UA-45667900-1

Thursday, 9 November 2017

Variable Expression of GABRA5 and Activation of α5 -  a Modifier of Cognitive Function in Autism?


Today’s post sounds complicated. We actually already know that the gene GABRA5, and hence the alpha 5 sub-unit of GABAA receptors, can affect cognition, but we do not know for sure in whom it is relevant.
Most readers of this blog are lay people, as such we tend to be predisposed to the idea that autism is somehow “hardwired”, something that just happened and cannot be reversed. Some of autism is indeed “hardwired”, you cannot take an adult with autism and “re-prune” his synapses, to produce a more elegant robust network in his brain. But much can be done, because many things in the brain are changing all the time, they are not fixed at all. Today’s post is good example.
GABA is the most important inhibitory neurotransmitter in the brain. There are two types of GABA receptor, A and B. These receptors are made up of sub-units. There are many different possible combinations of sub-units to make GABAA receptors. These combinations are not fixed, or “hard-wired”; they vary all the time.
The composition of the GABAA receptor changes its effect. It can change how you feel (anxiety) and it can change you think/learn.
You can actually measure GABRA5 expression in different regions of the brain in a test subject using a PET-CT (Positron Emission Tomography–Computed Tomography) scan and it has been done in some adults with high functioning autism. This machine looks like a big front-leading washing machine, just a bit cleverer. 

our primary hypothesis was that, compared to controls, individuals with ASD have a significant reduction in α5 GABA receptor availability in these areas.
Due to the small sample size, we could not examine possible correlations between GABAA binding and particular symptoms of ASD, age, IQ, or symptoms of comorbidities frequently associated with ASD, such as anxiety disorders, OCD and depression. We were also unable to address the effects of possible neuroanatomical differences between people with ASD and controls, which might lead to partial volume effects in PET studies. However, the modest magnitude of the volumetric differences seen in most studies of high-functioning ASD suggests that it is unlikely that these could fully explain the present findings.

These preliminary results suggest that potentiation of GABAA signaling, especially at GABAA α5-subunit containing receptors, might potentially be a novel therapeutic target for ASD. Unselective GABAA agonists and positive allosteric modulators, such as benzodiazepines, have undesirable features such as abuse potential and tolerance, but more selective modulators might avoid such limitations. Further research should extend this work in a larger sample of ASD individuals. It would also be interesting to use PET with the ligand [11C]Ro15-4513 to measure GABAA in disorders of known etiology characterised by ASD symptoms, such as Fragile X and 15q11-13 duplication
In summary, we present preliminary evidence of reduced GABAA α5 expression in adult males with ASD, consistent with the hypothesis that ASD is characterised by a defect in GABA signaling. 

The prevalence of autism spectrum disorders (ASDs), which affect over 1% of the population, has increased twofold in recent years. Reduced expression of GABAA receptors has been observed in postmortem brain tissue and neuroimaging of individuals with ASDs. We found that deletion of the gene for the α5 subunit of the GABAA receptor caused robust autism-like behaviors in mice, including reduced social contacts and vocalizations. Screening of human exome sequencing data from 396 ASD subjects revealed potential missense mutations in GABRA5 and in RDX, the gene for the α5GABAA receptor-anchoring protein radixin, further supporting a α5GABAA receptor deficiency in ASDs.

The results from the current study suggest that drugs that act as positive allosteric modulators of α5GABAA receptors may ameliorate autism-like behaviors 
  

Too many or too few the α5GABAA receptors or too much/little activity?

Regular readers will know that autism is all about extremes hypo/hyper, macro/micro etc. The same is true with α5GABAA, too few can cause autistic behaviors, but too many can impede learning. You need just the right amount.
The next variable is how well your α5GABAA are behaving, because even if you have an appropriate number of these receptors, you may not have optimal activity from them. Over activity from α5GABAA is likely to have the same effect as having too many of them.
Here it becomes very relevant to many with autism and inflammatory comorbidities, because systemic inflammation has been shown to activate α5GABAA. It has been shown that increased α5GABAA receptor activity contributes to inflammation-induced memory deficits and, by my extension, to inflammation-induced cognitive decline.

α5GABAA Receptors Regulate Inflammation-Induced Impairment of Long-Term Potentiation


Systemic inflammation causes learning and memory deficits through mechanisms that remain poorly understood. Here, we studied the pathogenesis of memory loss associated with inflammation and found that we could reverse memory deficits by pharmacologically inhibiting α5-subunit-containing γ-aminobutyric acid type A (α5GABAA) receptors and deleting the gene associated with the α5 subunit. Acute inflammation reduces long-term potentiation, a synaptic correlate of memory, in hippocampal slices from wild-type mice, and this reduction was reversed by inhibition of α5GABAA receptor function. A tonic inhibitory current generated by α5GABAA receptors in hippocampal neurons was increased by the key proinflammatory cytokine interleukin-1β through a p38 mitogen-activated protein kinase signaling pathway. Interleukin-1β also increased the surface expression of α5GABAA receptors in the hippocampus. Collectively, these results show that α5GABAA receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits.


We saw in an earlier post that overexpression of GABRA5 is found in slow learners and we know that this is a key target of Down Syndrome research, aimed at raising cognitive function.

What can be modified?
It appears that you can modify the expression of GABRA5, which means you can increase/decrease the number of GABAA receptors that contain an α5 subunit.
You can also tune the response of those α5 subunits. You can increase it or decrease it.
Activation of the α5 subunit is thought to be the reason why benzodiazepine drugs  have cognitive (reducing) side effects. By extension, inverse agonists of α5 are seen as likely to be nootropic.
One such drug is LS-193,268  is a nootropic drug invented in 2004 by a team working for Merck, Sharp and Dohme.
A complication is that you do not want to affect the α2 subunit, or you will cause anxiety. So you need a highly selective inverse agonist.
The new Down Syndrome drug, Basmisanil, is just such a selective inverse agonist of α5.
Basmisanil (developmental code names RG-1662, RO5186582) is a highly selective inverse agonist/negative allosteric modulator of α5 subunit-containing GABAA receptors which is under development by Roche for the treatment of cognitive impairment associated with Down syndrome.  As of August 2015, it is in phase II clinical trials for this indication.


A contradiction
As is often the case, there is an apparent contradiction, because on the one hand a negative allosteric modulator should be nootropic in NT people and appears to raise cognition in models of Down Syndrome; but on the other hand results from a recent study suggests that drugs that act as positive allosteric modulators of α5GABAA receptors may ameliorate autism-like behaviors.
So which is it?
Quite likely both are right.
It is exactly as we saw a long while back with NMDAR activity, some people have too much and some have too little. Some respond to an agonist, some to an antagonist and some to neither.
What we can say is that fine-tuning α5GABAA in man and mouse seems a viable option to enhance cognition in those with learning difficulties.
The clever option is probably the positive/negative allosteric modulator route, the one being pursued by big Pharma for Down Syndrome.
I like Dr Pahan’s strategy from this previous post, for poor learners and those with early dementia

to use cinnamon/NaB to reduce GABRA5 expression, which has got to consequently reduce α5GABAA activity.
All of these strategies are crude, because what matters is α5GABAA activity in each part of the brain. This is why changing GABRA5 expression will inevitably have good effects in one area and negative effects in another area. What matter is the net effect, is it good, bad or negligible?
The fact that systemic inflammation increases α5GABAA activity may contribute to the cognitive decline some people with autism experience.
We previously saw how inflammation changes KCC2 expression and hence potentially increases intra cellular chloride, shifting GABA towards excitatory.
Ideally you would avoid systemic inflammation, but in fact all you can do is treat it.
Increasing α5GABAA activity I would see as possible strategy for people with high IQ, but some autistic features.
I think those with learning problems are likely to be the ones wanting less α5GABAA activity.
The people for whom “bumetanide has stopped working” or “NAC has stopped working” are perhaps the ones who have developed systemic inflammation for some reason.  You might only have to measure C-reactive protein (CRP) to prove this.




More reading for those interested:-










69 comments:

  1. If mitochondria are dysfunctional or damaged, you will get an increase in inflammatory signaling which pertinent to this post can cause GABRA5 overexpression. Damaged mitochondria are passed from mother to offspring as paternal mitochondria are broken down and consumed immediately after fertilization of the egg.

    One particular strong maternally inherited phenotype happens to be obesity and one branch of research in explaining this fact is largely centered around the study of mitochondria and its potential role in causing hypometabolism in offspring such that cells are not consuming nutrients appropriately, leading to an excess of nutrients in the blood that may be deposited in fat, even when there is a net deficit in caloric intake that causes lean tissue to be cannibalized and fat to disproportionately accumulate.

    Maternal obesity is strongly linked to autism while mitochondrial dysfunction is linked strongly to both obesity and autism. A new paper looks a currently expensive to produce drug/vitamin called Nicotinamide Mononucleotide that is used in animal research for the study of raising NAD+ levels in cells via injections:

    Press Release:

    https://www.sciencedaily.com/releases/2017/11/171108102134.htm

    Paper:

    https://www.nature.com/articles/s41598-017-14866-z

    In this paper, they showed that two interventions rescued several of the negative inherited symptoms of offspring of obese maternal mice fed a high-fat diet to induce obesity.

    One intervention that worked in preventing obesity in offspring from obese female mice was lots and lots of exercise. One could speculate that girls born from obese mothers may be able to prevent obesity in themselves by constantly participating in sports or exercising at the gym when they are younger which prevents obesity, and then later in adult life when they become more sedentary, such as during pregnancy itself, they naturally rebound to the obese state they were metabolically programmed at birth to default to when their mitochondrial deficits catch up to them.

    The other intervention that worked were injections of NMN which is thought to raise NAD+ levels and improve cellular respiration and mitochondrial function. Orally consuming NMN is thought to not be practical for raising NAD+ levels, however Nicotanimide Riboside which has been I have discussed in length for its use for other purposes will raise NAD+ levels throughout the body via oral consumption. In fact, I am aware of an ongoing clinical trial at the moment where a 2000mg per day megadose of Nicotanimide Riboside is being given to obese women as an obesity treatment (most people who take it for aging related purposes take 250mg per day).

    ReplyDelete
  2. Also, while antipsychotics like Risperidone can cause obesity and breast growth all on their own, when medications are controlled for in the autistic population, people with autism still disproportionately suffer from obesity and metabolic syndrome disorders for reasons researchers can only still speculate on at the moment. Perhaps poor mitochondrial function which may be rescued from increasing NAD+ levels would be an interesting speculation to entertain, especially for those with autism who could of been injured from chronic inflammation via the mother due to obesity and/or a so-called western diet during pregnancy.

    While some of this might sound harsh and in the spirit of "blame the mother", I believe there is good objective evidence from this aforementioned research and others that simply raising NAD+ levels may significantly improve autism symptoms all on their own for many people with idiopathic autism with evidence of maternal obesity and/or inflammation being a contributing factor.

    Most people do 250mg per day, but it is an open question with respect to autism and mitochondrial function what speculative dose if any could potentially improve autism symptoms and at the very least reduce the comorbid risks of obesity in the autistic population.

    Finally, with respect to the original post by Peter, it is really hard to reduce low-grade systemic inflammation from obesity and its effects on the body (including GABRA5 overexpression), unless the patient is able to lose weight via a variety of interventions. This research suggests that in some people raising NAD+ levels may help people with stubborn obesity lose weight and for those with autism, one could posit reducing cytokine load in the body may improve the inhibition/excitation ratio as well.

    ReplyDelete
  3. Dear Dr Nemechek

    Thank your blog including many benefical information.

    Can synthetic NaBenz (food grade) be used?

    ReplyDelete
    Replies
    1. Food grade sodium benzoate should indeed work.

      Delete
  4. Tyler,

    I agree, every mito booster helps me, but some give stim-like behavior such as l-carnitine (glycine propionyl-l-carnitine did not stim me).
    Niagen feels restorative aswell as cordyceps, they feel like they refill the gas tank so to speak without being stimming themselves, they just provide energy when you need it.

    Still got a nearly full niagen bottle here at home, the stuff is crazy expensive though which sucks but it is indeed a very promising substance.

    ReplyDelete
  5. Peter, Does verapamil produce a similar effect to risperidone relating to dopamine?
    https://www.ncbi.nlm.nih.gov/m/pubmed/9619688/

    ReplyDelete
    Replies
    1. Tanya, there is research from the 1990s that shows verapamil can affect the level of dopamine, GABA and indeed serotonin. The effect was shown not to be caused via calcium channels, it is another effect of verapamil, I think sodium channels we suggested.

      This is not a surprise because many drugs have a multitude of effects, however there is often one main effect and half a dozen minor effects. The minor effects are often irrelevant for most people but explain the side effects experienced by some.

      Delete
  6. Tanya,hope your son is better,here we are,similar issues matter to us.Dopamine is a great topic for me.Also this is for Tyler,I didn´t understand if verapamil lowered dopamine concentrations in the brain,or acted like risperidone by just blocking the receptors,with chronic use, what we wouldn´t want. It seems that it has no effect on HVA levels.I also would like to know if B6 lowers HVA levels, or do you know something else? Valentina

    ReplyDelete
    Replies
    1. I am not aware of any direct effect of Verapamil on dopamine as I am mostly familiar with its effects on calcium channels or rather calcium pumps as a new paper I read today suggests.

      As to your more general question there is no simple answer. First off as you well know there are many different types of dopamine receptors, but the most important ones seem to be the D1 and D2 receptors so any drug that non-selectively blocks a lot of receptors, such as the case with many antipsychotics like risperidone, is going to have a myriad of side effects in the brain as well as the body. Drugs used for emergency situations in the short-term that in effect clobber entire classes of receptors should not be used long-term.

      Secondly, in development the number of synapses and receptors at each synapse are set at a basal value due to genetic and epigenetic factors so if for either of these reasons a neuron is programmed to have an excess of D2 receptors, you are going to likely have permanent D2 receptor sensitivity throughout life. Your choices here are to block the receptors with an antagonistic molecule or else try and limit the amount of the agonist molecules (dopamine) from circulating in areas of the brain where those receptors are located (such as BCAA's indirectly reducing the level of dopamine in the brain).

      Homovanillic Acid is just a metabolite of dopamine. It can indirectly give an idea of how much dopamine might be circulating in the brain if drawn from CSF. If drawn from blood like via an OATS test, then things are a lot murkier. Even if you know the exact amount of dopamine getting to various parts of the brain, you don't know for sure how easily dopamine is binding to the various receptors. Scientists can generalize and this generalization is the basis for pretty much all psychiatric medicine, including risperidone. You could have a receptor protein issue for a particular receptor that decreases the binding affinity so increasing dopamine release at the synapse (like in ADHD medication) won't do much to solve the problem, however, it may cause a lot of side effects with other dopamine receptors. Likewise, if there is an epigenetically programmed excess of dopamine receptors, and you also block the autoreceptors (receptors on the pre-synaptic cell to regulate its own activity), you are going to be meddling with the natural regulation of receptor count in ways that are very hard to predict or understand.

      In general, it is bad to have unnatural levels of neurotransmitters in the brain and usually when this is so and drugs are not involved, it suggests a problem with autoreceptors becoming desensitized and/or dysfunctional so to resensitize the autoreceptors means to decrease the levels of the neurotransmitter which is very counterintuitive to most people.

      With respect to B6, it is generally thought to be good for autism for many reasons such as it reducing the levels of cytokine IL-6. Also, low levels can cause higher levels of kynurenine and since B6 is needed to produce NAD+ from quinolinic acid, a lack of B6 can cause an excess of quinolinic acid to linger around which is generally thought to be bad since quinolinic acid is a very strong oxidant, can cause DNA damage on its own, and is considered a neurotoxin in significant amounts.

      Also, I don't know about B6 lowers dopamine levels, but I remember reading something about excess dopamine lowering stores of B6. I have supplemented P5P with my son since the beginning and it is probably in the top 10 of autism supplements people give their kids for various reasons.

      Delete
    2. Peter, Tyler and Valentina, sharing this quickly now and have more comments and questions for later
      https://spectrumnews.org/news/diverse-dopamine-defects-found-in-people-with-autism/
      Note comment on one variant re: glutamine and zinc. Both being so crucial for gut lining health.

      Delete
    3. https://www.google.com/amp/s/www.psychologytoday.com/blog/the-athletes-way/201405/neuroscientists-identify-new-brain-pathways-linked-autism%3famp

      Delete
  7. For whatever reason three very interesting papers came out on a Friday no less that all intimately deal with several of the big topics on this blog.

    The first paper addresses a long slog of work in figuring out how the calcium pump actually works and a few insights that are likely very relevant to autism such as:

    "We have identified a new closed state in the pumping cycle, that the pump can only enter if the calcium ion comes from the intracellular fluids and the pump has cleaved ATP. It cannot reach this state if the ion comes from the cell's surroundings. When calcium is released from this state, it is the 'point of no return'. This is the mechanism that explains that the pump works as a pump and not just a passive channel" - From the Press Release:

    https://www.sciencedaily.com/releases/2017/11/171110113943.htm

    Paper:

    https://www.nature.com/articles/nature24296


    The next very interesting paper today covers a recent topic on this blog concerning cerebrospinal fluid in that based on this research it is believed (by the researchers) that the vast majority of CSF and possibly all of the CSF exits the brain via the lymphatic system and not the veins as previously believed.

    Press Release:

    https://www.sciencedaily.com/releases/2017/11/171110084307.htm

    Paper:

    https://www.nature.com/articles/s41467-017-01484-6

    Obviously with respect to autism, targeting the lymphatic system for a sluggish CSF outflow might be a path of treatment to look into, especially for the macrocephaly autism phenotype.


    Last but not least, another autism mouse model study used clonazepam to rescue the induced autism behaviors that centered around developmental insufficiency of GABAergic interneurons throughout the brain.

    Press Release:

    https://www.sciencedaily.com/releases/2017/11/171110123611.htm

    Paper:

    https://www.nature.com/articles/s41593-017-0013-0

    I have not tried to scale the dosage of clonazepam given to the mice to what you might do in a human so I don't know off the top of my head if this is a big dose or else the low dose used in some studies. Perhaps this is not big news that interneurons don't work so well in autism, but the research does perhaps give more of a clue to the "why" and "how" that sorely need answered as simply blasting the brain with high dose GABAergics long-term can do more damage than what you might get from any short-term gains in cognitive function. Obviously, this last paper is very pertinent to the above blog post by Peter.

    ReplyDelete
    Replies
    1. No idea what the exact mechanism is behind low dose clonazepam, but it made me a monster, really aggressive for no reason and I absoluted hated everything and everyone it.

      Delete
    2. Not to trivialize your experience, but it sounds a bit like GABA signaling working in reverse which as you probably well know Peter has discussed in length on his blog but perchance you are not familiar, I would search some older posts on the matter. Interestingly, epilepsy seems to do the same paradoxical thing as well to interneurons which causes less inhibition overall and a greater risk of seizures in the future with each seizure increasing the frequency of the next seizure.

      Delete
    3. hi Tyler,

      Thanks for highlighting that, its easy to get lost in the vast amount of information on the internet, including oposite results in some studies.

      My experience with gaba enhancing substances/herbs/supplements is very very different for each substance.

      Ashwagandha and chinese skullcap are nice and relaxing in a good way.
      Taurine can be too disinhibiting if I do more than 2grams at once which can increase impulsivity and recklessness in me, but it does not give the aggression and feelings of hate like clonazepam did.

      It seems the receptor subtype of gaba that gets activated produces very very different results, It seems skullcap works through alpha2 and alpha3 receptors and I felt this benefited me big time.

      Ashwagandha works as a gaba potentiator and is a very good herb for autism in general, it lowers TSH and increases thyroid hormones aswell (subclinical hypothyroidism happens alot in ASD - myself included as im on 75mcg levothyroxine daily and this benefits me big time).

      Delete
  8. Aspie yet another thing my son has in common with you. We tried low dose clonazepam and the first very small dose didn’t notice anything then went up to the next tiny dose Peter discussed in his post and he was sleepy. Didn’t know if this was just a coincidence so decided to give an honest trial of more than 4 days in a row. That was a few weeks ago right at the time things started to go out of control here. Just read benzos promote dopamine. Probably why they can be addictive. Anything promoting dopamine makes my son aggressive . Quercetin the Catechins rutins too much green tea all of that. Probably even high tyrosine and high phenylalanine foods too

    ReplyDelete
    Replies
    1. Only tried one dose, I couldnt handle it, felt more of a hate fueled by incapability to feel anything at all to me.

      Also dopamine can be both inhibitory and stimulating, it is not that easy Tanya.

      Delete
    2. I always thought negatively of dopamine because my autistic son reacted with increased aggression to B6 (converts L-Dopa to dopamine) and zinc (DA re-uptake inhibitor). However, many supplements have multiple functions, and it is easy to blame a wrong function. For example, besides increasing dopamine, B6 and zinc are also co-factors of converting histidine to histamine. In other words, they increase histamine. After looking at all supplements my son reacted to with aggression, they all had one thing in common: they increase histamine. My son has MTHFR A1298C homozygous mutation, which is quite rare and significantly reduces dopamine, serotonin and melatonin production among other things. So, clearly my son needed dopamine. I tried Rhodiola and it clearly hit the right note. My son became more alert, playful, social. I am quite suprised how much attention here is given to GABA and benzos. Not all types of autism benefit from GABA agonism. I think there is a large group of autistic kids who have poor cortical function (due to poor blood circulation, hypoxia and traumatic injury, or developmental causes). They need stimulation of the cortical function in order to gain speech and other neurotypical functions. Increasing dopamine, nootropics, BDNF and other neurotrophic factors are just few examples of brain stimulation. I noticed that this blog is very negative on BDNF and anything that encourages neuronal network development. Bumetanide, being an NKCC1 inhibitor, is example of a drug that suppresses BDNF. There are many doctors in Europe who base their treatment of autism on promoting the brain activity rather than suppressing it (by clonazepam for example). One of the examples of a successful treatment of autism is cerebrolysin, which contains BDNF and other neurotrophic factors. You should consider trying things that boost brain function.

      Delete
    3. If you want to know for sure if dopamine is good or bad for your son's phenotype, give him some Mucuna Pruriens (basically L-DOPA), some Adderall or other strong dopamine releasing stimulant besides illegal and dangerous ones like heroin or cocaine and see if things are good, bad, or neutral. This method will give your son the precursors for dopamine (L-DOPA) and/or L-Tyrosine and a drug/compound that promotes dopamine release at the synapse. Caffeine might work too but caffeine does plenty of other things too, so ADHD drugs generally work better. Obviously don't overdo it, but this is really the only way to hazard a guess if your son's problem is dopamine or something else.

      Also, Rhodiola is an herb in kind of a grey area as to what it actually does and as an herb it has many different active compounds which makes studying it objectively difficult.

      Last but not least BDNF promotes LTP (Long-Term Potentiation) which is important for learning as it makes the synapse more sensitive, but if synapses are hyperplastic then nothing really sticks as what you learned yesterday is going to be overwritten the next day or else just muddled from neural noise. In most autism studies I have read suggested too much BDNF and too much LTP and too many synapses in general. With respect to GABA agonism, too much is very bad for the brain and leads to cognitive decline. I think most people here realize that, especially since the brain has many different types of interneurons and the types most relevant to autism (parvalbumin), but non-selective GABAergics may make up for some of the deficits of parvalbumin dysfunction, but perhaps add too much of a boost to the signaling of somatostatin neurons which function much differently. High frequency brain activity (gamma waves) is highly compromised in autism and those brain waves are thought to be driven primarily by parvalbumin interneurons.

      On top of that, interneurons may be dysfunctional because the glutamate receptors on them may be faulty as many interneurons are driven by excitatory activity and if they don't get the proper input because the synapses have a problem somewhere, they don't work.

      As for seeing if BDNF is good or bad for autism, transcranial magnetic stimulation using the intermittent theta burst protocol will reliably increase BDNF in the targeted areas. Most of the time I have instead seen the continuous theta burst protocol used for autism therapy research which is thought to dampen or disable neural activity in a particular area and dampen BDNF.

      Last but not least, when it comes to ictal activity (which is comorbid in 20% of those with autism), dopamine releasing agents and anything promoting LTP is thought to decrease the seizure threshold.

      This is all very tough stuff for us to decide on and for most parents, that go to the lengths we do it usually comes down to throwing a bunch of stuff at a wall and seeing what sticks. Deciding what to throw at that wall is I think what is discussed most on this blog, not whether something is always going to be good or bad for any particular child.

      Delete
    4. or you could just find out the COMT gene status as one clue. My son is +- v158m .

      Delete
    5. The other issue with dopamine could be if there is a PANDAS/PANS event - antibodies to dopamine receptor . My kid was/is also in the PANS category. He also has a ganglioneuroblastoma (cousin to neurofibromatosis that Peter has written about and is connected to autism) - which can secrete dopamine. It hasn't before for my son but we are now checking. It is very complicated. And no Aspie, I don't think anything is ever that easy. Maybe I should just start typing questions marks at the end of all of my sentences

      Delete
    6. Tanya,
      p5p/b6 also increases serotonin! b6 is the cofactor for many reactions, including AADC.

      https://en.wikipedia.org/wiki/Aromatic_L-amino_acid_decarboxylase

      Delete
    7. Tyler,

      Very interesting what you say about BDNF, as far as I know alcohol kills brain cells and initially causes LTD (long term depression), followed by LTP in the hangover? or am I wrong.

      Alcohol also strongly influences BDNF.

      As stated before I feel that my perception of self intelligence is holding me back from the full social experience in daily life.

      I only get this positive hangover of alcohol with drinking a very large amount (to the point where I can completely let go and be myself), this seems me to allow to process deep emotional thoughts and access them and erase them from my brain, allowing me to wake up the next day feeling reborn, this effect only lasts like 10hours... the next day I wake up im back to having ASDF again.

      I would like to test something that induces LTD in me and see how I react to it, can anyone please help me find something that does this.

      Delete
    8. Well alcohol does a lot of things in the body and brain but you first have to take into consideration that alcohol is a poison and in that sense will cause other downstream effects metabolically to handle the poison which may have further downstream effects on the brain.

      Alcohol does almost incalculable damage to society and especially to those in utero but it has cultural and historical significance in much of the world even though banning it would probably put most police out of a job, except for those around to enforce a ban on alcohol. That likely won't happen for another century or two so the best we can do is discourage young women from drinking while pregnant which is tough because a woman could of already had several nights of heavy wine drinking before she realizes she is pregnant and then the damage is already done via fetal alcohol syndrome which just in the United States is estimated to be involved in 5-15% of all births. The symptoms of FAS are very similar to autism so maybe some cases of FAS are misdiagnosed as autism. Drinking while pregnant is something few women will admit so definitive numbers are hard to pin down.

      There is no safe amount of alcohol while pregnant and as an adult having just one drink a day signicantly increases your risk of cancer. So if there sometimes happen to be paradoxical effects with alcohol or other poisons, it is usually the body trying to bounce back from the damage just as the immune system is thrown into high gear from an infection, even though the risk of death from sepsis is always a possibility. In fact women are thought to die of sepsis three times as much as men because testosterone depresses the immune system.

      In your particular case of feeling better rather than worse from a hangover, if you really care about your intelligence you will abstain from drinking as much as you practically can. If you have ever had the pleasure of listening to drunk people talk while being sober yourself, you will soon realize they have incredible confidence in their inner insight in spite of muttering nothing but mundane things about the world. Videotape yourself while drunk and then see how much of a genius you then appear to be at the time (-:

      Delete
  9. HI Peter, When he says "poor learners" I assume he means a certain type of learning -- perhaps poor learners in reading vs. math skills. I have been thinking about this -- that you would might get a lift -- but not necessarily in numerous cognitive areas? Also, cinnamon is probably cheapest and easiest way to see if a responder? Thanks for your posts. Always helpful and thoughtful.

    ReplyDelete
  10. Peter there is a new vasopressin receptor antagonists clinical trial by Roche Pharmaceuticals
    Theaviationtrial.com

    ReplyDelete
    Replies
    1. Are you going to join the trial Pierrette?

      They seem very organized. If you live in the area they want, it is worth a try.

      https://theaviationstudy.com/child-join.aspx

      Delete
  11. Tyler, this is the Vanderbilt professor doing research on dopamine transporter genes and autism. I️ am going to pay attention to his research - this is my hometown so maybe my son’s doctor knows something. And on the dopamine topic - his work is also on addictions and obesity connection. Thought you might be interested since you frequently comment on obesity. Although doesn’t apply to me or my son and most autism moms I️ know are not obese - more the maternal immune activation autism. But nevertheless, Just wanted to share:
    https://www.google.com/amp/s/news.vanderbilt.edu/2016/07/18/diabetes-drugs-may-ease-addiction/amp/

    ReplyDelete
  12. I have read a bit about GLP-1, but not in that context. You are right that this definitely has dual use applications though the researcher probably will get better luck in funding for obesity than for autism alone even though managing dopamine signaling in the brain is of paramount importance on autism, especially for those on the more severe side of the spectrum.

    Also, if you really believe in his research, you should talk to him and ask how you might be able to help. Rather than have relatives or your own family donate money to autism speaks or some other autism organization you could help with this research directly as it us actually practical to do so since you are local. Researchers these days spend a ridiculous amount of time chasing money like they are some startup business founder chasing venture capital and many of them if not most come up short because there is not enough NIH funding to go around and getting funded can be very arbitrary and frustrating. Then there are the papers and the journals which is another giant waste of time for researchers and postdocs especially who just want to do science but are always playing multiple rounds of the Hunger Games for a few mediocre paid jobs. My own cousin who is a neuroscientist spent 3 years on one research project and another 3 years trying to get his paper published and finally succeeded, but the point is there is a lot of red tape for researchers these days and most are very open to any kind of financial help without strings attached (such as from a drug company).

    ReplyDelete
    Replies
    1. thanks for the tip Tyler. I will do that.

      Delete
  13. Hi everyone,

    I have found a very interesting new article and the relevant paper - really worth a look:

    https://medicalxpress.com/news/2017-11-breakthrough-potential-treatment-autism-intellectual.html

    http://www.nature.com/articles/s41593-017-0013-0

    Enjoy!

    AJ

    ReplyDelete
    Replies
    1. AJ,
      They say HDAC3 is implicated in that model, sodium butyrate (and possibly clostridicum butyricum) might help with this, they are HDAC3-inhibitors.

      Delete
    2. Hi Aspie,

      Thanks for noting this! I have been considering Sodium Butyrate for a while. I'm going to look into it and may get some.

      I'll let you know if I get some, and how well it works.

      AJ

      Delete
    3. No problem AJ,

      I got sodium butyrate here at home, I find it activating by the way (600mg on empty stomach), apparantly the oxytocin like effect comes with chronic dosing.

      However a problem with sodium butyrate seems to be bioavailability in humans, clostridicum butyrate might be a better option by introducing this probiotic endogenous production of butyrate enhances.

      Delete
    4. Hi Aspie,

      Thanks for your insights as always!

      I actually have some Clostridium Butyrate in one of the probiotics I'm giving my daughter right now during her antibiotic / anti-yeast protocol.

      I'm hoping that we get rid of the bad bugs / yeast, replace with good bugs (including C butyrate)and S. boulardii, and also supplement with some sodium butyrate.

      I am thinking about using piperine with the sodium butyrate to increase bioavailability.

      Any thoughts (Aspie or others)?

      AJ

      Delete
  14. Hi everyone,

    And another interesting very interesting paper of note:

    NitroSynapsin therapy for a mouse MEF2C haploinsufficiency model of human autism

    http://www.nature.com/articles/s41467-017-01563-8

    Enjoy!

    AJ

    ReplyDelete
  15. Some very interesting research that refutes a lot of the fatty acid orthodoxy came out today, unbeknownst to me that the idea that Omega-6 fatty acids promote inflammation was based on a bunch of assumptions regarding their conversion to CRP (C-Reactive Protein) rather than actual experimental evidence.

    Many people (including myself) may have heard that you don't want too many Omega-6 fatty acids in your diet because it promotes inflammation and that it counters the beneficial effects of Omega-3 fatty acids in the sense you want some kind of balance. I think at this time Omega-3 supplementation is a winner, but diets avoiding Omega-6 intake maybe not so much.

    This latest paper actually measured CRP levels relative to serum linoleic acid levels and found that increased levels of Omega-6 fatty acid intake (linoleic acid) actually decreased CRP levels which contradicts established fatty acid orthodoxy.

    Press Release:

    https://www.sciencedaily.com/releases/2017/11/171113095430.htm

    Paper:

    https://www.nature.com/articles/s41430-017-0009-6

    CRP levels of are paramount interest in autism, so diets that avoid Omega-6 fatty acids might be doing more harm than good.

    There is a cottage industry of autism experts making recommendations on what the exact ratio of fatty acids should be in the diet of someone with autism, but as this study shows that you can't just make linear biological assumptions about fatty acids, rather it is important the recommendations of self-proclaimed experts are not just based on science, but actually are proven by science.

    ReplyDelete
  16. Here is another paper that links a high candidate autism gene called Ankyrin-B or ANK2 I read about a while ago from the same researcher in 2014:

    https://spectrumnews.org/news/mystery-gene-uncovered-in-autism-studies-may-steer-neurons/

    In the new paper, the researcher links Ankyrin-B to obesity in that if it is mutated or downregulated, glucose is shuttled into white fat cells at an accelerated rate:

    Press Release:

    https://www.sciencedaily.com/releases/2017/11/171113153824.htm

    Paper:

    http://www.pnas.org/content/early/2017/11/09/1708865114

    While there are likely multiple factors involved in the increased prevalence of obesity in the autistic population, this particular gene looks like a very strong candidate to perhaps explain what might be going on as this researcher's previous work suggests Ankyrin-B as being very important in the brain in shuttling proteins from the soma down the axons and dendrites so that axons can project (grow) to where they need to go. While mice lacking Ankyrin-B die at birth, they all seem to lack a corpus callosum which is dependant upon axons projecting long distances across the hemispheres of the brain.

    As I touched in some comments not long ago, if for whatever reason the body is sucking up all the glucose in the periphery, then not much will get to the brain and therefore cause hypoglycemia in the CNS. In this particular case one could imagine that the fat cells are starving the brain of glucose, as well as causing obesity and metabolic syndrome symptoms via fat spill over from the white fat cells no longer being able to absorb glucose or fats from the blood stream, thereby causing them to be deposited near organs.

    ReplyDelete
  17. Tanya, Ling, have you checked vitamin d3 recently? There is research connecting vitamin d3 with OCD like behaviours, PANS/PANDAS strep infections and autoimmune diseases.
    When I checked my son, due to hypocalcemia symptoms, I found out he is deficient (7 ng/ml). So far I have given 50,0000IU gradually and intend to keep it during the winter. Vitamin d3 helps make neurotransmitters.
    Really hope this proves helpful.

    ReplyDelete
    Replies
    1. Petra,
      Beware of d3 toxicity though, I was 3 times the upper tollerable level with doing 5-10.000iu/day for a few months in the past I have made a post about this is not to be neglected.

      Delete
    2. Petra, Can you give me the link for the vit d3 for ocd,and pans/pandas. Thanks, Maria

      Delete
    3. Maria, here is the title of the article:
      "Vitamin D Deficiency in Obsessive–Compulsive Disorder Patients with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infecti: A Case Control Study"https://www.ncbi.nlm.nih.gov/pubmed/28360763 -

      Delete
    4. Thanks Petra, I will check his levels soon. I did add a low dose in after your post. His levels have been low in the past. I never realized how much I was confusing just stimulatory behavior due to boredom with real OCD until this recent flare up with my son. I have never seen anything like this from him, and that includes after the first strep infection that resulted in the PANDAS diagnosis when he was 4. Things have gotten a little better since giving frequent antimicrobial dosing and the other supports for infections flares, like treating the "cytokine storm"..

      Delete
  18. Aspie, doctor told me to give 4.000IU daily for about six months. I give 2.000 for less than a month. I think it's too early to risk toxicity. I'll check next month, though, thanks.
    If you don't mind me asking, is there anything that has hepled you overcome bad memories? I know this is the biggest challenge for Aspergers, they never forget.
    I'm trialing cordyceps 500mg myself but so far I haven't felt anything profound still it seems well tolerated.

    ReplyDelete
    Replies
    1. Petra, This is the root of my son's current issues - his extreme situational anxiety that is emotionally triggered . Have you tried propranolol? Here is an excerpt from an article:
      "Other scientists have achieved impressive results with less extreme drugs. In 2008, Alain Brunet, a clinical psychologist at McGill University, identified 19 patients who had been suffering for several years from serious stress and anxiety disorders such as PTSD. (Their traumas included sexual assaults, car crashes, and violent muggings.) People in the treatment group were given the drug propranolol, a beta-blocker that has long been used for conditions like high blood pressure and performance anxiety; it inhibits norepinephrine, a neurotransmitter involved in the production of strong emotions. Brunet asked subjects to write a detailed description of their traumatic experiences and then gave them a dose of propranolol. While the subjects were remembering the awful event, the drug suppressed the visceral aspects of their fear response, ensuring that the negative feeling was somewhat contained.

      One week later, all the patients returned to the lab and were exposed once again to a description of the traumatic event. Here’s where things got interesting: Subjects who got the placebo demonstrated levels of arousal consistent with PTSD (for example, their heart rate spiked suddenly), but those given propranolol showed significantly lower stress responses. Although they could still remember the event in vivid detail, the emotional memory located in the amygdala had been modified. The fear wasn’t gone, but it no longer seemed crippling. “The results we get sometimes leave me in awe,” Brunet says. “These are people who are unable to lead normal lives, and yet after just a few sessions they become healthy again.”
      https://www.wired.com/2012/02/ff_forgettingpill/

      Delete
    2. Petra,

      4000iu/day for 6months seem to indeed be a recipy towards toxic levels (not sure what your sons weight is, but I weigh 95kilo and 6months of 5000iu-10000iu daily took me from average d3 levels to triple the upper tollerable limit).

      Cordyceps Im using at 2x 3gram a day now Petra it seems indeed a very safe substance, my guess is that it is working so well for me is that I have high urea levels and it is probably helping that bring down.
      Cordyceps also target inflammation and does a ton more, have you tried 2x 1gram a day?

      Also which cordyceps are you using, im using cordyceps militaris powder (the one by realmushrooms, which has quite high beta glucans and cordycepin content).

      Delete
  19. Hi AJ, what is Dr Goldenthal’s contact information, please? I️ am assuming he is still offering the Mito test?
    Thanks so much

    ReplyDelete
    Replies
    1. Hi Tanya,

      I used his e-mail address, which is mjg99@drexel.edu .

      When I reached out to him with my contact info and that I wanted a mito test, he sent me a kit (basically a few long q-tip like swabs and little plastic containers for the tips of the swabs once you've collected the cheek swabs) with instructions on how to collect and send back the samples.

      I had to but a little cooler, ice packs, etc. and sent that overnight via FedEx. It's extremely important that the samples be

      The cost was $200 US, so got a money order and included it with the cold samples. I believe he doesn't work on Mondays and Fridays, and I also believe he may be retiring around April, so while you still have time, don't wait until the spring.

      I hope this helps Tanya!

      AJ

      Delete
  20. Tyler, Iam thinking of trying uridine.It alters the way dopamine works but I don´t know in what way ,if it can help to fix the imbalance or just release more dopamine.Do you think that it is risky or could be of any help along with bcaas and fish oil? Someone here has tried it? Thanks!
    Valentina

    ReplyDelete
    Replies
    1. I believe Peter had a lengthy discussion about Uridine a year or so ago that mostly delved into whether lowering or raising uric acid levels is beneficial for autism. I don't think Uridine is risky and whether it is good or bad for your son will just require trying it or not. My guess is it would be neutral, especially with regards to dopamine because it does not increase extracellular dopamine in the brain, rather it only increases intracellular dopamine released across synapses. My guess here is that its exact effects on dopamine receptors are very receptor specific but I have nothing to back that up.

      I used to supplement inosine in my son which raises uric acid levels.

      Delete
    2. Valentina, I used Uridine 300mg/capsule from Double Wood supplements up to 900mg/day. As far as I can remember, it didn't bring any adverse effect and seemed well tolerated.
      I think it made my son to move a little bit out of his stagnation but I can't say much.
      When I take 300mg I don't really feel a dopamine rush.
      For the general population it is supposed to give benefits, for your son's dopamine issues you would have to risk.

      Delete
    3. Hi Petra,

      I use cdp-choline (250mg) which converts into choline and uridine basically, I wonder why I respond better to cdp-choline than pure UMP (uridine monophosphate).
      I have got UMP from nootropicsdepot (they test all their products and got a good reputation and consistency), have taken 250mg sublingual in the past a couple of times but it seemed to make me irritable (maybe the dose was too high?), Ive seen posts on reddit about people taking doses as low as 15-30mg.

      Uridine upregulates dopamine receptors by the way, and oddly enough it is elevated in most cases of autism.
      Really strange that cdp-choline works better for me than UMP, might have to try UMP in the future again but a very low dose as I still got the small bottle.

      Delete
    4. Thankyou Petra, what benefits your son, and Jane´s son, will benefit my son.He presents the same obsessions, in his case, as he is only 11, the fear or bad thoughts are to potencial dangers that could happen to him or our family, death in particular and all the details.From some time,he is obsessed with Micahel Jakson and the circumstances of his death.As he adores his music he knows all about him and read that the wrong pill given by his doctor had to do with it, he thinks that the same could happen to him, as he also takes pills.He can´t even watch the lego thriller tribute to MJakson because he has nightmares! I will not risk Uridine for the moment.
      Valentina

      Delete
    5. If he likes Michael Jackson, maybe you should introduce him to Weird Al Yankovic. To get my kids out the door in the morning and eat their breakfast, I blast "Eat It" by Weird Al on our Amazon Tap. That and "The Final Countdown" by Europe does the job these days.

      Delete
  21. Paul,I know you are very interested in the history of autism.Did you see this?
    https://www.ncbi.nlm.nih.gov/books/NBK436841/
    E-book,very long read.

    ReplyDelete
    Replies
    1. Roger, that is a mammoth book.

      If you want to hear Uta Frith, who comes up in all books on autism. There is a podcast below.

      I think she feels a little guilty for promoting this ever widening Autistic Spectrum and understands that the "original" autism is now getting overlooked, in favour of the new fashionable quirky autism.

      https://www.tes.com/news/school-news/breaking-views/listen-what-every-teacher-needs-know-about-autism-professor-uta

      Delete
  22. Tanya,

    Was it you that was giving your son the lysine?

    I started lysine myself since yesterday, took 1000mg on an empty stomach last night and noticed I started yawning alot and it felt like it helped me give better sleep, now today I took 1000mg between lunch and dinner and noticed the anti-anxiety effects (seems to help with overthinking), now tonight I took another 1000mg and started yawning again, seems like a good sleep aid to me.
    Considering I have had tons of sleep issues in the past (and to be honest my sleep is still not optimal but greatly improved) this is very nice.
    I wonder what its mechanism would be, it lowers serotonin levels but this study also suggest anticonvulsant like activity:

    L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor.
    https://www.ncbi.nlm.nih.gov/pubmed/8587651

    "The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding by L-lysine. This article shows the basic amino acid L-lysine to have a central nervous system depressant characteristics with an anti-PTZ seizure activity and an enhancement of [3H]FTZ binding similar to that of barbiturates but different from GABA."

    It feels as a 'natural' sleep remedy in that it does simply knock me out, but gradually makes me sleepier (I have used temazepam and zolpidem in the past and these just knock me out), lysine works very different on me, even compared to 5htp (supplement).
    I feel as it just makes me relaxed, allowing me to surrender to go sleep so to speak.

    ReplyDelete
  23. I give my son L-Lysine to help boost GABAergic activity basically for the reasons you mention. The idea I got from reading drug user forums (I don't use illicit drugs myself, but people have a lot of creative ideas in dealing with addiction that are too taboo to find on a site like WebMD.com) and one idea that came up with evidence to back it up was to use L-Lysine as a benzo booster (these were primarily people trying to handle their addiction to benzos that their doctor/psychiatrist prescribed them). So the idea they had was to reduce their benzo dosage by boosting its efficacy using L-Lysine. I want to boost GABA signaling in my son, but not with large doses of benzos which are addictive, build up tolerance rapibly, and have lots of negative side effects including permanently reduced cognition (yet doctors in the USA still routinely prescribe these in high doses for anxiety and other maladies in spite of the evidence of long-term damage in doing so). You can find my comments on L-Lysine a year or so back on this blog by searching for them.

    L-Lysine is also cheap and even though you can get plenty of it via diet (it is also non-essential) I didn't see it as an intervention with any discernable health risk. Good GABAergic interventions in autism are far and few between not only for the reasons mentioned above, but because of the wide variety of GABAergic interneurons in the brain that do many different things and have varying concentrations in different parts of the brain.

    ReplyDelete
    Replies
    1. Tyler,I am expecting lysine by first days of december, along with glucosamine, I expect to wean off valproate and use them instead.Since i give fish oil and citrulline, I could lower valproate to 250 mg a day and all seems really ok.
      Valentina

      Delete
  24. Thanks for that Tyler,
    I have used it in the past, but I was on a lot of other supplements then aswell so it is hard to figure out what is doing what, I only noticed the last 2 days that I used it how effective it is.
    And as you mentioned it is very cheap especially if you get the powder in bulk, great cost/efficiency ratio this supplement if you ask me, along with taurine.

    ReplyDelete
    Replies
    1. And thanks you Aspie for the link, I hope that Lysine helps with my son neuronal hyperexcitability, along with glucosamine.Valentina

      Delete
  25. Forgot to add, I am still on cordyceps & inositol, they seemed to have reduced my irritability from a scale of 10/10 to 1/10 and I seem more open, I especially notice people reacting different to me (in a positive way).
    Visiting the doctor this afternoon and going to ask for a new bloodtest to see if my b12 and urea have come down. I will also get vitamin d3 tested, see how much it has dropped in about 2 months.
    It was around 100 on a scale of 30-130 last time.

    ReplyDelete
  26. Aspie, thanks for the report and for the reminder - I had stopped a few things when my son’s flare intensified and will add it back in. I was giving in the evening because I had read reports of people commenting on how it helped their sleep. I am glad you are having such s positive response - very encouraging:)

    ReplyDelete
  27. An interesting study on nuts suggests that different types of nuts have different effects on brainwave activity:

    Press Release:

    https://www.sciencedaily.com/releases/2017/11/171115091809.htm

    Paper:

    http://www.fasebj.org/content/31/1_Supplement/636.24

    The general finding was that delta wave power was increased by peanuts (generally high in autism) and gamma wave power was increased by pistachios (low most of the time in autism and thought to be a marker for properly functioning parvalbumin interneurons).

    Now I just need to get my son to switch from constantly raiding our jars of peanut butter and eat pistachio butter instead.

    ReplyDelete
    Replies
    1. Funny that you mention peanutbutter tyler, its the food I used to have a strong addiction for it, along with orangejuice, especially when I was socially isolated.

      Delete
    2. By the way peanutoil (pretty sure also peanutbutter?) is one of the best sources of Arachidic acid (closely related to arachidonic acid but not the same)

      https://en.wikipedia.org/wiki/Arachidic_acid

      "ts name derives from the Latin arachis—peanut. It can be formed by the hydrogenation of arachidonic acid."

      Delete
  28. Hi Aspie,I use fresh freeze dried grown on rice cordyceps sinesis 500mg fron Terra Nova UK brand product, one I could really quickly get hold of in Greece.
    Knee joint pains disappeared, back pain diminished, I can control my body movement much better, which started to deteriorate after summer.
    Behaviourally it's complicated to explain. For example, I usually have an early long deep sleep. With cordyceps I find myself waking up in the early hours a couple of times finding myself overthinking. This is not annoying because I soon after go back to seep again, as if things are being resolved on their own, if this sounds understandable.
    I think I cannot tolerate more than 500mg every other day, it's nootropic.
    Aspie let me ask you something I may not have quite well understood, are you looking for something to increase long term potentiation?

    ReplyDelete
    Replies
    1. Hi Petra,

      There are indeed lots of cordyceps vendors out there and the controversy regarding the quality seems to come from the type of extracts and how they are artificially grown (wild cordyceps costs more than gold per kilogram by the way, this is not a joke).

      If you look over on reddit/r/nootropics you can find alot of information of people discussing the quality and the vendors being involved and explaining their extraction processes and such.

      My pick was realmushrooms due to extensive reading on there.

      Are you taking it early in the day or before bed? before bed it can definatly cause sleep problems, it is best taken in the early morning and my second dose I take at like 3pm.

      Im not sure wether I need more LTP or not petra, I have problems with overthinking and this prevents me living in the present (inositol and cordyceps help me with this).
      What I found striking is that a few days ago someone posted (not sure if it was Peter or a reader) about in some forms of autism people are unable to forget certain things, I really recognize myself in this, it is as if some memories are unable to be erased and I feel as if this forms a 'block'.

      ASD is very weird, high BDNF seems to be common alot, but also some cases of low BDNF.

      Delete
  29. Reuteri atcc6475, decent at colonizing after all?

    https://www.biogaia.com/pressrelease/lactobacillus-reuteri-reduced-bone-loss-in-older-women/

    http://mb.cision.com/Main/3271/2393934/753456.pdf
    Lactobacillus reuteri reduced bone loss in older women

    However this is a press release, im not sure if this study is funded by biogaia (yes its all about money after all...), if anyone can find the actual study, please forward the link on here.

    Because the effect on bone are apparantly there that is not to say its effect on the brain can be just as pronounced, time will tell, in the meanwhile im expecting clostridicum butyricum to arrive again, had better success with it compared to reuteri, I will keep you peeps updated.

    ReplyDelete

Post a comment