A reader left a comment on my site this week and asked a few question.

“THANK YOU KEN!!!

I have had great success with your diet/probiotic information and I cannot thank you enough for sharing your story with the world.

I have something that took my health to the next level and I wanted to share it.
Note: This was before I found your blog and had made no other changes to my diet or lifestyle. I have had CFS for 7 years.

For depression, my doctor prescribed Sertraline, a serotonin reuptake inhibitor (SSRI). The first 3 weeks I had a terrible reaction but persevered and after about 12 weeks, I experienced a HUGE reduction in symptoms.

In regards to people with CFS having low E.coli, I have found links between E.coli and Serotonin.
1. “Escherichia coli Nissle 1917 [Mutaflor Probiotics] enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance.”http://www.nature.com/articles/srep17324
2. http://www.ncbi.nlm.nih.gov/pubmed/21080162

Maybe low serotonin (low E.coli) resulted in exacerbated pain sensitivity and other symptoms? I believe Sertraline also lowered my stress levels which allowed my immune system to get back on its feet and heal my body.

I also wanted to throw in this little gem about blood type and intestinal microbiota composition, I thought it could be an important piece of information for the overall puzzle.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485159/
I was hoping your PubMed skills could interpret for us? I struggle to understand scientific papers and would love to understand more about this link to our health. My blood type is 0 positive.

Thank you again, Ken! Your work is so appreciated.”

Blood Types

Since blood type is connected to DNA, and your microbiome is connected with your DNA, I am not surprised. I suspect that in time we will find many conditions deemed to be inherited is not inherited by DNA proper, but inherited by microbiome. I include one of the diagrams from the article that you cited. I could not find any studies on fibromyalgia, CFS, IBS and blood types — it would be interesting to see a study on it!

For other microbiome dysfunction associated diseases,

• “[Crohn’s disease] Patients with blood type AB had a better response to Infliximab [IFX] while those with blood type A appeared to have a risk of losing response to IFX.”[2016]
• “Subjects with blood group “B” are at high risk while individuals with blood group “O” are at low peril of evolving type 2 diabetes.” [2016]
• “The frequency of AB blood group was significantly higher in type-1 diabetics; and Ablood group was significantly higher in type-2 diabetics. Furthermore, Rh negativity were significantly more frequent in type-2 diabetics.” [2016]
• ABO histo-blood group might modulate predisposition to Crohn’s disease and affect diseasebehavior.[2014]

Example of how strains varied according to blood type

Serotonin And Probiotics

Many probiotics help with serotonin, they tend to be the same ones that I suggest. “serotonin receptor modulators are used to treat IBS,”[2015]  I did a post on DNA and serotonin earlier this year that may interest some.

• Yakult: “Two weeks after the examination, the Lactobacillus casei strain Shirota (LcS) group had significantly higher faecal serotonin levels (P<0.05) than the placebo group.” [2016]
• Lactobacillus rhamnosus GG supernatant upregulates serotonin transporter expression in intestinal epithelial cells and mice intestinal tissues [2015].
• “L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels,” [2015]
• Melatonin production in Escherichia coli by dual expression of serotonin N-acetyltransferase and caffeic acid O-methyltransferase[2016].

Not good:

• “mice treated with either F. prausnitzii strain A2-165 and its culture supernatant (SN) exhibited significant decreases in intestinal permeability, tissue cytokines and serotonin levels.” [2015]

In my last post I learnt about how some bacteria defends themselves against herbal and spices. In this post, I will look at one that is easily available as a supplement Genistein, an isoflavone and antioxidant. There are some risks from high dosages (see wikipedia)

Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials.[2002] “It is possible that the apparent ineffectiveness of plant antimicrobials is largely due to the permeability barrier. ….The results show that the activities of the majority of plant antimicrobials were considerably greater against the gram-positive bacteria Staphylococcus aureus and Bacillus megaterium and that disabling of the MDRs in gram-negative species leads to a striking increase in antimicrobial activity. Thus, the activity of rhein, the principal antimicrobial from rhubarb, was potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling the MDRs.”
[Full Text]

• More on multidrug pump inhibitors: Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations [2014] “Another group of EPIs is called the quinoline derivatives, because of their structural similarity with quinolones [143].”  – interesting because Jadin’s protocol includes the concurrent use of quinolones with other antibiotics.
• “In Gram-positive bacteria, EPIs against the NorA system in S. aureus has been intensively studied. A large number of both synthetic and natural compounds have been found to be EPIs against S. aureus NorA, especially those of natural origins such as genistein isolated from Lupinus argenteus, spinosan A isolated from Dalea spinosa and Tiliroside isolated from Herissantia tiubae”  Genistein is available as a supplement.

So what does PubMed say about it?

• “After 6 and 12 months (of 54mg Genistein daily), our results indicate a strong correlation and a significant effect of genistein in reducing both Hot Flashes and visfatin in women with metabolic syndrome ” [2016]
• “significant reductions in CFUs were found for S. aureus and B. anthracis when cultured in the presence of 100 muM genistein. …However, L. reuteri, E. coli, S. sonnei, and K. pneumoniae were not altered by in vitro culturing in the presence of 100 muM genistein… the use of genistein in combination with probiotics may augment the effectiveness of antimicrobial therapies currently used in the management of infections” [2006]
• Genistein inhibits pro‑inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway.[2014] “Genistein significantly decreased IL-6 and IL-1β mRNA levels, as well as IL-6 production in PMA/A23187-induced mast cells activation. In addition, genistein inhibited the phosphorylation of ERK 1/2 in PMA/A23187-induced mast cell activation. However, phosphorylation of p38 was not altered. Thus, these findings indicate that genistein inhibited the inflammatory status of mast cells through inhibition of the ERK pathway.”

Bottom Line

There is a lot of articles on this, my main take away is that it appears to have no impact on families that are undergrowths in CFS and does impact overgrowth. It should help with mast-cell/histamine issues (for that subset), and may have additional benefits.

More research is needed, but this looks like a very promising supplement.

On Friday I was messaged by a reader that have had extreme constipation. I have not done a post on constipation yet, but I do have a case report from another reader that had severe constant constipation, no longer has it (nor needing to take any drugs for it)

“Dec 24, 2015 started with:

• Prescript Assist
• L. Casei  – 4 capsules per day or (Yakult etc)
• 15 mg gum arabic

January 9, 2016 – constipation effectively gone.

Remember oats, fruits, vegetables and whole grains”

Probiotics

Moving on to PubMed, remember some probiotics can increase constipation — it is not just probiotics, but the right ones!

• Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon-induced constipated mice[2015].“These results suggested that lactic acid bacteria prevent constipation in mice, among which LC-Qian was the most effective.”
• Effect of fermented milk containing Lactobacillus casei strain Shirota on constipation-related symptoms and haemorrhoids in women during puerperium. [2015] “Results of this study indicate that continuous consumption of fermented milk containing LcS might alleviate constipation-related symptoms, provide satisfactory bowel habit..”
• The effect of Lactobacillus reuteri supplementation in adults with chronic functional constipation: a randomized, double-blind, placebo-controlled trial. [2014] “L. reuteri is more effective than the placebo in improving bowel movement frequency in adult patients with functional constipation as previously demonstrated in children, even if it seems to have no effect on stool consistency.” [Sources of L. Reuteri]
• Systematic review of randomised controlled trials: probiotics for functional constipation. [2010] “In adults, data suggests a favourable effect of treatment with Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota, and Escherichia coli Nissle 1917 on defecation frequency and stool consistency. In children, L. casei rhamnosus Lcr35, but not L. rhamnosus GG, showed a beneficial effect.”
• “Probiotic treatment of irritable bowel syndrome in children.[2010]” reports success with constipation in IBS using Symbioflor-2.

There are no studies on Prescript Assist and constipation. Prescript Assist is well studied for IBS and found effective.

Herbs

• Gum Arabic in treatment of functional constipation in children in Sudan [2013]

• Constipation and Botanical Medicines: An Overview [2015]. “the most common botanical laxatives such as senna, cascara, frangula, aloe, and rhubarb and their use in the treatment of constipation.” rhubarb is also an effective antimicrobial especially against S.Aureus.
  • “[Antimicrobial activity and chemical differences between the two chemotypes of rhubarbs].” It suggested that the antimicrobial activity of rhubarb might be related to some unknown components which were of same accumulating pattern of rhein. The findings in present study provided some experimental evidence on categorizing rhubarb into two chemotypes through the difference of antimicrobial activity on S. aureus”

Unusual Finding

In reviewing the literature for this post, I came across this — an article that found that rhubarb effectiveness can be increased up to 2000 fold by taking with a multidrug pump inhibitor. Bacteria has “pump” that pushes out toxins — which can often be the antibiotics trying to kill it. By slowing or stopping these pumps — the bacteria succumbs to the antibiotic (be it prescription or herbal)

• Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials.[2002] “It is possible that the apparent ineffectiveness of plant antimicrobials is largely due to the permeability barrier. ….The results show that the activities of the majority of plant antimicrobials were considerably greater against the gram-positive bacteria Staphylococcus aureus and Bacillus megaterium and that disabling of the MDRs in gram-negative species leads to a striking increase in antimicrobial activity. Thus, the activity of rhein, the principal antimicrobial from rhubarb, was potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling the MDRs.”
  [Full Text]
  • More on multidrug pump inhibitors: Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations [2014] “Another group of EPIs is called the quinoline derivatives, because of their structural similarity with quinolones [143].”  – interesting because Jadin’s protocol includes the concurrent use of quinolones with other antibiotics.
  • “In Gram-positive bacteria, EPIs against the NorA system in S. aureus has been intensively studied. A large number of both synthetic and natural compounds have been found to be EPIs against S. aureus NorA, especially those of natural origins such as genistein isolated from Lupinus argenteus, spinosan A isolated from Dalea spinosa and Tiliroside isolated from Herissantia tiubae”  Genistein is available as a supplement.

Bottom Line

The successful elimination of constipation reported by the reader is supported by PubMed articles. There are additional probiotics reported with good results in the literature. Symbioflor-2 and Mutaflor are both cited.

Rhubarb and genistein taken together is another approach, one that I would suggest be tried before (and NOT concurrent with) probiotics. There is a significant herx risk from this.

— as always consult with your knowledgeable medical professional before making any changes in supplements.

A member of a Spanish group that I work with asked about Cistus Incanus. She knows that I am always interested in herbs — for two reasons, no prescription needed to get, likely less collateral damage than prescription medication. There are only 29 citations on PubMed. She reports very good response to it.The graphic below may explain part of the why.
UPDATED Mar,2020 — due to COVID-19. There are now 45 citations

from http://passion4luxus.com/?p=1904

“Cistus species … have been employed in Mediterranean folk medicine as herbal tea infusions for healing digestive problems and colds, as extracts for the treatment of diseases, and as fragrances…. Various preparations from Cistus species have traditionally been used as remedies in folk medicine around the Mediterranean basin, especially in Greece, Italy, Spain, and Turkey. The targeted conditions and diseases include anxiety, arthrosis, asthma, bronchosis, various types of cancer, bacterial and fungal infections, cardiopathies, catarrh, corn, diarrhea, duodenosis, dysendery, dyspnea, fracture, gastrosis, headache, hepatosis, hernia, hysteria, induration, infection, inflammation, insomnia, leukorrhea, myalgia, neuralgia, osteoarthritis, polyp, proctosis, rhinosis, sore, spasm, splenosis, ulcer, uterosis (Duke et al., 2008).

Organic and aqueous leaf extracts of C. monspeliensis, and also C. villosus (=incanus), growing naturally in Morocco and Tunisia were shown to have antimicrobial and antifungal properties that were mostly active against Staphylococcus aureus, Enterococcus hirae, and Pseudomonas aeruginosa and the yeast Candita glabrata (Bouamama et al., 2006).

Exhibited a rather weak activity against E. coli and P. aeruginosa, moderate against Candita albicans, Micrococcus luteus, and S. epidermidis, and most active against S. aureus and Bacillus subtillis (Demetzos et al., 1995), ” [2014]

• The effect of Cistus incanus herbal tea supplementation on oxidative stress markers and lipid profile in healthy adults. [2019] “Cistus incanus administration decreases cardiovascular risk factors including oxidative stress and dyslipidemia “
• CYSTUS052, a polyphenol-rich plant extract, exerts anti-influenza virus activity in mice. [2007]
• A polyphenol rich plant extract, CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. [2007]
• Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins[2016].
• Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes inhibition[2015].
• The Polyphenolic Composition of Cistus incanus Herbal Tea and Its Antibacterial and Anti-adherent Activity against Streptococcus mutans [2015].
• Cistus incanus (CYSTUS052) for treating patients with infection of the upper respiratory tract. A prospective, randomised, placebo-controlled clinical study[2009]. “. In cell culture and in a mouse model it exerts antiviral and antimicrobial activities… A score of subjective symptoms decreased significantly over the course of treatment with Cistus, whereas treatment with placebo resulted in a less distinct decrease of symptoms. Among the inflammatory markers investigated, the C-reactive protein was mostly affected by Cistus and decreased significantly in the treatment group.”
• Antioxidant activity and protective effect on DNA cleavage of extracts from Cistus incanus L. andCistus monspeliensis L [2000].
• Antibacterial and antifungal activities of Cistus incanus and C. monspeliensis leaf extracts[1999]. “All extracts showed inhibitory activity against microorganisms.” [which ones were not named
• Gastroprotective effect of aqueous extract of Cistus incanus L. in rats [1995].
• Members of the same family appear to be antifungal [2007]

Bottom Line

Recommended:  E.Coli is almost resistant to it (for CFS a very good thing), it is very effective against S.Aureus (a strong suspect). It has also a long history of being used in folk medicine for digestive issues — the type of herbal usage signature that I look for!

I am a modeler and the model that I ended up for FM/CFS/ME/IBS came out building “sub-models” that took collection of research findings and found a simple model that explains all of the research results.

Today, I chatted with a CFS person who has severe migraines and was wanting to try probiotics. She was wisely warned to delay starting them because some probiotics can give massive headaches — massive headaches on top of migraines will likely result in non-compliance to the approach.

Why would probiotics cause headaches? Probiotics produces antibiotics against other strains and species. These can kill off those bacteria — just like taking an antibiotic.

In this post I will describe the model that I use for the topics in the title. A model explains what is happening and thus can suggest things that could be tried.

The diagram below shows the model:

The root cause of all three symptoms is low oxygen delivered to the brain (or in the case of FM, to tissue).

• “Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia.[2000]”
• “Fibromyalgia syndrome: overnight falls in arterial oxygen saturation. [1996]
• “migraineurs are more vulnerable to Acute mountain sickness,” [2011] … Acetazolamide is effective for both conditions.

The symptoms are likely a result of DNA, see this page for DNA SNPs associated with Migraines, and for DNA SNPs associated with Fibromyalgia

Looking at what can cause low oxygen, hypoxemia,  we actually have a significant list:

• Thick blood aka hyper-coagulation. Blood moves slower and thus the volume of blood (oxygen) that gets delivered is reduced.
• Low iron — hemoglobin in the blood is what transfers oxygen. It needs iron.
• Inflammation – swelling of tissue and blood vessels means that the volume of blood that gets thru is reduced. Instead of having a 1″ garden hose, you have a 1/4″ hose.
• Vascular constriction – this may be due to inflammation OR due to other causes.
• There are a few other causes:
  • Living at altitude (i.e. one mile or 1.5 kilometer above sea level)
  • Mild carbon monoxide poisoning, as well as a variety of other chemicals

A few diagnostic points:

• Oxygen saturation in the blood may be normal (except for iron deficiency). The problem is with oxygen delivery and not the oxygen level in the blood. It can also be localized to specific spots (the brain or tender spots in FM) This is why SPECT brain scans for CFS  that show hypoperfusion (low oxygen delivery to brain tissue) is important.  [Post with references to studies]
  • “SPECT was performed on 5 patients with classical migraine and 18 patients with migraine accompagnée. At the time of investigation, all patients were symptom-free. Cerebral blood flow was decreased in all patients with migraine accompagnée, and often corresponded to the site of headache as well as to the topography of transient neurological symptoms. This reduction was most obvious in a patient with persisting neurological symptoms. Most patients with classical migraine, however, did not show any alteration of cerebral perfusion. It appears that migraine–and in particular migraine accompagnée–is characterized by a permanent alteration not only of cerebral blood flow but also of neuronal activity. Migraine attacks may occur in connection with exacerbations of preexisting metabolic alterations.” [1987]

Treatment

Our model above has multiple possible causes — someone with migraines can attempt to address one cause at a time to see if it reduces the severity of the migraine.  My suggestions (to be discussed with a knowledgeable MD always) are:

• Hypercoagulation: also see this post also:
  • Grape Seed Extract (as alternative to aspirin)
  • Alpha Lipoic Acid
  • Turmeric (with some black pepper mixed in)
  • Piracetam.
• Low Iron – a good PubMed article is here. It can be associated with H. Pylori and Giardiasis infections.
  • Iron supplements
• Inflammation – there are many herbs and supplements that are anti-inflammatory. Unfortunately there are no studies comparing their effectiveness in human patients.
  • My own preferences are the gums such as boswellia, mastic and myrrh. Many of these can be chewed in the mouth.
• Vascular constriction
  • Regular flushing niacin. This is also the cheapest niacin. You do NOT want no-flush niacin, nor time release. You want to turn red as a lobster!
  • “We have found that when red blood cells are exposed to abnormally low oxygen for long periods, they become depleted of an essential substance that they normally release to relax blood vessels in the lung,” [2005]

If any of the above does reduce the severity of migraines, then it points in a direction for further treatment. If you suffer from migraines, then a herx — dumping of toxins into the body will likely make the migraine very much worst.

Again, this is a model to provide a framework for experiments to deduce the cause. I believe strongly is systematic and progressive experiments. Almost all of the items above can be associated with microbiome shifts – which leads back to my model.