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Honey is appreciated the world over as one of Nature's most delicious foods, but did you know it may have potent anti-flu activity as well?

A fascinating new study published in the Archives of Medical Research titled, "Anti-influenza Viral Effects of Honey In Vitro: Potent High Activity of Manuka Honey," reveals that honey may actually provide a natural drug alternative to anti-flu drugs, but without the notorious side effects associated with this drug class which includes Tamiflu (oseltamivir).

The study tested a commonly researched H1N1 influenza strain known as A/WSN/3, infecting MadineDarby canine kidney (MDCK) cells with the virus, and then exposing them to various forms of honey, including manuka (L. scoparium), soba (F. esculentum; buckwheat), kanro (honeydew), acacia (R. pseudoacacia), and renge (A. sinicus).

Honey's Potent Anti-Viral Properties Against Influenza

The anti-influenza virus effects of the honey samples were evaluated by growing MDCK cells in 48-well plates and infecting them with influenza virus in the presence of 2-fold serially diluted honey samples. Two days after infection, the cells were fixed and stained in order to ascertain the degree to which they prevented the cytopathic effect (i.e., the degree to which influenza virus infection caused the cells to die and detach from the plate) of influenza virus.

The results of the study were represented pictorially in the figure below:

All tested honey samples suppressed viral infectivity in a dose-dependent manner, indicating their anti-viral activity, with manuka honey exhibiting the greatest potency.

The study also tested whether manuka honey is able to directly inhibit influenza virus growth through what is known as the plaque inhibition assay, as determined through the following 4 methods:

Pretreatment of cells: Adding manuka to the cells for 1 h and subsequently washed out before viral infection.

Pretreatment of virus: Mixing manuka with influenza virus suspension for 1 h before viral infection

Treatment during infection: Adding manuka during virus adsorption for 1 h and subsequently washed out

Treatment after infection: Adding manuka to the agarose gels

The most potent effect was exhibited with pretreatment of the virus itself, indicating manuka has potent virus-killing properties. Moderate reductions in plaque numbers were observed on treatment of cells with the honey during and after infection. The only method that did not demonstrate a growth inhibition was the pretreatment of cells.

Synergistic Effect of Honey with Conventional Anti-Viral Drugs

The study also looked at manuka honey's synergistic properties in combination with conventional anti-viral drugs in the neuraminidase inhibitor class known as Relenza (zanamivir) and Tamiflu (oseltamivir). The researchers commented:

"A combined use of synergistically active antiviral compounds that have different mechanisms of action may provide advantages over single-agent treatments."

The plaque inhibition assay protocal was reproduced, but this time the drugs were added to the honey mixture, with the result that manuka significantly increased the anti-viral effectiveness of both drug compounds.

How Honey Works and Further Implications

In the discussion section of the paper, the researchers pointed out that the anti-viral activities of the honeys tested are likely attributable in some part to the presence of a wide range of phytochemicals contained within them, especially phenolic acids and flavonoids. Independent research has already confirmed the anti-microbial properties of rutin and chrysin, which are found in relevant concentrations in most buckwheat and acacia honeys. Manuka honey, on the other hand, contains a compound known as methylglyoxal, which is found at concentrations approximately 20-160 fold higher than in any other honey yet tested, and which has already been verified to have anti-viral properties in foot and mouth disease virus.[1]

The study authors commented that we live in a time where there is an urgent need for new anti-influenza medicines. They pointed out that, in Japan, Tamiflu-resistant flu increased from 2.6% in 2007/2008 to over 99% in 2008/2009, illustrating a disturbing trend of increased drug-resistance. They point out that, "Because compounds or plant extracts that exhibit virucidal activity have broad-spectrum, it is possible that the virucidal activity of manuka honey is effective against H5N1 and H7N9 viruses," which are considered highly pathogenic viruses.

The researchers concluded their study on a promising note:

"In conclusion, the results obtained showed that honey, in general, and particularly manuka honey, has potent inhibitory activity against influenza virus, demonstrating a possible medicinal value. Further investigations are required to identify the active antiviral components in manuka honey and to determine its synergistic effects with known antiviral drugs."

Natural Anti-Influenza Alternatives Abound

This study is one of hundreds in existence today on the potential role of natural compounds in preventing infection, and reducing morbidity and mortality, against influenza. GreenMedInfo.com has collected over 100 such studies on its Influenza Research page detailing the role of natural interventions in this seasonal epidemic. A few highlighted interventions include:

Vitamin D : Sunlight exposure is of fundamental importance in supporting natural immunity against influenza. In fact, known as the 'seasonal stimulus hypothesis,' seasonal influenza may be triggered each year during the fall and winter months (especially in higher and lower latitudes), due to lower sunlight availability and a subsequent crash in immune factors dependent on sunlight-induced vitamin D production.[2] To this point, a 2010 study found that the simple addition of a vitamin D supplement is effective in preventing seasonal influenza A in schoolchildren, reducing risk by 59%. As a secondary outcome in children with a previous diagnosis of asthma, asthma attacks occurred in 2 children versus 12 who did not take D. [3] There is also evidence that lower solar ultraviolet-B radiation (and vitamin D) levels were significant contributing factors in reducing case-fatality rates from the 1918-1919 influenza pandemic in the Unites States.[4]

: Sunlight exposure is of fundamental importance in supporting natural immunity against influenza. In fact, known as the 'seasonal stimulus hypothesis,' seasonal influenza may be triggered each year during the fall and winter months (especially in higher and lower latitudes), due to lower sunlight availability and a subsequent crash in immune factors dependent on sunlight-induced vitamin D production.[2] To this point, found that the simple addition of a vitamin D supplement is effective in preventing seasonal influenza A in schoolchildren, reducing risk by 59%. As a secondary outcome in children with a previous diagnosis of asthma, asthma attacks occurred in 2 children versus 12 who did not take D. [3] There is also evidence that lower solar ultraviolet-B radiation (and vitamin D) levels were significant contributing factors in reducing case-fatality rates from the 1918-1919 influenza pandemic in the Unites States.[4] Elberberry : Something as simple as a purple berry may improve your chances of both preventing and fighting off influenza. A 2004 study found that elderberry was a safe and effective treatment for both influenza A and B strains, improving recovery time from influenza in 93.3% of the elderberry treated group within 2 days, and within 6 days in 91.7% of control group. [5] Another 2004 study found elderberry relieved symptoms of influenza on average 4 days earlier than those receiving a placebo.[6] Cell research has also demonstrated that elderberry flavonoids bind to and prevent H1N1 infection.[7]

: Something as simple as a purple berry may improve your chances of both preventing and fighting off influenza. A 2004 study found that elderberry was a safe and effective treatment for both influenza A and B strains, improving recovery time from influenza in 93.3% of the elderberry treated group within 2 days, and within 6 days in 91.7% of control group. [5] Another 2004 study found elderberry relieved symptoms of influenza on average 4 days earlier than those receiving a placebo.[6] Cell research has also demonstrated that elderberry flavonoids bind to and prevent H1N1 infection.[7] Green Tea: Drinking green tea has been found to reduce the incidence of influenza infection in Japanese school children.[8] It has also been found safe and effective in healthy adults (18-70) for preventing flu symptoms and for enhancing T cell function.[9] Green tea has also been found to contain compounds that inhibit the two primary molecular means by which influenza gains entry into the cell to infect it. [10]

Sweet News For Drug Alternatives

Finally, it should be pointed out that natural alternatives like honey are not just nice 'adjunctive' treatments for influenza to help the drugs work better. In fact, the drugs commonly used to suppress influenza are so toxic that they may actually be increasing the risk of severe health issues and even death in those taking them. Two years ago, the FDA approved the use of Tamiflu (oseltamivir) in infants under 1, despite a growing body of research indicating that severe complications can result, including meningitis and pneumonia. [11] Tamiflu and Relenza were also recently found by The Cochrane Collaboration to be ineffective in preventing serious outcomes, both in annual and pandemic influenza outbreaks.

Honey, therefore, given its obvious safety vis-à-vis pharmaceuticals, may be superior as a stand-alone intervention from the perspective of the precautionary principle and an honest risk/benefit assessment of the difference between natural and synthetic compounds. Honey also has dozens of well-established side benefits, which can be viewed on our Honey Research page. Best of all, while it may be tempting to look at honey as some 'new drug' or 'nutraceutical,' it is simply a food. This means incorporating it into one's daily nutritional regimen, especially as an alternative to sugar, may help you to ward off infection and disease without you ever knowing it is providing you enhanced protection in the first place.

References

[1] Ghizatullina NK. Effect of methyl glyoxal on infectivity and antigenicity of foot-and-mouth disease virus. Acta Virol 1976;20:380-386.

[2] Hope-Simpson RE. The role of season in the epidemiology of influenza. Journal of Hygiene. 1981;86:35–47. [PMC free article] [PubMed]

[3] Mitsuyoshi Urashima, Takaaki Segawa, Minoru Okazaki, Mana Kurihara, Yasuyuki Wada, Hiroyuki Ida. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 May;91(5):1255-60. Epub 2010 Mar 10. PMID: 20219962

[4] William B Grant, Edward Giovannucci. The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States. Dermatoendocrinol. 2009 Jul;1(4):215-9. PMID: 20592793

[5] Z Zakay-Rones, N Varsano, M Zlotnik, O Manor, L Regev, M Schlesinger, M Mumcuoglu. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med. 1995 Winter;1(4):361-9. PMID: 9395631

[6] Z Zakay-Rones, E Thom, T Wollan, J Wadstein. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res. 2004 Mar-Apr;32(2):132-40. PMID: 15080016

[7] Bill Roschek, Ryan C Fink, Matthew D McMichael, Dan Li, Randall S Alberte. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. 2009 Aug 12. PMID: 19682714

[8] Mijong Park, Hiroshi Yamada, Kumi Matsushita, Shinya Kaji, Takahiro Goto, Yuko Okada, Kazuhiro Kosuge, Toshiro Kitagawa. Green Tea Consumption Is Inversely Associated with the Incidence of Influenza Infection among Schoolchildren in a Tea Plantation Area of Japan. J Nutr. 2011 Oct ;141(10):1862-70. Epub 2011 Aug 10. PMID: 21832025

[9] Cheryl A Rowe, Meri P Nantz, Jack F Bukowski, Susan S Percival. Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances gamma,delta T cell function: a randomized, double-blind, placebo-controlled study. J Am Coll Nutr. 2007 Oct;26(5):445-52. PMID: 17914132

[10] Jae-Min Song, Kwang-Hee Lee, Baik-Lin Seong. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 2005 Nov;68(2):66-74. Epub 2005 Aug 9. PMID: 16137775

[11] Kai Siedler, Heino Skopnik. Oseltamivir for treatment of influenza in infants less than one year: a retrospective analysis. Pediatr Infect Dis J. 2010 Jun;29(6):495-8. PMID: 20035245