Category Archives: Lyme disease

Retroviruses and Chronic Fatigue Syndrome

Posted by on August 24, 2010 29 comments

One of the themes of this blog is that chronic infections, exacerbated by bad diets and malnutrition, are at the root of nearly all health problems.

With the invention of new tools for microbiology over the last 20 years, scientists are for the first time able to study chronic parasitic infections, albeit with difficulty. I mentioned a few weeks ago that this should be the dawn of a “golden era of antimicrobial medicine.” And maybe it is: careful studies are now linking specific pathogens to chronic diseases and discovering the mechanisms by which they cause disease.

A good example of emerging science is the progress made since 2002 in understanding a retrovirus family that is now firmly linked to cancer and chronic fatigue syndrome and may soon be linked to other diseases.

Beginning of the Story:  Human Anti-Viral Immunity and Chronic Fatigue Syndrome

Our story begins back in the 1970s with studies of the role of interferons in defending human cells against viruses. Interferons are a key part of the immune defense against intracellular pathogens – the ones that cause most human chronic diseases.

Following the effects of interferons, researchers discovered an enzyme known as ribonuclease L (RNase L). RNase L is upregulated by interferons and its function is to degrade RNA, both viral and human, to stop viral replication. [1]

Aside: High levels of RNase L destroy so much human RNA that the cell dies. This is probably adaptive for the host, since cell apoptosis also kills many pathogens within. However, it shortens lifespan. RNase L knockout mice have extended lifespans. [1]

In 1997, RNase L was found to be strongly upregulated in chronic fatigue syndrome patients. [2] This showed that chronic fatigue patients usually have viral infections. Whether the viruses were causing chronic fatigue, or just “hitchhiking” with a disease that suppressed the immune system (perhaps via a bacterial infection?), remained an open question.

A Link Between RNase L and Prostate Cancer

By the early 2000s it was established that a common (allele frequency 35%) gene mutation, the “R462Q” mutation which substitutes a glutamine for an arginine in the “hereditary prostate cancer 1” locus, raised the risk of prostate cancer. A man with two copies of this mutation has twice the risk of prostate cancer; one copy raises the risk by 50%. About 13% of prostate cancer cases were attributable to this mutation. [1, 3, 4]

It was important, therefore, to determine which protein this locus coded for. A breakthrough finding, made in 2002, was that the “hereditary prostate cancer 1” locus was the gene for RNase L. [5]

It was soon shown that the R462Q mutation decreased the effectiveness of RNase L at cleaving viral RNA. This placed prostate cancer in a new light: it implied that an unknown virus against which RNase L defends was a probable cause of prostate cancer. When RNase L function was impaired by the R462Q mutation, the infection became more virulent, and prostate cancer rates were higher. [1]

The search for this unknown virus was on.

The discovery of “xenotropic murine leukemia virus-related virus” (XMRV)

The strategy was basically to take prostate tumors and search for viral RNA, looking for viruses that were most common in patients who had the double R462Q mutation.

In 2006 one of these searches yielded fruit.  A new gamma retrovirus was found in 8 of 20 prostate cancer patients with double R462Q mutations, but only 1 of 66 patients without the double mutation. [6]

This gamma retrovirus shared a lot of RNA with a family known as the xenotropic murine leukemia viruses (MuLVs). It was dubbed “xenotropic murine leukemia virus-related virus” (XMRV). Despite the sound, it is not a murine (mouse) leukemia virus; it merely shares a lot of nucleic acids with those viruses.

Back to chronic fatigue syndrome

In 2009 a paper was published in Science reporting that XMRV was found in peripheral blood cells of 67% of chronic fatigue patients but only 3.7% of healthy controls. [7] This study was done by a group at the Whittemore Peterson Institute in Reno, Nevada.

Aside:  The Whittemore Peterson Institute has a nice Q&A about this virus and its role in chronic fatigue syndrome here.

A number of researchers tried and failed to reproduce these results. For instance, a group from the Centers for Disease Control failed to detect XMRV proteins in 51 chronic fatigue and 53 healthy patients. [8]

Perhaps proteins are just not the right molecules for detecting this virus. A new paper has just appeared that links XMRV more strongly than ever to chronic fatigue. It looked at DNA for viral genes inserted into the human genome and found XMRV sequences in 86.5% of chronic fatigue patients but only 6.8% of controls. [9] This paper was held back from publication since June because of its conflict with the CDC paper (see “Why I Delayed XMRV Paper”), but has now been released.

These percentages are impressive and, if they hold up, would seem to make it unlikely that XMRV is merely a “passenger” virus hitchhiking on a suppressed immune system. It may be causal for chronic fatigue.

Will anti-retroviral therapies be effective?

Clinical trials are extremely expensive and the drug companies seem to be waiting for XMRV to be proven as the cause of chronic fatigue before undertaking trials. From the Wall Street Journal:

Norbert Bischofberger, chief scientific officer at Gilead Sciences Inc., the leading maker of HIV drugs, said the company might consider a small pilot trial but would like to see stronger evidence that the viruses cause CFS before launching a large trial. Still, “I’m very open, and this would be a great opportunity,” he said.

A spokesman for Merck & Co., another major manufacturer of HIV drugs, said: “A clinical trial program would be possible to develop only after further substantial evidence of an association with CFS.” [10]

But some aren’t waiting for trials. Anti-retroviral drugs developed for AIDS are being prescribed off-label:

Jamie Deckoff-Jones, 56 years old, a doctor and CFS patient in New Mexico, has been blogging about her experiences and those of her 20-year-old daughter. Both tested positive for XMRV and are taking a combination of three anti-retrovirals.

Dr. Deckoff-Jones said a year ago she could only get up for short periods during the day. After five months on the drugs, she flew last week to Reno for an XMRV conference. Her daughter was able to go to a party and is enrolling in community college. “This is all very new, and there is no way to know if improvement will continue,” Dr. Deckoff-Jones wrote in an email, “but we appear to be on an uphill course.” [10]

Chronic fatigue patients are celebrating the progress:

Many [CFS patients] were ecstatic at news that the second study was being published.

“We’re really hoping this will blow the lid off,” said Mary Schweitzer, a historian who has written and spoken about having the illness. “Patients are hopeful that now the disease itself might be treated seriously, that they’ll be treated seriously, and that there might be some solution.” [11]

It’s sad that for decades many haven’t taken chronic diseases seriously. The absence of a known cause reflected only the lack, until recently, of microbiological tools capable of detecting and characterizing intracellular pathogens.

Had doctors taken these diseases seriously, the accumulating evidence that these were chronic infectious diseases caused by intracellular parasites might have encouraged them to look for the sort of dietary and nutritional therapies for chronic disease that we advocate on this blog. Though diet and nutrition by themselves will probably not cure these diseases, they can greatly slow disease progression and improve the odds of a cure.

A new name for XMRV: Human Gamma Retrovirus

The Whittemore Peterson Institute recently hosted the first official scientific symposium on XMRV. Dr. Joseph J. Burrascano reported from the symposium:

We formed a working group to be in constant touch and we plan to meet regularly because advances are coming so rapidly.

Big news that everyone should know and adopt is that we have proposed a name change for the virus.

This virus is a human, not mouse virus, and it is the first and so far only gamma-retrovirus known to infect people. Also, it is clearly not an “endogenous” retrovirus (one that is present in all genomes due to ancient infection).

Because of all of this, and because of the desire to begin on the right track, the new name of the virus is HGRV- Human Gamma Retro Virus. The illness caused by this infection is named HGRAD- Human Gamma Retrovirus Associated Disease.

We plan to announce this at the upcoming NIH retroviral conference this September.

Definitely stay tuned- the volume of new and important information about this virus and its disease associations is increasing rapidly and in my opinion should be a concern to every patient with chronic neuro-immune diseases, including those with chronic Lyme. [12]

It sounds like some exciting findings may be on the way.

Conclusion

This case is a fascinating illustration of the twisting turns that scientific research can take. The early discovery of a link between anti-viral immunity and prostate cancer may now lead to a cure for chronic fatigue syndrome. At least, we can hope so.

As one of the pioneers, Dr. Robert Silverman, describes it,

One of the remarkable aspects of being a scientist, is that you never know where your scientific journey will lead. [1]

Science takes a lot of patience, diligence, and persistence. It’s gratifying when all that work is rewarded by discovery.

References

[1] Silverman RH. A scientific journey through the 2-5A/RNase L system. Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):381-8. http://pmid.us/17681844.

[2] Suhadolnik RJ et al. Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res. 1997 Jul;17(7):377-85. http://pmid.us/9243369.

[3] Silverman RH. Implications for RNase L in prostate cancer biology. Biochemistry. 2003 Feb 25;42(7):1805-12. http://pmid.us/12590567.

[4] Casey G et al. RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat Genet. 2002 Dec;32(4):581-3. http://pmid.us/12415269.

[5] Carpten J et al. Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet. 2002 Feb;30(2):181-4. http://pmid.us/11799394.

[6] Urisman A et al. Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant. PLoS Pathog. 2006 Mar;2(3):e25. http://pmid.us/16609730.

[7] Lombardi VC et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23;326(5952):585-9. http://pmid.us/19815723.

[8] Switzer WM et al. Absence of evidence of xenotropic murine leukemia virus-related virus infection in persons with chronic fatigue syndrome and healthy controls in the United States. Retrovirology. 2010 Jul 1;7:57. http://pmid.us/20594299.

[9] Lo S et al. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. PNAS Epub before print August 23, 2010. http://www.pnas.org/content/early/2010/08/16/1006901107.abstract.

[10] Amy Dockser Marcus, “New Hope in Chronic Fatigue Fight,” Wall Street Journal, Aug 23, 2010, http://online.wsj.com/article/SB10001424052748703846604575447744076968322.html.

[11] David Tuller, “Study Links Chronic Fatigue to Virus Class,” New York Times, Aug 23, 2010, http://www.nytimes.com/2010/08/24/health/research/24fatigue.html.

 [12] http://www.forums.aboutmecfs.org/showthread.php?7001-News-from-WPI-symposium-Name-change-to-be-proposed-for-XMRV (hat tip http://health.groups.yahoo.com/group/infection-cortisol/message/1753).

Love’s Labors Lost

Posted by on August 10, 2010 14 comments

One of my favorite writers is Elizabeth Scalia, “The Anchoress,” now a blogger for First Things. She has long suffered from a condition diagnosed as lupus, an autoimmune disease, but now after many years has been discovered to have Lyme disease. Lyme is a treatable infectious condition. Elizabeth writes:

A too-long-undiagnosed bout with Lyme Disease has left me challenged with arthritis and some neurological damage. The arthritis has its uses: I can predict rain, and the pain gives me something to offer up in prayer, or as penance.

Not so the neurological issues. At the peak of my illness I was unable to figure out how to do the dishes; my organizational skills have never fully recovered, and verbally I sometimes wander into strange lands, referring to cereal as cookies, or to hats as helmets.

Regular readers of this blog will know that I am not surprised that an “autoimmune” disease has turned out to be an infectious disease. Autoimmunity (where it genuinely exists – chronic infections are often misdiagnosed as autoimmune conditions even where no autoimmunity is present) seems to be mainly a side effect of chronic infections – collateral damage in a guerilla war with pathogens that conceal themselves behind human “cellular shields.”

Antibodies against the thyroid and gut engendered by gluten disappear within six months after cessation of wheat eating. [1, 2] I suspect that most autoantibodies engendered by pathogens will disappear on similar time scales once the underlying infection is cured.

I have previously written of my conviction that Alzheimer’s is an infectious disease. This conviction that grew out of my own experience: I had a 17-year chronic illness characterized by increasingly severe and embarrassing memory loss. At its worst I could not remember a friend with whom I had shared a small office for a year, and could not write (because I could not remember the previous paragraph when starting a new one, nor recall illustrative examples). The whole illness was cured by diet and antibiotics, and my memory is back to normal. I suspect that nearly all cases of Alzheimer’s can be cured by the same methods (the most important of which can be found here).

Elizabeth writes of the effect these diseases can have on a marriage:

CBS News correspondent Barry Petersen recently filed a report on the early-onset Alzheimer’s that began affecting his wife, Jan Chorlton, at the age of forty. It is an undeniably moving story; after introducing the viewer to images of the beautiful and lively Chorlton, the report shows us Petersen’s sixty-year old, still-beautiful wife, now living in what appears to be a top-notch assisted-living facility. She is unable to sustain simple conversation or to recognize her husband. Chorlton talks of a man she will always love, while Petersen openly weeps. When he asks his wife if she can name that man, she giggles, “Mr. Happy.”

Medical experts are introduced and they declare that there is no treatment for Alzheimer’s Disease, and no way to prevent it. In the near-future, we are told, sixteen million Americans will be diagnosed with Alzheimer’s Disease.

Petersen reveals that he is now in a relationship with a widow; they live together, and they both love Jan in what one of them calls “this very peculiar new American family.” The piece closes challenging anyone to gainsay them, who has not walked in their shoes.

But, was it not precisely for such situations that marriage vows were designed? “For better, for worse, for richer, for poorer, in sickness and in health, together or apart.” Love, which is limitless, is supposed to be strong enough – even if we do not think we are – to survive these challenges.

One of the saddest aspects of chronic illness is the damage it can do to marriages. A perusal of chronic disease message boards, like the one I followed at cpnhelp.org, can easily turn up tales of disease sufferers abandoned by their spouses.

It terrifies me to consider where I would be had I not had the persistent support of a loving wife. It is hard to believe I could have recovered without her.

Our motive for writing The Perfect Health Diet is to help people regain and maintain good health – to create healthy centenarians. But perhaps one side effect will be to save a few marriages – to encourage “Mr Happy” to be “Mr Persistent-In-Love.”

Caring for a chronically ill spouse is a labor of love. The laborer deserves his wage, and love deserves its reward. If there is one bit of advice that is more important than any other, in marriage and in disease, it is this: Don’t give up! Don’t ever give up!

References

[1] Berti I et al. Usefulness of screening program for celiac disease in autoimmune thyroiditis. Dig Dis Sci. 2000 Feb;45(2):403-6. http://pmid.us/10711459.

[2] Mainardi E et al. Thyroid-related autoantibodies and celiac disease: a role for a gluten-free diet? J Clin Gastroenterol. 2002 Sep;35(3):245-8. http://pmid.us/12192201.

Eleven Steps for Overcoming Alzheimer’s and Other Chronic Infectious Diseases

Posted by on July 1, 2010 161 comments

If Alzheimer’s is due to bacterial infection, as I suggested yesterday (https://perfecthealthdiet.com/?p=126), then it can be treated by diet, supplements, and antibiotics.

Here are eleven steps that can help defeat chronic bacterial infections, including the infections that cause Alzheimer’s. (Note:  I will justify each of these eleven steps, and cite to the scientific literature, in follow-up posts.)

1. Normalization of Vitamin D Levels.

Vitamin D is needed for the transcription of anti-microbial peptides, such as the cathelicidin LL-37 and beta-defensin, which are essential for defense against intracellular bacteria and viruses. Vitamin D deficiency is a risk factor for every chronic infection, and chronic infections tend to increase in frequency with latitude and progress most rapidly during the winter when vitamin D levels are low.  In general, a serum 25-hydroxyvitamin D3 level of 40 ng/ml (100 nmol/L in SI units) is a good target. (Some people, such as Dr. John Cannell of the Vitamin D Council, believe there may be benefits to higher levels, but this is speculative.)

2. Restriction of Carb Intake to 400 Calories Per Day.

Eating a carb-rich diet is doubly bad:  it increases blood glucose levels and triggers insulin release, both of which promote bacterial infections.

Intracellular parasitic bacteria need glucose or its glycolytic products to obtain energy. Abundant cellular glucose, caused by high blood glucose levels, enable them to reproduce and generate immune-impairing proteins more prolifically.

Insulin represses immune defenses against parasitic bacteria, by blocking production of antimicrobial peptides.

To keep both blood glucose and insulin levels low, carbohydrate consumption should be restricted to about 400 calories per day – the amount in 0.3 pounds of cooked white rice, or 1.3 pounds of sweet potatoes.

3. Restriction of Protein.

Eating minimal protein helps in two ways: it deprives bacteria of amino acids necessary for growth, like tryptophan; and it promotes autophagy, the primary means by which cells kill intracellular pathogens.

Indeed, the body’s primary defense mechanism against C. pneumoniae is tryptophan deprivation. This is why people with chronic brain infections have symptoms of serotonin deprivation, including depression, anxiety, insomnia, fatigue, impaired ability to concentrate, and low self-confidence. It’s important not to relieve this by tryptophan or 5-HTP supplementation, both of which promote bacterial growth. If symptoms are intolerable, selective serotonin reuptake inhibitor (SSRI) antidepressants, like Prozac, Paxil, or Zoloft, might be able to provide symptomatic relief. (NB: We neither recommend nor disparage these drugs.)

4. Intermittent Fasting

Autophagy is the garbage collection and recycling process of human cells.  When resources are scarce, cells turn on recycling programs and send garbage collectors known as lysosomes to engulf and digest junk proteins and damaged organelles, enabling re-use of their amino and fatty acids.

Autophagy is a key part of the immune defense against parasitic bacteria.  Lysosomes not only digest human junk, they seek out bacteria and digest them. 

Autophagy is strongly turned after about 16 hours of fasting. The longer one fasts, the more parasitic bacteria are destroyed in lysosomes.  Fasting is an easy way to improve the relative balance of power between your body and intracellular pathogens. Fasting strongly promotes autophagy in neurons, and is of therapeutic value for Alzheimer’s.

A simple strategy of intermittent fasting is to confine meals to an 8-hour window each day, thus engaging in a daily 16 hour fast.  On this strategy, one might eat only between noon and 8 pm.

5. Ketogenic Fasting.

Two dangers of fasting are that it can lead to loss of muscle tissue as protein is consumed to generate ketones and glucose, and that neurons may be put under stress by glucose deprivation.

Both dangers can be ameliorated by eating ketogenic fats during the fast.  “Ketogenic” means generative of ketone bodies. Ketone bodies, which are generated from fats or some proteins during fasting, are the only neuronal energy source that bacteria can’t steal. There is a large literature showing that high circulating ketone levels are neuroprotective, and ketogenic diets have been successfully tested as Alzheimer’s therapies.

The most ketogenic fats are the short- and medium-chain fats found abundantly in coconut oil. Taking plentiful fat calories from coconut oil, but no carb or protein calories and few other fats, can enable fasts to be extended substantially longer with minimal loss of muscle tissue or neuronal stress.

On a ketogenic fast, eliminate carbs and protein for a 36-hour period, from dinner one day to breakfast on the second day.  During the intervening day, eat no protein or carbs, but do eat as much coconut oil as you like.

There is no limit on how much coconut oil may be consumed – but 12 tablespoons per day would produce a surfeit of ketones. NB: Always drink plenty of water during a fast. We also drink coffee with plentiful heavy cream.

6. Elimination of Wheat and Other Grains. 

Wheat is a toxic food that interferes with immune defenses and impairs vitamin D function. It also generates antibodies to the thyroid, which damage the thyroid status and further impair immune function.

7. Elimination of Omega-6-Rich Oils and Inclusion of Omega-3-Rich Fish.

A diet that minimizes omega-6 content by replacing soybean oil, corn oil, canola oil, and other omega-6 rich oils with butter, coconut oil, and beef tallow, and gets adequate omega-3 fats by eating salmon or other cold-water fish, optimizes the immune defense against intracellular pathogens.

A high omega-6 and low omega-3 diet weakens immune defenses against intracellular pathogens and re-directs the immune system toward extracellular threats.

Note that the combination of carbohydrate, protein, and omega-6 fat restriction necessarily means that half or more of calories should be obtained from saturated and monounsaturated fats.  It is important not to have a saturated fat phobia if you want to escape or defeat Alzheimer’s!

8. Fructose Minimization.

Fructose is a toxin and is deprecated on the Perfect Health Diet. One of its worst features is that promotes infections. In mice, blood levels of endotoxin, a bacterial waste product, are higher on a fructose-rich diet than on any other diet.

Therefore, sugary foods like soft drinks should be eliminated.  Fruit and berries are OK in moderation.  We recommend no more than 2 portions of fruit and berries per day. Most carb calories should be obtained from starchy foods, like sweet potatoes or taro or white rice.

9. Melatonin supplementation. 

Whereas vitamin D is the “daylight hormone,” melatonin is the “hormone of darkness.”  It is generated during sleep, and is favored by darkness.  Even a little bit of light at night, like the LEDs of an alarm clock or streetlights shining through a window, can disrupt melatonin production.

Melatonin is extremely important, not least because it has powerful antibiotic effects.

To maximize melatonin production, everyone should sleep in a totally darkened room, with windows covered by opaque drapes and all lights extinguished and LCD or LED clocks turned face down.

Unfortunately, people with chronic bacterial infections will generally still be melatonin-deficient, for the same reason they are serotonin-deficient:  melatonin is derived from tryptophan and serotonin. Fortunately, melatonin is easily supplemented.

A melatonin tablet can be allowed to dissolve in the mouth just before bed. High doses will generally produce a deep sleep followed by early waking; this can be remedied by using time-release capsules, or by reducing the dose.

10. Selenium and Iodine Supplementation and Thyroid Normalization.

This is basic for good health in all contexts, but optimizing thyroid hormone levels and maintaining iodine and selenium status are especially important for anyone with an infection.

Both selenium and iodine are required for proper immune function. To get iodine, white blood cells will strip iodine from thyroid hormone; for this reason, people with chronic infections are often somewhat hypothyroid, as indicated by TSH levels above 1.5.

There are too many tricks and pitfalls to thyroid normalization to describe the whole issue here, but a good start is to eliminate wheat from the diet, and to obtain 200 mcg selenium and at least 400 mcg iodine per day. Do not get too much selenium as it is toxic.  Selenium and iodine may be obtained from foods:  two to three Brazil nuts a day for selenium, and seaweed for iodine.

11. Vitamin C and Glutathione or NAC Supplementation.

These are important for immune function. Vitamin C supplementation is an important safety precaution because infections greatly increase the rate of loss of vitamin C, and can generate tissue scurvy with devastating consequences.

Glutathione is destroyed by stomach acid. We recommend buying reduced glutathione and taking it with a full glass of water on an empty stomach, at least 2 hours after and 1 hour before taking food. Alternatively, N-acetylcysteine (NAC) and glycine-rich foods like gelatin may be taken to promote glutathione synthesis.

Conclusion

This is by no means an exhaustive list of dietary and nutritional steps that can help against chronic infections.  However, we believe these are the most powerful and important steps.

Alzheimer’s and other diseases caused by chronic bacterial infections – possibly including multiple sclerosis, Lyme disease, chronic fatigue syndromes, fibromyalgia, rheumatoid arthritis, and many others – are preventable, treatable, and often curable.  These dietary steps, along with appropriate antibiotic therapy, are keys to a cure.