A reader wrote:

“Need your brain. 

Basic Actors

• GastroCrom  is Cromoglicic Acid ” is traditionally described as a mast cell stabilizer, …prevents the release of inflammatory chemicals such as histamine from mast cells.”
  • Since excessive histamine is common with CFS patients, I would ascribe that this is why it helps you so much. Earlier posts on histamine –Mar 14, Mar 15, Mar 16
• Tramadol ” is an opioid pain medication…
  • “As of 2015 tramadol was not approved in the United States for fibromyalgia.^[16] Based on three small trials with weak study design, there is fair evidence for tramadol as a second line treatment.^[16]”  It also “increase central serotonin neurotransmission. “[2016]
  • “Earlier studies suggest that CFS may be associated with genetic variability in genes important for serotonin (5-HT) signaling [3,4].” [2015]
  • “Chronic fatigue syndrome (CFS) or Myalgic Encephalomyelitis (ME) is characterized by…autoimmunity to serotonin” [2015]
• Aspartame ==> glutamate: I could only find studies indicating no evidence [1980] [1986] [1987], but did find
  • ” Plasma phenylalanine concentrations were significantly higher (p less than 0.05, paired t test) after ingestion of meals containing aspartame” [1982]
  • “Aspartame has conflicting evidence with two positive and two negative provocation studies [for causing headaches]. Observational studies provide modest evidence that gluten- and histamine-containing foods as well as alcohol may precipitate headaches in subgroups of patients.” [2016]

POTS

• “Selective serotonin reuptake inhibitors (SSRIs) are often prescribed in patients with postural tachycardia syndrome (POTS), and act at synaptic terminals to increase monoamine neurotransmitters.” [2014]
• ‘Pharmacologic treatment is recommended on a case-by-case basis, and can include… , mineralocorticoid agents to increase blood volume, and serotonin reuptake inhibitors.” [2010] (for mineralocorticoid see above diagram)

Bottom Line

The two drugs acts strongly on two different aspects of CFS:

• Excessive histamine is reduced (probably, microbiome associated)
• Improved serotonin signalling (possibly DNA associated), which may also impact POTS

They may act on other aspects but that is difficult to evaluate given the dominant aspects that they are known to act upon.

Second Question  – Calcium Channels

Now the explicit question about Calcium Channels.

• “It is suggested that chronic fatigue syndrome/fibromyalgia is caused by virus injury to the calcium channels leading to larger quantities than usual of calcium ions entering the striated muscle cells.”[1994]
• “Circulating autoimmune antibodies may produce symptoms of muscular fatigue by reacting with acetylcholine receptors or calcium binding channels … We were unable to detect any pathogenic antibodies.” [1997]
• ” We also report for the first time,… as well as decreased intracellular calcium within specific conditions in CFS/ME patients.” [2016]
• “Given the important roles of calcium (Ca²⁺) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients…. identified a number of SNPs and genotypes in genes… These may …. suggest a role for Ca²⁺ dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.” [2016]
• “TRPM3 activity and function in NK cells in CFS/ME patients is impaired, resulting in changes in Ca²⁺ ion concentration in the cytosol and intracellular stores which may, in turn, change the NK cells’ activation threshold.” [2017]

My take is that the impact of the two drugs mentioned above with calcium channel (still speculative, the “may” keyword) is far less than their impact on two established aspects of CFS.  It may be there, but these two drugs are not suitable to demonstrate that calcium channels (versus other things) is involved or effective for treatment.

In my last post, Cholestyramine appear as a good supplement based on surveys. Wikipedia describes it as ” a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong ion exchange resin, which means it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. The functional group of the anion exchange resin is a quaternary ammonium group attached to an inert styrene–divinylbenzene copolymer.” – a description likely above most CFS cognitive ability.

In terms of CFS, R.C. Shoemaker, M.D. first proposed it in his 2001 article on possible estuarine-associated syndrome (PEAS)   citing ” resolution with cholestyramine treatment suggests a neurotoxin-mediated illness.” as well as from Sick Building Syndrome [2005], [2006].

• [Chronic Lyme] “Patients coinfected with B burgdorferi and B microti derive measurable clinical benefit from prolonged treatment with atovaquone and cholestyramine” [2006] – 20% became asymptomatic, 64% improved.

On the negative side, 2010 study on a condition that often had fibromyalgia, found “Fatigue was associated with greater use of prescription medication (P < 0.01), in particular for antipruritics (cholestyramine: P < 0.001; rifampin: P < 0.001), proton pump inhibitors (P < 0.002), beta-blockers (P < 0.02), and antidepressants (P < 0.001), whereas those taking calcium and vitamin D appeared less fatigued (P < 0.05).” There are a number of articles on Irritable Bowel Syndrome with Diarrhea.

• “Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea.”[2015]
• ” An estimated 70% to 96% of chronic diarrhea patients with Bile acid malabsorption respond to short-course cholestyramine.” [2013]

Microbiome Impact

• “In vitro studies have shown that some bile salts inhibit the growth of intestinal bacteria…the number of ileal anaerobic microorganisms decreased significantly after both bile salt and cholestyramine treatment.”[1975] This is good because
  • “A significant increase of Gram positive facultative anaerobic faecal microorganisms in 108 CFS patients as compared to 177 control subjects (p<0.01) is presented in this report.” [2009] In other words it appears to counter one aspect of the microbiome shift seen in CFS.
• “Certain organisms such as Bacteroides fragilis are stimulated by bile acids and the activity of such bacteria may be decreased by the unavailability of bile acids bound to the resin [cholestyramine].  Secondly, certain bile acids exert a pronounced bactericidal effect at pH 5-6 and this decreases as the pH rises to 7-2 (Percy-Robb and Collee, 1972). ” [1978]

Bottom line: this is a prescription drug which appears to work well when prescribed, typically for Irritable Bowel Syndrome with Diarrhea. It does impact growth of different bacteria and may shift the population closer to normal in CFS patients.

If your MD is willing to prescribe it for 12+ weeks, around 80% of CFS patients may see improvement. Of course, it would be nice to an actual study on CFS patients with microbiome samples done before and after.

In my last post, I gave a Cookbook based on PubMed articles and some surveys on this site.  CFS patients often ask on support groups — what to take, and the quality of recommendations vary greatly! The ideal response or guidance for any supplement, probiotics or anti-infection agents would be:

• Probability of improvement
  • Degree of improvement is often very subjective
• Probability of problems / deterioration
• Quantity taken (many pubmed studies have no effect seen until a certain dosage was reached)

IN this post I will list survey sites that I found and list items that were not included in the Cookbook or the Surveys. Items need at least 10 responses in the survey to be included

• ME Association of UK 2010 Survey:
  • CORTICOSTEROID eg HYDROCORTISONE: Better 33% Worst 21.6%
  • THYROXINE: Better 41% Worst 10.8%
  • MODAFINIL/PROVIGIL: Better 37% Worst  29.6%
  • EICOSAPENTAENOIC AID (EPA) OMEGA 3 OIL: Better 36.3%  Worst 4%
  • L CARNITINE: Better 30.8% Worst 6.3%
  • INOSINE PRANOBEX/ IMUNOVIR: Better 25.8% Worst 24.2%
  • Enada/NADH: Better  19.9% Worst 16.8%
  • EVENING PRIMROSE OIL: Better  28.4%  Worst 5.4%
• https://beta.groups.yahoo.com/neo/groups/CFSFMExperimental/polls/close
  • EDTA (thylenediaminetetraacetic acid): 32.5% improved 12% worst
  • my experience with getting a saline drip has been (short term): Better 72% Worst 0%
  • low dosage naltrexone http://www.lowdosenaltrexone.org): Better 26%  Worst 26%
  • ImmunoPro (non-denatured whey): Better:  47%  Worst 24%
  • Alfred Blasi protocol (http://health.groups.yahoo.com/group/Al fredblasiprotocolFMSCFS/ ): Better: 46%  Worst: 11%
  • Salt/C Protocol (http: http://www.lymephotos.com):  Better 36%  Worst: 12%
  • Gookinaid: Better: 54%   Worst: 46%
  • the Hemex Protocol (anticoagulants, ISAC panel Mocha Panel): Better: 48%   Worst:  27%
  • Cholestyramine: Better: 58%   Worst: 8%
• http://www.storiesoutloud.co.uk/supplements/pollresultsall.py
  • Coconut Oil: Better: 81% Worst: 6%
  • Probiotics (not specific): Better: 69% Worst: 0%
  • Vitamins
    • B Vitamins: Better: 69% Worst 0%
      • B12: Better 59%, Worst 5%
      • Folic Acid or Methylfolate: Better 40%  Worst 15%
      • NADH: Better  27%, Worst 9%
    • Vitamin C: Better: 66%  Worst 0%
    • Vitamin D: Better  54%, Worst 14%
  • Minerals
    • Magnesium (Not Epsom Salts): Better: 74%  Worst 6%
    • Epsom Salts (Magnesium Sulfate):   Better: 92% Worst 0%
    • Calcium: Better  25%, Worst 17%
    • Sea Salt: Better: 83% Worst 0%
    • Selenium: Better 60%,Worst 10%
    • Zinc: Better 56%, Worst 6%
  • Digestive Enzymes: Better: 55% Worst 6%
  • Garlic: Better: 50%, Worst 0%
  • Turmeric/Curcumin: Better 60%, Worst 7%
  • Dehydroepiandrosterone (DHEA): Better 60% ,Worst 10%
  • Omega 3 (No Particular Oil): Better 47%, Worst 0%
  • N-Acetyl-L-Cysteine (NAC): Better  60%, Worst 13%
  • Spirulina: Better 40% , Worst 0%
  • Co-enzyme Q10 or Ubiquinol: Better 55%, Worst 19%
  •  Melatonin:  Better  56%, Worst 20%
  • Acetyl-L-Carnitine (ALC): Better  48%,Worst 9%
  • D-Ribose: Better 51% , Worst 18%
  • Evening Primrose Oil: Better 38%, Worst 8%
  • Ginkgo: Better 45% , Worst 18%
  • Milk Thistle: Better 46% , Worst 23%
  • Valerian:  Better 64% , Worst 29%
  • Chocolate or Cocoa:  Better 48% , Worst 24%
  • Ginseng (American or Asian/Korean/Panax or Siberian): Better  25%, Worst 8%
  • 5-HTP: Better 33% , Worst 40%
  • Echinacea:  Better  6%, Worst 25%
• http://curetogether.com/Chronic-Fatigue-Syndrome/survey/treatments/ (Associated with 23andMe.com — DNA). The details are not available so we cannot get the same odds ratio as above easily, I did items on the top of the list for effectiveness
  • Low-Dose Naltrexone: Better 62% Worst 11%
  • Recuperation (Mineral-rehydration supplement): Better 53% Worst 7%
  • B12 Injections: Better 47% Worst 8%
  • Far Infrared Heat (Migun Bed): Better 53%   Worst 10%
  • Thyroid hormone: Better  47% , Worst 10%
  • Probiotics (not specific): Better 42% , Worst  6%
  • Magnesium (Oral): Better 40%  Worst  5%
  • Chelation Treatments: Better 46%   Worst 6%
  • Eat more vegetables and fruits (Increase natural fiber): Better 34%  Worst 4%
  • Chonazepan  (Klonopin, Rivotril): Better  51%  Worst 19%
  • Diflucan (Antifungal): Better 33% Worst 3%
• 

Bottom Line

If you know of additional surveys/polls please pass their URL along.

A lot of items are sitting around 50% for helping…   so the first choice should be items with a low percentage of harming (i.e. 10% or less…) and at least a  50% for helping.. This gives a 5:1 risk factor. The top picks from above are:

• Zero risk of worst
  • Saline Drip – usually not practical
  • Sea Salt
  • Magnesium Sulfate
  • Probiotics (any)
  • Vitamin C
• High benefit to risk ratio ( with > 50% of being better)
  • 13.5 Coconut Oil
  • 12  B12
  • 8.6 Turmeric/Curcumin:
  • 7.25 Cholestyramine:
  • 7 Zinc
  • 6 Selenium
  • 6 Dehydroepiandrosterone (DHEA):

Dosages?  Most of the surveys do not say anything about dosages. I know a few dosages from studies, cited in this post. My rule of thumb is that the dosage on bottles are not-therapeutic dosages, and do not consider mal-absorption seen in CFS/FM/IBS. Take vitamin B1 (thiamine) as an example: This 2013 study found no improvement below 1500 mg/day and then a major improvement. The typical B1 dosage is:

• “For adults with somewhat low levels of thiamine in their body (mild thiamine deficiency): the usual dose of thiamine is 5-30 mg daily in either a single dose or divided doses for one month. The typical dose for severe deficiency can be up to 300 mg per day.”  [MedLinePlus.Gov]

IMHO, malabsorption is a major major factor — resulting in effective dosages being much higher than is normally accepted.

Why do we have brain fog?

Brain scans of CFS/FM/IBS/Lyme disease find abnormalities – typically “hypoperfusion”, a fancy way of saying low oxygen delivery to the brain. Also, the brain size decreasing by about 1% per year, likely caused by the lack of oxygen. Different ways of doing brain scans find or do not find abnormalities:

• Magnetic Resonance Imaging (MRI) from 14% (Lyme) to 78% (EBV) abnormalities
• Positron Emission Tomography (PET) about 50% with abnormalities
• Transcranial Doppler Sonography (TDS) – no statistics on % with abnormalities
• Single-photon emission computerized tomography (SPECT) From 70-80%

Getting a SPECT scan is the preferred brain scan for CFS patients. If you want more information on brain scans and links to the source articles on Pub Med, see this post.

Best Strategy: Know and correct root cause by LAB TESTS!

All brain fog is NOT the same. The same effect may happen — reduced oxygen to the brain, but the why may be different. The most common causes are:

• Hypercoagulation (thick blood)
• High Viscosity blood (slow moving)
• Lactic-Acidosis
• Inflammation – C-Reactive levels etc
• Iron issues with the blood (reduced ability to carried oxygen)
• Blood acid level (reduced ability to carried oxygen)
• Blood Clots
• Clogged Arteries
• Bacteria Dysfunction which alter the metabolites in circulation.
• Bacteria infection in brain (very low probability usually)

Many readers have asked for a simplify summary…

Supplements by Proven Benefits Level

1. Magnesium:  600-800 mg /day (Post)
2. Vitamin D3: 15,000 IU/day (post)
3. Neem (rotate)
4. Oregano (rotate)
5. Resveratol – 1000 mg/day
6. Licorice – 2 gms/day
7. Zinc 30-40 mg/day see this post
8. B12 1000 mcg/ 1 mg seems to be the effective ongoing dosage, see this post
9. CoQ10 300 mg/day – Studies in this post.
10. L-carnitine 500mg x 3 times a day – improvement after 4 weeks
11. NAC – 3 times a day
12. Folinic Acid (bio-active form of B9) 800 mcg/day
13. Myrrh  and boswellia (frankincense) gum

Cognitive (Brain Fog) Aids

1. bacopa-monnieri
2. piracetam

Probiotics

2 weeks on one, then move to the next

1. Miyarisan — Clostridium butyricum –converts d-lactic to butyric acid
2. Equilibrium – soil based organisms
3. Lactobacillus fermentum ME3 – converts lactic acid to acetic acid (some people have reported that they smell like vinegar when they start it)
4. Symbioflor-2  – E.Coli strains –documented to persist
5. L. Reuteri – produces B12
6. Mutaflor — E.Coli Nissle 1917
7. Prescript Assist soil based organisms
8. Align — Bifidobacteria infantis (B. infantis) 35624

Note that only 2 of the above are Lactobacillus probiotics – most Lactobacillus have negative or no effect.

Postlogue

With CFS, I have picked carefully when I put my energies. My main focus is to develop a model, constantly validate if it is consistent with new research and find candidate supplements and prescription drugs.  For each item, I research on PubMed to get the latest findings.

I use the terms candidate because, without actual (well done) studies on humans with CFS/IBS/FM, we do not know it they really have significant benefits. How long do studies take? Often 2-5 years if some researcher become passionate about it.

The model defines what we are wanting supplements and prescription drugs to do. The ideal is something that:

• Reduces all of the overgrowth of bacteria reported
• Increase the undergrowth of bacteria reported
• Does not increase, but decrease d-lactic acid levels
• Does not increase, but decrease histamine levels

The degree that I drill into everything is well above many CFS-suffers cognitive processing levels.A protocol is what a MD produces, I am a citizen scientist so I can only give suggestions to the best of my analysis.

There are really no good well-constructed studies of probiotics and CFS/FM/MCS. The few studies that there are,  use commercial mixtures often contain L.acidophilus which is contraindicated(bad) for CFS.

• “The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity in CFS patients…there were no significant changes in fatigue and physical activity scores.” [2009]

IBS has many studies (see this post). I worked off [Surveys] to a large extent. With these, the pattern is rotation: 2 weeks on one, then move to the next (so we have 16 weeks listed above).

There are many excellent candidate items not cited above.

As always, consult with a knowledgable medical professional before starting or changing supplements.

A reader wrote:

“Another thing I take to eliminate brain fog is Bacopa Monnieri. It’s sometimes called Brahmi too but Brahmi can also be another thing in Indian medicine (I think?). I don’t claim to be an expert on Ayuveda but all I know is there are several brands that call it each name and all of them work for me. Its effect is almost as strong as modafinil. However, it’s definitely using some other pathway because it’s subjectively different and it also stacks with other stimulants. Caffiene and modafinil both pair well with it and magnify the effects.

• Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress[2017].
  • “Bacoside A is considered as a major active component known to have 2016protective activities against morphine-induced cerebral toxicity, chemical-induced liver toxicity, and wound healing activity^7,8.”
• Effect of Bacoside A on growth and biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa [2017]. “At a subminimum inhibitory concentration of 200 μg·mL^-1, Bacoside A significantly removed ∼88%-93% of bacterial biofilm developed on microtiter plates”
• The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain [2017].
• Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury [2017].
• Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat[2016].
• Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial [2016]. “Statistically significant improvement was seen in the tests relating to the cognitive functions with use of Bacopa monnieri. Blood biochemistry also showed a significant increase in serum calcium levels (still within normal range).”
• Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline[2016].
• The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain[2017].

Bottom Line

There was been human studies and the reader report of dramatic improvement is very viable! Brain inflammation is common with CFS (typically seen in 75% of SPECT scans of CFS patients) and that this is effective in reaching the brain. A definite recommendation for anyone with brain fog.