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Thursday 27 August 2015

Cinnamon (Cinnamaldehyde), Mast Cells (Allergy) & Autism










A reader of the previous post on cinnamon left a helpful comment highlighting research that suggests yet another reason why Cinnamon might be an effective treatment for some types of autism.






Abstract
BACKGROUND:
Mast cells (MC) are main effector cells of allergic and other inflammatory reactions; however, only a few anti-MC agents are available for therapy. It has been reported that cinnamon extract (CE) attenuates allergic symptoms by affecting immune cells; however, its influence on MC was not studied so far. Here, we analyzed the effects of CE on human and rodent MC in vitro and in vivo.
METHODS:
Expression of MC-specific proteases was examined in vivo in duodenum of mice following oral administration of CE. Release of mediators and phosphorylation of signaling molecules were analyzed in vitro in human MC isolated from intestinal tissue (hiMC) or RBL-2H3 cells challenged with CE prior to stimulation by FcεRI cross-linking.
RESULTS:
Following oral treatment with CE, expression of the mast cell proteases MCP6 and MC-CPA was significantly decreased in mice. In hiMC, CE also caused a reduced expression of tryptase. Moreover, in hiMC stimulated by IgE cross-linking, the release of β-hexosaminidase was reduced to about 20% by CE. The de novo synthesis of cysteinyl leukotrienes, TNFα, CXCL8, CCL2, CCL3, and CCL4, was almost completely inhibited by CE. The attenuation of mast cell mediators by CE seems to be related to particular signaling pathways, because we found that activation of the MAP kinases ERK, JNK, and p38 as well as of Akt was strongly reduced by CE.
CONCLUSION:
CE decreases expression of mast cell-specific mediators in vitro and in vivo and thus is a new plant-originated candidate for anti-allergic therapy


In a later study by the same authors they identify Cinnamaldehyde as the main mediator of cinnamon extract in mast cell inhibition.



A chemistry note:

Cinnamon contains three major compounds (cinnamaldehyde, cinnamyl acetate and cinnamyl alcohol), which are converted into cinnamic acid by oxidation and hydrolysis, respectively. In the liver, this cinnamic acid is β-oxidized to benzoate that exists as sodium salt (sodium benzoate; NaB) or benzoyl-CoA.

As is often the case with natural substances with medicinal properties, it is unclear which constituent provides the benefit, or whether there is a synergistic benefit between them.

As I suggested in an earlier post, even though Sodium benzoate (NaB) has been shown to be the reason for some of cinnamon’s benefits and is widely available, I propose to use cinnamon itself.

The mast cell benefits of cinnamon come from cinnamaldehyde and may not be produced by the metabolite NaB.
  



Purpose

In terms of their involvement in allergic and inflammatory conditions, mast cells (MC) can be promising targets for medical agents in therapy. Because of their good compliance and effectiveness, phytochemicals are of great interest as new therapeutic tools in form of nutraceuticals. We found recently that cinnamon extract (CE) inhibits mast cell activation. Here, we analysed the effects of a major compound of CE, cinnamaldehyde (CA), on mast cell activation. 

Conclusions

CA decreases release and expression of pro-inflammatory mast cell mediators. This inhibitory action is similar to the effects observed for CE indicating CA as the main active compound in CE leading to its anti-allergic properties.



Conclusion

Today’s post gives a particular reason for people with autism, allergies and mast cell issues to trial cinnamon.

The only thing to be careful of is histamine intolerance.  This does affect several readers of this blog.

The main cause of histamine intolerance is an impaired histamine degradation caused by genetic or acquired impairment of the enzymatic function of DAO or HNMT.

One reader pointed out that the cheap 23andme genetic test includes the genes for histamine intolerance (this service is no longer available in all countries).

The sodium benzoate (NaB) produced by cinnamon is a DAO inhibitor and so will further impair histamine degradation in people with genetic impairment.  

In most people, even if they have allergies, a teaspoon of cinnamon will not affect their ability to degrade histamine.











6 comments:

  1. Hi Peter, cinnamon, cassia type, one teaspoon or 1000mg, is worth a try for my son? in which cases of autism wouldnt work? I didnt try baclofen, i saw a paper called baclofen induced diskynesias, my son is getting free from them but the movment disorder rremains. Could be a relation between ketosis and improvment in sensory issues? regards, Valentina

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    1. Hi Valentina, it is the other type of cinnamon (Ceylon not Cassia) that is best. Cinnamon Cassia contains something called coumarin, that is best avoided. This type of cinnamon is sold by health food stores, rather than supermarkets, it is not expensive. It is worth a try.

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  2. Peter, I don't understand the bit about histamine intolerance. If cinnamon is a mast cell stabilizer, shouldn't it actually help?

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    1. In most people cinnamon is fine, but some people have an adverse reaction because the NaB that is produced acts as a DAO inhibitor. This means that any histamine in circulation cannot be degraded, so it just keeps going around. So while one aspect of cinnamon might be positive, since mast cell degranulation is less, what histamine is released cannot be disposed of by the body, in those people. So the net effect in those people is negative. In most people the effect will be positive, or just negligible. People with this allergy have a problem with fizzy drinks, since they often contain NaB, so they would know about it.

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  3. Sodium benzoate also increases AMPc by activation of pKa. in some autistic patients gen ube3A is overregulated and by activation of PKA and phosphorilation of site T485 of ube3A gene is possible the regulation.
    Dup15 syndrome has this situation.
    Another compound that regulates ube3A by activation of pKA is Forskolin. Have you tried it? I have no read any post con your blog

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    Replies
    1. Thanks for the comment. I have not tried Forskolin, but I will read up on it.

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