Showing posts with label immunomodulation. Show all posts
Showing posts with label immunomodulation. Show all posts

Friday, 7 August 2015

Has anyone tried Cinnamon (or Sodium Benzoate) for Autism?

I have written several posts about Cinnamon and its metabolite Sodium Benzoate. I know that some readers are now using it for its cholesterol lowering and insulin sensitivity improving properties that were shown in the clinical trials I highlighted.

But has anyone tried it for autism?

The first time I wrote about it I did acquire a big bag of the correct variety (Cinnamomum verum or Ceylon Cinnamon) and also a bag of the very high flavanol (epicatechin) cocoa.  My cinnamon trial was limited to seeing what it looked/tasted like when added to the Polypill concoction Monty, aged 12 with ASD, drinks at breakfast.  It was rather like adding a teaspoonful of fine sand, so not much “testing” took place.

Now that Monty has shown an ability, and even enjoyment, for pill swallowing, things are much simpler.  The cinnamon can be put inside gelatin capsules; it’s a little messy, but no great trouble.

Having recently been researching about the gene enhancers and silencers, which are controlled by the 95% of your DNA that rarely gets studied (the exome is the part everyone studies and some people test for abnormalities), it did occur to me that I already have two safe substances, that I have both researched and acquired, which have a gene expression enhancing effect.

Cinnamon “Experiment”

Even though summer is the wrong time to test anything in Monty, aged 12 with ASD, since his pollen allergy triggers a regression, I decided to make a trial.  I have 1 kg of this special cinnamon, and so it’s not like I need to ration it.

I gave about 2.5ml of cinnamon split into three daily doses using some gelatin capsules that used to be full of another supplement (choline).

Results so far:-

Complete absence of summertime bad behaviors, which are already 90% subdued by Verapamil, but do sometimes present themselves.

Interesting behavioral developments:- 

·        Like many people with autism, Monty likes order.  So turn off lights, shut doors, wash dirty hands etc.  The latest surprise was that when I took something from the rear of my car and he shut the tail gate (boot). Given the size of my car, for someone of his small stature, this is quite an achievement, since he really has to stretch on his toes.  This is the first time he has ever done this and now he does it every time.

·        Monty can brush his teeth and get dressed, but his clothes are sitting there on his bed.  The other day when told to go upstairs and brush his teeth, he returned fully clothed, having chosen/found his clothes all by himself.

·        On awakening, sometimes Monty might say “can I have a glass of water”, to which he might be told go downstairs and get water, and usually someone would go down with him.  Recently I find him in the early morning sitting at the kitchen table playing on his iPad with the glass of water he served himself with.

·        Piano playing also seems to be going very well, indeed on Wednesday after his piano lesson the teacher started telling me that she has taught 73 children with autism and never has she had someone start at his beginning level and progress so far.  This is clearly not down to cinnamon (it was greatly helped by bumetanide, atorvastatin and NAC), but why is she telling me this now, after over three years of lessons?

·        Speech for people with Classic autism, even when it develops, is always a little odd, reading a book out loud or singing does not mean you can speak.  It is as if the mother tongue is a foreign language and needs to be translated in your head. So for me it would be like speaking German.  It is my fourth language, I know lots of words, but I cannot think in German.

Many people with autism like to know their schedule. Today Monty was going to go swimming, amongst other things, but a change of plan meant we had gone to eat.  So I said to Monty “I am too full to go swimming, we will go later”.

A few minutes later as I stopped the car, Monty says “swimming when Dad feels better”.

There is nothing super clever in that statement, but it is not the sort of unprompted comment I usually get to hear for son number two.

These are all little steps and may be coincidental, but normally with Monty things go backwards in summer.  Even effective interventions appear to lose their effectiveness. 

I still keep an open mind on cinnamon, but I did just order a big bag of empty gelatin capsules.

Anybody else tried Cinnamon?

It would be useful to know from people who found that Bumetanide or Sulforaphane were effective for autism, whether cinnamon also has a positive effect.

There are several reasons why it may help:-

·        Change in NMDA signaling, affecting the excitatory/inhibitory balance
·        Affects gene expression related to oxidative stress (why cinnamon helps reduce cholesterol and improve insulin sensitivity)
·        Increases BDNF, Brain-derived neurotrophic factor  (aka “brain fertilizer”)
·        NaB (sodium benzoate) reduces Microglial and Astroglial Inflammatory Responses
·        NaB exerts its anti-inflammatory effect through the inhibition of NF-κB
·        NaB suppresses the activation of p21ras in microglia
·        NaB can also regulate many immune signaling pathways responsible for inflammation, glial cell activation, switching of T-helper cells, modulation of regulatory T cells

NF-κB is the master regulator of inflammation in the same way that Nrf 2 is for oxidative stress.

Incorrect regulation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory

In autism it seems that we want to activate Nrf2 but to inhibit NF-κB.  Safely inhibiting NF-κB is the Holy Grail for many diseases.

We covered RAS in earlier posts.  The RAS protein is abnormally active in cancer.

So called RASopathies are developmental syndromes caused by mutations in genes that alter the Ras subfamily.  RASopathies are often associated with autistic symptoms and/or intellectual disability/mental retardation.

Common inhibitors of RAS are statins and Farnesyltransferase inhibitors.  Most Farnesyltransferase inhibitors are expensive cancer research drugs, but one is gingerol.

Since statins do very clearly improve the autism of Monty, aged 12 with ASD, I did try adding gingerol as my “Statin plus” therapy.  At the dose I used there was no noticeable effect.

However, I now learn that “NaB suppressed the activation of p21ras in microglia”.  P21, RAS, and p21ras are different names for the same protein.  So it would seem that NaB is therefore a RAS inhibitor and perhaps a more potent one than gingerol.
Too much BDNF, just like too much lawn fertilizer, may not be a good thing.

BDNF is low in schizophrenia, but is thought to be elevated in “most” autism.

Upon activation, microglia and astrocytes produce a number of proinflammatory molecules that participate in the pathophysiology of several neurodegenerative disorders. This study explores the anti-inflammatory property of cinnamon metabolite sodium benzoate (NaB) in microglia and astrocytes. NaB, but not sodium formate, was found to inhibit LPS-induced expression of inducible NO synthase (iNOS), proinflammatory cytokines (TNF-α and IL-1β) and surface markers (CD11b, CD11c, and CD68) in mouse microglia. Similarly, NaB also inhibited fibrillar amyloid β (Aβ)-, prion peptide-, double-stranded RNA (polyinosinic-polycytidylic acid)-, HIV-1 Tat-, 1-methyl-4-phenylpyridinium+-, IL-1β-, and IL-12 p402-induced microglial expression of iNOS. In addition to microglia, NaB also suppressed the expression of iNOS in mouse peritoneal macrophages and primary human astrocytes. Inhibition of NF-κB activation by NaB suggests that NaB exerts its anti-inflammatory effect through the inhibition of NF-κB. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on iNOS expression, and NF-κB activation by hydroxymethylglutaryl-CoA, mevalonate, and farnesyl pyrophosphate, but not cholesterol and ubiquinone, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the anti-inflammatory effect of NaB. Furthermore, we demonstrate that an inhibitor of p21ras farnesyl protein transferase suppressed the expression of iNOS, that activation of p21ras alone was sufficient to induce the expression of iNOS, and that NaB suppressed the activation of p21ras in microglia. These results highlight a novel anti-inflammatory role of NaB via modulation of the mevalonate pathway and p21ras.


ABSTRACT Experimental allergic encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), the most common human demyelinating disease of the central nervous system. Sodium benzoate (NaB), a metabolite of cinnamon and a FDA-approved drug against urea cycle disorders in children, is a widely used food additive, which is long known for its microbicidal effect. However, recent studies reveal that apart from its microbicidal effects, NaB can also regulate many immune signaling pathways responsible for inflammation, glial cell activation, switching of T-helper cells, modulation of regulatory T cells, cell-to-cell contact, and migration. As a result, NaB alters the neuroimmunology of EAE and ameliorates the disease process of EAE. In this review, we have made an honest attempt to analyze these newly-discovered immunomodulatory activities of NaB and associated mechanisms that may help in considering this drug for various inflammatory human disorders including MS as primary or adjunct therapy.


Rather to my surprise, Cinnamon does seem to have a noticeable cognitive effect in the type of autism I am interested in.  It appears, rather like the statin, to promote improved adaptive behavior by reducing inhibition and increasing spontaneous thought and actual decision making.

Of all the many possible modes of action, I am thinking that inhibition of NF-κB and/ or RAS inhibition are most likely since the effect is very similar to that produced by the statin.

I will certainly continue with cinnamon and when my size 000 gelatin capsules arrive, I will look at different doses.  Currently the dose is about 2.5 ml split three times a day, using size 00 gelatin capsules.