This month, a DNA analysis service did two things that may be important for CFS patients:

• They increased the number of single nucleotide polymorphisms  (SNP) detected to almost one million. SNP are the name for DNA changes that can be associated with diseases…
• They drop the cost to $99.00
• The lab that actually does it is LabCorp which is a standard certified medical lab.

The firm is 23AndMe.com A few years ago, they offered only 100,000 SNPs for $999. This is an effective 99% decrease in the price per SNP. These SNP are important if you are into genealogy because they indicate heritage. They are also important for health. The SNP indicate increased (or decreased) risk of certain diseases. For a list of what is covered see this page.

CFS and You

The SNP above is about 10% of your DNA, so it is not all of your DNA. Early in this onset of CFS, my DNA was tested by a MD for methylation issues. If you check PubMed, you will find about ten articles with interesting results.

• Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome. 2011 “Sixty-five SNPs were nominally associated with CFS”
  
• Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data. 2011 ” the gene WASF3 (aka WAVE3) possibly regulates brain cytokines involved in the mechanism of fatigue through the p38 MAPK regulatory pathway.”
• Serotonin receptor (5-HT 2A) and catechol-O-methyltransferase (COMT) gene polymorphisms: triggers of fibromyalgia? 2010 ” study of the rs4680 SNP of the COMT gene may be helpful to the identification of susceptible individuals.”
• Polymorphisms of adrenergic cardiovascular control genes are associated with adolescent chronic fatigue syndrome. 2011
• A functional polymorphism in the disrupted-in schizophrenia 1 gene is associated with chronic fatigue syndrome. 2010
• Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome. 2008
• Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome. 2006
• Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence. 2005

The SNP will not dictate if you have a condition, just if you are more likely or less likely, for example for Sjögren’s Syndrome or Crohn’s Disease (if you have IBS, this may be important).

When I get my results back, I will track down the SNP cited (and there will likely be new articles soon — there are more and more research in this area), and post a summary of how to use the 23andMe results with CFS and FM markers…

My last post dealt with CFS and Alzheimer’s Disease. They are very similar in many aspects and if CFS lacks the physical fatigue symptom, then they can become very difficult to separate – especially in individuals over 60. Under 65, Alzheimer’s Disease will rarely be suspected (if it occurs, it is called Early Alzheimer — as in under 65, it does not mean early-stage of Alzheimer).

In this post I want to review the list of amyloids conditions and suggest that CFS may actually fall into this spectrum. The hyper-coagulation model for CFS results in fibrin deposits instead of amyloid deposits. What’s the difference? According to Wikipedia…

• Amyloids are insoluble fibrous protein aggregates
• Fibrin is a fibrous, non-globular protein involved in the clotting of blood

So both are fibrous, proteins and not dissolved normally by the body.

In treating CFS, there are often two modes of attack:

• Break down the soluble fibrin monomers before they form deposits. Typically this is done with piracetam and / or turmeric.
• Break down any existing fibrin deposits. Typically this is done with fibrinolytics (bromelain, serrapeptase, nattokinease and lubrokinease). This will typically exposed infections in tissue and allow up to 10x better antibiotic penetration.

The reason for doing this is that both CFS and Chronic Lyme Disease both present(80-90%)  with Antiphospholipid Antibody Syndrome aka Hughes Syndrome according to studies on PubMed.

I decided to hit pubmed to see if the second list also had impact on amyloids. Two of them are documents as degrading (breaking down amyloids

• J Agric Food Chem. 2009 Jan 28;57(2):503-8.Amyloid-degrading ability of nattokinase from Bacillus subtilis natto.Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP.
• Exp Neurol. 2001 Feb;167(2):385-92. Alpha 2-macroglobulin-mediated degradation of amyloid beta 1–42: a mechanism to enhance amyloid beta catabolism. (Bromelain) Lauer D, Reichenbach A, Birkenmeier G.

I strongly suspect that the others two fibrinolytics also degrades amyloids. This implies that these four fibrinolytics may be of significant benefit to all of the amyloids diseases (as well as CFS and related). I should mention that each of these fibrinolytics appear to work in slightly different ways, so taking all four may be needed.

Amyloids Diseases

As a personal note, with my 2012 onset, I was able to keep working for many weeks by increasing the dosages of the fibrinolytics as symptoms worsen. Whether they were acting on fibrin alone or amyloids (or both) cannot be determined. My coagulation tests came back normal which suggests that fibrin may not be the sole issue. When I reached a dosage that resulted in easy bruising that did not go away, I was forced to stop the fibrinolytics. I went on a steep cognitive crash and went on sick leave within a few days.

Bacteria and Amyloid

The biggest quick decrease of neurological impairment that I observed in my treatment this time was when I started taking 3 herbs (Tulsi, Haritaki, Neem) that were reported on PubMed as being effective against Enterococcus. Enterococcus is a 24x overgrowth in CFS studies. So on speculation, I decided to see if Enterococcus is associated with Amyloids (or the above conditions). I found almost two dozen articles associating this bacteria with amyloid arthropathy in veterinary papers. It was also reported as an overgrowth seen with diabetic patient populations[1]. Improvement seen with supplementation of a specific species of Enterococcus in arthritis[2]. In general, there appear to be no studies done of the gut flora patterns for the above diseases 😦

A Science Daily article presented some interesting facts,
“In bacteria, two proteins—CsgA and CsgB—are involved in the process, each with its own precise function. The job of CsgA is to build up amyloid fibers, but only after CsgB—dubbed “the nucleator”—has set the stage.”

So bacteria produces the proteins, a shift in the bacteria may result in an imbalance and thus accumulation. The article further states

“Having one protein in charge of nucleation and the other in charge of fiber elongation is a clever strategy that allows for control of a process that otherwise might occur unpredictably, as seems to happen with disease-associated amyloids.”

What we need is studies of each amyloid-associated disease patient population to determine how gut bacteria is altered.

Until that time, patients (with an amyloid-associated condition) may wish to discuss taking Tulsi, Haritaki, Neem with their medical professionals. My own professional had no issues — these are all grandfathered (likely great grandfather 40x) herbs with centuries of use, making the benefit to risk very favorable. They had significant impact on neurological loss (after several days of headaches).

These words are the beginning of a classic CFS joke. The good news is “You are not going to die”, the bad news is “You are not going to die”.

There are two diseases that can present almost identically, both have no diagnostic tests, both have SNP associated with incidence (SNP means a gene mutation). I have been unable to find out if any of the SNPs overlapped… The two conditions are Alzheimer’s Disease(AD) and Chronic Fatigue Syndrome(CFS).

The easiest way to tell them apart is the presence of post-external-fatigue (PEM). Unfortunately, PEM is not always present and actually forms a research subset. So, for CFS patients without PEM, there can be a bit of an unresolved question. CFS is characterized by a 1% decrease in gray matter volume per year of the disease, as well as decreasing white matter volume. Similar are seen in AD.

SPECT Scans

The interesting thing is that AD, CFS and chronic lyme all show hypo-perfusion in the same areas of the brain. With chronic lyme, the right course of antibiotics results in SPECT becoming normal in 1-2 years according to PubMed studies.  The term right is very significant because it is not just a single antibiotic but several. My KISS model is that the SPECT results originates from gut bacteria dysfunction. The use of the right antibiotics would correct (or at least ameliorate) this. This would be in keeping this Philipe Bottero who found that many patients in psychiatric hospitals recovered fully when given the rotating antibiotics protocol for Rickettsia.

My interesting speculation is whether the progress of AD is significantly determined by gut bacteria dysfunction. I have been unable to find any studies on gut bacteria in AD.  Without such information, antibiotics are as likely to worsen instead of improve.

Life Expectancy

To return to the humor (or attempt there of), the other difference between CFS and AD is life expectancy.  AD has a greatly reduced life expectancy, CFS may have a slightly reduced life expectancy. If you are alive 10 years after onset, you likely have CFS and not AD.

This Christmas I sent a care package of various supplements to a CFS friend that is on SSI and having been having increasing problems. He is interested in my gut-bacteria model of CFS as well as needing neurological improvement.

Before sending the pills, I told him that he must run them past his medical professional before starting. There are always drug interactions etc. that are risks…

Often medical professional have no idea of what sequence to add various pills in. I tend to keep to the “no more than one new item every day (or even three days)” philosophy.  To assist his medical professional, I put together the sequence that seems to make the most sense (and why) below. It may be of interest to other readers’ discussions with their medical professionals. The goal is to have high risk of herx items later in the list and items likely to reduce inflammation (degree of herx) earlier in the list. The intent is not to send him to a herx-hell too fast!

4Olive Leaf ExtractProtects brain, will impact some gut bacteria

Notes:

• For chlorine tablets, after mixing 1 tablet in 1 qt of water, allow it to rest in a dark cupboard for 30 minutes. Keep it in a dark cupboard so minimize the breakdown.
• The ideal on day 13 or after a 7-10 pulse has ended, would be the addition of Mutaflor, Lacobacillus Reuteri, etc

I expect him to have a good headache and other signs of herx as he goes through the list (after approval by medical professional). When a herx starts, it is often best to stop adding more stuff until the herx ebbs (usually 4-7 days). If the herx gets too severe, stop the last item and wait 4 days before starting the next item. Often the herx will be a lot less severe on a second round/pulse.

My earlier post on Crohn’s Disease(CD) had some feedback asking for more herbs that are effective against Escherichia coli. This is not what a CFS patient want to use – their E.Coli levels are very low. This feedback was coming from Crohn’s patients because they could not tolerate some of the herbs. A person with Crohn’s that tried Mutaflor – Escherichia coli Nissle 1917 – (up to 3 capsules/day) reports much better symptoms and greater food tolerance since starting the Mutaflor. The Mutaflor replaces some of the bad E.Coli, but does not appear to be able to eliminate all of them.  For some people, several weeks or months of Mutaflor may be needed before trying/tolerating the herbs. Sorry, no overnight cures.

The key for this approach is simple:

We want to nuke the invasive strains and immediately repopulate with Mutaflor.

The following table should be helpful. I have ignored the extract method, I will leave that to advance herbalists. Some may require a visit to an oriental herbalist to obtain. All of these should be reviewed by a knowledgeable medical professional before starting.

It should be noted that resistance to herbs have been reported by repeat use [Study], thus two weeks on two followed by a different pair may be a good approach. Taking one capsule of Mutaflor (separated by 12 hours) may be beneficial. E.Coli is viewed as the most resistive of all bacteria [Study].  Less than 10% of herbs and spices will impact E.Coli – so make sure there is a study supporting the use of any herb, and not personal opinion. Because a herb work for a different bacteria, does not mean it will work for E.Coli.