my ideas on fibromylagia

Hi at all.

I'm sorry for this my post, I haven't fibromyalgia and I'm not a medical doctor. Then, why have I to write in this forum?
Let me a brief presentation: I'm a chemistry who is working on epilepsy since 1981, the same year of I was graduate, at the University of Genova, Italy. Thanks to the results of my studies I discovered a whey protein, alpha-lactalbumin (ALAC), able to control epileptic seizures. Thanks to the results obtained both in human both in animals ALAC is actually in the screening program of NIH (US). But this is another story.

Recently I was interested to fibromyalgia, then I was reading international forum, too, to verify different ideas on this pathology.

I looked for ALAC because the Markus’s papers reporting ALAC to be able to increase plasmatic tryptophan (trp), in fact, ALAC has been reported to be rich in trp and poor in the other amino acids competing with the BBB carrier, the LNAAs. But the trp levels are increased not by the trp arising from ALAC, but by the result of ALAC effects on intestine. Many intestinal actions are reported for ALAC, it’s able to decrease intestinal dysbiosis that is responsible of trp decarboxylation in indole and skatole. Urinary levels of these catabolites are markers of dysbiosis. Low trp/LNAA plasmatic ratio is reported in epileptic pts, I was able to evaluate an third reduction in brain trp uptake in epileptics vs controls. Furthermore high skatole levels are reported in urine of epileptic pts.

Trp is not only the only serotonin precursor, its intestinal level controls the brain synthesis of neuropeptides, i.e. NPY. NPY is named an endogenous anticonvulsant for the high anticonvulsant effect when it’s directly injected in the brain of animals. But NPY is responsible of pain threshold, too. Low trp intestinal levels correspond to low brain levels of NPY, then to a low pain threshold.

Fatigue and pain are reported in many neurological diseases, i.e. MS and Parkinson. In 1978 Monaco and Mutani reported low trp/LNAA plasmatic ratio in MS pts.

Different symptoms are linked to fibromyalgia, i.e. sleep disorders, rheumatoid arthritis (RA) . Sleep disorders are correlated with low serotonin levels in the brain. In experimental models of sleep disorders ALAC has been reported to be able to improve sleep, improving the time spent in deep sleep. RA is linked to elevate intestinal permeability, that it’s correlate with dysbiosis.

Please read forum rules.  You are giving medical advice here. 

Post Edited By Moderator (Sherrine) : 8/18/2010 5:01:52 PM (GMT-6)

I am always suspicious when unique research is published in a forum and not a proper journal. Any studies to confirm your hypothesis, before you triumphantly declare a new treatment protocol?! I'll give you that what you've said makes sense, but a quick flick through a few journals aren't showing anything directly related to your suggestion.

You can't draw conclusions from a cherry-picking of journals which treat illnesses which are merely related - life is not so simple!

Also, to tell patients a specific treatment method WILL result in symptom reduction is a little irresponsible - there can be no certainty in Medicine (or science). Any suggestions of a number needed to treat, or a specificity, for this treatment?

Take care,

James

Yes, SSRIs are administered to treat fibromyalgia, but not for their antidepressive action, while analgesic are inefficacy. Why?

SSRIs are studied to increase serotonin action in the brain, as tricycles they inhibit serotonin re-uptake, in this way allow more time to serotonin in the synaptic cleft, but…

Unfortunalty they don’t reach the brain in enough amount to produce this effect, as reported by Costa Guidotti and Pinna (Curr Opin Pharmacol. 2009 Feb;9(1):24-30. SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake.)
These authors suggest other mechanisms in the brain, but more likely SSRIs act on enteric brain, when orally administered. In fact, SSRIs are also used to treat gastrointestinal diseases, at low doses stop diarrhoea, at high doses they start it. Surprisingly at low doses SSRIs are anticonvulsants, at high doses they are proconvulsants (Jobe, J Neurochem 2005).
This confirm our results on anticonvulsant effect of SSRIs (Favale E, Rubino V, Mainardi P, Lunardi G, Albano C Anticonvulsant effect of fluoxetine in humans.Neurology. 1995 Oct;45(10):1926-7). Brain serotonin levels depend on the amount of trp uptaked in the brain (Chugani demonstrated it by PET), this amount depend on trp/LNAA plasmatic ratio. I was able to demonstrate an third reduction in trp brain uptake in epileptic pts (Lunardi G, Mainardi P, Rubino V, Fracassi M, Pioli F, Cultrera S, Albano C. Tryptophan and epilepsy. Adv Exp Med Biol. 1996;398:101-2.), then low serotonin level in the brain of epileptics.
Markus reports ALAC able to increase trp/LNAA plasmatic ratio, then it is a valid tool to increase brain serotonin. In this way it improves seizure control (Mainardi P, Leonardi A, Albano C. Potentiation of brain serotonin activity may inhibit seizures, especially in drug-resistant epilepsy Med Hypotheses. 2008;70(4):876-9.) The clinical data were showed at the 7th ILAE congress at Helsinki, 2007. But more important than clinical results it’s understand how ALAC and SSRIs control seizures.
Until ‘30s, intestine has a predominant role in neurological diseases, after the idea to be able to reach the brain with drugs able to correct neuronal mechanisms, put intestine behind the brain. Ketogenic diet was largely used in 30s to control seizures, and still now ketogenic diet is used in epilepsy (Elsevier asked me a review on KD, it’ll be printed in the first months of 2011), but not only: KD is suggested in MS, parkinson’s, Alzheimer, etc, too.
Then I supposed that are not ketones the responsible of anticonvulsant effect of KD (Mainardi P, Albano C. Is the antiepileptic effect of the ketogenic diet due to ketones? Med Hypotheses. 2008;70(3):536-9). In fact, it’s reported fats are able to restore good intestinal flora, as ALAC is reported to be a very good prebiotic food: it corrects intestinal pH, increases mucus, prostaglandin release. ALAC in the human milk is responsible of the activation of intestinal adsorption process. The role of intestine is more to protect us than to feed us. Intestine is like a second skin, it’s selectively permeable. The intestine of newborn is completely permeable, in few days ALAC decreases intestinal permeability.

Gut brain axis is the key, very important brain control functions are controlled by neuroendocrine system, depending on intestinal nutrients. Intestinal trp and/or serotonin control brain synthesis of neuropeptides, as norephineprine, it’s well know to be antidepressive and anticonvulsive, or NPY, it’s named an endogenous anticonvulsive. But NPY control pain threshold, too

I’m continuing studies on epilepsy, in the next months some papers will be printed, but all neurologists refer me fibromyalgia is a psychosomatic disease, I don’t believe it, but I’m not a doctor, I’m a chemistry.

My studies are now on autism, Alzheimer, MS, depression, too, but I don’t have any possibility to suggest studies on fibromyalgia. We have good results also in sleep disorders, they are considered a symptom of fibromialgia. It’s fantastic: how is it possible to link sleep disorder to fibromyalgia? Some one refers the pain so strong to make hard to sleep. But fibromyalgics experiences a not restorative sleep, this is different to don’t sleep. Results on experimental models of sleep show ALAC able to improve period time of deep sleep.

In conclusion, my hypothesis is a brain as an engime, if it is not fully fueled it don’t work well.

In intestine there are servo-controlled tools able to restore good brain functions.

"In conclusion, my hypothesis is a brain as an engime, if it is not fully fueled it don’t work well."

This is not a hypothesis, it is a metaphor, or at a push, an analogy. You shouldn't tell people a treatment will work, or even suggest one, if there is no direct supporting evidence. Especially as a scientist - your interpretation of epilepsy and autism as applied to FM patients should be published in a peer reviewed journal, rather than on an internet forum.

Please remember that very often, what is the case in theory is not what happens in practice, the body has too many co-dependent variables. This is why double blind, controlled studies inform evidence based medicine, rather than the archaic methodology of treating based on theory. Empirical evidence is key.

Thanks

Let's not get angry at this new person for introducing some thoughts here. He isn't selling anything. Let's take it easy. I'm intrigued by this line of thought. Please don't shoo him away.

Paolo, you mentioned this: "Ketogenic diet was largely used in 30s to control seizures, and still now ketogenic diet is used in epilepsy (Elsevier asked me a review on KD, it’ll be printed in the first months of 2011)"

I would like to understand more about this. How does one get to read one of these journals? Which journal will your review be published in?

I think ideas can come from all places - I don't shun any idea until I've had a chance to dissect it a little Maybe it is unusual to see a post such as this - but I'm going to look at it.

Paolo - yes, gastrointestinal disease is very common among fibromyalgia patients. I had what is referred to as IBS for at least 10 years before my fibro diagnosis. I had lactose intolerance for at least 20 years now - before my IBS diagnosis.

I did a little reading about this whey protein, alpha-lactalbumin (ALAC). It seems it is more plentiful in human milk, less so in cow's milk. Is goat milk a better source for this ALAC? I'm just about to try introducing lactose free goat's milk into my diet and am curious about the ALAC content.

Paolo - do you have a blog where you post your thoughts about these connections? I would like to read more about this.

Chickenprincess, You may be able to access journals from your local library electronic databases. If you know someone who is attending university or works at one, this person will definitely have access to journals. He or she may let you look up journals. Be sure to read peer-reviewed journal articles. On most sites you can select for peer-reviewed. If you get to a database and need help, e-mail me privately. If you Google, you will have to pay for almost every article you find. Do not trust things like Web MD or magazine articles that report on research. They often misconstrue the data and results and end up reporting information that is not actually published in the reputable journal.

Jay, I am interested in your grasp of the scientific process and empirical evidence. I work in a large university and few 21-year old students clearly understand these important concepts.

Paolo, why can you not conduct fibromyalgia research? I have not read the journals you cite, but if your hypotheses are based on findings of previous research, do you have a colleague who can follow up?
Sue

Statgeek - many thanks. I'll ask at my local library. If that fails, I'll email you for help. I'm excited to see journals talking about what is really being researched. This all fascinates me, even though I don't have a scientific background.

Paolo - Thanks for the additional information. What sorts of foods might a person want in this cocktail of prebiotics? I've been extremely interested in the angle of treating health issues with food for many years. I really don't feel there is anything to lose by testing foods.

Statgeek said...

Jay, I am interested in your grasp of the scientific process and empirical evidence. I work in a large university and few 21-year old students clearly understand these important concepts.

Hey, I'll be glad to clarify, although not right now as just dropped a Zopiclone... I'm not really a student. I mean, I'm enrolled on a degree, in Nanotechnology - but I've spent the last 2 months working full time. I tend to skip lectures, and what not, and just focus on the exams. Sacrifice grades in favour of time.

If your University is in America, I am not surprised at this, the education system is a lot "slower" developing - that is, Law School/Med School follows college, where in UK, you study a specific subject from the beginning. No optional classes, no off topic "electives". I also do a pretty unique course, there are only 12 of us enrolled on it (across the board).

Science (and technology) is basically my life, I pore over journals and read widely. My friends get very annoyed at me and my favourite phrases"Well I just read a study that says...." and "I was reading last night, and....." :D

So what is it you want to pull me up on? Perhaps we'd be better moving this out of the way, this is a little off topic.... and vision has gone blurry.

Take care

James

EDIT - this isnt as succinct as I normally try to be. I think I'll go to bed and recover. BAD pain tonight, BAD!

.

I suggest you to read these papers, are all free articles in pubmed:

Saulnier DM, Spinler JK, Gibson GR, Versalovic J. Mechanisms of probiosis and prebiosis: considerations for enhanced functional foods. Curr Opin Biotechnol. 2009 Apr;20(2):135-41

The technologies of metagenomics and metabolomics are broadening our knowledge of the roles the human gut microbiota play in health and disease. For many years now, probiotics and prebiotics have been included in foods for their health benefits; however, we have only recently begun to understand their modes of action. This review highlights recent advances in deciphering the mechanisms of probiosis and prebiosis, and describes how this knowledge could be transferred to
select for enhancing functional foods targeting different populations. A special focus will be given to the addition of prebiotics and probiotics in functional foods for infants and seniors.


Kolida S, Gibson GR. Prebiotic capacity of inulin-type fructans. J Nutr. 2007 Nov;137(11 Suppl):2503S-2506S.

The human gut microbiota plays a significant role in human health through its ability to digest food ingredients and manufacture metabolites. This can be positive or negative for host welfare. Moreover, the microflora plays an active role in host defense whereby colonization resistance affords protection against pathogens. Prebiotics are nondigestible food ingredients that target beneficial components of the gut microflora (mainly colonic), particularly the bifidobacteria. In vitro and in vivo evidence has accumulated to confirm the prebiotic effects of inulin-derived fructans.


Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995 Jun;125(6):1401-12.

Because the human gut microbiota can play a major role in host health, there is currently some interest in the manipulation of the composition of the gut flora towards a potentially more remedial community. Attempts have been made to increase bacterial groups such as Bifidobacterium and Lactobacillus that are perceived as exerting health-promoting properties. Probiotics, defined as microbial food supplements that beneficially affect the host by improving its intestinal microbial balance, have been used to change the composition of colonic microbiota. However, such changes may be transient, and the implantation of exogenous bacteria therefore becomes limited. In contrast, prebiotics are non digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon, and thus attempt to improve host health. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota. Nondigestible oligosaccharides in general, and fructooligosaccharides in particular, are prebiotics. They have been shown to stimulate the growth of endogenous bifidobacteria, which, after a short feeding period, become predominant in human feces. Moreover, these prebiotics modulate lipid metabolism, most likely via fermentation products. By combining the rationale of pro- and prebiotics, the concept of synbiotics is proposed to characterize some colonic foods with interesting nutritional properties that make these compounds candidates for classification as health-enhancing functional food ingredients.




This article is about the ability of FOS to decrease trp conversion in skatole and indole
Zi-Rong Xu, Cai-Hong Hu,* and Ming-Qi Wang Effects of fructooligosaccharide on conversion of L-tryptophan to skatole and indole by mixed populations of pig fecal bacteriaJ. Gen. Appl. icrobiol., 48, 83–89 (2002).

High skatole levels are found in urine of epileptics (A Mori et al. Gas chromatography of 5-hydroxy-3-methylindole (skatole) in human urine. Clinica Chimica ACta, 84 (1978) 63-68.)

This can explain low trp plasmatic levels in epileptics (and in other neurological diseases), corresponding to low brain levels of serotonin, norepinephrine and NPY.

Fascinating. Thank you, Paolo. This gives me ideas about what to search out. It gives direction for me.

I am extremely fortunate that you turned up just now on our discussion board - now that I'm in the aftermath of three weeks of illness that started from strong digestive symptoms, evolved into a fever of 102 and tachycardia, and put me in the hospital emergency room twice and doctor's office at least eight times. It eventually passed. The doctors felt it was viral, possibly. The experience has re-affirmed my desire to find better ways to do everything in my life - including tweaking my diet towards the right foods. So I am most grateful for your posts.

Food and supplements have made a difference in reduction of symptoms for me over the years. Maybe now I can go even further in bettering my health.

But, even if my trials would not work, at least there is no harm that can come from trying.

There was only one urine test ran in all these weeks. I just looked at the results, none of the tests were for the things you noted that would indicate permeability. I wish they had run those.

All other tests this month have been blood tests.

I noticed when I googled Lactolose, it mentioned something about being used in treating patients with liver disease. Interesting. I wonder if that information is important considering that my liver panel tests became slightly elevated, but have now (as of Monday) almost returned to the normal range.
August 10th results were:
Component Your Value Standard Range Units Flag
AST/SGOT 77 My value 14 - 46 Standard Range U/L H
ALT/SGPT 112 My Value 9 - 52 Standard Range U/L H
Again, my doctor said viral infections can cause this. However, she said we'll never know for certain. She said testing for a virus was almost pointless. However, I wonder too if my digestive system had been stronger, would I have properly fought off this illness without it making me so sick? Was I, or am I, having permeability issues? (Not asking for answers, just thinking aloud) It seems there can be no harm in trying to strengthen my digestive system.

I think this discussion is very fascinating.  I too tend to try to use food and suppliments to improve my general health.  I have been gluten free for about a year and a half and saw some major improvement in abdominal discomfort.  I also have ulcerative colitis and take sulfasalazine daily on a maintenance level dose.  I try to eat right-- fruits, vegies, meats, fish etc.  I also have increased my amino acids (protein) as per my ND instructions because my amino acid panel was very low.

I just wanted to say especially to Chicken Princess that there is a book I read about 5 years ago that I think will be intriguing to you.  It is called "The Second Brain" by Michael D. Gershon MD in which he discusses the gut as being as important as the brain.  It controls many things in our bodies and keeping it as healthy as possible is very important.

Yo-yo 

Yes Gershon was very important researchman in gut-brain axis history, but now very important results confirm it:
After 3 days from brain injure, as reported by experimental models in animals, the intestinal membrane results collapsed: an elevate permeabilty other than a physical damage.

The amount of ulcers in stomach, produced by HCl, has been demonstred to be correlated to the amount of convulsive drug injected icv in the brain.

In agreement with over 90% of comunications is from gut to brain, Dephour demonstred that producing intestinal inflammation, by croton oil, decreases epileptogenic threshold in animals. An inflammative process in intestine produces more seizures in experimental models of epilepsy

In my opinion these are very important results confirming the role of gut-brain axis, not only in epilepsy.