Prebiotics “is a general term to refer to chemicals that induce the growth or activity of microorganisms (e.g., bacteria and fungi) that contribute to the well-being of their host.” In general, they have been shown to help the growth of one or more bacteria families deemed helpful. As readers of this column know, some commonly deemed healthy bacteria actually pushes the CFS microbiome in the wrong direction – for example Lactobacillus usually suppress E.Coli (which CFS patients are extremely low in). A prebiotic that encourages the growth of bacteria that further shifts an unhealthy microbiome in the wrong direction. “A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health.” The gotcha is whether there are benefits for an unhealthy person?

This is the gotcha that is often forgotten:

What is good for healthy individuals (whose microbiome is balanced) may be wrong for people dealing with health challenges!”

This is actually stated well by a article published this year, “Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical.” [2015]

Since prebiotics have only been know since 1995, our knowledge about this “miracle food” is limited and likely very colored by rose-colored glasses (as are all new medical wonders). The ideal study to find are those that are well done with a specific condition such as Chronic Fatigue Syndrome. Be aware that “no results” or “negative results (making it worst)” have a tendency not to get published. I could find zero clinical studies on pubmed for this condition.

• “Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude.’ [2015]

Trying to tease our the studies

Most foods contains prebiotics naturally. Even something like coffee can qualify – “induced a significant increase in the growth of Bifidobacterium spp. (P<0·05) …also induced a significant increase in the growth of the Clostridium coccoides-Eubacterium rectale group [2015]”. Prebiotics are generally extracts from foods (often from food that are not in a modern western diet).  The key to this Gordian knot may be looking at what increases biodiversity in the gut. IMHO, changing diet is better option than keeping a bad diet and taking prebiotics.

My general impression has been that every disease that influence the gut (or the reverse) has decreased biodiversity. This is the criteria that I am using.

• What increases microbial diversity:
  • barley flakes, brown rice flakes, or a mixture of both increased microbial diversity, as well as a rise in the proportion of Firmicutes and a reduction of the Bacteroidetes phylum [source]
  • “Agrarian diets high in fruit/legume fibre are associated with greater microbial diversity and a predominance of Prevotella over Bacteroides.” [2015]
  • “The low FODMAP diet was associated with higher faecal pH, similar short-chain fatty acid concentrations, greater microbial diversity .. compared with the Australian diet.” [2015] and also improves IBS.
    • FODMAP -> A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols
    • Study on levels in various foods [Oligosaccharide Profile in Fruits and Vegetables as Sources of Prebiotics and Functional Foods, 2014]
• What does NOT increase microbial diversity
  • “the overall microbial diversity was not affected by treatment with [prebiotic dietary fibers such as xylo-oligosaccharides] [2015]
  • Synbiotic Lactobacillus acidophilus NCFM and cellobiose does not affect human gut bacterial diversity but increases abundance of lactobacilli, bifidobacteria and branched-chain fatty acids: a randomized, double-blinded cross-over trial [2014].
  • “Increased pharmaceutical usage … can contribute to reduced gut microbiota stability and diversity.” [2014]
  • “Analysis of fecal microbiota and dietary intake indicated that numbers of healthy gut bacteria decreased, while numbers of unhealthy bacteria increased parallel to reductions in the intake of polysaccharides after following the Gluten Free Diet.” [2010]

Bottom Line

My perception was turned upside down by doing this research, namely:

• Gluten Free Diet does not help a shifted microbiome get back to normal. It may reduce symptoms but moves you away from getting healthy as a result!
• Prebiotics have no effect on biodiversity
• A diet low in specific prebiotic substances is likely healthiest!
  • FODMAP -> A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols

You may disagree with this — if so, please find PubMed studies that support you and post as comments.  Common alternative medicine and beliefs may be very wrong and based on belief or naive scientific reasoning.

Traumatic Brain Injury or CFS Brain Injury do not differ in recovery techniques. Dr. Daniel Amen (well known from PBS) did a SPECT scan on one of my loved ones when she had acute CFS, his reading of over 50% of her brain having abnormality in blood flow. His best opinion of what he saw was massive inflammation caused by an infection (viral or bacteria).

If you magically eliminate the infection causing CFS today, it will take months for the inflammation to subside, with recovery ongoing for many years. You may get your energy back quickly, but cognitive function will likely be slower. People who went to immediate remission from fecal transplants, found their energy jump quickly as did cognitive ability (which does not mean full recovery of prior cognitive ability — often there is a need to retraining).

First, I will give what has been documented to help/work. Then, I will give my spin from my own experiences. As I stated in my last post, mild Traumatic Brain Injury (TBI) such as far a car accident, is in general far less challenging than the CFS Brain Injury.

PubMed Findings 

Regardless of the cause, pro-active treatment can greatly reduce the long term consequences. What treatments are available?

Note: “Recent systematic literature reviews have concluded that there is minimal evidence to support any specific treatment” [2015]  “Although the long-term effects of brain damage caused by differing modes of head injury seem to appear identical in the long term (Belanger et al., 2009)” [2015]

• Hyperbaric oxygen therapy: “Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas.” [2015]
• Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.[2015]
  • ” Brain “fog” characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as “minimal cognitive impairment,” an early clinical presentation of Alzheimer’s disease (AD), and other neuropsychiatric disorders. Brain “fog” may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases.”
• “Piracetam may reduce it, as may bright blue light.”[2014]
• Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats [2014].
  • Changing trends in the use of seizure prophylaxis after traumatic brain injury: a shift from phenytoin to levetiracetam[2013].
• “Data show that treatment using dietary and parenteral zinc supplementation can reduce TBI-associated depression and improve cognitive function, specifically spatial learning and memory.” [2013]  Zinc dosage: 30-40 mg/day see this post
• “we review relevant experimental and clinical data on supplemental substances (i.e., curcuminoids, rosmarinic acid, resveratrol, acetyl-L-carnitine, and ω-3 (n-3) polyunsaturated fatty acids) that have demonstrated encouraging therapeutic effects on chronic diseases, such as Alzheimer’s disease and neurodegeneration resulting from acute adverse events, such as traumatic brain injury.” [2014]
  • “Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. ” [2013]
• ” The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine)…. [resulted in ] statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy ” [2011]
• Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients [1994].
• “The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit.” [2013]
• “Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism,chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gutB microbiome therapeutically include changes in diet, probiotics, and prebiotics.” [2014]
  • “So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where positive benefits have been reported for a number of organisms including Bifidobacterium infantis.” [2013]
  • The gut reaction to traumatic brain injury. [2015]
• “Mast cell (MC) activation disorders present with multiple symptoms including… gastrointestinal complaints, irritability, headaches, concentration/memory loss and neuropsychiatric issues.” [2014]
• Treatment of chronic fatigue with neurofeedback and self-hypnosis [2001].
• [Neuroprotective mechanisms of cannabinoids in brain ischemia and neurodegenerative disorders] [2015] – no human studies have been done.

To rephrase for the cognitively impaired reader:

• Low histamine diet (or at least a wheat free diet)
• Bifidobacterium infantis (Align) and Prescript Assist probioitcs. Note that taking random probiotics may actually make things worst!
• Items that improves oxygen delivery to the brain
  • Exercise
  • Hyperbaric oxygen therapy
  • Piracetam and other nootropics, ginkgo and vinpocetine
  • alpha-lipoic acid and n-acetyl-cysteine (NAC)
  • Anti-coagulants: Grape seed extract, heparin,
  • Niacin
  • NOTE: hypercoaguation (too thick blood) is very common in CFS (read more here and
    Dave Berg Talk #4 ) and thus there is a double advantage of taking these.

Personal Experience

The items that resulted in the greatest observed improvement for me in cognitive function within minutes (in order of precedence)

1. Piracetam (and other racetams) – up to 6 x 800 mg /day
   1. One source of supply is https://smartpowders.com/brand/smart-powders/ and  http://smartmoleculeshop.com/
2. Niacin (flushing type — often 500mg 2-3 times a day. Consult with a MD before starting)
3. Aspirin / Grape Seed Extract

Note on Racetams

Racetams can be prescription in some countries and over the counter(OTC) in others. For one CFS episode, my source for piracetam was a CFSer in the Czech republic and India (purchased on site by a friend — manufactured in Europe).  Today, I have a 3 kg jar of if in storage from when it was available on some US web sites. As often happens, because it is effective FDA reclassified it as a drug and stopped OTC sales (hence purchasing the jar when word got out of FDA’s decision). The other racetams are still available but far more expensive, usually the cheapest form is powder and make your own “00” capsules.  for example: Aniracetam 750 mg 60 capsules – $40 for 45 gm  versus $22 for 100 gm of powder.

You should make sure that you read up on each, for example this site, http://nootriment.com/aniracetam-powder/   Each one has slightly different impacts and I ordered each one to determine which had the greatest apparent impact. For me, piracetam won! There are some studies supporting this “caused significant decrease of the CF severity, which was more prominent in the MS group, while in another group it was associated with a decrease of depression severity” [2006][2007]

Adapt and don’t lament where you were

Exercising your mind without stressing the mind is ideal. CFS patients tend to be Type A ([Relationship between chronic fatigue syndrome and type A behaviour[2009]). This personality type tends to push the envelope – whether this pushing is the result of excessive parental pressure when young or because of specific bacteria in the microbiome or … is unknown.  This personality trait also results in “push and crash” cycles that often result in zero or negative progress over time.

A classic mistake in recovery is pushing beyond your actual physical and mental envelope which can often result in actual setbacks and depression over your current state. I grew up with a handicap and learnt to strongly discipline myself in order to have a continuous series of small positive successes that built instead of a serious of major failures that destroyed confidence and produced stress…  And stress is well known to cause relapse in both CFS and brain trauma.

For example, you may start with easy Sudoku and once you literally get bored with it, then increase to the next level of difficulty. I recall sitting at my computer for hours playing the same game (pre-Sudoku) for months and then I found that I suddenly had become bored with it (while other symptoms were improving) and found a slightly more challenging game.  Again, the criteria is not pushing your limits (or even trying to find them!), rather boredom, keeping in your envelope.

Return to Work Strategy

I think that giving you examples from my own experience may illustrate the need to “downgrade your expectations and slowly, safely, work upwards keeping in a safe envelope.

Example 1

1. On a triple honors program with top marks in the nation on Physics and Mathematics contests (including better scores than Bill Gates), life path was suppose to be a Ph.D. and then a Professorship somewhere.
2. Adapation:
   1. Stop working on scholarship, paid for university by becoming a store clerk and dropped honors courses so I could get my degree, a lower level goal
   2. Instead of going to Grad School, did a professional year in Education to become a High School teacher
      1. Lots of pressure not to be so foolish…
   3. After 3 years teaching, became bored and mind seem to be recovering, so started a part time MBA program
   4. Did well and changed to a more demanding M.Sc. in Commerce completed, got accepted for a Ph.D. (but opted to work a few years in business instead, again, avoiding pushing the envelope and opted for the “low road”)
   5. Eventually moved to Microsoft as an employee, fully challenged etc..

Example 2

1. Onset happened while at Microsoft (bad boss and stress scenario)
2. On disability pay and appears to be recovering
   1. Did volunteer/unpaid work for local company. Started at 2hr/day and slowly worked upwards over several months to a full 8 hrs.
3. Took my time to find the “right job” – the job was one that required little new learning and heavily use of skills from prior to CFS onset. Goal was to minimize the need for learning with a recovering mind. Worked there for 3 years (during which my position went from Software Architect to Principle Software Architect to Engineering – Manager). I was offer the job of President, which I turned down because it was not a “safe choice”, it was stretching my proven limits — this is a no-no

Example 3

1. Onset happened while at Amazon (flu and “the amazon culture” was the triggering event)
2. On recovery, again looked for a job that required little new learning and heavily use of skills from prior.

Some example Strategies

• Say you were a biologist or chemist, instead of stepping back into the same position, find work as a laboratory assistant (yes, you may be overqualified, but the brain injury is a significant factor).
• If you were in sales management, perhaps consider returning to being a sales associate.
• If you have a master’s or a bachelor’s degree, consider becoming a substitute teacher, doing single days of work at different locations allows you to determine your limits in a safer way
• Do not set yourself to become embittered by setting your threshold for a job unrealistically high. You may have a Ph.D. but working at MacDonald will do you a lot more good than not working.
  • I know CFSers with a lot of secondary issues, back problems, headaches, noise sensitivity etc who have adapted to their restrictions and are building a personally rewarding employment opportunity.  “Adapt or become embittered!”

Yes — it is unfortunate that you cannot resume where you were! But really — would you prefer resuming with the same position and then do a disastrous job doing it which will undermine your confidence and possibly result in a very bad reference for your next job????

Once you have a job, if you find the job has challenges, see if your MD will give you an Americans With Disability letter. In general, most firms (except Amazon) will respect it and work with you to be successful.

For interviews, have a cover story ready for your choice of going for a ‘job downgrade’ — do not mention disability (they cannot ask if you will need an accomondation). Often demands and needs of a family member can be a good cover story for why you are applying for a job below you past work history. That is 100% truthful — the family member may actually be yourself!!

Bottom Line

After Brain Trauma, you are almost like a recent immigrant from another country. You need to learn your current capabilities (realizing they will evolve/improve constantly) given your current abilities (which most people tend to deny the loss of — unfortunate), as well as getting “re-credentialed” — you have been off the job market for a while and things have moved on. You do NOT want to add the stress of an aggressive learning curve to your recovery.

Today, I will typically go for several brisk 5 mile hikes in the mountains every weekend to keep up my physical state. Piracetam, aspirin and niacin are part of my regular supplements on work days — they still result in a significant improvement of cognitive skills for the day. I often have joked, “well, I am of the hippie generation, so doing mind altering drugs is expected — just how I need to alter the mind has changed and the stuff is legal ;-)!”

Brain Injury can happen many ways. The most common is blunt force trauma, typically from a car accident, called Traumatic Brain Injury (TBI) or from a stroke . TBI and stroke is easy for most people to understand and be emphatic towards.  In general the half-life of TBI preventing employment is 2 years [reference]. The rate of recovery depends on many issues and the ability to be employed is often dependent on the ability of the person or their recovery therapist to be adaptive. I know because I have been thru the process three times!

In the case of Chronic Fatigue Syndrome, it is not the result of an one instance in time like TBI.  It is the ongoing consequence of the disease process and has some unique characteristics such as loss of brain mass. As readers may know, I have had CFS three times – each time with significant cognitive loss (1st time going from a triple 1st class honors student to barely passing my courses the following year). The last time with CFS, the SPECT scan was (mis)read as early Alzheimer’s – which “agreed” with general memory issues.  An evaluation by a subsequent neurologist who was familiar with CFS, dismissed that diagnosis because my memory issues did not match Alzheimer’s — in fact those issues have been decreasing year after year since recovery started.

In this first post, I will give the facts, what may scare some of you but should be accepted and you should move on to acting upon this. In the second post, I will give my view on recovery strategies for brain injury (with reference to literature).

Brain Injury in Chronic Fatigue Syndrome

First the bad news, the scary news — far worst than brain injury from someone that suffered an automobile accident or a fall.

• ” The results indicated abnormalities of the cerebral function in the prefrontal region, orbitofrontal region, and right temporal lobe in CFS patients  “[2017]
• ” There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis)….  Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression.  ” [2018]
• “most of the studies found gray matter (GM) volumes reduced in some brain regions in CFS”[2015]
• Patients with chronic fatigue syndrome have reduced absolute cortical blood flow [2006].
• “Most patients showed autonomic nervous system dysfunction and circadian rhythm disturbances, similar to those observed in jet lag. 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]
• “Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms.” [2014]
• “Patients with AIDS dementia complex had the largest number of defects (9.15 per patient) and healthy patients had the fewest defects (1.66 per patient). Patients with chronic fatigue syndrome and depression had similar numbers of defects per patient (6.53 and 6.43, respectively). In all groups, defects were located predominantly in the frontal and temporal lobes.” [1994]
• “CFS subjects showed less perfusion in the anterior cingulate region, the change in CFS subjects’ activation of the left anterior cingulate region during the PASAT was greater than that observed for healthy subjects.” [2003]
• Patients with chronic fatigue syndrome have reduced absolute cortical blood flow.[2006]
• ” reports of WM [white Matter] volume losses and neuroinflammation in the midbrain, together with the upregulated prefrontal myelination suggested here, are consistent with the midbrain changes being associated with impaired nerve conduction which stimulates a plastic response on the cortical side of the thalamic relay in the same circuits.”[ Evidence in chronic fatigue syndrome for severity-dependent upregulation of prefrontal myelination that is independent of anxiety and depression.[2015]
• “Neuroimaging and EEG research has documented brain dysfunction in cases of CFS. Therefore, a quantitative EEG was done, comparing her to a normative data base. This revealed excessive left frontal theta brainwave activity in an area previously implicated in SPECTresearch.” [2001]
• “Bilateral white matter atrophy is present in CFS… Right hemispheric increased FA[piecewise fractional anisotropy] may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS.” [2015]
• “Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to those in patients with depressive illness.” [2000]
• “symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.” [2014]
• ” neurocognitive testing in CFS has demonstrated deficits in speed and efficiency of information processing, attention, concentration, and working memory.” [2013]
• “many magnetic resonance imaging (MRI) studies already suggest that small discrete patchy brain stem and subcortical lesions can often be seen in CFS. Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis–in both of which conditions chronic fatigue is characteristically present.” [1997]
• ” in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake.” [1998]
• “CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal. Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients.” [1998]
• ” In the midbrain, white matter volume was observed to decrease with increasing fatigue duration. For T(1) -weighted MR and white matter volume, group × hemodynamic score interactions were detected in the brainstem [strongest in midbrain grey matter (GM)], deep prefrontal white matter (WM), the caudal basal pons and hypothalamus. A strong correlation in CFS between brainstem GM volume and pulse pressure suggested impaired cerebrovascular autoregulation.” [2011]
• Sjögren syndrome presenting with encephalopathy mimicking Creutzfeldt-Jakob disease.[2013] Sjogren Syndrome is often co-morbid with CFS
• Brainstem perfusion is impaired in chronic fatigue syndrome. [1995]
• “The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS. Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity.” [1992]
• “The BP(ND) values of (11)C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in healthy controls.” [2014] via PET Scan

Bottom Line:

Next time that someone says “CFS is your head”, do not disagree, instead haul out the above and say that they are correct, it is physical disruption of the brain!

Recently I suddenly started encountering problems with getting sleep at night. The usual suspect, change, stress, etc were not there. Last night after waking up for the 2nd time at 2:30 AM, I decided to “waterpik”(Water Flosser) my mouth followed by a hydrogen peroxide rinse. I went back to bed and slept hard until the alarms went off. Speculation: chemicals, were being produced by bacteria in the mouth, were keeping me awake.

My wife also discovered a different biological sleep aid this week, something that caused her to sleep unusually hard – bed time probiotics:

• One Mutaflor and two Prescript Assist capsules.

Again, speculation is that either the chemicals produced by bacteria that cause excessive wakefulness OR chemicals caused by killing off bacteria that cause deep sleep is the root.

We know that microbiome bacteria impacts cognitive function, so the speculation seems appropriate.

If neither of the above help with sleep, then try 2-3 “00” capsules of Neem, Haritaki or Tulsi at bedtime.