Caffeine's possible impacts on methylation...

[pgoody]

About 4 years ago I initiated a nearly 6 month long string of panic attacks and having anxiety to point of feeling completely dead by consuming half of a caffeine tablet. That was the last time I consumed any amount caffeine. Caffeine is, of course something anyone with panic related disorders should avoid, and for me it was the agent that made me have panic in the first place, and I learned quickly.

Anywho, I was doing some research about adenosine last night, because I wanted to know a bit more about SAH and its inhibitory effects on methylation, and how adenosine plays a role in that. Apparently high levels of adenosine will inhibit SAHH function and will cause higher levels of SAH to potentially inhibit SAMe.

Caffeines primary mechanism of action is as a adenosine receptor antagonist. Now caffeine does a whole bunch of things that could potentiate a panic attack as a result of this, increasing nuerotransmission all around, and increasing adrenaline output (a biggy I think), and inhibiting GABA as well. Besides all this, I wondered what kind of impact caffeine could have on methylation. Would its antagonism of adenosine receptors cause a higher levels of adenosine that would inihibit SAHH function?

I found this article which discusses adenosine plasma levels as a result of caffeine intake. (http://wurtmanlab.mit.edu/static/pdf/921.pdf).
I don't know if plasma adenosine levels impact SAHH or not, as I am not quite sure where the methylation reactions occur.

Here is another interesting article about the synthesis of caffeine in caffeine containing plants. Apparently its synthesis requires methylation and flows down the adenosine metabolic pathway, no wonder it is mistaken for adenosine in our bodies. (http://www.sciencedirect.com/science/article/pii/S0014579301025121)

Caffiene can also be referred to as trimethylxanthine, as there are 3 methyl groups attached to it. I read somewhere else that it can act as a methyl donor as well by donating methyls in the liver.

So it seems to me that caffeine could potentially impact methylation negatively and positively in different ways. I just wanted to share this info because I thought it seemed interesting while reading about it.

 

[Patrick*]

I can report the results of a recent study on caffeine use in PWMEs. Using a cohort of 1, the study found a 100% correlation between increased caffeine and decreased energy.

 

[Victronix]

Sorry to hear of that kind of a response to a caffeine tablet. Glad you are doing some research.

When I took caffeine in pill form, long ago in the idiotic pms drugs, it only made me shakey and feeling awful.

As a non-PWME (but with numerous methylation issues) I notice that there is a bell curve on my energy from coffee -- too much and it just makes me sleepy, but just enough and it works well to increase energy. When I have my one shot of espresso for the day is the best time of the day -- the most productive, happiest, feeling the most normal, etc. It's almost remarkable what a beneficial effect it has for me, particularly in the midst of my various methylation start-up symptoms, which it can alleviate. So maybe that supports your hypothesis.

23andme said I have the genes of a "high metabolizer" of caffeine, but I didn't look into it any further. Espresso has a very different effect for me than coffee, which does almost nothing in comparison.

 

[searcher]

I have participated in a similar study with a cohort of 1. Caffeine decreases my energy and increases my brain fog 90% of the time (I keep trying to repeat this study in case the results come out differently.) I am lucky in that it doesn't cause me to experience panic attacks. I don't know if it's because of methylation but it has a significant effect on me. Modafinil has a very similar effect on me, but its mode of action is not known so I don't know if its negative effects are due to a similar pathway.

 

[Ema]

I gave up caffeine for four long, miserable years without it. I just recently added it back in and it makes me more energetic for sure. I think it stimulates ACTH release which can increase cortisol production. Things that increase cortisol production generally are positive for me.

I'm interested to know more about the mechanisms of how it works for sure though.

Ema

 

[Helen]

Very interesting thread and inputs!
Another aspect of coffee and caffeine is that caffeine increases adrenaline and with COMT gene defects it takes about 4 times longer than "normal" to break down the adrenaline, I have been told by a professor in molecular biology. That is also a reason why coffee and caffeine might make it difficult to fall asleep.
If you haven´t had any gene test, an indication of COMT defects can be if you get rapid heart beats from the dentists Xylocain injection that contains adrenaline (or from other medications that also contains adrenaline)

Helen

 

[pgoody]

Helen,

Very good point. COMT SNPs decrease the rate of breakdown of all catecholamines. I still have a few weeks before my 23andME results are in, and I am kind of anticipating a few SNPs in my COMT genes. Any adrenaline/ dopamine increasing substances I feel are not good for me. I have no known allergies, thank god, but I absolutely dread the idea of having to use an epipen or epinephrine from the hospital. I had a histamine blood test, which indicates I have high histmaine, but I normally don't show any symptoms of allergies (season, food, whatnot). I also think I have natural issues with high adrenaline in my body (abnormally high), I don't know if that is because I create large amounts of it, can't process it, or both. One thing I read is that the body naturally produces adrenaline in response to histamine to naturally combat the histamine (unfortunately in anaphylaxis it isn't enough). I kind of wonder if I have high histamine, but do not show any sort of allergic response due to higher adrenaline? <-- This is purely conjucture. I haven't researched the topic but ran into it once I think.

Here's another link to the whole caffeine methylation thing: (http://www.ncbi.nlm.nih.gov/pubmed/11237928)
I just google searched this connection because I read in another methylation article that "methylation demand and Hcy production is also increased by: high coffee consumption due to the O-methylation of chlorogenic acid, a polypehnol in coffee"

So not only does it appear to me that coffee will increase adrenaline, but it will compete for its methylation :thumbdown:.

 

[Helen]

Pgoody,

More interesting facts, thanks. I am allergic to wasp´s stings and my doctor is planning to give me an epipen this year too. I haven´t had to use any after an anaphylactic shock many years ago, but good to know that I should try to find another solution if possible. I hadn´t thought of this before.
In old times in Sweden people drank some alcohol after a wasp´s sting. That was said to save them from an allergic reaction. Is there any clue in that? Or maybe it was only a reason for another glass .

The adrenaline -histamine connection is interesting. I was told that any food sensitivity could cause increased heart rate as a reaction to check out for after eating the "bad" thing. Released histamine - then adreanaline?


Helen

 

[Victronix]

FYI, I'm COMT +/+ and coffee is my lifesaver. It's probably the combination of different SNPs that amount to a response, since there is so much overlap in what affects what.

 

[pgoody]

Helen,

Here is an article that talks about the body's manufacture of adrenaline in response to elevated histamine:
http://nobleboss.awardspace.com/mednotes/pharmanotes/chapter_set4/hist_antihist.htm
If you scroll down you will see this:
"There is a secondary rise in BP caused by adrenaline and noradrenaline which are secreted as a result of stimulation of the nicotinic receptors in the adrenal medulla by Histamine."

IIt might be the body's way of dealing with excess histamine. If you are at risk of anaphylactic for any reason I would definitely have an epi pen around. Also would be a good idea to have some benedryl around too if you don't think it's going to be a severe reaction. My mom had a severe reaction once, she took some benedryl, knew the reaction was going beyond that and asked for a ride to the hospital. My grandmother had a severe reaction to pecans, luckily found her neighbor at home next door and got a ride to the hospital. Now my mom has an epi pen, but she's obviously avoiding her allergen now. I would just say have one on hand to be safe.


If it's true that adrenaline is naturally secreted in reaction to histamine it might be the case that I am susceptible to having panic attacks as a result of allergic reaction. I spent a year abroad in China, and the first few months that I came home I was having some issues with food and panic that have died down. Getting reacclamated to the food and pollen, etc etc here could have been the issue.

 

[Helen]

Pgoody,

Thanks for another interesting article and for good advice. It takes some time for me to read though as English isn´t my mother language. The facts about histamine and adrenaline is really something to consider. I do hope you have found the cause of your panic attacs and will avoid them in the future. Many with panic attacks have had COMT SNP´s confirmed in a 23andme test. Dr Nancy Mullen has written that low doses of lithium orotate might affect the COMT expression. And physical activity is an antidote to adrenaline as you probably know. How would antihistamin medication affect a panic attack if you would have one? Could that be a test of its origin and possible help?

Coffee is a methyl donour according to Amy Yasko and with COMT SNP`s one should be careful with to much of them as you might know.
I get a little alert drinking decaffeinated coffee too, so maybe some other stuff in coffee is working. As you say, Victronix, there is so much overlap in what affects what.

 

[Santino]

For me, coffee and also green tea are the things which keep me functioning. And as long as coffeine is "working" in my brain, I can control my depression symptoms or anxiety symptoms better, because my concentration and energy is better. I also suffered from panic attacks over a and although coffeine is a stimulant in I could better avoid it during acute panic, it was surely more helpful then harmful. In psychology everybody advises you to avoid caffeine when dealing with anxiety. In my opinion, everyone has to experiment for itself. For there is the rule: Don´t use it if you already feel activated or even overactivated (then it can turn into irritability/anxiety and fall in depression afterwards) + Don´t use it after 3 pm (I am a slow metabolizer and it affetcs my sleep when using to much or using even small amounts too late).

KR

 

[Critterina]

I'm also a non-PWME, but I've always been sensitive to coffee, my go-to dose being 1 cup of half-caf. (LOL, I just wrote half-calf...but the spelling works ). Since I've been on my supplements (antioxidants plus methylation mostly) I can tolerate 2 cups of full-strength. I don't feel like I need it - I'm not an everyday coffee drinker - but after 35 years of a pretty established pattern, I'm suprised.