Combined therapy of Ulmo honey (Eucryphia cordifolia) and ascorbic acid to treat venous ulcers

OBJECTIVE: to assess the clinical effect of topical treatment using Ulmo honey associated with oral ascorbic acid in patients with venous ulcers. METHOD: longitudinal and descriptive quantitative study. During one year, 18 patients were assessed who were clinically diagnosed with venous ulcer in different stages, male and female, adult, with a mean injury time of 13 months. Ulmo honey was topically applied daily. The dressing was applied in accordance with the technical standard for advanced dressings, combined with the daily oral consumptions of 500 mg of ascorbic acid. The monitoring instrument is the assessment table of venous ulcers. RESULTS: full healing was achieved in 100% of the venous ulcers. No signs of complications were observed, such as allergies or infection. CONCLUSION: the proposed treatment showed excellent clinical results for the healing of venous ulcers. The honey demonstrated debriding and non-adherent properties, was easy to apply and remove and was well accepted by the users. The described results generated a research line on chronic wound treatment.


Introduction
Vascular ulcers cause repercussions in different spheres. Besides affecting health, they worsen the quality of life of patients and their responsible caregivers. Their evolution is slow, their duration undefined and relapses can extend for months or years. These lesions are predominantly venous, with single lesions, presenting exudate, extensive, causing functional limitations in the victims and further multidimensional repercussions (1) .
Ulcers cause a loss of workdays, early retirement and spending on prolonged treatment, with a great impact on the quality of life of the victims. The high prevalence of venous ulcer exerts a great impact in health resources. It is estimated that the management of venous ulcers uses between 1% and 3% of the annual budget in countries with developed health systems. In Chile, thousands of millions of pesos were spent in 2008 (2) .
In the 1960's, dressings started to be developed for chronic wound treatment in moist environments (APCAH), starting a rapidly changing career in the clinical research process, describing different treatments, growth factors, the application of microcurrent (3) , use of plasma rich in platelets for the healing of chronic ulcers in the lower limbs (4) .
On the other hand, the interest in complementary therapies has increased in recent years, which has lead to the investigation of products traditionally known as beneficial for venous ulcer healing. Various papers have reported on the speed and effectiveness of wound healing treated with honey, besides its low cost. Studies have been developed to reintroduce its use in wound treatment, analyzing its anti-inflammatory, antibacterial and healing properties (5)(6)(7) . Multifloral bee honey has demonstrated its effectiveness to treat burns, pressure ulcers and wounds (8)(9) . Recently, dressings have been developed for wound treatment based on Manuka honey from New Zealand (Bio18+Manuka Honey, Medihoney ® and L-Mesitran ® ). On the other hand, in Chile, the use of extract from monofloral Ulmo (Eucryphia cordifolia) honey has been patented with bactericidal and fungicidal properties (10) .
It is known that ascorbic acid is an essential factor in the regeneration process, as it promotes the proliferation of fibroblasts, AND synthesis and the mitochondrial metabolism, stimulates the development of the baseline membrane and reduces wound contraction (11)(12) . The action of this vitamin has been studied in wound healing in guinea pigs through oral administration. The results showed that oral vitamin C improved the collagenization of the wound in comparison with a control group of animals (on a normal diet but without an extra dose of the vitamin studied) (13) . The action of oral vitamin C was studied in mice injuries, demonstrating that its administration increased the levels of tissue hydroxyproline, improving the tissue healing and the tensile strength at the scar level (14) .
Few studies have demonstrated the synergic effect of Ulmo honey associated with ascorbic acid. Our research team assessed this effect experimentally in type B burns in guinea pigs (Cavia porcellus), histologically observing its regenerative effects (15) . In this study, it was demonstrated that the unique use of Ulmo honey reduces the possibility of infection, inflammation and edema, leading to rapid healing. The formation of granular tissue, however, the activation of fibroblasts, formation of baseline membrane and keratinization were faster and better when the therapy was associated with ascorbic acid.
The role of the baccalaureate nurse should be highlighted, who is in charge of the dressings and should be trained for the management of wound care. This implies a standard criterion in the healing process and the comprehensive assessment of the injury evolution.
To comply with these criteria, since the year 2000, the ministerial incorporation of a series of clinical guidelines has gained importance with a view to the management and treatment of wounds and ulcers (2) , in response to the need to train specialized monitors. According to article No. 113 of the Chilean Health Law (16)  In view of this problem, this study was developed, whose main objective was the clinical assessment of the effect of treatment using Ulmo honey and oral vitamin C in patients with venous ulcers.

Method Study design and selection of patients
This study, which is part of the project DIUFRO

Results
The After the monitoring period, five patients presented an ulcer relapse, after a mean period of six months, whose main cause was non-compliance with the postdischarge relapse prevention measures. The healing time according to the venous ulcer classification is indicated in Table 1. All lesions constituted epithelialization islets that soon gave way to healing bridges. In Figures 1 and 2, images of the treatment based on Ulmo honey and ascorbic acid are shown for a female patient with type 3 venous ulcer (VU).
The wound had existed for approximately one year.
Twenty days after the treatment, the wound showed less than 50% of necrotic tissue. At the end of the treatment, the re-epithelialized area corresponded to 100%, without any edema surrounding the ulcer, and the patient was discharged after one month. In Figures 3 and 4, images of the treatment based on Ulmo honey and ascorbic acid are shown for a male patient with type 3 venous ulcer (VU). At the end of the treatment, the re-epithelialized area corresponded to 100% and the patient was discharged after one month.
All treated patients showed a healing mechanism by secondary intention, with dressings applied according to the established protocol, without the need for dermoepidermal grafts. Wound after 20 days of treatment, less than 50% of necrotic tissue, 50% of granular tissue, edema surrounding the ulcer (+) and granulation and epithelialization bridges.     (17) .
No signs of infection appeared in the patients studies, which did happen in other treatments, such as autotransplantation, with a 3% infection rate (18) . To achieve this antibacterial action, the osmolarity, acidity and the presence of phytochemical compounds are important. In addition, the glucose oxidase enzyme present in honey is activated, catalyzing a slow production of H2O2, which inhibits the bacterial growth.
This capacity varies among different types of honey.
The main sugars in bee honey in general are fructose and glucose, with about 20% of humidity, proteins, vitamins and enzymes; it contains 35 minerals, lipids and flavonoids, besides another series of elements, among which germicide and inhibin stand out, which serve as natural antibiotics (19) . The honey from the Manuka tree (Leptuspermun spp.) is more effective when compared to treatment using Hydrogel. Its excellent antibacterial effects were demonstrated (20) , but comparative studies between Manuka and Ulmo (Eucryphia cordifolia) honey have showed that the latter achieved a better antibacterial effect for species like Staphyloccus aureus, Escherichia coli and Pseudomonas aeroginosa (21) . The group of patients treated includes diabetic and hypertensive patients and patients with infected wounds. These were no reason for exclusion, nor did they affect the healing of the wounds treated, as these diseases were controlled and medically stabilized.
No evidence was found as to the best option for the topical treatment of venous ulcers. Most authors agree about the benefits of honey for wound healing, showing statistical evidence of its superiority in terms of the healing time when compared to other products (22) .
Research suggests that the ideal alternative is a simple dressing, which is low-cost, non-adherent and acceptable to the patient (23) , properties of the proposed treatment based on Ulmo honey and vitamin C. The antioxidant capacity of bee honey has been endorsed.
In addition, it activates the monocytic line, with the consequent release of cytokines, tumor necrosis factor alpha and interleukins (24) . If these qualities of honey are combined with the benefits of ascorbic acid, such as its great anti-inflammatory power, direct stimulation of collagen fiber synthesis and four-times higher proliferation of fibroblasts (25) , it could be inferred that we are boosting the honey-based treatment through the daily consumption of this vitamin.

Conclusion
The