https://www.amazon.com/dp/B07GBFJLXM/

See https://cfsremission.wordpress.com/2018/08/02/an-awesome-clinical-trial-for-ibs-folks/

This is a review of recent studies recorded on PubMed. The focus is on new information – so studies reporting prior information will rarely be mentioned.

Fibromyalgia

• “The Food and Drug Administration (FDA) has recently included a black box warning on fibromyalgia like symptoms with fluoroquinolones … The risk of fibromyalgia with FQs is similar to that with amoxicillin and azithromycin.” [2018]
  • Comment: Hints that fibromyalgia is a microbiome dysfunction with a similar shift as seen with the above antibiotics.
• Intestinal dysbiosis and hormonal neuroendocrine secretion in the fibromyalgic patient: Relationship and correlations.[2018]
• Is Fibromyalgia Risk Higher Among Male and Young Inflammatory Bowel Disease Patients? Evidence from a Taiwan Cohort of One Million [2018].
  • the IBD patients had a greater FM risk
• Gray Matter Changes Following Cognitive Behavioral Therapy for Patients With Comorbid Fibromyalgia and Insomnia: A Pilot Study. [2018]
  • “Our pilot study presents novel evidence suggesting that CBT-I may slow or reverse cortical gray matter atrophy in patients with fibromyalgia and insomnia.”
  • Reduction of gray matter is also seen with CFS, see this post. So we also see this with Fibromyalia.
  • Cerebral magnetic resonance changes associated with fibromyalgia syndrome. [2017]
    • “Modifications in gray and white matter volume, as well as in levels of N-acetylaspartate, choline or glutamate, among other metabolites, have been observed in the hippocampus, insula, prefrontal and cingular cortex. “
  • Gray matter abnormalities associated with fibromyalgia: A meta-analysis of voxel-based morphometric studies. [2016]
  • Reduced selective learning in patients with fibromyalgia vs healthy controls. [2018]
  • Cognitive Impairment in Fibromyalgia: A Meta-Analysis of Case-Control Studies [2018].
    • Cognitive impairment across different cognitive domains was found in individuals with fibromyalgia compared with healthy controls.
• Effects of vitamin D optimization on quality of life of patients with fibromyalgia: A randomized controlled trial [2018].
  • “This study suggests that vitamin D supplementation has significant therapeutic benefits in the management of FMS, especially in pain reduction of patients with fibromyalgia. According to our results, a combination of vitamin D supplements and a conventional antidepressant, when given to vitamin D-deficient fibromyalgia patients, could significantly improve both physical and psychological symptoms.”
• A Pilot Randomized Controlled Trial to Explore Cognitive and Emotional Effects of Probiotics inFibromyalgia[2018].
  • Our results indicated that probiotics improved impulsivity and decision-making in these patients.
  • “Lactobacillus Rhamnosus GG^®, Lactobacillus Casei, Acidophilus, and Bifidobacterium Bifidus.”
  • Past studies suggest that Lactobacillus Casei Shirota (Yakult) may be the most significant one.
• Low-grade chronic inflammation mediated by mast cells in fibromyalgia: role of IL-37. [2018]
• Fibromyalgia and Risk of Dementia-A Nationwide, Population-Based, Cohort Study [2018].
  • “The study subjects with fibromyalgia had a 2.77-fold risk of dementia in comparison to the control group.”
• Systematic analysis of the cerebrospinal fluid proteome of fibromyalgia patients [2018].
  • “Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.”
• Evidence-Based Non-Pharmacological Therapies for Fibromyalgia. [2018]
  • “No particular diet is found to have a meaningful impact in FM”
  • “Current literature does not support the routine use of acupuncture for improving pain or quality of life in FM; however, given its benign side effect profile, it should not be discouraged”

Bottom Line

We continue to lack any significant studies on microbiome shifts for FM. A microbiome dysbiosis model fits well — including the increased risk of progression into dementia (which have greater dysbiosis). L. Casei and Vitamin D are both known modifiers of the microbiome.

This is another one of a series of posts dealing with various conditions that appear to be microbiome related. My first posts dealt with Alzheimer’s Disease, ALS and Parkinson’s Disease. Additional posts are listed here. My personal suspicion is that a significant catalyst (if not actual cause) is the lost of microbiome as we age. For all of these conditions, it appears microbiome correction moderates the condition.

The Light Bulb Event

Almost a decade ago, I had a relapse of a condition that I had before and was sent for a SPECT scan. The radiologist suggested that it may be early onset Alzheimer’s. I was having problems with memory then, especially retaining recent memories. In 2017, for the same condition, a patient died and when their brain was examined, this study found

“Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to Alzheimer’s disease plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia. “

For myself, I went into remission. Memory and other issues faded — I am not 100% as strong in some cognitive aspects that I was prior, but to most people they cannot detect the remaining issues.

The condition that I had was successfully treated using a protocol that altered the microbiome. What if this was true for other similar conditions — especially the untreatable ones? Recent literature appears to support this (this is only a fraction of 2017 and 2018 studies)

• Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model. [2018]
• Gut microbiome and pediatric multiple sclerosis. [2018]
• An introduction to the microbiome and MS. [2018]
• Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis. [2018]

CSF Proteins Dimension

A 2011 Study found that Cerebrospinal Fluid Proteomes were different for my condition, a normal population and PTSD. These CFP’s are also heavily studied with MS   “Statistical analysis evidenced different levels on 23 proteins: 8 proteins showed lower levels in multiple sclerosis patients with respect to controls”[2018].

• Decreased Neuro-Axonal Proteins in CSF at First Attack of Suspected Multiple Sclerosis[2017].
• Exosomal proteome analysis of cerebrospinal fluid detects biosignatures of neuromyelitis optica and multiple sclerosis[2016].
• Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis[2016].

Working Hypothesis

My working hypothesis is that these CSF proteins are due to microbiome disruption. This disruption may not be a magic bacteria that causes it, but due to undersupply or oversupply of metabolites causing epigenetic changes in the bacteria resulting in these new proteins.  With MS there are a large number reported (see image below)

Hypothesis Tests

The hypothesis implies that there would distinctive shifts in bacteria seen with MS. What does the literature say? I actually listed many studies a year ago in this post, Multiple Sclerosis and microbiome. Remember a change of diet means a change of the microbiome.

I have added a few more recent studies below.

• Is there an effect of dietary intake on MS-related fatigue? – A systematic literature review.[2018]
  • “Dietary intake holds the potential to lower MS-related fatigue, but solid conclusions are not possible based on the existing evidence. Sparse evidence points towards an effect of adequate magnesium and folate intake and a trend for decreased fatigue.”
• “Several individual dietary components and patterns demonstrate potential for significant impact in MS. Definitive answers regarding the ability of diet to act as a disease modifier in MS will ultimately require large-scale clinical trials.” [2018]
• “There was a decrease in numbers of Escherichia coli with normal enzymatic activity, which was replaced by atypical forms of E. coli, Enterobacter spp. and fungi of the genus Candida, and, during treatment with glatiramer acetate, by atypical forms of E. coli, Proteus spp., Parvimonas micra. These differences indicate the effect of the therapy on the intestinal microbiota composition.” [2018]
• “Patients with multiple sclerosis and controls showed differences in the proportion of Euryarchaeota, Firmicutes, Proteobacteria, Actinobacteria, and Lentisphaerae phyla and in 17 bacterial species” [2018]
• A probiotic modulates the microbiome and immunity in multiple sclerosis. [2018]
• Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model. [2018]

Bottom Line

If you are a carer for someone with MS, you may wish to get a 16S analysis done ( for example uBiome.com – < $100) and upload the results to http://microbiomeprescription.com/. The suggestions there are based on hundreds of studies of what shifts different members of the microbiome. It’s a free site and the information is not available easily any wherelse.

An example of getting suggestions is shown in this post.

I have updated the MS Microbiome template on that site,  and added it as a symptom (Official Diagnosis). The number of bacteria changes reported is very large.

Look at the suggestions generated and discuss them with your treating physician.

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

This is the third of a series of posts dealing with various forms of cognitive impairment that are often age related. My first posts dealt with Alzheimer’s Disease and Parkinson’s Disease. My personal suspicion is that a significant catalyst (if not actual cause) is the lost of microbiome as we age.

The Light Bulb Event

Almost a decade ago, I had a relapse of a condition that I had before and was sent for a SPECT scan. The radiologist suggested that it may be early onset Alzheimer’s. I was having problems with memory then, especially retaining recent memories. In 2017, for the same condition, a patient died and when their brain was examined, this study found

“Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to Alzheimer’s disease plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia. “

For myself, I went into remission. Memory and other issues faded — I am not 100% as strong in some cognitive aspects that I was prior, but to most people they cannot detect the remaining issues.

The condition that I had was successfully treated using a protocol that altered the microbiome. What if this was true for other similar conditions — especially the untreatable ones? Recent literature appears to support this.

• “More recently, microbial dysbiosis has been associated with a number of brain pathologies, including autism spectrum disorder, Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), suggesting a direct or indirect communication between intestinal bacteria and the central nervous system (CNS). ” [2018]
• “Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. ” [2018]
• “Here we present evidence that intestinal dysfunction and dysbiosis may actively contribute to ALS pathophysiology.” [2017]

CSF Proteins Dimension

A 2011 Study found that Cerebrospinal Fluid Proteomes were different for my condition, a normal population and PTSD. These CFP’s are also heavily studied with ALS ( 2015 Study) ” Ten proteins were differently regulated in ALS CSF compared to controls in at least 2 studies. ” [2017]  – both have novel proteins (i.e. proteins not seen in a healthy population). “We identified significant differences in the CSF proteomebetween living and post mortem ALS subjects, as well as living and post mortem control subjects. We also noted differences in the CSF proteome of ALS subjects that have exhibited symptoms for varying lengths of time and between ALS and Alzheimer’s Disease subjects at end-stage of disease.” [2007]

Working Hypothesis

My working hypothesis is that these CSF proteins are due to microbiome disruption. This disruption may not be a magic bacteria that causes it, but due to undersupply or oversupply of metabolites causing epigenetic changes in the bacteria resulting in these new proteins. Unlike both Parkinson’s Disease and Alzheimer’s disease, I could not find any studies of ALS and Bacteroides fragilis with humans. But with ALS mice (G93A), we see that in studies. 

• “When stressed, overpopulated or pathogenically stimulated, B. fragilis releases a remarkably complex array of endotoxins and exotoxins (such as fagilysin), lipooligosaccahrides (LOS), lipopolysaccharide (LPS), including an extremely proinflammatory B. fragilis LPS (BF-LPS), microRNA-like sncRNA, and a wide variety of bacterial-derived amyloids (9–11, 56, 57, 64–66). ” [2018]

You may wish to read  my Reducing bacteroides fragilis

Hypothesis Tests

The hypothesis implies that there would distinctive shifts in bacteria seen with AD. What does the literature say?

• “In a small study of ALS patients and healthy controls, investigators also found decreased levels of butyrate-producing bacteria. ” [2018]
• “The comparison between ALS subjects and healthy group revealed a variation in the intestinal microbial composition with a higher abundance of E. coli and enterobacteria and a low abundance of total yeast in patients. ” [2018]
• “In mice fed with butyrate, intestinal microbial homeostasis was restored, gut integrity was improved, and life span was prolonged compared with those in control mice.” [2017]
• “These changes were associated with a shifted profile of the intestinal microbiome, including reduced levels of Butyrivibrio Fibrisolvens, Escherichia coli, and Fermicus, in G93A mice. The relative abundance of bacteria was shifted in G93A mice compared to wild-type mice. Principal coordinate analysis indicated a difference in fecal microbial communities between ALS and wild-type mice. ” [2015]
• “the top 10 microorganism populations were analyzed at genus level, and average ratios f Bacteroides, Faecalibacterium, Anaerostipes, Prevotella, Escherichia, and Lachnospira between groups A and H were 0.78, 2.18, 3.41, 0.35, 0.79, and 13.07 (Figure ​Figure33). Furthermore, supervised comparisons by LEfSE (LDA > 4.0) were performed to find the significant changed bacteria, and the relative richness of Firmicutes at phylum level, Clostridia at class level, Clostridiales at order level, Lachnospiraceae and Family XIII at family  level, Oscillibacter, Anaerostipes and Lachnospiraceae at genus level in group H were significant higher than that in group A, while Bacteroidetes at phylum level, Bacteroidia at class level, Bacteroidales at order level and Dorea at genus level were significant higher in group A” H:Health A: ALS [2016]
• “The present study suggested that higher intake of fat and protein, particularly from meat at early stage of the disease, could prolong the survival of ALS patients. ” [2018] This modifies the microbiome, see this summary.
• “A large portion of patients with ALS exhibited poor dietary intake and changes in body zinc status. The zinc deficiency found in half of the ALS patients may contribute to a worsened prognosis and should be the target of nutritional intervention that aims to correct this deficiency.” [2017] This modifies the microbiome, see this summary
• Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis. [2016]
• ” In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT.” [2016] l-serine modifies gut bacteria.

Bottom Line

If you are a carer for someone with amyotrophic lateral sclerosis, you may wish to get a 16S analysis done ( for example uBiome.com – < $100) and upload the results to http://microbiomeprescription.com/. The suggestions there are based on hundreds of studies of what shifts different members of the microbiome. It’s a free site and the information is not available easily any wherelse.

An example of getting suggestions is shown in this post.

I have updated the ALS Microbiome template on that site, i.e.

Look at the suggestions and discuss them with your treating physician.

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

A reader sent me an interesting email that interested me greatly about her daughter. Some extracts

“confined to her bed or at least her house with CFS for 5 -7 years. We’ve been following your suggestions as best we can, given my goofiness about science, and we’ve had some modest success, but in the last three weeks she began to get stirrings of energy. Her doctor…has had great success with other non-CFS patients  using HCG, which here …  is fashionable, along with a diet, for weight loss. … He talked her into trying HCG 3 weeks ago  (without the diet- she’s on a Mediterranean diet as you recommend), first on 2 doses of .4  of 125 iu  a day, which seemed to achieve nothing, then 10 about days ago, he increased it to 2 doses of 150iu a day. Within 3 days of that, she unexpectedly got out of the house at 6AM to go the airport to welcome a friend home, then stayed up all day travelling (though not driving) 130 km by car and was still awake and bubbly at 9 pm. Only a little delayed exhaustion and rattiness the next day- usually after this she’d expect to be laid out for a week or more with slurred speech etc The next two days she was on the go…. A low energy three days followed – but today as I write she’s out and about finding out what the shops look like these days!   She’s begun to think about what she’d like to do in the world!”

What do we know about hCG beyond this single report?

• Potential Therapy for Neisseria Gonorrhoeae Infections With Human Chorionic Gonadotropin[2015].– has some antibiotic characteristics
• Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice [2007].
• “Human chorionic gonadotropin (hCG) and the other human glycoprotein hormones (luteinizing hormone [hLH], follicle stimulating hormone [hFSH], and thyroid stimulating hormone [hTSH]) are biochemically very similar.. an hCG-like material was produced by a bacteria they called Progenitor cryptocides…. epitopes reacting with hCG polyclonal antibodies were present on several strains of bacteria including: Staphylococcus (ATCC 19433, 27848), Enterococci coli (ATCC 25922), and Pseudomonas maltophilia (ATCC 13637)….Pseudomonas maltophilia possessed an hCG/hLH binding site  [1992]
• SelfHacked reports impairment of working memory, increased cancer risk, and increased anxiety (with references)
• Unusual cause of profound weight loss in a young woman.[2016]– cause was high hCG
• “The human chorionic gonadotropin or “hCG diet” is such a diet, which after half a century still has no evidence to support its efficacy; …based on current data, these may do more harm than good.” [2016]
• [Serious complications to a weight loss programme with HCG] [2014].
  • thrombosis and pregnant while on pill!
• “Recombinant human chorionic gonadotropin (hCG) is commonly misused as a weight reducing or performance enhancing agent but is associated with increased risk of thromboembolic events.” [2015]
• First manic episode associated with use of human chorionic gonadotropin for obesity: a case report[2014].
• “The HCG diet has very few efficacy studies and no significant safety studies associated with its use. Six relevant studies were identified for assessment of efficacy, and only 1 was associated with a significant weight reduction in the HCG diet study population. All of these studies evaluated the use of the HCG diet via injections of the hormone and significant calorie restriction, which is known as the Simeons method. Currently marketed HCG products include sublingual drops, lozenges, and pellets, but none of these methods has an evidence-based efficacy and safety standard.” [2013]
• An unfortunate resurgence of human chorionic gonadotropin use for weight loss [2012].
• “Reported acute adverse effects include mild hypotension, hypoglycemia, constipation, and fatigue [23]. There is also a theoretical concern of increased thrombosis risk with IM injections of HCG [24]. However, there has been a paucity of evidence for this dietary agent with multiple studies showing that weight loss was generally related to diet restriction as opposed to HCG injections [23, 25, 26].” [2012]

Bottom Line

The risk factors for continued use is high. I am pleased for this patient’s mother to see the change that occured, but there is too much risk and too little basis to even suggest it as an experiment for others. Some of the adverse effects (hypotension, hypoglycemia, constipation, fatigue) hints that it does cause alteration of the microbiome — but there are no studies on what the alterations are.

I would be inclined to discontinue use and see what the consequences are (it may have done the essential work and addition dosages may not have benefit — even for maintaining).

NOT RECOMMENDED

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.