Vvvvvimp Main
Vvvvvimp Main
Vvvvvimp Main
art ic l e i nf o a b s t r a c t
Article history: Background: Honey is a natural product made from the nectar of flowers by honey bees and has over 200
Received 19 July 2018 compounds in it, including sugars, water, organic acids, minerals and polyphenols - the exact structure
Received in revised form and composition of honey often determined by which plant source(s) the honey bee took the nectar
19 December 2018
from. Honey has been used in diets and medicines for thousands of years; however, this review, for the
Accepted 25 December 2018
Available online 3 January 2019
first time, aims to look at its place in modern medicine concerning oral health.
Highlight: The present review for the first time attempted to address the protective effect of honey in the
Keywords: oral care.
Honey Conclusion: For the first time this review addresses the usefulness of honey against Streptococcus mutans
Oral health
infections, dental plaque and caries, gingivitis and halitosis. Honey was also useful in preventing side effects
Oral malodor
associated with treatment of cancers of the head and neck, namely, radiation induced mucositis, xerostomia
GingivitisOral cancer
and poor wound healing. This is well supported by evidence in literature and was examined in this review.
& 2018 Published by Elsevier B.V. on behalf of Japanese Association for Oral Biology.
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2. Chemistry of honey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3. Traditional and pharmacological uses of honey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4. The oral cavity and oral health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4.1. Honey in mitigating infections of Streptococcus mutans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.2. Honey in mitigating dental plaque . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.3. Honey in gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.4. Honey in mitigating malodor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.5. Honey in oral cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.6. Honey as an anticancer agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.7. Honey in mitigating treatment-induced ill-effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4.8. Honey protects against radiation-induced mucositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4.9. Honey is effective in preventing radiation-induced salivary gland destruction and xerostomia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4.10. Honey as an adjunct to conventional therapies: enhancing refractory wound healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Conflict of interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Ethical statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
n
Corresponding author.
E-mail address: [email protected] (M.S. Baliga).
https://doi.org/10.1016/j.job.2018.12.003
1349-0079/& 2018 Published by Elsevier B.V. on behalf of Japanese Association for Oral Biology.
E.I. Ramsay et al. / Journal of Oral Biosciences 61 (2019) 32–36 33
1. Introduction from the polyphenols, and as with all other components of honey,
their quantity depends on the source of the nectar [5,8].
Honey is a natural product made from the nectar of flowers by
honey bees. Honey bees visit hundreds of flowers and ingest their
nectar into their ‘honey stomachs’ where digestive enzymes act on 3. Traditional and pharmacological uses of honey
the sucrose of the nectar to break it down into glucose and fructose.
A single bee will regurgitate this nectar and spit it into the mouth of The use of honey has been documented for thousands of years
another bee and the process repeated severally (for about 20 min) in both diets and medicines, proof of which is shown in Stone Age
until the nectar is fully digested into raw honey. The bees spit the paintings [4]. Ancient civilizations of Egypt, Assyria, China, Greece,
raw honey onto the cells of the honey comb, flap their wings to dry Rome and India commonly consumed honey presumably due to its
it and then seal their produce in with wax [1,2]. Chemically, 17–20% sweet taste and high nutritional content while ancient medical
of honey is made of water but this along with the rest of its make- texts by the fathers of medicine, like Aristotle, Hippocrates, and
up, flavor and color (which can be anywhere between colorless, the Arab and Ayurvedic physicians, recorded the medicinal bene-
straw-like, amber and black [3] is dependent on the flower the fits of honey against various ailments [4,9]. In response to these
nectar came from. Bees can forage the nectar from one type of plant historic uses and the growing resistance to antibiotics, in the last
or many types to make honey and so it can be categorized as twenty years scientists have looked at the part that honey can play
monofloral or multifloral (also known as polyfloral) [3]. in today's medicine. Their studies have shown that honey has
many pharmacological actions, making it beneficial against various
injuries and illnesses. These actions include antioxidant, anti-
2. Chemistry of honey inflammatory, antibacterial, antimutagenic, wound healing, anti-
diabetic, antiviral, antifungal and anti-tumoral effects [4,9]. Hence,
The chemical composition of honey has been studied in great work has been done to investigate what benefits honey can have
detail and it is believed that there are more than 200 compounds in oro-dental care, and this will be the focus of this review.
in the natural substance [4,5]. About 90–95% of the dry matter of
honey is sugar, followed by water, organic acids, and mineral
compounds [3]. The sugars found include monosaccharides - 4. The oral cavity and oral health
fructose and glucose; disaccharides -maltose, sucrose, maltulose,
turanose, isomaltose, laminaribiose, nigerose, kojibiose, gentio- The mouth and the body have historically been treated as two
biose, and B-trehalose; and trisaccharides - maltotriose, erlose, separate entities, with dentistry dealing with the problems of one
melezitose, centose 3-a5, isomaltosylglucose, l-kestose, iso- and medicine dealing with the problems of the other. Modern
maltotriose, panose, isopanose, and theanderose, and they are teaching practices aim to resolve this with the view that holistic
present regardless of the type of honey [5–7]. In addition, honey treatment is what matters in patient care because the two are not
also contains 4 to 5% fructo-oligosaccharides. Fructo-oligo- discrete; they are hugely influential on each other [10]. More than
saccharides are indigestible molecules that can help digestive 100 systemic diseases and more than 500 medications have oral
health as they are a good source of prebiotics, which aid the manifestations, with 145 commonly prescribed drugs causing dry
probiotics in our intestines [8]. Other compounds found in honey mouth, and evidence showing that oral health can affect systemic
that are good for systemic health include enzymes (such as glu- conditions like diabetes and atherosclerosis [11]. As the beginning
cose oxidase and catalase), amino acids [5], vitamins (including of the alimentary system, the oral cavity also has a relationship
vitamins B1, B2, B3, B6, and C), calcium, iron, zinc, and potassium, with the external environment and the responsibility of functions
to name a few. Acetic, butyric, and citric acids are among the or- like chewing and speech, while also playing a big role in a person's
ganic acids that have been found in honey, along with many mental well-being [12]. Some of the most common oral dental
polyphenols. Many of the pharmacological effects of honey come ailments/diseases include dental plaque, gingivitis, halitosis,
Table 1
Pharmacological properties of honey those are useful in oro-dental care.
Antibacterial effects on oral pathogens Honey is shown to exert antibacterial effects on nearly 60 species. Reported to be effective on Streptococcus mutans and
to prevent development of resistance [9,18,19].
In dental plaque Manuka honey has been shown to be effective in preventing growth of the biofilm organisms and to reduce the pro-
duction of acids [24].
In gingivitis Manuka honey has been shown to be effective in reducing gingivitis [24].
RCT studies indicate honey to be an alternative to traditional remedies for the prevention of dental caries and gingivitis
following orthodontic treatment [25].
Double-blind, randomized controlled field trial has shown that manuka honey and raw honey as effective as chlor-
hexidine as a mouthwash. However chlorhexidine showed the maximum reduction in mean plaque and gingival score
[26].
In mitigating malodour Honey, shown to reduce malodour in people with oral squamous cell carcinomas [27].
Honey shown to be as effective as silver-coated bandages in mitigating odour [28,29].
Anticancer effects Tualang honey (1–20%) shown to possess cytotoxic effects on cultured oral squamous cell carcinomas [38].
Prevent/reduce radiation-induced mucositis Multiple reports indicate honey was effective in delaying/preventing/mitigating radiation induced mucositis in people
undergoing curative radiotherapy for their head and neck cancer [46–56].
Prevent/reduce radiation-induced xerostomia Study indicates honey was effective in delaying/preventing/mitigating radiation induced xerostomia in people under-
going curative radiotherapy for their head and neck cancer [59].
Honey enhances healing of refractory wound Topical application of honey was effective in enhancing wound healing and to mitigate the pain without causing any
adverse effects [64].
Honey is shown to be effective in enhancing wound healing in head and neck cancer patients previously exposed to
radiotherapy [65].
Tualang honey is also shown to be effective in enhancing post tonsillectomy healing process in children [66].
34 E.I. Ramsay et al. / Journal of Oral Biosciences 61 (2019) 32–36
malodor, microbial infections, and cancers. In the following sec- studies to look at how much of this initial success is due to the
tions, and in Table 1 and, the usefulness of honey in preventing/ honey being chewed, which increases salivary flow rate, as well as,
mitigating these conditions are addressed. the buffering and clearing action of saliva. Singhal et al.’s study in
2018 examines this in an indirect way by comparing raw and
4.1. Honey in mitigating infections of Streptococcus mutans manuka honey mouthwashes to chlorhexidine on plaque and
gingivitis scores. All 135 cases showed reduced levels of plaque
Conservative estimates are that there are between 500 and 700 and gingivitis scores, with chlorhexidine having the best result,
different microbial species on different surfaces of the oral cavity proving that honey-based mouthwashes have antimicrobial effects
[13–17], with a person's oral health and hygiene dictating the ratio on the oral cavity [26].
of these species. Healthy mouths tend to have more gram-positive
bacteria and simpler colonies; unhealthy mouths tend to have 4.4. Honey in mitigating malodor
more anaerobic, gram-negative bacteria and complex, diverse co-
lonies [14]. Scientific studies have shown that Honey was effective Oral malodor (also termed: Fetor oris or Fetor ex ore) or hali-
against nearly 60 species of gram-positive, gram-negative, anae- tosis, that is sensed during a person's speech has a very unpleasant
robic, and aerobic bacteria. One of these is Streptococcus mutans odor. In the oral cavity, the posterior portion of the tongue's dor-
[9,18,19], a pathogen involved heavily in dental caries. Unlike an- sum, subgingival areas (e.g., periodontal pockets and interdental
tibiotics, evidence has found that so far, bacteria do not become spaces), faulty restorations (e.g., leaking crowns and bridges),
resistant to honey [20]. Thus, it is useful to know which infections dental implants, dentures, and abscesses, are most prone to har-
honey can be used against. This continued sensitivity may be be- boring halitosis-causing elements. Furthermore, transient oral
cause honey has a different antimicrobial activity from that of dryness, brought about by a temporary reduction in saliva flow,
antibiotics. Instead of acting on intracellular metabolism or the cell also plays an important part in promoting this condition. With
wall of a microorganism, honey acts to stop the growth of mi- regard to honey, there is some evidence to show that it can combat
crobes with its high sugar content and low pH (bacteriostatic the malodor of oral squamous cell carcinomas (Drain and Fleming,
action) and kill bacteria via its antibacterial factors, especially [27]), but this might be no more effective than silver-coated ban-
hydrogen peroxide [21–23]. dages [28,29]. The theory behind it is that manuka honey's anti-
bacterial action combats bacterial colonization of healing wounds
4.2. Honey in mitigating dental plaque and provides nutrients for the bacteria such that they produce
lactic acid during metabolism rather than malodorous gases [30].
Dental plaque is the thin biofilm, which accumulates on tooth Again, while available evidence is promising, more research is
surfaces. Bacteria in the plaque (particularly S. mutans, which will required on honey's positive effects against infections in the oral
be discussed further in the review) metabolize fermentable car- cavity.
bohydrates (especially sucrose) from the diet and produce acids.
These acids are responsible for demineralizing and disintegrating 4.5. Honey in oral cancer
tooth structure, and are held in close contact with the tooth by the
matrix secreted by the plaque biofilm. This prevents the clearing Of all the ailments and diseases affecting the oral cavity, cancer is
and remineralising actions of saliva and topical fluoride, resulting the most severe and dangerous. Recent reports from the GLOBCAN
in the initiation and progression of dental caries if the biofilm is indicate that more than 550,000 cases of head and neck cancers,
not mechanically disrupted by tooth brushing. There is a report most of which are oral cancers, are reported annually [31]. Oral
showing that manuka honey was effective against plaque forma- cancer is the sixth most common cancer in the world and two to four
tion, preventing growth of the biofilm and reducing the amount of times more common in men than women [31]. Pathologically, more
acid produced [24]. than 90% of all oral cancers are squamous cell carcinomas [32].
Conventionally, depending on the cancer stage, surgery, chemother-
4.3. Honey in gingivitis apy and radiotherapy, either alone or in combination are used to
cure/control the tumor growth. In the early stage (I), when excisable,
Gingivitis is the inflammation of the gingival tissues in re- oral cancers are preferably treated with surgery and may be backed
sponse to the presence of bacteria in the plaque biofilm. It is up with radiation [33]. In advanced stages (stage II and III) a com-
characterized by erythematous and bleeding gingivae, which are bination of surgery and radiation/chemo-irradiation (60–74 Gy de-
typically swollen at the gingival margins, due to the loss of ‘knife- livered in 2 Gy fractions 5 days/week) may be used. In stage 4, when
edge papillae’ - a characteristic feature of gingival health. Gingi- the cancer has metastasized to a distant site, depending on the
vitis is reversible with good oral hygiene practices, but if not general health of the patient, radical surgery followed by post-
corrected, can progress to the irreversible loss of clinical attach- operative radiation therapy or the use of palliative radiation therapy
ment and the alveolar bone - the features of periodontal disease - or chemotherapy may be used [34].
as plaque migrates towards the apex of the tooth, initiating an
inflammatory reaction from the host.This inflammation is similar 4.6. Honey as an anticancer agent
to that found in inflamed wounds, which manuka honey has, for
hundreds of years, shown to rapidly clear bacteria from [24]. Atwa Honey has been investigated for its anticancer properties in
and coworkers [25] conducted a randomized control trial of 20 various cultured neoplastic cell lines and reports suggest that it is
female orthodontic patients to examine the effect of chewed effective [35–37]. Seminal studies by Ghashm and co-workers
honey on pH, bacterial counts and bacterial growth compared to (2010) [38] have shown that treatment of oral squamous cell
sucrose. The trial found that the pH did not go below the threshold carcinomas (OSCC) with various concentrations of Tualang honey
pH of 5.5, reduced bacterial counts, and inhibited bacterial growth. (1–20%) was effective in causing a dose- and time-dependent cell
With only 20 patients involved, the authors recognized that the death [38]. The 50% inhibitory concentration (IC50) was observed
study was limited and further studies should be done to explore to be at 4% and maximum inhibition of cell growth (Z80%) was
the possibility that honey, even with its acidic pH and high sugar obtained at 15%. Morphological studies also showed that honey
content, may actually help prevent demineralization and gingivitis induced a time and dose-dependent inhibitory effect [38]. Al-
in patients when chewed. It would also be worthwhile for future though not in oral cancer cells, mechanistic studies indicate that
E.I. Ramsay et al. / Journal of Oral Biosciences 61 (2019) 32–36 35
honey modulates inflammatory cascade, cell cycle, cell growth and salvage surgery [65]. Additionally, studies have shown that Tualang
proliferation, and induces apoptosis [5,39–41]. With limited evi- honey is effective in enhancing post-tonsillectomy healing in chil-
dence in this field (especially with oral cancer models), more re- dren [66]. Based on these observations it can be inferred that honey
search needs to be done to understand the usefulness of honey as is effective as a wound healing agent during and after radiation.
an anticancer agent.
Radiation is a very useful tool in the treatment of head and In conclusion, honey has been recognized as having great
neck cancers and can be used after surgery/chemotherapy or with medical worth for thousands of years, and is now finding its place
small, weekly doses of chemotherapy (called chemoradiation, the in modern medicine. Various studies have shown the benefits of
chemotherapy drug often used is either cisplatin or carboplatin) to honey against diseases of the oral cavity such as caries, gingivitis,
increase the number of tumor cells killed [42,43]. This use of ra- and radiation-induced mucositis but more work is needed in these
diation has proven effective at increasing 5-year survival rates Table 1 and Fig. 1. Perhaps a more pressing need for research
[42,43], but with major side effects. Localized radiation to the head however lies in the uses of honey in head and neck cancers treated
and neck causes mucositis, xerostomia and impairs wound healing by radiation as it has been shown to be effective against xer-
in the area. When these side effects cause the need for treatment ostomia and wound healing, but evidence is not yet conclusive
breaks, the therapeutic benefit of radiation is reduced, as is disease enough for honey application to become a standard practice in
prognosis. Hence, the following sections of this review look at the treating these patients. On the down side, studies have shown that
effects of honey in preventing or improving mucositis, xerostomia, the use of baby comforters with honey enhances the risk of de-
and refractory wound healing. veloping caries [67]. These concerns have been raised by some
investigators [68] and need to be studied. Honey has the potential
4.8. Honey protects against radiation-induced mucositis to be of immense use in oral care against inflammatory ailments
and bacterial infections, but only when gaps in the evidence base
Radiation-induced mucositis is arguably the most prominent are bridged.
side effect of curative radiotherapy and causes immense pain and
morbidity [42,44]. Influential studies by Biswal and coworkers [45]
showed for the first time that honey was effective in preventing Conflict of interest
radiation mucositis. Since then many studies carried out around
the world have shown that honey was beneficial in reducing the The authors declare that they do not have any conflict of in-
incidence of radio/chemotherapy-induced oral mucositis, reducing terest regarding the study topic.
treatment interruptions, weight loss, and delaying the onset of
oral mucositis [46–56].
Ethical statement
4.9. Honey is effective in preventing radiation-induced salivary
gland destruction and xerostomia The authors declare that they have abided with ethical guide-
lines regarding the study.
The salivary glands are often irradiated during the radiation
treatment of cancers of the head and neck. The damage reduces
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