Author Archives: lassesen

Unknown's avatar lassesen 11:57 pm on March 15, 2016  

Carnitine supplement

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
Unknown's avatar lassesen 11:51 pm on March 14, 2016  

Choline Supplements

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.

Unknown's avatar lassesen 4:14 pm on March 13, 2016  

Vagus Nerve infection hypothesis and the Driscoll Theory

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

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 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.

Family and Botanical Name Type of Extract (Solvent) Plant’s Parts AChE Inhibition (%)
Amaryllidaceae
Crinum jagus MeOH Leaf 74.25 (42 µg/ml)
Anacardiaceae
Spondias mombin MeOH Root bark 64.77 (42 µg/ml)
Arecaceae
Phoenix dactylifera Hexane Seed 52.96 (300 µg/ml)
Asteraceae
Pulicaria stephanocarpa CHCl3 Leaf 61.43 (0.2 mg/ml)
Boraginaceae
Onosma bracteata MeOH Leaf 59.73 (250 µg/ml)
Burseraceae
Boswellia socotranao CHCl3 Resin 71.21 (0.2 mg/ml)
Cistaceae
Cistus laurifolius EtOH Leaf 80.07 (200 µg/ml)
Cucurbitaceae
Eureiandra balfourii MeOH Tuber 58.61 (0.2 mg/ml)
Cupressaceae
Juniperus phoenicea EtOH Leaf 53.44 (400 µg/ml)
Juniperus turbinata Phenolic Leaf 83.84 (400 µg/ml)
Euphorbiaceae
Alchornia laxiflora MeOH Stem bark 41.12 (42 µg/ml)
Cephalocroton socotranus CHCl3 Bark 51.1 (0.2 mg/ml)
Fabaceae
Genista tenera EtOAc Aerial 77.0 (70 µg/ml)
Peltophorum pterocarpum MeOH Leaf Stem bark 49.5 (42 µg/ml) 68.85 (42 µg/ml)
Guttiferaceae
Callophyllum inophyllurn MeOH Root bark 56.52 (42 µg/ml)
Lamiaceae
Cyclotrichium niveum EtOAc DCM Whole plant 83.11 (250 µg/ml) 70.82 (250 µg/ml)
Hyssopus officinials Hexane Whole plant 55.0 (400 µg/ml)
Marrubium vulgare Acetone Aerial 62.70 (25 µg/ml)
Salvia chionantha Essential oil Aerial 56.7 (500 µg/ml)
Salvia fruticosa DCM Whole plant 51.07 (100 µg/ml)
Moraceae
Dorstenia gigas CHCl3 Leaf 65.12 (0.2 mg/ml)
Orchidaceae
Orchis mascula MeOH Root 56.99 (250 µg/ml)
Papaveraceae
Corydalis intermedia MeOH H2O Whole plant Tuber Whole plant Tuber 84 (100 µg/ml) 97 (100 µg/ml) 57 (100 µg/ml) 78 (100 µg/ml)
Papaveraceae
Corydalis solidassp. laxa MeOH H2O Whole plant Tuber Whole plant Tuber 89 (100 µg/ml) 96 (100 µg/ml) 78 (100 µg/ml) 85 (100 µg/ml)
Corydalis solidassp. slivenensis MeOH H2O Whole plant Tuber Whole plant Tuber 82 (100 µg/ml) 97 (100 µg/ml) 48 (100 µg/ml) 87 (100 µg/ml)
Pinaceae
Pinus halepensis EtOH Essential oil Needle Twig 60.15 (200 µg/ml) 83.91 (200 µg/ml)
Pinus pinaster Pycnogenol Bark 63.33 (200 µg/ml)
Poaceae
Cymbopogon jawarancusa MeOH Whole plant 72.36 (250 µg/ml)
Rubiaceae
Galium odoratum Hexane Whole plant 53.1 (400 µg/ml)
Morinda lucida MeOH Leaf 40.15 (42 µg/ml)

 

Unknown's avatar lassesen 6:04 pm on March 12, 2016  

Celiac Disease, Microbiome – a different path?

Once a microbiome dysfunction happens, it can evolved into more symptoms as the bacteria shifts more. Some of these evolutions may put someone out of the CFS diagnosis into a different medical diagnosis.  Some of these diagnosis can be worst than CFS, i.e. Crohn’s disease.

A reader in Europe indicated several CFS/Celaic people in their group, so I will look at Celiac disease in this post.

Celiac Disease

“Celiac disease (CD) is a frequent chronic inflammatory enteropathy caused by gluten in genetically predisposed individuals that carry disease susceptibility genes (HLA-DQ2/8).” [2015]

At first browsing of PubMed, we see close associations just like “depression and CFS” has.

  • The Overlap between Irritable Bowel Syndrome and Non-Celiac Gluten Sensitivity: A Clinical Dilemma.[2015] ” Some patients with celiac disease may remain asymptomatic or have only mild gastrointestinal symptoms and thus may qualify for the diagnosis of IBS in the general clinical practice… While the treatment of NCGS is exclusion of gluten from the diet, some, but not all, of the patients with IBS also improve on a gluten-free diet. “
  • Chronic fatigue syndrome and non-celiac gluten sensitivity. Association or cause? [2015]  “From my point of view fibromyalgia and chronic fatigue (FM/CFS) are not defined diseases but just syndromic terms that reflect reality… The following case, treated during the preparation of this manuscript, illustrates this relationship: a 23 year old woman with 3 years since the onset of FM/CFS with severe fatigue … After one year of follow-up, after starting diet without gluten or dairy, she presented complete remission of all her symptoms, with a normal life, practicing sports and without medication. She chose not to eat triggering foodstuffs.”
  • Celiac symptoms in patients with fibromyalgia: a cross-sectional study[2015].  A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001).”
  • Fibromyalgia and chronic fatigue syndrome caused by non-celiac gluten sensitivity. [2015] “The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiacdisease or nonceliac gluten intolerance.”
  • Fatigue in adult coeliac disease. [2005] “In coeliacs, fatigue is a common finding, which ameliorates with the gluten-free diet and is strictly correlated to depression although coeliacs on a gluten-free diet showed more frequent and more severe depression symptoms than coeliacs on a normal diet.”

 Microbiome Dimension

What do we know about changes in the microbiome? We have a lot detail than with IBS..

  • ” In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients.” [2016]
  • “children following an African-style gluten-free diet for at least two years were subjected to a change of diet to an Italian-style gluten-free diet for 60 days. Significant differences were identified in the salivary microbiota and metabolome when Saharawi celiac children switched from African- to Italian-style dietary habits. An Italian-style gluten-free diet caused increases in the abundance of Granulicatella, Porphyromonas and Neisseria and decreases in Clostridium, Prevotella and Veillonella, …High concentrations of acetone and 2-butanone during treatment with the Italian-style gluten-free diet suggested metabolic dysfunction in the Saharawi celiac children.” [2015]
  • “The main differences were obtained in ecological indexes belonging to the genus Lactobacillus, with significant richness, diversity and habitability reduction in CD patients. In CD bands were categorized primarily with Streptococcus, Bacteroides and E.coli species. In HC the predominant bands were Bifidobacterium, Lactobacillus and Acinetobacter, though the Streptococcus and Bacteroides were lower.” [2015] so CD has:
    • Less Lactobacillus – ditto CFS
    • Less Bifidobacterium — ditto CFS
    • Less Acinetobacter — ditto IBS [2015]
    • More Streptococcus — ditto CFS
    • More Bacteroides — ditto IBS [2015]
    • enterobacteria tended to increase in celiac children.[2015]

Jumping to Conclusions

CD has a specific DNA SNP associated with it, FM has a series of DNA SNP associated with it. What if all of these were the same condition (a bacteria shift) — with DNA determining the symptoms/presentations?  Where as the conventional 2015 literature cites “The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers.” [2015]

If this is true, than the IBS probiotics would also apply to CFS and CD. Similarly, other aspects of treatment for the dysfunction described on this site would also apply to CD.

What about wheat free? dairy free? — as stated in the articles, it helps some — why? because it will likely starve some of the bacteria involved (remember there are MANY MANY, see this post on IBS)

Probiotics?

Far less studies, with Bifidobacterium having positive results — just like IBS.

 

 

Unknown's avatar lassesen 5:29 am on March 12, 2016  

IBS Probiotics

The following are a list of probiotics effective (i.e. improve, not necessarily cure) Irritable Bowel Syndrome according to studies on PubMed.com. IBS is co-morbid with CFS and thus they become recommended probiotics for CFS. For this I raised the criteria to studies on humans and not on mice. In general mixtures were eliminated with the exception of “unique mixtures” – Prescript Assist and VSL#3

NOTE: Probiotics do produce natural antibiotics. It is strongly recommended that the probiotics below be rotated and not taken continuously. Two weeks on one and then move to the next. Why?  We want to minimize the risk of antiibiotic resistance to the natural antibiotics produced by the probiotics.

“Overall, more than 50% of trials presented negative outcomes. The majority of the single-strain probiotictrials employing lactobacilli or Saccharomyces were negative, whereas trials employing bifidobacteria showed positive results.” Probiotic Therapy of the Irritable Bowel Syndrome: Why Is the Evidence Still Poor and What Can Be Done About It? [2015]

“because bifidobacteria concentrations have been found to be reduced in IBS compared with healthy controls, it seems reasonable, logical and safe to use prebiotics to enhance the growth of bifidobacteria and other beneficial bacteria to improve symptoms in these patients. However, based on available evidence, general use cannot be recommended in patients with IBS [2018].

Only Positive Effects

Prescript Assist – multiple species

Symbioflor 2 – E.Coli Probiotic

Mutaflor — E.Coli Nissle 1917

Clostridium butyricum probiotics

Incidental Positive

Inconclusive or negative effects

I am tough here — if there is disagreement between studies, the probiotic is dropped into the list below. One of the main reason is that only 1 in 10(100?) negative studies get published, but every positive one gets published.

Lactobacillus Plantarum

 Yakult – Lactobacillus Shirota

VSL#3 Multiple Lactobacillus, Bifidobacterium, Streptococcus

Lactobacilus GG

May be effective for children only.

Bottom Line

Lactobaccilus probiotics all show little effect (and possibly negative effect). Prescript Assist, E.Coli Probiotics and Bifidobacterium probiotics show effects (but only one strain is well reported).