EAE cure of the week. Cinnamon

Mondal S, Pahan K.Cinnamon Ameliorates Experimental Allergic Encephalomyelitis in Mice via Regulatory T Cells: Implications for Multiple Sclerosis Therapy. PLoS One. 2015 Jan;10(1): e0116566.

Upregulation and/or maintenance of regulatory T cells (Tregs) during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Cinnamon is a commonly used natural spice and flavoring material used for centuries throughout the world. Here, we have explored a novel use of cinnamon powder in protecting Tregs and treating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS. Oral feeding of cinnamon (Cinnamonum verum) powder suppresses clinical symptoms of relapsing-remitting EAE in female PLP-TCR transgenic mice and adoptive transfer mouse model. Cinnamon also inhibited clinical symptoms of chronic EAE in male C57/BL6 mice. Dose-dependent study shows that cinnamon powder at a dose of 50 mg/kg body wt/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, oral administration of cinnamon also inhibited perivascular cuffing, maintained the integrity of blood-brain barrier and blood-spinal cord barrier, suppressed inflammation, normalized the expression of myelin genes, and blocked demyelination in the central nervous system of EAE mice. Interestingly, cinnamon treatment upregulated Tregs via reduction of nitric oxide production. Furthermore, we demonstrate that blocking of Tregs by neutralizing antibodies against CD25 abrogates cinnamon-mediated protection of EAE. Taken together, our results suggest that oral administration of cinnamon powder may be beneficial in MS patients and that no other existing anti-MS therapies could be so economical and trouble-free as this approach.

Who needs drugs when we have herbs and spices? 

Why go to a Neuro when you can pop down to your local supermarket? 

We have heard of the potential beneficial effects of tumeric and now it is the turn of cinnamon powder. This paper will be one that the media takes up, as it was also reported that Cinnamon can treat Parkinsons disease, so I thought that I would have a look.

This study is based on an earlier study where it was reported that addition of 2.5mg/ml to 10mg/ml of sodium benzoate, a food preservative and a metabolite of some components in cinnamon, cranberries and ripe cloves, placed into drinking water could inhibit EAE. This means that about 10-50mg of sodium benzoate, with a mouse drinking 3-5ml a day, inhibited EAE. In this study they gave 50-200mg/kg of cinnamon powder (about 1-4mg) of cinnamon orally, so I wonder how much metabolised to sodium benzoate? All of it and more would have to to create 10mg of sodium benzoate.

Anyway the data look clear and there is an inhibitory effect when the cinnamon powder was given around disease onset, suggesting that this can suppress the immune system.

It was shown that cinnamon powder limited immune activation and white cells entering the CNS, therefore inhibits everything down stream of this, like demyelination cytokines, etc, as would be expected.

The action appears because it is increasing regulatory T cells, (Tregs) inhibiting Th17 and switching Th1 to Th2 and so we have the full regulatory gamut, but the action was via Tregs that could suppress EAE as shown by transfer and by blockade of T cell function.

However, guideline 19 of the ARRIVE guidelines  (about reporting animal experiments) requests discussion the translatability of the work. Whilst we know that PLOS One has not been implementing these guidelines as we showed recently.  Feeding of mice with 50-100mg/kg of cinamon powder is equivalent of eating about 3.5g/day more ususally 7g/day or a quarter/forth of a 35g jar of cinnamon spice a day in human terms. However, if the "rule of twelve" of dosing mouse to man applies then it is not a quarter of a jar but half a gramme and about a fiftieth of a jar.  

I like cinnamon, so out of interest I had a quick look this morning. I got the weighing scales out, but had not got up to 1g and there was loads of powder. So I can say cinnamon powder floats on water, after all it is bark dust. In this study they mixed it with methly cellulose i.e. wall-paper paste in this study to get it into suspension/solution.

I must admit even a small amount on a teaspoon tasted disgusting and very over powering. Maybe if it were mixed with ice cream. Alternatively how much cinnamon toothpaste could you eat? 
Seriously,if they dosed properly, the mice would not have tasted it as the dosing bypasses the tongue.

The control in this study was just wall paper paste and water.What would the effect have been with nutmeg or garam marsala used as a control?  

One question could be if "stress" in response to an adverse effect of cinnamon powder was the mechanism of action of cinnamon and if the inhibitory effect of stress is mediated by T reg cells, then blocking the T reg response would block the inhibitory effect of cinnamon. 

However, if this level of cinnamon was so good at blocking the immune response, then I would expect that you would see consequences of immune-suppression in cinnamon eaters. 

Do we?

This is the problem I have with nutriceuticals, is that as they are normally taken with essentially no side-effects. How can this be?, if they really are that active.

Will trials be done in MS? I guess the authors will have the problem... who will pay for them.  But for a £1 a week it would be cost effective if cinnamon powder really did work.

The data look compelling and it should be an easy experiment to see if cinnamon can really effect T reg function in humans. This could be done in a few days based on the work presented here, before any trials are needed and this would cost a lot less than the animal work shown in this study. 

I suggest that this is shown before you start consuming a few teaspoons as day, as we have already had salt water and a load of other things that can be just as effective in EAE.

Wouldn't it be funny if cinnamon could knock pharma of their perches..but do you think this would ever happen? 

CoI: None