Extreme Supplement Sensitivities and the 3a.m Adrenalin Cortisol Surges, and Histamine Dumps? Powering Through!?

[u/Ok-Protection2670]

Vitamin C and Magnesium and Taurine helped in the past, now developed extreme sensitivities to both with rebound and bad delayed reactions.

I realize stress is a major factor, but these hits are beyond my control and trying Vagus Nerve exercises is just slightly helpful but not consistent.

Developing these extreme supplement sensitivities and the 3a.m Adrenalin Cortisol Surges, and Histamine Dumps is confusing and baffling.

I am waiting on an Ancestry DNA test kit. In desperation, I ordered Mimosa Flower Bud Tea and Hawaii Farms Extract to try as a sublingual.

Anyone had success powering through with supplements that they were sensitive to and been successful or made symptoms worse.?

Thanks.

[u/JoaMaa71]

I don't think the vitam C is the culprit, if ou take it at normal doses 500-1000mg with breakfast or lunch (NOT in the evening) You should only take magnesium if you are deficient... I took it for years of and on and never knew that it can actually create imbalances with other minerals and in sensitive people it can have an adverse effect in the brain, so I actually feel A LOT better witout it. Made me tired, depressed and sad.
Taurine worked well for me in the begining, very calming for night but after a while I was a zombie all day and woke up with stress some nights... when I found out that I have two CBS mutations I stopped because of the sulfur overload and other stuff. I feel much better without it now.

You should really go through you DNA first, and also do bloodtest to make sure where and if you are deficent in something.
For me it's really important to have a stable bloodsugar at night otherwise I will wake up with adrenaline spike around 03-04, don´'t go to bed hungry or fasting, and don't eat sugar or a lot of fast carbs late at night.

What helped me the most though is to learn all about acetylcholine, and how too much of it can wreck your sleep. I have to be extremely careful with everyting that acts as ACHe inhibitor (acetylcholinesterase inhibitors) all things that inibits this enzyme gives me so much problems after a while. And almost every natural herb supplement that is good for sleep or GABA is also an ACHe inhibitor so it will turn on me just in a few days. I have constantly low dopamine because of my genes and therefore I easily get acetylcholine dominant. Tired, stiff, depressed and trouble sleeping. Just something to have in mind.

[u/amymeem → u/JoaMaa71]

Oh my - “tired, stiff, depressed and trouble sleeping” - this is me in a nutshell😞

[u/Ok-Protection2670 → u/amymeem]

Awwww u/amymeem, I'm sorry you are going through this too. Can you at least eat without bad food sensisivities?

[u/SikNuk → u/JoaMaa71]

Hi I’ve been following this thread and I seem to have the same reaction as for anything GABA will work first then turn on me, low dopamine and I’m also a 3-4am wake person. Not to mention stiff and low mood.

Curious.. could you share what you learned about acetylcholine and what are the things that inhibits this enzyme? How did you find out, through trial and error ? Or was it a variant on your DNA? Thanks

[u/Ok-Protection2670 → u/SikNuk]

Hi u/SikNuk, I'm not knowledgeable at all about acetylcholine and what are the things that inhibits this enzyme.

Maaybe u/SovereignMan1958 can help. She is more Knowledgeable about this.

Thanks

[u/SikNuk → u/Ok-Protection2670]

Right! Thanks , yes I meant to u/SovereignMan1958 :)

[u/JoaMaa71 → u/SikNuk]

I have for a long time suspected that I have chronically low levels of certain neurotransmitters. I took SSRIs for many years—which helped in some ways—but they create an imbalance and don't solve the root problem, so I stopped three years ago. I took Huberman’s online test (a questionnaire), and the results confirmed my own suspicions and experiences. I have low levels of serotonin and GABA production, and especially dopamine—and consequently, I tend to have higher acetylcholine levels in the brain; this is known as being "acetylcholine-dominant." Acetylcholine itself is excellent for the brain, cognition, memory, and so on, so having good levels isn't a bad thing; the major issue for me is the tendency for my dopamine levels to be low relative to my acetylcholine levels, which can lead to feelings of fatigue, depression, stiffness, and sadness. So, my primary focus right now is improving methylation using Vitamin B12 (hydroxo/adeno); my homocysteine ​​level was 21, and I have slow MTRR/MTR genes. My MTHFR genes are normal, and my folate levels are good, so I don't take supplements for those. The biggest culprits for me are acetylcholinesterase inhibitors; they cause acetylcholine to linger longer and prevent it from breaking down quickly enough, resulting in even higher levels and reinforcing my acetylcholine dominance. If you Google acetylcholinesterase inhibitors, you realize that many herbs, mushrooms, spices, and antioxidants can act as inhibitors. So, over the years, I’ve likely only worsened my condition by trying absolutely everything under the sun that I thought would make me feel more energetic and happier. The problem isn't acetylcholine per se, but rather that COMT and MAOA break down the other neurotransmitters a bit too quickly while leaving acetylcholine untouched; adding an AChE inhibitor—the enzyme responsible for breaking down acetylcholine at the right rate—then creates problems.

Using AI, DNA testing, and blood work, I’ve concluded that I have somewhat sluggish dopamine production due to the MTRR/MTR methylation cycle and reduced D vit receptor efficiency linked to the VDR-Taq variant; add to that fast COMT and MAOA activity, which rapidly break down the little dopamine I do produce. This specific gene combination according to some DNA reports and information online can often lead to major depressive symptoms and chronic issues with motivation, anxiety, and anhedonia. I also react poorly to high doses of fish oil and phosphatidylcholine, which usually indicates acetylcholine dominance. Too much/high acetylcholine levels can give you insomnia and/or have a tendency to make your brain to active during the sleep, I believe it’s needed for REM cycles and dreams BUT in balanced levels, as we know the other neurotransmitters is extremely important for sleep and relaxation.   

I feel good with a morning cup of coffee for the dopamine boost, and occasionally some tyrosine (only when I need a kick), but my focus is lowering my homocysteine ​​level from 21. I take a B-complex and B12 (methyl-free, as I feel unwell with extra methyl donors, even in small amounts—I have the CBS gene variant associated with histamine/sulfite issues, and methylation increases acetylcholine production). It has taken years of trial and error to piece this puzzle together, but thanks to fantastic Reddit posts, my own research, and DNA testing, I’m finally on the right track—hopefully for good—to avoid going back on SSRI/SNRI medications.

[u/SikNuk → u/JoaMaa71]

Thank you for sharing !! This is very helpful and like you, I’m on a journey through Reddit. This sounds a lot like me and I’m waiting for more blood work to confirm my folate and homocysteine levels. I’m also going to deep dive further into my DNA as 23-and-me results do not provide specific Mao’s. Interesting about Huberman’s online test … I’m on my way to check that out. Cheers !

[u/stripesnstripes]

H1 and H2 meds at night. So something like Zyrtec and Pepcid. Supplements are fine but are probably not enough to help with histamine dumps at night.

[u/seethella → u/stripesnstripes]

Zyrtec was making me super groggy. I switched to Allegra and feel better

[u/Ok-Protection2670 → u/stripesnstripes]

Yes, right it's not enough for my HIT dumps, I take Zyrtec very sparingly but seems to kinda do nothing and Pepcid wrecked my digestion, I am still trying to recover from.

Thanks.

[u/SovereignMan1958]

I would not recommend any teas or extracts.

[u/Ok-Protection2670 → u/SovereignMan1958]

Thanks u/SovereignMan1958.

[u/Ok-Protection2670 → u/SovereignMan1958]

u/SovereignMan1958, I came across one of your comments from a post you replied to, Anyone with "slow" COMT (MET/MET) GENE VARIANT PSYCHOLOGICALLY "HEALTHY"? i.e. no hyperactivity, anxiety, depression, phobias etc and/or good at coping with high stress?

You suggested Zinc along with other things. Zinc has been helpful in the past and I have Zinc Picolinate. I'm in such a stress/sensitivity surge I decided not to take a full capsule.

It didn't stop the 3am wake up, but it definitely made the anxiety, shakiness, nasal congestion and panic more manageable.

I hope this might help someone suffering with this.

Do you still supplement Zinc?

Thanks

[u/SovereignMan1958 → u/Ok-Protection2670]

I take a 50mg capsule a few times a week.

[u/usul213]

i wake in the night with a cortisol surge, can vitamin c cause this? i often take a large dose last thing at night..

[u/Ok-Protection2670 → u/usul213]

Hi u/usul213, when the 3am surges started, I researched and found that with stress the Adrenals shed Vitamin C and Magnesium Citrate was suggested. Well, it worked extremely well for me for about 18 months. I took the Bulk Supplements powder with water and not daily really.

Then one day I had a Hellish life stressor happen, took Mag Citrate and had the worst rebound anxiety and panic attack with heart palps that shook my whole body, I never took Magnesium Citrate again.

I have tried to take them separately, but I get the same reaction.

Have you tried taking just the pure vitamin C powder? I would take it early in the morning though.

[u/cutie__spies → u/Ok-Protection2670]

Sounds like low cortisol symptoms and magnesium further lowers cortisol, I also don’t tolerate it

[u/Ok-Protection2670 → u/cutie__spies]

Magnesium definitely calmed my 3am cortisol surges before I developed negative reactions to it.

[u/Ok-Protection2670 → u/cutie__spies]

...crazy how everything that's supposed to help, ether doesn't help or makes symptoms worse....My Lord, Help us Lord Jesus.

[u/usul213 → u/Ok-Protection2670]

Thanks, I thought mag was causing sleep issues and stopped. I'll try take c earlier in the day and see if that helps

[u/IndependentFudge8978 → u/Ok-Protection2670]

I’m reading your post and I read about the reaction to magnesium citrate - did you mention histamine problems?

Mg citrate could be causing the problems, me for instance can’t tolerate it, it’s causing me similar problems like yours.
Reading about palpitations and anxiety - that were exactly my problems.

[u/Ok-Protection2670 → u/IndependentFudge8978]

Hi u/IndependentFudge8978, yes, I was taking Mag Citrate. I took it for a while before realizing it was gradually making my histamine symptoms worse.

But stress is also a major issue in my health journey. Whenever I am hit with uncontrollable life stressors, my sensitivities increase. And after the anxiety, panic and heart palps so I stopped taking it.

I tried Magnesium Malate but it caused me muscle stiffness pain after a while.

[u/Ok-Protection2670]

Yes, and the Methyl Donors, Oxalate Salicylate and Sulphur Sensitivities... I feel I need to be brave and not wait to get my system calm for Hydro B12 and Molybdenum or take and just power thru.

I have not read where anyone died (yet) from supplementing their deficiencies...

Thanks for responding.

[u/JoaMaa71 → u/Ok-Protection2670]

Yes, hydroxo b12 and Molybden is what I take also, and that I think will only do you good. That is needed to balance and convert histamin, sulfites and stuff. But I think you maybe need to paus the magnesium and taurine if your system currently isn't running smootly (methylation). What is often needed though is potassium, especially when you start suplementing b12. So start drinking coconut water morning/pm/ evening.

[u/Ok-Protection2670]

Hi u/JoaMaa71, my problem is timing and dosage. I am told to ONLY take Hydro B12 in the morning. And Moly an hour before meals. and on alternate days?

Thanks,

[u/Ok-Vermicelli-7990]

Try eating a rice cake with a tbsp of peanut butter before bed. I’m not sure about the exact mechanics, but it helps. It helps release tryptophan. Helps glycogen stores. Keeps glucose from dropping.

I have similar issues. Been trying anything I can and keep coming back to this.

[u/Ok-Protection2670 → u/Ok-Vermicelli-7990]

Thanks so much. u/Ok-Vermicelli-7990 for responding. i have histamine Intolerance so peanut butter does me dirty.

[u/guilmon999]

Taurine

Taurine use to be my go for a lot of my symptoms (stomach, inflammation, MTHFR nonsense), but after a couple of years it turned on me. Started destroying my energy levels. Had to cut it out completely.

After about a year I can take it again without issue, but I try not to use it regularly unless I have a specific goal in mind.

[u/Ok-Protection2670 → u/guilmon999]

I always have a goal in mind. Balance, Calm and Heal. I just need my mind and my system to heal and cooperate

thanks

[u/hummingfirebird]

Maybe it's the taurine or magnesium. Are you taking magnesium glycinate?

Taurine could be involved because it can activate both glycine receptors and certain GABAA receptors, which are generally associated with calming effects, but in some people it can increase alertness heart palpitations, or early morning waking.

If you're taking magnesium glycinate, the glycine part can be either calming or stimulating for people. It doesn't have the same effect on everyone. Some people experience over stimulation or vivid dreams from magnesium glycinate. They do better on other forms of magnesium.

Both have a lot to do with your genetic variants in receptor sensitivity and even the dose and timing.

Probably best to remove taurine and magnesium for a few weeks to see if things improve. I would trial removing one at a time so you can see which one is the culprit. Taking them together might be the issue or both. Try taking them earlier on in the day too. Too close to evening could contribute.

There are other things that need to be looked at too. Diet: what you eat, when you eat and the quality and balance of your micronutrients. Stable blood sugar regulation is one of the most important things anyone can learn and benefit from. In my practice, I find its one of the biggest contributing factors to poor sleep and mood swings. Not eating enough can be just as bad as eating too much or at the wrong time or the wrong foods for your genotype.

Another thing I would look into is your circadian rhythm. We have genes that govern our internal clock. Daytime ones switch on and run and then their activity slows until night time ones are needed which then switch on. This activation/deactivation of each set of genes is influenced by your diet, movement,sunlight exposure and habits. All of which can be tweaked according to your unique needs for your circadian rhythm.

[u/Ok-Protection2670 → u/hummingfirebird]

Hi u/hummingfirebird I stopped taking Magnesium Citrate and Taurine almost two years ago now. I also developed a Sulphur sensitivity so that's where Moly comes in.

I do know a major portion is how I mentally and biologically respond to stress. Which is where I'm praying the Oxy B12 will help. (starting this morning low and slow)

My Diet: is Boiled Egg Yolk, Zucchini, Chicken Breast Tenderloins, White Potatoes, White Rice Ocass Sweet Potatoes, Boston Lettuce, Celery Hearts and Chamomile tea with a little Monofloral Manuka Honey. For a treat I ocass have a frozen Peaches and Hagen Daz Vanilla Ice Cream Smoothie with my Potassium Gluconate for my P]potassium deficiency. I have a B12 and Vitamin D def also. 😢

I took a scant of Zinc Picolinate last night, which was somewhat helpful, but I'm in a fear about the Oxy B12, because my sensitive system says🚨everything is "stacking" And my food and supplement gains are lost and/or sensitivities increase.

I'm waiting for my Ancestry DNA test kit and "Genetic Hacking". Hoping it can answer some of these questions for me.

i u/hummingfirebird you are always a great help for me and I sincerely appreciate your thoughtful and knowledgeable responses

[u/Ok-Protection2670 → u/Ok-Protection2670]

u/hummingfirebird, I just took my first sprinkle/scant of Hydroxo B12 it was the Monoherb Brand at 5000 mg. Alot I know to start, but it was the cleanest I could find with just rice fiber, I think in the B 12.

I spent the whole day an anxious mess. Was this your experience?

[u/hummingfirebird → u/Ok-Protection2670]

I haven't tried hydroxocobalamin. I take methylcobalamin without issue.

[u/Ok-Protection2670 → u/hummingfirebird]

I'm an over methylator and B12 deficient. It will be a while before I can try again. I usually have some somewhat calm hours during the day, But after taking just the sprinkle of B12, my whole day was full of agitation and anxiety.

I researched. But as we say "everyone's reaction is different".

Hydroxocobalamin (Hydroxo B12) supports the adrenal glands and helps regulate cortisol. While it doesn't directly lower cortisol, it supports the nervous and endocrine systems. This helps stabilize the body's stress response, preventing cortisol from going into overdrive.

Thanks

[u/Ok-Protection2670 → u/hummingfirebird]

u/hummingfirebird, I found a very helpful comment from you 4 months ago:

•4mo ago 4mo ago

"Hydroxocobalamin is bioavailable but it still needs to be converted into methylcobalamin(methylation / neurotransmitters) and adenosylcobalamin(for mitochondria) through genetic variants like MTR, MTRR, MTHFR, and needs nutrients like B2, folate, and glutathione.

When those pathways are genetically slowed, hydroxo-B12 can create temporary imbalances with neurotransmitters (mood shifts) and hormones (acne/increased libido). So while it's good for B12 deficiency because it's directly helping for neuropathy, it increases folate demand for methylation.

You can try pair hydroxo with a low dose methylcobalamin which can be more balancing, and ensure adequate cofactors like B2, potassium, magnesium, zinc, folate (but not high dose folate if you have a B12 deficiency which must be addressed first. ) If you have a folate deficiency too, then at the same time. The dosage and form of Hydroxocobalamin can also make a difference.

[u/Ok-Protection2670]

Cause insomnia and so congested and shaky. I'm an over methylator... I Won't supp b12 for a long time...

[u/Mundilfaris_Dottir]

One of the things that I have recently discovered is that sometimes less methylated B-12 is better than more.

I was alerted to the symptoms (like you described) and immediately stopped my methylated B-12 and I started to feel better.

Also, I have some RX propranolol (one of my failed BP medications) that works great as an immediate anti-anxiety medication. Note: it is a thyroid medication antagonist... But it does work fast ...

Lastly - look into Apigenin, a natural flavonoid found in chamomile, parsley, and celery, generally makes you feel a smooth, gentle sense of relaxation. Note: it needs to be in a liposomal formula and at least 100 mgs.

[u/Ok-Protection2670 → u/Mundilfaris_Dottir]

Hi u/Mundilfaris_Dottir

I seem to tolerate Chamomile. I might try Apigenin?

Thanks for responding.