Different D3 - Different Reactions

[Dysfunkion]

Lately I've been doing some deeper digging online on others reactions to D3 and came across a topic on another forum with someone in a situation very similar to mind. Where different D3 supplements produced radically different results. So I decided to give vegan D3 apparently derived from lichen a go at 5000 IU (which I plan to take every other day). This morning I prepared for the worst, gulped it down, and....I felt much better. My senses brighter, brain a bit faster, somewhat more cognitive, and I instantly got a little more drive to do things. Don't know how stable this will be, if I'll get better, or if the benefits will fade over the next month but I'll be closely monitoring how this goes. How could this be? On the bottle it's apparently the same form but just from a different source. Normal D3 supplemented makes me extremely lethargic and crashes me for over a day.

 

[Dysfunkion]

So I tried multiple different types of D to get to the bottom this, D2 I react horribly to with extreme fatigue and brain fog. The vegan D3 lost it's initial boost of energy I got from it and then I did worse with lower doses with more side effects. So I heard some people did better with igher doses around 10,000 iu and up. So I went with 10,000 iu yesterday and this avoided more of the side effects but still makes me feel a bit wonky and tired. I think I'm going to stay at this dose every 3 days and see how I do. With it my brain feels more connected to itself and I'm overall a bit more cognitively improved. The same pattern persists though, anything I find that gives me more energy back quickly gets shut down and then I'm back to square one with this stupid condition.

I'd really like to know what that is because it happens through multiple avenues and it appears to have something to do with interplay between my immune system and nervous system as if my body is doing something to limit itself. B12, mag citrate at one point, the first doses of 5000 iu vegan D3, very rarely cistus will trigger an increase in energy but I can't consistently get it to do this, and any kind of stimulants don't appear to touch it. Coffee under certain conditions will work later in the day and since getting on the D3 I'm the most energetic around 5-8 PM. For some reason occasionally getting a traditional probably specific immune response from someone like spraying room spray will be able to give me more energy for example but despite my MCS I normally can't get my immune system to rev up enough to do that though under D3 supplementation it is functioning a bit more normally consistently.

 

[Dysfunkion]

Today I decided to try 1000 iu of the vegan D3 drops but on my skin. Again more strange results (what else is new lol). I got more raw physical energy but it did kick up my immune system, made me increasingly anxious as the day went on with the signature "tired and wired" feeling, and just generally feeling like an anxiety ridden, jumpy mess tonight. Though topical unlike the oral doses doesn't induce the same fatigue as oral had after any dose of any form after a while. I think I'm done experimenting with D3 but thats interesting how variable everything about it with me is. So in a nutshell right now I have the anxiety powered strength of CFS superman with worse cognition and everything else. I'm obviously in PEM right now and this makes it worse but overrides a single physical component. Can also tell cause my tinnitus is raging right now.

Update from this morning - Had some more trouble falling asleep and had the weird looping, distressing dreams thing that tends to happen with D3 reactions. Still feel a bit wired this morning but I'm riding it out, just can't relax too easily. Usually I get those strange distressing dreams in a migraine like state which topical D3 also appears to induce but in a less extreme way than orally. Brain feels like there is too much runaway signalling going on like any traditional PEM episode with that signature "no space to think" feeling as if it's taking up the space of other cognitive processes. Like for example socializing in this state is much more difficult as well as focusing on anything smaller. Last night I was barely even able to use my voice properly which is always one of the first major things that tanks in a state like this. I suspect today at work will be the same but slightly better. I'm just going to see long this reaction takes to fade out and where it leaves me mentally and physically. Working in a state like this is hellish too because I'll always have this vague "I'm going to lose my mind" feeling with no tipping point like a balloon about to pop. I noticed last night my startle reflex was also extreme so I'm wondering is part of reactions from D3 in any form like this that induce the extreme anxiety like feelings (it's kind of a muted anxiety, D3 also calms something down in my brain. very hard to explain) unusually elevated serotonin? There appears to be a bell curve where if I have a ton of D3 I'll experience a reduction in anxiety through too much signalling of something and as it wears off I always get into a state like I am this morning.

update from this evening - Still feeling pretty heavy anxiety but it's a bit better, I can at least sit here and enjoy some music and having some cistus tea helped a bit. Tinnitus is still pretty annoying but also not as bad. Throughout the day I got a little dry mouth but nothing like yesterday which from the small amount I had wasn't too bad in the first place but that's also something that happens every time I have D3 apparently. Have some pretty nasty post nasal drip and some nasal passage inflammation. I'm suspecting for reason shocking any hormonal system in my body just causes neuro-immune chaos and the vitamin D receptor is of the worst for some reason. The amount from 1000 iu in MCT oil absorbed in skin would have probably been less than 200 iu into the blood almost directly. I kind of regret doing this experiment but I'm probably going to be a bit happier when this reaction finally tones itself down because this gives me more of a window into what is happening in my body whatever it specifically means. Hopefully have a lot of garlic in my dinner tonight will make me feel somewhat better, I don't know why but eating large amounts of garlic always helps situations like this. I wonder if it's the large amounts of natural magnesium (I do want to try supplementing elemental magnesium) or something else.

update from 7/12 evening - I had a capsule of Irish sea moss which at the expense of making me feel more depressed for a day calms my system down and extra activated charcoal this morning/later tonight as a last resort and helping clear out whatever was kicked up by the topical D3. Today was slightly better than yesterday overall but still felt extremely on edge throughout the day which got worse and better at random points. From where I am currently late at night here it's not too bad and I think my second dose of activated charcoal after my cistus and green tea helped calm things down a bit. Currently for once in the past 3 days I feel like I'm actually ready to get some good rest which has also been largely absent in the past few days. Glad this appears to be almost over.

 

[Dysfunkion]

This morning I decided to try the topical D3 that gave me a ridiculous reaction last time I tried it meaning the specific brand and dosage rubbed into my wrists. Again I'm perplexed at this D3 mystery with me. This time I had a mild relaxed feeling that morphed into high anxiety and mild anhedonia later. Just a dull anxious feeling and as of now rather tired but other than that nothing much. It really is a wild card with me, I never know what I'm going to get, there is no solid repeatable I can establish with this stuff. The big question now is what is going on here? What is being modified that is so random, that every time I use the stuff the reaction propels me into a different neurological state loop? I don't think there is anything left for me to do with this stuff, I just can't get anything consistent out of it.

 

[Wishful]

What is being modified that is so random, that every time I use the stuff the reaction propels me into a different neurological state loop?

Given how complex the body is, with all the interacting subsystems, it's more amazing that we can get reliable results from some things.

Some experimental bad results are useful, since they can help you identify other things to avoid, or they can identify a pathway that you could look for treatments to try. Inconsistent results are less helpful. If it gave you some major improvements some times, it might be worth pursuing further, but for inconsistent minor improvements, you might be better off trying something else.

 

[Dysfunkion]

Given how complex the body is, with all the interacting subsystems, it's more amazing that we can get reliable results from some things.

Some experimental bad results are useful, since they can help you identify other things to avoid, or they can identify a pathway that you could look for treatments to try. Inconsistent results are less helpful. If it gave you some major improvements some times, it might be worth pursuing further, but for inconsistent minor improvements, you might be better off trying something else.

True, I have some baseline of reliable reactions to things but even those can shift a bit or just be ineffective sometimes. I'm definitely made a lot of progress in learning what is making things worse and what to avoid though which has resulted in some overall baseline improvements. This D3 thing is gonna be a mystery to me for a long time I feel because another factor is let's say I eat a lot of salmon, nothing happens at all. Not in the good or bad way from consuming D3 in non-fortified foods. I just ate some fish and was happy because it was tasty.

This appears to have a similarity with my B12 situation that I just posted about where ingested b12 from food like the D3 in natural sources doesn't really do anything. No energy, no decrease either, just ate some food. I'm starting to wonder if these are shock reactions because my body for some reason isn't making much of the end products from anything.

 

[Wishful]

This appears to have a similarity with my B12 situation that I just posted about where ingested b12 from food like the D3 in natural sources doesn't really do anything. No energy, no decrease either, just ate some food.

None of the supplements I tried changed my perceived energy levels. Even injected B12 had no noticeable effects. Well, one time a B12 tablet made me feel strongly suicidal, but just that one time, so I can't even be sure that it was the B12 at fault.

While "the microbiome" isn't the answer to all questions, I do think it can have a strong influence on ME. I've certainly noticed that myself. So, it's possible that what happens to nutrient molecules in food or capsules/tablets depends on the digestive system including the microbiome. Does a rapid release of B12 at a certain stretch of the intestines cause a strong change in the microbiome, causing some strains to explode in population while others wither, resulting in a change of molecules absorbed by the bloodstream? The possibilities certainly complicate understanding why we react to certain ingested substances. Does a B12 tablet make someone feel better because it's boosting production of a certain protein somewhere in the body, or is it because it changes the ratio of two different bacterial strains?

Theories about why something affects our ME are interesting, but more practically, our food choices come down to "makes me feel better" or "makes me feel worse". If you're lucky, you might notice that the response is consistent with the level of some molecule in the food, without any counterexamples, so you can reasonably assume that it's that molecule causing the response and can make food choices based on that. If you're really lucky, you might theorize other molecules that would have the same effect, leading to other possibilities for treatments. If you're unlucky, you get stuck with a perplexing mystery.

I think getting some reactions from different foods and supplements is more interesting than getting no responses. At least it offers some hope of a beneficial reaction or if it's a bad reaction, at least it might be a hint that leads to a way to counter that reaction.

Have you experimented with boosting your VitD levels via UV-skin?

 

[Wayne]

Hi @Dysfunkion -- I find your diaries of your D3 experiments quite interesting. I watch a lot of Dr. (DC) Eric Berg's videos, and he continually stresses how important it is to supplement with Vit. D, and usually recommends relatively high doses.

A couple of the reasons for the high doses is because many of us become "Vit. D resistant" as we age, and thus need far more than when we were younger. Also, many health care practitioners have found high doses Vit. D to be helpful for many autoimmune conditions, such as Hashimoto's, which I have.

I've been taking about 10,000 IUs daily for the past few months, and haven't really noticed anything that I can definitively idenitfy. I just started taking 20,000 IUs, and still haven't really noticed anything (which might be a good thing). I'm also starting to take cod liver oil, which has a fair amount of Vit. D, but a LOT of Vitamin A, so I'm limited on how much D I can get from it.

Which leads me to a curiosity question: Have you tried, or considered getting Vit. D from a high quality cod liver oil? If so, given your varied experiences with other Vit. D supplementation, what your experiences might have been. BTW, thanks for sharing your experiences in detail. It's been a catalyst for me to try to monitor more closely what reactions my own supplementation might initiate.

Just to mention, it appears it's not a good idea to take more than 1 tsp of cod liver oil a day, because of its very high Vit. A content. 1 tsp will apparently yield about 400 IUs of Vit. D.

 

[Dysfunkion]

Hi @Dysfunkion -- I find your diaries of your D3 experiments quite interesting. I watch a lot of Dr. (DC) Eric Berg's videos, and he continually stresses how important it is to supplement with Vit. D, and usually recommends relatively high doses.

A couple of the reasons for the high doses is because many of us become "Vit. D resistant" as we age, and thus need far more than when we were younger. Also, many health care practitioners have found high doses Vit. D to be helpful for many autoimmune conditions, such as Hashimoto's, which I have.

I've been taking about 10,000 IUs daily for the past few months, and haven't really noticed anything that I can definitively idenitfy. I just started taking 20,000 IUs, and still haven't really noticed anything (which might be a good thing). I'm also starting to take cod liver oil, which has a fair amount of Vit. D, but a LOT of Vitamin A, so I'm limited on how much D I can get from it.

Which leads me to a curiosity question: Have you tried, or considered getting Vit. D from a high quality cod liver oil? If so, given your varied experiences with other Vit. D supplementation, what your experiences might have been. BTW, thanks for sharing your experiences in detail. It's been a catalyst for me to try to monitor more closely what reactions my own supplementation might initiate.

Just to mention, it appears it's not a good idea to take more than 1 tsp of cod liver oil a day, because of its very high Vit. A content. 1 tsp will apparently yield about 400 IUs of Vit. D.

I've tried D3 at 10,000 iu before and like how everything else with it went it was a wild card, I got extremely lethargic but felt a reduction in overall inflammation though I also got more brain fog even though I was more social and emotional. It's just bizarre I know. What supplement do you reccomend for cod liver oil? I haven't tried that myself but I'd give it a go since I can consume fish just fine.

 

[Dysfunkion]

https://www.longecity.org/forum/topic/109486-vitamin-dbut-why/

So I found a curious topic on the Longecity forum from someone with the exact same problem I have and lifelong one at that. Same exact presentation and like this person it's lifelong and with me has been somewhat progressive or at least got worse as infections hopped on too. Same zoned out thing, same realizing what was going on but not being able to do anything about it because my body wasn't/isn't producing something it should that transcends all dietary/lifestyle choices. After reading this whole sad topic and dealing with the same misunderstandings from others posting in it that a genetic disorder like this can not possibly exist a lot makes sense. Like this person too when whatever this is gets resolved by the one miracle supplement they're almost totally normal. I wish I could chime in and ask them more questions, but it's years old now and I doubt this user is still around.

BUT THEN! One day they found a magical D3 supplement (in my case it was also methyl-b12 but this just seems to patch some energy thing and isn't without pitfalls, my case in the fine genetic details obviously won't be the EXACT same thing going on). Like them too K is also one of the only other things that helps whatever this is. Like I said before after I'm done doing what I'm currently doing I want to try my vegan D3 under the stablized methyl-b12 dosing and see what happens. I also want to try individual D3 metabolites but have no idea how I'd go about doing that. Guess I'm carrying this person's torch now.

 

[Dysfunkion]

So I found a place online that sells calcifediol which apparently completely bypasses the liver and I can't find anything too bad on it besides one person reporting feeling good and then getting a migraine later but there also across the internet doesn't appear to be many reports from people that used it. I'm not sure when I will get it but it says the order was fulfilled already so hopefully soon.

 

[Wayne]

What supplement do you reccomend for cod liver oil?

Here's a link to what I buy on Amazon. The orange flavor makes it almost taste-free. I'm going to try lemon flavor next, which should work well with some of the grains I prepare with lemon juice in it.


Nordic Naturals Arctic Cod Liver Oil, Orange - 16 oz - 1060 mg Total Omega-3s with EPA & DHA - Heart & Brain Health, Healthy Immunity, Overall Wellness - Non-GMO - 96 Servings

 

[Dysfunkion]

Here's a link to what I buy on Amazon. The orange flavor makes it almost taste-free. I'm going to try lemon flavor next, which should work well with some of the grains I prepare with lemon juice in it.


Nordic Naturals Arctic Cod Liver Oil, Orange - 16 oz - 1060 mg Total Omega-3s with EPA & DHA - Heart & Brain Health, Healthy Immunity, Overall Wellness - Non-GMO - 96 Servings

Ill bookmark it, im also a bit concerned about the large amounts of vitamin A in it. Though if the calcifediol works out for me ill give it a spin. Hoping for a positive result for once with it. Hasn't shipped yet so it may be a while before I get to try it though.

 

[Dysfunkion]

Today I was reading into the RCCX Genetic module theory and CYP21A2 related to it. I decided to look up it's relation to D3 and came across some interesting information and there is way more to this than I thought regarding vitamin D.

https://pubmed.ncbi.nlm.nih.gov/22561756/ - ""1α,25-Dihydroxyvitamin D(3) was found to alter the promoter activity via a VDR-mediated mechanism, including the comodulators VDR interacting repressor (VDIR) and Williams syndrome transcription factor (WSTF). The involvement of comodulator VDIR was confirmed by gene silencing. We identified a vitamin D response element in the CYP21A2 promoter. Interaction between this novel response element and VDR, WSTF and VDIR was shown by chromatin immunoprecipitation assay. When this sequence was deleted, the effect of 1α,25-dihydroxyvitamin D(3) was abolished, indicating that this sequence in the CYP21A2 promoter functions as a vitamin D response element. Interestingly, an altered balance between nuclear receptors and comodulators reversed the suppressing effect of vitamin D to a stimulatory effect."

https://f1000research.com/articles/3-155/v1 - ""CYP21A2 is a steroid 21-hydroxylase catalyzing the production of deoxycorticosterone and 11-deoxycortisol, which are precursors for the production of corticosterone, aldosterone and cortisol. 21-Hydroxylase deficiency may lead to severe conditions such as congenital adrenal hyperplasia and Addison´s disease48. CYP21A2 is exclusively expressed in the adrenal cortex28. Therefore, glucocorticoids and mineralocorticoids cannot be synthesized in other tissues than the adrenal cortex"

So to try to wrap this up into something coherent this CYP21A2 enzyme in the RCCX Module containing CYP21A2, TNXB, and C4 is thought to based on the actions of these factors be the final common pathway for stress induced shutdown of the mitochondria. CYP21A2 hydroxylates steroids at the 21 position. 21-hydroxylase is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol. D3 is thought to downregulate CYP21A2 but upregulate CYP17A1. CYP17A1 is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. It's also exclusively in the adrenals and the gonads.

Now because of all of the possible response elements modulating how the body reacts to D3 and states of those reactions changing based on nuclear receptor balance and comodulators what can happen can get highly unpredictable and different depending on what exactly gets lodged in that VDR. D3 is referring to in these studies the final byproduct of the D3 pathway calcitriol. So this is just one final metabolite in a limited set of conditions.

People will often report even though unlike that person like me in a link above with the severe D supplementation problem and other genetic issues that there still will be differences in effect and tolerance of D3 and D2 supplemented even based on the carrier of it. So never mind just the D itself, something is further making this reaction with the CYP- involved factors even more complex. From the little out there, not much negativity and variation appears to be associated with calcifediol supplementation. Someone got a migraine, someone else got nausea, and someone else got a somewhat elevated BP and insomnia. Very ordinary side effects that are far more tame than the wildcards many get from all forms of D3 and D2 with different carrier factors. My theory is that it is bypassing the mechanism altogether that causes such reactions by first sitting in the VDR but not activating it leading to more more efficient raising of the D3 levels and binding by only the internally produced D3 end product which does not cause as many issues. For what reason I don't know but hopefully it works out for me and I have more information after I try it.

 

[Dysfunkion]

Because I'm impatient, live on the edge, and had the time I decided to give the calcifediol when I got home as it was here when I got back from work. After a took a couple in some minutes I felt a little power struggle break out in my body. At first I felt more calm but in this weird way where it seemed to cut down my peak excitory output (feeling excited, strong emotions, sex drive took a hit, just that general driving dopamine feeling but these things were still able to fire but things just got more slow). As the evening went on I felt under this excitory capping a kind of restless energy and my tinnitus also picked up a bit. My senses became much more clear and my face/brain burn crap completely simmered down though but later it came back a bit. This reaction is somewhat similar to my reaction to a large amount of protodiocin from asparagus and if this has the same rebound tomorrow that'll be interesting.

That's the story so far with it, I'll see how I feel tomorrow but this stuff does bypass the initial wild reactions that D3 and D2 in all forms with diversity depending on a lot of factors I can't entirely identify cause. It doesn't measure up to the best that D3 offered though in between the wild symptoms. I'm honestly stumped here on what is going on with this stuff. I do want to try calcitriol itself but I don't have a way to I can find right now.

 

[Dysfunkion]

Update from today - I decided to try the calicifediol again but at half the dose and I handle this better and feel better on it, so I guess the higher initial dose was too much of a shock to my system.

Though I think I'm better and more stable with it, its not the answer to everything and my rare neuro-cognitive windows still remain unexplainable and appear to be initiated by something related to the phase 1 metabolism d3 and d2 go through. The mystery grows deeper.

edit - What I'm going to do tomorrow is take a drop of the vegan D3 and see what happens post calcifediol which I took today in the morning, the only other condition that different is my methyl-b12 ia now at 3000 mcg than 2000. Not sure if that would influence any results but should be interesting.

 

[Dysfunkion]

So I tried the 1000 iu vegan D3 drops this morning, interestingly post califediol I can tolerate them. A bit headachy and a slight sense of dry mouth but that's in. Senses brighten more and my mood feels a bit better. As with the calcofediol at first my libido takes a hit and I'm now wondering if this is because of calcifediol and the conversion to it is largely what causes that as I got it from the higher dose of calcifediol and it also comes with the flatter/duller mental feeling but this is overridden to a limited extent when supplementing D3 directly. Tomorrow I'm going to reduce my dose of methyl-b12 back to the 2000 mcg baseline with the 1000 iu now weirdly tolerated vegan D3 drops and see if the tolerance sticks and stays there. I don't know what is going on here but I seem to be getting some kind of idea now.

edit - initial side effects went away, doing fine right now. Decent energy but like I said we'll see if it sticks as well as the D3 tolerance and benefit once I reduce the methyl-b12.

edit 2 from next morning - I definitely can now tolerate 1000 iu of vegan D3, I plan to try to get to a previous 2500 iu baseline starting tomorrow and see how that goes. My energy has been odd, sometimes it's up, sometimes it's down, same with my mood, I feel like it's going to take my body some time to adapt again. All in all I don't really know how I feel right now, just going with the flow of this.

 

[Dysfunkion]

I got to try the dry rice flour only D3 2500 iu cap this morning and I handle this one far better so there actually is something about oil carriers with me that gives me a strange reaction but specifically to D3 being in them, that is weird. I'll give an update here later in the day in how things went but so far so good on this one right off the bat.