Honey: An Overview

on Sunday, 21 April 2013. Posted in Honey Research

Honey has long been documented as having medicinal properties, and its uses as a wound dressing and...

Historical Uses of Honey
Honey has long been documented as having medicinal properties, and its uses as a wound dressing and an antiseptic have been recorded since ancient times. The earliest written records of honey used as medicine is in Egyptian papyri and Sumerian clay tablets dated from 1900 to 1250 BC and in one of these, honey was used in 30% of the prescriptions. Ancient Egyptians also used honey in embalming. They made salves with it for treating diseases of the eyes and skin. As well, the ancient Greeks are reported to have used honey to treat fatigue: athletes drank a mixture of honey and water before major athletic events. Hippocrates (460-357 BC) found that honey cleaned sores and ulcers of the lips and healed buncles and running sores. As well, the healing properties of honey were mentioned in the Holy Quran 1400 years ago.

Honey has continued to be used in folk medicine ever since, with mention of its use in the Middle Ages reported by Daude de Pradas in approximately 1200 AD. Similarly, honey has been documented as being used as a remedial agent throughout Europe, as well as through areas of Arabia and China. Generally, honey has been used as a remedy for gastric and intestinal complaints, although the sedative and soporific powers of honey have also been mentioned. In addition, the diuretic effect of honey has been recorded, and it has been a favored remedy for kidney inflammations and stones. Attic honey, in particular, was thought to have special curative powers for eye disorders, and honey, in general, has been documented as having being used for the treatment of skin diseases and smallpox, as well as in surgical dressings.

The Hindu people also had great faith in the medical virtues of honey, using it mainly for coughs, pulmonary issues and gastric disorders. Similarly, populations in rural communities from almost all nations have documented the use of honey through time. German women, specifically, believed that a mixture of honey and crushed bees would have a beautifying and strengthening effect, and that it would regulate menstrual flow.

In more recent times, honey has played a relatively minor role in medicine, mostly due to it not being accepted by Western practitioners in a world where antibiotics and other pharmaceuticals are seen as the remedies of choice. Among the Chinese, Hindu, Arabic and African races, however, honey is still considered to be a valuable internal and external remedy. Slowly the use of honey in Western medicine is gaining recognition; particularly as scientific evidence continues to be produced demonstrating its efficacy, often in situations where more usual remedies are ineffective. The antibacterial properties of honey (see Section 1.3) and its wound-healing capabilities, in particular, have gained substantial recognition in the last 10–15 years, although only now are researchers beginning to understand the processes by which this occurs. We are also beginning to understand that honey may indeed be the elixir that the ancient people believed, as research is showing a number of health-related benefits, including a laxative effect, beneficial effects on blood glucose levels, anti-inflammatory and immunestimulating properties and potentially a cancer-preventative action.

Composition of Honey
Honey is primarily a highly concentrated mixture of sugars in a syrupy solution, although it usually also contains other minor components including enzymes, vitamins, flavanoids and organic chemicals.

The main sugars found in honey are fructose and glucose, usually in a ratio of 1.2:1.0, these two sugars together accounting for 85–95% of the total carbohydrate content. However, the ratio of these two sugars can differ depending on the floral source and other factors such as the level of processing undertaken by the bees. Other sugars found in minimal quantities include sucrose, reducing disaccharides and higher oligosaccharides. The number of different oligosaccharides found in honey seems to vary depending on the floral source, although numbers of between 20 and 30 have been reported previously.

Honey also contains a number of enzymes including glucose oxidase, amylase and invertase, their presence in honey appearing to originate from the bees producing the honey . Catalase and acid phosphatase have also been found in some honeys, these most likely being derived from the pollen and nectar of certain plants. Of these enzymes, glucose oxidase appears to be of particular significance as it is responsible for the generation of gluconic acid and hydrogen peroxide, hydrogen peroxide being one of the key factors involved in the antibacterial activity of honey. Other acids, besides gluconic acid, are also present in honey (albeit in low concentrations), the overall result being that undiluted honey typically has a pH in the range of 3.2–4.5.

Additional research has also demonstrated that certain honeys can also contain low levels of minerals, trace elements and proteins, although their nutritional significance is likely to be negligible due to their low concentrations. However, anecdotal and scientific evidence suggests that honey may also contain small quantities of unidentified but physiologically active components. For example, it has been suggested that something in honey may help suppress coughing, aid in desensitizing pain receptors, have a laxative effect and help with lowering blood glucose levels. As well it has been documented as possibly having neurotransmitter activities.

Generally, honey is considered to be a stable substance although changes in color and flavor can occur over time. Minor changes in composition can also occur in certain honeys due to the continuing action of enzymes. The sucrose content, for example, has been shown to decrease over time, this being attributed to the activity of invertase added by the bee.

The Antimicrobial Activity of Honey
Although the medicinal uses of honey have been documented for centuries, it has only been in recent times that the specific bioactivities have been investigated and elucidated. Of these, the antibacterial activity of honey is the most researched and best understood.

The significance of the antibacterial activity of honey relates more to its external uses as a wound dressing or skin-care agent, although it may also play a role in maintaining the balance of internal micro-flora after consumption. As well, honey has been shown in one clinical trial to be effective against bacterial diarrhea, and to aid in the treatment of eye infections. In addition, the hydrogen peroxide produced by honey may have additional actions in the body besides its antibacterial activity. For these reasons, the antibacterial activity will be summarized below, although readers are directed towards the review of Molan for more detail.

Osmolarity and Acidity
The antimicrobial activity of honey is due to a number of factors, several of which are endemic to all or most honeys, irrespective of floral source and geographic origin. The first of these is osmolarity. Because of the high sugar content of honey, the osmotic pressure of honey is high and the water activity (aw) is low (reported range = 0.562–0.62). Osmolarity is responsible for a large proportion of the antimicrobial activity of honey, even at lower honey concentrations. The growth of many bacterial species, for example, is completely inhibited when the aw is in the range of 0.94-0.99. This corresponds to a typical honey (with an aw of 0.6) being diluted in the range of 2– 12% (concentration is proportional to –log aw).

The second factor common to all honeys is acidity. Approximately 30 organic acids exist in honey, although the major contributor is gluconic acid in equilibrium with its lactone. This acid is produced by the activity of the enzyme glucose oxidase, the resultant concentrations in honey ranging from 0.23–0.98%.

Although once thought to be a major factor, more recent studies have shown that acidity actually plays a very small role in the antibacterial activity of honey. Several authors noted that there appeared to be no correlation between the pH of a honey and the level of antibacterial activity. This may be confounded by the fact that the pH of a diluted honey is dependent on both the buffering capacity of the honey and on the dilution medium used.

In contrast a small number of research articles have suggested that certain specific acid substances may have significant antibacterial activity. Acid components identified as antibacterial are mainly aromatic organic acids including caffeic acid and ferulic acid and benzoic acid derivatives.
Hydrogen Peroxide
Hydrogen peroxide was shown to be a significant contributor to the antimicrobial activity of honey when Dold found that certain honeys exhibited inhibitory activity over and above that expected from osmolarity alone.

It has also been demonstrated that hydrogen peroxide can have a more potent antibacterial activity when present in honey than when added exogenously, as there are other compounds present in honey that can potentiate its antibacterial effects. The bactericidal action of hydrogen peroxide, for example, is increased when 0.1 mmol/l ascorbic acid and metal ions are added to the test solution. Similarly, the sporicidal action of hydrogen peroxide can be increased by copper at 10 mmol/l. The antibacterial potency of hydrogen peroxide is also enhanced 10-fold by the addition of 0.83 mmol/l iron, copper, chromium, cobalt or manganese. All of these ions occur naturally in honey (albeit in lower concentrations than those reported above, suggesting that maximal rates of hydrogen peroxide-induced antibacterial activity can occur when using honey as the antibacterial agent.

Rates of Hydrogen Peroxide Production in Honey
The ability to accurately quantify glucose oxidase activity, or more importantly, the inherent level of hydrogen peroxide produced/accumulated in a given honey sample depends largely on the methodology employed. There are many different methods available for the measurement of hydrogen peroxide, but whereas these methods produce reliable and accurate results with standard water-based solutions, they have been shown to not accurately detect and measure hydrogen peroxide in honey due to various side reactions.

Recently, an assay not based on the use of peroxidase was developed using an oxygen electrode to fully elucidate the hydrogen peroxide production profile in different dilutions of honey. These authors demonstrated that this method was not prone to interference from other components of honey, and that hydrogen peroxide levels could be measured in honey concentrations of up to 80%. Various single- and multi-floral honeys were assayed in this study (including Ling Heather, Rewarewa, Clover, Wildflora, Bush and Pasture) and the profiles were primarily the same for all samples. Hydrogen peroxide production ranged from 0.3–1.4 mmoles/30 mins in 10% dilutions of honey, to 0.9–2.9 mmoles/30 mins in 30% solutions. Peak rates of production occurred at 30–40% honey and, in all samples, the rates of hydrogen peroxide production were virtually the same at 10% and 70% honey dilutions. Levels of accumulated hydrogen peroxide over time ranged between samples. Peak levels were accumulated after 6 and 24 hours, respectively, in a Ling Heather and Rewarewa sample, with total loss of all detectable hydrogen peroxide after 24 and 48 hours.

Other Components
Following the discovery that the antibacterial activity of honey was primarily due to hydrogen peroxide, it was suggested that non-peroxide factors in honey likely play a minor role in the antibacterial action. However, a number of researchers demonstrated the presence of non-peroxide antibacterial factors when they found that particular honeys exhibited an antibacterial activity even after the honey had been heat-treated or after treatment with catalase to remove the hydrogen peroxide.

In recent times, much research has focused on the non-peroxide antimicrobial activities of New Zealand Manuka (Leptospernum scoparium) honey. Analysis of an ether extract of Manuka honey demonstrated that Manuka honey contained components with antibacterial activities including syringic acid, methyl syringate and phenolic acids. It is believed that these compounds may be responsible for the non-peroxide activities observed in this type of honey.

As well as the non-peroxide antimicrobial properties of Manuka honey, certain honeys have also been shown to contain a number of other antibacterial compounds. These include the plant-derived flavonoids pinocembrin, pinobanskin and chrysin and the phenolic compounds caffeic acid and ferulic acid.

Antioxidant Capacity of Honey

Oxidative Stress
Oxidative stress is defined as the imbalance between free radical production and the antioxidant defense system resulting in an excess of oxidation. Oxidant free radical molecules are produced during normal metabolism in the cell and evidence now suggests that the excessive generation of these molecules can lead to DNA damage (Holmes et al., 1992; Ames et al., 1993) and contribute to the development of certain agerelated pathologies including arthritis, strokes, atherosclerosis and some cancers. Antioxidants are compounds that can reduce levels of oxygen free radicals, thus countering their toxic effects. They can occur endogenously within the body or be provided by dietary sources. There is a large amount of evidence in the literature to suggest that consumption of foods, in particular fruit and vegetables, can boost levels of antioxidants thereby playing a significant role in reducing the incidence of cerebovascular and other diseases.

Antioxidants in Honey
Within the last 10 years, several studies have shown that honey does have an antioxidant capacity in vitro. Furthermore, honey has been shown to prevent lipid oxidation in cooked ground turkey meat, with honey concentrations as low as 5% significantly reducing lipid oxidation by approximately 70% after 1–3 days. In addition, honey (5%, w/w) was more effective than α-tocopherol and butylated hydroxytoluene, two commonly used phenolic antioxidants, after both 1 and 3 days.

Honeys from different floral sources have also been shown to inhibit the enzymatic browning of fruit and vegetable homogenates (Oszmianski and Lee, 1990; Chen et al., 2000). In the latter study, honeys reduced the browning of baking potato, sweet potato, red delicious apple and d’Anjou pear by up to 45%, but it was less effective than the commercial browning inhibitors ascorbic acid and sodium metabisulphate.

More recently, a small number of studies have investigated the in vivo antioxidant capacity of honey. Gheldof found that the serum antioxidant capacity, measured using oxygen radical absorbance capacity (ORAC), was increased by 7% in individuals who had consumed a 500 ml solution of Buckwheat honey (160 g/l), but not in those who consumed 500 ml of black tea or black tea plus 160 g/l of a syrup of mixed sugars (45% fructose, 35% glucose, 20% water). Similarly, in another study, plasma antioxidant capacity increased by 12–25% six hours after the ingestion of a single dose of Buckwheat honey (1.5 g/kg body weight), and the plasma total-phenolic content was increased by 4–8%. No significant effects on either parameter were reported in subjects who consumed an equivalent amount of corn syrup . The plasma reducing capacity was also shown to be improved by approximately 10% following ingestion of honey. In a 2-week rat feeding study in which animals were fed diets containing 65 g of carbohydrate (starch, honey or a mixture of fructose and glucose as in honey) per 100 g of diet, honey-fed rats had higher plasma α- tocopherol levels, lower plasma nitrogen oxide levels and a lower susceptibility of lipid peroxidation in the heart. In contrast, pro-oxidative effects were observed in rats fed the fructose/glucose mixture.

The antioxidant capacity of honey has been attributed to several factors including α-tocopherol, polyphenolics, organic acids, ascorbic acid, β-carotene and enzymes. In particular, research has suggested that the antioxidant capacity of honey is largely due to its total phenolic content, and several studies have demonstrated that many honeys do have a rich phenolic profile consisting of benzoic acids and their esters, cinnamic acids and flavonoid aglycones. In one study a chromatographic analysis of the phenolic fractions of 8 honeys of different floral sources suggested that most honeys have quantitatively different phenolic profiles, and that a linear correlation exists between phenolic content and ORAC activity. This same study reported that whereas phenolic compounds contributed significantly to the antioxidant capacity of honey, they were not solely responsible. These authors also found a positive correlation between protein content and ORAC activity and acknowledged that other antioxidant components were also involved. Several authors have also reported that there is a significant positive correlation between antioxidant capacity and honey color, the darker colored honeys having higher antioxidant activities. Whether this is due to different phenolic profiles in the different colored honeys, or due to other floral factors is unknown. The antioxidant capacity of honey is directly correlated to the water content.

Anti-Inflammatory Activity of Honey
Inflammation is an important component of the normal reaction to infection or injury involving a series of inter-related events between immune cells, phagocytes, cytokines and other inflammatory mediators. However, when it occurs in excessive amounts or for prolonged periods of time it can actually be detrimental, preventing healing from occurring or even causing further damage.

The most serious consequence of inflammation is the production of oxidant free radicals in the tissues. This, in turn, can lead to the breakdown of lipids, proteins and DNA, thereby resulting in loss of cell functioning and tissue damage. In certain situations, reactive oxygen species can be produced in excessive amounts. During phagocytosis, for example, H2O2 and O2 are produced and these recruit more lymphocytes, thereby creating a self amplification cycle. As well, reactive oxygen species can activate tissue protease which causes greater damage than just that due to the free radicals formed from the H2O2 and O2.

Importantly, there is now evidence to suggest that there are strong correlations between inflammation and many health disorders. Chronic inflammation, for example, is now considered to be a major contributing factor in several diseases including arthritis, cancer and inflammatory bowel disease. As well, systemic inflammation has been shown to either initiate or worsen autoimmune disorders (including type I Diabetes), pre-senile dementia (Alzheimer’s disease) and atherosclerosis. The formation of atherosclerosis, in particular, is a particular consideration in this thesis as Diabetes is a major risk factor for its formation because of hyperglycemia-induced endothelial dysfunctions. However, whilst several studies have demonstrated that inflammation is a key part of atherogenesis researchers are now suggesting that nutrition may be used as an intervening factor.

Recent data from large clinical studies has also demonstrated that there is an association between inflammation and neuropsychiatric symptoms seen in aging, with elevated circulating levels of C-reactive protein, interleukin-6, interleukin-10, tumour necrosis factor and serum amyloid A. This is also an important factor to consider in this thesis as many of the impairments of cognitive function are known to occur because of oxidative stress in the brain.

It has recently been suggested that obesity may also be a chronic inflammatory illness, as there is an increase in inflammatory markers in the circulation of obese individuals, and macrophages have been identified in their white adipose tissue. This too, may be significant to consider in relation to this thesis as the different effects of sucrose and honey on weight regulation are an important measure in several studies in this thesis.

Although it is possible that honey may have an anti-inflammatory effect after consumption, most of the research into this area has primarily centered around the use of honey as a topical agent. Numerous studies, for example, have reported that honey applied to wounds reduces the localized swelling, heat and pain associated with inflammation.

Though the process by which honey acts as an anti-inflammatory agent has yet to be fully elucidated, the effect has been widely observed clinically. Manuka honey incorporated in a gel for topical use was shown to suppress the itching and erythema associated with mosquito bites and other inflammatory skin reactions due to local anaphylactic reactions. These symptoms are produced by the increased liberation of prostaglandins resulting in development of localized hot areas. This indicates that honey acts to decrease prostaglandin synthesis. Indeed, in one small clinical study (n=12) consumption of honey was shown to have significant effects on urinary total nitrite and prostaglandin concentrations. In this study, patients were given a solution of either honey (80 g in 250 ml water) or artificial honey (30 g sucrose and 38 g fructose in 250 ml water). Urinary prostaglandin E2 levels were decreased by 4%, 6% and 31%; prostaglandin F2-α by 15%, 28% and 44% and thomboxane B2 by 15%, 36% and 67% at 1, 2 and 3 hours after drinking the honey. In contrast, ingestion of artificial honey increased these parameters at most time intervals.

Honey has also been observed to reduce inflammation when applied to unbroken skin, indicating that the anti-inflammatory activity may be able to diffuse through the skin. Furthermore, honey decreased the stiffness of inflamed wrist joints in guinea pigs, a standard test for anti-inflammatories.

Importantly, it has also been shown in histological studies of wounds in both animals and humans that honey is effective even when there is no infection present. This suggests that the anti-inflammatory effect of honey is a direct effect, and not a secondary effect resulting from the removal of inflammation-causing bacteria.

Prebiotic Effect of Honey
Ever since Alexander Fleming discovered the antibacterial properties of the fungus Pencillilum spp. in 1929, the world has seen the rapid dominance of antibiotics for the treatment of bacterial infections. However, whilst antibiotics are effective in most cases, they are also inherently associated with a number of drawbacks. When ingested for the treatment of gut infections, for example, antibiotics do not discriminate between the pathogens and the beneficial intestinal micro-flora. Furthermore, several gut bacteria are now developing antibiotic resistance, and many of these bacterial infections are recognized as serious health threats.

Global organizations including the World Health Organization are now suggesting that the use of antibiotics be reduced in human medicine and that other means of disease/infection treatment be developed. One such approach that has quickly gained popularity is the concept of probioitcs, a general term for nutritional supplements containing one or more cultures of living organisms (typically bacteria or yeast) that, when introduced to a human, have a beneficial impact on the host by improving the endogenous microflora. This is generally achieved by the formation of bacteriocins, competition with pathogens for nutrients as well as lowering of the gut pH by fermentation.

A large amount of research has been undertaken to investigate the probiotic effects of bacteria, showing that improved gut health (including reduced diarrhea, constipation, inflammatory bowel disease) is often associated with Lactobacillus and Bifidobacterium spp. Food manufacturers have readily tapped into this new market with the development of probiotic-supplemented foods, fermented dairy foods such as yogurts appearing to be the preferred choice.

The use of probiotics can also pose a number of practical difficulties though. First, all foodstuffs are prone to a particular shelf-life, and the effectiveness of the probiotic bacteria can be limited due to the development of acidity by fermentation, development of toxins or loss of viability. Secondly, L. acidophilus and Bifidobacterium spp. are classified as microaerophillic and anaerobic, respectively, and their survival in an oxygen-based environment is limited. Yogurts incorporate a considerable amount of dissolved oxygen during manufacture, and the packaging materials used are generally not oxygenimpermeable. Limited studies have investigated the viability of lactobacillus and bifidobacteria spp. in yogurts and the available data suggests that the effectiveness of commercial probiotcs may be limited despite the fact that oxygen scavengers are often used.

With the difficulties associated with the survival and maintenance of probiotic cultures, a second approach towards improving gut health has evolved involving the use of prebiotcs, these being “food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria (usually bifidobacteria) in the colon”. In most instances stimulation of bifidobacteria growth occurs due to the presence of particular carbohydrates, particularly those that are non-digestible by the enzymes of the human digestive system. These carbohydrates can include fructo-oligosaccharides (FOS) and inulin, transgalactosylated oligosaccharides (TOS) and soybean oligosaccharides.

Besides the stimulation of growth of lactobacilli and bifidobacteria, prebiotics have been demonstrated to have several other beneficial gastrointestinal benefits. These can include increased fecal biomass, a mild laxative effect and an osmotic effect in the small intestine. In addition, other improvements have been reported with prebiotics, including increased immune function, reduced dental caries, stimulation of apototsis and an anti-carcinogenic effect.

Importantly it has also been shown that intake of prebiotics may help improve calcium uptake, this being a significant finding as many individuals consume less than two thirds of the recommended daily intake of calcium. The improvements in calcium uptake with prebiotics are thought to occur in a number of ways. These include the binding of calcium to the non-digestible sugars, thereby preventing the formation of the insoluble hydroxyapatite, and fermentation of the non-digestible sugars in the lower gut to produce acidic conditions, again preventing hydroxyapatite formation. As well, an osmotic effect resulting from prebiotic intake can lead to the opening of gap junctions between mucosal cells in the intestine, thereby increasing calcium absorption through a paracellular route.

Other Health Properties of Ingested Honey
In addition to the well-recognized bioactive properties of honey that have been discussed earlier in this chapter (i.e. antibacterial, antioxidant and prebiotic effects), recent research has also discovered a number of other properties that may support health and wellness.

Gastric Health
In recent years, a small number of studies have been undertaken to assess the gastro-protective effects of honey in rats. In an earlier study, rats given oral solutions of honey (0.078–0.625 g/kg body weight) 30 minutes prior to ischaemia- and reperfusioninduced gastric lesions exhibited significantly fewer gastric lesions, and reduced intraluminal bleeding and vascular permeability compared with animals pretreated with water only. Similar results were also obtained with pre-treatment with the free-radical scavenger dimethyl sulphoxide (DMSO) (0.02–0.08 g/kg body weight, intraperitoneally), suggesting that free radical damage may be involved in the pathogenesis of ischaemia-reperfusion-induced mucosal injuries, and that the gastro-protective effects of honey may be due to its antioxidant properties.

Natural honey (0.078– 0.625 g/kg body weight) prevented the increase in vascular permeability that was observed following exposure to ethanol, although this effect was diminished if the animals were pre-treated with the sulphydryl blocker N-ethylmaleimide (0.05 g/kg) prior to being administered the honey. Thus, it has been suggested that the protective effects of honey may be mediated through sulphydryl-sensitive processes, as well its antioxidant content. Similar conclusions were also drawn by Ali (2003) when it was shown that both honey (0.312–1.25 g/kg body weight) and sulcralfate (0.25–1.0 g/kg) prevented the formation of ammonia-induced gastric lesions, and reversed the decrease in non-protein sulphydryls that resulted from the ammonia treatment.

In two studies, honey has again been demonstrated to have gastro-protective effects, it preventing the gastric lesions induced by ethanol and indomethacin and acidified aspirin. Importantly, both of these studies also tested the effects of a mixture of glucose, fructose, sucrose and maltose, and demonstrated gastro-protective effects that were only slightly less than those of the honey, suggesting that the protective effects of the honey may be substantially due to its carbohydrate content. In the two studies by Gharzouli, however, the concentrations of the four sugars used in the sugar mixture were supposed to be representative of the levels found in the honey (38.2% fructose, 31.3% glucose, 1.5% sucrose and 7.3% maltose). But, due to the authors not taking the density of honey into account, and adding only 17.5 ml of water rather than making the solution to a total of 100 ml, the sugar mixture they prepared was considerably more concentrated than that found in a typical honey. It has suggested, therefore, that the gastro-protective effects of the sugar mixture were most likely due to it simply forming a physical barrier over the mucosal surface of the stomach.

Honey may also have a possible role in the improvement of gastric health, via the improvement of naturally occurring peptic ulcers. In a small number of in vitro studies, Manuka honey has been shown to inhibit the growth of Helicobacter pylori, the organism thought to be responsible for the development of dyspepsia and peptic ulcers. In the earlier study, Manuka honey was shown to have bacteriostatic properties against H. pylori at concentrations of 5% (v/v), with most clinical strains showing complete inhibition of growth with honey concentrations of 20% (v/v). Importantly though, solutions of glucose, fructose and their combinations have also been shown to inhibit the growth of H. pylori at concentrations ≥ 15% suggesting that the inhibition may be due to the osmotic action of the honey/sugar solutions rather than any inherent antibacterial activity. In addition, whereas Manuka honey has been shown to be effective at retarding the growth of H. pylori in vitro, it has not been demonstrated to have any effect in vivo. In a small clinical study, all patients (n=6) remained positive for H. pylori four weeks after a 2-week regime of a tablespoon of Manuka honey, taken four times a day. No other clinical studies appear to have investigated the efficacy of honey as a treatment for dyspepsia or gastric ulcers, although it would certainly be of interest to further study its clinical efficacy given the above findings that honey can minimize the formation of gastric ulcers when taken as a preventative measure. In particular, ammonia is liberated in the stomach of H. pylori-infected individuals, and it has been implicated in the pathogenesis of peptic ulcer diseases. Thus, honey may offer an effective therapeutic treatment for gastric ulcers, both via its antibacterial effect on the H. pylori organisms directly, and via prevention of ammonia-induced gastric lesions.

Honey may also be an effective treatment for ulcerative colitis of the gut, as limited research in rats has demonstrated that honey significantly reduced intestinal mucosal injury scores when given as a 50% solution (2 ml) rectally for 7 days following induction of colitis. Importantly, in this same study, treatment with prednisolone and disulfiram (pharmaceuticals that are standard therapy for inflammatory bowel disease) had no effect, the degree of intestinal damage (ulcers and erosions) being similar between these animals given these two treatments and those in the control saline group. Similarly, in a second animal study, honey provided dose-dependent protection against acetic acid-induced colonic damage, when taken orally and rectally for four days, with induction of colitis on day three (i.e. after the first two days of honey treatment). Honey at a concentration of 5 g/kg body weight afforded nearly 100% protection, whilst a mixture of glucose, fructose, sucrose and maltose (as in honey) had no protective effect . In both studies, honey also restored malondialdehyde levels (an indicator of lipid peroxidation) back towards normal levels.

In other clinical studies, it has also been suggested that honey may aid in the treatment of diarrhea and gastroenteritis, 169 infants presenting with gastroenteritis were given either standard rehydration therapy (oral and/or intravenous fluids containing glucose and electrolytes) or honey-based rehydration therapy (oral and/or intravenous fluids, with the oral solution containing honey in place of glucose such that the electrolyte content was the same). When taken as a whole, there were no significant differences between the two treatments for the mean recovery time, nor the mean rehydration time; however, when only those patients with bacterial gastroenteritis were considered, infants given honey (50 ml/l) had significantly reduced mean recovery times compared with the control group (58 vs 93 hours). It has been suggested that honey may have this effect due to its high sugar content promoting absorption of sodium and water from the gut, although it is likely that other factors may be involved also. In contrast, honey has also been suggested as a good remedy for constipation – this being due to the fact that consuming honey has been shown to have a laxative effect in vivo.

Anti-Cancer Effects of Honey
A small number of studies have investigated the anti-cancer properties of honey in recent years, with interesting results. In the earlier study, honey (1–25%) significantly inhibited the growth of bladder cancer cell lines when tested in vitro. In addition, intralesional injections of honey (6 and 12%) significantly reduced the growth of tumours resulting from cancer cells that were implanted into the abdomen of mice. No comparisons with other sugar solutions were undertaken in this study, but it was suggested that the effects may have been due to its chemical constituents as another study has reported that administration of hydroxycinnamates from honey significantly inhibited benzopyrene-induced neoplasia of the forestomach in mice.

Similarly, solutions of honey (1–2 g/kg bodyweight) given orally via a gastric tube for 10 days significantly reduced metastasis formation in mice and rats with transplanted carcinoma in the lungs, but only when it was taken as a preventative measure. In contrast, animals receiving honey therapy that began 2 days after tumor cell inoculation had no reduction in tumor nodule formation, with a few animals even exhibiting enhanced tumor growth in their lungs. Importantly, no controls were carried out with these studies, although it was also reported in one study that royal jelly also reduced the formation of metastases when it was conadministered with the tumor cells.