Overstimulation, hyperxciteability, and things that help

I am reading here about a lot of people having overstimulation/overexciteability issues. I get them from time to time myself (such as new due to flea product exposure and re-exposure). I know it's weird because it seems to have the opposit effect for many of you, but DHEA calms me down. (It's just that in the face of flea control product exposure the DHEA gives out early and I don't want to take more). I just ran across this at www.heartfixer.com and thought I'd report it:
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Excitotoxicity The CBS up regulation leads to excess production of alpha-ketoglutarate, which is converted in to glutamate, a stimulatory neurotransmitter. Under normal circumstances, glutamate will be converted in to GABA, a calming neurotransmitter, but the enzyme systems that convert glutamate in to GABA are compromised by lead and mercury, the clearance of which seems to be compromised in individuals with methyl cycle defects (here is a situation where dysfunction of a genetically abnormal enzyme leads to acquired dysfunction of a genetically normal enzyme system). The result is excitotoxicity, stimulatory behavior in autistic kids (stims) and anxiety and sleeplessness in adults. We approach this problem by limiting alpha-ketoglutarate and glutamate rich foods from your diet (more on Excitotoxicity to follow; diet tips in appendix) and by supplementing you with GABA, aiming to restore GABA:Glutamate balance. GABA is initiated at 500 mg once or twice a day, advancing the dose as you see fit by your response.
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Some of you may have the CBS +/+ genetic mutation like me, some may have heavy metal poisoning. But this paragraph suggests that what is happening is glutamate toxicity. Well estrogen prevents glutamate toxicity! (There is a study which proves it, I had it on my old memory stick that I lost...ugh - finding these studies again can be a bear....let me see if I can do it: hang on I will return). Ok, here is one reference: Goodman, Y., Bruce, A. J., Cheng, B. and Mattson, M. P. (1996), Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid ?-Peptide Toxicity in Hippocampal Neurons. Journal of Neurochemistry, 66: 18361844. doi: 10.1046/j.1471-4159.1996.66051836.x


I also tried a product called Lentra one day -- one pill damped me down but two almost made me sleep. It is from Sanseco where I had my adrenal testing done. They say it has magnesium taurate, L-theanine, P5P, lactium - a GABA receptor agonist, and NSB, some kind of delivery system. I left it at my Dad's so I can't try it again right now to see if I like it if I only take 1.

I guess I am opening a topic for people to tell what they have tried and how it has worked. It seems to be a very common problem here.

Here's something about the effects that various hormones have. You note that estrogen must be methylated to have some of these effects (for instance, apparently it is methylated estrogen that prevents fibroid tumors and that is a potent anti-cancer agent that is being patented.

Key: Hcy = homocysteine; GSH = glutathione; BH4 = tetrahydrobiopterin

Estrogen (17?-estradiol) (E2):
Raises BH4, reduces oxidative stress (eliminates high blood pressure) (1)
Promotes formation of cystathione and GSH (3)
Estradiol maintains folate levels after menopause and lowers Hcy, mainly after a methionine load. (4)

E2 O-methylates (requiring SAMe) to 2-methoxyestradiol (recently trademarked under the trade name Panzem): (**See NOTE)
o one of the most potent anti-carcinogenic estrogen metabolites. (9,10)
o an exceptionally tiny amount has anti-proliferative, anti-angiogenic, and apoptotic effects on uterine fibroid cells. (11)
o potent effects against pancreatic and gastric cancer cells (12)
o reduced the amount of chemotherapeutic drugs needed to kill ovarian cancer cells (13)
o induces apoptisis in prostate cancer cells (17)
o effective against aggressive breast cancers (18)
**NOTE: Prolonged stress could reduce the methylation of estrogens, if the required methyl groups get used by the body to make adrenaline instead. Stress reduction strategies can reduce cancer risk. (14-16)

Estrogen:
NMDA receptor agonist (Hcy-induced neurotoxicity is dependent on the overstimulation of the NMDA receptor) (6)
induces expression of the PEMT gene and allows women to make more needed choline endogenously (19)

2-hydroxy-estrogens:
strongly inhibit enzymic methylation and biological inactivation of neurotransmitters (20)

Progesterone:
Progesterone blocks at the NMDA receptor (Hcy-induced neurotoxicity is dependent on the overstimulation of the NMDA receptor) (6)

Estrogens and progesterone:
Protects neurons against glutamate toxicity (5)
Protects neurons against lipid peroxidation induced by FeSO4 (5)
Protects neurons against amyloid ?-peptide (A?) toxicity (5)
Protects neurons against glucose deprivation (5)
Attenuate A?- and glutamate-induced elevation of intracellular free Ca2+ concentration (5)
Protect against hcy induced neuronal death (6) Hcy is a glutamate agonist which causes an increase on Ca(2+) influx via activation of NMDA excitatory amino acid receptors (6)
Up-regulate the activities of SOD and GPx. (6) whereas Hcy downregulates them (6).

Corticosterone:
Exacerbates glutamate toxicity (5)
Exacerbates lipid peroxidation induced by FeSO4 (5)
Exacerbates amyloid ?-peptide (A?) toxicity (5)

Testosterone:
Upregulates C?S 2 fold (lowering homocysteine) (2)
Blocks formation of cystathionine and thus reduces GHS (3)

(1) Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats, Lam, Kwok-Keung, et al, Menopause, 2006, Vol 13, issue 2, p294-302)
(2) Modulation of homocysteine metabolism and redox homeostasis via regulation of cystathionine beta-synthase, Prudova, et al., The University of Nebraska - Lincoln, 2006)
(3) Geier, D., and Geier, M. A Clinical and Laboratory Evaluation of Methionine Cycle- Transsulfuration and Androgen Pathway Markers in Children with Autistic Disorders. Hormone Research 66: 182-188, 2006.
(4) Ventura, Cagnacci, Malmusi, Panini, Baldassari, Arangino, Volpe, Salvioli, 2001, Continuous combined hormone replacement therapy with oral 17[beta]-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women. Menopause: V8, Issue 4, 252-258, 2001
(5) Goodman, Y., Bruce, A. J., Cheng, B. and Mattson, M. P. (1996), Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid ?-Peptide Toxicity in Hippocampal Neurons. Journal of Neurochemistry, 66: 18361844. doi: 10.1046/j.1471-4159.1996.66051836.x
(6) Wing Man Wu, AN INVESTIGATION INTO THE NEUROPROTECTIVE EFFECTS OF ESTROGEN AND PROGESTERONE IN A MODEL OF HOMOCYSTEINE-INDUCED NEURODEGENERATION, THESIS, Rhodes University, 2005
(7) Jon Nilsen and Roberta Diaz Brinton, 2003, Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling. Department of Molecular Pharmacology 1050610511 _ PNAS _ September 2, 2003 _ vol. 100 _ no. 18
(8) Shuhua Chen, Jon Nilsen, and Roberta Diaz Brinton, 2006, Dose and Temporal Pattern of Estrogen Exposure Determines Neuroprotective Outcome in Hippocampal Neurons: Therapeutic Implications. Endocrinology 2006 147:5303-5313
(9) Cancer Metastasis Rev. 2000;19(1-2):173-9.
(10) Acta Biochim Pol. 2002;49(1):59-65.
(11) J Soc Gynecol Investig. 2006 Dec;13(8):542-50.
(12) J Gastroenterol Hepatol. 2007 Sep;22(9):1469-73.
(13) Eur J Gynaecol Oncol. 2004;25(6):699-701.
(14) J Psychosom Res. 2009 Mar;66(3):255-8.
(15) Cancer. 2008 Sep 1;113(5):1048-57.
(16) Drugs Today (Barc). 2009 Feb;45(2):115-26.
(17) Cancer Invest. 2006 Oct;24(6):588-92.
(18) Nordquist RE, Adalsteinsson O. Work in progress.
(19) Steven H. Zeisel, Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline. IUBMB Life, Volume 59, Issue 6 2007 , pages 380 387
(20) Journal of Clinical Endocrinology & Metabolism Vol. 34, No. 4 736-746
doi:10.1210/jcem-34-4-736
Copyright 1972 by the Endocrine Society.
(21) Peter Ball, Rudolph Knuppen, Margitta Haupt, Heinz Breuer, 1972, Interactions Between Estrogens and Catechol Amines III. Studies on the Methylation of Catechol Estrogens, Catechol Amines and other Catechols by the Catechol-O-Methyltransferase1 of Human Liver. Journal of Clinical Endocrinology & Metabolism Vol. 34, No. 4 736-746

I take TheaNAQ to bring down my glutamate (tested high, along with glycine). It contains NAC, ALA, Co Q10, and L-theanine. Helps quite a lot with OI symptoms, but not with sleep. TravaCor (5htp, Theanine, Taurine) seemed to help too.

I've tried melatonin for sleep, which made ME symptoms quite a bit worse, probably because melatonin causes/worsens OI. I just stopped Amitriptyline because pain has been worse since I started it and I feel like a zombie until 2 hours before bed time. I'll probably start the TravaCor again now that I'm off the Amitriptyline - didn't want to mix drugs boosting Serotonin action.

i dont know if u can say certain hormones do certain things, its abit to simplistic, its a matter of balance. cortisol causing glutamate toxicity?? too much can, but not enough cortisol has its own problems, also alot of flow on effects from certain steriods eg increasing testosterone in men can increase estrogen via aromitization, progesterone can have flow on effects and increase cortisol levels. there are many flow on effects of hormones and negative feed back issues as well. Heres a link showing hormone pathways http://www.biodia.com/TechnicalCharts/SteroidalHormonechart.pdf , hormones dont always seem to follow these pathways as in pregnenolone steal where majority of pregnenolone is shuttled towards cortisol production at the expense of sex steroids like dhea, estrogen, testosterone, even aldosterone.

I agree that overstimulation is a problem for many, its finding where along the hormone or neurotransmitter pathway thats effected. Dr Jay Goldstein had some success using drugs to modulate NMDA issues. Alot of stimulation issues can also be from cytokines produced from infections and our response from the immune system.
I will try and find a link but read recently about how low cortisol levels can allow allow noradrenaline signalling to continue, once cortisol and adrenal hormones are brought into balance this noradrenaline signalling is reduced, which can help with insomnia and anxiety etc I think it was a Dr Mariano who specialises alot in this area, its over my head but trying to understand and getting some good info out of it. He seems to be able to explain the whole HPA axis with neurological, hormonal and immune systems and there dysfunctions relate to each other.

cheers!!!

Valentijn said:

I take TheaNAQ to bring down my glutamate (tested high, along with glycine). It contains NAC, ALA, Co Q10, and L-theanine. Helps quite a lot with OI symptoms, but not with sleep. TravaCor (5htp, Theanine, Taurine) seemed to help too.

I've tried melatonin for sleep, which made ME symptoms quite a bit worse, probably because melatonin causes/worsens OI. I just stopped Amitriptyline because pain has been worse since I started it and I feel like a zombie until 2 hours before bed time. I'll probably start the TravaCor again now that I'm off the Amitriptyline - didn't want to mix drugs boosting Serotonin action.

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Hmm. A lot of people seem to take NAC. I would say w/o difficulty but I had to pause and wonder if it could be the cause of difficulties? Fredd has severe problems with the methyl cycle on NAC and I am afraid of it because it is known to cause problems for many autistics which I may be.

What is OI? I was surprise to have a theanine formula do anything for me because I make a lot of taurine so that is a do-nothing for me. Speaking of theanine, ...it is a component of tea which I was starting to switch to but now I am afraid of tea.

I read that the reason tea inhibits cancer is because it breaks the folate pathway! I don't want that. I don't suppose anyone else knows anything b=about that?

Good to know there are other natural products that work.

Realy cool diagnram heaps. I have one similar with my labs...it used to be available at www.meridianvalleylab.com - maybe still is.
think the way to deal with keeping hormones where they should be is via supplements (like to keep testosterone levels - use alpha-reductase inhibitors and aromatase inhbitors). Meridian Valley labs says certain supplements affect which estrogen metabolites ar emade vs others (broccoli helps, for instance).

I always wondered why I dont do well on progesterone -- I will study your chart. I suspect it has something to do with cortisol but I thought DHEA could make cortisol as well? I am in half brain mode as I am in a class and the instructor is trying to figure out where his code went wrong. Gotta go

rydra_wong said:

What is OI?

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Orthostatic Intolerance, a common symptom in ME/CFS. The two most common forms for us seem to POTS (Postural Othorstatic Tachycardia Syndrome) and NMH (Neurally Mediated Hypotension).

Both cause light-headedness due to regulation problems with cardiovascular system. With POTS it happens as soon as you sit up or stand up, and is measured by a spike in heart rate. With NMH it can happen after sitting upright or standing upright for a while, especially if not moving much, such as standing in a slow line. In that case, pulse pressure (difference between systolic and diastolic measurements) drops below 25 or so.

NMH causes me "fatigue" after I've been sitting upright for 1-3 hours. Then I need to lay down, and feel better after half an hour to an hour, but don't fall asleep.

I know next to nothing about it despite that I may have it but isn't orthostatic hypotension one of the rule of thumb tests for adrenal problems? I seem to recall my doctor wanting me to measure my b.p. before I got up in the morning and then immediately after I got up to detect adrenal issues (but I never did it). We just did the lab and found I do have such issues, at least during allergy season. In fact now that I know what it s I know exactly when I have it because my blood pressure goes low despite 3 genes that cause high. I go into and out of adrenal issue mode due to the severity of my allergies and now apparently to toxins like flea control products.

Hyperexcitablility can occur in conditions of abnormal circulatory control (NMH and POTS) as a consequence of the bodies poor attempts to compensate for reduced cerebral perfusion or autoregulation. Peripheral sympathetic system innerves the cerebral and can trigger/potentiate cerebral excitation.

This i think is high on my symptoms list. I've been taking SAMe which helps my body relax and gives me more energy through the day. On the 400mcg.
When i have something i'm sensitive to, i always become more sensitive to light and noise. I'm working on correcting it with more boundaries/psychological barriers, hopefully that assists me. It tends to dump me into overprocessing in my head too so the more i learn how to process stuff and get out of it, the less it will become a longer term problem.

I'm gonna try P5P and TMG next. Hopefully people have more ideas. I think when the hyperexcitability mode hits harder than normal, it makes it impossible to diet right, do the wrong things, cant meditate, get crabby, dont want to work even more than usual.