Monday, 12 January 2015

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

22 comments:

  1. If you think it is sodium benzoate then that is already added to many foods as a preservative... Just seen it on a jar of pickled herring in mustard sauce and a bottle of ketchup.

    ReplyDelete
    Replies
    1. yes but the maths dont work there is not enough cinamon to produce the level of sodium benzoate to work

      Delete
  2. I read a year or two ago that caffine can cure EAE. Also that drinking caffine can cure tinnitus. I'm not so sure, what do you think MD about caffine curing EAE?
    I do have some ear sensations like something goes into spasm in my ear occasionally and am seeing an ENT consultant in two weeks time. I am sensitive to caffine and it agrivates me, it makes my anxiety worse. When my anxiety gets worse my MS seems to worsen.

    ReplyDelete
    Replies
    1. There seems to be quite a lot of data showing that caffeine can be neuroprotective, though obviously there are side-effetcs.

      Delete
    2. Your experience suggests that caffine is not a cure...but it was an "EAE Cure of the Week" and as to curing EAE I think it unlikely, but we have do data on this and so can not speak with any authority.

      Delete
  3. "I must admit even a small amount on a teaspoon tasted disgusting and very over powering. Maybe if it were mixed with ice cream".
    Home made doughnuts, put some clear runny honey on top and spinkled with a good helping of cinnamon.. Very yummy...

    ReplyDelete
    Replies
    1. but 7 grammes, so a few tablespoons what would Mary Berry think of that?

      Delete
    2. one teaspoon in a mango smoothie is very good

      add one tsp cinnamon, 1 tsp gingerpowder, 1 tsp tumeric 2 cups nut milk, 1 mango, 1 tsp honey

      Delete
  4. A possible Ph.D. project?

    ReplyDelete
    Replies
    1. Maybe.
      i had a terrible sore throat this morning was it an infection due to immunosuppression because of the cinnamon or because i was sitting in a windy cold football stadium?

      Delete
  5. Why do some people insist on over indulging........food, alcohol and cinnamon? http://well.blogs.nytimes.com/2013/04/22/consequences-of-the-cinnamon-challenge/?_r=0
    Please no shots of cinnamon at the corner spice tavern :-)

    ReplyDelete
    Replies
    1. Thanks Steve S...this makes my point...this girl is taking one spoonful and she finds this is disgusting and can spit it out so she gets a fraction of the intended dose.

      However the poor old mice cannot spit it out, but their stomachs may be burning from the effects of the spice, hence my glimb comment about using nutmeg or something similar to give the unpleasantness control. Because if the end result is a massive stress to the mouse there will be no EAE...not a wondercure... but the same old stuff that perhaps taints EAE research I call it the building site effect.....put lab mice near a building site and your EAE work is doomed...maybe they sense the vibrations/ultrasonics from the building work

      Delete
  6. Right I'm off to bulk buy some cinnamon :-) I did go through a phase of drinking ginger tea and putting flax seed in my porridge when I was first diagnosed.
    MD - My book of healing foods says pomegranate help sore throats.

    ReplyDelete
    Replies
    1. Bulk buy because of cooking not for health reasons..this paper does not give such evidence.

      Thanks for the advice about pomegrante juice but an aspirin and a bit of hydration did the trick

      Delete
    2. l bought Ceylon Cinnamon - from Bulk lngredients - Amazon - its very cheap. 500g. And l put a spoonful into hot milk at night. And a spoonful in the cafetiere with my espresso coffee in the morning. Just made cinnamon/nut/chocolate fudge - l am also taking Turmeric so getting really spicy.

      Delete
  7. Sorry, my comment was said tongue in cheek. I'm sticking to my DMT for now. Cinnamon will be plan B.

    ReplyDelete
  8. Cinnamon mixed with honey is rather tasty. But beware, do not eat too much. The substance coumarin in cinnamon can cause damage to the liver:
    http://www.nlm.nih.gov/medlineplus/druginfo/natural/1002.html

    ReplyDelete
    Replies
    1. certainly more appetising than Steve S's suggestion ;-)

      Delete
  9. cinnamon verrum has much less couramin than cinnamon cassia and is therefore far less toxic

    ReplyDelete
  10. I take Ceylon Cinnamon and I'm pretty sure it helps. I take 1/2 a tspn in hot water, twice a day. I'm pretty sure that they conducted clinical trials at a university in California and found that this was the case.

    ReplyDelete
  11. The 3.5g dose isn't right. You don't simply scale for weight: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/.
    In a nutshell, in order to correct for differences in metabolic rate and surface to volume ratio, a correction factor is used. For mouse to human, its .081. So 100 mg/kg in a mouse is 8.1 mg/kg in a human. Thus a person who weighs 60kg would take 480mg - about half a gram.

    Also you definitely want Ceylon cinnamon. It's sweeter than the cassia sold as cinammon and has much less coumarin. Tastes great in a smoothie :)

    ReplyDelete
    Replies
    1. Please read the post we comment on scaling click on mouse to man (above)
      and half a gramme is what we said

      Delete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.