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Glutamate causes orthostatic intolerance? I didn't know that.

hapl808

Senior Member
Messages
2,117
I definitely noticed this - which was unexpected. Kefir and such improved my gut, but I noticed it significantly worsened my already bad tachycardia, so I mostly had to stop. I don't think all probiotic supplements do the same.
 

Violeta

Senior Member
Messages
2,952
I definitely noticed this - which was unexpected. Kefir and such improved my gut, but I noticed it significantly worsened my already bad tachycardia, so I mostly had to stop. I don't think all probiotic supplements do the same.
Wow, I used to make home made kefir and depend on it for a lot of nutrients. Your message just made me realize that's why it was bothering me so much. One time I was at work and couldn't pick my head up off the lunch room table. They had to call my husband to drive me home. I didn't know about orthostatic intolerance back then, so I never figured out why it was doing that to me, I just stopped drinking it.


I just looked up kefir+glutamate and it says that "Lactobacillic fermentation of milk is known to produce glutamic acid (a glutamate precursor), but at least one species present in kefir grains (Lactococcus lactis subsp. lactis) has been shown to convert glutamic acid to GABA (γ-aminobutyric acid, the body's primary neural-relaxant)."

Would this mean that if kefir causes orthostatic intolerance that that's not happening well enough and there's still too much getting converted to glutamate?

Yogurt does bother me, too. But I always had thought of glutamate symptoms as being like the symptoms that bone broth gave me...up all night with horrible agitation in my gut and brain. This is interesting.
 

Violeta

Senior Member
Messages
2,952
Holy cow! 😳

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Violeta

Senior Member
Messages
2,952
I read this study back in 2019, but time to read it again.

I have read that low cellular energy production issues play a part in glutamate excitotoxicity and was wondering if thiamin deficiency was involved.
.
I found this:

https://www.hindawi.com/journals/tswj/2013/309143/
Thiamine deficiency has been proposed to lead to mitochondrial dysfunction that determines impaired cellular metabolism, glutamate excitotoxicity, and oxidative stress in the thalamus, mammillary bodies, and other diencephalic structures.

Glutamate plays a significant role in the development of thiamine deficiency lesions. In fact, glutamate excitotoxicity is the primary mechanism of cell death in the PTD model associated with diencephalic amnesia.

The neurocytopathological changes induced by PTD are identical to those that have been described in glutamate-induced excitotoxic lesions.
 

Violeta

Senior Member
Messages
2,952
Selenium can help with glutamate mitochondrial damage. I had no idea.

This might be why sodium selenite almost immediately gives relief from a feeling of very high anxiety that I sometimes have.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378533/

Glutamate Induces Mitochondrial Dynamic Imbalance and Autophagy Activation:
Preventive Effects of Selenium


"Abstract
Glutamate-induced cytotoxicity is partially mediated by enhanced oxidative stress. The objectives of the present study are to determine the effects of glutamate on mitochondrial membrane potential, oxygen consumption, mitochondrial dynamics and autophagy regulating factors and to explore the protective effects of selenium against glutamate cytotoxicity in murine neuronal HT22 cells.

Our results demonstrated that glutamate resulted in cell death in a dose-dependent manner and supplementation of 100 nM sodium selenite prevented the detrimental effects of glutamate on cell survival.

The glutamate induced cytotoxicity was associated with mitochondrial hyperpolarization, increased ROS production and enhanced oxygen consumption. Selenium reversed these alterations. Furthermore, glutamate increased the levels of mitochondrial fission protein markers pDrp1 and Fis1 and caused increase in mitochondrial fragmentation.

Selenium corrected the glutamate-caused mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria.

Finally, glutamate activated autophagy markers Beclin 1 and LC3-II, while selenium prevented the activation. These results suggest that glutamate targets the mitochondria and selenium supplementation within physiological concentration is capable of preventing the detrimental effects of glutamate on the mitochondria.

Therefore, adequate selenium supplementation may be an efficient strategy to prevent the detrimental glutamate toxicity and further studies are warranted to define the therapeutic potentials of selenium in animal disease models and in human."
 

datadragon

Senior Member
Messages
397
Location
USA
Selenium corrected the glutamate-caused mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria.

Selenium provokes zinc release by Metallothioneins (MT), via reduction of glutathione peroxidase. This fact is crucial because high MT may be unable to release zinc with subsequent low intracellular free zinc ion availability for immune efficiency, metabolic harmony and antioxidant activity. https://pubmed.ncbi.nlm.nih.gov/18991691/
that may be very important in restoring immune function that is lost due to being sequestered in the cell with an infection present also.

As a constituent of selenoproteins, selenium is needed for the proper functioning of neutrophils, macrophages, NK cells, T lymphocytes and some other immune mechanisms. https://pubmed.ncbi.nlm.nih.gov/12879758/ Zinc supplementation induces killing activity of primary NK cells from healthy donors. A rapid zinc influx after zinc deficiency boosts the NK cell cytotoxicity. https://www.sciencedirect.com/science/article/abs/pii/S1756464618303621 Zn deficiency has been associated with thymic atrophy, impaired B, T, and NK cell responses, and T helper-1 (Th1) cytokine production https://www.cell.com/immunity/pdf/S1074-7613(13)00428-7.pdf


As far as POTS, to give you a starting point. Plasma norepinephrine (NE) is often elevated in patients with POTS, resulting in consideration of dysfunction of the norepinephrine transporter (NET) encoded by the SLC6A2 gene. SLC6A2 NET regulates norepinephrine homeostasis and is responsible for the reuptake of norepinephrine (and dopamine in prefrontal regions) into the presynaptic neuron. https://www.nature.com/articles/s41380-019-0461-x Familial orthostatic tachycardia due to norepinephrine transporter deficiency https://pubmed.ncbi.nlm.nih.gov/11458707/

However, It appears from my digging that norepinephrine transporter methylation is associated with NET expression and Norepinephrine transporter (NET) expression was decreased by Zinc deficiency alone. DNA methylation is an effective epigenetic process that is frequently linked to changes in gene expression. Zinc is a vital micronutrient that plays a crucial role in DNA methylation. Therefore, abnormal zinc levels may cause aberrant DNA methylation and other diseases.

https://www.sciencedirect.com/science/article/pii/S0166432815000820
https://www.sciencedirect.com/science/article/pii/S240584402202103X
https://www.nature.com/articles/s41380-019-0461-x

Epigenomic changes associated with impaired norepinephrine transporter function in postural tachycardia syndrome. Butyrate increases NET and is found low by the NIH in ME/CFS. https://pubmed.ncbi.nlm.nih.gov/27345145/ Butyrate functions including HDACs also are dependent on zinc covered some before.

Otherwise some other areas like BH4/Nitric Oxide is also regulated by zinc https://forums.phoenixrising.me/thr...s-chronic-fatigue-syndrome.90582/post-2453550
https://mybiohack.com/blog/postural-orthostatic-tachycardia-syndrome-pots-intolerance

@Mary @Violeta
 
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