Statins and H5N1 Infection Mitigation

My husband takes prescription cholesterol lowering medication and when the news started circulating around the Cyber Flu Community back in the fall of 2005 I sat up and took note.  Statins are ubiquitous in the US since doctors seem to like to prescribe them at the first hint of cholesterol elevation.

As this piece from one of the Reveres at EffectMeasure states, the research is intriguing and logically indicates that statins may be beneficial should those taking them become infected.  Please be aware that it is presumed that you must be on them for at least (guess) a month prior to infection to see the positive (if any) effects, but the benefits may mean the difference between living and dying.

From EffectMeasure (old site) [They have since moved: New Site]

Thursday, September 29, 2005

Bird flu and statins 

In an extremely interesting article in the Clinicians Biosecurity Network Weekly Bulletin (issue of 9/27/05) Borio and Bartlett review a suggestion of David Fedson, an expert on vaccines (and former Director of Medical Affairs at Aventis Pasteur), that statins (tradenames Zocor or Lipitor) might be helpful in preventing serious complications of influenza, perhaps by dampening the cytokine response.

The statins are widely used and available drugs used to lower cholesterol. They also have anti-inflammatory activities, perhaps by preventing activation of the transcription factor NF-kappaB. One mechanism thought to underlie the virulence of the H5N1 virus is production of a "cytokine storm," an unregulated systemic inflammatory response that results in a rapidly developing generalized clotting disorder, hemorrhage, kidney failure and fluid-filled lungs. The phenomenon is similar to or the same as what is called gram-negative sepsis or septic shock, a serious complication of bacterial infections that claims 400,000 to 500,000 lives each year in the US and has 50% to 70% mortality. Treatment for sepsis is a high priority independently of any role for the same or similar mechanism in influenza.

The idea that statins might be helpful for sepsis or influenza is based on more than speculation about mechanism. In 2004 Almog et al. (Circulation, Aug 17 2004;110(7):880-885) reported that patients admitted to the hospital with acute bacterial infections and who were on statins for more than a month for other reasons had a dramatically reduced incidence of severe sepsis (19% versus 2.2%) and reduced admission to the Intensive Care Unit (12.2% vs. 3.7%). An interesting point is that patients on statins might be expected to be at greater risk because they are taking a medication for a pre-existing medical condition.

Another study (.pdf available free on line here) looked back at the experience of over 700 patients that were admitted to a hospital for pneumonia. About 100 of them were also taking statins. Using 30-day mortality as a measure of outcome, the statin group had about two thirds fewer deaths than the non-statin group (odds ratio .36, 95% confidence interval .14 - .92).

Borio and Bartlett also report on an article from The Netherlands by Enserink to appear shortly in Science (hence not available to me other than through their summary). Enserink examined influenza seasons between 1996 to 2003, and using a database of 60,000 primary care patients compared those with at least two statin prescriptions in the previous year to those without. There was a 26% lower risk of pneumonia in the statin group. Because of the imprecision of the measure of statin use, I would expect the statin effect to be even greater than reported here.

Borio and Bartlett conclude:

These studies suggest that statin therapy may ameliorate the course and/or prevent complications of influenza. In these studies, it appears that all of the people were already receiving statins when they got infected. Whether statins would be beneficial after the onset of symptoms is still unknown. However, further investigation is merited. This is particularly important given the likelihood that vaccines and antiviral agents will be in short supply during an influenza pandemic, and statins are widely available and may be produced relatively inexpensively.

This is extremely interesting work. It is too early to say that prophylactic statin use in a pandemic is a reasonable strategy, but it is worth considering.

There is also an OTC product, Red Yeast Rice (the base ingredient in many statins) that is cheap and easily obtained.

The entry on Red Yeast Rice from the Mayo Clinic's site:

[snip]

Red yeast rice is the product of yeast ( Monascus purpureus ) grown on rice, and is served as a dietary staple in some Asian countries. It contains several compounds collectively known as Monacolins, substances known to inhibit cholesterol synthesis. One of these, "Monacolin K" is a potent inhibitor of HMG-CoA reductase, and is also known as Mevinolin or Lovastatin (Mevacor®, a drug produced by Merck & Co., Inc).

Red yeast rice extract has been sold as a natural cholesterol-lowering agent in over the counter supplements, such as Cholestin ^TM (Pharmanex, Inc). However, there has been legal and industrial dispute as to whether red yeast rice is a drug or dietary supplement, involving this manufacturer, the U.S. Food and Drug Administration (FDA) and the pharmaceutical industry (particularly producers of HMG-CoA reductase inhibitor prescription drugs or "statins").

[snip]

Uses based on scientific evidence

High cholesterol

Since the 1970s, human studies have reported that red yeast lowers blood levels of total cholesterol, low-density lipoprotein/LDL ("bad cholesterol"), and triglyceride levels. Other products containing red yeast rice extract can still be purchased, mostly over the Internet. However, these products may not be standardized, and effects are not predictable. For lowering cholesterol, there is better evidence for using prescription drugs such as lovastatin.

[snip]

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older):

1,200 milligrams of concentrated red yeast powder capsules have been taken two times per day by mouth with food.

The average consumption of naturally occurring red yeast rice in Asia has been reported as 14-55 grams per day.

Children (younger than 18 years):

There is not enough scientific evidence to recommend red yeast for children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

There is one report of anaphylaxis (a severe allergic reaction) in a butcher who touched meat containing red yeast.

Side Effects and Warnings

There is limited evidence about the side effects of red yeast. Mild headache and abdominal discomfort can occur. Side effects may be similar to those for the prescription drug lovastatin (Mevacor®). Heartburn, gas, bloating, muscle pain or damage, dizziness, asthma, and kidney problems are possible. People with liver disease should not use red yeast products.

In theory, red yeast may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. A metabolite of Monascus called mycotoxin citrinin (CTN) in fermentation may be harmful.

While no one knows if Statins or Red Yeast Rice will have any beneficial effects on an infection of H5N1 I will be utilizing them as prophylactic countermeasures for my family, but most especially for my son who is smack in the middle of the most-at-risk age group for dying from it.  I am fully cognizant of the risks and downsides.  I have done my homework and read all of the available information (scant though it is) and made a conscious and informed decision that the potential benefits outweigh any of the potential risks.  Should you consider these as options for yourself I suggest you do the same.  Nothing in life is entirely risk free, and everything generally comes at some price, the key is knowing enough to make informed and intelligent decisions.

My plan of attack is to utilize the supplement Red Yeast Rice once a Pandemic Influenza strain manifests and switch to the prescription Statin once the virus is in my area.  As can be appreciated, I have a lot more of the OTC supplement than I have of the prescription medication.  Timing will be all important.  My thanks to Bannor at PlanForPandemic for the idea of best use of the resources.

SZ