Mānuka honey as Rongoā for animals in agriculture

ABSTRACT

The Mānuka tree is unique to Aotearoa New Zealand and was recognised by early Māori traditions as a taonga (treasure) due to its wide variety of uses and is the first globally recognised taonga. Mānuka honey (MH) is reported to have exceptional antioxidant and antimicrobial properties. The objective of this review is to summarise the current published peer-reviewed literature for benefits of the use of MH as a Rongoā (traditional medicine) in ruminant livestock and companion animals to support the potential use of MH as a therapeutic for companion animals and livestock. The key finding was that there is very little peer-reviewed literature providing scientific evidence for the use of MH as a therapeutic in livestock and companion animals. There are a wide range of products now commercially available that have MH as an active ingredient. However, further scientific studies are required to evaluate the direct effects of MH relative to its effects when used in conjunction with other compounds, dose–response effects, and the effect of the Unique Mānuka Factor and methylglyoxal levels on efficacy in order to provide scientific evidence to support the efficacy of MH as a functional food or therapeutic in livestock and companion animal species.

KEYWORDS:

• Manuka honey
• Rongoā
• livestock
• Māori
• ruminants
• companion animals

Introduction

Sustainable resource use, ecological production, equitable distribution of provisions and community wellbeing are cornerstones of the traditional Māori way of life, founded in Kawa (etiquette) and Tikanga (culture). Māori landowners want to optimise their land use and connect their supply to customers via a ‘product’ that is grounded in Te Ao Māori. A key goal is to maximise a wide range of ‘values’ (environmental, cultural, social, and economic), and express kaitiakitanga (stewardship) over their natural resources, identity, and future.

Mānuka (Leptospermum scoparium) is unique to Aotearoa New Zealand and was recognised by early Māori traditions as a taonga (treasure) due to its wide variety of uses (Bil 2016). Mānuka is the first taonga that has gone global. Māori have a cultural connection to Mānuka based on our whakapapa. Tane Mahuta separated his parents Ranginui and Papatuānuku and through various unions gave rise to Mānuka and other native species.

Aotearoa New Zealand agriculture is under increasing pressure to reduce chemical and drug input and the farming community is seeking solutions to enhance animal health, wellbeing, and productivity through natural products. Furthermore, incentives are needed to encourage Māori landowners to develop underutilised whenua and new business opportunities are needed to support sustainable land use, economic growth, and community wellbeing.

The production of honey and its related products for domestic and export markets is an important economic activity in Aotearoa New Zealand. Zuchetta et al. (2022) recently reviewed the scientific literature, technical literature and traditional knowledge databases describing the chemical properties and biological activity of four New Zealand monofloral honeys to support the visions and aspirations of Māori. Mānuka honey (MH) is the most prominent with well-established uses in humane medicine, however, its use in veterinary medicine is relatively new. Thus, there is limited science-based evidence for benefits of the use of MH in livestock or companion animal species. The aim of this review is to summarise the current peer-reviewed literature on the potential value proposition for use of MH as Rongoā for animals, notably livestock species (e.g. cattle, sheep, alpaca, pigs, horses) and companion animals (dogs and cats).

Rongoā Māori

Rongoā Māori is the traditional healing system of the indigenous Māori people of New Zealand (Ahuriri-Driscoll 2014; Mark et al. 2017). Rongoā is rooted in ancient knowledge passed down through generations and embodies the use of plants and other natural resources as well as spiritual healing, massage and incantations (the power of karakia) to promote physical, spiritual and emotional healing. Tohunga Rongoā (practitioners) consider both the underlying causes of an ailment (e.g. environment, lifestyle, spiritual state) and the symptoms to address imbalances and restore equilibrium. Rongoā also fosters a profound connection with nature with Tohunga Rongoā drawing on the wisdom of the land and indigenous plants which are taonga (treasures) with inherent healing properties. The sustainable and respectful use of these resources reflects the Māori belief in reciprocity with the natural world. This ancient practice continues to enrich the lives of Māori communities, preserving their traditions and promoting well-being in a comprehensive and meaningful way.

Rongoā Rākau (tree or wood) is a specific branch of Rongoā that focuses on the medicinal use of native plants and trees (Williams 2001). Identifying and using various parts of trees including leaves, bark, roots and resins to create remedies for a wide range of health conditions is a key part of Rongoā Rākau. The Tohunga Rongoā possesses an intricate understanding of the healing properties of different native plant species and when and how to harvest and process them. They have passed down this knowledge through generations, ensuring the preservation of their traditional healing practices. Many indigenous plant species possess unique medicinal attributes, and the preparation of remedies involves specific rituals and protocols to harness their healing powers effectively.

Classification and biological properties of MH

Mānuka honey is a unique mono-floral honey obtained from the Mānuka myrtle tree that belongs to the Myrtaceae family which grows as a shrub or small tree throughout New Zealand and Eastern Australia (Brophy et al. 2000). MH can be classified according to two properties: Unique Mānuka Factor (UMF) and methylglyoxal levels (MGO). The UMF factor is based on its antiseptic properties and can range from 5 + to 28 + mg/kg. MGO is the primary non-peroxide antibacterial constituent with quantities ranging from 83 + to 1450 + mg/kg. A range of carbohydrates and polyphenolic compounds are also implicated in the classification of MH (Alvarez-Suarez et al. 2014). Mānuka honey has a high osmolarity, low pH (3.5-4.5), and high sugar content which inhibits microbial growth (Brosseau et al. 2020).

Mānuka honey is highly valued for its non-peroxide anti-bacterial properties, largely attributed to its exclusive MGO content, is rich in a wide range of macro- and micro-nutrients and has been found to confer various health benefits credited to its unique chemical composition (reviewed by El-Senduny et al. 2021). Honey, including MH, is a natural product enriched with multiple phenolic compounds, enzymes and sugars with antioxidant, anticarcinogenic, anti-inflammatory, and antimicrobial properties (Carter et al. 2016; Scepankova et al. 2021). One of the primary uses of MH in veterinary medicine is in wound healing because of these antimicrobial properties.

Wound healing

Wound healing is a complex multi-stage process whereby the integrity and function of the tissue are restored (Fossum 2012; Scepankova et al. 2021). A wide range of topical treatments are commercially available to support wound healing, with honey as the active ingredient. Based on small animal studies, honey confers specific benefits for wound healing including acceleration of dermal repair and epithelialization, angiogenesis promotion, immune response promotion and a reduction in healing-related infections with pathogenic microorganisms (Scepankova et al. 2021). Mānuka honey has been reported to have therapeutic advantages in wound healing compared to other honeys due to its potent antibacterial and antioxidant properties (Alvarez-Suarez et al. 2014; Taskandi 2021). The reported beneficial effects of MH on wound healing in humans are postulated to be due to the stimulation of macrophage migration, increasing tissue turnover and the creation of a protective surface barrier that promotes healing (Alvarez-Suarez et al. 2014). MH may also have pro-inflammatory effects increasing the release of cytokines from leucocytes that regulate angiogenesis and fibroblast proliferation along endothelial cells based on horse (Bischofberger et al. 2013) and rat studies (Nooh and Nour-Eldien 2016). Lu et al. (2019) also reported that when used at appropriate concentrations, Mānuka honeybased wound dressings may provide a promising treatment for infected chronic wounds including those with P. aeruginosa biofilms. Honey-based treatment strategies for burns and infected wounds based on recent pre-clinical research have recently been reviewed by Krishnakumar et al. (2020).

Medical grade honey (MGH) is a term used by healthcare professionals to refer to honey used in wound treatment (Maruhashi 2020) and must fulfil specific criteria (reviewed by Taskandi 2021). Medical grade honey is reported to be a promising wound therapy due to its wide spectrum of antimicrobial efficacy with no known resistant strains and is effective against clinical bacterial and fungal isolates and their associated biofilm formulation (Taskandi 2021). It is also cost-effective, safe and is considered to be a potential alternative to antibiotics or complementary therapy for treatment of locally infected wounds (Taskandi 2021). Most commercially available MGH are formulated with MH as it is one of the most well-studied honey varieties in the world and is the first honey type to obtain the status of MGH (Scepankova et al. 2021).

Ruminant/pseudo-ruminant species

The peer-reviewed literature on the potential therapeutic evidence for MH in ruminant/pseudo-ruminant species was sourced using the publicly available bibliographic databases Scopus, PubMed and Google Scholar. All articles where MH was evaluated in ruminants were included in. In the review by Vogt et al. (2021), there was only one study in ruminant species where potential effects of MH on wound healing were reported (Paramasivan et al. 2014). Since that review, a further six studies in ruminants (goats, sheep and cattle) and one study in alpaca where MH has been used in wound healing treatments have been reported (Table 1). Chigerwe et al. (2020) reported on the use of MH as part of a treatment regime to heal burns in sheep, goats and pigs following wildfire injuries, and Williams et al. (2022) reported on chronic wound healing involving the use of MH in a goat. However, while MH was used as part of the treatment regime in both case studies, the specific effect of MH on wound healing was not directly measured. Iacopetti et al. (2020) reported that MH treatment of open wounds in sheep through daily application of MH enhanced the healing process through promotion of cell proliferation and neovascularization, resulting in a pro-inflammatory effect. Immunomodulatory effects were also reported during the healing process. However, wound closure time was not influenced by MH application in that study. These authors recommended administration of MH to wounds that appear to be non-healing or chronic as MH has a long-term effect on the healing process.Poza et al. (2023) reported on a case study evaluating response to antimicrobial therapy whereby MH was placed in the cavity following the removal of a masseter abscess in an adult alpaca. This animal successfully recovered, however as there was only one animal in the case study, and there was no comparison without MH, it is not possible to determine if MH contributed to wound healing in this case. Collectively, these studies highlight the potential benefits for MH in wound healing in livestock species, particularly for treatment of chronic or non-healing wounds. However, except for Iacopetti et al. (2020), studies to date have been case studies and therefore do not provide a robust comparison of the potential wound healing benefits of MH relative to other topical treatments.

Table 1. Effect of Manuka honey on external wound healing/antimicrobial activity in ruminant species.

Animals	Type of study	Situation	Treatments	Delivery method	Duration	Outcome	Reference
Goat	In vivo	Treatment of severe chronic wounds on both forelimbs. The wound was covered with MH, during the initial period of debridement.	MH	Applied upon wound area	12 days	Effect of MH not measured.	Williams et al. (2022)
Goat/ Sheep /Pigs	In vivo	Used as topical application around the eyes, nose, ears and mouth or to treat burn skin.	MH wax salve	Applied upon wound area	Applied every 12 h until patients were discharged	Effect of MH not measured.	Chigerwe et al. (2020)
Sheep	In vivo	Bilateral wounds were surgically created on the backs	MH, hyaluronic acid (HA), and acemannan gel (AG), control (phosphate saline buffer)	Applied upon wound area	Applied daily for 42 d	HA was the best treatment for acute wounds where the priority is the reduction of healing time. MH and AG did not reduce wound closure time.	Iacopetti et al. (2020)
Cattle	In vitro	Bacteria strains isolated from cow’s milk suspected of mastitis	MH, hydrogen peroxide honey, and artificial honey dosed at 0.1, 1, 5, 10%			Six bacteria species were completely inhibited by MH at 5%.	Allen and Molan (1997)
Cattle/ sheep	In vitro	Bacteria isolated from cow’s milk, sheep’s milk, and from the Czech Collection of Microorganisms	MH-MGO100+, MH–MGO400+, and 5 types of blossom honeys at 20 and 30%	-	-	MH-MGO400 + had 100% inhibitory effect on all bacterial strains even at 20%.	Klimešová et al. (2018)
Alpaca	In vivo	Removal of masseter abscess	MH	Swab soaked in MH54	One application for 24 h	Successful response to the antimicrobial therapy.	Poza et al. (2023)
Ovine	In vivo	Frontal sinuses (Staphylococcus aureus was inoculated in sheep frontal sinuses)	In each sheep, 1 sinus was flushed with a panel of MGO concentrations ranging from 0.5–7.2 mg/mL alone and flushed with a panel of with 16.5% wt/vol MH enriched with MGO at the same range of concentrations (0.5-7.2 mg/mL; designated MH/MGO). Contralateral sinuses were flushed with saline control.	Topical application (flushes)	Twice daily for 14 d	Sinus irrigation with MH/MGO at MGO concentrations between 0.9 and 1.8 mg/mL is both safe to mucosa and efficacious against S. aureus biofilm	Paramasivan et al. (2014)

In vitro studies (Table 1) have indicated anti-bacterial effects of MH (MGO400 + but not MH-MGO100 + or blossom honey) when applied to bacteria isolated from cow and sheep milk (Klimešová et al. 2018). Indeed, complete inhibition was observed in bacterial strains isolated in milk from cows suspected of having mastitis when 5% MH was applied (Allen and Molan 1997). Paramasivan et al. (2014) reported that MH-MGO at concentrations between 0.9 and 1.8 mg/ml is safe and efficacious against S. aureus biofilm when used as a sinus irrigation. These studies highlight potential anti-bacterial effects of MH in ruminants. However, further in vivo studies are required to further explore the wound-healing and anti-microbial effects of MH in ruminants.

Monogastric livestock

The peer-reviewed literature on the potential therapeutic evidence for MH in monogastric species was sourced using the publicly available bibliographic databases Scopus, PubMed and Google Scholar. All articles reporting on the use of MH in monogastric livestock were included. The literature describing the potential effects of MH in wound healing in monogastric livestock species is presented in Table 2. The review by Vogt et al. (2021) reported a range of responses to MH in the healing of created skin wounds in horses, including a more organised granulation tissue bed early in wound repair (Bischofberger et al. 2016), reduced wound retraction, and overall healing time (Bischofberger et al. 2013; Tsang et al. 2017). However, Bischofberger et al. (2015) reported wound healing variables did not differ between MH gel, activated protein C, commercial antibiotic ointment, or no treatment control. Mandel et al. (2020) reported that intralesional application of MGH (not specifically MH) can improve the repair of lacerations in horses. Healing times of contaminated equine distal limb wounds were improved following application of a MH gel (Bonifer-Engelhardt 2020), and surgical site infections have also been reported to be reduced following a single application of MH compared to untreated control wounds (McGovern and Bladon 2021). Horses that underwent colic surgery have also been reported to have reduced incisional infections following MH application to the linea alba prior to skin closure (Gustafsson et al. 2021). Anis et al. (2021) also report improved healing of created skin wounds in donkeys when MH was included in a composite with many other ingredients, however specific effects of MH were not reported in that study. In contrast, McIver et al. (2020) reported no effect of MH-UMF20, MH-UMF5, or MH-UMF5 + 1% cannabinol application to skin wounds contaminated with faeces in horses.

Table 2. Effect of Manuka honey on external wound healing/antimicrobial activity in monogastric large animals.

Animals	Type of study	Situation	Treatments	Delivery method	Duration	Outcome	Reference
Donkeys Experimental study	In vivo	Created skin wounds	MH, gentamycin 0.1%, zinc (zinc oxide 20%), Revan (honey, calendula extract, aloe vera extract, tea tree oil, panthenol, vit E, propolis, centella sciatica, myrrh, triclosan, vit C, silicon) and the composite ointment (chamomile oil, rosemary oil, clover flower bee honey)	Applied upon wound area	Daily until one of the bilateral wounds healed completely	Wounds treated with the composite were healed firstly, while all other wounds were still opened.	Anis et al. (2021)
Horses	In vivo	Lacerations treated by flied practitioners	MH (n = 69), and control cases (n = 58)	Applied upon wound area	Applied prior skin closure	Intralesional application of MGH in repaired lacerations improved the descriptive observations.	Mandel et al. (2020)
Horses	In vivo	Metacarpi created skin wounds, contaminated with faeces	MH UMF20, MH UMF5, MH UMF5 + 1% cannabinol	Applied upon wound area	Daily for 42 days	No effects.	McIver et al. (2020)
Horses	In vivo	Contaminated distal limb wounds	MH gel	Applied upon wound area	Daily until healing	Decrease in the healing times of equine distal limb wounds	Bonifer-Engelhardt (2020)
Horses	In vivo	Laparotomy incisions	MH, and control (no treated)	Applied to the linea alba prior to skin closure	Single application	MH reduced the surgical site infection.	McGovern and Bladon (2021)
Horses	In vivo	Horses that underwent colic surgery	MH, and control (no treated)	Applied to the linea alba prior to skin closure	Single application	The prevalence of incisional infections was decrease with MH.	Gustafsson et al. (2021)
Pigs	In vivo	Fifty standardised wounds on two pigs were infected with Staphylococcus aureus	Topically applied MH, and intramuscular gentamicin	Topically applied	Applied daily for eight days	No treatment difference on S. aureus count. Wound area was unchanged with MH treatment but decreased with gentamicin.	Muhrbeck et al. (2022)
Pigs	In vivo	Either canine or 1st premolars were extracted. One of the four treatments were assigned	MH incorporated membrane in fully closed extraction site or not, control membrane, and neither membrane	-	-	No treatment differences were observed. Though, unlike control membranes, MH membrane site were covered with epithelium at 4 weeks.	Evensky et al. (2019)
Horses	In vivo	Created skin wounds	non-contaminated control wounds; contaminated (faeces) control wounds; contaminated wounds treated daily with Manuka honey gel.	Applied upon wound area	10 days	Manuka honey gel resulted in a more organised granulation tissue bed early in wound repair.	Bischofberger et al. (2016)
Horses	In vivo	Created skin wounds	MH gel, activated protein C (ACP), commercial antibiotic ointment (bacitracin–neomycin–polymixin B ointment), petrolatum, and control (not treatment)	Applied upon wound area	Daily throughout healing	Wound healing variables between MH, ACP and Control did not differ.	Bischofberger et al. (2015)
Horses	In vivo	Created skin wounds	MH, Control (no treatment)	Applied upon wound area	Daily for 12 d	MH reduced wound area by reducing retraction but did not affect overall healing time.	Bischofberger et al. (2011)
Horses	In vivo	Created skin wounds	MH, and MH gel (UMF20+)	Applied upon wound area	Daily for 12 d or until completion of the treatment	Treatment of wounds with MH and MG gel reduced wound retraction and overall healing time compared with gel and untreated control wounds.	Bischofberger et al. (2013)
Horses	In vivo	Case study	MH	Topical application	One application	MH was used as an adjunct treatment	Herdan et al. (2012)
Horses	In vivo	Created skin wounds	MH-UMF20, MH-UMF5, generic multifloral honey (GH), and saline (control)	Topical application	Daily for 12 d	Treatment with MH-UMF20 reduced overall wound healing time compared with wounds treated with GH and control wounds	Tsang et al. (2017)

In pigs, Muhrbeck et al. (2022) did not observe any difference in S. aureus count between topically applied MH 15 + or intramuscular gentamicin in wounds infected with S. aureus. Additionally, wound size was not reduced in the MH relative to gentamicin-treated animals. These observations suggest that MH dressings may be an alternative to antibiotic treatment to prevent the progression of wound infection, but not for accelerating healing. Similarly, Evensky et al. (2019) reported no differences in wound healing when MH was incorporated into a resorbable membrane compared to control treatment for tissue regeneration in pigs.

Companion animals (dogs and cats)

The peer-reviewed literature on the potential therapeutic evidence for MH in companion animals (dogs and cats) was sourced using the publicly available bibliographic databases Scopus, PubMed and Google Scholar. All articles reporting on the use of MH in cats and dogs were included. In the review by Vogt et al. (2021), only one study reported on the effect of MH on wound healing in companion animals. In that study, Apaydin et al. (2019) reported that both MH and a 0.01% Ethacridine lactate (an antibacterial drug) antiseptic solution had similar effects on healing of infected wounds in cats. The authors recommended further clinical and experimental studies to be undertaken using microbiological, biochemical or histological parameters to further explore this finding. Since the review by Vogt et al. (2021), a further 10 studies have been reported in cats and dogs (Table 3).

Table 3. Effect of Manuka honey on external wound healing/antimicrobial activity in companion animal species.

Species	Type of study	Situation	Treatments	Delivery method	Duration	Outcome	Reference
Cats	In vivo	Bilateral tooth extractions	MH-based ointment, and no treatment (control)	Sockets were filled with MH after thought extraction		Reduces redness, improves flap viability, and enhances wound healing.	Pleeging et al. (2022)
Cats	In vivo	Infected wounds in different areas of the body	MH, and Ethacridine lactate	Applied upon wound area	-	Similar results between treatments.	Apaydin et al. (2019)
Dogs	In vivo	Surgical wounds created bilaterally on the trunk.	MH, and standard–of–care (calcium alginate)	Dressing	-	Wounds healed in the same amount of time.	Repellin et al. (2021)
Dogs	In vivo	Postoperative outcome for inflammatory interdigital nodules surgery	MH	Applied upon wound area	-	Wound management avoiding antibiotics can be used without impaired healing or increased complication rate.	Frey and Varjonen (2023)
Dogs	In vivo	Canine nasal intertrigo (skin fold dermatitis)	MH (n = 13), and placebo hydrogel (n = 16)	Applied upon wound area	Daily for 21 days	The therapeutic effect of MH was inferior to the placebo.	Brosseau et al. (2020)
Dogs	In vivo	Otitis externa	MH, and chlorhexidine-Tris-ethylenediaminetetraacetic acid (EDTA)	Applied to affected ears	Daily for 10 days	Some benefits to treatment of clinical signs and reduction in number of years in affected dogs.	Fregeneda-Grandes et al. (2020)
Dogs	In vitro	Staphylococcus Pseudintermedius strains obtain from dogs with canine pyoderma	MH-based gel, propolis, tea tree oil, and Rosmarinus officinalis oil	-	-	MH-based gel presented the lowest minimum inhibitory concentration.	Meroni et al. (2020)
Dogs	In vitro	Staphylococcal isolates originated from human and canine skin infections; Pseudomonas spp., from canine otitis externa cases	40%, and 80% w/v MH	-	-	Both MHs were effective against common cutaneous pathogens. The 40% MH was more effective against Pseudomonas spp.	Cremers et al. (2020)
Dogs	In vitro	S. pseudintermedius strains	MH, penicillin (1 unit), tetracycline (30 μg), chloramphenicol (30 μg), gentamicin (10 μg), and oxacillin (1 μg)	-	-	Strains were inhibited by 12% (wt/vol) MH, but tolerance was observed by the 5 antibiotics. MH increase susceptibility of 4 antibiotics but oxacillin.	Brown et al. (2020)
Dogs	In vitro	Drug-resistant strains isolated from chronic otitis	MH, Acacia, Liden, and Rapeseed honey			MH had the most effective antimicrobial activity.	Hulea et al. (2022)
Cats	In vivo	Infected wounds	MH, and Ethacridine lactate (Rivanol)	Applied upon wound area	-	Similar results between treatments	Apaydin et al. (2019)

Dental diseases, and in particular periodontal disease, is the primary health condition affecting domestic cats (O’Neill et al. 2023) and dogs (O’Neill et al. 2021) often requiring tooth extraction. Pleeging et al. (2022) reported that after extraction, intra-socket application of MGH resulted in decreased inflammation, improved mucoperiosteal flap viability and promoted wound healing at both 3- and 7-days post-extraction providing a potent adjuvant therapy to support intra-oral wound health.

Due to its antimicrobial activity and chemical properties that enhance wound healing and tissue regeneration (White 2016; Scepankova et al. 2021), MH is commonly used to support wound healing in dogs (e.g. Frey and Varjonen 2023). Repellin et al. (2021) reported that a proprietary MH essential oil hydrogel application to small acute, full-thickness open wounds in healthy dogs did not differ in wound contraction and histological scores compared to control standard-of-care dressings. However, it was noted by the authors that there may be beneficial effects of this hydrogel in the early proliferative stage of wound healing and where wounds would benefit from early robust epithelialization. MH has also been found to be an alternative to the antibacterial drug Rivanol (Ethacridine lactate) in the treatment of infected wounds in cats (Apaydin et al. 2019).

Bacterial resistance to antibiotics is a growing global crisis that threatens the ability to treat infectious diseases in both humans and animals (Casadevall 2017). Intertrigo is a skin fold dermatitis that commonly requires recurrent treatment with topical antiseptics or antibiotics. Brosseau et al. (2020) reported that MH was able to alleviate pruritus providing a mild short-term benefit, but was not able to treat the microbial, cytological and clinical components of the disease. As a result, the authors did not recommend the use of MGH as an alternative to topical antimicrobials in the control of canine nasal intertrigo. In contrast, Fregeneda-Grandes et al. (2020) reported preliminary findings that suggest MGH may be effective in the control of clinical signs and microbial colonisation in dogs with otitis externa. Staphylococcus pseudintermedius (SP) is a gram-positive bacterium that can act as a skin commensal or a pathogen when the skin barrier is compromised. It is one of the main causative agents of canine pyoderma (Larsen et al. 2018) and can cause ear, wound and post-surgical infections in domestic animals, especially dogs (Bannoehr and Guardabassi 2012). In addition to its zoonotic potential, with the emergence of multidrug resistance, treating both animal and human SP infections can be difficult. Meroni et al. (2020) reported that a MH gel and propolis had the lower minimum inhibitory concentration against 23 strains of SP isolated from canine pyoderma as compared to tea tree (Melaleuca alternifolia) and rosemary (Rosmarinus officinalis), highlighting the significant antibacterial effect of MH. In vitro, it has also been observed that MH at either 40 and 80% w/v concentrations was effective against common cutaneous pathogens Staphylococcus spp. (human and canine skin infections) and Pseudomonas spp. (canine otitis) (Cremers et al. 2020). Brown et al. (2020) also reported that in vitro, MGH inhibited all 18 of the genetically diverse SP strains sequenced and tested in the study. Together, these studies highlight the potential for MH to be used against SP infections. Furthermore, when the effect of different honeys against certain bacterial/fungal ATCC strains and multidrug-resistant strains isolated from chronic otitis in dogs was evaluated, MH showed the greatest antimicrobial activity (Hulea et al. 2022).

Collectively, these studies provide supporting evidence for the potential veterinary application of MH, in particular MGH, for use in wound healing and as an alternative to traditional topical antibacterial and antibiotic formulations for treating skin conditions such as SP infections, and to prevent the progression of wound infection. There are a wide range of wound types (ulcers, burns, tooth extractions, injuries, surgical incisions, chronic wounds, etc.) that may require different interventions. Further studies are recommended to generate additional evidence for the veterinary use of MH in both livestock and companion animal species.

Gastrointestinal function

The review by Vogt et al. (2021) described the supporting literature for potential anti-inflammatory, anti-tumorigenic, and anti-ulcer benefits of MH in murine species and various cell lines potentially through its anti-inflammatory and antioxidant properties. These studies highlight the potential for MH to have potentially beneficial effects on gastrointestinal function when ingested either as part of the diet (functional food) or when applied topically as a therapeutic. However, to the authors’ knowledge, there is no peer-reviewed literature describing the effect of MH on gastrointestinal function in livestock species (e.g. cattle, sheep, goats, horses) or companion animals.

Gastrointestinal disorders and associated morbidity and mortality are common in livestock and companion animals. Young stock are particularly affected, with a wide range of gastrointestinal disorders observed including abomasal damage in veal calves (Bus et al. 2019) and lambs (Vatn and Ulvund 2000), neonatal scours or enteritis in calves (Maier et al. 2022) and lambs (McCoard et al. 2021). However, adult animals are also affected, e.g. gastric ulceration in horses (van den Boom 2022), cattle (Munch et al. 2019) and sheep (Smith et al. 2023) and dogs (Davis and Williamson 2016). There is a wide range of causative factors including diet quality, diet type (especially rapidly fermentable diets), feeding management, stressful conditions, nonsteroidal anti-inflammatory drug administration, and infectious disease. Treatment options currently include electrolyte therapy (e.g. for non-infectious scours) or administration of drug therapies. Therefore, alternative preventative and/or therapeutic approaches are of significant interest.

Evidence from rodent models suggests that MH may have a beneficial effect on gastrointestinal function. Prakash et al. (2008) reported that oral treatment with 5 g/kg or 10 g/kg body weight of MH was able to reduce colonic inflammation in an inflammatory model of colitis. In that study, all biochemical parameters were reduced, and lipid peroxidation was restored and antioxidant parameters improved. Almasaudi et al. (2016) demonstrated that MH (2.5 mg/kg) provides gastroprotective effects in an acute (ethanol-induced) gastric ulcer model in rats by protecting the enzymatic and nonenzymatic antioxidants, maintaining glycoprotein, inhibiting lipid peroxidation, and reducing inflammatory cytokine production. These authors also reported that oral treatment with MH (2.5 mg/kg) in rats with acetic acid-induced gastric ulcers has potent antiulcer activity that may be due to its antioxidant abilities that interfere with the inflammatory process and reduces lipid peroxidation Almasaudi et al. (2016). Whether similar beneficial effects observed in murine species can be demonstrated in livestock and companion animal species remains to be investigated.

Other physiological responses

There is very little peer-reviewed literature that suggests that MH may have other physiological benefits to improve health, wellbeing and/or productivity in livestock or companion animals (Table 4). Whyte et al. (2017) reported that a commercially available combination of MH and aloe vera (Cow and Calf Formula, DairyCare Ltd, NZ) fed to dairy cattle improved milk production by 5.5% during peak lactation and 4.7% throughout the whole season. These authors postulated that this combination may have improved nutrient availability for milk production, however, no supporting data to demonstrate the mechanisms of action were reported. Positive effects on teat condition have also been reported with daily treatment of teats in lactating dairy cows with 0.5% iodine/14.5% emollient MH vs. 0.5% iodine/5% emollient (Thomas and Nydam 2011).

Table 4. Use of Manuka honey in production animals – production responses.

Animals	Type of study	Situation	Treatments	Delivery method	Duration	Outcome	Reference
Cattle	In vivo	Grazing milking cattle	5 ml/d of a commercial supplement containing MH + Aloe vera (n = 400), and control (no treated; n = 600)	Fed	Milking period	Milk production was increase 5.5% during the peak and 4.7% over the whole season.	Whyte et al. (2017)
Cattle	In vivo	Teat’s degree of teat-end hyperkeratosis was evaluated	0.5% iodine/14.5% emollient MH post-milking dip (n = 81), and 0.5% iodine/5% emollient teat dip (n = 93)	Applied to the teat end.	Daily for 8 wks.	The teat condition score improved with the use of MH.	Thomas and Nydam (2011)

It is important to highlight that with the exception of one study in horses (McIver et al. 2020), neither UMF or MGO levels are reported in any of the animal studies that evaluated MH effects on sheep (Chigerwe et al. 2020; Iacopetti et al. 2020), goats (Williams et al. 2022), alpaca (Poza et al. 2023), pigs (Evensky et al. 2019; Chigerwe et al. 2020; Muhrbeck et al. 2022), dairy cattle (Allen and Molan 1997; Thomas and Nydam 2011; Whyte et al. 2017), cats (Apaydin et al. 2019; Pleeging et al. 2022), dogs (Brosseau et al. 2020; Brown et al. 2020; Cremers et al. 2020; Fregeneda-Grandes et al. 2020; Meroni et al. 2020; Repellin et al. 2021; Hulea et al. 2022; Frey and Varjonen 2023) and horses (Bonifer-Engelhardt 2020; Mandel et al. 2020; De Clercq et al. 2021; Gustafsson et al. 2021; McGovern and Bladon 2021;). While the biological activity of MH increases as UMF increases, there is no clear evidence that the effect of the MH on wound healing and other physiological responses in livestock species or companion animals is related to the UMF or MGO. There are reports suggesting that the antibacterial properties are associated with the MGO or UMF (Georgescu et al. 2017), however, others reported that such association does not exist (Girma et al. 2019; Muhrbeck et al. 2022). Curtis (2018) suggests that the MH used for wound management needs to have a minimum of 10+ UMF. Muhrbeck et al. (2022) suggested that the antimicrobial effect of MH was through hydrogen peroxide or other phytochemical components rather than through MGO. Girma et al. (2019) suggested that, as the MGO is generated from dihydroxyacetone (DHA) during the maturation of honey for at least one year, the estimated UMF may not reflect the actual MGO content at the time of use of the MH. Therefore, MH’s MGO or UMF content will vary with the time of its estimation and that may be the cause of lack of effect observed when comparing MHs with different UMF levels. Further studies are required to determine whether the UMF or MGO levels are related to the level of activity and/or efficacy of MH and whether minimum thresholds exist.

Conclusion

Based on the findings of this literature review, there is good supporting peer-reviewed literature for the antibacterial action of MH to prevent and/or manage infection, and some supporting evidence for wound healing in livestock and companion animal species. However, the biological mechanisms of action have not been elucidated. Furthermore, whether the UMF or MGO indexes influence the effects of MH has not been scientifically evaluated. Based on murine and in vitro studies, there is significant potential for MH to have beneficial effects beyond wound healing, especially for improving gastrointestinal function and alleviating inflammation, and well as potential productivity effects (e.g. increased milk yield). There are a wide range of products now commercially available that have MH as an active ingredient. However, further scientific studies are required to evaluate the direct effects of MH relative to its effects when used in conjunction with other compounds, dose–response effects, and the effect of UMF and MGO levels on efficacy to provide scientific evidence to support the efficacy of MH as a functional food or therapeutic in livestock and companion animal species. If these benefits can be proven, MH may provide an important alternative to drug therapies to support health, wellbeing, and performance. However, potential risk factors and/or negative effects have been poorly explored and warrant further investigation. Collectively, the evidence generated from scientific studies to date highlights future opportunities to promote the use of MH in Rongoā and support the growth and development of MH-based enterprises for Iwi, hapū and whanau. We advocate that randomised controlled trials are undertaken in both livestock and companion animal species to determine efficacy and safety of MH in these species.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by AgResearch Māori Strategic Science Investment Fund.