The Use of a Sea Salt-based Spray for Diabetic Foot Ulcers: A Novel Concept

Several patients present to wound healing specialists seeking a natural or alternative medical approach to their wounds. The purpose of this prospective, case-cohort study of 10 patients was to evaluate the use of Oceanzyme Wound Care Spray (Ocean Aid, Inc, Boynton Beach, FL) in improving healing in diabetic foot ulcers during a 12-week period.This product contains water purified by reverse osmosis, coral reef sea salt, lysozyme, and sodium benzoate. The primary endpoint was wound closure, and secondary endpoints were infection rate and wound area reduction. Overall, 2 patients healed, 2 withdrew, and the remaining 6 had an average of 73% reduction in wound area. While more study is needed, the use of this sea salt-based spray may provide a viable alternative for patients seeking a natural therapy for their wound care.  

The Centers for Disease Control and Prevention (CDC) estimates 29.1 million Americans (9.3% of the U.S. population) live with diabetes, including 28% who are unaware of their disease.  Additionally, it is estimated that 37% of adults ≥ 20 years, and 51% of those ≥ 65 years have prediabetes, or just over one-quarter of the entire U.S. population.¹ Equally alarming is that diabetes costs the United States nearly $250 billion dollars, in both direct and indirect expenditures.¹ Foot ulcers are a frequent complication of diabetes. The cost associated with treating a diabetic foot ulcer (DFU) alone has been documented to be between $25 000 and $60 000.²

Diabetes leads to peripheral polyneuropathy, affecting all 3 divisions of the peripheral nervous system (sensory, motor, and autonomic). Sensory loss in the feet results in the inability to appreciate any minor trauma from ill-fitting footwear or normal walking, which may result in a chronic DFU. A DFU is often the precursor to amputation, especially in the presence of infection or ischemia.³ 

While surgery is indicated for many DFUs, dressings and topical medications are needed to support the surgical intervention and prevent infection. Due to the ease of bringing new natural healing products to market, there are countless natural topical remedies available to treat DFUs, including honey, mud, and minerals. Some patients may even prefer a natural product to a synthetic one.

The study authors evaluated the use of a sea salt solution containing natural enzymes in the healing of 10 DFUs. Seawater has been used for centuries to assist with wound healing because of the abundance of minerals it contains. Wounds require a moist environment, with a bacterial bioburden below the threshold of critical colonization for healing.⁴ Seawater may be able to aid in those goals.

The concept of using a product derived from seawater to heal wounds provides some intrigue. To appreciate the efficacy of these seawater components, the authors’ study was performed over a 12-week period to determine if Oceanzyme Wound Care Spray (Ocean Aid, Inc, Boynton Beach, FL), a sea salt-based spray, would improve wound healing or reduce infection. 

The sea salt-based spray the authors evaluated consists of coral reef sea salt, lysozyme, and sodium benzoate, in addition to water that has been purified through reverse osmosis. Coral reef sea salt contains trace elements and minerals that are essential for living cell function, which are present in human tissues and fluids. Lysozymes are a group of glycoside hydrolases found in a human’s natural immune system, which act as catalysts in bacterial cell wall hydrolysis.⁵ Lysozymes are commonly found in biological liquids such as tears, saliva, blood, and urine, and they occur naturally in many organisms such as plants, insects, birds, reptiles, and mammals. The original antimicrobial properties of lysozymes were discovered in 1909 within egg whites, and they provide defense from many gram-positive microbes.^6,7 Humans have significant lysozyme activity in the conjunctiva, where its failure leads to conjunctivitis.⁸ The same theory has been applied to wounds, whereby lysozymes can act as a natural barrier to prevent further colonization and infection from pathogenic bacteria. Sodium benzoate is the sodium salt of benzoic acid, and it has been used by food manufacturers for more than 80 years to inhibit microbial growth. It can prevent growth of almost all microorganisms including yeast, bacteria, and fungi.⁹

The aqueous solution in the sea salt-based spray is based in water purified via reverse osmosis. Reverse osmosis is a process in which an applied pressure is spread over a semipermeable membrane that prevails over a particular gradient, creating osmotic pressure. By doing so, most solutes (chemicals, heavy metals, pesticides, pathogens, bacteria, viruses, radioactive materials, and other contaminants) are barred from crossing this membrane, leaving a pure solvent (water) to cross. The reverse osmosis semipermeable membrane is rated at 0.0001 micrometers thick (0.00000004 in), creating a pure form of water.

This Western institutional review board-approved study commenced at a single center in the United States, which specializes in DFU care, over a 12-week period to determine if a sea salt-based spray had a beneficial effect on DFU healing in a 10-patient cohort. Secondary objectives of the study were to track the incidence of wound infections, change in wound area, and the percentage of wounds achieving a 100% granular base by the end of treatment. Clinical outcome data focused on the number of infection-free days experienced during treatment.

Ten diabetic subjects were recruited from patients at an outpatient clinic specializing in DFU care. Inclusion criteria consisted of patients with type 1 or type 2 diabetes under a physician’s management for glycemic control and at least 1 DFU > 1 cm² (University of Texas San Antonio [UTSA] classification 1A) present for > 30 days and < 12 months. Subjects were required to have adequate circulation to the affected extremity, as demonstrated by either palpable dorsalis pedis and posterior tibial pulses on the index extremity or an ankle-brachial index (ABI) with results between 0.7 and 1.2 within the preceding 60 days. Subjects who provided informed consent were willing to participate in all procedures and follow-up evaluations necessary to complete the study. 

Exclusionary criteria included any wound infection, target ulcers probing to bone (UTSA Grade 3A-D), and ulcers > 30 cm². Subjects with recent steroid, recombinant human platelet-derived growth factor, or bioengineered tissue use within 4 weeks prior to screening, or antibiotic use within 1 week prior to screening were excluded as well as those who had collagen vascular disease or autoimmune connective tissue disease, which were
determined by medical history and their physicians. Finally, subjects with a known history of poor compliance with medical treatments or those with known sensitivity to lysozyme, sea salt, or lactoferrin were also excluded. 

All patients were appropriately screened to determine eligibility and then signed informed consents. Medical histories, including complete medication lists, were obtained, and vascular and diabetic foot exams were performed. All foot ulcers were sharply debrided of nonviable tissues during visits when necessary and offloaded with the appropriate device as determined by the investigator. All patients were seen weekly (+/- 2 days) for the duration of the study. Computerized photo measurement of the surface area and depth of the study ulcer were recorded at the initial visit, weekly, and at study exit or withdrawal, using the Silhouette imaging device (ARANZ Medical, Christchurch, New Zealand). This imaging device is a U.S. Food and Drug Administration (FDA)-cleared wound documentation device that has been shown to accurately measure DFUs in previous clinical trials.¹⁰ Each patient was asked to keep a diary to record each dressing change performed between the weekly required visits. The study ulcer was cleansed with the sterile sea salt-based spray solution. Rinsing, swabbing, and irrigation were all acceptable methods of cleansing. After cleansing the ulcer with the spray, the investigator applied a wound dressing of gauze sponges soaked in the sea salt-based spray on the targeted ulcer. This primary dressing was then dressed according to the investigators’ standard of care, such as covered with foam or dry gauze, gauze roll, and an ACE wrap. 

The subject was instructed to wet the primary dressing, without removing it, 3 times per day with the spray. All subjects were offloaded using a removable cast walker (Aircast Diabetic Walker; DJO Global, Vista, CA). The subjects returned to the clinic weekly for treatment for up to 12 weeks or until complete wound healing was achieved.

If an infection developed over the course of treatment, the ulcer was treated with aggressive sharp debridement, as required, and appropriate systemic antibiotic treatment until the infection resolved. The investigator treated the infected ulcer according to the standard of care. The patient continued to use the sea salt-based spray in combination with the standard of care treatment for wound infection.

The final visit data were collected at either the conclusion of the study (week 12) or upon early withdrawal from the study. The following procedures, evaluations, and/or assessments were obtained at the final visit: patient diaries, medication and therapy reviews, assessments of targeted ulcer, further debridement of targeted ulcer if deemed clinically necessary, and photography and measurement of targeted ulcers with the imaging device. Closure was defined at 100% epithelialization without drainage. The patients were asked to return 1 week following closure to confirm the wounds remained closed.

Ten ulcerations in 10 subjects with type 2 diabetes were entered into the study (7 male, 3 female), with an average age of 58 years (38–79 years) and a mean body mass index of 35.2 (25.2–44.3). Data are presented in Table 1. Six ulcerations were located in the midfoot with the remaining 4 in the forefoot. Eight were plantar in location, 1 was dorsal, and 1 lateral. Ulcers were present for an average of 101 days (30–180 days) and measured at a mean area of 3.1 cm² (0.6 cm² – 9.3 cm²). 

One patient was hospitalized due to a coronary episode and was terminated from the study after the fifth visit, though it should be noted that the ulceration at termination measured 0.1 cm².

At the conclusion of the 12 weeks, 2 wounds achieved complete wound healing (1 plantar, 1 dorsal), 2 patients withdrew, and the remaining 6 patients had an average wound size of 1.15 cm² (0.1 cm²–6.1 cm²). Of these remaining 6 patients, 3 developed infections (2 methicillin-resistant Staphylococcus aureus infections within wounds and 1 with cellulitis, all treated with linezolid). No other patients who either healed or completed the study had positive cultures. Upon review of the patient diaries, only 4 out of 8 subjects who completed the study (1 healed, 3 not healed, and 1 infected) were compliant with recording the 3 daily applications. The patients who did not comply with logging the 3 daily doses, applied the sea salt-based spray 2.4 times per day on average.

The novel idea of compounding the key ingredients found in seawater, which has been used as a cleansing agent for centuries, into an easy-to-use spray to promote healing in DFUs is a promising concept. The application of lysozyme, a natural antimicrobial, has been scientifically shown to reduce bacterial loads, provide a protective barrier against possible pathogens, and prevent pathogens from recolonizing in previously debrided ulcerations. Both lactoferrin and lysozyme are bacteriostatic, but in combination have been shown to be bactericidal.¹¹

Wound products are subject to various approval processes set forth by the FDA, but they do not all follow the same pathway. The most stringent pathway is the New Drug Application for new drugs to be used on wounds or for infections.  It requires years of study in the efficacy and safety of the drug. On the medical device side, the Prior Market Approval pathway is similar and involves study of both efficacy and safety.  The 510k pathway is less stringent and is implemented when a predicate device is determined to be similar to the new device under review.  In this case, the efficacy from the predicate device is used but safety data still has to be shown. The 361 pathway is common for human tissue products, such as amniotic tissue, and it has a fairly low bar for approval.  But natural products, especially when determined for cosmetic use, are not regulated by the FDA.  Since the regulatory burden is low, many natural products are available for use in wounds or skin injury.  

Approximately 30%–50% of patients in industrialized nations use some form of complementary or alternative medicine to prevent or treat health problems.¹² Patients who become anxious about the risks of pharmaceuticals may seek natural alternatives. The ingredients in the product evaluated herein provide patients with a natural option in wound care treatment. In this small study, the approach was not harmful to patients.

The study’s major drawback was the subjects’ level of compliance regarding the study protocol’s multiple daily applications of the spray. Only half of the subjects who completed the trial were compliant with the 3 daily applications, indicating the frequency may have been burdensome. Because of the small sample size, noncompliance could not be evaluated as an independent variable in the study’s outcomes. In addition, as a pilot case-cohort, the study was not powered to an appropriate size, nor controlled. However, in the subjects who completed the study, 2 healed and 6 had an average wound area reduction of 73% in 12 weeks. In many studies on wound healing, area reduction alone is not emphasized as an endpoint, but the speed of wound healing may be just as important as other endpoints measured, such as closure, infection rate, and amputation rate. Further study is needed to determine if certain treatments speed 1 phase of wound healing, thus shortening the overall healing time, though not intended to bring the wound to complete closure.

To the authors’ knowledge, this study is the first to report on the effects of a sea salt-based spray on DFU healing and infection rate in 8 subjects who completed the study. The study’s authors believe there is promise in using seawater components to promote the healing of DFUs and to lessen the likelihood of infection along with a low per-use cost, but more studies are required to confirm these hypotheses. This pilot study opens the door for a unique, new natural therapy to aid in daily wound care.

The authors would like to thank Catherine Gregor, MBA, CCRP for her assistance in the design, approval, and management of the study.

From the Sherman Oaks Hospital, Los Angeles, CA; and Indiana Foot & Ankle, Jasper, IN

Address correspondence to:
Lee C. Rogers, DPM
Sherman Oaks Hospital
Department of Surgery
4911 Van Nuys Boulevard
Los Angeles, CA 91403
lee.c.rogers@gmail.com 

Disclosure: Dr. Rader was the principal investigator of the study, and Dr. Rogers authored the protocol.