by  Raul Corredor MD

The answer to this question has two parts. The first part is clear. Diet rich in polyphenols including anthocyanins helps the human immune system to work more efficiently to protect against viral infections.

The second part is a little bit more complex, specific types of anthocyanins may have a direct effect in decreasing influenza viruses infectivity by decreasing the ability of the virus itself to get into the human cells [1-3] or to be released from infected cells [4]; or by having a viricide effect [4-7], it means that some anthocyanins may kill viruses when they are in the lumen of the respiratory or intestinal tract. From this perspective, anthocyanins are very helpful in our battle against influenza.

Does it mean that anthocyanins can prevent influenza virus infections?

That is not the case; the only way to develop permanent immunity to a given virus is by allowing the immune system to fully respond to it (after exposition to the virus or to some antigenic vaccines).

However, increasing evidence suggests that anthocyanins may help by modulating the efficiency of the immune response in such a way that severity of symptoms and tissue damage may be substantially decreased. This characteristic gets more importance in the light of the increased risk of epidemic spread of new, deadly strains of influenza virus as in the case of the bird flu and the swine flu.

Why some people suffer milder forms of the disease, while others die despite being infected for the same viral strain and despite having similar treatment?

There are some obvious reasons for this, like the genetic background, immunization and the overall nutritional state. However, there are two additional factors: viral load related to the number of viral particles present at a given time in tissue or fluids; and secondary tissue damage [8-10] characterized by the death of cells that are not infected with the virus yet:
This includes at least three aggravating factors, release of free radicals (ROS) and toxic mediators from dying cells infected with the virus; release of ROS and inflammatory (by activation of the pro-inflammatory NF-kB signaling pathway, by inducing airway hyperreactivity, and by gating apoptosis mediated by mitochondrial DNA oxidative damage) mediators by immune cells, and side effects of antiviral medication[11-16].

Both of these factors are modified by mechanisms that were described above to be associated with the therapeutic effects of anthocyanins. As example, In the immune system anthocyanins induce macrophages to secrete tumor necrosis factor alpha (TNFα) [17, 18], TNFα has a strong viricide effect [19] decreasing influenza viral counts up to 28% in cultures of kidney cells [17].

Similarly, polyphenols neutralize influenza A virus directly in culture [4, 20, 21], and inhibit viral adhesion to cell membrane receptors in vitro [1, 3]without affecting cell viability [2].

Unfortunately, only few clinical studies showing the importance of anthocyanins in influenza treatment and prevention have been performed [22, 23], just enough to put in evidence the need for additional research studies.

However, extensive research in vitro[4, 24] and in animal models in vivo [25], constitutes demonstration of anthocyanins-mediated antiviral effects; which is of particular importance if it is noted that the antiviral effect of polyphenols is not significantly affected by viral mutations because they are binding to the viral envelope lipids or sugar moieties [6].

How much is an adequate, therapeutically effective doses of anthocyanins?

There is clear justification to consider anthocyanins in the treatment and prevention of the flu (specially having into account that in case of an epidemic outbreak, it may be potentially difficult and stressing to get the formal antiviral treatment from the health system; no antiviral medication is 100% effective, and viral responses to medications change over time).  However, although not toxicity has been reported with anthocyanins, it is not clear the amount of them required.

 Medox™ is a presentation of anthocyanins with the highest (80mg), standardized concentration of anthocyanins available (and includes additional 115mg of other polyphenols).  Anthocyanins have been shown to help in the seasonal flu [23], and are a good alternative to complement other measurements; including diet, since this amount of anthocyanins and polyphenols (equivalent to the amount contained in Medox™) would imply daily consumption of many pounds of a combination of anthocyanins-containing fruits and vegetables. 

References:

 1.            Nakayama, M., et al., Inhibition of the infectivity of influenza virus by tea polyphenols. Antiviral Res, 1993. 21(4): p. 289-99.
2.            Ehrhardt, C., et al., A polyphenol rich plant extract, CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. Antiviral Res, 2007. 76(1): p. 38-47.
3.            Yingsakmongkon, S., et al., In vitro inhibition of human influenza A virus infection by fruit-juice concentrate of Japanese plum (Prunus mume SIEB. et ZUCC). Biol Pharm Bull, 2008. 31(3): p. 511-5.
4.            Knox, Y.M., et al., Anti-influenza virus activity of crude extract of Ribes nigrum L. Phytother Res, 2003. 17(2): p. 120-2.
5.            Liu, A.L., et al., In vitro anti-influenza viral activities of constituents from Caesalpinia sappan. Planta Med, 2009. 75(4): p. 337-9.
6.            Kotwal, G.J., Genetic diversity-independent neutralization of pandemic viruses (e.g. HIV), potentially pandemic (e.g. H5N1 strain of influenza) and carcinogenic (e.g. HBV and HCV) viruses and possible agents of bioterrorism (variola) by enveloped virus neutralizing compounds (EVNCs). Vaccine, 2008. 26(24): p. 3055-8.
7.            Song, J.M., K.H. Lee, and B.L. Seong, Antiviral effect of catechins in green tea on influenza virus. Antiviral Res, 2005. 68(2): p. 66-74.
8.            Rossi, A., et al., Protective effects of anthocyanins from blackberry in a rat model of acute lung inflammation. Free Radic Res, 2003. 37(8): p. 891-900.
9.            Serraino, I., et al., Protective effects of cyanidin-3-O-glucoside from blackberry extract against peroxynitrite-induced endothelial dysfunction and vascular failure. Life Sci, 2003. 73(9): p. 1097-114.
10.          Wang, Q., et al., Cyanidin-3-O-beta-glucoside inhibits iNOS and COX-2 expression by inducing liver X receptor alpha activation in THP-1 macrophages. Life Sci, 2008. 83(5-6): p. 176-84.
11.          Valcheva-Kuzmanova, S.V. and A. Belcheva, Current knowledge of Aronia melanocarpa as a medicinal plant. Folia Med (Plovdiv), 2006. 48(2): p. 11-7.
12.          Hamauzu, Y., et al., Phenolic profile, antioxidant property, and anti-influenza viral activity of Chinese quince (Pseudocydonia sinensis Schneid.), quince (Cydonia oblonga Mill.), and apple (Malus domestica Mill.) fruits. J Agric Food Chem, 2005. 53(4): p. 928-34.
13.          Karlsen, A., et al., Anthocyanins inhibit nuclear factor-kappaB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. J Nutr, 2007. 137(8): p. 1951-4.
14.          Ruchko, M., et al., Mitochondrial DNA damage triggers mitochondrial dysfunction and apoptosis in oxidant-challenged lung endothelial cells. Am J Physiol Lung Cell Mol Physiol, 2005. 288(3): p. L530-5.
15.          Youdim, K.A., A. Martin, and J.A. Joseph, Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radic Biol Med, 2000. 29(1): p. 51-60.
16.          Park, S.J., et al., Anthocyanins inhibit airway inflammation and hyperresponsiveness in a murine asthma model. Food Chem Toxicol, 2007. 45(8): p. 1459-67.
17.          Obi, N., et al., Inhibitory Effect of TNF-alpha Produced by Macrophages Stimulated with Grifola frondosa Extract (ME) on the Growth of Influenza A/Aichi/2/68 Virus in MDCK Cells. Am J Chin Med, 2008. 36(6): p. 1171-83.
18.          Imanishi, N., et al., Macrophage-mediated inhibitory effect of Zingiber officinale Rosc, a traditional oriental herbal medicine, on the growth of influenza A/Aichi/2/68 virus. Am J Chin Med, 2006. 34(1): p. 157-69.
19.          Van Campen, H., Influenza A virus replication is inhibited by tumor necrosis factor-alpha in vitro. Arch Virol, 1994. 136(3-4): p. 439-46.
20.          Sawai, R., et al., Anti-influenza virus activity of Chaenomeles sinensis. J Ethnopharmacol, 2008. 118(1): p. 108-12.
21.          Awadh Ali, N.A., et al., Antiviral activity of Inonotus hispidus. Fitoterapia, 2003. 74(5): p. 483-5.
22.          Wang, X., W. Jia, and A. Zhao, Anti-influenza agents from plants and traditional Chinese medicine. Phytother Res, 2006. 20(5): p. 335-41.
23.          Zakay-Rones, Z., et al., 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. 32(2): p. 132-40.
24.          Galvano, F., et al., Bioavailability, antioxidant and biological properties of the natural free-radical scavengers cyanidin and related glycosides. Ann Ist Super Sanita, 2007. 43(4): p. 382-93.
25.          Droebner, K., et al., CYSTUS052, a polyphenol-rich plant extract, exerts anti-influenza virus activity in mice. Antiviral Res, 2007. 76(1): p. 1-10.