Many infections have been implicated in chronic fatigue syndrome (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 treatment helped (though not a lot).

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!

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:

• 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 treated.

• 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.