Nutraceuticals and nootropics for anti-aging

Last February Dr. Zarkov’s article on the LifeLink website discussed Bird Flu and the use of supplements to fight it. Now, nine months later, Bird Flu is big news in the mainstream media. Are there any new developments we should know about?

There are three developments I’d like to mention: the spread of Bird Flu, the irresponsible responses by officialdom, and a new understanding of how Bird Flu damages the body. I’ll outline the typical course the disease takes if not treated. Then I’ll discuss some supplements that are in my own survival kit for the pandemic.

In this article the phrase ‘Bird Flu’ will mean the diseases that are caused by the H5N1 strain of influenza A viruses. ‘H’ and ‘N’ are two proteins in the shell that surrounds each viral particle. Variations in these two proteins are considered to define the various strains and substrains of influenza A viruses. The H5N1 strain is a particular family of closely related substrains. Since these viruses are constantly mutating and exchanging genetic material with each other and with other kinds of viruses, there are countless new substrains of H5N1 being generated every day. All of them are examples of Bird Flu viruses.

The spread of Bird Flu

During the summer of 2005, migratory birds carried several substrains of Bird Flu viruses from China across Asia into Europe and the Middle East. Other substrains were carried from Vietnam into Indonesia and the Philipines. Infected birds will soon be in Africa, Canada, and the United States if they are not already there.

Only a few humans are known for sure to have been infected in these newly invaded regions — mainly in Indonesia — but it is widely suspected that many more human infections have occurred and gone unrecognized and unreported. Unusually severe epidemics of respiratory diseases and encephalitis have been occurring this year in India, Nepal, Pakistan, Bangladesh, and elsewhere, but have been attributed to other diseases, not Bird Flu, even though testing for Bird Flu has seldom been carried out.

When large numbers of migratory birds began mysteriously dying across Asia, most of the affected countries avoided doing the kind of testing that would have identified Bird Flu infection had it been present, and instead tried to convince the world that their domestic fowl were not infected and that, besides, they have the disease “under control”.

Information-gathering by the World Health Organization (WHO)

The WHO is the United Nations’ agency that compiles information about epidemics and coordinates responses to them at the international level. Unfortunately, when it comes to information-gathering, the WHO is at the mercy of national governments. If a government wants to hide the fact that it has a serious epidemic on its hands, it may be able to prevent the WHO from obtaining any solid information about the situation. That is exactly what has happened in a number of countries, including China and Indonesia, in which the Bird Flu has become entrenched in bird populations. As a result, the whole world is left to speculate about the developing threat to all our lives.

The WHO has become the object of contempt for critics who think that it should be more aggressive in dealing with uncooperative national governments. Some say that the WHO has willingly collaborated with governments that have consistently lied, refused to accurately report disease statistics, and failed to follow agreed-upon protocols for fighting disease outbreaks. On the other side are those who say that the WHO’s hands are tied, and that governments might refuse to cooperate at all were the WHO to become more aggressive.

Whether the WHO’s timid approach to dealing with irresponsible governments has been right one is hard to say. The WHO’s recommendations for treating infected people, on the other hand, are clearly poor ones.

Treatment recommendations of the World Health Organization

For reasons that are hard to fathom, the WHO has been promoting a single antiviral drug as the world’s weapon against Bird Flu. That drug is oseltamivir (‘Tamiflu®’), a hard-to-make, expensive treatment manufactured by the Swiss company Roche Pharmaceuticals. Tamiflu has not been tested in humans for protection against H5N1 strains of Bird Flu, but in mice its effectiveness varies drastically depending on which substrain of Bird Flu the mice are infected with. For some substrains, Tamiflu decreases mortality by 80%; for other substrains it is completely ineffective.

Although Tamiflu has been used in Asia to treat H5N1 Bird Flu patients, it has never been tested in a controlled clinical trial for any substrain of H5N1. In mice it was found that Tamiflu must be administered within 36 hours of an H5N1 infection in order to have any benefit.¹ But according to the WHO protocol, Tamiflu must be administered within 48 hours of the appearance of symptoms — a criterion based on experience with other strains of influenza, not Bird Flu. Considering the unreliable reports that the WHO has been supplying to the news media about Bird Flu outbreaks in Asia, I am skeptical of their statements about everything, including Tamiflu. Unless I see evidence to the contrary, I’m going to assume that the mouse data represents the true picture for H5N1 infections: Tamiflu is useless unless given within 36 hours of infection, regardless of whether or not the patient shows symptoms.

When Tamiflu was used in human clinical trials to treat non-H5N1 flu infections, it reduced the intensity of the symptoms, and shortened their duration by about 1.3 days.² If the infection had been caused by H5N1 Bird Flu, Tamiflu might have made a difference in the amount of lung damage caused by the virus. But, since you may need to start treatment before any symptoms appear, how would you know whether the treatment is even needed? The answer is: you wouldn’t know — you would either take Tamiflu constantly, as a preventative, or you would undergo a course of Tamiflu whenever you think you may have been exposed to the virus. These are expensive approaches to Bird Flu treatment.

Tamiflu may prove useful for stamping out localized epidemics in their initial stages, but it makes little sense for health agencies to promote it as a general treatment during a pandemic. Tamiflu is unreliable, expensive, hard-to-obtain, and hard-to-administer, and there are better treatment options available.

How Bird Flu damages the body

In recent years there has been an increasing realization that, in many diseases, the damage to tissues by ‘free radicals’ can exceed any damage done by the microorganisms that cause the diseases. (Free radicals are molecular fragments that damage the macromolecules of our tissues, leaving them unable to carry out their functions.)

In particular, it has become apparent that the damage to lungs and other organs seen in Bird Flu infections is not directly caused by the presence of viral particles in the infected cells, but rather is the result of an over-response of the immune system.³ Cells of the immune system are normally summoned to infected tissues, where they use free radicals to kill infected cells and to destroy viral particles. But in Bird Flu infections too many immune cells are summoned, too many free radicals are produced, and too many cells are killed — infected cells and healthy cells alike.

Bird Flu patients die from lung damage caused by their own immune systems. This suggests that the disease can be treated not only by drugs that target the H5N1 virus itself, but also by substances that regulate the immune response, or that neutralize the free radicals produced by the immune system.

What to expect from an untreated Bird Flu infection

More than a hundred people have been hospitalized in Asia since 1997 for Bird Flu infections. From the clinical data collected from these patients, we can state the following:²¹

• The time from viral exposure to first symptoms ranges from 2 to 8 days; 3 to 4 days is most common.
• The first symptoms almost always include high fever, cough, and shortness of breath. Other early symptoms seen in some patients are pain in muscles or abdomen, headache, diarrhea, vomiting, sore throat, or runny nose.
• The lungs start filling with fluid and debris, patients develop breathing difficulties and usually require a respirator within 48 hours after seeing a doctor.
• Some patients develop encephalitis or kidney failure.
• The death rate for different substrains of Bird Flu has ranged from 33% to 100%. The time from first symptoms to death ranges from 4 to 30 days; 8 to 12 days is most common.
• Most deaths are attributed to lung failure.

The death rates given above may be somewhat misleading. They are the death rates of those whose symptoms were serious enough to land them in the hospital. There may have been people who survived Bird Flu infections because their symptoms were mild — people who never saw a doctor and whose survival was not counted in the statistics. This is just speculation, of course, since we have no evidence that these people exist. On the other hand, we do know that some substrains of Bird Flu have the potential to be 100% fatal. The substrain that killed thousands of birds at Qinghai Lake in China last spring (the same substrain that is now in Europe and the Middle East) was tested on eight chickens and eight mice. All sixteen of the experimental animals died within four days.²²

Supplements for treating Bird Flu

There are more than a dozen supplements and drugs that would be worth stockpiling in preparation for a Bird Flu pandemic. I’ll deal here only with some of the supplements — the ones I consider especially helpful, based on information in the medical literature. A more thorough discussion, that includes both drugs and supplements and ways of using them (even for advanced Bird Flu infections), is being prepared for a website that will be located at FluDoc.org. (It is not yet online.)

• NAC (N-acetyl-cysteine)

N-acetyl-cysteine is an antioxidant with a history of use both as a supplement and as a treatment for viral infections, including AIDS.⁴ In experiments with flu viruses, NAC prevented flu symptoms in two thirds of the infected patients and reduced the severity of symptoms in the other third.⁵

The recommended oral dosage is 600 mg twice per day, but I plan to take at least twice this much if a flu pandemic occurs. NAC’s low cost and lack of toxicity enables it to be used throughout a pandemic, as a preventative, rather than just as a treatment after an infection occurs.

LifeLink carries N-acetyl-cysteine in 600 mg tablets.

• Green Tea Extract (EGCG, Epigallocatechin gallate)

The antioxidants in green tea are under intense study because of their anti-cancer effects. But these substances also have anti-viral properties.⁶ One of them, EGCG (epigallocatechin gallate), has been found to strongly suppress the replication of flu viruses.

As luck would have it, EGCG is the principal active constituent in green tea extract. In fact, a single capsule of LifeLink’s green tea extract (Green Tea Rx) contains 7 times the amount of EGCG needed to achieve 50% inhibition of flu viruses in the human body. (I’ve done the arithmetic here, and taken into account the bioavailability of the supplement when taken orally.)

Why is EGCG such a powerful flu virus inhibitor? Probably because it acts against influenza A viruses (like Bird Flu) in two independent ways. First, it inhibits the neuraminidase enzyme -- the enzyme that enables new virus particles to be released from infected cells.⁷ Second, it alters the protein coat of infectious viral particles, causing the particles to clump together, and rendering them unable to infect human cells.⁸ Having these two independent modes of action makes EGCG an effective viral replication inhibitor even in at very low concentrations.⁷

Like NAC, EGCG can be used routinely, without waiting for exposure to a flu virus. I’m going to take 133 mg of EGCG three times per day during the pandemic, but if I get exposed to the virus I’ll increase that to 1000 mg three times per day. This should be enough to obtain maximal protection from the supplement.

LifeLink carries green tea extract (Green Tea Rx) in 500 mg capsules, containing 133 mg of EGCG.

• Quercetin

Quercetin is an antioxidant that is plentiful in plants and widely used as a nutritional supplement. Experiments in mice and tissue culture have shown that this substance protects lung and nerve tissue from damage during viral infections.⁹ The protection seems to be indirect — the result of quercetin’s effects on other antioxidants. For example, quercetin activates genes that cause increased production of the body’s native antioxidants superoxide dismutase, glutathione, and catalase.¹⁰

Quercetin has a 20-hour half-life in the human body, so twice-per-day dosing is adequate. The normal dosage range is 200 to 1200 mg/day. During a Bird Flu pandemic, I plan to use 500-1000 mg twice per day.

LifeLink carries Quercetin in 500 mg capsules.

• Alpha-lipoic acid (ALA)

ALA is one of the body’s native antioxidants and is popular as an anti-aging nutritional supplement. It has been studied and used as an antiviral co-treatment for HIV since the 1980s.

Bird Flu infections cause the immune system to produce a flood of inflammatory cytokines and free radicals. A central role in this process is played by a messenger molecule called NF-κB (Nuclear Factor Kappa-B).¹¹ Viral infection of a cell activates NF-κB which then stimulates many pro-inflammatory genes, including those for cytokines. The resulting ‘cytokine storm’ is responsible for overactivating the immune system and flooding the tissues with free radicals that destroy the body’s cells indiscriminately. ALA happens to be a suppressor of NF-κB.

During a Bird Flu pandemic I will be using at least 500 mg of ALA (mixed isomers) twice per day.

LifeLink carries alpha-lipoic acid in 250 mg capsules.

• DHA/EPA (fish oil)

Fish oil is an extract of fish fat, which is a major source of omega-3 fatty acids.¹² ‘Omega-3’ refers to the location in fat molecules of features that determine how the molecules interact with structures in and around human cells. Two omega-3 fatty acids, ‘DHA’ (docosahexaenoic acid) and ‘EPA’ (eicosapentaenoic acid), are of special interest to us here because of their effects on inflammation.

The anti-inflammatory actions of DHA and EPA are well established from human and animal studies, and from ex vivo experiments. These omega-3 acids suppress the production of inflammatory cytokines, increase the production of anti-inflammatory cytokines, and regulate the activity of the immune cells that use free radicals to kill infected cells.^13,14,16

When mice were fed diets high in fish oil and then infected with influenza, the killing of lung cells by the immune system was reduced.¹⁵ This translates into less damage to healthy cells in the lungs. (The fish oil dosage used in these experiments — 17% of total food intake — was vastly greater than would be used in a human setting. Such huge doses had the side effect of slowing the clearance of the virus from the body. At more reasonable doses, viral clearance would not be a problem, but the benefits would be less dramatic than in these mouse experiments. This is why a combination therapy is needed for dealing with Bird Flu — fish oil plus other supplements that work by different mechanisms.)

My regimen during the Bird Flu pandemic will include about 1000 mg twice per day of omega-3 fatty acids.

LifeLink carries fish oil as DHA Complex in 500 mg softgels.

• Vitamin C (ascorbic acid)

It has been several decades since Linus Pauling focused people’s attention on vitamin C as a treatment for colds and flu, and the subject is still a source of contention. Some studies of high-dose regimens have shown a substantial reduction in symptoms, other studies using different regimens have failed to show a benefit.^17,18 These inconsistencies are probably the result of inadequate doses or timing in the studies where no benefits were found.¹⁹

I base my confidence in vitamin C as a flu treatment on a 1999 study of 463 students. Those who were treated with 1000 mg of vitamin C every six hours on the day symptoms appeared, and 1000 mg three times per day thereafter, experienced an 85% reduction in cold or flu symptoms compared with the symptoms of those treated with pain relievers and decongestants.¹⁷

There are also reports in the medical literature and elsewhere of dramatic benefits from very large doses of vitamin C, taken either orally or intravenously.²⁰

As for me, during the pandemic I will be using several grams of vitamin C per day routinely, and if I develop flu symptoms I will immediately increase this to the maximum I can tolerate without causing gastro-intestinal side effects.

LifeLink carries vitamin C in 1000 mg tablets and in 250 gram jars of undosed powder.

CONCLUSION

A bird-flu pandemic is expected to occur in the near future. It may already have taken root somewhere in the world and be upon us within weeks. Or it may take longer than that. No one can yet predict how contagious it will turn out to be, or how deadly. Health agencies are trying hard to avoid saying anything that will cause panicky reactions, and are therefore distorting or withholding information in their public statements. Consequently, you have to be skeptical about the details of everything they say. Assume the worst and prepare accordingly.

Although the antiviral drug Tamiflu is being touted by the health agencies as the only effective treatment for a Bird Flu infection, the truth is that other treatments appear to be just as good or better. Although Tamiflu has some merits and would be nice to have, it will be unavailable to most people, it is expensive, and hard to know when to start. In contrast, the substances discussed above are available, can be used in advance of infection, and work by different mechanisms than Tamiflu. They target the immediate causes of lung damage rather than the viral replication cycle. My Bird Flu treatment kit will consist of a combination of these substances plus a couple of drugs that fall outside the scope of this website. (See the discussion at TruthMed.org.)

— Dr. Alexis Zarkov, Ph.D.

You can contact Dr. Zarkov at AskDrZarkov@yahoo.com.

Last modified 2006.July.18

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References indicated above

[1] Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir. Antimicrob Agents Chemother. 2001 Apr;45(4):1162-7.

[2] FDA report on Tamiflu

[3] Role of free radicals in viral pathogenesis and mutation. Rev Med Virol. 2001 Mar-Apr;11(2):87-101.

[4] NAC: first controlled trial, positive results. AIDS Treat News. 1996 Jul 5;(no 250):1-3.

[5] Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J. 1997 Jul;10(7):1535-41.

[6] Differential inhibition of HIV-reverse transcriptase and various DNA and RNA polymerases by some catechin derivatives. Nucleic Acids Symp Ser. 1989;(21):115-6.

[7] Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 2005 Nov;68(2):66-74. Epub 2005 Aug 9.

[8] Inhibition of the infectivity of influenza virus by tea polyphenols. Antiviral Res. 1993 Aug;21(4):289-99.

[9] Effect of Quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection. Int J Exp Pathol. 2003 Jun;84(3):127-33.

[10] Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection. Exp Lung Res. 2005 Jun;31(5):449-59.

[11] Hostile takeovers: viral appropriation of the NF-kB pathway J Clin Invest, January 2001, Volume 107, Number 2, 143-151

[12] Constituents of fish oil. U. S. Food and Drug Administration publication

[13] Fatty acids and lymphocyte functions. Br J Nutr. 2002 Jan;87 Suppl 1:S31-48.

[14] Relationship of Plasma Polyunsaturated Fatty Acids to Circulating Inflammatory Markers. J Clin Endocrinol Metab. 2005 Oct 18

[15] Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus. Clin Exp Immunol. 2000 Feb;119(2):287-92.

[16] The acute respiratory distress syndrome: role of nutritional modulation of inflammation through dietary lipids. Nutr Clin Pract. 2004 Dec;19(6):563-74.

[17] The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999 Oct;22(8):530-3.

[18] A trial of ascorbic acid in the treatment of the common cold. Br J Prev Soc Med. 1977 Sep;31(3):189-91.

[19] Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses. 1999 Feb;52(2):171-8.

[20] Vitamin C, Titrating to Tolerance

[21] Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85.

[22] Highly Pathogenic H5N1 Influenza Virus Infection in Migratory Birds Science, 2005 Aug 19; 309:1206.

Other references

Book:

The Great Influenza, by John M. Barry (Penguin Books, 2004). This is an interesting account of the 1918 flu pandemic, with special emphasis on the people and techniques used to understand and fight the disease.

A good tutorial about flu viruses:

The "Flu"

Other references relevant to this article:

Quercetin and green tea for flu prevention

Some information on anti-flu drugs

The Flu Clinic at CurEvents.com

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Disclaimer: The information provided in this “Ask Dr. Zarkov” article contains no medical advice whatsoever — it contains ‘biological information’. Nothing in the article constitutes an effort to persuade readers to use, or not to use, this biological information as a basis for action.