This year the flu season continues …

Resveratrol Fights Influenza Virus
… by inhibiting the swine flu virus’s ability to replicate

By Will Block

”The time has come,” the Walrus said,
“To talk of many things:
Of shoes — and ships — and sealing-wax — 
Of cabbages — and kings — 
And why the sea is boiling hot — 
And whether pigs have wings.”

— Lewis Carroll, “The Walrus and The Carpenter”
(Emphasis added)

I nfluenza viruses are classified in accordance with their protein composition. They are divided into types A, B, and C, with type A having numerous subtypes. Type A viruses are the most dangerous to humans and are associated with the most severe disease outcomes. Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. Occasionally they are transmitted to domestic poultry, which may cause an outbreak or lead to human influenza pandemics. Influenza viruses originating from swine, which may also be of the A type, were the cause the three major influenza pandemics of the 20th century.

Indeed, swine were the gateway for avian influenza virus genes to enter human populations as reassortment viruses (the mixing of the genetic material of a species into new combinations in different individuals). Reassortment viruses are responsible for some of the major genetic shifts in the history of the influenza virus. Chief among these was the influenza pandemic of 1918 –1919, which is believed to have killed 50 – 100 million people worldwide, with 675,000 deaths in the U.S. alone.1,2

This pandemic killed more people than World War I and is cited as the most devastating epidemic in recorded world history. More people died of influenza in a single year than in four-years of the Black Death Bubonic Plague from 1347 to 1351.2

Flu from Animals Is Not New

The threat of animal influenza is, however, not new. Thousands of possible outbreaks, spanning centuries, and even millennia have been reported but never examined systematically, even in retrospect, given the advanced tools we now possess.


As of February 6, the flu-associated
hospitalization rate among
people 65 and older is the highest
rate recorded since CDC
began tracking that data in 2005.


Dr. Anne Schuchat, director of CDC’s National Center for Immunization and Respiratory Diseases, said that American cases of the flu virus of 2009 were found to be made up of genetic elements from four different flu viruses — North American swine influenza, North American avian influenza, human influenza, and swine influenza virus typically found in Asia and Europe — an unusually mongrelized mix of genetic sequences.3

Influenza A Type in Bats

New findings now indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses, especially type A viruses that have become a global public health issue.

A recent discovery of novel influenza A viruses in fruit bats identified another mammalian species that may serve as an important source of influenza virus genetic diversity and support reassortment with human influenza viruses.4 Since bats represent about 20% of all classified mammals, this is of considerable significance. In addition to the remarkably promiscuous influenza A virus, fruit bats are also thought to be the source of Ebola [see sidebar, “Ebola Likely to Go Airborne”].

Ebola Likely to Go Airborne

New analysis has found that the limited airborne transmission of Ebola is “very likely.”1 The available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission. However, this conclusion is based on a limited number of studies.

The researchers project that there are key areas requiring further study, including:

  • Aerosol transmission’s role (either via large droplets or small particles in the vicinity of source patients)
  • Environmental contamination and fomite (any object or substance capable of carrying infectious organisms) transmission’s role
  • The degree to which minimally or mildly ill persons transmit infection


The researchers hypothesize that
Ebola viruses have the potential to
be respiratory pathogens with
primary respiratory spread.


  • The length of time clinically relevant infectiousness persists
  • “Superspreading events” and the role they may play in driving transmission dynamics
  • Whether strain differences or repeated serial passage in outbreak settings can impact virus transmission
  • What role wild or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013 – 2015 West Africa situation

In this review, the researchers address what we know and what we do not know about Ebola virus transmission. They also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.

Reference

  1. Osterholm MT, Moore KA, Kelley NS, et al. Transmission of Ebola viruses: what we know and what we do not know. mBio 2015;6(2):e00137-15. doi:10.1128/mBio.00137 – 15.

To make matters worse, the effectiveness of antiviral therapies for influenza has been limited by the emergence of drug-resistant viral strains. Therefore, there is an urgent need to identify novel antiviral therapies.

Swine Flu Continues to Dominate

Despite declines in some key indicators, the 2014 – 2015 flu season remains widespread across most of the country and severity indicators are still high.5 According to the CDC, “The timing of flu is very unpredictable and can vary in different parts of the country and from season to season. Flu activity most commonly peaks in the U.S. between December and February. However, seasonal flu activity can begin as early as October and continue to occur as late as May.”


The 1918 pandemic killed
more people than World War I and
is cited as the most devastating
epidemic in recorded world history.


This season, activity began increasing in early December, and as of early February, flu remains widespread across most of the United States. As of February 6, in line with the CDC’s assessment, while national influenza-like-illness levels are declining slowly, in some regions of the country, the influenza incidence is increasing. According to Google Flu Trends,6 which uses aggregated Google search data and has received a brand new engine this flu season,7 the flu intensity is also increasing. Curiously, it is just now peaking in colder climate countries such as Sweden, Russia, Germany, and Austria, according to an experimental section of Google Flu Trends.

Also, the CDC says that H3N2 flu viruses (swine flu) continue to dominate across the country, hitting older people hard. As of February 6, the flu-associated hospitalization rate among people 65 and older is the highest rate recorded since CDC began tracking that data in 2005. Overall, nearly 60 percent of flu-associated hospitalizations have been among people 65 years and older.


Interferon-beta is likely to act
synergistically with resveratrol to
inhibit H1N1 replication.


Testing Resveratrol for Flu Potencies

In a new study, Chinese researchers tested the effects of 300 traditional Chinese medicines on the replication of various influenza virus strains in a lung cell line, using an influenza-specific luciferase reporter assay.8 Such assays use bioluminescence (the emission of light) to gives researchers unparalleled sensitivity when investigating questions that involve gene regulation.


Because of the emergence of
drug-resistant viral strains,
there is an urgent need to identify
novel antiviral therapies.


Of the traditional medicines tested, Polygonum cuspidatum (commonly called Japanese knotwood) and its active components, resveratrol and emodin, were found to reduce influenza viral replication in the lung cells, emitting light as a measure of their efficacy.

They preferentially inhibited the replication of influenza A virus, including clinical strains isolated in 2009 and 2011 in Taiwan and also from the H1N1 swine flu virus.


Polygonum cuspidatum
(commonly called Japanese
knotwood) and its active components,
resveratrol and emodin, were found
to reduce influenza viral replication
in a lung cell line.


In addition to inhibiting the expression of hemagglutinin and neuraminidase — key proteins in swine flu — Japanese knotwood and two active components, emodin and resveratrol, also increased the expression of interferon beta (IFN-β) through Toll-like receptor 9 (TLR9). The first, a protein produced as part of the innate antiviral defense system, and the second, another specialized protein that plays a fundamental role in pathogen recognition and activation of innate immunity.

Moreover, the anti-viral activity of IFN-β or resveratrol was reduced when the lung cells were treated with neutralizing anti-IFN-β antibodies or a TLR9 inhibitor, suggesting that IFN-β likely acts synergistically with resveratrol to inhibit H1N1 replication.

Limited Antiviral Drugs

At this time, there are only two classes of antiviral drugs approved by the FDA to treat or prevent influenza virus infections: M2 ion channel inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir).9 However, the use of M2 inhibitors is not practical due to widespread drug resistance. Only neuraminidase inhibitors provide any uncompromised treatment for seasonal and pandemic influenza. Nonetheless, common side effects include nausea and vomiting, rendering them undesirable.


The following nutritional supplements
have been shown to be beneficial for
reducing the likelihood that you — 
especially if you’re 65 or older — will
fall prey to the flu:
resveratrol, quercetin,
N-acetylcysteine, EGCG (from green
tea), vitamin C, and Vitamin D.


Consequently, new antiviral therapies are much in need, especially natural ones to strengthen the immune mechanisms of the body and thus enable avoidance of both seasonal and pandemic influenza.

The new study strongly suggests that components of Japanese knotwood bolster antiviral mechanisms, involving direct inhibition of virus replication and simultaneous activation of the host immune response, a feature that has not been previously described for a single antiviral molecule.

In conclusion, data support the use of resveratrol or emodin for inhibiting influenza virus replication directly and via TLR-9-induced IFN-β production. Unfortunately, emodin is only available at high cost, but the cost of resveratrol has come down considerably and it is now widely available as a supplement.

Do Not Let Viruses Take Advantage of Your Good Health

In addition to resveratrol, the following nutritional supplements have been shown to be beneficial for reducing the likelihood that you — especially if you’re up in years, say, 65 or older — will fall prey to the flu: quercetin, N-acetylcysteine, EGCG (from green tea), vitamin C, and Vitamin D. Even as the flu season is winding down, all of these nutrients possess other benefits to keep you healthy and happy.

References

  1. Johnson NPAS, Mueller J. Updating the accounts: global mortality of the 1918 – 1920 “Spanish” influenza pandemic. Bull Hist Med. 2002;76:105 – 15
  2. Billings M. The Influenza Pandemic of 1918. Stanford University. June 1997, modified February 2005. http://www.stanford.edu/group/virus/uda/. Accessed: February 22, 2015.
  3. Hasan Z. SARS to Swine flu (H1N1) in the present Global Recession. Science 2.0. April 29, 2009. http://www.science20.com/contagious/blog/sars_swine_flu_h1n1_present_global_recession. Accessed February 10, 2015.
  4. Mehle A. Unusual influenza A viruses in bats. Viruses. 2014 Sep 17;6(9):3438 – 49.
  5. What You Should Know for the 2014-2015 Influenza Season. The Center for Prevention and Disease Control. February 10, 2015. http://www.cdc.gov/flu/about/season/flu-season-2014-2015.htm. Accessed: Febraury 12, 2015.
  6. Explore flu trends - United States. Google.org. https://www.google.org/flutrends/us/#US. February 8, 2015. Accessed: February 12, 2015.
  7. Google Flu Trends gets a brand new engine. October 31, 2014. http://googleresearch.blogspot.com/2014/10/google-flu-trends-gets-brand-new-engine.html. Accessed: February 14, 2015.
  8. Lin CJ, Lin HJ, Chen TH, Hsu YA, Liu CS, Hwang GY, Wan L. Polygonum cuspidatum and Its Active Components Inhibit Replication of the Influenza Virus through Toll-Like Receptor 9-Induced Interferon Beta Expression. PLoS One. 2015 Feb 6;10(2):e0117602. doi: 10.1371/journal.pone.0117602.
  9. Jackson RJ, Cooper KL, Tappenden P, Rees A, Simpson EL, Read RC, Nicholson KG. Oseltamivir, zanamivir and amantadine in the prevention of influenza: a systematic review. J Infect. 2011 Jan;62(1):14 – 25.

Sepsis and Severe Sepsis Increase with the Flu

People who are infected with an influenza virus such as the swine flu may develop a serious condition called sepsis (aka septicemia or blood poisoning). Sepsis is the body’s often-deadly response to infection or injury. In severe cases of sepsis, one or more organs fail. In the worst cases, sepsis causes blood pressure to drop and the heart to weaken, leading to septic shock. Once this happens, multiple organs may quickly fail and the patient can die. This is similar to what happens to Ebola victims.


Doctors have found that rates of
sepsis and severe sepsis tend to rise
during so-called flu season, up to a
16% to 17% increase.


This condition kills and disables millions, and requires early identification and rapid treatment for survival. According to the CDC, hospitalization from sepsis increased from 621,000 in the year 2000 to 1,141,000 in 2008.1 Between 28 and 50 percent of people who get sepsis die. Doctors have found that rates of sepsis and severe sepsis tend to rise during so-called flu season, up to a 16% to 17% increase. Sepsis is also an increased risk due to antibiotic-resistant bacteria.2

(Also see “Can Galantamine Treat Sepsis?” from the November 2010 issue, and “Keep a Supply On Hand for … When You Need It But Can’t Get It” in the July 2013 issue of Durk Pearson & Sandy Shaw’s Life Extension News.)

References

  1. Centers for Disease Control and Prevention: Sepsis Questions and Answers. May 22, 2014. http://www.cdc.gov/sepsis/basic/qa.html#ftn1. Accessed: February 22, 2015.
  2. Pradipta IS, Sodik DC, Lestari K, Parwati I, Halimah E, Diantini A, Abdulah R. Antibiotic resistance in sepsis patients: evaluation and recommendation of antibiotic use. N Am J Med Sci. 2013 Jun;5(6):344 – 52.

Weight Loss Synergy: Resveratrol and Quercetin

As we reported 2 months ago (see “Resveratrol Ups Memory Performance” in the January 2015 issue), resveratrol along with quercetin enhance memory performance. Also, we know that quercetin enhances resveratrol bioavailability (see refs in the mentioned article).

The goal of a new study1 was to analyze whether the combination of resveratrol and quercetin showed additive or synergic effects on body fat accumulation and triacylglycerol metabolism in adipose tissue from rats fed an obesity-producing diet.


The combination of a combination
of resveratrol and quercetin led to
a significant reduction in the
fat depots analyzed.


Rats were divided into four dietary groups: a control group and three groups each treated with resveratrol (15 mg/kg/day; RSV), quercetin (30 mg/kg/day; Q), or both (15 mg resveratrol/kg/day and 30 mg quercetin/kg/day; RSV + Q) for 6 weeks.

White adipose tissues from several anatomical locations were dissected and serum parameters were analyzed. Also, the activities of fatty acid synthase and heparin-releasable lipoprotein lipase were measured, and protein expression of acetyl-CoA carboxylase, adipose tissue triglyceride lipase, and hormone-sensitive lipase by western blot.


When resveratrol and quercetin are
taken together, a great number of
metabolic pathways involved in
adipose tissue triacylglycerol
accumulation are affected.


The administration of either resveratrol or quercetin separately did not induce significant reductions in adipose tissue weights. By contrast, the combination of both molecules together led to a significant reduction in all the fat depots analyzed. The percentage of reduction in each tissue was greater than the calculated additive effect. Heparin-releasable lipoprotein lipase activity was reduced in RSV and RSV + Q groups. The activity of hormone-sensitive lipase was not modified. By contrast, acetyl-CoA carboxylase was inhibited and adipose tissue triglyceride lipase increased only by the combination of both polyphenols.

These results demonstrated a synergistic effect between resveratrol and quercetin, and suggest that when these molecules are combined, a great number of metabolic pathways involved in adipose tissue triacylglycerol accumulation are affected.

Reference

  1. Arias N1, Macarulla MT, Aguirre L, Milton I, Portillo MP. The combination of resveratrol and quercetin enhances the individual effects of these molecules on triacylglycerol metabolism in white adipose tissue. Eur J Nutr. 2015 Feb 11. [Epub ahead of print]


Will Block is the publisher and editorial director of Life Enhancement magazine.

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