Cause of fatigue

[Ziggyzugg]

Can any of you wise owls explain this? I am not anaemic and have normal RBC s but am B12 Def. How does this cause my fatigue. I understand that the fatigue was due to megaloblastic rbcs not being capable of transporting the oxygen. But I don't have this.

[fbirder]

No, that's a commonly believed fallacy. Red cells are flexible little blighters and even a severe B12 deficiency only increases their volume by about 20% - which means their diameters have increased by about 6%. That will not make a significant difference in their ability to pass through capillaries.

If it did then the result would be a lot worse than fatigue. The bad symptoms of sickle-cell anaemia is because the red blood cells sometimes get stuck in blood vessels. That causes severe pain as well as other problems.

Many people with a B12 deficiency do not have macrocytic anaemia (so their red cells are normal sized) but still have fatigue.

I've read a few explanations for the fatigue caused by a B12 deficiency. Most of them sound plausible. They range from the fact the B12 is involved in the generation of energy from same fats, through the inability to make sufficient DNA, through to the reduction in the ability to regulate enzymes in the electron transport chain by the methylation of DNA.

The methylation problem caused by an insufficiency of S-adenosylmethionine can affect a lot of bodily processes.

[Ziggyzugg in reply to fbirder]

Thanks fbirder, that's really interesting and has cleared up my confusion. I appreciate your knowledge on the subject. Do you think there could be an effect on the mitochondria?

[fbirder in reply to Ziggyzugg]

The mitochondria are where the electron transport chain, and the Krebs Cycle happens, so I'm reasonably sure that is where whatever causes the fatigue happens.

[Ziggyzugg in reply to fbirder]

Thanks again for your quick reply All if a sudden I don't feel so stupid.

[FlipperTD in reply to Ziggyzugg]

[Here he goes again...!]

Mitochondria are present in the reticulocytes [which are juvenile red cells, up to about 2 days from release from the bone marrow.] Red cells normally last about 115 days, and they've lost their mitochondria by day two. Mitochondria are ubiquitous little beasts, thank goodness, and are responsible for the production of ATP amongst other things. A mature red cell relies on the Embden Meyerhof glycolitic pathway to produce ATP, and without that, the red cell is doomed to a very early death. In PA, there may well be a mild jaundice, due to 'ineffective erythropoiesis' because the bone marrow has problems making decent, complete red cells, and this is almost certainly down to defects in DNA synthesis, due to a lack of B12. But the cells that are produced are reasonably competent. I'll stop now or I could go on for hours, and I apologise anyway!

[Ziggyzugg in reply to FlipperTD]

Thanks. This is facinating stuff flipper TD. Makes a lot of sense.

[FlipperTD in reply to Ziggyzugg]

Glad you appreciate it; it makes it all worthwhile. Sometimes I think I'm tending to rabbit on a bit!

[Nackapan]

I also gave debilitating fatigue have a normal hb count have got my ferritin levels up. I've lots of other symptoms too. Throughput I've eaten well. Have some pysio even when bedbound tk reduce muscle wasting walked. It's the most common complaint and medics appear to think the only one at times.

Reserch research

I've been told chronic fatigue but this I'd a symptom of so many illness not the cause.

[Leils]

Good question! I have wondered all sorts of things about the neurological effects of low B12....

For me I think it is the combination of low B12 and low other things:

Since starting on B12 treatment I have also found out I was short of B2 and taking extra has really helped with the fatigue.

Adding more magnesium has also helped increase my stamina levels

[Litatamon in reply to Leils]

Leils can you tell me how much b2 you take? And since b2 is in so many foods, does this denote it is some kind of absorption issue?

[Sleepybunny]

Hi,

I've read that B12 is a co-factor in making of neurotransmitters such as dopamine and seretonin. I'm guessing that low levels of B12 can affect amount of neurotransmitters in the brain and that this might lead to fatigue.

Article about brain and B vitamins (lots of scientific language in this one)

ncbi.nlm.nih.gov/pmc/articl...

[Ritchie1268 in reply to Sleepybunny]

Very Interesting Sleepybunny & what a vicious cycle it can be!!

When I became addicted to OxyContin, my brain stopped producing Dopamine, known as the "feel good" neurotransmitter.

The reason being, the more Opiates consumed, the less Dopamine the brain produces as it gets it artificially from the Opiates, so it doesn't need to produce as much, until it stops producing altogether the longer, & higher the dose of Opiates.

When I was coming off all the OxyContin & tapering the dosage, my brain still hadn't started to produce Dopamine & I was no longer getting it artificially from the Opiates. Hence the deep dark depression, anxiety & feeling suicidal.

Different antidepressants did nothing so I refused to take anymore. That's when the FBC was done & PA confirmed.

It has taken time, and since regular injections, my mental health has never been better.

[Sleepybunny in reply to Ritchie1268]

Hi,

Thanks for sharing your experiences. My mental health is also much better than it used to be.

I have some symptoms suggestive of problems with dopamine levels eg mild dystonic type symptoms and restless legs syndrome and a few others which I think is linked to B12 issues.

[fbirder in reply to Sleepybunny]

I've just given this a quick gander, and it seems that B12 has a minor role. A B12 deficiency can, via the folate trap, result in a functional deficiency of dihydrofolate. DHF is involved in neurotransmitter synthesis via the Tetrahydrobiopterin Salvage Pathway (see figure 2). B12 itself seems not to be directly involved.

That's a really interesting article. I had no idea how the other B vitamins were so heavily involved in almost everything,

[Litatamon in reply to Sleepybunny]

In the study it talks about having a functional folate deficiency, so that means that you can have normal values but still have an issue, correct? And this is due to absorption issues?

So experimentation with supplementation/changes in diet is the only way to determine this? But then again if it is absorption am I making any sense?

This is all so interesting. Thanks in advance.

[fbirder in reply to Litatamon]

No, not absorption issues.

A functional deficiency is when you have plenty of the vitamin floating around in your blood, but it's not doing the job it is supposed to do.

WIth folate it's can be caused by what's called The Folate Trap.

There are lots of different types of folate and they are all interconverted in the folate cycle. Two of them are methyltetrahydrofolate and tetrahydrofolate. To convert the former to the latter the body needs B12. If there isn't enough B12 then almost all the folate in the body is trapped as methyltetrahydrofolate and there is a deficiency of all the other types.

The folate blood test measures all the different types. So it sees lots of methyltetrahydrofolate and reports that you have lots of folate in your blood. But all the other important jobs (like making DNA and neurotransmitters) isn't happening - because you lack the other forms of folate.

There's a more detailed explanation of the folate trap here - b12science.com/B12Science/D...

[Litatamon in reply to fbirder]

Thank you.

So if I have a normal folate reading and I am taking b12 then there is no possibility that there is a functional folate issue? Because I have adequate b12 to convert the folate into the proper form. Is that correct?

Asking because I openly so wondered if taking methylfolate could make a difference with my fatigue, but my numbers are normal. So I have refrained.

[fbirder in reply to Litatamon]

There's only one way to tell. Buy 90 tablets of methylfolate (400 mcg) and take one a day for three months.

It can't hurt.

[Litatamon in reply to fbirder]

I will. Thanks.

[Litatamon in reply to fbirder]

"Methyl Folate is also known as methyltetrahydrofolate. It enters the folate cycle at a point that bypasses the MTHFR conversion. As such, some people with one particular mutation (homozygous C677T) in the gene for MTHFR may find it worth paying ten times the price to take methylfolate instead of folic acid."

fbirder , because I have this gene issue folic acid might not work, correct?

But that gene has nothing to do with a functional folate issue, right?

[fbirder in reply to Litatamon]

Some people suggest that being homozygous for the C677T mutation in the MTHFR gene might cause a functional folate deficiency. The MTHFR enzyme is responsible for converting methylenetetrahydrofolate into methyltetrahydrofolate. If, for some reason, the MTHFR enzyme stopped working then all the folate in the body would get trapped as methylenetetrahydrofolate and the body would be incapable of making DNA and you would die.

As there are about 700,000,000 people on Earth living with that mutation it's obvious that, despite what many interweb sites say, it doesn't stop the MTHFR enzyme from working.

Having that mutation makes the MTHFR enzyme less efficient, by about 70%. But the body can easily overcome this problem - it just makes more of the enzyme.

But there's little doubt that some people with that mutation do benefit from taking methylfolate. Most don't, probably because most of the folate in food is methylfolate. So if you can get enough folate in your diet, being homozygous for C677T doesn't matter.

youtu.be/MzT-iU8UIwo(Not working as expected?)

[Litatamon in reply to fbirder]

Thanks fbirder. Appreciate it. I know how you feel about the gene theories, and it has been very helpful to hear. I simply thought I remembered that the only theory you held with those genes was choosing methylfolate over folic acid.

I must be remembering incorrectly. But hey I do have a b12 deficiency!

Thanks again.

[fbirder in reply to Litatamon]

As I said, I'm firmly of the opinion that some people definitely benefit from taking methylfolate instead of folic acid. Mostly because of my own experience. healthunlocked.com/pasoc/po....

[Litatamon in reply to fbirder]

Wonderful.

And the best part of wonderful - my memory is still functioning! Great news.

Thanks fbirder.

[Litatamon]

Thank you for your question Ziggyzugg, great discussion.

I have always been confused about taking proper b12 supplementation and still experiencing fatigue.

[Ziggyzugg in reply to Litatamon]

Litatamon

Good to hear I at not alone in being confused as to why we have these symptoms. And that I am not alone in wondering why the intense fatigue hasn't lifted despite a X6 alte hirnate day SI regime. It would be lovely to hear that someone the forum found the same but persevered and it cleared.

Again, you are all a fantastic support during these difficult times.

[Litatamon in reply to Ziggyzugg]

Yes it would be great to have some insight. I have been very lucky. I had at least thirty symptoms due to a b12 deficiency and most of them have dissipated. But the remaining, especially fatigue, have been frustrating.

[fbirder in reply to Litatamon]

I've been injecting twice a week and I still have problems with fatigue.

My stamina is pretty good. I can walk miles with the dogs. But my capacity for short-term not-very-heavy exercise is near zero. I carried a box of printer paper (about 12.5 kg) 20 m from the front door to the kitchen and I had to site down for five minutes.

It can't be the B12 (injecting more often doesn't help and injecting every two weeks doesn't make it worse).

I've tried almost everything. I'm now taking Vitamin B2 as somebody I trust says that it might help. There may be a slight improvement.

[Litatamon in reply to fbirder]

I saw that - b2. And thought about it myself. Thanks.

All the best with it.

[fbirder in reply to Litatamon]

If you take high dose B2 don't be panicked at the colour of your wee. Yellow highlighter pen is a good match,

[Ziggyzugg in reply to fbirder]

That's really strange that you can walk the dogs ok but are worn out with a bit of carrying. It can't be a different physiological mechanism. I am more the opposite. Walked out to get something from the care and was wiped out for a while, and stairs seem to be getting steeper but carrying is ok. Fingers crossed B2 will make a difference.

[fbirder in reply to Ziggyzugg]

Walking the dogs is gentle exercise. Carrying something heavy is more strenuous. I get the same problem if I try running alongside the young dog. Which is a great shame as he likes to trot along.

[Ziggyzugg in reply to Litatamon]

Well that is encouraging litatamon. Something's have improved for you. I think I'll try B2 as fbirder mentioned (well as daily b12 and folate) see what happens. In for a penny, infor a pd. will look out for yellow pee! Any dosage suggestions for B2?

[Litatamon in reply to Ziggyzugg]

I have asked about the dosage upthread.

Hope something makes a difference for you Ziggyzugg.