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.

I have mentioned Ginseng in several posts, but have not done one doing a deep dive into it. Asian Ginseng has a reported benefit (40%) on the surveys and sSupplementation helped 56% in one PubMed study (2005)

• “Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample.” [2004] – so the effect is small (if at all).
• “Ratings on the Visual Analogue Scale (VAS) revealed a reduction in pain (of Fibromyalgia) in the P. ginseng group (p < .0001), an improvement in fatigue (p < .0001) and an improvement in sleep (p < .001), with respect to baseline characteristics, but there were no differences between the three groups. With respect to anxiety, improvements occurred in the P. ginseng group compared to baseline (p < .0001); P. ginseng reduced the number of tender points and improved patients’ quality of life (using the Fibromyalgia Impact Questionnaire – FIQ); however, there were no differences between groups. “[2013]
• “consumption of white or red Korean ginseng (WG or RG) powder significantly increased the number of total bacteria and Lactobacillus strains compared to the control group.” [2014]

The main impact of ginseng appears to be on coagulation (and thus improved oxygen delivery resulting in less pain caused by cellular hypoxia).

• ” herbal medicines that inhibit platelet function (e.g., garlic, ginseng, or ginkgo)”  [2015]
• The influence of herbal medicine on platelet function and coagulation: a narrative review [2015]. “ginseng, green tea, and St John’s wort were found to have potential interactions with warfarin.”
• Study on improving blood flow with Korean red ginseng substances using digital infrared thermal imaging and Doppler sonography: randomized, double blind, placebo-controlled clinical trial with parallel design[2013].

Bottom Line

The amount of information on ginseng is less than ideal. It appears to have only a limited impact on the microbiome. I ascribe most of its positive effects are due to improving blood flow.

Cost to benefit appear low, so I would place it low on desired herbs and supplements.There are other items that are cheaper, just as effective on improving blood flow and more effective in shifting the microbiome.

Back in 2001, it was speculated that ” the dietary supplements glutathione, N-acetylcysteine, alpha-lipoic acid, oligomeric proanthocyanidins, Ginkgo biloba, and Vaccinium myrtillus (bilberry) may be beneficial [for CFS].” [2001] This suggestion is repeated 6 years later – “It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids.” [2007].

Positive results were obtained from combined use of ” glutamine, N-acetyl cysteine and zinc… A good clinical response is significantly predicted by attenuated IgA and IgM responses to LPS, the younger age of the patients, and a shorter duration of illness (< 5 years).” in [2008]. Similar mixtures of “L-carnitine, coenzyme Q10, taurine + lipoic acid, with or without curcumine + quercitine or N-acetyl-cysteine, zinc + glutamine” study ended up with the need to do proper controlled studies.. [2014]

Well, some 16 years after it was suggested, we do not find actual studies! So, let us see what we find using our model…

• Antibacterial effects of N-acetylcysteine against endodontic pathogens[2016].
  • “we conclude that NAC has excellent antibacterial and antibiofilm efficacy against endodontic pathogens”
• “An increase (P < 0.05) in gut Lactobacillus and Bifidobacterium, accompanied with a decrease (P < 0.05) in Escherichia coli counts, was also observed in the NAC group.” [2014]
• ” NAC appears to be a promising, non-antibiotic alternative to prevent biofilm-associated infections.” [2017]
• “N-acetylcysteine (NAC) enhances the release of histamine” [1991]

Bottom Line

When you take NAC, one half of it will be out of your body in 6 hours [5.6 hrs half life]. If you take it once per day, the amount left before you take it again is just 1/16 (8%) of when you took it. I would suggest taking NAC  every 8 hours to get the maximum benefit.

It definitely have benefits when taken with anti-infection herbs and some probiotics. If you have histamine issues, you may wish to take care.