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Taking Charge of Your Health


Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
a personalized study plan with exclusive videos, practice questions and flashcards, and so
much more. Try it free today! Vitamin B12 deficiency refers to low levels
of Vitamin B12 in the body. This can lead to a variety of problems ranging
from anemia to soreness of the tongue and neurological dysfunction. Vitamin B12, also known as cobalamin, is a
complex organometallic compound found in animal and dairy products like meat, eggs or milk. Dairy and animal products are broken down
in the stomach by pepsin, which is the active form of a gastric enzyme called pepsinogen,
to release B12. Then, a protein made by parietal cells in
the stomach, called intrinsic factor, can bind to B12, and the B12-intrinsic factor
complex passes into the intestines. When the complex reaches the terminal ileum,
the enterocytes, which are the special cells lining the intestines, recognize intrinsic
factor and absorb the whole complex. Inside the enterocytes, intrinsic factor gets
removed and a special protein called transcobalamin-II binds the free B12 and transports it into
the blood and from there, to various target tissues. Some of the transcobalamin-B12 complex gets
to the liver, where B12 can be stored for several years. B12 is used to synthesize DNA precursors,
which is essential for cell division. First, vitamin B12 accepts a methyl group
from methyl tetrahydrofolate or methyl-THF, making methylcobalamin and free tetrahydrofolate,
or THF in the process. THF then gets an extra “methylene” group
from serine, an amino acid found within the cells. THF quickly transfers the methylene to a nucleotide
called deoxyuridine monophosphate, or d-UMP for short. As a result, d-UMP becomes d-TMP or deoxythymidine
monophosphate, which can then be converted to thymidine, one of the nucleotides used
to build DNA. Going back, the methylcobalamin that was formed
along with THF transfers its methyl group to homocysteine and converts it into an essential
amino acid called methionine, thus lowering the levels of homocysteine in the body, too
much of which can be harmful. Alternatively, B12 can be used by the mitochondria
in another active form called “adenosylcobalamin” – which is basically B12 with an adenosyl
group clinging to it! Adenosylcobalamin acts as a coenzyme for methylmalonyl
coenzyme A mutase, an enzyme which converts methylmalonyl co-A into succinyl co-A. This
helps reduce the levels of methylmalonic acid, which can also be harmful if it builds up. So in short, the consequences of B12 deficiency
are that cell division is impaired, and there’s too much homocysteine and methylmalonic acid
in the body. When cell division grinds to a halt, rapidly
dividing cells in the bone marrow are affected, like red and white blood cells, as well as
platelet precursors. Inside the bone marrow, red blood cell precursors
are normally big and plump, and they undergo a series of cell divisions which results in
smaller mature RBCs. Now with B12 deficiency, at first, the bone
marrow pumps out larger, but still mature RBCs called macrocytes. These RBCs are destroyed in the spleen, which
causes a decrease in the total RBC count, or anemia. In response, the bone marrow compensates by
releasing abnormally developed RBC precursors, called megaloblasts, into the blood, and the
final result is macrocytic, megaloblastic anemia. B12 deficiency also affects white blood cell
production – so the bone marrow starts releasing large, immature neutrophils, with hypersegmented
nuclei – meaning their nucleus has more than 5 lobes. Finally, severe B12 deficiency may also decrease
the production of megakaryocytes, which are the platelet precursors in the bone marrow. So when all 3 blood cell lines are affected,
this results in pancytopenia, which is when red blood cell, white blood cell and platelet
count is low. And folate deficiency also decreases white
blood cell, red blood cell, and megakaryocytes production in the bone marrow, also resulting
in pancytopenia. Other rapidly dividing cells are mucosal epithelial
cells, especially those of the tongue mucosa. Have you ever noticed how fast your tongue
heals if you accidentally bite it? That’s because old epithelial cells are
replaced with new ones in the blink of an eye! Okay, not literally that fast, but it is pretty
quick. In B12 deficiency, old epithelial cells aren’t
replaced, and this slows down the healing of normal wear and tear of the tongue, which
ultimately leads to inflammation of the tongue, known as glossitis. Next, when homocysteine builds up in the body,
some of it is excreted in the urine leading to homocystinuria. They also build up in the blood, where they
bind to the endothelial cells lining blood vessels, causing them to secrete molecules
called proinflammatory cytokines. These attract immune cells like leukocytes
to the area and cause inflammation, which leads to atherosclerosis, or plaque build
up inside the arteries. This narrows the arteries and could lead to
ischemia of the tissue supplied by them. Homocysteine also binds to platelets and makes
them stick together to make blood clots. All of this increases the risk of ischemic
heart disease and stroke. Lastly, when there’s too much methylmalonic
acid in the body, it builds up in the neurons – specifically, in the myelin sheath, which
degenerates. Myelin helps transmit electrical impulses
from one neuron to another at very high speed – so with B12 deficiency, communication between
neurons gets significantly slower, which leads to impairment of neurological and muscle function. Kinda like the difference between optic fiber
and the old dial-up internet connections. Ok, now, B12 deficiency can result either
because of impaired absorption or decreased dietary intake. Impaired absorption can result from a number
of causes. For example, in pernicious anemia, there’s
increased production of overzealous IgA antibodies against intrinsic factor or the parietal cells. Either way, this interferes with intrinsic
factor’s ability to bind to B12. In Crohn’s disease, the enterocytes in the
terminal ileum are often damaged, so B12 can’t bind to transcobalamin to get to the target
tissues. In people that get a gastric bypass, the ingested
food passes through the stomach quickly, so even if intrinsic factor is produced, it can’t
get to the food to bind B12. Besides these, infestation in the terminal
ileum with Diphyllobothrium latum, also known as fish tapeworm, or bacterial overgrowth
in the blind loop of bowel can also reduce absorption, leading to vitamin B12 deficiency. Decreased dietary intake is seen in individuals
who avoid all animal products – like long time strict vegans who don’t take B12 supplements. Now, B12 deficiency most commonly causes signs
and symptoms of anemia like pallor, shortness of breath and easy fatigability; soreness
of the tongue due to glossitis. In some cases, they may also present with
signs and symptoms of ischemic heart disease, like chest pain, or signs of stroke like slurred
speech and paralysis. Lastly, in very severe cases, B12 deficiency
may lead to impairment of neurological function, where individuals present with loss of memory
function, decreased reflexes and psychosis. Diagnosis of vitamin B12 deficiency relies
on a peripheral blood smear, which shows large red blood cells and hypersegmented neutrophils. On a blood sample, a Mean Corpuscular Volume
or MCV, larger than 100 fL suggests macrocytosis. A bone marrow study can also be done to look
for the megaloblastic changes in RBC precursors at various stages of differentiation. Homocysteine and methylmalonic acid levels
are also elevated. After confirming that there is a B12 deficiency,
the cause should be found. First, low dietary intake should be ruled
out. Then, to pinpoint the cause of decreased absorption
– one can look for anti-intrinsic factor antibodies for pernicious anemia, or carry out endoscopic
or imaging studies in patients that might have Crohn’s disease. When the cause of B12 deficiency is dietary,
it’s treated with oral B12 supplements. When the problem is absorption related, it
could be treated with either really high oral B12 doses to allow for passive diffusion in
the gut, or with intramuscular B12 injections for a couple of months, which can be followed
with oral supplements if needed. Additionally, treatment of the underlying
cause, when possible, should also be started. Alright, as a quick recap…Vitamin B12 deficiency
is a clinical condition caused by low levels of Vitamin B12 in the body, which impairs
cell division and causes excess levels of homocysteine and methylmalonic acid in the
body. This can lead to macrocytic megaloblastic
anemia causing pallor, shortness of breath and fatigability; glossitis or inflammation
of tongue leading to swelling and soreness, difficulty in talking and swallowing; and
myelin damage resulting in changes in reflexes, poor muscle function, memory problems, and
psychosis in some extreme cases. Diagnosis of B12 deficiency can be made by
doing a peripheral blood smear, measuring the MCV and serum levels of vitamin B12, as
well as serum homocysteine, and methylmalonic acid levels. B12 deficiency is treated with, well, B12
– either as oral supplements or intramuscular injection.

90 thoughts on “Vitamin B12 deficiency – causes, symptoms, diagnosis, treatment, pathology

  1. I have an annoying sensation it just like pricks throughout my body.. Or like there're pins running within my blood ..I was told it can be B12 deficiency

  2. That moment when in you are in summer holidays but you still watch Osmosis cause it made your life easier throughout the year. Thank you Osmosis. I cant stop being grateful 💕

  3. The great thing for vegans is there are foods and plant based milks that are fortified with Vitamin B12 so this condition can be easily avoided (:

  4. Also (PPIs) drugs can reduce Vitamin B12 level, because the intrinsic factor needs Acidic Media to do it's function.
    + Taking Metformin also can decrease Vitamin B12 level

  5. Lithium Orotate plays a role in B12 transport into cells.  Cobalt is an essential trace element and a central component of the vitamin cobalamin, vitamin B12

  6. "The only organisms to produce vitamin B12 are certain bacteria, and archaea. Some of these bacteria are found in the soil around the grasses that ruminants eat; they are taken into the animal, proliferate, form part of their gut flora, and continue to produce vitamin B12."

    You don't need meat, you need dirt.

  7. I was diagnosed with vitamin b12 deficiency. My doctor said my levels were very unusually low for my age. I'm 25 and I eat plenty of meat, eggs, and dairy. I dont have a whole lot of energy but I've gotten the rounds of b12 injections and I take supplements now and I really dont notice anything different. I was also quite low in D3 and iron so I take supplements of those as well. Still dont notice a change. I dont really know what to make of these vitamin deficiencies.

  8. Treatment = pills and injections. How about swapping out some high glycemic, high fiber plant products for some soil building, non intestinal permeability causing, pasture raised ruminant meat?

  9. been vegan for 9 years never took b12 in any form not once never had any of the symptoms…..but whenever something oges wrong with my body i keep thinking oh maybe its b 12 deffeciency …..so recnetly i've been having inflamed gums and tongue and it goes away and comes back…so i was thinking could it be it? oh maybe i'm just allergic to flouride in toothpaste and water? its not not bad its just uncomfortable and it has nothing to do with gum deasease …..but i never not once had any neurological symptoms evryone mentions

  10. YOU ARE SOOOOO SOOOOO GREAT … Thank you!! I´ve got pathophysiology and pathology oral exam next month and your videos help me a lot !!!

  11. What about extremely high levels of B 12 ? Could it possibly mean that the cells are not accepting B12 at all and hence suggestive of a deficiency ?

  12. Vitamin B12 is conspiracy by the meat industry.
    I don't believe in this vitamin B12 at all.
    Why this vitamin B12 available only in animal products?
    Total lie

  13. Hey! Id like to remind you all that you DO NOT NEED to consume animals to get b12.
    B12 is only naturally found in soil. Because we live in a hygienic society, and cattle is mostly fed non organic food (that does not contain b12) it is actually injected into cows so that we then consume it! So maybe try to investigate where that b12 in your beef is coming from.
    SO, getting b12 form supplements is about as natural as getting it from supermarket meat.
    (this goes out to any potential vegan that is scared that they’ll get sick)

  14. Thanks a lot!! Found a lot of other videos and books but none explained the topic in such a straightforward and concise manner.

  15. I currently have B12 deficiency… my symptoms are: numbness and tingling all over my body including the face constantly – which is kind of scary thinking "wth is going on, a stroke??!! " Fortunately, I got blood tests done and I have B12 deficiency.

    The reason I am writting this is for your information:

    I used to have GERD problems for a while (Gastroesophageal reflux disease), I used to take over the counter pills for the heartburn and then switched to Omeprazole which healed me, I also started a much "healthier diet" reducing meat, going more veggies and whole wheat grains, great! but………the stomach pills are the reason I have B12 deficiency because these kind of pills don't let B12 get absorbed into your body after you eat, also I started my "healthy diet" at the worse timing, because by reducing meat, combined with the pills, I also reduced my B12 intake even more. My blood tests showed 155pg/mL of B12 which is very very low.

    So watch out those who have GERD and take pills, increase your B12 intake before it's too late – it really sucks having all these numbness problems each and every day, they do take you down physically and psychologicaly

    I am glad I figured all this out, and I hope I get better soon.

  16. Fajul information hai .Time waste karna hai toa dekh lo. Medical students be samaje nahi paige ki yeh kayabakwas ker raha hai.

  17. Part of the video use the same audio clip from the Folate deficiency video. It seems lazy to me, but it works since B12 and folate deficiency can have similar symptom

  18. What a great video from which I've learned a lot. But please tell me which form of B-12 intramuscular supplementation is the best: Methyl-, Hydroxi- or -Cyano-?
    Subscribed!

  19. Hi Osmosis, explain this one (if you can)…. Microcytic Megaloblastic Anemia……. Deficient in B12, B6, Folate and Iron…. (yes l said Microcytic MCV 75 with Megaloblastic Cells, MCV has been as low as 60 in the past)

  20. I really like your content and way of teaching! Whenever I have difficulty in learning I watch ur videos and it makes it so easy ..

  21. B12 is from a bacteria that forms on plants but due to chemicals we can’t get it from plants, we get it from animal products from the food they eat but in the modern day even what they eat is chemical filled and kills the bacteria that has b12

  22. Should be mentioned that cyanocobalamin is a very bad supplement type due to VERY low bioavailability and high doses have shown to be damaging in studies.

  23. I had my vitamin B12 levels checked so I'm waiting on results. I told my doctor I sometimes feel pinches all over my body and she said it's my nerves could be due to low B12.

  24. i testetd and i have b12 deficiency . if sombody has similar symptoms then let me know . i started with ibs C and i try to fic that with diet by eating fiber and less meat and mostlynplant abased. then i have insomnia once or twice in 8 months .then i had serious insomnia and sleep apnea. i went to doctor and tested i had b12 deficiency . if any bos has similar story then let me know.

  25. This is another good video to make basic concepts about megaloblastic anaemia. Though I prefer listening to the other “iconic voice” of osmosis. Great job team!

  26. Mostly great information but once loading injections injections stop symptoms may returns . Best to see how your doing as may need for a lifetime at regular amount depending on how severe symptoms are and how quickly they return.
    Not all damage is iIrreversible and so treatment should be aggressive and long-term shots
    some are lucky enough to switch to all or sublingual.
    Don’t base your diagnosis purely on B12 serum look at homocystine and MMA as a certain level is not a gold standard and is set too low and range should probably be around 500-200 for better health .

  27. I have a burning sensation all over my body, the pain is just horrible and scary like literally I am on a grill, my tongue is swollen, stabbing and needles pain, my skin is dry AF that it hurts when I bend my fingers and toes, persistent headache, fatigue and tiredness all the time. All that shit and not a single doctor thought that it might be a b12 deficiency!!

  28. I have just subscribe to your channel it's the most calming an very informative video i have listen to . This is excellent work here once again i really give compliments so you can be very proud of yourself.

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