Health benefits of Manuka honey
Active constituent of Manuka honey and its properties
If you are one of those intensely passionates about nature and life, use to visit from time to time herbal shops and have a look to herbal news sites, you may have heard about a very special honey type, the Manuka honey, which prices reache 2'5 times the prices of other regular honeys available in the market and has been claimed to exert many health benefits and properties. But what makes Manuka honey so special?
Manuka honey gets its name from the tree from which is being produced, the Leptospermum scoparium, Manuka tree, tea tree or simply Leptospermum, a shrub native to New Zealand [7]. Manuka flowers have been used by honey bees in New Zealand to produce one of the most famous and expensive honeys of the world, Manuka honey.
The high demand on the market caused by claims that recent scientific studies and clinical trials made on the properties of Manuka honey, ranging from its anti-Helicobacter pylori properties to its antibacterial, anti-plaque, anti-gingivitis, burn healing and skin protecting effects, and even some suggesting it may help to against certain types of cancer, entailed a price increase that may or may not be justified, let's have a look at that. Image: Manuka flower by John Tann under CC license (CC by 2.0).
LEPTOSPERMUM SCOPARIUM
Family: Myrtaceae
Genus: Leptospermum
Common name: Manuka tree, tea tree, Leptospermum, Jelly bush.
Methylglyoxal is the active constituent responsible for its beneficial properties, it was first found in Manuka honey by Professor Dr. Thomas Henle, at the Technische Universität in Dresden, Germany, in 2008.
Identification of Manuka honey active constituent Methylglyoxal
One thing all types of honey have in common is their antibacterial activity, something for which hydrogen peroxide is responsible for. The antiseptic and antibacterial activity of hydrogen peroxide that is produced in honey is caused by the enzyme glucose oxidase [17]. Hydrogen peroxide is formed in a slow-release manner by the enzyme glucose oxidase present in honey [18], consequently the more hydrogen peroxide produced the more antibacterial and antiseptic properties the honey exerts. But in Manuka honey this mechanism works a little bit different. Photograph Leptospermum by (2007) Dr. David Midgley licensed under a Creative Commons Attribution-Noncommercial 3.0 Unported License (CC BY-NC-ND 2.0).
But Hydrogen peroxide is not responsible for the antiseptic and antibacterial properties of Manuka honey, another active constituent is, methylglyoxal, and active constituent that could also have negative effects on the structure and function of other proteins/peptides in manuka honey, including glucose oxidase, the one responsible in common honeys to generate hydrogen peroxide [19].
In April 2008, Professor Dr. Thomas Henle, at the Technische Universität in Dresden, Germany, published a study on which he clearly established what was this mysterious active constituent exerting antibacterial properties in Manuka honey. He identified this active constituent as methylglyoxal (MGO) [8], an aldehyde form of pyruvic acid that can also be found in lower quantities in other types of honey. What was then so different in Manuka honey? Well, out of six samples of New Zealand Manuka (Leptospermum scoparium) honey, the average amounts of methylglyoxal found on them ranged from 38 to 761 mg/kg, which is up to 100-fold higher compared to conventional honeys [8].
Antibacterial properties of Methylglyoxal from Manuka honey
But the findings of Professor Dr. Thomas Henly wouldn't have much
influence on the claims of Manuka honey antibacterial properties if he wouldn't have demonstrated that methylglyoxal was the active constituent exerting those antibacterial properties. In the study mentioned above [8], Professor Dr. Thomas Henle analysed the activity of methylglyoxal found in Manuka honey against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial strains. In both cases Manuka honey methylglyoxal exhibited antibacterial activity when diluted to 15-30%, which demonstrates that the pronounced antibacterial activity of New Zealand Manuka honey directly originates from methylglyoxal [8].
What is Active Manuka honey?
Active Manuka honey is said to be that exerting a certain level of antibacterial effect, measured in a scale known as Unique Manuca Factor, or UMF. In order to consider Manuka honey as "active" the Unique Manuka Factor in laboratory tests should be equal or higher than 10 UMF.
The average amounts of methylglyoxal found on Manuka honey ranged from 38 to 761 mg/kg, which is up to 100-fold higher compared to conventional honeys [8].
What is the Unique Manuka Factor UMF?
The Unique Manuka Factor is, as we mentioned above, a rating measuring the antibacterial properties of Manuka honey using an agreed scale. It is considered that ratings equal or higher to UMF 10 can be considered apt for therapeutic use. The unique manuka factor (UMF) value, expresses as phenol equivalents of its bactericidal activity [14].
Some concerns were raised about the possible dangers that higher ratings, as for example UMF 20 or higher, could have on human health, however recent studies done on healthy individuals aged 42-64 years that were administered Manuka honey with a UMF 20 for a 4 week period demonstrate that these concerns are not founded [1].
A new active constituent found in Manuka honey, Leptosin may play also a role in the UMF rating
Recent investigations on the content of active constituents found in Manuka honey indicated that a new active constituent named "leptosin" after the genus Leptospermum [14], may also play a very important role on the Unique Manuka Factor on Manuka honey. In the referenced study, the concentration of leptosin in manuka honey was positively correlated with the unique manuka factor (UMF) value, which is expressed as phenol equivalents of its bactericidal activity [14].
But leptosin is not the only active constituent found only in Manuka honey, among the active constituents specifically found in Manuka honey we can mention kojic acid, 5-methyl-3-furancarboxylic acid, 3,4,5-trimethoxybenzoic acid esterified with maltose, unedone, 2-methoxybenzoic acid, 4-methoxyphenyllactic acid, 3-hydroxy-1-(2-methoxyphenyl)-penta-1,4-dione and methyl syringate [20].
Facts about Methylglyoxal
In spite all these claimed health benefits and exerted properties may make Manuka honey a perfect complement in our diets, are there no contraindications?
Recent studies on Manuka's active ingredient "properties" showed in spite methylglyoxal exerts many beneficial properties for certain ailments and affections, not all are benefits. Methylglyoxal, the so-called main active constituent found in Manuka honey should be avoided in certain cases and it may be recommended in some others.
Methylglyoxal from Manuka honey induces apoptosis in Sarcoma
Some studies suggest that methylglyoxal might initiate an apoptotic event in malignant cells [10]. Other studies showed how methylglyoxal could acta as a potent inhibitor of the polyamine biosynthetic pathway, on the growth of human osteosarcoma HuO9. This inhibition of polyamine synthesis results in the suppression of growth rate of osteosarcoma HuO9 cells, eventually inducing apoptosis (natural cell death) in these human osteosarcoma cells, both in vitro and in vivo [11,12].
In studies performed in murine models, Methylglyoxal showed to be able to profoundly stimulate host's immune response against tumor cell by producing reactive oxygen intermediates and reactive nitrogen intermediates [13].
Manuka honey for plaque and gingivitis
It is already known that Manuka honey has superior antimicrobial properties that can be used with success in the treatment of wound healing, peptic ulcers and bacterial gastro-enteritis, but its use against plaque and gingivitis wasn't yet confirmed.
In a study done on Manuka honey with a UMF 15 rating, it was demonstrated how Manuka honey could be used to reduce dental plaque and clinical levels of gingivitis. In this 21 day trial, Manuka honey product, or sugarless chewing gum were given to two groups, for 10 minutes, three times a day, after each meal. Plaque and gingival bleeding scores were recorded before and after the 21-day trial period. The results indicated that there were statistically highly significant reductions in the mean plaque scores and the percentage of bleeding sites in the manuka honey group, with no significant changes in the control group, suggesting that there may be a potential therapeutic role for manuka honey for the treatment of gingivitis and periodontal disease.
Methylglyoxal, cognitive function and cerebral atrophy in elderly people
At least two study suggest that there may be a link between increased levels of Methylglyoxal and cognitive decline and neurodegeneration [2,3].
Methylglyoxal and diabetes
Most of the studies analysed refer to macrovascular complications, including hypertension. The concentration of methylglyoxal significantly increases in plasma from diabetic patients. Increased plasma methylglyoxal level seems to be associated with diabetic microvascular complications [9].
MANUKA HONEY FOR VARICELLA ZOSTER VIRUS
In a study aimed to determine the in vitro anti-viral effect of honey on varicella zoster virus clover and Manuka honey showed antiviral activity against varicella zoster virus in vitro, being and inexpensive and excellent remedy against zoster rash, specially useful in developing countries where antiviral drugs are expensive or not easily available [21].
REFERENCES
[1] Two major medicinal honeys have different mechanisms of bactericidal activity. Kwakman PH, Te Velde AA, de Boer L, Vandenbroucke-Grauls CM, Zaat SA. Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
[2] Methylglyoxal, Cognitive Function and Cerebral Atrophy in Older People. Srikanth V, Westcott B, Forbes J, Phan TG, Beare R, Venn A, Pearson S, Greenaway T, Parameswaran V, Münch G. Head, Stroke and Aging Research Group, Neurosciences, Deparment of Medicine, Southern Clinical School, Level 5, Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
[3] Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Beeri MS, Moshier E, Schmeidler J, Godbold J, Uribarri J, Reddy S, Sano M, Grossman HT, Cai W, Vlassara H, Silverman JM. Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY 10029, United States.
[4] Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment. Ahmed N, Ahmed U, Thornalley PJ, Hager K, Fleischer G, Münch G. Department of Biological Sciences, University of Essex, Colchester, Essex, UK.
[5] New Zealand kanuka honey has high levels of methylglyoxal and antimicrobial activity. Holt S, Johnson K, Ryan J, Catchpole O, Zhang S, Mitchell KA.
[6] Manuka honey inhibits cell division in methicillin-resistant Staphylococcus aureus. Jenkins R, Burton N, Cooper R. University of Wales Institute Cardiff, Western Avenue, Cardiff CF5 2YB, UK.
[7] Wikipedia article on Leptospermum scoparium via http://en.wikipedia.org/wiki/Leptospermum_scoparium
[8] Identification and quantification of methylglyoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand. Mavric E, Wittmann S, Barth G, Henle T. Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany.
[9] Exploring mechanisms of diabetes-related macrovascular complications: role of methylglyoxal, a metabolite of glucose on regulation of vascular contractility. Mukohda M, Okada M, Hara Y, Yamawaki H. Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
[10] Methylglyoxal induces mitochondria-dependent apoptosis in sarcoma. Ghosh A, Bera S, Ray S, Banerjee T, Ray M. Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India.
[11] Growth inhibition of human osteosarcoma HuO9 cells by methylglyoxal bis(cyclopentylamidinohydrazone) in vitro and in vivo. Satoh N, Hibasami H, Mori K, Kaneko H, Wakabayashi H, Hirata K, Sonoda J, Nakashima K, Uchida A. Department of Orthopedic Surgery, Mie University, Tsu-city, Mie 514-8507, Japan.
[12] Induction of apoptotic cell death in three human osteosarcoma cell lines by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP). Mori K, Hibasami H, Satoh N, Sonoda J, Yamasaki T, Tajima M, Higuchi S, Wakabayashi H, Kaneko H, Uchida A, Nakashima K. Department of Orthopedic Surgery, Faculty of Medicine, Mie University, Japan.
[13] Methylglyoxal induced activation of murine peritoneal macrophages and surface markers of T lymphocytes in sarcoma-180 bearing mice: involvement of MAP kinase, NF-kappa beta signal transduction pathway. Pal A, Bhattacharya I, Bhattacharya K, Mandal C, Ray M. Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
[14] Identification of a novel glycoside, leptosin, as a chemical marker of manuka honey. Kato Y, Umeda N, Maeda A, Matsumoto D, Kitamoto N, Kikuzaki H. School of Human Science and Environment, University of Hyogo, Himeji, Hyogo, Japan
[15] Leptosins isolated from marine fungus Leptoshaeria species inhibit DNA topoisomerases I and/or II and induce apoptosis by inactivation of Akt/protein kinase B. Yanagihara M, Sasaki-Takahashi N, Sugahara T, Yamamoto S, Shinomi M, Yamashita I, Hayashida M, Yamanoha B, Numata A, Yamori T, Andoh T. Department of Bioinformatics, Soka University, Hachioji, Tokyo, Japan.
[16] The effects of manuka honey on plaque and gingivitis: a pilot study. English HK, Pack AR, Molan PC. Discipline of Periodontology, School of Dentistry, University of Otago, Dunedin, New Zealand.
[17] The effect of dilution on the rate of hydrogen peroxide production in honey and its implications for wound healing. Bang LM, Buntting C, Molan P. Honey Research Unit, Department of Biological Sciences, University of Waikato, Hamilton, New Zealand.
[18] Wikipedia article on Hydrogen peroxide.
[19] Methylglyoxal-induced modifications of significant honeybee proteinous components in manuka honey: Possible therapeutic implications. Majtan J, Klaudiny J, Bohova J, Kohutova L, Dzurova M, Sediva M, Bartosova M, Majtan V. Institute of Zoology, Slovak Academy of Sciences, Dubravska cesta 9, 845 06 Bratislava, Slovakia; Department of Microbiology, Faculty of Medicine, Slovak Medical University, Limbova 12, 833 03, Bratislava, Slovakia.
[20] Classification and characterization of manuka honeys based on phenolic compounds and methylglyoxal. Oelschlaegel S, Gruner M, Wang PN, Boettcher A, Koelling-Speer I, Speer K. kojic acid, 5-methyl-3-furancarboxylic acid, 3,4,5-trimethoxybenzoic acid esterified with maltose, unedone, 2-methoxybenzoic acid, 4-methoxyphenyllactic acid, 3-hydroxy-1-(2-methoxyphenyl)-penta-1,4-dione, and methyl syringate
[21] In vitro antiviral activity of honey against varicella zoster virus (VZV): A translational medicine study for potential remedy for shingles. Shahzad A, Cohrs RJ. Department of Neurology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
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