Statins, Coenzyme Q10, and Pregnenolone for Addressing CFS

Once again I'm convinced that God has a great sense of humor!

For decades I've talked about how cholesterol medications (called statins) are overused in general, and especially so in fibromyalgia where they can cause more pain (by causing hormone and coenzyme Q10 deficiency). I suspect that except for those with known heart disease, where they can be lifesaving, statins have caused more harm than good. But there may be a silver lining to the statin medications' dark cloud.

New research suggests that statins might have a very helpful antiviral effect at high dose, and they may even hold promise as an effective new therapy for CFS and fibromyalgia if special (and simple) precautions are added in. The new theory I will present today also offers new possibilities for helpful and easy testing and therapy, while offering an understanding of a large new piece of the CFS/FMS puzzle.

Although time will tell how big a role this new concept will play in CFS, it offers simple testing and therapy that can be helpful NOW!

An Important Cautionary Note

I usually prefer to have broader research and more direct clinical and personal experience exploring new therapy theories before I start reporting on them (which would take 1-2 years). I have chosen instead to put the theory out there to invite discussion. Bringing many expert perspectives to bear will help it get tempered closer to the truth more quickly. Much of what I discuss below is new, controversial and hypothetical, and should be discussed with your holistic practitioner or CFS specialist before attempting a trial of the statin prescriptions.

Fortunately, the testing proposed is simple, fairly low cost (usually covered by insurance), performed at most labs, and easy — and may be a simple indicator of the presence of ongoing viral infection in CFS/FMS. The tests may point to a host of possible therapies, most of which are natural, non prescription, and known to help clinically. And they may markedly increase the safety of statin cholesterol-lowering medications, which have strong antiviral effects.

For me to be recommending statins in fibromyalgia makes for an unexpected story. So I will take some time in its telling. I hope you will find it as promising and as exciting as I do — and worth the time needed to read it.

What Prompted This New Idea?

What stimulated my interest was a recent study in the journal PLoS showing a direct link between the pathways that make cholesterol and viral infections.¹ According to Professor PeterGhazal at the University of Edinburgh, "What we have discovered is that a key immune hormone (interferon) stimulated upon infection can lower cholesterol levels and thereby deprive viralinfections of the sustenance they need to grow."²

Curious as to whether statins, which block cholesterol production, might have an antiviral effect, I did an Internet search on "statin and antiviral" to see if there was anything at all.

Almost a half-million hits popped up!

Background

Many infections have been implicated in CFS, including the viruses Epstein Barr (EBV), Cytomegalovirus (CMV), Human Herpes Virus 6 (HHV6), and XMRV/MLV. As part of their reproductive cycle (i.e., making more viruses and infecting new cells) many viruses require cholesterol-related molecules for many different functions, including making their protective coat. As part of your body's defensive functioning, each cell has its own defense system (called innate immunity) in addition to your body-wide defenses. This innate immune system is involved in other changes seen in CFS (for example, elevated RNAse L). In addition, your cells make an important immune molecule called interferon, which seems to work in part by decreasing the cholesterol production pathway and starving the virus.

Interferon levels (there are several types) can be both high or low in CFS. This may occur as the levels rise early in infection, but then may drop as the immune system exhausts. In CFS patients whose illness started with what I call the "Drop Dead Flu," interferon alpha tends to be low and two other types of interferon are elevated (as was seen in an excellent new WPI study that we'll discuss in an upcoming newsletter). Interestingly, interferon injections (used for viral infections such as hepatitis C) can trigger symptoms that feel like CFS. Paradoxically, in a small subset of CFS patients interferon therapy helped (though not a lot).^3-4

So the interferon may help you fight the numerous different viral infections present in CFS — but may aggravate CFS symptoms at the same time.

So what to do? You might be able to "eat your cake, and have it too" by starving the virus while giving your body what it needs. This new research opens possible ways to suppress the many viral infections in CFS, even retroviruses such as XMRV!

Found — A Key Missing Piece of the CFS Puzzle!

Although the energy crisis and associated hypothalamic dysfunction (from many causes, including infections), along with direct gland failure (e.g., low thyroid from Hashimoto's and adrenal exhaustion) explained most of the abnormalities we see in CFS and fibromyalgia, there have been a few missing pieces over the years that were not explained by these — which frankly left us puzzled. But I usually find there is more exciting new stuff to be learned from what is not explained by our current theories than what does make sense. Here are a couple items I've scratched my head over in CFS:

1. Occasional very low or high cholesterol levels are often seen in CFS. High cholesterol levels are easy to explain, being caused by the low thyroid function and (in men) low testosterone. And these high levels usually come down when those two hormone deficiencies are addressed.
2. We very often see dramatically low levels of a hormone called pregnenolone. Made from cholesterol, pregnenolone (not to be confused with the more commonly discussed hormone progesterone) is the critical and essential building block for steroid hormones such as cortisol, DHEA, estrogen, progesterone and testosterone. Though low hypothalamic function (the main control center for hormone production), menopause/andropause, and adrenal fatigue could account for most of the hormonal deficiencies we see, it would not be expected to cause these very low pregnenolone levels. And adding pregnenolone supplementation is often helpful, though not curative.

This study now explains why cholesterol and pregnenolone are sometimes very low in CFS. Viral infections cause your body to make interferon, which suppresses the mevalonic acid pathway that makes cholesterol and pregnenolone.

This is likely another key reason — along with the hypothalamic dysfunction, gland dysfunction and receptor resistance — for the widespread hormonal disorders we see in CFS/FMS.

So this is all very interesting. But, as my kids tease me when I ramble on like this ("blah blah blah"), why should you care? The reason this is significant is that in addition to suggesting that low cholesterol or pregnenolone in CFS may be caused by a viral infection (normal cholesterol does not rule out an infection), this new understanding offers a host of new possible therapies!

Key Points

This work uncovers a potential novel cause of CFS involving the process your body uses to make cholesterol. This pathway is critical to making key hormones (cortisol, DHEA, estrogen, progesterone and testosterone) as well as a key energy metabolite coenzyme Q10 (CoQ10). What's new is the research suggesting that viral infections "hijack" this pathway to make their protective outer coats. In response, our body makes interferon (which is made by immune cells and known to "interfere" with viral replication) which suppresses the cholesterol pathway and starves the virus. This plan works for a short while, but long-term suppression of this important pathway eventually may also starve our body of CoQ10 and key hormones — which appears to be part of what happens in CFS.

Here's what I suspect is happening in CFS/FMS patients with viral infections:

1. Viral infections result in production of interferon within a cell.
2. This is part of each cell's individual defense system (innate immunity).
3. Interferon works by blocking the mevalonate pathway, which makes cholesterol along with other key items (e.g., CoQ10 and pregnenolone needed for hormone production).
4. Viruses consist largely of threads of DNA or RNA. To replicate and spread, the virus has to hijack your cells mevalonate pathway to make the outer protective lipid coats for the new viruses.
5. Blocking the mevalonate pathway may keep viruses from reproducing (or they make dead viruses).
6. Your body makes interferon to block this pathway and starve the virus.
7. Blocking the mevalonate biochemical pathway works well short term in fighting infections by starving the virus. But it works for acute infections better than the chronic viral infections (e.g., EBV, HHV6, CMV, etc.) suspected in CFS. Why? Chronic suppression of this key biochemical pathway also starves the body of several key factors at the same time. This pathway makes:
   
   1. Coenzyme Q10 — A key metabolite for making energy (along with B vitamins, magnesium and ribose). This means chronic viral infections, or chronic cholesterol statin medication use, will cause CoQ10 deficiency.
   2. Pregnenolone — the key "mother hormone" or building block your body needs to make adrenal hormones (e.g., cortisol and DHEA) and estrogen, Progesterone, and testosterone.
   3. Key lipids needed to make your body's cell walls, which include their important signaling messengers (how cells communicate with the outside world; If ineffective, it may make them resistant/insensitive to hormones, etc.). 
8. This means starving the virus for too long a period may also starve the body in critical ways — in fact, in ways we see occurring in CFS.
9. Cholesterol blockers mildly block the same pathway as interferon and can actually have a mild antiviral effect at low dose (and a strong effect at high dose). These medications are used long term to address high cholesterol and therefore starve the body and may flare CFS/FMS. So I recommend against them unless you also give the body what it is being starved of at the same time.
10. Over time, interferon levels may eventually "exhaust" and be low (or high, or even both as there are different members of the interferon family) in CFS. In these cases, cholesterol may normalize but still reflect loss of ability to fight infections — which the statins and supplements may help restore.

Implications for Diagnosis

The presence of a low or low-normal pregnenolone level in someone not taking statins suggests your body is making elevated levels of interferon to fight a chronic viral infection. Low cholesterol levels suggest the same thing, though low thyroid or low testosterone (in men) will falsely raise cholesterol levels. So if you have low cholesterol levels, it may be from your body fighting a viral infection. I would check the pregnenolone level even if the cholesterol level is normal, especially if your insurance covers testing (the diagnoses of weight gain, low libido, irregular periods or low blood sugar may make the test more likely to be covered).

Low pregnenolone suggests a high risk of inadequate hormone production and CoQ10 deficiency as well as hinting at a chronic viral or other interferon-producing infection.

Implication for Therapies

Have the pregnenolone and cholesterol blood tests performed. If either is low or low normal:

1. Take CoQ10 at 200-400 mg a day (I recommend a good brand such as Enzymatic therapy).
2. Take pregnenolone 100-200 mg a day (over the counter) to get pregnenolone up to the upper 1/3 of the normal range. Cost is about 20 cents for 100 mg. If you can't do the blood level, it is OK to simply take 100 mg a day for 3 months to see if it helps.
3. Take an omega-3 (fish oil) supplement to help give your cell walls what they need while your body is blocking cholesterol production.

These three supplements are in common use and have been found in our experience to be safe and helpful in CFS/FMS.

In addition to showing that you are at risk of several deficiencies, I suspect the low pregnenolone may also be a marker for a viral infection. Though it does not identify which infection, it does offer a potentially powerful new way to stop the virus from growing. It might not kill them, but it will make it hard for them to reproduce.

So here is an overall regimen to consider — especially if your CFS began with flu-like symptoms and has not improved adequately with other therapies:

1. Take zinc 25 mg a day for 3 months. Chronic infections will routinely cause zinc deficiency and immune dysfunction. So get a bottle of 100 tablets at any supermarket or health food store and take them until they are done to replace zinc deficits. Then the 15 mg a day in a good multivitamin powder (or other good multivitamin supplement) should be enough to maintain optimal zinc levels.
2. For 4-6 weeks, also take the pregnenolone, CoQ10, and omega-3 as described above. Continue these for at least 3 months after taking the medication described below. These by themselves may leave you feeling a lot better at 6 weeks.
3. Here is the more experimental part that you will need to discuss with your physician (though it is a commonly used therapy for high cholesterol).
   
   1. Your physician may consider adding the statin medication Zocor (Simvastatin — get the generic 40 mg tabs at 10 cents a day instead of $5 per pill for the brand name). Take 20 mg a day to 2-4 weeks (to make sure it does not cause side effects — it usually will not, but if it does, stop it), then 40 mg a day for 3-4 weeks. If you feel OK on the medication, they can raise the dose to 80 mg a day. Continue for 3-4 months more and check or recheck your lab numbers (AST, ALT and CPK. If on pregnenolone, also check the pregnenolone and cholesterol levels. Draw the blood about 2-4 hours after taking the pregnenolone).
   2. At 3-5 months, you should be able to tell if the therapy is helping your symptoms (and likely much sooner). If not helping after 4-5 months on the Zocor, I would stop it.
   3. Statins can cause liver and muscle inflammation. This is unusual, but it is why the testing is important. And you should not use the statins if you have liver inflammation (hepatitis). Overall though, to put it in perspective, I consider them safer than Motrin or acetaminophen.
   4. Because we will not be killing the viruses — we'll just be making them infertile — we hope we will not see the die-off reaction sometimes seen with antivirals. On the other hand, this should drop their population dramatically (see below).
4. I would consider Gamma Globulin 2 cc im (intramuscular injections) each week for 6 weeks (Gammar) after you've been on the statin medication for 4-6 weeks as these have profound anti-infectious effects and may help put any surviving virus particles on the ropes. These injections can be very helpful in CFS and are much less expensive than the IV gamma globulin. Though less helpful, other antivirals (e.g., Isoprinosine, Famvir and Valcyte) have also been suggested to help in CFS, and offer more ways to attack the virus at the same time.

Why Would Statins Act as Antivirals?

Cholesterol-lowering statin medications also block the same pathway that interferon does, so it could make a good antiviral. It fact, numerous studies show it does (see below).

The problem? Unfortunately, in addition to blocking production of cholesterol, both interferon and statins block production of other important molecules (your body makes cholesterol for a good reason!). Especially important are pregnenolone and CoQ10. So when your body has been fighting a viral infection for years by making high levels of interferon, the interferon itself will cause eventual hormone and CoQ10 deficiencies — aggravating the CFS.

Has Research Shown That Statins Suppress Viral Infections?

Yes, and that is why I found the new study (showing that interferon from viral infections blocked the cholesterol pathway) so exciting! By itself, it tied in the unexplained low pregnenolone finding we had seen for years. It was when I searched the Internet for statins and antiviral and got over a half-million hits that I got really excited!

Statin (cholesterol blocking) medications, which I believe have been over-marketed to address high cholesterol and may have caused significant toxicity by blocking the production of CoQ10 and key hormones and worsening muscle inflammation, may actually offer a lot of promise in helping that subset of CFS/FMS with viral infections.

Interestingly, osteoporosis medications called biphosphonates (e.g., Fosamax — see N-BP in the previous diagram) also block part of the same pathway as statins, but do so downstream. Though they have antiviral effects as well, they have a much smaller impact than statins at the dosing typically used in real life.⁵

Currently, the available list of statin drugs includes:

• Altoprev® (lovastatin extended-release)
• Crestor® (rosuvastatin)
• Lescol® (fluvastatin)
• Lescol XL (fluvastatin extended-release)
• Lipitor® (atorvastatin)
• Mevacor® (lovastatin)
• Pravachol® (pravastatin) — May not be effective.
• Zocor® (simvastatin) — What I would use.

Which Viruses Have Been Shown to Be Suppressed by Statins?

Many different families of viruses, suggesting a broad antiviral effect. These include:

1. Epstein Barr Virus (inhibits its triggering lymphoma)⁶
2. West Nile Virus⁷ — An RNA Virus
3. Rotavirus — In this FDA "test tube" study, the authors noted an approximately 99% drop in some viral tests, and a bunch of deformed inactive viruses⁸
4. Polio⁹
5. Hepatitis C — but effects were mixed^10-12
6. HIV 1 (a cousin to the AIDS and XMRV viruses)¹³
7. RSV — Respiratory syncytial virus¹⁴
8. And perhaps even the flu virus¹⁵

Does This Mean I Need to Avoid Cholesterol in Food?

No. The studies I've seen suggest that the branch of the chemical pathway that needs to be blocked for the antiviral effects occur before the cholesterol step, and adding cholesterol did not impact the statins antiviral activity. In fact, adding an egg or two a day (a good cholesterol source along with other nutrients) may be helpful to protect your cell membrane production.

Still to Be Answered

A lot. For example, with this theory if cholesterol levels are high, pregnenolone should not be low. But in real life, we often see a mismatch. So there are other pathways and issues going on here, and this is reflected in the studies referenced below. In addition, there are many members of the interferon family, and some are low while others are high in CFS. Also, dozens of other immune chemicals may be altered in CFS — though interferon may be a key "conductor of the cytokine orchestra," and the theory we are discussing today is meant to be an oversimplification. In addition, normal pregnenolone and cholesterol do not mean there is no virus or that the therapy above won't help. But low levels are suggestive of a viral issue.

So we have a lot to learn. We always will ;-)

But we do know CoQ10 helps. We know pregnenolone is often low (and is very important). And we know that statins show antiviral effects in many studies. So we have a really good start!