Written by Angeline A. De Leon, Staff Writer. Compared to the control group, application of ozone following wound debridement significantly improved the rate of wound healing in the fifty participating diabetics with diabetic foot ulcers.

diabetesAccording to recent reports, one of the most challenging complications associated with diabetes mellitus are diabetic foot ulcers (DFU) 1. Retrospective studies show that DFUs account for almost 20% of diabetes-related wounds and in the U.S., diabetes is the leading cause of non-traumatic lower extremity amputations 2. DFUs generally involve impaired tissue healing, delayed wound closure, and reduced collagen levels due to lower expressions of endogenous growth factors in the wound 3. Early-stage treatment for DFUs, therefore, have targeted the upregulation of various growth factors involved in wound healing (e.g., vascular endothelial growth factors, VEGF; transforming growth factors-β, TFG-β; platelet-derived growth factors, PDGF) 4. The antioxidative capacity of ozone, along with its ability to increase oxygen levels in the body, make it a powerful therapeutic agent in the facilitation of wound healing 5. Animal studies suggest that the administration of ozone may prevent development of atherosclerosis 6, and although the number of clinical trials which have examined the efficacy of ozone therapy for DFU wound healing is limited, a few studies have reported improved diabetic outcomes as a result of ozone treatment 7. In fact, one study found that the use of ozone therapy in conjunction with conventional treatment was better than standard treatment alone in facilitating the complete healing of DFUs 8. Based on current findings, a study 9 published in Oxidative Medicine and Cellular Longevity sought to evaluate the impact of ozone therapy on early-stage DFU wound healing as well as expressions of VEGF, PDGF, and TFG-β.

Using a randomized, controlled trial design, the present study recruited a total of 50 type 2 diabetic patients (aged 18 years or older) suffering from DFUs (classified as Wagner stage 2-4). Following debridement (medical removal of dead or infected tissue), half of patients were randomly assigned to ozone therapy or control. Noninvasive oxygen-ozone treatments involved administration of 52 µg/mL ozone (total volume 20-50 mL) in a special bag for 30 minutes daily for 20 days using an ozone generator device, in addition to standard treatment. Control patients received only standard treatment (involving debridement once every two days and appropriate wound dressings). Wound sizes were measured at baseline and Day 30 (and evaluated on a scale of 0 to 3, 0 indicating no change or worsening and 3 indicating complete wound healing), and tissue biopsies were performed at baseline and Day 11 to detect collagen deposition. Expressions of growth factor proteins in tissue specimens were measured using immunohistochemical examinations.

At the end of treatment, efficacy rate of wound healing (based on number of patients whose wound healing improved over the course of treatment) was significantly higher in the ozone group vs. controls (92% vs. 64%, p = 0.037). At Day 20, wound size reduction of the ozone group was also found to be significantly greater than that of controls (6.84 +/- 0.62 vs. 3.19 +/- 0.65 cm2, p < 0.001), and the ozone group showed a higher amount of collagen fiber in their wounds than the control group (4.48 +/- 0.43 vs. 3.07 +/- 0.23, p = 0.012). In addition, after treatment on Day 11, expressions of VEGF, TGF-β, and PDGF proteins were significantly higher in the ozone vs. control group (3.34 +/- 0.27 vs. 2.03 +/- 0.16, p < 0.001; 7.83 +/- 0.49 vs. 6.10 +/- 0.45, p = 0.018; 4.09 +/-. 0.14 vs. 3.06 +/- 0.13, p < 0.001, respectively).

Overall findings indicate that oxygen-ozone treatment can significantly improve the effective rate of wound healing in DFU patients, suggesting the involvement of an upregulation process for enhanced expression of endogenous growth factors in the local wounds. The presence of increased collagen content associated with ozone treatment provides further evidence for ozone therapy as a promising, non-invasive early-stage approach to managing wound care in diabetic patients.

Source: Zhang, J, Guan M, Zie C, et al. Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers. Oxidative Medicine and Cellular Longevity. 2014; 273475. DOI: 10.1155/2014/273475.

Click here to read the full text study.

Posted June 13, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. The Lancet. 2005;366(9498):1719-1724.
  2. Wilcox JR, Carter MJ, Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA dermatology. 2013;149(9):1050-1058.
  3. Jude E, Blakytny R, Bulmer J, Boulton A, Ferguson M. Transforming growth factor‐beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers. Diabetic Medicine. 2002;19(6):440-447.
  4. Hanft J, Pollak R, Barbul A, et al. Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers. Journal of wound care. 2008;17(1):30-37.
  5. Delgado-Roche L, Martínez-Sánchez G, Re L. Ozone oxidative preconditioning prevents atherosclerosis development in New Zealand white rabbits. Journal of cardiovascular pharmacology. 2013;61(2):160-165.
  6. Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Medicinal research reviews. 2009;29(4):646-682.
  7. Martínez-Sánchez G, Al-Dalain SM, Menéndez S, et al. Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology. 2005;523(1-3):151-161.
  8. Wainstein J, Feldbrin Ze, Boaz M, Harman-Boehm I. Efficacy of Ozone–Oxygen Therapy for the Treatment of Diabetic Foot Ulcers. Diabetes technology & therapeutics. 2011;13(12):1255-1260.
  9. Zhang J, Guan M, Xie C, Luo X, Zhang Q, Xue Y. Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers. Oxidative medicine and cellular longevity. 2014;2014.