Experimental Research on Stimulation of Wound Healing by n-3 Fatty Acids

Akihiko Futamura, PhD; Takashi Higashiguchi, MD, PhD; Akihiro Ito, MD, PhD; Yoshiyuki Kodama, MD; Takeshi Chihara, PhD; Takaaki Kaneko; Akiko Tomatsu; Kan Shimpo, PhD


Wounds. 2013;25(7):186-192. 

In This Article

Abstract and Introduction


Objective. The objective of this study was to investigate the wound healing effects of n-3 fatty acids and to identify factors that stimulate wound healing.

Materials and Methods. Four-week-old male Wistar rats were subjected to full-thickness skin wounds and assigned to 3 experimental diet groups (an n-3 fatty acid-fortified diet, a diet with a 1:3 ratio of n-3 to n-6 fatty acids, and an n-6 fatty acid-fortified diet). Intergroup comparisons were conducted for the changes in wound areas, the number of days to wound healing, and blood cytokines, blood hydroxyproline, and blood chemistry test values on the day before and after wound healing.

Results. The number of days to wound healing in the n-3/n-6 fatty acid group (18.4 ± 1.8 days) was significantly shorter than in the n-3 fatty acid-fortified diet (21.6 ± 1.6 days) and n-6 fatty acid-fortified diet groups (21.9 ± 1.8 days). This suggests that the n-3/n-6 fatty acid diet stimulates wound healing (P < 0.05). Changes in wound area, however, were not significantly different. The n-3 fatty acid-fortified diet was found to have potent immunopotentiating and anti-inflammatory effects in the group receiving this diet, as evidenced by total blood lymphocyte count and plasma levels of interleukin-1 beta (IL-1β) and sialic acid on day 1 after wounding. The plasma hydroxyproline concentrations noted in the groups with a diet containing n-3 fatty acids indicate that this fatty acid type stimulates wound healing.

Conclusions. Findings suggest that n-3 fatty acids have anti-inflammatory and immunopotentiating effects, and are beneficial in the wound healing process, particularly during early inflammation.


Persisting pressure, rubbing, and underlying disease morbidity are the major causes of pressure ulcers, but malnutrition is another important factor. Research comparing the body measurements of patients with pressure ulcers, and the finding that 46% of these patients have serum albumin levels < 3.5 g/dL, highlight the importance of better nutrition for the prevention and healing of pressure ulcers.[1–3]

Among nutrients, fatty acids are precursors of bioactive substances. The types and ratios consumed are therefore important considerations. The n-6 fatty acid linoleic acid, for instance, produces eicosanoids derived from arachidonic acid within the body and is a key contributor to the initiation of the inflammatory response among other functions associated with the body's defenses.[4] In contrast, the n-3 fatty acids competitively inhibit the conversion of arachidonic acid into bioactive substances, thereby suppressing inflammatory cytokine production. Resolvins, metabolites of n-3 fatty acids, have recently been shown to stimulate the resolution of inflammation as anti-inflammatory mediators.[5–6] Moreover, the n-3 fatty acids are immunonutrients that activate intestinal immunity, protect the cardiovascular system, suppress weight loss in cancer patients, and play other important roles in maintaining and improving immunity.[6] Research is now characterizing the anti-inflammatory and immunopotentiating effects of n-3 fatty acids, but it is the authors' understanding that the role of these substances in the wound healing process remains quite limited.

The effects of n-3 fatty acids on inflammatory cytokines in the wound healing process, and the ability of n-3 fatty acids to stimulate wound healing in wounded rats fed a diet fortified with n-3 fatty acids, were investigated.