 26 g, enteral (Bufa, Uitgeest) Placebo  Alanine, 51.2 g (Bufa, Uitgeest), isocaloric amounts	5	Randomized, double blind, placebo controlled	Wound healing  Neutrophil influx  Angiogenesis  Re-epithelialization Wound fluid  Arginine  Arginase-1, sum of nitrite+nitrate	V=P (d2, d5, d10) V=P (d2, d5, d10) V=P (d5, d10) V>P (d2, d5) V=P (d2, d5)
De Luis et al.37	115	Patients with oral and laryngeal cancer undergoing elective surgerya Age: 63±1 BMI: 25.7±0.4	Verum 1  Enteral formula highly enriched with arginine (20 g) Verum 2  Enteral formula enriched with arginine (12.3 g)	≥10d	Randomized, double blind	Wound-healing complications  Fistulas  Wound infection	V<C V=C
Debats et al.33	35	Patients undergoing autografting as a part of reconstructive surgerye Age: 44±3 BMI: 26.2±1.0	Verum  Arginine, 30 g, i.v. Placebo  Alanine, 25.2 g, i.v. (isovolumetric, isonitrogenous amounts) (both: Bufa, Uitgeest)	5	Randomized, double blind, placebo controlled	Wound healing  Neutrophil influx  Angiogenesis  Reepithelialization	V=P (d2, d5, d10) V=P (d0, d2, d5, d10) V=P (d5, d10)
Blass et al.41	20	Trauma patients with disorders in wound healingf Age: V: 45, P: 46 (medians) BMI: V: 27.6, P: 25.8 (medians)	Verum  ONS Glutamine plus® (Fresenius-Kabi), two servings/day  Intakeg  Energy: 81 kcal  Glutamine: 19 g  Vit C: 480 mg  Vit E: 160 mg TE  β-carotene: 3.1 mg  Zinc: 6.3 mg  Selenium: 96 μg Placebo  Maltodextrine (Dr. Steidle) (isocaloric amounts)	14	Randomized, double blind, placebo controlled	Microcirculation in wound area (2 mm tissue depth)  Oxygen saturation  Relative haemoglobin  Blood flow  Blood velocity Vascular growth factor A (serum) Wound temperature Time to wound closure	V ø, P↓ V ø, P ø V ø, P ø V ø, P ø V ø, P ø V ø, P ø V<P

Data on age (years) and on BMI (kg/m²) are means±SEM. Means were calculated as weighted means from the data of individual groups if not provided by the authors. Missing SEMs were calculated by SDs or SEMs of individual groups.

^aWithout severe impaired hepatic and renal function, ongoing infections, autoimmune disorders, ONS in previous 6 months, severe malnutrition (weight loss>10%).

^bBased on own calculations considering an energy intake of 32 kcal/kg body weight/d and a mean body weight of 68 kg.

^cFormulation was given until patients could ingest at least 1,500 kcal and 1.0 g protein/kg BW/day orally.

^dFormulation was given until patients could ingest at least 1,700 kcal and 1.0 g protein/kg BW/day orally.

^eDue to burns, trauma, malignancy, and other reasons; exclusion criteria: kidney or liver failure, immune deficiency diseases, diabetes.

^fMain diagnosis: fractures, partly with soft tissue trauma; comorbidities: vascular diseases, diabetes mellitus, hypertension, dementia, pressure ulcer.

^gConsidering an intake of 96% of target dose.

BW, body weight; FA, fatty acid; i.v., intravenous application;↑, significant increase;↓, significant decrease; ø, no significant changes.