# Honey-Based Medicinal Formulations: A Critical Review
## 4 Discussion  
Most commercial and noncommercial honey-based medicinal formulations seem to be targeted at topical wound care applications with only a few products aiming for alternative routes of administration (e.g., syrups, eye drops, pastilles). All commercially available gels, dressings, ointments, creams, and pastes have common topical uses. They are, for example, indicated as OTC formulations for the treatment of minor abrasions, lacerations, minor cuts, minor scalds, and burns, whereas, under professional healthcare professional supervision, they are used for non-draining to moderately evuding wounds. They are also commonly intended for the management of diabetic foot ulcers, leg ulcers (venous stasis ulcers, arterial ulcers, and leg ulcers of mixed etiology), pressure ulcers/sores (partial and full thickness), first-degree and second-degree partial thickness burns, donor sites, and traumatic and surgical wounds. Reviewing the literature on commercial and noncommercial honey formulations, it transpires that, to date, only a few different types of honey have been used in these preparations. As briefly outlined below, for most of these honey, evidence of bioactivity supporting their use in these medicinal formulations is available. _Leptospermum_ honey, also called Manuka honey, appears currently to be the honey used in a majority of the commercial formulations, most likely as it has been widely demonstrated to have high antioxidant and antibacterial activities, which are beneficial for most intended medicinal applications. Manuka honey contains methylglyoxal (MGO), which is derived from the precursor molecule dihydroxacetone (DHA) present in the pollen and nectar that the bees collect from many _Leptospermum_ species. Next to a low pH and high osmolarity (which is common to all honeys), MGO has been demonstrated to be a major contributor to the observed antibacterial activity of _Leptospermum_ honey [6,8]. Different concentrations of _Leptospermum_ honey have been used in commercial formulations ranging from 25% to 100% (Table 1). Some in vitro studies demonstrated promising activity for noncommercial formulations prepared with _Leptospermum_ honey (13-80%), for instance, antibacterial activity, thereby promoting wound healing (Table 2) [27,52,53]. Next to Manuka honey, Revamil source (RS) honey is a medical-grade honey that is presently approved for clinical application. The manufacturer withholds the details on the origin of this honey, stating only that it is produced by a standardized process in greenhouses which contributes to reproducible activity that is an important criterion for clinical application. [39]. The commercially available Revamil gel is, for instance, prepared from pure RS honey (Table 1). As mentioned previously, buckwheat honey, a dark honey high in antioxidant activity [54], has been formulated into dressing by Dermagenics in the USA under the brand name of MelMaxTM and MelDraTM. Researchers at Brock University revealed that buckwheat honey has strong antibacterial effects against antibiotic-resistance bacteria [54]. In a separate study comparing buckwheat honey with Manuka honey, scientists found that buckwheat honey contains a higher percentage of sugars, proteins, and total phenolics, as well as less MGO, and it exhibits equivalent antibacterial activity against the bacteria _Staphylococcus aureus_ and _Pseudomonas aeruginosa_[55]. Like Manuka honey, Buckwheat honey contains many minerals that play an important role in human health and normal physiological functioning, although its concentrations of Fe, Mn, and Zn are even higher than those found in Manukahoney [55]. To what extent these minerals contribute to the honeys' bioactivities in a range of medicinal applications is, however, not documented in the literature. Kanuka honey is produced from the New Zealand Kanuka bush (_Kunzea ericoides_). It has negligible MGO levels but contains hydrogen peroxide. As demonstrated in in vitro studies, it shows antibacterial and antioxidant activity [55].