Nutraceuticals and nootropics for anti-aging

There is a growing epidemic of the deadly Marburg virus in Africa right now. If efforts to contain it fail and it spreads to the rest of the world, what can individuals do to protect themselves?

The Marburg virus is a close relative of the Ebola virus. Both are examples of ‘hemorrhagic’ viruses, which means that they cause victims to bleed to death. The strain of Marburg that is currently loose in Africa is easily transmissible and very virulent — the death rate so far has been 100% of those infected.

Overview

Both Marburg and Ebola viruses are thought to reside most of the time in one or more non-human animal species in southcentral and southeast Africa. Outbreaks in humans presumably occur when some kind of contact occurs between these animals and humans. Efforts have been made to identify which species harbor this viral reservoir, but without success. Human-to-human transmission of these viruses occurs through contact with infected bodily fluids or excretions.

The symptomless incubation time for Marburg ranges from 5 to 10 days; there is then a sudden onset of a flu-like illness with severe headache, fever, and chills, progressing to nausea, vomiting, abdominal pain, and diarrhea. The virus infects internal organs, causing them to swell and fail. When the liver is attacked, it stops producing the clotting factors that are needed to prevent leakage of blood from blood vessels. This leads to hemorrhaging both internally and externally. Patients typically experience convulsions, coma, and death from shock.

The first recorded Marburg outbreak took place in 1967 in Germany and Yugoslavia among lab staff who were working with monkeys imported from Uganda. 25 people were infected by contact with the monkeys, and 6 others by contact with the infected workers. The overall death rate was 28%. Other outbreaks have occurred in Africa in 1975, 1980, 1982, and 1987, each involving only one to three people, and in 1998-2000 involving 149 people. There may have been many unrecorded outbreaks, possibly dating far back into the past.

Research

Marburg virus particles gain a foothold in the body by attacking and manipulating the immune cells that would ordinarily initiate an antiviral response. The molecular details of how this occurs are beginning to be understood.

Research into treatment and prevention of hemorrhagic viral diseases is, however, in a sorry state. Many approaches are being investigated, but nearly all of them are exotic, hi-tech methods that will be unavailable in any practical sense for years, even if they turn out to work. (Let me make it clear that I definitely approve of exploring such approaches. But they should not preclude the study of simpler concepts that can be applied immediately to outbreaks in the real world. Yet there is essentially no effort going into simpler approaches.)

Because of this failure by the institutions that fund medical research, we find ourselves utterly without treatment and prevention tools specific to this disease. We are left with generic prevention methods (quarantine and contact-tracing) and generic symptomatic treatments (such as infusions of liquids and platelets). The effectiveness of these symptomatic treatments can be judged by noting that the Marburg fatality rate is currently 100%.

Will Marburg become pandemic?

If past outbreaks of Marburg and Ebola are any indication, it does not seem likely that the current outbreak in Angola will lead to a global pandemic. Previous epidemics of these hemorrhagic viruses have always remained localized — perhaps partly because most of them took place in locales that have relatively little traffic with the rest of the world, and also because the disease has a favorable symptom-transmissibility relationship: patients do not become contagious until the sudden and dramatic onset of symptoms; these symptoms can serve as a warning to other people to stay clear.

The Marburg outbreak in Angola may devastate southern Africa, despite all efforts to stop it, but it will not necessarily become a global disaster. The disease can probably be confined geographically by decisive actions by the rest of the world to quarantine travellers from the affected areas.

As things stand, a global ‘Bird Flu’ pandemic seems more likely than a Marburg pandemic. Previous flu epidemics have typically tended to become global, and there is every reason to expect that the one developing in Vietnam will do so.

Still, suppose this Marburg epidemic evades containment, and reaches our own communities. What advance preparations can an individual make, and when should they be made?

Prevention

The easiest answers have to do with prevention. The key concept is to stay home during the epidemic. If at all possible, avoid going out, and avoid receiving visitors. That means that you should do the following, and urge your friends and relatives to do the same.

• stockpile enough food (canned goods, not frozen food) to last for at least a month;
• stockpile some water, too, if your water supply is uncertain;
• stockpile any other supplies that you normally rely on.

If you cannot avoid making an excursion away from your home, take these precautions:

• Try to avoid touching objects that others have touched.
• Wear a face mask — not so much to protect against airborne infection, but rather to prevent yourself from touching your own mouth or nose with a hand that may have picked up infected residues from objects others have touched.
• Gloves are probably not worthwhile for mere excursions — gloves can pick up residues as easily as your hands can.
• After any excursion, wash your hands well and rinse them with an antiviral solution. (An antiviral solution damages virus particles and renders them harmless. It can be as simple as diluted laundry bleach. Or you can make an antiviral oil-water-detergent mixture such as this one: In a small bowl put a cup of water, a spoon of vegetable oil, and a quarter spoon of liquid dishwashing detergent. Agitate vigorously with an egg-beater or fork until the mixture is cloudy and has foam on top. Use each batch only once, and use it before the mixture separates.)

Do not wait until the epidemic has reached your community before you purchase your supplies — by that time, there will be panic buying, and you may have to wait in long lines of people, some of whom may already be infected. You should make your purchases before you even know that they will be necessary. Think of it as insurance.

Pandemics tend to occur in waves, each wave consisting of a different collection of strains of the disease. A given community will usually see each wave as a several-week-long epidemic which subsides and is then followed a few months later by another epidemic, often with somewhat different characteristics — different symptoms, different length of illness, and different virulence and fatality rates. For example, in the 1918 influenza epidemic in the U.S., the first wave was a nasty flu, but the second wave a few months later was much worse.

Treatment

Treatment is a thornier issue. Everything I’m going to suggest is based purely on theory, not on clinical studies — because there haven’t been any clinical studies. The general concept is to start treatment as soon as you think you might have been exposed to the virus — before the virus has established a foothold in your body and done much damage. You must begin treatment before there are any symptoms, and before you even know whether or not you’ve been infected. In practice, then, you would start treatment if there is any possibility of your having been exposed to the virus — for example, if someone in your household made an excursion away from the house, or if you received a visitor. If, despite your efforts, Marburg symptoms appear, then it is time to go to a hospital or quarantine center — not so much for your own benefit, but to spare those around you.

Since this kind of treatment strategy has not been tried before, and there is no ‘standard protocol’ for it, we must develop our own, based on what we know about the Marburg virus. We must choose treatments that are readily available to individuals at affordable prices — not expensive drugs or chemicals that are under the control of money-grabbing physicians and autocratic government agencies. Thanks to the Dietary Supplement Health and Education Act of 1994, we do have a source for such substances: dietary supplements.

I’m going to suggest three types of treatments:

• inflammation regulators: TNF inhibitors, antioxidants
• viral replication inhibitors
• blood clotting inhibitors.

TNF inhibitors. TNFs are signalling molecules that the body makes and uses to regulate immune responses. The body’s production of TNF is often associated with increased inflammation. It has been shown that suppression of TNF improves the survival of mice with Marburg infections. There are risks associated with anti-TNF therapy, since TNF plays a useful role in the body’s immune response to certain kinds of infections. Still, the risks seem worth taking during a Marburg epidemic.

The following TNF inhibitors are found in plants: calagualine, kamebakaurin, acanthoic acid, petrosasponiolide M, parthenolide, ergolide, and isohelenin. Of these, I’m going to recommend calagualine, mainly because of its availability. Calagualine is best obtained as a water extract of the rhizomes (roots) of the fern Polypodium leucotomos (also known as ‘calaguala’ or ‘samambaia’), . A product called ‘Anapsos’, from Spain, contains a high concentration of calagualine. If you decide to buy the powdered herb instead of Anapsos, get the powdered rhizomes of the plant, not the leaves, and use it to make an herbal tea.

Antioxidants. Free radicals are destructive molecules produced in the body by a variety of processes; their destructive effects include causing excessive inflammation. Antioxidants reduce inflammation by eliminating these free radicals. Different antioxidants are required for dealing with free radicals in different tissues and different parts of cells. Because of this, and because so little is known about the Marburg virus, it would be prudent to use a variety of antioxidants, such as the following:

• Pine Bark Extract (OPCs, catechins)
• Vitamin C and E
• N-Acetyl-Cysteine
• Sodium Selenate (selenium)
• Quercetin
• trans-Ferulic Acid
• alpha-Lipoic Acid
• Rosmarinic Acid
• Idebenone

Viral replication inhibitors. It has been known for decades that licorice root (Glycyrrhiza glabra) contains compounds that interfere with the replication of many viruses. Two of these compounds are glycyrrhizin and glycyrrhetinic acid, one of which has actually been studied as an inhibitor of Marburg virus replication. Licorice root extract is a readily available supplement in the U.S., and should be considered a front-line “people’s treatment” in case of a Marburg epidemic.

Blood clotting inhibitors. Since hemorrhaging is the hallmark of Marburg disease, one might think that a treatment that decreases blood clotting would be the last thing one would want. Paradoxically, this is not so. Intravascular clotting plays a major role in causing the uncontrollable hemorrhaging that makes Marburg so horrific and so fatal.

Various supplements have anti-clotting effects in the human body. But two of them, taken together have shown promise for synergistic regulation of the clotting process. Oddly enough, both of these supplements were suggested above — one of them as an antioxidant and the other as a viral replication inhibitor. They are:

• Licorice root extract
• Sodium selenate

Summary

The Marburg virus may depopulate southern Africa this year, but rigorous quarantines can probably prevent it from causing major epidemics in other parts of the world. Nevertheless, if Marburg should become a pandemic, individuals can protect themselves by stockpiling supplies and staying home while the epidemic takes its course. In case of exposure to the virus, one may be able to ameliorate an infection by taking a combination of supplements starting immediately after exposure. Such a combination could include: Anapsos (calagualine), antioxidants, licorice root extract, and sodium selenate.

— Dr. Alexis Zarkov, Ph.D.

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

Last modified 2005.April.13

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References

Anti-TNF-alpha therapies: the next generation (PDF, 2012 KB)

Calagualine inhibits nuclear transcription factors-kappaB activated by various inflammatory and tumor promoting agents. Cancer Lett. 2003 Feb 20;190(2):171-82.

In vitro studies on the immunomodulating effects of polypodium leucotomos extract on human leukocyte fractions. Arzneimittelforschung. 1995 Aug;45(8):901-4.

Anapsos (Polypodium leucotomos) modulates lymphoid cells and the expression of adhesion molecules. Pharmacol Res. 2002 Aug;46(2):185-90.

Inactivation of Ebola virus with a surfactant nanoemulsion. Acta Trop. 2003 Aug;87(3):315-20.

Prevention of murine influenza A virus pneumonitis by surfactant nano-emulsions. Antivir Chem Chemother. 2000 Jan;11(1):41-9.

Inflammatory responses in Ebola virus-infected patients. Clin Exp Immunol. 2002 Apr;128(1):163-8.

Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway. J Virol. 2005 Jan;79(1):547-53.

Progress towards Ebola treatment

Summary of treatment options for Ebola virus haemorrhagic fever

Factors that make an infectious disease outbreak controllable PNAS, April 20, 2004, vol. 101, no. 16, 6146-6151

Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor. Thromb Res. 2003;112(1-2):93-8.

Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature. 1979 Oct 25;281(5733):689-90.

The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Drug Metab Rev. 2001 May;33(2):125-47.

Inhibition of Marburg virus reproduction by glycyrrhizinic acid and its derivatives Dokl Akad Nauk. 1995 Oct;344(5):709-11.

Chemical modification of glycyrrhizic acid as a route to new bioactive compounds for medicine. Curr Med Chem. 2003 Jan;10(2):155-71.

Experimental study on the possibility of treatment of some hemorrhagic fevers. J Biotechnol. 2000 Sep 29;83(1-2):67-76.

Effects of tumor necrosis factor antiserum of the course of Marburg hemorrhagic fever Vestn Ross Akad Med Nauk. 1998;(3):35-8.

Exotic emerging viral diseases: progress and challenges. Nat Med. 2004 Dec;10(12 Suppl):S110-21.

Link to tutorial on clotting and clotting factors.

Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis. 2004 Aug;4(8):487-98.

Emerging roles of tissue factor in viral hemorrhagic fever. Trends Immunol. 2004 Sep;25(9):461-4.

Marburg haemorrhagic fever in Angola - update

Brief Report: Outbreak of Marburg Virus Hemorrhagic Fever --- Angola, October 1, 2004--March 29, 2005

TKH Virology Notes: Marburg Hemorrhagic Fever

Effects of acanthoic acid on TNF-alpha gene expression and haptoglobin synthesis. Mediators Inflamm. 1998;7(4):257-9.

Vaccine research efforts for filoviruses. Int J Parasitol. 2003 May;33(5-6):583-95.

Survival of Marburg virus infectivity on contaminated surfaces and in aerosols] Vopr Virusol. 1996 Jan-Feb;41(1):32-4.

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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.