Lowering Glutamate & Protecting Against Glutamate Damage

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Obviously diet is one of the most important, if not, the most important step in lowering glutamate. However, these may prove beneficial in helping those when experiencing a peak of symptoms related to high glutamate and neurological inflammation, i.e. following consumption of a high glutamate food, trauma or a “flare” from PANS (pediatric autoimmune neuropsychiatric disorder) or PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections).  Additionally, working to lower inflammation/glutamate by treating underlying sources inflammation (metals, microbial imbalances, parasites, microglial activation, poor detoxification pathways, various toxins, etc.) will also be hugely beneficial.  We’ve personally found homeopathy to be great for this. The following list is not comprehensive as it is simply all the I’ve had time to gather at the moment.   Not all of these are REID approved.  I  do not have personal experience with all of them, nor would I recommend all of them (especially the pharmaceutical options).You will want to read the comments as some of the items used to temporarily lower glutamate, can actual work to increase glutamate/glutamate sensitivity over time. The information shared within this blog has been gathered by a mother, not a physician, and should not act as medical advice. Under no circumstances shall I, or any contributors and affiliates of the blog, be responsible for damages arising from use of the blog. 

Natural Options

Acorus gramineus (Calamus Root aka Sweet Flag) This essential oil has shown to inhibit NMDA receptor activity, increase GABA and lower glutamate upon inhalation.  “These results demonstrated that EO extracted from AGR exhibited neuroprotective effects on cultured cortical neurons through the blockade of NMDA receptor activity, and that the glycine binding site appeared not to be the major site of action. ” http://www.sciencedirect.com/science/article/pii/S0024320501009444   

  • “Furthermore, inhalation impressively inhibited the activity of gamma-aminobutyric acid (GABA) transaminase, a degrading enzyme for GABA as the inhalation period was lengthened. The GABA level was significantly increased and glutamate content was significantly decreased in mouse brain by preinhalation of the essential oil. The above results suggest that the anticonvulsive effect of this AGR oil is originated by the enhancement of GABA level in the mouse brain, because convulsion depends partially on GABA concentration which can be properly preserved by inhibiting GABA transaminase. Moreover, fragrance inhalation progressively prolonged the pentobarbital-induced sleeping time as inhalation time was lengthened.” https://www.ncbi.nlm.nih.gov/pubmed/12843622/.

Ashwaganda (Withania somnifera) Protects against glutamate. Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity. “ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.” https://www.ncbi.nlm.nih.gov/pubmed?term=ashwagandha%20AND%20%22multiple%20sclerosis%22

Alpha Lipoic Acid–  (found in low amounts in spinach, broccoli, yams, etc) ALA helps glutamate transport proteins, which help in the removal of excess extracellular glutamate. “Another particularly destructive product is 4-hydroxynonenal (4-HNE), an aldehydic lipid peroxidation product found in abundant supply in cases of neurodegeneration. Interestingly, peroxylnitrite and 4-HNE are found in the same neurons. This lipid peroxidation product has been shown to be especially destructive of synaptic connections and mitochondrial enzymes and can significantly inhibit glutamate transport proteins. It is neutralized only by alpha-lipoic acid, glutathione, and certain flavonoids.”“In summary, these findings show that low doses of LA were able to modulate glial functions and it appears to have remarkable therapeutic potential in neurological diseases involving oxidative stress by improving glutamatergic metabolism.” Spinach, broccoli, yams, and liver contain low amounts of alpha lipoic acid. http://www.jpands.org/vol9no2/blaylock.pdf

  • “In summary, these findings show that low doses of LA were able to modulate glial functions and it appears to have remarkable therapeutic potential in neurological diseases involving oxidative stress by improving glutamatergic metabolism.” https://www.ncbi.nlm.nih.gov/labs/articles/23286972/

Andrographis (andrographolide)– inhibits microglial activation “Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia” “Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-κB and microglial activation, and reduction in the production of cytokines including TNF-α and IL-1β, and pro-inflammatory factors such as PGE2. Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990163/

Apigenin flavonoid (found in chamomile, parsley, celery, thyme, lemon balm, cloves, etc.)– After years of homeopathy, we discovered that the best remedy during a “flare” or times that we may be a little off, was a low dose of the homeopathic remedy, chamomilla.  So I decided to do a little research and of course discovered that it inhibits glutamate because of its high concentration of the flavonoid, apigenin.  “The flavonoid inhibited also peak amplitude and frequency of spontaneous postsynaptic excitatory currents (sEPSCs). Finally, apigenin is neuroprotective against glutamate-induced neurotoxicity in cerebellar and cortical neurons in culture. Our data reveal the antagonistic effect of apigenin on GABA and NMDA channels.” https://www.ncbi.nlm.nih.gov/pubmed/15464088

Bee Pollen- Many in the group, including myself, have avoided the use of bee pollen due to a higher glutamic acid content. However, wondering if in the natural form (without any sort of degradation) it may actually be beneficial. Was researching the glutamate/propionic acid connection when I came across this article. Also, interesting note that propionic acid (often associated with clostridia, gut bacteria imbalances, protein and/or carbohydrate fermentation in the gut & a diet high in grains) can induce glutamate excitotoxicity. “The results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent.
In conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440900/

Beta-caryophyllene (found in Cannabis, Copaiba EO, etc) and CBD-  Protects against glutamate. “β-Caryophyllene Protects The C6 Glioma Cells Against Glutamate-Induced Excitotoxicity Through The Nrf2 Pathway.. Available from: https://www.researchgate.net/publication/265393128_b Caryophyllene_Protects_The_C6_Glioma_Cells_Against_Glutamate-Induced_Excitotoxicity_Through_The_Nrf2_Pathway [accessed Oct 26 2017].” https://www.researchgate.net/publication/265393128_b-Caryophyllene_Protects_The_C6_Glioma_Cells_Against_Glutamate-Induced_Excitotoxicity_Through_The_Nrf2_Pathway

  • Cannabis “Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas. Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation, affecting glutamate release, inhibiting receptors and transporters function, reducing enzyme activity, and disrupting glutamate synaptic plasticity after prolonged exposure.” https://www.ncbi.nlm.nih.gov/pubmed/26987641
  • “The endocannabinoid system provides a framework for many of cannabis’ protective benefits. The cannabinoid type I and II receptors (CB1 and CB2) are powerful regulators of glutamate release, can be anti-inflammatory, and facilitate anti-oxidant effects.” “This important role for CB receptors supports the benefits of THC, which directly activates CB1 and CB2 receptors, and CBD, which indirectly activates them. CB1 receptors are found on brain cells and their activation by endogenous cannabinoids or THC dampens their communication.Particularly, CB1 receptors have a profound ability to reduce glutamate release, highlighting the potential for prominent cannabinoids to suppress the harmful effects of glutamate following brain trauma. Since excessive glutamate signaling is a main contributor to early stage damage after brain injury, this is an important place to start to limit the risk of severe brain damage and even death.” “How were THC and CBD protective? Reduced glutamate signaling protects brain cells from dying after an injury and cardiovascular event. But the potential for behavioral recovery also depends on the levels of free radicals and brain inflammation. Low doses of THC can be anti-inflammatory, but high-doses may increase inflammation, which highlights the importance of proper dosing.” https://www.leafly.com/…/cannabis-effects-brain-damage…
  • “Neuroprotection: CBD oil has been seen to enhance the production of myelin to maintain the myelin sheath structure around neurons. This structure works as a neuroprotector and prevents the neurons from aging and degeneration. People can use it to reduce the frequency of cognitive mental disorders such as Alzheimer’s’, Multiple Sclerosis and Dementia which progress with age. CBD oil can also help in repairing of brain cells and reduction in hyperstimulation” http://www.tgdaily.com/health-opinion/cbd-oil-an-all-natural-supplement-that-supports-healing
  • “Cannabis is blocking excess glutamate: Fixing the gut and avoiding these toxins is key. But finding something that blocks the effects of them would be better. At least for the big pharma industry. This is exactly what they are after. Finding something that can be produced in a lab. That’s why there is a United States patent on cannabinoids. This is why the producer of MMR (Safoni Pasteur) is trying to push a breast cancer medication called Rilutek on autistic “volunteers”. What is the mechanism of Rilutek? You guessed it- it’s a glutamate inhibitor with many side effects. The cost is over $2,000 for 30 pills (not including side-effect-incurred costs). Memantine is a glutamate inhibitor, used in Alzheimer’s patients, who have long-term memory problems similar to autistic individuals. Will it be approved for autism soon? It certainly is pointing in that direction. Please read more here. Desperate demand. Limited supply. Higher profit. You get the point.
    It has been shown that cannabinoids are helpful for a garden variety of neurological disorders (e.g. those of multiple sclerosis, Alzheimer’s, stroke patients, etc.). Autism was not mentioned, but falls into the same bucket with similar fundamental neurological functionalities. Cannabinoids are known to interact with the glutamate receptor, basically making sure that excess glutamate will not cause the neuron to fire, the brain will cool down and Homeostasis is reestablished.
    If you integrate the work of Drs. Mechoulam and Russo and use the U.S. government patent paper along with this information, it gets really interesting. Here some highlights of some of the best evidence:
    “The ability of glutamate agonists to reverse cannabinoid-induced memory impairments is limited by the behavioral toxicity associated with this class of compounds. Additional difficulties arise when the mnemonic effects of cannabinoids are compared with those of antagonists of glutamatergic receptors. There are several reports suggesting that working-memory (i.e. short term) systems are largely spared by doses of N-methyl-D-aspartate (NMDA) antagonists such as phencyclidine and dizocilpine (MK801) [editor’s clarification: these two are pesticides] that disrupt the consolidation and retrieval of long-term reference memories, while cannabinoids tend to produce the opposite spectrum of effects.”
    – Cannabinoids as Therapeutics, Raphael Mechoulam, MD & Ethan Russo, MD
    “Although it has been unclear whether cannabimimetic activity plays a role in neuroprotection against glutamate induced neurological injury, the teaching in this field has clearly been that a cannabinoid must at least be an antagonist at the NMDA receptor to have neuroprotective effect.”
    -United States Government Patent US6630507, Cannabinoids as antioxidants and neuroprotectants
    “In the presence of glutamate alone (100 pM Glu), and in the presence of glutamate and 5 pM cannabidiol (CBD) or 5 pM THC, it was demonstrated that CBD and THC were similarly protective.”
    -United States Government Patent US6630507, Cannabinoids as antioxidants and neuroprotectants
    At cannabinoid meetings in the past, very few representatives of the pharmaceutical companies were present. Now the picture has changed. At least two synthetic cannabinoids are in advanced phase III clinical trials. Cannabis is currently a Schedule I drug, which federally is defined any substance that does not have any medical purpose, yet they are studying and coming out with the forbidden plants’ main constituent (THC) synthesized in a dish. SR-141716, a CB1 antagonist, developed by Sanofi (also producer of MMR), represents a new type of appetite modulator, and HU-211, developed by Pharmos, is a neuroprotectant in head trauma.
    Of course, we do need to address the gastrointestinal system as well. Avoidance of GMO foods, MSG and anything that could harbor glyphosate is imperative! It is of no surprise that many parents see improvement in symptoms just by adding probiotics to the diet, to add those “good” bacteria back that were destroyed by glyphosate. Unfortunately, it probably requires more for the gut to heal. Organic raw juices definitely are a great start. I recently heard about a mother who took her son for a fecal transplant and his symptoms were gone after 2 weeks and now is doing better than ever. More studies are needed to see what the best way to heal an inflamed gastrointestinal system of course, but this all links together just so beautifully.”http://www.phytoelements.com/…

Berberine (Alkaloid) Containing Herbs (Goldenseal, Barberry, Goldthread)-  (heads up it also lowers*** blood sugar and can help with SIBO. “Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478787/

Bergamot Essential Oil  Neuroprotective and prevents glutamate accumulation “Prevention of Glutamate Accumulation and Upregulation of Phospho-Akt may Account for Neuroprotection Afforded by Bergamot Essential Oil against Brain Injury Induced by Focal Cerebral Ischemia in Rat.” https://www.ncbi.nlm.nih.gov/pubmed/19607983

Black Cumin Seed (Nigella Sativa) “The secretion of different amino acids was studied in primary cultured cortical neurons by high-performance liquid chromatography (HPLC) using a derivation before injection with dansyl chloride. NS modulated amino acid release in cultured neurons; GABA was significantly increased whereas secretion of glutamate, aspartate, and glycine were decreased. The in vitro findings support the hypothesis that the sedative and depressive effects of NS observed in vivo could be based on changes of inhibitory/excitatory amino acids levels.” https://www.hindawi.com/journals/bmri/2010/398312/

Cat’s Claw (uncaria tomentosa)- NMDA Inhibitor  “Rhynchophylline and isorhynchophylline are major tetracyclic oxindole alkaloid components of Uncaira species, which have been long used as medicinal plants. In this study, the effects of rhynchophylline and isorhynchophylline on the ionotropic and metabotropic glutamatereceptor-mediated current responses were examined using Xenopus oocytes injected with total RNA prepared from rat cortices or cerebelli.” “hese results suggest that rhynchophylline and isorhynchophylline act as noncompetitive antagonists of the NMDA receptor and that this property may contribute to the neuroprotective and anticonvulsant activity of the Uncairaspecies plant extracts.” http://www.sciencedirect.com/science/article/pii/S0014299902025815

Chinese Club Moss (Lycopodii Serrati)– Neuroprotective by blocking the NMDA channels “Thus, on the one hand, HUP-A could be used as a pretreatment against OPs and it might also be a valuable therapeutic intervention in a variety of acute and chronic disorders by protecting against overstimulation of the excitatory amino acid pathway. By blocking NMDA ion channels without psychotomimetic side-effects, HUP-A may protect against diverse neurodegenerative states observed during ischemia or Alzheimer’s disease.” https://www.ncbi.nlm.nih.gov/pubmed/11920920

Chinese Skullcap (Scutellaria Baicalensis)– neuroprotective against glutamate damage/metabolizes glutamate. “Thus, S.B. extract exhibited neuroprotection against excitotoxic cell death, and this neuroprotection was mediated through the inhibition of NMDA receptor function by interacting with the glycine binding site of the NMDA receptor.” https://www.hindawi.com/journals/tswj/2014/459549/

  • “Baicalein, a Constituent of Scutellaria baicalensis, Reduces Glutamate Release and Protects Neuronal Cell Against Kainic Acid-Induced Excitotoxicity in Rats” “This study is the first to demonstrate that the natural compound baicalein inhibits glutamate release from hippocampal nerve terminals, and executes a protective action against kainic acid-induced excitotoxicity in vivo. The findings enhance the understanding of baicalein’s action in the brain, and suggest that this natural compound is valuable for treating brain disorders related to glutamate excitotoxicity.” https://www.ncbi.nlm.nih.gov/pubmed/27430911

Cysteine-  Reduces excess glutamate. Found in oats, broccoli, red pepper, onion, banana, garlic and will become an antioxidant when converted to glutathione. The body converts the supplement NAC to cysteine. “If you take NAC, you’re giving your body an efficient way to soak up excess glutamate, and reducing oxidative stress and inflammation over time by giving it glutathione. As a result, this helps alleviate a number of different mental health issues.” http://www.optimallivingdynamics.com/blog/the-powerful-antioxidant-proven-to-treat-6-mental-illnesses

Curcumin (Turmeric)  Protects against glutamate and inhibits glutamate release. “Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB” https://www.ncbi.nlm.nih.gov/pubmed/18420184

Frankincense- While some of these studies are geared towards arthritis, they indicate that frankincense (from the Boswellia genus) can be protective against glutamate, cytokine damage, unregulated calcium and help with neuroinflammation.  It can even help against the spread of cancer.

  • Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and Apoptosis in PC12 and N2a Cells https://www.ncbi.nlm.nih.gov/pubmed/27494534
  • Boswellia frereana (frankincense) suppresses cytokine-induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage http://onlinelibrary.wiley.com/doi/10.1002/ptr.3055/full
  • “The resinous part of Boswellia serrata possesses monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids i.e. β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid, responsible for inhibition of pro-inflammatory enzymes” Boswellia Serrata, A Potential Antiinflammatory Agent: An Overview https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309643/
  • “Frankincense oil appears to distinguish cancerous from normal bladder cells and suppress cancer cell viability. Microarray and bioinformatics analysis proposed multiple pathways that can be activated by frankincense oil to induce bladder cancer cell death. Frankincense oil might represent an alternative intravesical agent for bladder cancer treatment” https://www.ncbi.nlm.nih.gov/pubmed/19296830
  • “Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells” https://www.ncbi.nlm.nih.gov/pubmed/22171782

GABAwouldn’t suggest supplementing with GABA. “GABA itself can be converted back into glutamine, which is then converted back into glutamate through a metabolic pathway called the GABA shunt. So GABA supplementation can end up increasing glutamate in some people as well. According to Dr. Datis Kharazzian, brain expert, if you have any effect from GABA, (positive or negative) that means you have leaky gut. GABA is a large molecule that should not be able to cross the blood brain barrier, if it does, the blood brain barrier is impaired due to leaky gut.” http://www.holistichelp.net/blog/how-to-increase-gaba-and-balance-glutamate/

Ginger- “From these results, we can say that the ginger extract has a neuroprotective role against monosodium glutamate toxicity effect.” https://www.ncbi.nlm.nih.gov/pubmed/19579948

Gingko biloba- Neuroprotective effects of Ginkgo biloba extract. “Antagonistic effects of extract from leaves of Ginkgo biloba on glutamate neurotoxicity” https://www.researchgate.net/publication/13217791_Antagonistic_effects_of_extract_from_leaves_of_Ginkgo_biloba_on_glutamate_neurotoxicity

Ginseng inhibits inflammation caused by microglial/immune activation and therefore lower glutamate and cytokine levels (microglia are activated as a first step in immune response and they signal additional glutamate/cytokines/etc).

  • “Ginseng extracts also inhibit immunoexcitotoxic activation of microglia, an important factor in preventing the destructive process of Alzheimer’s disease. In fact, components in American ginseng, Korean red ginseng, and Panax ginseng all inhibit inflammation caused by microglial activation. Regulation of microglial activity is critically important in brain protection because these specialized immune cells can either be beneficial or quite harmful, depending on what state they are in. The protective activation mode stimulates the microglia to act as cells that clean up dangerous debris collected in the brain, such as dead or dying brain cell components and especially beta amyloid, the substance seen in Alzheimer’s disease.””Korean red ginseng contains a gensinoside that stimulates the microglia to assume this beneficial type of immune function — that is, it stimulates phagocytosis. Think of phagocytosis like the video game Pacman, which scurries around gobbling up dangerous brain debris.” “Korean red ginseng appears to be especially potent in reducing excitotoxicity, protecting brain cells from apoptosis (programmed death), stimulating brain repair, reducing brain inflammation, and reducing brain amyloid plaque and hyperphosphorylated tau, two products that accumulate in brains affected by Alzheimer’s disease.” “American ginseng has also shown great promise in preventing many of the processes that lead to Alzheimer’s dementia. For example, it has been shown to stimulate the growth of neurites, which are connections that allow brain cells to communicate.http://www.newsmax.com/Health/Dr-Blaylock/ginseng-Alzheimers-amyloids-Panax/2016/03/23/id/720541/
  • “The protective effects of ginseng on neurological disorders are discussed in this review. Ginseng species and ginsenosides, and their intestinal metabolism and bioavailability are briefly introduced. This is followed by molecular mechanisms of effects of ginseng on the brain, including glutamatergic transmission, monoamine transmission, estrogen signaling, nitric oxide (NO) production, the Keap1/Nrf2 adaptive cellular stress pathway, neuronal survival, apoptosis, neural stem cells and neuroregeneration, microglia, astrocytes, oligodendrocytes and cerebral microvessels.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503934/
  • “Block NMDA-induced current, inhibits calcium influx, contains neuroprotectant notoginsenoside, reduction in excitotoxicity-related cell death” https://www.ncbi.nlm.nih.gov/pubmed/19224577
  • Anti-inflammatory mechanism of ginseng saponins in activated microglia http://www.sciencedirect.com/science/article/pii/S0165572809000253

Grapeseed extract inhibits glutamate induced cell death “Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons.” “All these data suggest that GSPE inhibits 0.1 mM [Mg²⁺]o- and oxygen glucose deprivation-induced neurotoxicity through inhibition of calcium signals and NO formation in cultured rat hippocampal neurons.” https://www.ncbi.nlm.nih.gov/pubmed/21810275

“Polyphenols extracted from grape seeds are able to inhibit amyloid-beta (Abeta) aggregation, reduce Abeta production and protect against Abeta neurotoxicity in vitro.” “Amyloid plaques and microgliosis in the brain of Alzheimer’s mice fed with GSE were also reduced by 49% and 70%, respectively.”
Consumption of Grape Seed Extract Prevents Amyloid-β Deposition and Attenuates Inflammation in Brain of an Alzheimer’s Disease Mouse (PDF Download Available). Available from: https://www.researchgate.net/publication/24346721_Consumption_of_Grape_Seed_Extract_Prevents_Amyloid-b_Deposition_and_Attenuates_Inflammation_in_Brain_of_an_Alzheimer%27s_Disease_Mouse “

Hesperidin Flavonoid (found in citrus)- “The citrus flavonoid hesperidin exerts neuroprotective effects and could cross the blood-brain barrier. Given the involvement of glutamate neurotoxicity in the pathogenesis of neurodegenerative disorders, this study was conducted to evaluate the potential role of hesperidin in glutamate release and glutamate neurotoxicity in the hippocampus of rats.)””These results demonstrate that hesperidin inhibits evoked glutamate release in vitro and attenuates in vivo KA-induced neuronal death in the hippocampus. Our findings indicate that hesperidin may be a promising candidate for preventing or treating glutamate excitotoxicity related brain disorders such as neurodegenerative diseases.”  https://www.ncbi.nlm.nih.gov/pubmed/26342684

  • “Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases.” https://www.ncbi.nlm.nih.gov/pubmed/16964766

Japanese Knotwood- Japanese knotwood is a good source of Resveratrol, which reduces glutamate toxicity in the brain (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133838/)

Kudzu (aka Puerarin)Neuroprotective Effect of Puerarin on Glutamate-Induced Cytotoxicity in Differentiated Y-79 Cells via Inhibition of ROS Generation and Ca2+Influx “Furthermore, our data indicated that the neuroprotective effect of puerarin was potentially mediated through the inhibition of glutamate-induced activation of mitochondrial-dependent signaling pathway and CaMKII-dependent ASK-1/JNK/p38 signaling pathway. The present study supports the notion that puerarin may be a promising neuroprotective agent in the prevention of retinal degenerative diseases.”https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964484/

Lavender- Inhalation of lavender was also noted to inhibit convulsion induced by pentylenetetrazol, nicotine, or electroshock in mice [33]. Linalool, one of the major components of lavender oil, has been shown to inhibit the convulsion induced by pentylenetetrazol and transcorneal electroshock in different animal models [3435], an effect that may induce via a direct interaction with the glutamatergic NMDA subreceptor as well as GABAA receptors [36]. The neuroprotective effect of lavender oil on cerebral ischemia/reperfusion injury was investigated in mice. Focal cerebral ischemia was induced by the intraluminal occlusion. An aqueous extract of lavender has been shown to diminish glutamate-induced neurotoxicity in rat pups cerebellar granular cell culture [37]. Lavender oil significantly decreased neurological deficit scores, infarct size, and the levels of mitochondria-generated reactive oxygen species and attenuated neuronal damage in focal cerebral ischemia induced by the intraluminal occlusion in mice [38]. https://www.hindawi.com/journals/ecam/2013/681304/

  • “As a result, L. angustifolia protected the neurons against glutamate toxicity.” The effects of aqueous extract of Lavandula angustifolia flowers in glutamate-induced neurotoxicity of cerebellar granular cell culture of rat pups http://www.sciencedirect.com/science/article/pii/S0378874102002866
  • “In order to investigate the pharmacodynamic basis of the previously-established anticonvulsant properties of linalool, we examined the effects of this compound on behavioral and neurochemical aspects of glutamate expression in experimental seizure models. Specifically linalool effects were investigated to determine its inhibition of (i) L-[3H]glutamate binding at CNS (central nervous system membranes), (ii) N-methyl-D-aspartate (NMDA)-induced convulsions, (iii) quinolinic acid (QUIN)-induced convulsions, and the behavioral and neurochemical correlates of PTZ-kindling. The data indicate that linalool modulates glutamate activation expression in vitro (competitive antagonism of L-[3H]glutamate binding) and in vivo (delayed NMDA convulsions and blockage of QUIN convulsions). Linalool partially inhibited and significantly delayed the behavioral expression of PTZ-kindling, but did not modify the PTZ-knidling-induced increase in L-[3H]glutamate binding.” Anticonvulsant properties of linalool in glutamate-related seizure models http://www.sciencedirect.com/science/article/pii/S0944711399800440
  • Linalool is can also be high in citrus containing essential oils

Lemon Balm (Melissa officinalis L)- increases GABA “These results suggest that MOE increases cell proliferation, neuroblast differentiation and integration into granule cells by decreasing serum corticosterone levels as well as by increasing GABA levels in the mouse DG.” https://www.ncbi.nlm.nih.gov/pubmed/21076869

Licorice Root (Glycyrrhizin) high in Carbenoxolone – “Liquiritigenin effectively reduced glutamate-induced early apoptosis through inhibition of Ca(2+) influx, intracellular reactive oxygen species (ROS) production, and lipid peroxidation.” https://www.ncbi.nlm.nih.gov/pubmed/24012889

Lion’s Mane– Reduces neuronal excitability from glutamate “Extract suppressed the excitation of neurons caused by L-glutamic acid application. The assumption is made that the H. erinaceus extract contains substances that may activate receptors that cause an inhibition of spike activity. The inhibitory effect of extract was not induced by GABA and serotonin receptor activation or activation of M- and N-cholinoreceptors. Inhibition of spike activity was caused by hyperpolarization of the neuronal membrane during extract application.” http://www.dl.begellhouse.com/journals/708ae68d64b17c52,0d49dda96a2a7147,504922782f5fa5ea.html

Luteolin- A type of flavonoid found in celery, chamomile, carrots, celery, parsley, thyme, oregano, sage, basil, peppermint, artichoke and spinach is known to reduce brain and systematic inflammation by CALMING MICROGLIAL CELLS and therefore lower glutamate and cytokine levels (microglia are activated as a first step in immune response and they signal additional glutamate). Mixing these food sources with coconut oil or olive oil will help increase absorption. It is also a strong inhibitor of mast cells and helps autoimmune disorders with the reduction of immune cells. Luteolin has also been shown to stimulate brain repair, reduce exitotoxicity (from glutamate and other excitotoxins), reduce oxidative stress, improve memory, improve attention and sociability in children with ASD, and increase brain levels of the memory neurotransmitter acetylcholine. http://www.naturalnews.com/030082_luteolin_inflammation.html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307240/  Additional info gathered from the Dr. Russell Blaylock Heath Report Vol 14 #3

Magnesium- found in dark leafy greens, squash seeds, nuts, whole grains, beans and avocado is beneficial in many ways.  Magnesium protects against glutamate damage, sits on the NMDA glutamate receptor, calms cells, helps to raise GABA, improves motility and can help to resolve many various health issues. It is also my understanding that one will quickly burn through magnesium due to neuron firing when in an excitotoxic state (or a flare). Low magnesium is also associated with oxidative stress and a significant fall in cellular glutathione, low vitamin D and a dramatic increase in free radical generation. “improvements in neurological function not only are limited to sensory or motor function but also involve behavior and cognition.” “One of the vital functions for CNS magnesium is modulation of the NMDA glutamate receptor. Low levels of magnesium significantly enhance excitotoxic sensitivity and may be one of the mechanisms by which magnesium depletion precipitates seizures in otherwise healthy individuals. Furthermore, magnesium deficiency has been demonstrated in neurodegenerative disorders, such as AD, where it was correlated with cognitive scores. Patients with lowest magnesium levels had the lowest Global Deterioration Scale scores and Clinical Dementia Ratings. A review of studies found that magnesium may be useful in improving cognitive function and other symptoms in AD patients.”https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307240/#ref61 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765911/

Melatonin- “The present report demonstrates that melatonin is able to offer neuroprotection against neurotoxicity induced by glutamate and the three glutamate receptor agonists” http://annalsofneurosciences.org/journal/index.php/annal/article/viewArticle/79/262

  • Neuroprotection by melatonin from glutamate-induced excitotoxicity during development of the cerebellum in the chick embryo. “Our results show that melatonin has a neuroprotective effect against glutamate-induced excitotoxicity. This effect is morphologically revealed by the lack of neural cell death in the embryos treated with melatonin prior to glutamate injection and also by the degree of a synaptogenesis similar to that exhibited by the control group. Likewise, we corroborate the absence of teratological effects of melatonin on chick cerebellar development. Although the possible mechanisms involved in the neuroprotective effect of melatonin are discussed, i.e., direct antioxidant effects, up-regulating endogenous antioxidant defenses, and inhibiting nitric oxide formation activated by glutamate, further studies are required to establish the actual mechanism involved in the neuroprotective effect of melatonin.”  https://www.ncbi.nlm.nih.gov/pubmed/10709969
  • “Melatonin disrupts circadian rhythms of glutamate and GABA in the neostriatum of the aware rat: a microdialysis study” “The results also suggest that the day:night variations in GLU and GABA may relate to daily changes in endogenous melatonin production, while DA and its metabolites are minimally influenced by this secretory product.” https://www.ncbi.nlm.nih.gov/pubmed/11068943

Milk Thistle (contains flavonoid, silymarin)– inhibits microglial activation. “Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation” .https://www.ncbi.nlm.nih.gov/pubmed/12473078

Mitochondrial Supports CoQ10, L-Carnitine, ALA– “Increasing energy production, using coenzyme Q-10,, L-carnitine, alpha-lipoic acid, and other metabolic precursors and substrates can significantly reduce glutamate excitotoxic damage”  http://www.encognitive.com/…/A%20POSSIBLE%20CENTRAL…

NAC- “If you take NAC, you’re giving your body an efficient way to soak up excess glutamate, and reducing oxidative stress and inflammation over time by giving it glutathione. As a result, this helps alleviate a number of different mental health issues.” http://www.optimallivingdynamics.com/blog/the-powerful-antioxidant-proven-to-treat-6-mental-illnesses

Naringenin Flavonoid (found in citrus, grapes, etc.)- ” Furthermore, naringenin induced the brain-derived neurotrophic factor and other neuroprotective cytokines, and markedly improved the survival rates of the neurons 24 h following glutamate exposure. The observed results suggest that the naturally occurring bioflavonoid (naringenin) exerts neuroprotective effects via highly specific molecular targets in neurons.”
Protective effect of naringenin on glutamate-induced neurotoxicity in cultured…. Available from: https://www.researchgate.net/publication/276868364_Protective_effect_of_naringenin_on_glutamate-induced_neurotoxicity_in_cultured_hippocampal_cells

  • “There was significant recovery of glutathione content and all the antioxidant enzymes studied. Also in case of behavioural parameters studied, naringenin showed decrease in seizure severity. All these changes were supported by histological observations, which revealed excellent improvement in neuronal damage.”  Effect of Naringenin (A naturally occurring flavanone) Against Pilocarpine-induced Status Epilepticus and Oxidative Stress in Mice https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407108/

Pomegranate- “Neuroprotective effects of pomegranate effects are reducing accumulations of amyloid plaques in hippocampus, preventing neuronal tissue loss, modulating GABA and glutamate levels, inhibiting acetylcholine esterase and inhibiting lipid peroxidation in brain.” A comprehensive review of the neuroprotective effects of pomegranate.

Pyrroloquinoline quinone (PQQ)- Widely found in bacteria and foods such as spinach, celery, parsley, kiwi papaya and beans. It is known to stimulate the production and efficiency of mitochondria, protects against free radicals and reduces nitric oxide production. Defiencies in PQQ are associated with immune deficiency, dry skin, infertility and low overall fitness. “our results indicated that PQQ could protect primary cultured hippocampal neurons against glutamate-induced cell damage by scavenging ROS, reducing Ca2+ influx, and caspase-3 activity, and suggested that PQQ-activated PI3K/Akt signaling might be responsible for its neuroprotective action through modulation of glutamate-induced imbalance between Bcl-2 and Bax.” http://www.sciencedirect.com/science/article/pii/S0041008X11000524 Additional info gathered from the Dr. Russell Blaylock Heath Report Vol 14 #3

Quercetin- Inhibits glutamate release and is found in onion (highest in red onion), raw chili peppers, asparagus, kale, berries, plums, peppers, broccoli, sophora japonica leaf/flowers “These results suggest that quercetin inhibits glutamate release from rat cortical synaptosomes and this effect is linked to a decrease in presynaptic voltage-dependent Ca(2+) entry and to the suppression of PKC and PKA activity.” https://www.ncbi.nlm.nih.gov/pubmed/23933436

  • Protective effects of onion-derived quercetin on glutamate-mediated hippocampal neuronal cell death “This is the first report on the detailed mechanisms of the protective effect of quercetin on HT22 cells. Onion extract and quercetin may be useful for preventing or treating neurodegenerative disorders.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793334/

Qing Brick Tea Our results showed that QBT intake was effective in protecting monosodium glutamate-induced obese mice against metabolic syndrome and involved in the Nrf2 signaling pathway in the skeletal muscle.”

Red Sage/Dan Shen Red sage aka dan shen, inhibits glutamate release. “These results show that tanshinone IIA inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca(2+) entry and MEK signaling cascade” https://www.ncbi.nlm.nih.gov/pubmed/23542145

Resveratrol– found in red grapes, red wine, blueberries, peanuts and dark chocolate, calms microglial activation. “Resveratrol reduced glutamate-induced damages” “Resveratrol interacts with the complex III of the respiratory chain, is a radical scavenger and also suppressor of radical formation in the mitochondria. It reduces the intracellular calcium levels in pre- and postsynaptic neurons and also may inhibit the pro-apoptotic factors in glutamate overflow that occurs, e.g. in excitotoxicity. In cell cultures, glutamate overflow leads to formation of free radicals and results in apoptosis.” https://www.ncbi.nlm.nih.gov/pubmed/23459926

  • “Our findings reinforce the protective role of this compound in some brain disorders, particularly those involving glutamate toxicity. However, the underlying mechanisms of these changes are not clear at the moment and it is necessary caution with its administration because elevated levels of this compound could contribute to aggravate these conditions.” https://www.ncbi.nlm.nih.gov/pubmed/17554623

Selenium- “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” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378533/42

Taurine “The amino acid taurine increases the GAD enzyme and consequently GABA levels. Additionally taurine doubles as an inhibitory neurotransmitter and can bind directly to GABA receptors, so it can help provide balance naturally in that manner as well. Higher levels of any inhibitory neurotransmitter help lower high levels of any excitatory neurotransmitter. Taurine is found in high levels in the brain and cardiac tissue, indicating its importance in these areas. Taurine is found most abundantly in seafood and animal protein, so it is often deficient in one’s diet. If taurine is deficient, then the GAD enzyme may be low as well, therefore, supplementing with taurine can be used to manage the GABA and glutamate balance and protect from neuron death. However, there are a couple genetic polymorphisms (particularly CBS and SUOX gene mutations) that can result in negative effects from taurine supplementation, because these mutations result in excess levels of sulfur in the body and taurine is sulfur based. If one has these gene mutations, they may also need to avoid other supplements that are high in sulfur and limit sulfur based foods. These mutations can also impair ammonia [converts to glutamate as well] detoxification as well. B6 and SAMe increases the activity of these gene mutations, so supplementation with these substances may compound the problem too.” Beef, lamb, dark chicken meat and eggs are food sources of taurine.  http://www.holistichelp.net/blog/how-to-increase-gaba-and-balance-glutamate/

Theanine “Another popular choice for increasing GABA is l-theanine. L-theanine is a glutamate analog. Which means if you fall in the category of people who is having problems converting your glutamate to GABA, this could lead to excess glutamate rather than GABA. Additionally l-theanine is derived from tea or mushrooms, it is an artificial means of supplementing glutamate, not natural. Furthermore, it could have traces of caffeine or fungi since from its original source, which could be problematic as well. Therefore, l-theanine may work for some, but have the opposite effect for others. I prefer to avoid it,” http://www.holistichelp.net/blog/how-to-increase-gaba-and-balance-glutamate/

Valerian Root – Increases GABA. “ In addition, pretreatment with valerian extract or valerenic acid decreased the brainstem inhibitory effects produced by muscimol (both P < 0.05), suggesting that these compounds play an important role in the regulation of GABAergic activity. Data from this study suggest that the pharmacological effects of valerian extract and valerenic acid are mediated through modulation of GABA(A) receptor function” https://www.ncbi.nlm.nih.gov/pubmed/14742369

Vitamin B1 (Thiamine) (found in sunflower seeds, macadamia nuts, beans & lentils helps to convert glutamine to GABA- “Extracellular glutamate is increased in thalamus during thiamine deficiency-induced lesions and is blocked by MK-801.” https://www.ncbi.nlm.nih.gov/pubmed/8245970

Vitamin B6- “The biochemistry of vitamin B6 is basic to the cause of the Chinese restaurant syndrome” https://www.ncbi.nlm.nih.gov/pubmed/6724532

Vitamin B12- “Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell culture. Chronic administration of methylcobalamin protects cultured retinal neurons against N-methyl-D-aspartate-receptor-mediated glutamate neurotoxicity, probably by altering the membrane properties through SAM-mediated methylation.” https://www.ncbi.nlm.nih.gov/pubmed/9112980

Vitamin C- Vitamin C is intertwined with glutamate signaling and glutamate release. It has the ability to neutralize free radicals, reduce oxidative stress, improve mitochondrial function and offer protection during glutamate release. The use of whole food sources such as rose hips, guava, kiwi, strawberry, cherry, blackberry, blueberry, raspberry, beet, carrot, spinach, broccoli, kale, cabbage, parsley, brussel sprouts, ginger, cauliflower, cranberries, asparagus, etc. are much preferred over supplementation in my opinion (glutamate risk and may contribute to oxalate issues).

  • “Vitamin C also has antioxidant properties that may prove to be helpful in treating HD. Inside the body, ascorbic acid (vitamin C) changes form to become the negatively charged ascorbate. Ascorbate can then directly neutralize very reactive free radicals by donating its own electrons to them. In this way ascorbate can protect other cell components from oxidation by free radicals. Oxidation can cause cell components to lose their ability to function normally, and excessive oxidative damage may eventually lead to nerve cell death. It has even been found that ascorbate prevents free radicals from oxidizing its fellow vitamin, vitamin E! The release of ascorbate from nerve cells is actually linked to the uptake of another molecule into the nerve cells. This molecule is glutamate, an excitatory neurotransmitter that can be toxic to nerve cells. It can exert toxic effects either when it is present in large amounts or when the nerve cells are overly sensitive to it, as are nerve cells in many people with HD. Because glutamate is excitatory, it is often released by nerve cells during times of motor activity. When it is released by one nerve cell, it travels to the next nerve cell to stimulate it. When glutamate has done its job as messenger, it can either be broken down or taken back up by the nerve cells that released it.
    Researchers found that when glutamate is taken back up by the nerve cells, these cells simultaneously release ascorbate. Because glutamate release is tied to increased production of free radicals, this ascorbate release mechanism might have evolved in order to protect nerve cells. The more glutamate that is released by the nerve cell, the more is taken back up later. Because glutamate is “exchanged” with ascorbate when it goes back into the nerve cell, the cell can regulate how much ascorbate it releases based on how much glutamate was originally released. This mechanism allows the cell to release appropriate amounts of ascorbate because it can measure how much free radical production may have been stimulated by the glutamate release. But glutamate is not the only factor responsible for increasing free-radical formation during this time. When a cell is more active, it has to carry out more metabolic processes, and at a faster rate, which also increases the natural production of free radicals. Therefore, the levels of extracellular ascorbate should be highest during times of motor activity: this is a time when the cells are most likely producing increased levels of free radicals themselves and may need extra protection from glutamate toxicity.” http://web.stanford.edu/group/hopes/cgi-bin/hopes_test/vitamin-c/

Zinc-  New study presents a working model that could point to a better understanding of autism’s underpinnings. “The new study, led by Stanford neuroscientists John Huguenard, PhD, and Sally Kim, PhD, and then-graduate student Huong Ha, PhD, showed that zinc is required for the proper behavior of two related proteins, Shank 2 and Shank 3, that hang out at most synapses in the brain. Among their duties, Shank 2 and Shank 3 can reshuffle the subunits of a receptor that dots the receiving end of most nerve cells. This receptor gets tripped off by an incoming chemical signal called glutamate.
In the developing brain, glutamate receptors undergo a process of maturation in the form of internal alterations that are catalyzed by Shank 2 and Shank 3. The substitution of one type of subunit for another type in these receptors endow the receptor with more-prolonged signaling strength, a better “memory” of how often it’s been previously tripped off by the arrival of a glutamate molecule, and a correspondingly more-pronounced propensity to respond heartily to such chemical messages in the future. (This collection of characteristics, which neuroscientists call “plasticity,” is the molecular essence of memory and learning.)
Kim, Huguenard, Ha and their colleagues showed that zinc is absolutely necessary to this development-associated maturation of glutamate receptors by Shank 2 and Shank 3. When triggered by glutamate, a receiving nerve cell opens itself to a temporary but substantial influx of zinc, molecules of which bind to Shank 2 and Shank 3. This, in turn, spurs those two proteins’ active reshuffling of the cell’s glutamate-receptor molecules — an essential and permanent step in the brain circuitry’s development.
Glutamate-receptor maturation is particularly critical in late fetal and early-childhood brain development, when synapses are being formed at an amazing rate. And zinc deficiency is especially pronounced in the very youngest patients diagnosed with ASD. So it’s only natural to ask whether zinc supplementation can stave off the syndrome.” https://scopeblog.stanford.edu/2018/11/12/is-zinc-the-link-to-how-we-think-some-evidence-and-a-word-of-warning/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817734/ FANTASTIC ARTICLE ON HERBS AND GLUTAMATE


Pharmaceutical & Drug Options


“There are many drugs that target your GABA receptors like Ativan, Xanax, Klonipin, Valium, and Neurontin (Gabapentin) and others. These drugs look similar in chemical structure as gamma-aminobutyric acid so they can fit in your GABA receptors, which artificially stimulates them, but they do not actually increase production. Therefore they do not address the underlying problem of not producing enough, because there must be some level of GABA present in order for these drugs to have an effect. Furthermore, anytime a substance is used to artificially stimulate a neurotransmitter the brain responds by reducing production or responsiveness, which results in more depletion of the neurotransmitter, which in this case is GABA. Therefore, any drugs that target GABA receptors or manipulates GABA or glutamate, will inhibit your ability to acquire and maintain balance.” http://www.holistichelp.net/blog/how-to-increase-gaba-and-balance-glutamate/


Amantadine- “Amantadine is an antiviral drug. The action against viruses is not entirely known. For treating other conditions in people (Parkinson’s disease), its effects are attributed to an increase in dopamine in the CNS. However it also is an N-methyl-D-aspartate (NMDA) receptor antagonist. As an NMDA antagonist, it will decrease tolerance to other analgesic drugs (e.g., opiates), but it probably does not possess many analgesic properties when used alone. There is only limited pharmacokinetic data available for animals” https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/amantadine

Dextromethorphan- (commonly found in cough syrup & not necessarily REID approved)- Glutamate receptor antagonist. “Dextromethorphan (DM), a sigma receptor agonist and NMDA receptor antagonist, protects neurons from glutamate excitotoxicity, hypoxia and ischemia, and inhibits microglial activation” http://onlinelibrary.wiley.com/doi/10.1002/glia.22639/abstract

Ibuprofen- Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro “Thus, NSAIDs protected neurons against glutamate excitotoxicity in vitro, and deserve further consideration as neuroprotective agents in Parkinson’s disease” https://www.ncbi.nlm.nih.gov/pubmed/10961664

Low-dose naltrexone (LDN)– inhibits microglial activation “Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/

Memantine (Namenda)- Is a glutamate blocker drug that has been used for those with Alzhimers but has recently gained popularity in the autism and PANS community.  Use of these glutamate blocker drugs do not come without risk.  Since some level of glutamate is necessary, blocking receptors triggers the body to create additional receptors.  The more receptors you have, the more sensitive you can become. Many find that they have to continually increase the dose and/or have problems coming off of the drugs. “Glutamate receptors are overactive, and N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential for the treatment of AD and other neurological disorders. Memantine is a noncompetitive NMDA antagonist that is considered a neuroprotective drug. Memantine’s capacity has been demonstrated in preclinical studies, and it is considered a useful symptomatic treatment for AD.” https://www.ncbi.nlm.nih.gov/pubmed/15844753