A year ago, I did a post on herbs and supplements that are biofilm breakers. A reader raised a question about probiotics that could do the same…. interesting question! Warning: there are many types of biofilms! That is,  a biofilm created by one bacteria is different from the next bacteria.

I found a very good article on the concept published in Nature

Probiotics to counteract biofilm-associated infections: promising and conflicting data[2014]. [Full Text]

• “In recent years, the ability of other commonly used probiotic strains (Lactobacillus acidophilus DSM 20079, Lactobacillus paracasei DSMZ 16671, Lactobacillus plantarum 299v, Lactobacillus rhamnosus GG [Culturelle], Lactobacillus reuteri strains PTA 5289 and L. reuteri SD2112, etc.) to hamper S. mutans growth and biofilm formation in vitro has been evaluated, and these results suggest that the antimicrobial activity of Lactobacilli seems to be strain-specific and pH-dependent“
• “probiotic L. salivarius W24 was able to affect the compositional stability of the microbial communities derived from individual saliva and appeared to have a cariogenic potential“
• “On the one hand, there are studies reporting that probiotics are able to inhibit biofilm formation of intestinal pathogens, but on the other hand different experimental data seem to support the enhancing of enteropathogens biofilm biomass in the presence of probiotics.”
• “In 2010, Hancock and coworkers investigated the biofilm-forming capacity of Nissle 1917[Mutaflor] and found that this strain was a significantly better biofilm former than enteropathogenic, enterotoxigenic and enterohaemorrhagic E. coli strains, with the exception of being able to out compete such strains during biofilm formation”
• “three probiotic strains (L. rhamnosus GG, B. longum NB667, and Bifidobacterium animalis IPLA-R1) have been demonstrated to increase the adhesion of Enterobacter sakazakii ATCC 29544 and E. coli NCTC 8603, Salmonella enterica serovar Typhimurium ATCC 29631 and Clostridium difficile ATCC 9689”
• “However, data are still scarce and not always consistent to look at probiotics as tool to avoid biofilm formation and/or to disperse pre-formed pathogenic biofilms.”

I found a few newer articles, but the full text version cited above gives far more detail on which probiotics (and mixtures) increases or decreases biofilm – the data is very very fuzzy. On the plus side:

• Mutaflor does not destroy biofilms, it just create it’s own biofilms better!
• Lactobacillus rhamnosus GG [Culturelle] appears to be a breaker (of some biofilms)

This is the fourth of a series looking at the supplements in Driscoll’s Theory Patented Supplement Parasym Plus.  Only the specific ratio is patented — you can take the items freely, and even replicate the ratios (likely at much lower cost!) — just don’t sell it!

This supplement had an unexpected surprise — it reduces lactic acidosis in some situations.

From 1999, “These data provide preliminary evidence of reduced functional B vitamin status, particularly of pyridoxine, in CFS patients.”

• [1999] “, a recent dietary survey yielded no evidence that such patients had low intakes of pyridoxine, riboflavin, thiamine or various other vitamins and micronutrients1 … A placebo controlled double-blind study of a polynutrient supplement including pyridoxine, riboflavin and thiamine has shown significant improvements, particularly fatigue scores, after six weeks’ treatment”
• “The absence of blood thiamine deficiency and the efficacy of high-dose thiamine in our patients suggest that fatigue is the manifestation of a thiamine deficiency, likely due to a dysfunction of the active transport of thiamine inside the cells, or due to structural enzymatic abnormalities.” [2013] The last phase would include dysfunctional microbiome.
• “The patient and his family responded to treatment with high doses of riboflavin and thiamine with a remarkable and sustained fatigue and muscle symptoms improvement” [2015]
• High-dose thiamine improves the symptoms of fibromyalgia.[2013]
• Aggravation of thiamine deficiency by magnesium depletion. A case report[1985]. — so magnesium supplementation concurrent is imporant
• “We report 5 cases of acute vitamin B-1 induced lactic acidosis in surgical patients receiving parenteral nutrition. In all patients treatment with vitamin B-1 induced a dramatical improvement of clinical findings.” [1990]  I include this citation because lactic acidosis is common in CFS. These citations are NOT for CFS.
  • “Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients.” [1997]
  • “After thiamine administration, the patient very quickly recovered with dramatic reestablishment of the acid-base balance.” [2004]
  • “patients were subsequently diagnosed as having thiamine deficiency-induced lactic acidosis.” [1993]

Benfotiamine

This is a synthetic version of B1 – chemically slightly different (see earlier post). So whether it has the same impact as thiamine on lactic acidosis is an unknown (i.e. not studied)

Bottom Line

As with our last supplement, labs will likely show normal levels BUT supplementation results in significant improvement of symptoms. What is particularly interesting is that thiamine reduces/reveres lactic acidosis, a very significant factor for CFS patients.

You should supplement with magnesium (which I hope every one is doing already) when taking it.  Dosage, “100 mg  two- three times daily”. Three times per day cited on National Institute of Health for another condition. Two times for above cases of lactic acidosis.

This is the third ingredient in Driscoll Protocol’s supplement. Unlike the prior two, the evidence is strongly favorable to it’s use — symptoms will reduce BUT if you stop, they will return.

Below is a summary of the major findings on PubMed

• “The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue…. it may be of benefit in treating Alzheimer’s dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions… There were no significant differences in plasma or urinary total, free or esterified (acyl) carnitine between UK patients with CFS and the control groups or in renal excretion rates of these compounds.” [2012]
• “In patients with chronic hepatitis C and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine.” [2011]
• “Contradictory reports have suggested that serum free carnitine and acylcarnitine concentrations are decreased in patients with chronic fatigue syndrome (CFS) and that this is a cause of the muscle fatigue observed in these patients. Others have shown normal serum free carnitine and acylcarnitines in similar patients.” [2005]
  • “The previously reported decreased level of acylcarnitine in CFS patients was not confirmed. There were also no significant differences in levels of total carnitine, free carnitine and 20 carnitine esters between CFS patients and controls.” [2000]
• A randomised controlled trial comparing duloxetine and acetyl L-carnitine in fibromyalgic patients: preliminary data [2015]. “randomised to receive duloxetine 60 mg/day or acetyl L-carnitine 1500 mg/day (500 mg three times a day) … Both drugs had a positive effect on the physical component of the quality of life, but only duloxetine improved the psychological component.”
• Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.[2007]  “Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated.”
• ” The level of L-carnitine was 6.4336 +/- 3.4225, significantly lower than that of the control group and the L-carnitine level was increased 2 weeks after supplementary treatment, together with improvement of symptoms.” [2005]
• “Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasmacarnitine levels correlated with clinical improvement.” [2004]
• Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity. [2011]

Bottom Line

• Carnitine is unlikely to be low when measured, BUT
• Supplementation of l-carnitine results in improvements with both IBS and CFS
  • 500 mg of acetyl L-carnitine taken three times a day showed results.
  • This must be ONGOING — if you stop, the benefits will be loss. This is symptom mitigation only

In my last post, I reviewed one of the four ingredients in Parasym Plus,  Acetylcholine-Esterase Inhibitors, the patented supplement sold by the Driscoll Protocol. In this post, I will move on to a second ingredient (with the other two reviewed over the next two days).

Low choline levels appear to come into play with some CFS patients. This can be exposed from headaches using piracetam etc. The question of supplementation arose — and it does not look like it is a simple question to answer.

• “The MR spectroscopy (MRS) study revealed remarkable elevation of the choline/creatine ratio in the patients with CFS.” [2000]
• “Patients with hepatitis C virus (HCV) infection frequently complain of symptoms akin to the chronic fatigue syndrome… we have shown elevations in basal ganglia and white matter choline/creatine ratios in patients with histologically-mild hepatitis C, compared with healthy volunteers and patients with hepatitis B. This elevation … suggests that a biological process underlies the extrahepatic symptoms in chronic HCV infection.” [2001]
• Relative increase in choline in the occipital cortex in chronic fatigue syndrome[2002] “The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008).”
• Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. ” A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group”
• ” the regional brain areas in CFS have shown increased peaks of choline derived from the cell membrane phospholipids.” [2004]
• “The choline/creatine ratio of the GWS group was not different from that for either control group.” [2004] Suggesting that Gulf War Syndrome and CFS are different….
• “Radiological imaging studies (SPECT, Xe-CT, and MRS) revealed decreased blood flow in the frontal and thalamic areas, and accumulation of choline in the frontal lobe.” [2004]
• ” The findings produced by neuroimaging techniques are quite similar in both illnesses[CFS and MS]  and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels.”

There are some web pages worth reviewing on

• PhoenixRising [2005]  – no clinical trials of possible treatment
• “it sounds as though you have an unusual response to choline supplementation. Elevated acetylcholine in the central nervous system can cause depression. My guess is that your body may overproduce acetylcholine, or it may not be able to break acetylcholine down as rapidly as normal, and one or the other of these may account for the depression on supplementing choline. This sounds like a genetic issue…” Rick van K
• Dr. Myhill advocates supplementation if your temperament indicates it.

Bottom Line

It appears individual genetics may be the key factor in supplementation (or not to supplement). If you supplement and things improve — good, if things get worst, stop.

The root cause appears to be believed to due to phages / immune response /etc.  In my model, likely the microbiome shift.

Vagus Nerve infection hypothesis

This hypothesis is circulating and getting a readership in some CFS circles. I am a PubMed person, and I have been asked my opinion… so to PubMed I go.. There are just 13 articles

• Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis. [2013] ” The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies.” — so I expect published studies testing this to have been published on PubMed by now…. no luck.
• “Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve.” [2014] Wait a minute, no infection of the vagus nerve — rather the chemicals from gut bacteria impacting it instead!
•  ” an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.” [2012] – again no infection cited.
• “this action of cytokines (chemicals) can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve” [2007]
• Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome[ 1995].
• Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome.

In short, if there is an infection involved — it should have been identified by now by just sampling the tissue and papers published. Despite some sites promoting this, it appears to be a re-wrapping of old news in a new paper. For example, I see references to EBV on some of these websites — EBV re-activation has been known to be very high in the CFS population for generations (literally).

I would love to see the explanation of how an infection in the vagus nerve orchestrates different microbiome shifts. The theory of an infection is very easy to test with a mouse model, infect the vagus nerve of the mouse   and see what their but bacteria is like in 6 weeks — there is no report confirming this (and not finding it would likely not result in a report being published). IMHO, it is a failed hypothesis.

Driscoll Protocol

Also, in connection to the Vagus Nerver, I was referred to a story on http://thelowhistaminechef.com/ involving Dr. Diana Driscoll, an optometrist (eye doctor) who has published a book, “The Driscoll Theory® Newly Revised: The Cause of POTS in Ehlers-Danlos Syndrome and How to Reverse the Process” as well as a custom supplement that she sells and has patented Parasym Plus(Thiamin(vitamin B1), ACP Choline AL-carnitine, Huperzia)  (Patent, Patent).

I noticed that Dr. Driscoll ” is also a patient herself and mom to children also affected by, but now mostly recovered from these disorders and has now returned to work full time” In other words, what she advocates resulted in an improvement but not a full remission for her and her family. Her facts on symptoms are largely correct, one of her goals is to raise acetylcholine.

In reading the Patent, in her own words:

• “it was found by the present inventor that bowel disorders secondary to vascular nerve compression or damage to the preganglionic vagus nerve, eventually leads to organ dysfunction resulting in poor absorption of numerous other nutrients necessary to prevent signs and symptoms of dry eyes, dry mouth, delusions, motor dysfunctions, numbness and nystagmus.”
• ” majority of patients with these chronic syndromes resulting in such organ dysfunction are found to have numerous genetic defects“
• “”a bowel movement” was cited 7 times in each patent as an indicator as successful treatment.

The goal was a compound  “comprising a choline compound; a cholinesterase inhibitor; and Acetyl-L-Carnitine,”

For CFS/IBS/FM, I have reservations about doing directly raising acetylcholine:

• “Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients.” [2004]
• “We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition… clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia.” [2003]
  • So the a cholinesterase inhibitor valid.
• “recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism….acetylcholine (ACh).. the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects.” [2003]
• “Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.” [2016]

Statement of two models

• Driscoll theory appears to be symptom mitigation. You needs to continue taking the supplements for symptom relief. She identifies that bowel disorder is a significant factor but does nothing about it (in what I have read). She admits that neither herself nor her family members being 100%, she is able to work again.
• Microbiome model is centered on the belief that most, if not all, symptoms are caused by the bowel disorder — including vagus nerve issues.  I view that I have recovered to 100% multiple times: working as a software engineer at Microsoft, Amazon means 100% mental capacity and ability to work 60+ hr weeks under stress for long period of times.

Acetylcholine-Esterase Inhibitors

There are studies supporting that this helps  [2003], but there have not been much followup for treatment. In reviewing this on PubMed, I found some interesting studies:

• A Further Investigation of the Effects of Extremely Low Frequency Magnetic Fields on Alkaline Phosphatase and Acetylcholinesterase[2016].  – some CFS/FM/IBS are sensitive to EMF (wifi, cell phones etc) — this may be the mechanism for this sensitivity
• “Comparison of Inhibition Kinetics of Several Organophosphates, including Some Nerve Agent Surrogates, using Human Erythrocyte and Rat and Mouse Brain Acetylcholinesterase [2016]. – Organophosphates have also been implicated in CFS

A common supplement that is such an inhibitor is Huperzine A. I have tried it (i.e. purchase a bottle and took it until it was empty, with no apparent effect). It is recommended by Dr.Lapp (based on other conditions). There are no studies on PubMed of Huperzine-A with Chronic Fatigue Syndrome. Another is Galantamine, this site mentions that synergy speculated that “Stacking an acetylcholinesterase inhibitor with a racetam/choline stack may have great benefits for cognition.” — I am a strong advocate of racetam (i.e. Piracetam etc) for brain fog relief. The site goes on to warn “Side effects can occur with higher levels of acetylcholinesterase inhibitors as well as racetam nootropics.”

A 2013 article review natural AChE inhibitors. It states “. Most of the drugs currently available for the treatment of AD are AChEi: tacrine (1), donezepil (2), rivastigmine (3) and galanthamine (4), all of which have limited effectiveness and some kind of side effect [1].” They have a very long list of plants tested, I have extracted a list of the ones with significant inhibition below. I was delighted to see Boswellia was one of them, a supplement that I already recommend strongly.