Melatonin – what do we know?

Melatonin has often been mentioned in my posts, without a deep dive into it.

Melatonin, also known as N-acetyl-5-methoxy tryptamine,[1] is a hormone that is produced by the pineal gland in animals and regulates sleep and wakefulness” [Wikipedia]

The more likely cause of sleep disorders with CFS/FM/IBS is hypoxia (low oxygen) which is known to cause severe sleep problems. Melatonin can help with that, but other oxygen delivery items should be considered too.

On the flip side, there some some bacteria that are associated with a lack of sleep: Partial Sleep Deprivation. On DataPunk.Net we read:

ENHANCES: 

INHIBITS: 

In other words, it contributes to a shift of the firmicutes/bacteroidetes ratio.

  • ” in particular through [Melatonin] ability to decrease the Firmicutes-to-Bacteroidetes ratio and increase the abundance of mucin-degrading bacteria Akkermansia, which is associated with healthy mucosa. ” [2017] – Checking Akkermansia levels first (most are low, but a few are high).

 

Bottom Line

If someone has a high firmicutes/bacteroidetes ratio (i.e.  firmicutes > 1.2x and /or bacteroidetes < .8x) then melatonin is a reasonable supplement, especially if there is overgrowth of  Coriobacteriaceae or Erysipelotrichaceae.  This applies to a subset of CFS patients.

Example:

f

On the Family Level

f2

The dosage is unclear. The literature reports: “0.1 mg to 50 mg/kg “, so for 100 lb individual:

  • 4.5 mg/day to
  • 2 gram/day

“For trouble falling asleep: 0.3 to 5 mg of melatonin daily for up to 9 months has been used. For sleeping problems in people with sleep-wake cycle disturbances: 2 mg to 12 mg taken at bedtime for up to 4 weeks has been used.” [WebMD]

Poison Control reports:

pc

“307 articles were elicited and 9 were related to Melatonin adverse effects. The range of MLT dose involved in the adverse reactions oscillated between 1 mg and 36 mg. The adverse reactions were: one patient with autoimmune hepatitis, one case of confusion due to MLT overdose, one case of optic neuropathy, four subjects with fragmented sleep, one psychotic episode, one case of nistagmus, four cases of seizures, one case of headache and two cases of skin eruptions.” [2001]

As always, consult with your medical professional before starting or altering your supplements.

 

Review of Drs. Naviaux and Davis and Suramin Work

A reader forwarded me a transcript of a conversation with Dr. Naviaux [Sep 13, 2017]. There are many points of interest raised so I thought that I would do a review.

For background on the Drs, see these MEpedia links

What is Suramin?

Suramin is a treatment for African sleeping sickness and river blindness. It is being tested for Zika virus.

What is Purinergic Sugnalling?

” form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP.” [wikipedia]

What is adenosine is a mononucleoside consisting of adenine and D-ribose.[source]

Comments on Transcript

“A major misconception in medicine is that diseases that are “caused by different triggers are different diseases”. I believe this is wrong. The vast majority of chronic diseases are caused by the body’s response to stress or injury, and not the initial injury itself. In other words, over half of all chronic disease is caused by blocks in the healing process caused
by pathological persistence of the cell danger response (CDR). This is a categorically different way of thinking. It is different from the way doctors are trained to think about treating “acute” diseases like a strep infection, a broken leg, or a heart attack. “Chronic” disease needs to be analyzed and treated in a completely different way.”

  • absolutely agreed, for one class of these diseases it is the persistence of a microbiome dysfunction which presents as a metabolic disorder with metabolic abnormalities. Why — the microbiome is the producer of many metabolites.

“The most important medical decision is to determine:

  • if the person has an active infection or not. If yes, this must be treated.
  • If there is not an active infection, then we also need to determine if they have a household or occupational exposure to toxins that is ongoing.
  • If the answer to both investigations is “no”, then the patients would be eligible for the first pilot study.
  • Since our hypothesis is that antipurinergic therapy with suramin will treat the root problem of ME/CFS that is common to all patients, then you could say that the hypothesis we are testing in the first small pilot study of 10 patients, is that purinergic signaling abnormalities are common to ALL patients with ME/CFS, regardless of any “subset” they might belong to.”

Absolutely agreed for the first steps — the key is confirms actual infections with reliable tests (most Lyme tests do not meet that criteria); the second item should include oral/dental issues.

Bacteria Aspect

D-Ribose is produced by Bacillus subtilis which according to DataPunk, clusters with (seen with), Lactococcus lactis, Bacillus clausii, Lactobacillys plantarum and others. The bacillus genus also produces: Norepinephrine, Dopamine and Vitamin B12

Adenine (once known as Vitamin B4) is produced by E.Coli [1975]

In short: purinergic signaling abnormalities may be associated with microbiome changes.

The cost Aspects of doing CFS Studies..

“I estimate the CFS1 study of N = 10 patients will cost about $400,000…. so the cost of the clinical trials has nothing to do with the cost of the drug. Typically, it takes 15-30 people
on the clinical investigation team at each medical center to conduct a Phase III study. The main cost of the clinical trial is the salaries of the staff…the total cost of suramin drug development, from Phase I/II to Phase III trial is $20-$30 million.

What do we know about how Suramin impacts the microbiome?

Bottom Line

One of my frequent quotes is “They got the treatment right, but the theory behind may be incorrect”.  The drug, suramin, that they are wishing to test based on their hypothesis/theory does not exclude the hypothesis of a persistence microbiome dysfunction if they are successful. While information is sparse on the microbiome impact of suramin, the fact that it impacts candida indicates that it very capable of microbiome changes.

 

 

 

 

 

Beware nullifying probiotics by other “good stuff”

To illustrate the importance of being aware of interactions (which unfortunately can require retention levels above many CFS cognitive levels 😦 ) Consider the following:

A reader wrote this morning:

” The doctor has just prescribed mutaflor and ampicillin.”

We would love to believe that MDs, NDs, etc have complete understanding.

The Reality

I went to Mutaflor site and read:

“Antibiotic sensitivity of E. coli strain Nissle 1917

As a bacterial isolate from the pre-antibiotic era, E. coli strain Nissle 1917 (Mutaflor) is sensitive to all antibiotics  which are predominately directed against Gram-negative bacteria, e. g. coli bacteria.

A certain loss of ­Mutaflor-efficacy must be taken into account. Nevertheless, a protective ­Mutaflor-therapy should be initiated in addition to antibiotic therapy.

– Amikacin, [aminoglycoside]
— Amoxicillin/Clavulanic acid, [penicillin group of beta-lactam antibiotics]
— Ampicillin [penicillin group of beta-lactam antibiotics]
— Azlocillin [acylampicillin]
– Cefaclor [cephalosporin]
— Cefazolin [cephalosporin]
— Cefoperazone [cephalosporin]
— Cefotaxime [cephalosporin]
— Ceftriaxone [cephalosporin]
— Cephalotin [cephalosporin]
–Chloramphenicol [Amphenicol]
–Ciprofloxacin [quinolone]
– Doxycycline [tetracycline]
– Gentamicin [aminoglycoside]
– Latamoxef [penicillin beta-lactam]
– Mezlocilin [penicillin beta-lactam]
– Nitrofurantoin [macrolide]
— Norfloxacin [quinolone]
– Pipemidic acid [fluoroquinolones],
— Piperacillin [penicillin]
– Tetracycline [tetracycline],
— Ticarcillin [carboxypenicillin],
– Tobramycin [ aminoglycoside]
– Trimethoprim [Folic acid inhibitor]
– Sulfamethoxazole [sulfonamide]

Combination with antibiotics – natural antibiotic resistance of E. coli strain Nissle 1917

Mutaflor is not sensitive to antibiotics which are predominately directed against Gram-positive bacteria. That is why EcN may be combined with these ­antibiotics.

– Cefsulodin, Clindamycin [lincosamide]
– Erythromycin [macrolide]
– Metronidazole [Nitroimidazole]
– Penicillin G [Penicillin]
– Quinupristin/Dalfopristin [streptogramins]
– Rifampin [rifamycin]
– Teicoplanin [glycopeptide]
– Vancomycin [glycopeptide]”

Bottom Line

Trying to restore E.Coli has two probiotics available:  Mutaflor (covered above) and Symbioflor-2 . Both are known to take up residency and at least 1 is known to be human sourced. Studies found that Symbioflor-2 appears to have the same sensitivity [2008].

If antibiotics are taken, they should be done before E.Coli probiotics if one of the top list is prescribed. Antibiotics on the bottom list can be taken with E.Coli Probiotics. Personally, I suspect a cocktail of Metronidazole, Erythromycin and an E.Coli probiotic may play a similar role to CFS/IBS/SIBO etc as combination drug therapy does for H. Pylori infections.

Lactobacillus probiotics also kill off E.Coli!

The same issue exists with herbs and spices.  a rough way to get some guidance is to type the name of the herb/spice and “Gram-negative bacteria” (which E.Coli is)

search1

search2

 

 

 

Your mouth can trigger flares

The microbiome includes the mouth — and the bacteria in the mouth can repopulate the gut with bad bacteria. I have done several posts on the important of oral health. Today, a reader sent his experience using one of my suggestions: mastic gum. It is a interesting account:

“Hello Ken,

I’ve been taking your recommendation of chewing and swallowing mastic gum and to my amazement I seem to be getting my appetite back. It’s like the feeling of an empty stomach is back for me after 2 years. What else I discovered from chewing mastic gum was that is also seemed to have triggered my cfs symptoms again in an erratic way.

 

Now while this may seem paradoxical, I’ve looked into this further and found that the times when chewing gum made my cfs worse was specifically when I used the gum right against my back wisdom tooth which has significant decay under it. It seems like whenever I chew my gum anywhere else my energy and willpower stay constant, while if I chew the mastic gum over my wisdom tooth I have my energy diminish. I’ve trialed this multiple times, and am doing so right now as well. I can chew the mastic gum anywhere over my mouth and still feel fine, but when it gets into hard contact with my decaying wisdom tooth, my cfs symptoms re-emerge.

 

This is a critical piece of the puzzle for me, as I now know the amalgam likely created the environment for the infectious bacteria to flourish in my mouth, and now with the amalgam gone, the bacteria no longer stay thriving as they once used to, but they are still there lurking, and certain triggers may be able to bring them back into a larger presence within my microbiome.

 

As my decaying wisdom tooth is on the same side my amalgam once was. I believe I got 100% of the old amalgam out on my second dental visit, along with the tooth being cleared out. However the surrounding teeth are still likely to be suspect, and my experience with mastic gum proves it.”

 

For myself, mastic gum caused ‘night-time dry mouth’ to disappear.

Reference posts:

Bottom Line

“Your mileage may vary” – that is. different results from above may occur for different people.  I usually chew mastic gum with a little myrrh  and frankincense (boswellia sap) — the latter two are an ‘acquired taste’.

epigenetics-international.com Probiotics

A reader forwarded me a link to their site and ask for comments.

Cost?

For fairness, it was not specified species against not specified species.

I Spot Checked Lactobacillus Gasseri:

  • 50 servings of 5 BCFU  = 250 BCFU for £23.53  ==> $31.32 

Reference:

  • Swanson’s  60 capsules x 3 BCFU x 2 = 360 BCFU for $16.00 ==> £12.02

I Spot Checked Lactobacillus Reuteri etc

  • 50 servings of 5 BCFU  = 250 BCFU for £23.53  ==> $31.32 

Reference:

  • Swanson’s  30 capsules x 7 BCFU x 2 = 420 BCFU for $11.00 ==> £8.27

Bottom Line

While they are more expensive and lack strain information — a few hard to find by themselves species are available.

On the other hand, for items Bifidobacterium Infantis – Align If you got a FRESH BOX … the study dosage is 10 capsules per day (10 BCFU) if you want to repro a successful study
that is $7.50/day. While the strain is unknown, Epigenetics product may be a lot cheaper (at 5 bn CFU/serving) or  $0.95/day.