B12 Deficiency: Uncovering the Silent Threat to Neurological and Vascular Health

In today’s episode of Daily Value, we take a closer look at a commonly overlooked but essential nutrient: vitamin B12. Known as cobalamin, vitamin B12 deficiency can lead to severe neurological, hematological, and cognitive issues if left unchecked. We’ll cover the causes behind this growing issue, from dietary intake to malabsorption.

Episode Talking Points:

• The role of B12 in nervous system function and red blood cell production.
• Causes of B12 deficiency, including dietary factors, autoimmune conditions, and genetic predispositions.
• Treatment approaches, including supplementation methods and the importance of early diagnosis.

https://pubmed.ncbi.nlm.nih.gov/38987879/ 

https://www.nature.com/articles/nrdp201740

Support the show

Episode Transcript

Speaker 0 (00:00):
Hello everyone, welcome back to Daily Value.
I'm William Wallace and todaywe'll be having an overview
discussion of cobalamindeficiency or vitamin B12
deficiency.
This is a condition thataffects a growing number of
individuals due to a variety offactors, including dietary
intake and malabsorption.

(00:21):
B12 deficiency is oftenoverlooked, but its consequences
can be severe, leading toneurological, hematological and
cognitive issues.
Today's episode will cover thepathophysiology of B12
deficiency, diagnosticchallenges and best practices
for achieving optimal B12 statusbased on the most recent

(00:43):
research.
Before we begin, pleaseremember that this podcast is
for educational purposes onlyand is not intended as medical
advice.
If you or someone you know hasor is being treated for a B12
deficiency, please consult yourprimary healthcare professional
before beginning or alteringtreatment.
Now let's dive into some of thescience behind B12 deficiency

(01:04):
and its management.
Vitamin B12, or cobalamin asit's called, is an essential
water-soluble vitamin that playsa crucial role in the
functioning of the nervoussystem and the production of red
blood cells.
It acts as a cofactor invarious biochemical processes,
including DNA synthesis and themethylation cycle.
B12 is primarily synthesized bycertain bacteria and RK.

(01:26):
Because of this, b12 is notreally found in plant food
products.
Certain plant-based fermentedfoods and algae, like chlorella
may contain B12, but in foodit's primarily found in animal
tissues, in ruminant animals.
A ruminant animal is one thathas a special digestive system

(01:47):
designed to break down toughplant material like grass.
They have a multi-chamberedstomach, with the largest
chamber being called the rumen.
That's where bacteria andmicrobes help ferment and digest
their food.
Animals like cows, sheep anddeer are what we would call
ruminants, and they regurgitatefood to chew it again, what we

(02:07):
call chewing cud, to help withdigestion.
This process allows them to getmore nutrients from plant-based
diets than other animals thatcannot easily digest plants.
The fermentation of the foodthey eat allows them to get B12
into their system, which makesits way to their tissues, which
we benefit from when we consumeanimal products as such.

(02:29):
In humans, b12 is primarilyobtained through the consumption
of animal products such as meatand dairy.
When we do not consume enoughvitamin B12 from food,
supplementation may be warranted.
However, b12 absorption is acomplex process that involves
multiple steps, including theproduction of what's called
intrinsic factor by the stomachlining and its subsequent

(02:50):
absorption in the ileum, whichis part of the small intestine.
Intrinsic factor is a proteinmade in the stomach that's
essential for absorbing vitaminB12.
Without intrinsic factor.
Even if you eat plenty ofB12-rich foods like meat or
dairy, your body can't properlyabsorb B12.
The vitamin.
There are certain autoimmuneconditions like atrophic

(03:11):
gastritis or pernicious anemia.
The former can be caused by thelatter, where the body produces
antibodies against intrinsicfactor.
This can result in B12malabsorption due to the absence
of intrinsic factor and,eventually, b12 deficiency.
There are three primarymechanisms through which one may

(03:31):
develop a B12 deficiency.
One would be a dietarydeficiency.
This is the most common causeof B12 deficiency.
It is insufficient intake ofB12-rich foods, particularly in
populations that followvegetarian or vegan diets.
B12 absorption can also declinewith age due to decreased
gastric acid production, whichis necessary to release B12 from

(03:53):
food.
Two would be malabsorption.
Autoimmune conditions that arecharacterized by the destruction
of gastric parietal cells thatproduce intrinsic factor can
lead to B12 malabsorption.
Additionally, gastrointestinalsurgeries like gastric bypass
and diseases such as Crohn'sdisease also impair B12

(04:15):
absorption.
Three would be drug use.
Chronic use of drugs likeproton pump inhibitors and acids
and drugs like metformin, aswell as recreational nitrous
oxide, can deplete B12 levels byinterfering with its metabolism
, can deplete B12 levels byinterfering with its metabolism.
Two lesser understood mechanismsof B12 deficiency may be

(04:37):
genetic familial deficiency,meaning traits that are
inherited through geneticmutations or predispositions
passed down from parents tooffspring.
The second would be epigeneticcauses.
These involve changes in geneexpression without altering the
underlying DNA sequence.
These changes can be influencedby environmental factors,
lifestyle or diet and may notnecessarily be passed down from

(05:01):
generation to generation.
Interestingly, past research inthis area has shown that
children of some families withnormal vitamin B12 intake
present with B12 deficiency,children of some families with
normal vitamin B12 intakepresent with B12 deficiency.
In these cases, it was foundthat B12 deficiency was present
in the mother during pregnancy.
It's possible that may lead towhat are called epigenetic

(05:24):
alterations in children whichnegatively impact
gastrointestinal B12 absorptionlater in life.
This might fall under what'scalled the transgenerational
effect of possibilities.
On the other hand, genetics cansignificantly impact how much
vitamin B12 you have in yourbody.
There are 15 genetic mutationsrelated to the absorption,
transport and metabolism of B12that can affect B12 levels.

(05:45):
One well-known gene, fut2, orthe fucosal transferase 2, gene
FUT2, or the fucosal transferase2, can influence your total B12
levels, but it mostly increasesthe amount of inactive B12 by
10 to 25 percent rather than theactive form that your body uses
.
That's calledholotranscobalamin.
Unfortunately, many clinicalsymptoms of B12 deficiency are

(06:07):
nonspecific.
Many individuals with B12deficiency present with
neurological symptoms.
These include numbness andtingling in the hands and feet,
often described as pins andneedles.
Over time, it can cause balanceproblems and difficulty walking
due to nerve damage.
People may also experiencememory loss, confusion and mood
changes, including depressionand irritability.

(06:29):
Another presentation of B12deficiency is a type of anemia
in the form of megaloblasticanemia, which is caused by
pernicious anemia.
Pernicious anemia, again, is anautoimmune condition where the
body attacks the cells in thestomach that produce intrinsic
factor, a protein needed toabsorb vitamin B12.
Without intrinsic factor, thebody can't absorb enough B12,
leading to a deficiency.

(06:50):
This lack of B12 affects theproduction of red blood cells,
causing them to become large andimmature, a condition known as
megaloblastic anemia.
These oversized red blood cellscan't function properly,
leading to symptoms like fatigue, weakness and neurological
issues.
A folate deficiency can alsocause megaloblastic anemia.

(07:13):
Most people in Western countrieswith B12 deficiency do not
present with anemia ormacrosytosis, that's when red
blood cells are larger thannormal.
In fact, anemia is present infewer than one-fifth of people
with a vitamin B12 deficiency.
It's not entirely known whysome people with B12 deficiency
present with neurologicalsymptoms and some develop

(07:33):
megaloblastic anemia.
One of the key issues inmanaging B12 deficiency is that
diagnosis can be complex due tononspecific symptoms and
variability in laboratoryresults.
Again, common symptoms includeneurological.
This includes peripheralneuropathy, memory problems and
cognitive impairment.
There are hematologicalsymptoms such as macrocytic

(07:55):
anemia, fatigue and weakness,and there are also psychological
symptoms that include moodswings, depression and
irritability.
The most common biomarkers usedto diagnose a vitamin B12
deficiency include methylmalonicacid and total homocysteine.
These markers become elevatedin vitamin B12 deficiency.

(08:17):
Homocysteine these markersbecome elevated in vitamin B12
deficiency, reflecting impairedenergy metabolism and
methylation respectively.
However, their use iscomplicated by factors such as
kidney function and certainmedications like antibiotics
that can also influence theirlevels.
Methylmalonic acid is not avery sensitive marker of B12
deficiency.
It may be more representativeof not having a certain amount

(08:38):
of another active form ofcobalamin, that being
adenosylcobalamin, also known ascobalamide.
This active form of vitamin B12is present in the mitochondria
of a cell and is used by theenzyme methylmalonyl-CoA mutase
to convert methylmalonyl-CoAinto succinyl-CoA.
As for homocysteine, that canalso be elevated in a folate

(09:00):
deficiency or a vitamin B6deficiency.
Thus, elevated methylmalonicacid or homocysteine may confirm
B12 deficiency, but they maynot.
Holotranscobalamin is anothercommon biomarker.
This is the active fraction ofB12 in the blood and may offer
better diagnostic accuracy thantotal serum B12, but it and may
offer better diagnostic accuracythan total serum B12, but it's
not widely available and stillhas some limitations.

(09:21):
Holotranscobalamin is theactive form of vitamin B12 that
your body can actually usebecause it's bound to a
transport protein that deliversit to your cells.
On the other hand, serumcobalamin measures the total
amount of vitamin B12 in yourblood, but this includes both
active and inactive forms, theinactive form being called
haptochorin.

(09:42):
So even if your serum B12levels are normal, it doesn't
necessarily mean your body hasenough usable B12.
Holotrans cobalamin gives amore accurate picture of how
much B12 is available to supportimportant functions like DNA
production and red blood cellformation.
While serum B12 levels arecommonly used to screen for
deficiency, their accuracy islimited.
Many patients may present withsymptoms even after their serum

(10:04):
B12 levels are within normalrange.
The treatment of vitamin B12deficiency depends on its cause,
whether due to dietaryinsufficiency or malabsorption.
The human body stores between 1and 5 milligrams of vitamin B12
, and we lose anywhere from 1.4to 5.1 micrograms of the vitamin
per day.
Healthy adults require anywherefrom 4 to 7 micrograms of

(10:26):
vitamin B12 a day to maintainnormal levels.
With age, absorption decreases,so elderly people may need more
, and in fact, vitamin B12 islisted as a nutrient of public
health concern in people over 65years of age.
In people with severe vitaminB12 deficiency, iv or
intramuscular doses of B12usually wipe out symptoms more

(10:46):
rapidly and, once stabilized,maintenance may be switched to
oral supplementation which,depending on the doctor
prescribing, is usually given inthe form of cyanocobalamin or a
preparation of the two activeforms of B12, that being
methylcobalamin andadenosylcobalamin.
It's worth noting that ifsomeone has a B12 deficiency and
is supplementing with manycompounds, high doses of folate

(11:09):
or folic acid can also mask aB12 deficiency, especially if
anemia is present due to B12deficiency.
Now it's important to note thatit is usually recommended in
cases of symptomatic B12deficiency due to malabsorption,
that B12 be administeredintramuscularly, as oral
supplementation would beineffective.

(11:32):
Once treatment is started underthese circumstances, it's
usually suggested that it may bemaintained for life or until a
clinician says otherwise.
I need to be very clear instating that there is not enough
evidence to suggest the bestB12 dose and frequency for
long-term health outcomes, asthis will likely vary between

(11:52):
individuals.
Treatment schemes and doses varyquite a bit from country to
country.
Treatment schemes and dosesvary quite a bit from country to
country.
For instance, the Netherlandsstandard is to use 1000
micrograms of hydroxycobalaminvia intramuscular injection
twice weekly.
In the UK this is usually givenon alternate days.
Hydroxycobalamin has replacedcyanocobalamin as the preferred

(12:12):
treatment choice in manycountries.
As hydroxycobalamin is retainedin the body longer than
cyanocobalamin, the dose andfrequency chosen by one's
clinician may take severalmonths or even years to resolve
symptoms, depending on theseverity and length of the
deficiency.
Before treatment, it'ssuggested that, even once
symptoms subside, that the doseor frequency of injection not be

(12:34):
suddenly reduced, as to preventa rapid symptom onset.
The recommendation is togradually increase the interval
between doses over time whilemonitoring symptoms.
The frequency of intramuscularinjections once symptoms have
subsided can range from twiceweekly to once every two to
three months, depending on theindividual.

(12:56):
It's important to note thatcyanocobalamin in very high
doses is contraindicated inpeople with impaired kidney
function and that there's not alot of data comparing different
forms of vitamin B12 being usedto treat a B12 deficiency on a
large scale.
It's also important to notethat there are no studies
available that would make itobvious which individuals could
safely transition fromintramuscular therapy to oral

(13:18):
supplementation of B12.
The clinical goal of B12 therapyis to reverse symptoms and
improve the patient's quality oflife, rather than simply just
normalizing serum B12 levels.
Neurological symptoms inparticular may take months or
even years to resolve and insome cases may not fully

(13:39):
disappear.
Monitoring for recurrence ofsymptoms is crucial, as rapid
reduction in injection frequencycan lead to a symptom relapse.
Some patients experienceneuropathic symptoms that
improve with B12 supplementation, even if they do not exhibit
classic signs of deficiency inlab tests.
For those patients, atherapeutic trial of B12

(13:59):
injections is usuallyrecommended, especially if other
causes of neuropathy have beenruled out.
While studies suggest that oraldoses of 2,000 micrograms or
more may be absorbed passively,intramuscular injections remain
the standard of care for thosewith severe deficiency or
malabsorption disorders.
Lifelong supplementation istypically required for
individuals with malabsorption.

(14:20):
For patients who respond wellto treatment, the frequency of
injections may be reduced, butmonitoring for symptom
recurrence is essential.
Co-balliman deficiency is aserious condition, but it's a
treatable condition.
Early diagnosis andindividualized treatment are
critical to prevent irreversibledamage, particularly to the
nervous system.
In this case, whether throughoral supplementation or

(14:41):
intramuscular injections,restoring B12 levels can
significantly improve quality oflife and mitigate the long-term
effects of deficiency.
Thank you for tuning in toDaily Value.
If you found today's episodeinformative, be sure to
subscribe and share with otherswho might benefit.
As always, stay healthy.