354 replies to this topic

[Lufega]

Funk,

I've been using Eleuthero for two months now and I can't really tell if it's doing anything. My dose is 2 grams or more each morning, fasted. I admit, this time I didn't research this herb fully, I was expecting it to calm me now. But now that you mention that it can raise cortisol, I've been suspecting Adrenal fatigue for sometime. I tested the AM and PM cortisol a couple days ago and both came back normal. I was stunned as my fatigue has been unrelenting and I was dead sure it would be low. My body temperature was also variably low although my thyroid function tested normal. However, the Anti-TPO showed a result BELOW the normal range. I'm still trying to figure out what that means. I've ask a few of my professors and no one seems to know! Anyways, maybe the Eleuthero had some effect after all. I have noticed that I am more anxious and irritable as of late (increased corstisol effect?) but the fatigue persists. To this I will add that I tried magnesium ascorbate this morning and the combination had an awsome effect! I've used alsmost every mag. combo out there but this one was special. It lifted my mood and calmed my anxiety but I was more attentive/energetic. What surprise. I hope it wasn't placebo.

Have you been to a cardiologist? Do you have any valvular problems such as mitral valve prolapse/regurgitation? You fit the profile of a marfan habitus and Dysautonomia (orthostatic hypotention) commonly appears along with the MVP earning the name of MVP syndrome. I have this myself. OH seems to be caused by a B1 deficiency which is itself affected by the magnesium status. You can test for this by performing a functional B1 test for transketolase.

I used to have a pretty bad case of Or. Hypotension. Getting up from a chair made me light-headed and riding in cars was intolerable. I rid this problem by using fursultiamine (TTFD), a fat soluble B1. This form, unlike benfotiamine, crosses the BBB working centrally.

Read my posts below;

http://www.imminst.o...showtopic=25772

http://dinet.ipbhost...p...262&hl=ttfd

[rwac]

I tested the AM and PM cortisol a couple days ago and both came back normal. I was stunned as my fatigue has been unrelenting and I was dead sure it would be low.

Hey Lufega,

Did you test for DHEA levels ?
I have very high cortisol, but borderline low DHEA (after using 50mg DHEA for months).

So what are your Thyroid numbers ?
I believe lots of people are hypothyroid, with normal thyroid tests.

Also, do you take selenium ? That would reduce TPO values.

Edited by rwac, 07 February 2009 - 02:35 AM.

[FunkOdyssey]

Lufega, thanks for the input, I will look into the B1 and OH relationship. I don't have any documented heart problems and have not seen a cardiologist. EKG is normal. However I do have "crazy things" happen with the heart that defy description which I have pinned on Lyme. These have diminished in severity and frequency with treatment.

Here's the interesting study I found on eleuthero:

Life Sci. 2001 Dec 14;70(4):431-42.
The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes.
Gaffney BT, Hügel HM, Rich PA.

School of Nursing. Faculty of Nursing and Health, Griffith University, Meadowbrook, Queensland, Australia. B.Gaffney@mailbox.gu.edu.au

A clinical trial was undertaken to investigate the effects of Eleutherococcus senticosus (ES) and Panax ginseng (PG) on competitive club-level endurance athletes engaged in their normal in-season training. Participants were matched for training stress and received a 33% ethanolic extract (8 mL/day) containing either ES, PG (equivalent to 4 g and 2 g/day of dried root, respectively), or a placebo. A pre-test and post-test were used to evaluate the effects of six weeks of supplementation on cortisol, testosterone, and testosterone to cortisol ratio (TCR) as well as circulating numbers of total T-cells, T-helper cells (CD4), T-suppressor cells (CD8), CD4 to CD8 ratio, natural killer cells, and B lymphocytes. None of the immune system variables changed significantly nor showed any clear trend from pre to post test in any of the treatment groups. No significant change in testosterone, cortisol or TCR was observed in the PG group. In the ES group, however, TCR decreased by 28.7% from 0.0464 to 0.0331 (P=0.03). The main contribution to this decrease appeared to be a non-significant (P= 0.07) 31% trend towards increased cortisol rather than a very small non-significant (P = 0.36) 7% decrease in the calculated mean for testosterone. This result suggested that contrary to initial expectation, ES increased rather than decreased hormonal indices of stress, which may be consistent with animal research suggesting a threshold of stress below which ES increases the stress response and above which ES decreases the stress response.

PMID: 11798012

Edited by FunkOdyssey, 07 February 2009 - 03:17 AM.

[Lufega]

Thanks for the study Funk. This seems to explain why I've been sooooo stressed out lately. I've been so stumped about this. I read that about selenium and low anti-TPO. Come to think about it, I have been taking selenium for a few months now Would this work as well if you had HIGH TPO values? What a great therapeutic tool this would be!

I did not test for DHEA but I will add it next time I get tested. I tested for blood cortisol. Saliva tests are not available in this country. Go figure, if I tested for copper ceruloplasmin levels and they had to ship it to the states. I'm having the Western blot for Lyme done next week but it'll take a good month before I get results.

Right now I'm having all these prostate related problems; Unexplained penis pain, pain on ejaculation, urine retention and others. I'm taking Maca and maybe that's raising my testosteron too much? But I also take Nettle root and that's supposed to keep DHT down. Not sure. I didn't use Maca today and I haven't had the problem. I'll try again tomorrow and confirm. I'm reaching a point where I don't know what to do anymore! All these mysterious symptoms come and go on their own...I'll test for PSA just to be careful/.

Edited by Lufega, 07 February 2009 - 04:28 AM.

[youandme]

I have been taking selenium for a few months now Would this work as well if you had HIGH TPO values? What a great therapeutic tool this would be!

Lufega
This is interesting Ive High TPO's about at 1000 !
Ive read one report that suggested Selenium helped reduce TPO's in Autoimmune Thyroiditis patients..however soon after I read another where it did not..!

All my best for finding out whats going on with you.

[rwac]

I have been taking selenium for a few months now Would this work as well if you had HIGH TPO values? What a great therapeutic tool this would be!

Lufega
This is interesting Ive High TPO's about at 1000 !
Ive read one report that suggested Selenium helped reduce TPO's in Autoimmune Thyroiditis patients..however soon after I read another where it did not..!

All my best for finding out whats going on with you.

You should try supplementing with Selenium (reduce TPO) and Vitamin D3(general help for autoimmune issues)
Do you have a regimen right now ?

[FunkOdyssey]

Right now I'm having all these prostate related problems; Unexplained penis pain, pain on ejaculation, urine retention and others.

This is more likely a chronic infection. I've had similar symptoms that disappeared with antibiotics.

[ajnast4r]

brands?

no personal experience with it standalone, but i like this brand. i've also found this companies extracts to be particularly potent.

[pycnogenol]

I'm with ajnast4r on the Nature's Plus brand. They make good stuff plus you get a CoA package insert from an
independent analysis company in each bottle.

Edited by pycnogenol, 07 February 2009 - 02:25 PM.

[FunkOdyssey]

Before I get too carried away megadosing several different adaptogens (that's the direction I was taking) I am going to try Ortho-Adapt and its low-dose content of glycerrhizin for awhile. I will probably take only two or three capsules for 100-150mg glycerrhizin. The study I found which demonstrated a testosterone lowering effect from glycerrhizin used 500mg and it reduced average testosterone from ~740ng/dL to 420ng/dL on day 4, but then it was beginning to rebound and was 484ng/dL on day 7. They only followed them for 7 days, so I wonder if the body was adjusting to the glycerrhizin and testosterone would have continued to rise toward normal. In any event, day 7 was the last day of treatment, and by day 10 testosterone was back to normal. At 100-150mg it should only have a small effect which may prove to be transient with continued use.

I am uncomfortable relying upon poorly documented herbs with varying levels of actives to consistently raise cortisol levels (eleuthero was the only adaptogen that was even suggested in the literature to possibly do this). I also don't like the brief, spiking nature of hydrocortisone supplementation. The few times I've played around with it, it felt like I was somehow overshooting the mark even with only 2.5mg, I'd get this brief moment of euphoria and warmth, and then some kind of crash after only a couple hours. Even though it raised my body temp to almost normal and prevented the orthostatic hypotension, it felt like I was riding some kind of well-being rollercoaster. Clearly, the body's natural steady trickle of cortisol is preferable. I like the fact that glycerrhizin acts as a multiplier of the body's natural production of cortisol and it seems to produce more consistently positive effects.

[rwac]

Funk,

Since there's all this fuss about Grouppe Kurosawa.
I looked up lyme, and guess what, they suggest curcumin as a supplement.
Also, they suggest dissolving it in fat (milk, cream, etc) to improve bio-availability.

http://grouppekurosa...sible_trea.html

[ajnast4r]

funk, take a look at enzymatic therapy's ADRENERgize products (2 versions, one herbal one glandular)..

[Lufega]

Funk,

Since there's all this fuss about Grouppe Kurosawa.
I looked up lyme, and guess what, they suggest curcumin as a supplement.
Also, they suggest dissolving it in fat (milk, cream, etc) to improve bio-availability.

http://grouppekurosa...sible_trea.html

Thanks for the link! I've been trying to get access to this protocol for weeks! I almost forked over $75 to subscribe!! I can attest to how well Curucmin works for reducing arthritis. When the arthritis pain mysteriously began a few years ago, curcumin was the only think I used to keep it at bay. I stopped using curcumin a while ago to experiment with other supplements but I will start again. I must say that too this day, my arthritis symptoms are not as bad as they were back then.

Edited by Lufega, 09 February 2009 - 05:05 AM.

[FunkOdyssey]

Funk,

Since there's all this fuss about Grouppe Kurosawa.
I looked up lyme, and guess what, they suggest curcumin as a supplement.
Also, they suggest dissolving it in fat (milk, cream, etc) to improve bio-availability.

http://grouppekurosa...sible_trea.html

I do think that would be very effective for reducing the symptoms of Lyme arthritis. However, I don't think it should be considered a complete Lyme protocol because it does not address the underlying infection. I do take some curcumin but I am not trying to megadose it with maximum bioavailability because 1) I barely have any joint pain, my symptoms are primarily neurological (neuroborreliosis) and 2) megadosing a highly bioavailable source of curcumin will powerfully shift and suppress aspects of your immune system.

This does not seem particularly safe or wise to me, since you are assuming to fully understand the status and interplay between many immune system cytokines, when you have no way to directly measure them and the interrelationships are impossibly complex. There may be undesirable or unpredictable consequences of this intervention. Other drugs that suppress one particular immune cytokine completely tend to have bothersome side effects like, for example, increasing the risk of cancer or fatal infection.

funk, take a look at enzymatic therapy's ADRENERgize products (2 versions, one herbal one glandular)..

I did take a look at that, and I like the general idea they have, but AOR does it better with Ortho-Adapt. Enzymatic Therapy includes a homeopathic dose of glycerrhizin, when that is actually the main player or the "active ingredient" in the formula. Supplement manufacturers are generally scared of glycerrhizin because it can produce high blood pressure in excessive doses. I've looked far and wide, and so far, AOR seems to make the only product on the market with an effective dose of glycerrhizin (50mg per capsule).

[FunkOdyssey]

Updates made to regimen in original post on first page.

Removed:
LEF Pyridoxamine - expensive, cost/benefit ratio is poor compared to P-5-P
LEF HepataPro - test to determine whether NAC or PPC was saving my pancreas, hoping it was not PPC, too expensive
L-Arginine - became paranoid about potential negative long-term effects
Quercetin - don't like the effect on liver enzymes, new philosophy prohibits meddling with poorly understood aspects of immunity, did not seem to really help anything anyway
Piracetam - ran out, going to see how I do without it in the interest of cost savings
Jarrow MK-7 - replaced with LEF product
Carlson MK-4 - replaced with LEF product
Diflucan (fluconazole) - I don't think its doing anything and I was never convinced it works for Lyme despite what my doctor said and despite the single positive German study. No mechanism of action has been established. Fairly liver toxic. Interferes with production of adrenal hormones.

Changed:
Vitamin A reduced to 10,000iu daily - I gave it a month at 20,000+ iu, liver stores are probably topped off
Glutamine increased to 20g daily - this seems to have dramatically improved digestive health even though I started taking it for immunity. In the past I had played around with 3-4g daily and it didn't do anything. It has become clear to me that this supplement doesn't "put out" until you get serious with it. 15g was good, but I want more, and more (even 60-80g) has been shown clinically to be exceptionally safe.

Added:
Doctor's Best PureWay-C 2g daily - I've bought into the hype surrounding this sustained release formulation of vitamin C. Actually has some "pubmed cred".
LEF Advanced K2 Complex - best Vit K product on market
Twinlab Super Probiotic (GanedanBC30) - another clinically tested super strain, because three wasn't enough and I must have the latest designer bacteria. I don't care how many billions of CFU of anonymous crap you've got, its all about specific strains and the clinical, pubmed'able evidence supporting them.
Nature's Way Andrographis - Andrographolides have documented anti-microbial activity against many bacteria (as well as viruses) and many evil spirochetes in particular and reach high concentrations in privileged tissues like the brain. Starting with 90mg andrographolides daily and will ramp up over time.
Jarrow BroccoMax - sulforaphane induces phase II detox enzymes, recommended by progressive Lyme physicians.
AOR Ortho-Adapt - will start this at 3 caps daily when it arrives in a couple days.
Nature's Way Olive Leaf Extract - 12% oleuropein, 250mg caps, 3 daily. I attempted 500mg caps of 18% oleuropein extract from Olympian Labs and it knocked me out with the same herx type symptoms I was getting while ramping up on tetracycline. I'm not sure what its doing exactly but I assume it is something good (studies show induction of autophagy by oleuropein, maybe gobbling up intracellular bacteria). I will switch to the higher dosage OL product as tolerated.

My positive results with high dose glutamine and hydrocortisone/glycerrhizin have convinced me that a couple of "fad" diagnoses that are currently unrecognized by mainstream medicine, leaky gut and adrenal fatigue, do actually seem to exist and respond to treatment in this particular patient. I feel it would be a mistake to think either disorder could occur in isolation, independently from a more complex etiology, but in the context of my chronic Lyme they may be real problems that can be treated with positive consequences for overall health and Lyme recovery.

Edited by FunkOdyssey, 09 February 2009 - 07:37 PM.

[Brainbox]

I've been looking for a link between niacinamide depletion and chronic bacterial (lyme) issues, but was not able to find any. Do any of you have any thoughts on this?

[FunkOdyssey]

It is my understanding that cytokines elevated due to chronic infection lead to IDO induction (an enzyme that degrades tryptophan into harmful metabolites). This reduces the availability of tryptophan for conversion into niacinamide and could result in niacinamide deficiency.

I think any modest, typical amount of niacinamide supplementation (50-100mg daily) would be more than enough to prevent deficiency even in this context. The tryptophan depletion might have other negative implications for serotonin and melatonin production (depression, anxiety, many other psychiatric disorders, insomnia). You would not want to supplement with more tryptophan as this would result in even more of the harmful metabolites, and I can attest that tryptophan makes me feel awful.

Here's a link to someone's myspace blog (??) that discusses this in great detail, there is also a paper in the full member section I requested last year on the topic, its an excellent read.

http://blogs.myspace...logID=460799711

Edited by FunkOdyssey, 09 February 2009 - 09:30 PM.

[sdxl]

Twinlab Super Probiotic (GanedanBC30) - another clinically tested super strain, because three wasn't enough and I must have the latest designer bacteria. I don't care how many billions of CFU of anonymous crap you've got, its all about specific strains and the clinical, pubmed'able evidence supporting them.

As far as I can see I don't see how this particular strain of Bacillus coagulans is superior to other B. coagulans like in Sabinsa's LactoSpore. I can't find anything on this GanedenBC³⁰ on PubMed and the Ganeden's website isn't of much help either.

[FunkOdyssey]

It is probably similar to, and not necessarily superior to, Sabinsa's LactoSpore.

[Lufega]

I have not seen any studies that suggest there is any relationship between manganese intake and Lyme Disease outcomes. It would be logically appealing to assume there might be, however I don't think it makes much difference. Since Lyme does not produce symptoms of manganese deficiency, and no deficiency has been reported, the implication is that Lyme does not use all of the manganese available in the body and that it is not a limiting factor in growth. Therefore, I am skeptical that restriction of manganese would be useful or would be more helpful than harmful to the host.

Found this article published a few days ago. It seems like manganese is a limiting factor for the growth of BB.

http://www.utsouthwe...les/517121.html

Feb. 9, 2009

Dallas, Texas


Researchers at University of Texas Southwestern Medical Center have
identified a protein that may help give Lyme disease its bite.

The findings suggest that the bacterial protein, which aids in
transporting the metal manganese, is essential for the bacterium that
causes Lyme disease to become virulent.

“We believe our findings provide a foundation for further defining metal homeostasis in this human pathogen and may lead to new strategies for thwarting Lyme disease,” said Dr. Michael Norgard, chairman of microbiology at UT Southwestern and senior author of a study now online and in an upcoming issue of the Proceedings of the National Academy of Sciences. [.....]

[.....]To establish infection, however, the bacterium also must acquire a
number of essential nutrients, including metals like manganese from its
mammalian and tick hosts. Until now, no metal transporter responsible
for this acquisition had been identified in this bacterium.

In the current study, microbiologists examined whether bacteria
genetically engineered to lack this manganese transporter, called BmtA,
transmitted Lyme disease to ticks and mice. The bacterium lacking the
transporter, Dr. Norgard said, grows a bit more slowly in the test tube
but is not dramatically different from the normal version.

“When you try to grow it in a mouse, however, it can’t grow,” he said.
“The fact that the bacterium without this particular manganese
transporter can’t grow in a mouse raises important questions about what
aspects of physiology and metabolism contribute to the pathogenicity of
the organism.”

Lead author Dr. Zhiming Ouyang, postdoctoral researcher in microbiology
at UT Southwestern, said another newly discovered characteristic about
the bacterium that causes Lyme disease is that it doesn’t seem to
require iron to function, something most other pathogens need to survive.

“Out of the thousands of bacteria known, the Lyme disease agent and only
one or two other bacterial species do not require iron for growth,” Dr.
Ouyang said. “That raises the question as to what other metal co-factors
the Lyme disease bacterium depends on to carry out the work that iron
does for all these other biological systems. Our research suggests that
manganese is a really important one.”

The next step is to understand the exact mechanism of how manganese
functions in the organism.

I started using manganese last week to correct a possible deficiency (per hair analysis) and ever since then I've been feeling god awful. It feels like my normal (abnormal?) signs and symptoms multiplied exponentially. The fatigue and cognitive problems have been unbearable and right now I feel like I'm going to pass out at any second. Today was so bad that I walked out of rotation. I suspect I am Lyme positive (pending diagnosis) and we know that lyme uses manganese instead of iron in its metabolism. I had doubts about adding more coal to the fire but decided to go for it since manganese is needed for proper connective tissue formation. I think the way I've been feeling speaks volumes. If you have or suspect Lyme disease, avoid all manganese supplements....on the other hand, maybe supplementing with manganese can help confirm a diagnosis by making BB more virulent????

Lactoferrin interrupts iron binding by bacteria, is this correct? Is there a similar substance that can do the same for Borrelia burg.?

I will stop using the manganese supplement but is there anything I can do to recover from this fatigue? None of my usual energy supps are working (maca, rhodiola, tyrosine, royal jelly, coconut oil, etc..) Grrrrr....I have midterms next week!

Edited by Lufega, 11 February 2009 - 04:26 PM.

[rwac]

Be careful. Manganese is used for more than just connective tissue.

It can affect Insulin release. It is also used in manganese SOD.
I started taking Manganese because it made it me feel better.

http://www.ncbi.nlm....6?dopt=Abstract

Dynamics of insulin and glucagon release in rats: influence of dietary manganese.

Baly DL, Curry DL, Keen CL, Hurley LS.

The effect of manganese on endocrine pancreatic function was examined in manganese-sufficient (control) and manganese-deficient (Mn-) Sprague-Dawley rats. Pancreatic insulin release was lower (P less than 0.05) in Mn- rats than in controls in response to both a 300 mg/dl and a 100 mg/dl glucose stimulus. The 300 mg/dl glucose stimulus induced the synthesis of 19.4 micrograms insulin/g pancreas in control rats. Additionally, no appreciable intracellular degradation of insulin occurred over an 80-min perfusion period. By contrast, in Mn- rats, there occurred an intracellular insulin degradation amounting to 7.8 micrograms/g pancreas. This enhanced degradation was partially compensated by a net insulin synthesis of only 3.4 micrograms insulin/g pancreas. Initial (min 1-3) insulin release by Mn- rats in response to 10 mM arginine was lower (P less than 0.05) than that observed in controls. Pancreatic glucagon release in response to 10 mM arginine was not affected by manganese deficiency. These findings demonstrate that manganese deficiency results in depressed pancreatic insulin synthesis and enhanced degradation. These factors may be responsible for the abnormal carbohydrate metabolism observed in Mn- animals.

[Brainbox]

It is my understanding that cytokines elevated due to chronic infection lead to IDO induction (an enzyme that degrades tryptophan into harmful metabolites). This reduces the availability of tryptophan for conversion into niacinamide and could result in niacinamide deficiency.

I think any modest, typical amount of niacinamide supplementation (50-100mg daily) would be more than enough to prevent deficiency even in this context. The tryptophan depletion might have other negative implications for serotonin and melatonin production (depression, anxiety, many other psychiatric disorders, insomnia). You would not want to supplement with more tryptophan as this would result in even more of the harmful metabolites, and I can attest that tryptophan makes me feel awful.

Here's a link to someone's myspace blog (??) that discusses this in great detail, there is also a paper in the full member section I requested last year on the topic, its an excellent read.

http://blogs.myspace...logID=460799711

Yes. But as far as I understand this is not related to the cause of inflammation. I just wondered if the depletion of NAD or the disruption of metabolism that produces it could be linked to a bacterial cause. I agree with your view that looking for causes of auto immune issues should not be limited only to internally derailed mechanisms, but could also be targeted to "external" causes, like chronic bacterial infection. But my original question was a bit naive in the sense that finding something specific is not trivial...

[FunkOdyssey]

It is my understanding that cytokines elevated due to chronic infection lead to IDO induction (an enzyme that degrades tryptophan into harmful metabolites). This reduces the availability of tryptophan for conversion into niacinamide and could result in niacinamide deficiency.

I think any modest, typical amount of niacinamide supplementation (50-100mg daily) would be more than enough to prevent deficiency even in this context. The tryptophan depletion might have other negative implications for serotonin and melatonin production (depression, anxiety, many other psychiatric disorders, insomnia). You would not want to supplement with more tryptophan as this would result in even more of the harmful metabolites, and I can attest that tryptophan makes me feel awful.

Here's a link to someone's myspace blog (??) that discusses this in great detail, there is also a paper in the full member section I requested last year on the topic, its an excellent read.

http://blogs.myspace...logID=460799711

Yes. But as far as I understand this is not related to the cause of inflammation. I just wondered if the depletion of NAD or the disruption of metabolism that produces it could be linked to a bacterial cause. I agree with your view that looking for causes of auto immune issues should not be limited only to internally derailed mechanisms, but could also be targeted to "external" causes, like chronic bacterial infection. But my original question was a bit naive in the sense that finding something specific is not trivial...

I've learned a bit more about this in the past couple of days that provide additional clues. IFN-gamma (produced in response to the infection) induces IDO, which depletes tryptophan. In the brain, this can lead to neurotoxicity through the production a tryptophan metabolite called quinolinic acid.

What is the purpose of this immune response? There seem to be two possibilities. First it may be a strategy to withhold a valuable nutrient from the pathogens, in the same way the body attempts to starve infections of iron. Secondly it may be a strategy to increase NAD availability for the immune cells (despite adequate niacin intake). I was reading more about B3 and NAD -- different tissues and different cells can only obtain NAD from specific sources, depending on which enzymes they have at their disposal. Nicotinic acid and niacinamide for example do not directly elevate NAD in neurons, only nicotinamide riboside can do that. Tryptophan and its metabolites are the primary source of NAD for the liver, regardless of niacin intake.

So I suggest that NAD production might be another reason for the induction of IDO in response to infection. Regardless of the intention, a definite consequence is reduced availability of tryptophan for serotonin production and this has a variety of negative implications for the patient. I think this is a cause or at least a contributing factor to many cases of anxiety, depression, insomnia, etc.

Edited by FunkOdyssey, 12 February 2009 - 08:42 PM.

[youandme]

Funk

Question on you using 'Glutamine' what does it do for the immune system if anything do you think ?

You are taking Probiotics but you are also taking Biotic eliminators like Olive Leaf..are you just trying to replenish while you try to kill off the bad biotics. ?


Cheers

[FunkOdyssey]

Why glutamine:

Wien Klin Wochenschr. 1996;108(21):669-76.

[Glutamine: effects on the immune system, protein balance and intestinal functions]
[Article in German]

Roth E, Spittler A, Oehler R.

Chirurgisches Forschungslaboratorium, Universitätsklinik für Chirurgie, Allgemeines Krankenhaus, Wien.

Glutamine is the most abundant free amino acid of the human body. In catabolic stress situations such as after operations, trauma and during sepsis the enhanced transport of glutamine to splanchnic organs and to blood cells results in an intracellular depletion of glutamine in skeletal muscle. Glutamine is an important metabolic substrate for cells cultivated under in vitro conditions and is a precursor for purines, pyrimidines and phospholipids. Increasing evidence suggests that glutamine is a crucial substrate for immunocompetent cells. Glutamine depletion in the cultivation medium decreases the mitogen-inducible proliferation of lymphocytes, possibly by arresting the cells in the G0-G1 phase of the cell cycle. Glutamine depletion in lymphocytes prevents the formation of signals necessary for late activation. In monocytes glutamine deprivation downregulates surface antigens responsible for antigen preservation and phagocytosis. Glutamine is a precursor for the synthesis of glutathionine and stimulates the formation of heat-shock proteins. Moreover, there are suggestions that glutamine plays a crucial role in osmotic regulation of cell volume and causes phosphorylation of proteins, both of which may stimulate intracellular protein synthesis. Experimental studies revealed that glutamine deficiency causes a necrotising enterocolitis and increases the mortality of animals subjected to bacterial stress. First clinical studies have demonstrated a decrease in the incidence of infections and a shortening of the hospital stay in patients after bone marrow transplantation by supplementation with glutamine. In critically ill patients parenteral glutamine reduced nitrogen loss and caused a reduction of the mortality rate. In surgical patients glutamine evoked an improvement of several immunological parameters. Moreover, glutamine exerted a trophic effect on the intestinal mucosa, decreased the intestinal permeability and thus may prevent the translocation of bacteria. In conclusion, glutamine is an important metabolic substrate of rapidly proliferating cells, influences the cellular hydration state and has multiple effects on the immune system, on intestinal function and on protein metabolism. In several disease states glutamine may consequently, become an indispensable nutrient, which should be provided exogenously during artificial nutrition.

Olive Leaf Extract I'm taking for the effects of oleuropein (anti-bacterial, anti-viral, proteasome stimulator) and hydroxytyrosol which is very similar to resveratrol but has not gotten much attention for some reason. Out of all my supplements, this in particular causes antibiotic-like herx reactions severe enough that I absolutely could not tolerate 500mg 18% oleuropein capsules. I'm on 250mg 12% oleuropein capsules now, and I will attempt to take two at a time and then graduate to 500mg 18% over time as tolerated.

It may be killing some gut bacteria but so are the antibiotics I take and likely the andrographis. The daytime is dangerous for my gut flora. However, I don't take anything that could hurt them at bedtime, and thats when I dose all my probiotics, so they have 8-9 hours to propagate through my system and hang out before the attack resumes in the morning. I have thus far avoided any gut-related complications of antibiotic therapy (knock on wood) despite taking them in high doses for about 7 months now, so my probiotic regimen combined with a low carbohydrate diet works (for me).

Edited by FunkOdyssey, 13 February 2009 - 02:19 PM.

[rwac]

Would manganese supplementation be contraindicated for Lyme? BB uses manganese instead of of iron for all it's enzymatic activities. I tested low for manganese on a hair mineral analysis and want to start supplementing for it's many functions in connective tissue. Maybe the low levels of manganese could explain why my case isn't as bad as others like I saw in the "under our skin" documentary.

Would supplementing with this stimulate the bacteria to multiply and enhance the progression of the disease?

Lufega,

Thanks for that info. I've been feeling ill lately, and I didn't know why.
Dropping the Manganese seems to have done the trick.

[Lufega]

Would manganese supplementation be contraindicated for Lyme? BB uses manganese instead of of iron for all it's enzymatic activities. I tested low for manganese on a hair mineral analysis and want to start supplementing for it's many functions in connective tissue. Maybe the low levels of manganese could explain why my case isn't as bad as others like I saw in the "under our skin" documentary.

Would supplementing with this stimulate the bacteria to multiply and enhance the progression of the disease?

Lufega,

Thanks for that info. I've been feeling ill lately, and I didn't know why.
Dropping the Manganese seems to have done the trick.

It was all wild speculation from my part. Every morning I was utterly exhausted and I couldn't explain why. I started dropping supps. one by one and moving some to the evening to rule them out. Nothing worked until I dropped manganese and subsequently raising my dose of glutamine improved the problem. I've also been eating a lot of nuts lately, most which are high in manganese.

[Brainbox]

I've learned a bit more about this in the past couple of days that provide additional clues. IFN-gamma (produced in response to the infection) induces IDO, which depletes tryptophan. In the brain, this can lead to neurotoxicity through the production a tryptophan metabolite called quinolinic acid.

What is the purpose of this immune response? There seem to be two possibilities. First it may be a strategy to withhold a valuable nutrient from the pathogens, in the same way the body attempts to starve infections of iron. Secondly it may be a strategy to increase NAD availability for the immune cells (despite adequate niacin intake). I was reading more about B3 and NAD -- different tissues and different cells can only obtain NAD from specific sources, depending on which enzymes they have at their disposal. Nicotinic acid and niacinamide for example do not directly elevate NAD in neurons, only nicotinamide riboside can do that. Tryptophan and its metabolites are the primary source of NAD for the liver, regardless of niacin intake.

So I suggest that NAD production might be another reason for the induction of IDO in response to infection. Regardless of the intention, a definite consequence is reduced availability of tryptophan for serotonin production and this has a variety of negative implications for the patient. I think this is a cause or at least a contributing factor to many cases of anxiety, depression, insomnia, etc.

There might be a third one, although I have to admit it's a very gross thought. As seen from the perspective of a parasite, neuro-toxicity in a host that induces a passive behaviour could be beneficial...
We still don't know all the cause - effect pathways involved, our knowledge is for a significant part based correlation as far as I understand, so I guess this (or other explanations) are possible. Hence my quest for information regarding a IDO / NAD / bacterial / fungal / whatever relation. It makes sense for a parasite to lower the immune response of a host as well, so that part is contradicting this hypothesis.

Edited by Brainbox, 14 February 2009 - 07:04 PM.

[youandme]

Olive Leaf Extract I'm taking for the effects of oleuropein (anti-bacterial, anti-viral, proteasome stimulator) and hydroxytyrosol which is very similar to resveratrol but has not gotten much attention for some reason. Out of all my supplements, this in particular causes antibiotic-like herx reactions severe enough that I absolutely could not tolerate 500mg 18% oleuropein capsules. I'm on 250mg 12% oleuropein capsules now, and I will attempt to take two at a time and then graduate to 500mg 18% over time as tolerated.

It may be killing some gut bacteria but so are the antibiotics I take and likely the andrographis. The daytime is dangerous for my gut flora. However, I don't take anything that could hurt them at bedtime, and thats when I dose all my probiotics, so they have 8-9 hours to propagate through my system and hang out before the attack resumes in the morning. I have thus far avoided any gut-related complications of antibiotic therapy (knock on wood) despite taking them in high doses for about 7 months now, so my probiotic regimen combined with a low carbohydrate diet works (for me).

Thanks Funk
Good Explanation..and the fact that gut is acting as normal proves your theory well.
Gonna get me some Glutamine...not sure on the Olive Leaf Extract...I always wonder if Herx reactions are Herx reaction's or something other...I know you believe they are...are they becoming less radical ?

[FunkOdyssey]

Olive Leaf Extract has become more tolerable at 250mg 12% Oleuropein 3x daily. In a week or two I may try to increase the dose.

Removed:
Twinlab Super Probiotic - This didn't agree with my system. Might have been a little too hardy and dominated the other friendly bacteria, I'm not sure.
Carlson B-Compleet w/C - This tablet is too difficult to swallow, got stuck in my throat a couple times. I also decided I want my only supplemental NAD precursor to be nicotinic acid. I might also have been impacted a little by the study I poked fun at andre about -- I now want to keep riboflavin lower.

Changed:
L-Glutamine- Increased dose to 7.5g 3x daily (22.5g total)
Lithium Orotate- Increased dose to 5mg elemental lithium 4x daily (20mg total)

Added:
AOR Advanced B Complex - Replacement for Carlson B-Compleet with no niacinamide and RDA level dose of riboflavin.
Nature's Way Nicotinic Acid - 100mg 4x daily (400mg total). Using this as my main NAD precursor input should raise NAD levels in most tissues without inhibiting SIRT1 with excessive niacinamide. However, sufficient niacinamide will still be available to tissues that cannot utilize nicotinic acid after NAD is recycled into niacinamide.
Now NAD lozenges - 25mg NAD 4x daily. I added the nicotinic acid first and may have noticed some improved energy and mood from that. Unfortunately, I don't think the addition of NAD lozenges is doing anything noticeable. I will try to skip some days and see if any difference can be observed. If not, I will use only nicotinic acid because it is far cheaper.
Natrol 5-HTP TR (Time Released) - 100mg a bit before bedtime. Using to circumvent broken tryptophan metabolism due to chronic infection. Instant release 5-htp seems to wreak havoc on everything with brief, super high serotonin spike. Noticed improved sleep quality and daytime alertness and mood with the time released version.

I also added Olga's regimen to the original post. Now that we are married I thought it was worthy of documentation.