Functional GABA Deficiency May Be Cause Of Autism

[Lokzo]

A small clarification - all 3 of these vitamins participate in GABA synthesis. They are not GABA "receptor" agonists, but increase its synthesis. If you Google each one of them followed by "GABA pubmed" you will find the studies you need. Some of the studies with pyridoxine and biotin are posted on the forum too so searching the forum for things like "biotin GABA" should give the relevant results.

Wicked, thanks sir!

 

[DaveFoster]

i really dont notice any GABA raising effects from niacinamide at all. id like to see some studies which support this

Niacinamide has similar effects of benzodiazepine (gabergic) drugs but probably via different mechanisms.

Diazepam (Valium) has a central nervous system (CNS) depressive effect, and in experiments, it slows the head turning of animals. In the full study (mentioned in the study at the end of this post by Prousky,) niacinamide actually abolished diazepam' slowing of head turning, but niacinamide did not have any effect on head turning when administered by itself, which shows that it actually lacked some of the effects of benzodiazepines.

"Inosine and nicotinamide have been proposed as endogenous ligands for the brain benzodiazepine receptor. An in vivo method for detecting drugs with GABA-mimetic properties was used to examine the effects of inosine, nicotinamide and diazepam in the rat globus pallidus. Inosine and nicotinamide completely prevented the GABA-mimetic action of diazepam but neither compound alone had any GABA-like activity. These findings suggest that inosine and nicotinamide are able to antagonize but are not able to mimic the GABA-like actions of diazepam at the benzodiazepine receptor."

Reference: Effects of diazepam and muscimol on GABA-mediated neurotransmission: Interactions with inosine and nicotinamide - ScienceDirect​

In the diabetic brain, niacinamide tends to lower serotonin and increase GABA levels:

"Studies of neurotransmitter uptake and release by isolated rats brain cortex synaptosomes demonstrated that [2-14C]serotonin uptake was by 41% lower in streptozotocin-diabetic rats as compared to control. The [U-14C]GABA uptake was considerably elevated. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation, especially during the first 3 minutes. Nicotinamide (NAm) administration (200 mg/kg body weight daily, 14 days) to diabetic rats restored synaptosomal serotonin uptake up to control levels, while the GABA uptake tended to decrease in diabetic rats. With this dose of NAm the partial restoration of serotonin and GABA release was achieved. The modulating effect of in vivo administered NAm acts via NAD which binds specifically with synaptic membranes. It has been shown that brain NAD(P)/NAD(P)H decreased while sorbitol level increased in streptozotocin-diabetic rats as compared to control. The NAm administration to diabetic rats is accompanied by the increase of NAD(P)/NAD(P)H and the reduction of brain sorbitol level. Data obtained confirm the important role of NAm in the pathogenesis of diabetic encephalopathies."

Reference: [Effect of nicotinamide on the uptake and release of serotonin and GABA by cerebral cortex synaptosomes in rats with diabetes induced by streptozot... - PubMed - NCBI​

Niacinamide tends to slow down synaptic firing between brain cells (as a CNS depressant, and as with many benzodiazepine drugs):

"The actions of nicotinamide and inosine were investigated on rat cerebellar Purkinje cells using ionophoretic and extracellular recording techniques. Ionophoretic application of nicotinamide or inosine showed that they were potent inhibitors of Purkinje cell firing. This inhibition differed from that induced by benzodiazepines in that it was not reversed by the GABA antagonists bicuculline methiodide and picrotoxin. RO 15-1788, the specific benzodiazepine antagonist, did not reverse the effects of nicotinamide. Chlordiazepoxide has been shown to increase significantly social interaction between pairs of male rats and this increase can be reversed by RO 15-1788, 20 mg kg-1 i.p. Nicotinamide also caused a small increase in social interaction but this effect was not reversed by the benzodiazepine antagonist. Inosine did not increase social interaction. [3H]-flunitrazepam binding studies showed that nicotinamide and inosine have only low affinities for the benzodiazepine binding site. These results suggest that while nicotinamide may exert some neuronal depressant and anxiolytic activity, its site of action appears not to be associated with the benzodiazepine receptor site. Similarly, inosine exerts a neuronal depressant effect dissimilar from that of benzodiazepines."

Reference: Central effects of nicotinamide and inosine which are not mediated through benzodiazepine receptors. - PubMed - NCBI​

Here's the full discussion section from the first paper by Prousky with a reference link to the full paper:

"It is of no surprise that this patient benefited tremendously from the benzodiazepines. Benzodiazepines bind to a macromolecular complex that is found within the CNS and is referred to as the GABA-benzodiazepine receptor-chloride ion channel complex. 7 When benzodiazepines bind onto or near this macro-molecular complex they potentiate GABAergic synaptic inhibition through membrane hyperpolarization, thus enhancing the conductance of the chloride ion by increasing the frequency of channel-opening events. 7 The net result is the reduction of anxiety and related symptoms via the diminution of neurotransmission (i.e., neuronal firing) among many brain regions such as the spinal cord, hypothalamus, hippocampus, substantia nigra, cerebellar cortex and cerebral cortex. 7 It appears that niacinamide has similar anxiolytic properties to that of the benzodiazepines. This is supported by the fact that the patient did not feel any difference, in terms of response and effectiveness, between the benzodiazepines and niacinamide. He was able to switch with little difficulty from the daily use of a benzodiazepine to niacinamide. Furthermore, during the transition he did not experience common withdrawal symptoms such as insomnia, recurrent anxiety or panic attacks. However, unlike the benzodiazepines, the pharmacologic data pertaining to the anxiolytic properties of niacinamide are not well known since its precise mechanisms of action upon the central nervous system (CNS) have yet to be conclusively determined.

Möhler et al. suggested that niacinamide is pharmacologically similar to benzodiazepines due to its presynaptic inhibition, as demonstrated in the cat lumbo-sacral spinal cord, anticonflict effect, and anticonvulsant, muscle relaxing and hypnotic effects. 8 Based on these results, these investigators suggested that the endogenous ligand for the benzodiazepine receptor in the mammalian brain was niacinamide. Slater and Longman used a rat headturning model as a method of evaluating whether niacinamide and inosine affect the GABA-mimetic actions of diazepam in vivo. 9 Diazepam caused a highly statistically significant slowing of the head-turn, which is to be expected when injected into the globus pallidus. However, when diazepam was combined with niacinamide, the slowing of the head-turn initially produced by diazepam, reversed to its pretreatment time. In other words, niacinamide may have negated or abolished the effects of diazepam. From these results, it was assumed that niacinamide antagonized the effects of diazepam, therefore interacting with the benzodiazepine receptor in vivo. However, niacinamide administered by itself did not result in reduced headturning behaviour, and did not mimic the benzodiazepine properties of diazepam when tested with the head-turning model. The authors concluded that niacinamide probably does have benzodiazepine-like properties at different benzodiazepine receptor sites in the CNS, but its effects are unrelated to the actions of GABA. In rat studies, Kennedy and Leonard assessed the similarity between the action of niacinamide and diazepam on neurotransmitter metabolism. 10 They considered neurotransmitter turnover of serotonin, noradrenaline (norepinephrine), dopamine and GABA. In their three experiments on rats, they found that niacinamide had a qualitatively similar effect to that of diazepam. It was further concluded that niacinamide exerted its effects by influencing the turnover of serotonin, noradrenaline, dopamine and GABA in those areas of the brain thought to be unbalanced in anxiety. Lapin compared the effects of putative endogenous benzodiazepine receptor ligands (i.e. niacinamide, inosine and hypoxanthine) against kynurenine and pentylenetetrazol, agents that have benzo-diazepine receptor affinity and induce seizures in mice. 11 Niacinamide decreased the kynurenine-induced seizures in C57BL/6 adult male mice and prolonged the latency of pentylenetetrazol seizures. Niacinamide could possibly be a competitive antagonist for the benzodiazepine receptor since it prevented the binding of kynurenine to the benzodiazepine receptor."​

Reference: http://www.orthomolecular.org/library/jom/2004/pdf/2004-v19n02-p104.pdf
​

I've also attached Prousky's paper as a PDF, titled "Niacinamide’s Potent role in Alleviating Anxiety with its Benzodiazepine-like Properties: A Case Report".

 

[Rinse & rePeat]

“Another benefit of the sprouting process is that it softens the bran layer of the rice, allowing the rice to cook faster, softer and easier to digest than traditional brown rice. Sprouted brown rice has four times the GABA content of regular brown rice, and over ten times the GABA of white rice!”

Sprouted Rice Explained

www.usarice.com

 

[Lokzo]

“Another benefit of the sprouting process is that it softens the bran layer of the rice, allowing the rice to cook faster, softer and easier to digest than traditional brown rice. Sprouted brown rice has four times the GABA content of regular brown rice, and over ten times the GABA of white rice!”

Sprouted Rice Explained

www.usarice.com

Nice find! :)

 

[Rinse & rePeat]

Nice find! :)

Thanks! I was pretty proud of that one too!

 

[Beatrix_]

This might be connected

 

[youngsinatra]

Dr. Gregory Russel Jones also wrote about this.

It‘s functional B2 deficiency impairing the GAD enzyme, if I remember correctly.