The Inverse Relationship between Glucose and GABA

The deeper I go into my research, the power of salt to right what sugar wrongs in a battle of good versus evil continues to amaze me. If salt can get past the biofilms created by eating sugar, of course, but that's for another post. (Claritin, or loratadine, and/or magnesium may help with that.) Lately I've been using Redmond's real salt for food and La Baleine Lower Sodium salt for water because it dissolves better. Both of these salts have a balance of minerals. Potassium is critical to balance with sodium, particularly in diabetics who are extremely prone to cardiac disease. Salt can be extremely healing when at an optimal, healthy level in the body - it's anti-bacterial, anti-viral, and anti-parasitic. An expensive nasal spray I found online called Enovid was shown in a Phase 3 clinical trial to reduce viral load in COVID-19 patients by more than 94% in 24 hours, and 99% in 48 hours. Its main ingredient: sodium chloride. Processed sugar only greatly promotes the proliferation of all bacterial, viral and parasitic ailments. It's death, it's poison; there's really no other description for it. Remember consuming caffeine and sugar (spiking insulin) will flush out your sodium, so you're starting your day out depleted if you're consuming caffeine and a pastry, donut, cereal or sweet oatmeal, yogurt or granola bar. 

I've improved, but I'm still not exactly the best at playing pancreas. I used to over-calculate my insulin requirements all the time, and I'd end up low all day every day and it was just excruciating. I saw my life flash before my eyes regularly. During this period, I was sitting in my endocrinologist's interrogative plain white office, and she asked how often I was going low. Hmm, I said, definitely more than a few times a week. Not exactly a lie. Her expression read, I'm disappointed. Well, best not to tell her I'm seeing Jesus at the white gate a couple of times per day then, I thought. But we did make some insulin adjustments and I’ve been wearing the Freestyle Libre 3 with the alarms on and I credit it with my life, it’s been a game changer. It's interesting to me that when your blood sugar is dropping like a kettlebell (which for a person still producing their own insulin will happen after a massive spike from sugar), the first thing your body does is slow you way down. I become incredibly tired. I've thought about why and I believe it's because if you keep moving, your blood sugar will only drop more with the exertion. So it's interesting that we have this non-stop sugar and subsequent caffeine cycle much of society is addicted to. The adrenaline and cortisol rush from caffeine (and of course, more sugar), will bring blood sugar and your mood back up. All in all, those on the sugar/caffeine blood sugar see-saw all day every day are some salt-deprived people. And many times I notice the one change people will make for their health is just to start drinking like 100 gallons of pure water every day. I cannot imagine the Magnus Ver Magnusson grip their bodies have on what little salt reserves they have left.

I've been following Dr. Ben Bikman at Insulin IQ, and in one particular video I watched "The Metabolic Classroom Episode 12: Salt and Insulin Sensitivity" he discusses some useful information. An interesting point that was made is that heart disease is the leading killer in the world, but very often cardiac arrest is spurred by a diabetic state. Diabetes is never listed as the cause of death, but what really is the leading killer?

GABA (gamma-aminobutyric acid) is a calming neurotransmitter produced in pancreatic beta cells. GABA depletion is the name of the game in a great deal of mental illness, in addition to other ailments, including tinnitus. Sugar and junk food diets greatly deplete GABA; salt restores it. Interestingly, GABA supplementation has also been shown to ameliorate Type 1 diabetes, Sjogren's Syndrome, and Multiple Sclerosis, in addition to improving symptomology in autism. GABA also blocks histamine from becoming over-abundant and hyper-active.

Some research papers:

The 2001 paper Correlation between GABA release from rat islet beta-cells and their metabolic state found: "Pancreatic beta cells express glutamate decarboxylase (GAD), which is responsible for the production and release of GABA. GABA release is 40% reduced by glucose...Less GABA is released in conditions of elevated glucose metabolism."

The 2006 paper Glucose inhibits GABA release by pancreatic beta-cells through an increase in GABA shunt activity states: "We conclude that GABA release from beta-cells is regulated by glutamine and glucose. Glucose inhibits glutamine-driven GABA formation and release through increasing GABA-T shunt activity by its cellular metabolism." 

In the 2015 study Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study states: "Studies both in adults and in children have shown that antibodies, in particular anti-GAD, are also present in a proportion of non-diabetic individuals who do not develop diabetes over many years and who do not have close relatives with autoimmune diabetes."

The 2007 paper Higher accumulation of gamma-aminobutyric acid induced by salt stress through stimulating the activity of diamine oxidase in Glycine Max (L.) Merr roots states: "GABA accumulation in plant cells has generally been thought to be primarily from the activation of glutamate decarboxylase (GAD)...It has been generally supposed that GABA accumulation induced by salt stress results from the activation of GAD. In this report, however, GABA content during salt stress increased significantly, and was concomitant with decreases in polyamines and an increase in diamine oxidase (DAO) activity...The present studies indicated that the higher accumulation of GABA (about 39%) under salt stress could come from PA oxidation due to an increased DAO activity." Salt stress is simply putting plants into a high salt environment. 

The 2015 paper Wakefulness is Governed by GABA and Histamine Cotransmission concluded: "The two components may work together to regulate the amount of wakefulness. If this balance of GABA-histamine cotransmission changes unfavorably, mania-like behaviors could emerge."

The 2016 paper Effect of an Excess of Salt on Resistance to Histamine in Rats states: "An excess of salt for short periods above the apparent requirement in rats in which the depots of saline solution have been filled enhances the natural resistance of the animal to large amounts of histamine."

The 2013 paper Effect of GABA treatment on plasma substance P and calcitonin gene-related peptide levels in children with asthma concluded: "GABA can significantly decrease plasma levels of SP and CGRP in children suffering from acute asthma."

The 1976 article Changes in the GABA system in experimental allergic encephalomyelitis-induced paralysis found: "The content of GABA, but not glutamate, and the uptake of GABA by synaptosomes was reduced in the lumbar cord of guinea pigs during experimental allergic encephalomyelitis induced hind limb paralysis."

The 2022 paper GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models stated: "Given that GABA-treatment preserved saliva and tear production which are the most salient symptoms of Sjogren's Syndrome and is safe for consumption, it may provide a new approach to help ameliorate SS."

The 2018 paper Homotaurine, a safe blood-brain barrier permeable GABA(A)-R-Specific agonist, ameliorates disease in mouse models of multiple sclerosis found: "Thus, treatment with homotaurine after the clinical onset... inhibited disease progression in both monophasic and relapsing-remitting mouse models of MS."

The 2018 paper Reduced GABA Levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis concluded: "This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of relapsing-remitting multiple sclerosis and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS."

The 2015 paper Reduced gamma-aminobutyric acid concentration is associated with physical disability in progressive multiple sclerosis states: "This study supports the idea that modulation of gamma-aminobutyric acid neurotransmission may be an important target for neuroprotection in multiple sclerosis."

The 2007 paper Salt stress-enhanced GABA in tomato fruit concluded: "These results show for the first time that salt stress enhances the GABA content in tomato fruit."

The 2004 study Effect of a High-Salt Diet on Gamma-Aminobutyric Acid Mediated Responses in the Nucleus Tractus Solitarius of Sprague-Dawley Rats found "high-salt intake enhances both GABA(A) receptor and GABA(B) receptor-mediated responses within nucleus tractus solitarius, thereby inhibiting elevation of arterial pressure."

The 2022 paper Homotaurine ameliorates the core ASD symptomatology in VPA rats through GABAergic signaling: Role of GAD67 states: "Dysregulated GABAergic signaling is reported in Autism Spectrum Disorder (ASD)...homotaurine treatment was able to ameliorate the aberrant core behavioral deficits, decreased oxidative stress, decreased pro-inflammatory and increased anti-inflammatory cytokine profile with preservation of the Purkinje cell density in the cerebellum, decreased pyknosis in the prefrontal cortex and normalized the expression of GAD67. Thus, HT can be a useful therapeutic agent in ASD and requires further clinical evaluation."

The 2016 paper Increased anxiety-like behavior and altered GABAergic system in the amygdala and cerebellum of VPA rats- an animal model of autism found autistic rats had decreased levels of GAD65 and GAD67 mRNA in the cerebellum compared to controls. "These findings support the existence of a relationship between increased anxiety-like behavior and changes in the regulation of the GABAergic system."

The 2012 study Presence of GAD65 autoantibodies in the serum of children with autism or ADHD found: "Serum anti-GAD65 antibodies may be a common marker of subgroups of patients with autism and ADHD. Reactions of serum antibodies with the cells in the cerebellum in these patients suggest direct effects on brain function."

The 2021 paper Benzodiazepines in autism spectrum disorder- wise or otherwise? stated: "Several genetic mouse models of autism spectrum disorder show a reduction in the number of cortical GABAergic interneurons, especially the parvalbumin subtype. Thus, increasing GABAergic signaling might improve behavioral outcome by compensating a potentially excessive glutamatergic neurotransmission. In the same vein, the BDZ, clonazepam, has also proven to ameliorate symptoms in preclinical models of neurodevelopmental disorders associated with autism." This study also made a good point: "Clinicians are generally reluctant to prescribe benzodiazepines in ASD on the ground that children and especially those with neuro-disabilities are at a heightened risk of paradoxical reactions." It's always best to be monitored by a physician if you're going to start playing with neurotransmitters. Eliminating sugar, junk foods and caffeine alone may help greatly. Please take the time to read the incredible 1966 paper Relative Hypoglycemia as a Cause of Neuropsychiatric Illness by Harry M. Salzer, MD. 

You're considered positive for GAD65 antibodies if you get the value 4 or higher on your lab report. All my page said was "greater than 250." There wasn't an exact number. I would never have found this out if I didn't call my doctor's office after diligently researching the second my eyesight came back and I could see my phone again.

On a website for lab testing, I saw a description for GAD65 Antibody titled Presence of GAD65 antibody predicts development of type 1 diabetes: "GAD is present in highest concentration in brain and pancreatic beta cells," it read. "Antibodies specific for the 65 kDa isoform of glutamic acid decarboxylase comprise the majority of pancreatic islet cell autoantibodies. They appear years before the onset of clinical diabetes...Anti-GAD65 autoantibodies are detectable in the sera of 76% of patients at the time of diagnosis of type 1 diabetes mellitus." The 2015 study Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study states: "Anti-GAD and other antibodies against pancreatic antigens can often be detected many years before the clinical onset of autoimmune-mediated diabetes, indicating a long "pre-diabetic" phase of autoimmune activity."

A huge puzzle piece came into place for me when I found out about these antibodies with regards to how I had been feeling for years leading up to my diagnosis. For instance, I remember reading Robyn Davidson's book Tracks and thinking, this woman can walk by herself across the desert, and I have a hard time grocery shopping without having a full-blown panic attack. I can even remember calling my now-husband, and having him meet me at the mall because I could not get up from a couch in a department store my panic attack was so bad. I needed him to walk me to my car. It's difficult to even remember what that felt like, it crushes me how I existed at that time, how I was scared to the point of paralysis. Additionally, my hearing was all distorted, sounds seemed too loud. I'd lay my head down on my pillow at night and in the silence I'd hear this relentless beeping tinnitus. I discretely read every book I could on anxiety on my Kindle. Anxiety Free, Unravel your fears before they unravel you! was one I read over and over again. The only one I also bought in paperback. Writing this is actually bringing back a lot of memories, like when I put a lot of the pointers from this book in my notes on my phone so that if I felt an attack coming on, I could just look at them and hopefully relax. No one would notice, it would be like I was just looking at my phone. This was probably around four years before being diagnosed. I watched countless videos on YouTube, a sweet Irish man in his series Panic Away!, listened to meditation after meditation. It saddens me to reflect on my younger self getting ready for work, listening to positive affirmation meditations in an attempt to calm myself enough to get through the shift. I spent too much of my young adulthood in this exhausting perpetual fight or flight state, and it took so much out of me. My spirit was drained. Even if I wasn't satisfied with where I found myself in life, I clung to what I had because I was entrapped in fear, absolutely certain on a daily basis that I was mere moments from completely unraveling and developing some devastatingly serious mental illness.

A lot of time has gone by for me in a state of ill health. I knew the second I finally had this diagnosis that my life was just beginning. The more I research, the more I feel I now have the right weapons to fight for my life back.

Let's look at the research:

The 2015 paper The GAD65 Knock out Mouse- A Model for GABAergic Processes in Fear-and-Stress-Induced Psychopathology states: "The GABA enzyme GAD65 is critically involved in the activity-dependent regulation of GABAergic inhibition in the central nervous system. It is required for the maturation of the GABAergic system during adolescence, a phase that is critical for the development of several neuropsychiatric diseases. Mice bearing a null mutation of the GAD65 gene develop hyper-excitability of the amygdala and hippocampus, and a phenotype of increased anxiety and pathological fear memory reminiscent of post traumatic stress disorder."

The 2018 paper Enhanced susceptibility to stress and seizures in GAD65 deficient mice concluded: "Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by medial ganglionic eminence stem cell transplantation." 

The 1999 paper Increased anxiety and altered responses to anxiolytics in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase reports: "Mice deficient in GAD65 exhibit increased anxiety-like responses in both the open field and elevated zero maze assays...We propose that stress-induced GABA release is impaired in GAD65-deficient mice, resulting in increased anxiety-like responses and a diminished response to the acute effects of drugs that facilitate the actions of released GABA."

The 2014 paper The GABA-synthetic enzyme GAD65 controls circadian activation of conditioned fear pathways states: "Our data suggest a role of GAD65-mediated GABA synthesis in the encoding of circadian information to fear memory. GAD65 deficits in a state-dependent manner result in increased neural activation in fear circuits and elicit panic-like flight responses during fear memory retrieval."

The 2019 study Tinnitus Correlates with Downregulation of Cortical Glutamate Decarboxylase 65 Expression but Not Auditory Cortical Map Reorganization found that "tinnitus was significantly correlated with downregulation of GAD65 in the auditory cortex."

The 2019 paper Elevated Glutamate Levels in Type 1 Diabetes: Correlations with Glycemic Control and Age of Disease Onset but Not with Hypoglycemia Awareness Status found: "In conclusion, brain glutamate levels are elevated in people with type 1 diabetes...this suggests a potential role for glutamate as an early marker for hyperglycemia-induced cerebral complications of type 1 diabetes."

The 2018 paper GABA Dramatically Improves Glucose Tolerance in Streptozotocin-Induced Diabetic Rats Fed with High-Fat Diet found: "GABA or insulin therapy improved blood glucose, insulin level, intraperitoneal glucose tolerance test, insulin tolerance test, gluconeogenesis pathway, glucagon receptor, body weight and body fat in diabetic rats. GLUT4 gene and protein expression increased. GABA, whose beneficial effect was comparable to that of insulin, also increased glucose infusion rate during an euglycemic clamp." 

The 2017 paper Cytoprotective Effects of Citicoline and Homotaurine against Glutamate and High Glucose Neurotoxicity in Primary Cultured Retinal Cells states: "These results showed that a combination of citicoline and homotaurine synergistically decreases proapoptotic effects associated with glutamate and high glucose treated retinal cultures. This study provides an insight into the potential application of citicoline and homotaurine as a valuable tool to exert neuroprotective effects against retinal damage."

Lastly, these final studies are extremely fascinating to me, and also demonstrate why processed sugar consumption creates a literal hell on Earth for the human species. Everyone becomes immuno-compromised. Who loves a host on sugar the very most? Parasites and their biofilms. In addition to flushing out parasite-blasting salt, sugar promotes the formation of biofilms, which are essentially impenetrable, protective slime walls surrounding the parasites, making them extremely difficult to kill.

The 2015 paper Toxoplasma gondii infections alter GABAergic synapses and signaling in the central nervous system states: "During infections with the protozoan parasite Toxoplasma gondii, GABA is utilized as a carbon source for parasite metabolism and also to facilitate dissemination by stimulating dendritic-cell motility...taken together, these data support a model in which seizures and other neurological complications seen in Toxoplasma-infected individuals are due, at least in part, to changes in GABAergic signaling." In an interview with NeuroScience News, the authors said they "repeated the experiment many times before we believed the results." The scientists found GAD67 was misplaced in rodent brains with toxoplasmosis.  

The 2015 paper Toxoplasma gondii and anxiety disorders in a community-based sample found: "Our findings indicate that T. gondii infection is strongly and significantly associated with generalized anxiety disorder."

The 2015 study Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis concluded: "The findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia re-activation of latent T. gondii infection may occur."

I’ve taken some profoundly needed time to myself in the last six months, and I’ve allowed myself to peacefully mourn the hope of ever conjuring any sense of normalcy in my life. I was on a plane up to Connecticut and there was a woman sitting next to me watching this dating hook-up reality show with people in hot tubs arguing non-stop on her tablet. Which is fine, but those shows aren't for me. I was reflecting on how I could align my book just so to cover up her screen, and wondering: what would it be like to be distracted in normalcy, to not be thrown into the deep end? The bottom of the Mariana Trench at times, if you will? To not have soul-wrenching health problem after health problem come at you like a dark, impervious riddle you have to figure out yourself? I was in a fragile state, still deeply in the throes of finally expelling so much resistance. Also I was quite depressed initially, hours would go by taking long walks on the tree-shaded shell path at my local park, thinking all day about research articles, wondering if I would always be on the bench while the game was going. But I’ve shed a great deal of much needed weight from my psyche, and I’ve completely, at last, released the wish for a simple, easier life. Released what could have been. If there are to be more challenges sent my way, which I’m certain there will be, I only say bring it on. Because I have already won many battles and I am ready.