Common CFS symptoms from a vitamin deficiency despite supplements

[Sea]

The usual screening tests for fatigue (and CFS) include a CBC, which would show anemia and/or macrocytosis. That is how a B12 deficiency would normally be picked up before the patient is given a diagnosis of CFS. I don't think these problems fly "under medical radar" as much as you might imagine. It is basic first-line screening.

I had an elevated MCV on every blood test that I've been able to check since 2008. It was never mentioned to me by any doctor. It has responded to supplementing B12 and folate, returning to normal over 6 months.

 

[Hip]

Yes I know about those pathways but the something that goes wrong starts before that and impacts those pathways. I haven't had the energy to dig enough to propose what that something might be.

You said that: "so for the case of CFS/ME and B12 problems, I don't know what would be equivalent to the effect of oxidative stress on B6 dependant enzymes."

Methionine synthase is a B12-dependent enzyme, and seems to be sensitive to oxidative stress and nitrosative stress.

 

[Chocolove]

This might be the missing piece for many:

Lithium transports B12 and folate into your cells.

So someone could have good serum B12 levels, but still not be able to get any B12 into their cells (where it's needed) without lithium.

Since our water is now frequently demineralized through reverse osmosis and distillation we may be suffering from increased lithium deficiency across the population, from the loss of lithium in water.

Lithium support is a critical missing piece with many supplement programs, particularly for those using high dose B12, and those with SHMT+, MTR+ and/or MTRR+ mutations.

According to Dr. Amy Yasko's findings in http://feelgoodbiochem.com/chapter-1/

The role of lithium in B12 transport into the cell is potentially critically important.

Peer reviewed work by Tisman, Herbert, and Rosenblatt published in the British Journal of Haematology, was the first to illustrate that ingestion of lithium is related to B12 binding. Continuing this research, Vanyo and coworkers (Lithium in Biology and Medicine) discuss the finding that lack of lithium and B12 deficiency share physiological features, and that support with lithium enhances B12 transport into cells. According to these researchers, lithium is associated with elevated levels of serum B12 binding capacity. Furthermore, this group was able to show that lithium increases the transport of folate into the cell, as well as that of B12.

Additional peer reviewed work by Schrauzer (Biological Trace Element Research) also supports the role of lithium in B12 transport. The addition of lithium was shown by Cervantes et al to lower elevated serum B12 levels, again illustrating lithium’s effecting B12 transport into cells.

• • Lithium was associated with elevated levels of serum unsaturated B12 binding capacity
  • In the cell model tested, lithium increased uptake of B12 and folate

http://www.scribd.com/doc/125176090...-of-Vitamin-B12-Folic-Acid-and-DNA-Metabolism

Ensure that you have adequate lithium prior to adding high dose B12, because increasing B12 in the absence of lithium support may further deplete lithium levels due to the use of lithium to aid in the transport of the added B12. Ideally, lithium should be in balance prior to adding excess B12 so as not to create lithium depletion. Lithium plays a range of additional roles in your body aside from B12 and folate transport into your cells, so it is important not to deplete this pivotal trace mineral. Lithium’s impact on mood stabilization has been known and used clinically for many years, despite the fact that the mechanism by which this occurs has not been fully elaborated. Norepinephrine imbalances have been implicated in attention disorders, and Sastre and coworkers have illustrated an impact of lithium on balancing norepinephrine levels.

Researchers have noted and published effects from lithium on neurological conditions. Beta amyloid may play a role in Alzheimers Disease and lithium has been shown to have neuroprotective effects against beta amyloid. Research from Spain illustrates that lithium has a positive impact on neural repair after traumatic injury. Maurer (2009) showed that lithium can enable mitochondrial function, which may be particularly useful in the presence of toxic metals. Increases in the grey matter of the brain have been tied to lithium support (Moore) and research from the National Institute of Health (NIH) showed the induction of brain derived neurotrophic factor (BDNF) by lithium. Especially relevant to this program, lithium was reported by Hashimoto (2002) to protect against glutamate excitotoxity.

B12 functions at a very critical juncture in the process of making methyl groups, as well as a range of other functions in your body. You want to be certain that you have adequate lithium in your body prior to adding high doses of B12 because of the interaction of lithium with B12 transport. If you add B12 and other supplements that activate what I call the long route around the methylation cycle, the route that uses Methionine Synthase (MTR) and Methionine Synthase Reductase (MTRR), prior to being sure that you have enough lithium in your body, then you run the risk of further depleting your lithium levels, which can cause symptoms and consequences.

Low dose lithium orotate is recommended. Lithium orotate is available over the counter as a supplement.

 

[alicec]

Methionine synthase is a B12-dependent enzyme, and seems to be sensitive to oxidative stress and nitrosative stress.

Yes I assume something like this is the source of the problem. I'd like to do a though literature review to see what I can find about mechanism and other possibilities but I never have the energy to complete the project.

 

[CFS_for_19_years]

I had an elevated MCV on every blood test that I've been able to check since 2008. It was never mentioned to me by any doctor. It has responded to supplementing B12 and folate, returning to normal over 6 months.

I'm glad you had this excellent resolution. I think that most doctors can't be bothered to follow up on an elevated MCV unless the patient is anemic.

 

[Chocolove]

richvank said:
"Adenosylcobalamin is used in the mitochondria, especially in the muscle cells. It acts as a coenzyme for the methylmalonate pathway. This pathway is used to feed several fuels into the Krebs cycle, to support making ATP by the mitochondrial. ATP supplies the energy to drive muscle contraction. Some of the fuels involved are several of the amino acids, propionate, and the odd-chain fatty acids.

This pathway feeds the fuels in at succinyl CoA, which is downstream of the partial block at aconitase, which limits the use of carbs and fats for fuel in ME/CFS. So boosting adenosyl B12 can make a big difference in this disorder.

In the simplified methylation protocol, hydroxo B12 is used, and the cells can normally convert it to both methyl B12 and adenosyl B12, but these processes can be slow if glutathione is badly depleted. In this case, adding adenosyl B12, as Freddd does in his protocol, can make a beneficial difference."

I wonder if taking AdoCbl (in addition to MeCbl), along with lithium orotate for cellular delivery, might not be best for reducing fatigue and increasing stamina.

 

[Deltrus]

I actually don't like this theory anymore, seems too unlikely. It is more likely that b12 is just inhibited. Still, I found it interesting that methylation can still happen without b12.

Spoiler

I have another theory. What if there is a very large increase in intracellular choline and betaine-homocysteine methyltransferase which then crowds out b12 and creates a functional folate deficiency?

Perhaps this can explain why people get fatigue from racetams, which increase choline uptake into cells? And also depression from excess choline supplementation?

Personally I experienced terrible side effects from fasoracetam, which is a drug that heavily increases high affinity choline uptake. This takes up extracellular choline and puts it into cells.

Another side effect from excess choline would be a lowered amount of acetyl-CoA through ChAT. Acetyl-CoA also is essential to the Kreb cycle. Acetyl groups are taken from acetyl-coa for every acetylcholine neurotransmitter.

I had severe depression and fatigue before I got CFS. I experimented with stuff like bacopa, DMAE, Alcar, aniracetam, noopept, all of which have effects on choline.

I also had pericarditus and bouts of severe sickness during this time, and those are more likely the problem, but still I have a nagging doubt in my mind that nootropics were a factor. What if oxidative stress from my illness depleted b12, and then nootropics increased intracellular choline, causing cells to swap to TMG instead of folate for methyl groups?

Spoiler: relevent pic

I wonder if reduced choline intake into cells would increase the efficacy of b12? If only there was an easy way to do this, I can't find anything.

EDIT: https://en.wikipedia.org/wiki/Choline_transporter

And there is also a choline transporter to mitochondria, which is where choline gets oxidized into TMG.

Turns out Hemicholinium-3 inhibits choline uptake. Not sure if safe in humans.

I also am wondering if the gut microbiome can supply choline, I remember seeing that some gut bacteria create acetylcholine.

 

[Chocolove]

Deltrus, do you happen to know what your lithium status was? Lithium deficiency can cause mood issues and according to Dr. Yasko, she is seeing a lot of lithium deficiency in her practice.

 

[Deltrus]

Deltrus, do you happen to know what your lithium status was? Lithium deficiency can cause mood issues and according to Dr. Yasko, she is seeing a lot of lithium deficiency in her practice.

I don't think there is a way of testing lithium status, but I supplemented it and didn't get any noticeable results.

 

[Sea]

I'm glad you had this excellent resolution. I think that most doctors can't be bothered to follow up on an elevated MCV unless the patient is anemic.

Sadly I was anemic too, that didn't bother them either

 

[Chocolove]

@Sea, Don't know if you are familiar with this one but it is a great summary of all the B12 info.

http://howirecovered.com/active-b12-therapy-faq/


Active B12 therapy and methylation FAQ
May 21, 2013 302 comments

An Index to ‘B-12 the Hidden Story’

When I discovered methylation and B12 therapy, I became obsessed with understanding it (and my startup reaction). I read through the entire ‘Hidden Story‘ thread (maybe 80 hours worth) on Phoenix Rising (and watched all of the methylation videos I could get my hands on). It seemed to me that lots of valuable information was buried in the ‘Hidden Story’ and I wanted to make it accessible to people without the time on their hands (or clarity) to read 2,750+ posts.

So here, I’ve pulled out the discussion that might interest the greatest number of readers.

 

[CFS_for_19_years]

Sadly I was anemic too, that didn't bother them either

Well that certainly sucked. Did you have to ask to be treated or did you just manage it on your own?

 

[Sea]

Well that certainly sucked. Did you have to ask to be treated or did you just manage it on your own?

I managed it on my own, with lots of helpful information from this forum and researching on my own. I was seeing a doctor at one point who would test me for things that I asked for which was helpful even though he had no advice for management. I was also donating blood to a research group several times a year and although I didn't get results for everything they were looking at they always sent results for the basics which included the MCV.