Glutamate, Diabetes and Vit D.


I recently found out that I have Glutamic Acid Decarboxylase auto-antibodies (GAD Ab). Glutamic Acid Decarboxylase is an enzyme that turns glutamate into GABA essentially. So having antibodies against this enzyme basically means more glutamate and neurotoxicity and less GABA.

These GAD Ab are associated with all sorts of neurological disorders like Stiff Person Syndrome and are also associated with metabolic dysfunctions, including T1D and late onset T1D. Most likely the metabolic dysfunctions are a result of low GABA levels. GABA has been found to reverse T1D when taken in large quantities in some cases.

So what's the verdict, then? Whether and for whom GABA can be useful tool to improve his or her blood glucose management is virtually impossible to tell based on the study at hand. In spite of the fact that the scientists observed only minor adverse events such as transient dizziness and a sore throat, a further reduction of glycated albumin levels is not necessary an advantage that's worth having elevated insulin and glucagon levels. The latter would after all promote the use of proteins or rather amino acids as substrate for gluconeogenesis, the process of which the scientists believe that it is responsible for the non-existent instantaneous glucose response in the study at hand, while the former, i.e. the increase in insulin levels, is well-known for its negative effects on fatty acid oxidation.

Overall, "the verdict" is thus that we need additional research in both, healthy and diabetic individuals to be able to tell for whom the benefits of chronic high(er) dose (3x2g per day) GABA supplementation outweigh potential side effects. If you asked me for an educated guess, though, I would say (pre-)diabetics benefit while the average individual sees either no relevant benefits or detrimental effects due to the repeated need to re-stabilize the blood sugar levels... a phenomenon of which I have by the way previously said and written that it may explain the paradoxically agitating effects the ingestion of GABA has on some individuals - most likely those with already low(ish) blood glucose levels.

Strangely enough, it also looks like calcitriol can reverse the expression of these GAD65 least in some Chinese children. Calcitriol is the "active" form of Vitamin D. Most often you hear of people supplementing with cholecalciferol, which is Vit D3. This is different. Cholecalciferol is hydroxylated twice, in the liver and then in the kidney to become calcitriol.

J Diabetes. 2013 Sep;5(3):344-8. doi: 10.1111/1753-0407.12023. Epub 2013 May 29.
Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol.

Papadimitriou DT1, Marakaki C, Fretzayas A, Nicolaidou P, Papadimitriou A.

Based on recent knowledge of the possible involvement of 1,25-dihydroxyvitamin D in the pathogenesis of type 1 diabetes (T1D) and the results of its administration in animal models, we conducted a clinical trial by treating high-risk children, positive for T1D autoantibodies, with oral calcitriol.

The present prospective trial was performed on 12 children (1.5-13 years old) who were investigated for the potential risk of T1D because of an already diagnosed association of celiac disease and autoimmune thyroiditis (four girls), autoimmune thyroiditis at a very young age (two girls, two boys), a diagnosis of T1D in siblings (two boys), and impaired glucose tolerance (IGT; one boy, one girl). Serum autoantibody levels, including islet cell autoantibodies, anti-glutamic acid decarboxylase (GAD) 65, insulin autoantibodies (IAA), and anti-tyrosine phosphatase, and markers of calcium metabolism were evaluated prior to and at 6-monthly intervals after the initiation of 0.25 μg/day calcitriol for 1-3 years.

In all children, persistent negativation of the anti-GAD65 antibodies and IAA was observed within 0.4-2.1 years. Of the two children with IGT, the boy proved to have maturity onset diabetes of the young (MODY) 2, whereas the glycemic profile was normalized in the girl.

Despite the small number of subjects and the absence of a control group in the present study, 0.25 μg/day calcitriol effectively negativates anti-GAD65 antibodies and IAA after a median time of 6 months. This simple, safe, and low-cost strategy may prove effective in the prevention of T1D in the future.
© 2013 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Here's the kicker....basically the entire Marshall Protocol is based on lowering 25-OH D levels down to nothing in order to make sure that calcitriol, 1,25D, is lowered as well.

Sometimes, especially when inflammation is high, people measure both forms of Vit D and it turns out that the 1,25 form is WAY over range, indicating some sort of dysregulation. But I'm wondering if the high 1,25 D levels are actually in some way protecting the brain from neurotoxins like excessive glutamate and that lowering them, a la the Marshall Protocol, is a Very Bad Idea.

I wonder if there are any significant risks to taking extra calcitriol to try to turn off the GAD Ab response, like they did in this Chinese study? Side effects seem mostly related to hypercalcemia and my blood calcium has always been at the bottom of the range anyway.


Well-Known Member
If you take Vit K and magnesium with it, it should keep the calcium in the bones and not in soft tissue and arteries. They test for this with POTS. I didn't have it. But I do think some of the sympathetic overdrive in it is connected to high glutamate. When there is autoimmune issues, sometimes the testing doesn't show accurate. I however have low Vit D and my calcium is more higher rather than lower.


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