Effects of nutritional supplementation on chronic wound healing

Patients with pressure ulcers often have trouble meeting their nutritional needs with normal food intake. Providing an oral nutritional supplement (ONS) in addition to regular food intake is a logical way to replenish the shortage of macro- and micronutrients to preserve skin tissue, strengthen its resistance and promote tissue repair.

Of special interest are medical foods rich in proteins added with Arginine, Vitamins A, C and D with Zinc which have been shown to reduce the time in the healing process of chronic wounds.

Proteins are responsible for the synthesis of enzymes involved in tissue repair; they also participate in cell multiplication, collagen and connective tissue synthesis.

All stages of healing require adequate levels of protein and increased protein administration has been linked to improved healing rates.

The NPUAP/EPUAP/PPPIA guideline recommendation is to provide 1.25 to 1.5g protein/kg/day for patients with chronic wounds. If the patient is catabolic, has more than one wound, or the wound is stage III or IV, 1.5 to 2 g protein/kg/day is required. (1)

Arginine is a conditionally essential amino acid that acts as a substrate for protein synthesis, collagen deposition and cell growth.

Arginine supplementation has been shown to increase nitric oxide production (bacterial toxicant, platelet aggregation inhibitor, vasodilator and neurotransmitter), improve immune function and wound tensile strength in acute wounds. (2)

There is a growing body of moderate-quality evidence supporting the positive effect of protein supplementation, enriched with arginine and micronutrients, to promote chronic wound healing. (3) 

Heyman and coworkers (4),

conducted an open-label study in 2008 in which they recruited 245 residents (mean age 82.2 ± 10.1 years) from long-term care facilities in Belgium and Luxembourg; all had stage II, III or IV pressure ulcers.

All received their normal diet or enteral feeding plus three servings of a supplement providing, 20 g total protein, 3 g arginine, plus other micronutrients.

The primary outcome was a reduction in the mean pressure ulcer surface area. There was a significant reduction in surface area after 9 weeks.

In an RCT, Van Anholt et al.(5)

investigated a supplement rich in protein, arginine, and micronutrients to improve healing in well-nourished adults with category II, III, and IV pressure ulcers (PUs).

Participants recruited from 8 health centers in 4 European countries were randomized to receive an oral nutritional supplement (ONS) containing 20 g of protein, 3 g of arginine, and antioxidants, 3 times daily between meals for 8 weeks (group 1) or 200 ml of a no-calorie placebo (group 2) for the same period.

Supplementation with the specific ONS (group 1) accelerated UP healing, as indicated by a significant reduction in ulcer size compared to group 2 after 8 weeks. The decrease in severity score, PUSH, in the supplement group differed markedly from the control group.

Cereda E et al (6), conducted a multicenter, blinded, randomized controlled trial with 200 malnourished adult participants with stage II, III and IV PU. The intervention consisted of supplementing an oral formula with 20 g of protein, 3 g of arginine and antioxidants twice a day (group 1) or an equal volume of an isocaloric isonitrogen formula (group 2) for 8 weeks.


Supplementation with the enriched formula (n = 101) resulted in a greater reduction in PU area (mean reduction, 60.9% [95% CI, 54.3% to 67.5%]) than with the control formula (n = 99) (45.2% [ CI, 38.4% to 52.0%] (adjusted mean difference, 18.7% [CI, 5.7% to 31.8%]; P = 0.017). A more frequent reduction in the 40% or greater area was also observed at 8 weeks (odds ratio, 1.98 [CI, 1.12 to 3.48]; P = 0.018).

Nutrisite® HMB is a special medical purpose food that provides 23 g of Whey Protein Isolate, 3 g of L-Arginine plus Vitamins A, C and D with Zinc. Read more

In addition, Nutrisite® HMB provides 1 g of HMB per serving. We know that the loss of muscle mass equal to or greater than 20% alters the healing mechanisms, since the body gives priority to other vital processes and directs the substrates to the preservation of these functions.


Nutrisite’s high protein content (Leucine-rich Whey Protein Isolate) plus the addition of HMB are a strong stimulus for the activation of the mTOR protein complex, which stimulates protein synthesis, preventing catabolism and paralysis of the healing process.