Oral B12 causing irritability and insomnia

[cristi_b]

I have the following problem: whenever I take oral B12(cyano/hydroxy/methyl) I become edgy, irritable, nervous and I get insomnia, it's like my sympathetic nervous system goes into overdrive, you can't even joke with me because I might misinterpret it as a personal attack. The only thing that I found to get me out of the state, is to stop taking B12 and take Methyl Folate for a while(luckily it goes away in a few days).

Now I can go without taking B12, as I am not deficient, but my father really needs it(he has low B12) and he gets the same reaction. I'm really stumped as to how to proceed, for several months I've been looking for a solution or at least an explanation for this, but with no success.

Since both me and my father have the same reaction, it must be something genetic or something viral, but I could not pinpoint it. Some of the stuff I've considered:
- overmethylation
- Candida overgrowth(S.I.F.O.): I've read this microbe can irreversibly damage an enzyme needed in the methylation cycle
- Aluminum intoxication: since Aluminum is neurotoxic it might affect cognition and supplements that deal with this intoxication have a good effect on me(but not enough to tolerate the B12)
- Iron overload: too much iron inhibits absorption of Manganese which is a cofactor in several metabolic reactions and is also needed in the brain

Has anyone encountered this problem?

 

[JES]

Common problem for people with ME/CFS, see for example this, this or this thread.

Overmethylation, could be, provided that such a condition actually exist. What people have found over here is that niacin (or niacinamide), which supposedly does the opposite i.e. promotes undermethylation, can reverse the effects. I don't buy into this over/undermethylation simplification much, but I did note niacinamide has helped me when I struggled with the effects of taking B12 and certain other B vitamins.

Candida, doubt it would happen that quickly as the negative reaction I get when taking B12. Aluminum or iron, I have done blood and hair tests and didn't find these elements in excess, so unlikely in my case.

You might want to trial B12 shots and see if that works better for you. In my case it still ramped up the sympathetic nervous system, but the effect from one shot was less negative than from taking a much smaller amount orally for a week.

It might not be too productive to try to figure out the ultimate cause for this, at least it wasn't in my case. I noticed most B vitamins revved up my neuropathic pain while I am not deficient in any B vitamin, so these symptoms are more likely immune mediated.

 

[Rufous McKinney]

Has anyone encountered this problem?

YES

I ordered really good pure B-12 drops and to date, can't handle it.

I took LESS THAN a drop...figure it was sort of a bubble at the tip of the dropper. I could "barely taste some" so I know I got a tiny amount. I did that a few times, then tried the SINGLE DROP.

the single drop made me very ILL and I felt just AWFUL. It was almost as bad as the day I did the castor oil packs and lost it throwing up in the kitchen sink.

Profound nausea. Giant bubble in brain, metal on tongue.

I think its the overmethylizatoin or just that it caused the detox pathways to start up and this seems to be a state I can't handle.

I take b-vitamins in my multi, including the methyl ones....at some point, how can one drop make anyone that sick?

 

[Rufous McKinney]

I noticed most B vitamins revved up my neuropathic pain while I am not deficient in any B vitamin, so these symptoms are more likely immune mediated.

I recently doubled my daily vitamin (the multi..).

I wonder if thats contributing to my feeling PEM lousy when I've been thinking I was not stressing myself out.

 

[Tammy]

It caused irritability/agitation when I first started taking it. Gradually that went away. Never had insomnia with it.................actually the opposite. It helped with sleep.

 

[Rufous McKinney]

when I first started taking it. Gradually that went away.

I seem to simply not know how to reach the: and then it went away part.

After a few days of anything which causes me to detox, I can't handle it and quit.

 

[Tammy]

I seem to simply not know how to reach the: and then it went away part.

After a few days of anything which causes me to detox, I can't handle it and quit.

I had to drop my dosage and gradually work up. For you though....... don't know how you get less than 1 drop unless you put 1 drop in a little bit of water and then just drink some of the water. Did you try every other day or every second, third day instead of every day? I"ve had to do that with some supplements.

 

[Rufous McKinney]

For you though....... don't know how you get less than 1 drop unless you put 1 drop in a little bit of water and then just drink some of the water. Did you try every other day or every second, third day instead of every day? I"ve had to do that with some supplements.

I'm going to try to get it going again....

I did not take it every day.

I think I have decided I am not pacing effectively, and must regroup of the entire concept.

 

[cristi_b]

I took LESS THAN a drop...figure it was sort of a bubble at the tip of the dropper. I could "barely taste some" so I know I got a tiny amount. I did that a few times, then tried the SINGLE DROP.

That is one of the things I wanted to try but I haven't yet: take very tiny amounts of B12 and combine them with larger amounts of Methyl Folate(since I know that reverses the irritability). The hope is my tolerance would increase, but this has some drawbacks: it will take a long time to raise B12 levels and Methyl Folate feeds Candida.

On my 23andMe test there was a genetic mutation involved in methylation that I did not understand at that point, so I looked it up again and it seems rs1801394(that's MTRR A66G / MTRR I22M) is involved in recycling methyl groups for B12, while the specific mutation that I have, affects the FMN(active form of B2) binding domain of MTRR. source1 source2 source3

If I'm not mistaken MTRR is precisely the enzyme that Candida irreversibly destroys(sorry for my bad memory but I don't have a link to backup this claim, I simply don't remember where I read it).

So probably I should add riboflavin-5′-phosphate(FMN) to the mix. This means ordering one more supplement just to test if I can tolerate B12(I usually take each vitamin as a separate pill so I don't get into situations where I don't know where an effect is coming from).

 

[datadragon]

You can test methylation status through the use of a whole blood histamine test which is different from a plasma histamine test as I mentioned here https://forums.phoenixrising.me/thr...ation-excess-of-methionine.90348/post-2438042 You can combine this with a homocysteine test to get additional info as this can be higher with lower folate or B12. Someone who has an SNP that might predispose them to impaired methylation does not mean they actually have impaired methylation. In fact, they could have completely normal methylation! On the other hand, a person who has no SNPs in their methylation genes could have severe methylation imbalance and may therefore benefit from some treatment but usually only when something is far too much in one direction causing health issues.

B12 is released from proteins by stomach acid and digestion. Older people and those with low stomach acid or faulty digestion may develop B12 deficiencies (along with other nutrient deficiencies) because of this. Enzymes, particularly the proteases, digest the proteins and may make more B12 available (along with other nutrients). If you take anything that inhibits digestion or stomach acid, then you are inhibiting B12 release and absorption: like calcium carbonate with meals, Tums, Rolaids, and certain medications which affect stomach acid. Further in regards to ME/CFS, inflammation turns out it lowers our zinc levels which is needed for stomach acid production along with B1 and B6. Prolonged inflammation can deplete your B12 over time. If you have an injured gut by any means, you sharply reduce your ability to absorb B12. If you go grain and dairy free in addition to this, you are very likely to be B12 deficient. There is quite high B12 in milk, most better tolerate A2 milk vs normal A1 milk. vitamin B12 can not be manufactured by any plants, and therefore is only found in animal products.

B12 is absorbed in the ileum, the very last part of the small intestine. Most everything else is absorbed before that in earlier parts of the intestine. B12 combines with something called Intrinsic Factor in order to work. The stomach acid issues can affect the Intrinsic Factor availability too. Intrinsic Factor is necessary to bind with the B12 in the stomach to "protect" it in the upper small intestine and from the stomach acid. Then the Intrinsic Factor attaches to some receptors at the end of the small intestine in the ileum aiding the B12 uptake. So at times it is the Intrinsic Factor and the fact it cannot attach to the receptors to facilitate transport and absorption into the body that is the problem and the cause of B12 deficiency. The sublingual B12 is highly preferred for this reason because it gets the B12 into the system and bypasses the entire Intrinsic Factor mechanism.

The Methylmalonic Acid Test, also called an MMA Test is a more accurate test of B12 deficiency. Methylmalonic Acid, also called Methylmalonate, is a waste product that builds up in the blood and is excreted in the urine when Vitamin B12 is not available to transform into the energy metabolite Succinic Acid. Because it begins to build up within ten days after a Vitamin B12 deficiency begins, it is not only the most accurate marker, but it is the earliest detectable marker of Vitamin B12 deficiency. And because Methylmalonic Acid is found in both blood and urine in amounts relative to the degree of deficiency, both urine and blood tests are good tests for Vitamin B12 deficiency.

 

[perchance dreamer]

Other forms of B12 include adenosyl and hydroxy. My doctor recently recommended looking into those since my homocysteine was a little high for the first time. I can't quite get all the way to the recommended dosage of my methyl B12 combination shot because the full amount gives me insomnia. Pure Encapsulations makes a combo adenosyl/hydroxy in either liquid or capsule form.

Often another recommended supplement if you have MTHFR mutation is methylfolate, but it gives me insomnia. I just found a form I'm tolerating really well: Doctor's Best Fully Active Folate with Quatrefolic. It's available in 400 mcg and 800 mcg. My physician's assistant recommended the 400 mcg since so many things give me insomnia.

It did take several days for me to get used to (felt keyed up at first), but I'm now feeling better with this addition. I take it as soon as I wake up.

 

[datadragon]

Other forms of B12 include adenosyl and hydroxy. My doctor recently recommended looking into those since my homocysteine was a little high for the first time. I can't quite get all the way to the recommended dosage of my methyl B12 combination shot because the full amount gives me insomnia. Pure Encapsulations makes a combo adenosyl/hydroxy in either liquid or capsule form.

Homocysteine when high can increase inflammation (see below for more) but there are a number of other areas that can also modify inflammation levels to compensate that are rarely also considered. So doing a c-reactive protein test for example could show whether inflammation is actually high as it may not be due to compensation in the other genes/areas as suggestion prior to attempting to lower it.

Homocysteine activates the inflammation pathways as it activated NLRP3 inflammasomes in THP-1-differentiated macrophages and promoted subsequent production of IL-1β and IL-18 in macrophages, which were blocked by NLRP3 gene silencing or the caspase-1 inhibitor Z-WEHD-FMK. https://pubmed.ncbi.nlm.nih.gov/28394319/

High homocysteine following folic acid or vitamin B12 deficiency also down-regulates peroxisome proliferator-activated receptor (PPAR) expression. Homocysteine has recently been found to be a competitive inhibitor of the nuclear transcription factors: Peroxisome proliferator activated receptors (PPARs) alpha and gamma. https://link.springer.com/article/10.1186/1475-2891-3-4 These are main anti-inflammation pathways.

Hydroxocobalamin (OH-Cbl), cobinamide, and dicyanocobinamide (CN(2)-Cbi) potently inhibited all Nitric Oxide isoforms NOS1, NOS2, and NOS3, whereas cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. https://pubmed.ncbi.nlm.nih.gov/19328848/ The extracellular NO scavenger hydroxocobalamin prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner. https://link.springer.com/article/10.1007/BF02976435