Before I could get Nattokinase as capsule, I was getting it from a Japanese desert food called “Natto” that was available at our local market (which happened to be owned by a Japanese family that has been in the US since 1900).

It’s main characteristics are:

• Anti-hypertensive
• Cleaves cross-linked fibrin
• Decreases red blood cell aggregation and shear-viscosity of blood cells
• Inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity
• Increases activated factor VII levels
• Maximum dosage: 4000 Fibrin Units (any more on a continouse basis may result in bruising or bleeding risk)
  • US Orders[2000 FU @ 90 capsules $12]
  • UK Orders[2000 FU @ 90 capsules £16]

As always, consult with your knowledgeable medical professional before adding any new supplement.

The use of nattokinase(STN) as functional foods to improve blood circulation is getting attention because STN actively degrades fibrin. Our results demonstrate that widely occurring unsaturated fatty acids such as linoleic, eicosapentaenoic, and docosahexaenoic acids enhance the fibrinolytic activity of STN. Thus, the intake of natto or STN supplements in combination with unsaturated fatty acid-containing oil can be a novel way to gain cardiovascular benefits.

Unsaturated fatty acids enhance the fibrinolytic activity of subtilisin NAT (nattokinase) [2020]

I was first introduced to bromelain because it potenated antibiotics. Many antibiotic resistant infection were found to be eliminated if bromelain was added with studies going back to 1950.

Bromelain shows impacts  various cytokines such as TNF, IL-1 beta, CD14, COX-2 and IL-6. Bromelain is also an anti-funga, anti-edema, anti-inflammatory, and inhibits coagulation

• Increases serum fibrinolytic activity, reduces fibrinogen synthesis, and directly degrades fibrin and fibrinogen
• Increases antibiotics penetration, especially for tetracyclines
• Impact plateaus at 12-16 hours – which is important for correndating antibiotics with bromelain.
• Increases serum fibrinolytic activity
• Inhibits fibrinogen synthesis
• Fibrinolysis enzyme activator

It is the cheapest and also the one with the longest half-life. It is my recommendation for the first one to try.

• US Orders[2400GDU @ 120 capsules $17]
• UK Orders[3000GDU @ 90 capsules £17]

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.