Acetylcholine Deficiency plays a big role in why people with ADHD have multiple troubling symptoms/tendencies.

[Eclecticentric77]

As if lacking Dopamine, Serotonin, Norepinephrine, GABA etc. was not enough? As some of you on here have read and noticed, I am a strong supporter and user of helpful supplements to combat the negative side effects that come come with taking continued ADHD stimulant medication. I take a low dose stimulant medication and a group of different supplements for multiple reasons. Anyway I'm not here to talk about that, I have an entire post dedicated to explaining that incase you're interested. I have studied ADHD for a few years now and am in grad school to become an MFT Psychologist; the only reason I mention this in my posts is to demonstrate that there is some merit to my posts (and that I'm not just some schmuck flapping my lips on here).

Anyway, so recently in my studies I have discovered that the neurotransmitter Acetylcholine plays a vital role in ADHD, mainly because people who have ADHD (particularly Combined Types according to this study I found) lack Acetylcholine because of a Choline gene Variation. What is Choline and what does it have to do with Acetylcholine? Choline is a macronutrient that is important for muscle movement, nerve function, and brain development just to name a few. It can be found in beef, liver, eggs, salmon etc. Choline is also highly important for making Acetylcholine. So where exactly does the root of the problem stand, especially for those who consume a high Choline diet? The root of the issue is in how the brain of someone with ADHD transports Choline. There is apparently a gene variation within the presynaptic choline transporter (CHT, SLC5A7) that causes an up regulation when we need to have sustained attention. Interestingly enough it is thought that out of the 7 major Dopamine receptors there is a similar variation in the D4 Dopamine receptor that causes a faster reuptake of Dopamine in the brain of people with ADHD. If that sounds too biological or physiological, think of ordering a package of a large amount of chairs for a wedding for example. And let us say that those chairs are being transferred from truck to truck at different stops, and in one of those stops (the gene variation), the truck driver impatiently leaves after only a few chairs are loaded into the truck, thus leaving behind like 80% of the chairs (Choline) and arriving at the wedding (area of Acetylcholine production) with only a few chairs. Nothing against truck drivers haha, I have a good friend who is one and an uncle, just the quickest example I could come up with (I blast "Turn the Page" quite often while driving). So what are the symptoms of someone with a low levels of Acetylcholine supposedly? :low energy levels of fatigue, memory loss, cognitive decline, learning disabilities, muscle aches, nerve damage, mood changes or disorders. When I saw that I said wow, I have a problem with all of that and I have Inattentive ADHD not Combined Type. I take a supplement called R-Alpha Lipoic Acid (RALA) for the immensely strong Antioxidant effect against my stimulant medication's oxidation. RALA also helps the brain use the Acetylcholine it has more efficiently. Considering I have little Acetylcholine to begin with, I started trying out different different supplements to help out with Acetylcholine synthesis in the brain, keep in mind this is completely different from eating foods high in Choline, this is because certain supplements go straight to the root of Acetylcholine production in the brain by crossing the blood brain barrier or by falling into a different transporter area. Ironically enough, nicotine once it enters the brain attaches to Acetylcholine receptors and mimics the actions of Acetylcholine. This is one of the reasons why you see a lot of people with ADHD who are smokers. I grew up playing in many bands and many of my friends were musicians who smoked cigs like crazy, and interestingly enough a lot of them now are finding out they have ADHD.

Supplements I tried were: Alpha GPC, Gotu Kola, and CDP Choline. CDP Choline so far has worked the best for me, because there is a much lower dosage available compared to the other two I mentioned. Also CDP choline slightly boosts up Dopamine, Serotonin, and Norepinephrine which people with ADHD also lack. I take specific supplements for those other neurotransmitters but thankfully the small boost from CDP Choline has not caused a problem. Cognitively because of taking CDP Choline my mind has much better reasoning, it is a lot easier for my thoughts and speech to keep up with one another, and most of all my body feels much at ease and does not feel irritated like usual. Just something I wanted to share. What works for me might not work for you, and Alpha GPC or Gotu Kola might work better for you. Just a heads up that with Alpha GPC I felt Acetylcholine a bit too much in my opinion and it somewhat dulled my other neurotransmitters I felt, and Gotu Kola worked well but left me in a really bad mood once it wore off which did not go good with my medication. There are multiple other supplements out there to help with Acetylcholine but after reading the risks involved with some, I narrowed the verdict down to CDP Choline. I take CDP Choline 250mg by Jarrow Formulas (one of my favorite companies). Anyway hope some of you found this helpful, best regards.

[ZoeyHarper]

Fascinating and thought provoking. All the best with your continued studies!

[Faithfull]

Good luck I ain't got a clue

[Hidden]

Thank you for the information Electic...77 😊

[cuaster]

Great information. Thank you!

[Laufer]

Hi - I imagine there are not studies showing interactions between your stimulant medication and the various supplements you take. How do you know that they are not decreasing the effectiveness of your stimulant? Or causing other side effects?

I know that is a common discouragement coming from the mainstream medical people, and I understand why they say that. What is your thought?

[Eclecticentric77 in reply to Laufer]

Every supplement I take has a very specific purpose. When someone creates their nootropic stack (supplements they take), it is highly advised that they know what exactly they want to improve/get out of it. My nootropic stack aims to help increase the availability of neurotransmitters that because of my condition, are low. I also take other supplements that are not for neurotransmitter increase, but for neurogenesis, neuroplasticity, to keep my heart safe, and for more fluid thoughts and reasoning. In my last 8 years of studying psycholog, the idea of a unique neurochemistry is frequently brought up. Everyone's neurochemistry is different, but studies have shown that dificiencies in specific neurotransmitters is common amongst people with ADHD, with some variation in amounts among the 3 ADHD subtypes. Your body/mind reaction is a good indicator of whether a supplement goes with you or not. A good website that demonstrates scientific peer reviewed articles on research based off supplement intake is. ncbi.com. I believe supplement intake is crucial for successful results when taking stimulant medication. For example, if I do not take CoQ10, my heart starts pumping more than usual when I do cardio in the gym, which is not good. This happened to me when I first started taking my stimulant medication, and as soon as I started taking CoQ10, my heart rate went back to normal thankfully. Some supplements I take are crucial to the medication working well for me, others like PS100 and Coconut oil for example, are not as crucial to my medication working well but are rather for my overall health. I had to do a lot of research and trial and error with some supplements. At the end of the day my aim is to be the best me I can be. Nootropic stacks are taken by many people outside the ADHD community, and even among a good amount of neurotypicals. Supplements here in the states still are considered more of an alternative/eastern thing, this is something I really hope to help change. As for the mainstream, I would recommend anyone to steer clear and do research on your own before believing what's presented to you, a lot of the time there is double motive involved. In my opinion, the mainstream could make supplements look useless and negative, perhaps because of being in ties with Big Pharma, and Big Pharma loses money when people start noticing that supplements are a much less expensive alternative with fewer to no side effects. What's the best way to steer people away from buying supplements? Bad publicity and false/biased reports. Stuff of that nature has been happening for decades. In the end, it's all up to the individual, and I recommend people look into perhaps building a nootropic stack with the aims of they themselves, being the best them they could be.

[Kai999]

Thank you for the information,

Can you tell us more about the connection between acetylcholine and cigarette smoking? Will my acetylcholine level increase if I quit smoking? Thanks

[Eclecticentric77 in reply to Kai999]

When someone smokes cigarettes, our brain perceives the nicotine in cigarettes as Acetylcholine, and makes more of it for that reason. Since people with ADHD lack Acetylcholine, smoking large quantities of cigarettes is not uncommon, since they're essentially self medicating without knowing it.

If you quit smoking, your Acetylcholine levels will revert back to their lower levels. For this I would highly recommend the supplement R-Alpha Lipoic Acid 100mg by Jarrow Formulas. It works great for helping the brain with Acetylcholine synthesis and helps it last a much longer time than cigarettes (which is why you'll see some people having cigarette breaks every 15min). I would add the supplement N-Acetyl Tyrosine to your list as well, since it helps with Dopamine and Norepinephrine, and cigarettes are known to give a slight Dopamine boost. Dopamine and Norepinephrine are low in people with ADHD as well, and most stimulant medications primarily work by helping the brain with Dopamine and Norepinephrine.

So if you take both R-Alpha Lipoic Acid and N-Acetyl Tyrosine, it should help replace cigarettes and should help lessen some uncomfortable symptoms that are common when someone stops using cigarettes.

[Kai999 in reply to Eclecticentric77]

Thanks a lot, I just ordered choline and R-Alpha Lipoic Acid. Unfortunately Tyrosine affects thyroid function. Do you have any suggestions as far as omega 3? Some people swear by it for a ADHD.

[Eclecticentric77 in reply to Kai999]

Nice, and gotcha. Omega 3 fatty acids, along with omega 6 and 9, are helpful for people with ADHD, I take flaxseed oil (which includes all 3).

Here is a link of a google doc I made that includes supplements that are helpful for people with ADHD, and the ones I take and why.

docs.google.com/document/d/...

[Kai999 in reply to Kai999]

Thank you, you're awesome, I just did some research about Phosphatidylserine and found the following :

ncbi.nlm.nih.gov/m/pubmed/2...

I wonder why doctors don't know these things.

[Eclecticentric77]

thanks for the kind words and link. Phosphatidylserine ie. PS100, is such a great supplement to aid the issues of having bad short term memory because of having ADHD. NCBI is such a great website, have found tons of AMAZING articles on there.

That's a question that I have been asked frequently. The reason why has to do with multiple things, mainly the fact that supplements have only until recently started to be taken seriously by the Psych. community to the point where studies have been increasing in the ADHD community and released to the public. My studies in grad school have me reading material that is current, and even from these current books, very little is mentioned about supplements as aids to people who have ADHD. The only thing I recall reading about in a book 2 years ago, was about the supplement Ginkgo Biloba showing some helpful potential to people with ADHD, that's been all I have seen. Considering a good amount of doctors and psychiatrists got their Phd.'s years ago, I don't expect them to know much or anything about supplements, besides what some of their meetings or seminars perhaps explain. My psychiatrist had not heard of half of the supplements I take.

[JV001]

Hi, first of all I want to thank you for this in-depth article about the link between Acetylcholine and ADH. It is written very understandble and thought provoking.

The part that also got my attention is the following: You mentioned that you also take specific supplements for those other neurotransmitters (Dopamine, serotonine,..) . Can I ask you which supplements and for which specifik outcome?

I'm also diagnosed ADHD since I was 7 and constantly searching for "non-chemical" methods to enhance some of the "downsides" of adhd. Nevertheless also using the benefits of ADHD as an asset in life/business ;-).

I'm sorry for my broken English and looking forward to your reply.

Thanks.

Jochen (Belgium)

[JV001]

Okay my ADHD took advantage of me, I missed the link above

Thanks man!

docs.google.com/document/d/...

[Eclecticentric77 in reply to JV001]

You're very welcome, hope all goes well brother

[Setchan]

This is honestly lifechanging for me, I'm going to try CDP-Choline. I've been taking L-Tyrosine and 5-HTP and it's made a huge difference in my focus and mood, but I can't shake the difficulties I have committing behaviors to habit. Learning that a deficiency in acetylcholine is a factor in why these thoughts and impulses don't stick to memory was devastating, and you've given me hope again that I can continue to improve. Before now, I felt like no amount of hard work would actually manifest in change.

[PizzaAthlete]

Hi, finding your post feels like finding the holy grail. I have trawled online for information about the acetylcholine connection with adhd. I have combined subtype and my prescribed stimulants help but only so much. Before diagnosis I was heavily dependent on caffeine to achieve anything requiring thinking and this was unsustainable on meds. I sampled some Alpha GPC while trying different supps which are safe with my meds and it was profound. Would you be willing to share any references/research you have found re acetylcholine and adhd? I am keen to bring this to my next meds review. Great work! 👍

[Eclecticentric77 in reply to PizzaAthlete]

Hi there, thank you! Here's a link of someone who has quite a bit of info on acetylcholine, supplements, etc. I'd also recommend looking for articles on ncbi.com

nootropicsexpert.com/alpha-...

[HCStymie]

This guide is great. Been looking into a lot of stuff lately and it is quite overwhelming the amount of information and supplements etc. out there.

Do you know of anything that may help upregulate neural receptors to undo the opponent process of stimulant increase of neurotransmitters?

For me, I am on long term relatively high dose Amphetamine based meds. And am Dependent. Research tells me that my brain is no longer regulating dopamine, norepinephrine, and serotonin efficiently and relies on the Adderall to do it. Concern for me is that L-Tyrosine, L-Tryptophan, L-Phenylalanine and things like that which help boost neurotransmitters, may exacerbate the acute tolerance which causes the downregulation of receptors. i.e. trigger the opponent process even more. I tried those 3 mentioned and a combined nootropic called "True Focus" from Now brand. Did have to increase my dosage of Adderall but can't tell for sure if that was due to what I just mentioned, an increase in my Mounjaro dosage (which delays gastric emptying which may be a factor and seemed to be when I first started taking it) and/or my horrible sleep habits and staying up overnight to work while researching and doing chores etc. during the day.

So, after finding out about neurotoxicity, oxidative stress, etc. I've been more focussed on neuroprotection. Want to switch meds and see if the Modafinil Atomoxetine combo would work for me. Atomoxetine has opposite side effects from amphetamines and are positive in my case. But don't know if my brain can handle the withdrawal from adderall without high dose of Modafinil (if Modafinil even works for me).

Started taking N-Acetyl L-Cysteine (NAC) 2 days ago. Being a supplement skeptic wasn't expecting anything. But seems to actually be making me able to focus longer and not need a nap in the middle of my day, so to speak. Will have to see if it is the occasional fluke or not, but hopeful.

If you can, I'd see if you can get your hands on some Lovaza. You mentioned a sensitivity to fish oil. But Lovaza (and generics of course) are highly purified Omega-3 fish oil with both DHA and EPA. Since it is a prescribed substance it is regulated. 1 Lovaza is equal to 3 or 4 OTC softgels. And OTC supplements are designated as food so they are not regulated and may contain trace impurities such as mercury, not have nearly as much as they state on the package, etc. Can say that my skeptic self has been able to detect the difference between skipping my Lovaza or not. Even tested it to be sure. I take 4 grams a day.

Tidbits:I didn't notice any difference with taking antacids before my Adderall. Supposed to absorb better. Tried sublingual MOA. People swear by it, no difference noted. Have noticed drinking a can of soda half way through my day causes faster offset of the meds (elimination due to increased acidity to the best of my knowledge). High fat intake is not associated with any difference in absorption. But has been shown to slightly increase duration. One day I was surprised my meds work working so incredibly well. Then I realized my company ordered lunch and I got the chicken curry salad sandwich. I looked it up online. 60 grams of fat. Don't know if it was the amount of fat, or since it was mostly mayo it might have been made with oils containing Omega 3, 6, 9 or something else that worked so well with the meds. One of the best tasting sandwiches I ever had too. But not a good long term option LOL.

[Eyrana]

Hi there, thanks a lot for your great article! 🙏 May I ask, what do you think of donepezil and other Acetylcholinesterase inhibitors by ADHD? Could these meds help and be safe at the same time?

[AlldayDreamHopeDance]

neurosciencenews.com/geneti...

Summary: Mice with the Val89 choline transporter variant had reduced rates of choline uptake and a diminished capacity to sustain acetylcholine production during attention-demanding conditions. The effect led to decreased cognitive performance when the mice were faced with additional challenges.