A reader in Australia has had CFS for 2 years. She wishes to exclude other treatable diseases that could mimic CFS (and potentially be treatable). The Research definition of CFS states that CFS should only be given as a diagnosis AFTER excluding other possibilities. This is unfortunately not always the case. “Any unexplained abnormality detected on examination or other testing that strongly suggests an exclusionary condition needs to be resolved before attempting further classification.”

[1994 CDC] Any past or current diagnosis of:

• major depressive disorder with psychotic or melancholic features
• bipolar affective disorders
• schizophrenia of any subtype
• delusional disorders of any subtype
• dementias of any subtype
• anorexia nervosa
• or bulimia nervosa
• Alcohol or other substance abuse, occurring within 2 years of the onset of chronic fatigue and any time afterwards.

Or

• untreated hypothyroidism,
• sleep apnea,
• narcolepsy, and
• iatrogenic conditions such as side effects of medication.
• Severe obesity is defined as having a body mass index equal to or greater than 45

Or

• diagnosable illnesses may relapse or may not have completely resolved during treatment.
  • hepatitis B or C virus infection
• Brain Injury – Traumatic or by prior infection

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Other items

• Phosphate Diabetes: 10% of CFS patients had been misdiagnosed and had phosphate diabetes [1998]
• Pfisteria
  

• From British Medical Journal 2015
  • “Infectious mononucleosis antibody titer indicates past infection and fatigue could last a month or 2 at most.”
  • “post parvo virus B19 fatigue. This post viral syndrome is the easiest to spot as it always shows isolated low red cell count.”

• Young-Onset Monogenetic Parkinsonism [2011]

 

In a series of past posts, I walked thru the many pages of a OATS looking at each line:

• Organic Acids Tests (OATS) and Autism #1
• Organic Acids Tests (OATS) and Autism #2
• Organic Acid Tests (OATS) and Autism – #3
• Organic Acid Tests (OATS) and Autism #4

A reader of that page presented me with a challenging question: “Which probiotic would reduce ….. ?” I checked the US National Library of Medicine studies — nothing. I am a lateral thinker (read Edward de Bono since I was a teenager) and it occurred to me that, theoretically, we can use data from KEGG: Kyoto Encyclopedia of Genes and Genomes because they have the gene sequence of many probiotics and thus their enzymes. Enzymes are mini-factories that consumes some metabolites and produces other metabolites. There are 5200+ different compounds reported on KEGG.

Since I have all of the data in a friendly (to me) datastore, it was just a matter of constructing a few complex queries and creating some web pages. The result was this page: Probiotics to Change KEGG Compounds

In the video below, I walk thru how we use OATS result and this page. Other test results can be used. OATS happened to be inspiration for this feature.

The reader provide the following history (shortened)

Person’s Narrative

Sample BiomeSight:2021-02-24 In addition to my usual CFS symptoms I had a lot of trouble with gastritis. I was taking Slippery Elm, Marshmallow root, DGL, melatonin, magnesium, probiotic Bio.me Femme UT. I mostly avoided other supplements due to gastric issues. When the results came back I was only able to eat a few foods, so I couldn’t really follow the suggestions. I decided to wait until my stomach got better and retest.

Sample BiomeSight:2021-08-23 Taken after I’ve been on PPIs for 3 months. I haven’t been eating dairy for months which decreased B. Wadsworthia somewhat. I ate a lot of soy milk and soy yogurt. Mostly gluten-free, but eating lots of oatmeal. The combination of PPIs and yogurt made Streptococcus Thermophilus very high. The supplements at the time were melatonin, magnesium, zinc carnosine, d3 & k2, vit A, Omega 3, probiotic Bio.me Femme UT, occasional Slippery Elm to calm the stomach.

After I got results back I started taking:
– Miyarisan (Kegg AI Computed Probiotics),
– glycine (Kegg AI Computed Supplements),
– inulin, burdock root, L. Rhamnosus, L.Reuterii, almonds, oregano tea (suggestions from Targeted bacteria based on symptom Impaired memory & concentration).
I alternated modifiers so I wasn’t taking all of them all of the time.

I stopped:
– vit A and Slippery Elm (suggestions from Targeted bacteria based on symptom Impaired memory & concentration)
– yogurt (high S. Thermophilus)- oatmeal (it seemed to cause hypoglycemia. Replaced with tsampa – roasted barley flour)

Interestingly, Kegg AI Computed Supplements at level <15% reported Iron and 6 weeks later I was found to be anemic. That was an excellent prediction! I wish I would have gone and tested my iron status right away.

Sample BiomeSight:2021-11-28 Still on PPIs. Taken one month after I started taking prescription iron pills and lactulose to help with resulting constipation. Still eating soy milk daily, but no dairy, no yogurt. Taking more supplements at this point.

Analysis

Reading the history, my first question is to see if the predicted shifts from doing PPI (Proton Pump Inhibitors) is reflected between samples. Keep in mind that there are other microbiome compounders (i.e. other eating pattern changes). To this end, I’ve created a new page where you can pick a before, after and a modifier.

See Full Post on Microbiome Prescription Blog with images

What is interesting to note is that the impact diminished overtime (80 -> 65). This agrees with my base model that rotation and re-testing is essential.

We can do combinations, for example PPI and melatonin between first and second sample. We lack studies on combinations and thus have to resort to this experiential approach to see how well predictions agree with actuals.

If a substance did not cause more improvements(Agrees versus Differs), then they are possible items to drop. Remember, the suggestions are theoretical prediction looking at many hundreds of bacteria. This allows you to objectively measure whether they worked well for you! They will not work for every one because of differences in DNA, diet, gender, age etc. I spot checked items like Slippery Elm (46.8 Agrees, 27 Differs), Miyarisan (KEGG Suggestion) (40.8 Agrees, 15 Differs) and was pleased with the results.

Looking at the next Step

Above, we (to my delight) verify that the suggestions are causing changes in the predicted direction for this person (based on their microbiome samples). Looking at predicting symptoms, we had 72% correct for the top 11 items ( So where do we go from here? Remember, the goal is to focus on the bacteria that likely contributed the most to the dysfunction (often high ones)

• From KEGG, the best probiotic is Sun Wave Pharma/Bio Sun Instant, if it is available. It has several species suggested in it.
• Looking at KEGG Products out of range — 7 were too low and 190 were too high. We are looking at an overproduction scenario.

I looked thru the predicted symptoms bacteria and there were a lot of secondary matches(shown with a # but very few direct matches. When we moved on to KM outliers, we had 25 items listed — 2 families and 5 genus with these items of considerable note — both for high percentile and high numbers:

• (family) Oscillospiraceae – 99.8%ile -18%
• (genus) Streptococcus – 98%ile – 4.2%
• (genus) Phocaeicola – 99%ile – 3.6%

So I did a hand picked with just these more extreme values. I tossed in everything we had. No prescription items showed up on the to take, but many (and a few b-vitamins) showed up on the to avoid list.

In terms of typical ME/CFS, we found only two matches, both two high:  Bacteroides ovatus and Streptococcus. In terms of this small subset — only one item was above 0.29 — Human milk oligosaccharides (prebiotic, Holigos, Stachyose) with iron and B-12 being on the to take list.

We also note that the Unhealth Bacteria page, was full of Streptococcus

I tossed all of these into our hand-picked list and ask for new suggestions — the suggestions did not change expect for minor shifts of confidence.

Bottom Line

Two probiotics:  lactobacillus plantarum (probiotics) and the mixture Sun Wave Pharma/Bio Sun Instant. I see the recommendation leads to the same type of breakfast that is regular for me: Barley/Oats with inulin and wheat bran. For all of the items, make sure you check the dosage links (where available)

I had cholesterol issues with ME/CFS flares in the past. My last labs done 3 months ago — physician was very pleased with my cholesterol – pretty much ideal. This is confirmed in studies for a subset.

Many of the pathways and metabolites that were abnormal in CFS are also known to be features of dauer, a well-studied, long-lived survival and persistence state triggered by environmental stress (35, 36) (Table 5). Interestingly, we found that the direction of CFS abnormalities was opposite to metabolic syndrome (37) and opposite to the metabolic response to infection, inflammation, or environmental stress that has been called the CDR (7). For example, cholesterol, phospholipid, sphingolipid, and purine metabolism are all decreased in CFS and dauer but are increased in metabolic syndrome and the stereotyped CDR (Table 5). These facts suggest that CFS is an evolutionarily conserved, genetically regulated, hypometabolic state similar to dauer that permits survival and persistence under conditions of environmental stress but at the cost of severely curtailed function and quality of life.

Metabolic features of chronic fatigue syndrome [2016] A response is here

Remember that cholesterol issues are because of the ratio of good and bad cholesterol; not total cholesterol. This is shown in this study

The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol.

Lipid and protein oxidation in female patients with chronic fatigue syndrome [2012] Higher LDL, Lower HDL, Higher Triglycerides, Lower total Cholesterol .

What Can you do?

My opinion is that the root cause is a static microbiome dysfunction – and thus correcting the microbiome is the ideal long term approach (addressing the cause and not the symptoms). According to the US National Library of Medicine studies:

• Jerusalem Artichoke (and by inference, inulin) [2020]
• Dill [2021]
• Fenugreek [2020]
• Whey protein [2020]
• Beta glucan (Barley and Oats) [2021]
• L-Carnitine Supplementation [2019]
• Black Cumin Seed – Nigella sativa [2020]
• Spirulina (blue-green algae) [2019] [2016]
• Vitamin D [2019] [2017]
• Turmeric and Curcuminoids [2019] [2017]
• Tulsi (Holy Basil) [2012] [2010]
• Sweet Potato ( Ipomoea batatas) [2021] [2021]
• Beans (Navy,black, pinto, kidney) – Canned Beans [2021]
• Soy protein(30+ grams/day) [2011] [2007]
• TWO apples per day [2020]
  • Warning: WHOLE APPLES, not juice “Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers” [2013]
• Only improves LDL – thus improves the ratio
  • α-linolenic acid
  • Grape Seed Extract (resveratrol) [2020]
  • Canola Oil [2018] Lowers LDL only (compared to sunflower oil),
    • No Olive Oil ” Also OO consumption reduced …significantly less than other plant oils.” [2019]
• Avoids
  • Avoid Eggs [2017] – One per day is acceptable [2020] – i.e. does not increase further.
  • Cinnamon [2021]
• No Impact (or not statistically/clinically significant)
  • Selenium [2017]
  • l-arginine [2020]
  • Folic Acid [2021] [2019]
  • Pomegranate [2017]
  • Blueberry [2021]

Please note what Apples demonstrated above — avoid D contains A and thus D must have the same effect. In general, the “raw natural form” is preferred over any processed form

Name of herb	Biological effects
Basil	Lowering LDL and total cholesterol, increase of HDL
Blueberry	Lowering triglyceride and LDL levels
Celery	Decreasing serum triglyceride, total cholesterol, LDL-C and hepatic triglyceride
Dandelion	Decreasing serum triglyceride, total cholesterol, LDL-C and increasing HDL-C
Dill	Decreasing serum triglyceride
Eugenol	Decreasing serum triglyceride, total cholesterol, LDL-C and increasing HDL-C
Evening primrose oil	Decreasing serum triglyceride, total cholesterol
Fenugreek	Decreasing serum triglyceride, total cholesterol, HDL-C
Ginger	Decreasing serum LDL-C and increasing HDL-C
Ginseng	Decreasing serum triglyceride, total cholesterol, LDL-C and increasing HDL-C
Grape	Lowering oxidized LDL and elevate HDL-C level
Green tea	Suppresses adiposity and affects the expression of lipid metabolism genes
Nigella	Decrease in triglyceride and increase in HDL-C
Psyllium	Decrease in LDL

Bottom Line

What strikes me about the above items is that they are often the same items suggested by the artificial intelligence algorithms on Microbiome Prescription for people with ME/CFS who have done a 16s Microbiome sample and uploaded it there.

A reader asked me to put together a list of test that could/should be done. I divide the tests into two categories:

• Actionable — the results lead immediately to an accepted treatment with high possibility of success
• Informational — this shows that there is a problem, there may be treatment of a sort – typically symptom mitigations (i.e. prescription painkillers — which hides the pain, not remove the source of it)

Actionable

These tests may result in actions. In some cases, we work the system to get a desired action.

• Lyme Disease — often a false positive will result, but this can be used to justify a minocycline prescription.
  • Testing for mycoplasma — again, to justify a minocycline prescription.
• HHV-6, EBV, CMV — suitable antivirals [2016] See this list of virus to test for
• Coagulation Panel — see A quick revisit to Coagulation Testing for ME/CFS
• Vitamin D — usually low to very low, you want to raise it to the top of the normal range
  • See Vitamin 25D and 1,25D measure – one reduces symptoms and one indicates CFS state
• All of the usual vitamin and mineral levels. You want to be at least at the middle of the normal range for all of them
• 16s Microbiome Test

Informational

These tests are ones that I would not pay for out of pocket. They do not help move you to remission

• Vitamin 1,25D – this will often be very high — characteristic, not directly treatable (see Vitamin D above)
• TH1 and TH2, see TH1 / TH2 ratio and Probiotics
• From my English book draft, I list the following items as Lab Manifestations (download the book for citations and more information):
  • Aldosterone
  • CD4/CD8 Ratio
  • Choline
  • Cortisol
  • Cyclo-oxygenase-2
  • Cytokines
  • C-Reactive Protein
  • Galantamine
  • Glutamine
  • Inducible NO synthase
  • Lysozyme
  • N-acetyl cysteine
  • Natural Killer (NK) Cell Subsets
  • NFkappabeta
  • Neopterin
  • Norepinephrine
  • Plasma Osmolality
  • Plasma Renin
  • RNase-L
  • Red Blood Count
  • Transforming Growth Factor – Beta
  • Brain Scans:
    • Magnetic Resonance Imaging
    • Positron emission tomography
    • Transcranial Doppler Sonography
    • SPECT
      

Bottom Line

Download the book above, every page is loaded with references like shown below